CX 2018 Book

Vascular and Endovascular
Controversies Update—
40 Years of Looking Forward
BIBA Publishing, BIBA Medical Limited, 526 Fulham Road, Fulham, London, SW6 5NR.
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First published in 2018 by BIBA Publishing.
ISBN: 978-0-9570419-6-7
©Roger M Greenhalgh, 2018
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Published by BIBA Publishing, 2018
IX Contributors
XXI Introduction
Acute stroke controversies
Carotid controversies
5
Debate: Routine completion assessment is essential after carotid
endarterectomy—for the motion
C Knappich and HH Eckstein
13
Debate: Routine completion assessment following carotid
endarterectomy is essential—against the motion
AP Coupland, A Thapar and AH Davies
19
The majority of patients neither require surveillance nor reintervention
after carotid stenting/endarterectomy
AR Naylor
25 I s there a role for carotid endarterectomy or carotid stenting in

preventing dementia?
S Ball and C McCollum
31 Is protamine reversal of heparin safe during carotid endarterectomy?

JD Kakisis, C Antonopoulos, KG Moulakakis and G Geroulakos
Cerebral controversies
39 CSVI appraisal is again required

C
L Machan and T Traboulsee
41 uantitative analysis of embolic filter debris load during carotid artery

Q
stenting in asymptomatic patients
F Grego, M Piazza, F Squizzato, A Angelini and M Antonello
IV
Thoracic aortic controversies
Technique and technologies controversies
53 New thoracic descending thoracic aortic stent graft

H Yammine, JK Ballast and FR Arko III
57 EVAR using a new visceral manifold device

T
B Safran and TS Maldonado
Controversies associated with underlying pathologies, connective tissue disor-

ders, and dissecting aneurysm
65 ndovascular repair in patients with connective tissue disorders—

E
infrarenal
L Bertoglio, V Ardita, T Cambiaghi, L Apruzzi, G Melissano and R Chiesa
73 izing matters when it comes to remodelling and false lumen

S
thrombosis after TEVAR
H Yammine, J Ballast and F Arko III
Radiation controversies
81 educed radiation and choice of imaging modality for endoleak

R
detection and correction
CJ Schulz, P Geisbüsch and D Böckler
89 eficiencies in operator behaviour—premature atypical malignancies

D
in high-volume operators
N Pakroo and B Modarai
Stroke from Thoracic Endovascular aortic Procedures (STEP) controversies
97 The use of filter protection in TEVAR patients—lessons learned from

a single-centre experience
G Grover, R Gibbs and M Hamady
103 ranscranial Doppler—the ultimate cerebrovascular monitoring

T
technique for arch and supra-arch interventions
AB Lumsden and Z Garami
V
Juxta-renal (complex abdominal aortic) controversies
115 Controversies in management of short, angulated, wide and

challenging aortic proximal necks—chimney, FEVAR and open
L Bertoglio, L Apruzzi, D Mascia, A Melloni, G Melissano and R Chiesa
123 se of EndoAnchors for elective EVAR

U
SR Goudeketting, RC Schuurmann and JPPM de Vries
129 Use of covered stents for visceral and aortoiliac injuries

MA Ruffino, M Fronda, A Discalzi, D Righi and P Fonio
137 Predictors of long-term survival after fenestrated endovascular aortic

repair
AJ Fowler, A Draper and B Modarai
143 ebate: FEVAR is best for juxta-renal aneurysm repair—for the motion
D
AS Patel, JS Cho and B Modarai
149 ebate: FEVAR is best for juxta-renal aneurysmal repair–against the

D
motion
KP Donas, GT Taneva and G Torsello
Abdominal aortic controversies
Screening and centralisation of services
159 Screening for abdominal aortic aneurysm is cost-effective and a policy

on 2.5–2.9cm aortic diameters
P Söderberg, K Thorbjørnsen, S Svensjö and A Wanhainen
167 Evidence on patient volume, outcome and units of trading for EVAR
and open repair
U Ronellenfitsch, M Grilli and D Böckler
175 How volume and endovascular aneurysm repair impact outcomes for
ruptured abdominal aortic aneurysm treatment
C Nicolajsen, K Mani and J Budtz-Lilly
181 Generation of high-performance teams in emergency aortic surgery—

simulated leadership and team training is effective
A Sharrock, AJ Batchelder, C Riga and C Bicknell
VI
EVAR in women controversies
191 Risk of abdominal aortic aneurysm among relatives of abdominal

aortic aneurysm patients
KM van de Luijtgaarden, F Bastos Gonçalves, MJ van Rijn, S ten Raa, SE
Hoeks, RJ Stolker, D Majoor-Krakauer and HJM Verhagen
197 VAR does not have worse outcomes in women

E
C Mascoli, C Lomazzi, E Gallitto, R Pini, C Fenelli, M Goretti, GL Faggioli, A
Stella, S Trimarchi and M Gargiulo
Internal iliac artery preservation controversies
205 Establishing evidence for endovascular aneurysm repair of the iliac

axis: Data from pELVIS
GF Torsello and GB Torsello
209 arallel graft use for internal iliac artery preservation

P
C Blanco, G Mestres, X Yugueros and V Riambau
Results and follow-up of EVAR
219 evice labelling is not always in the patient’s interests

D
DST Chong and TM Mastracci
225 Risk factors for iliac limb occlusion—one-year data with latest
generation EVAR devices
S Ancetti, E Gallitto, C Mascoli, R Pini, G Faggioli, A Stella and M Gargiulo
233 einterventions after EVAR: “On”and “off” instructions for use

R
MJ Grima and I Loftus
239 en-year EVAR follow-up vs. open repair with second-generation EVAR
T
G Pratesi, M Barbante, R Biscegli, G Citoni and A Ippoliti
245 rediction of less vigorous follow-up based upon the first

P
postoperative CT scan
H Baderkhan and K Mani
251 Tomographic ultrasound measures associated with abdominal aortic

aneurysm growth
M Khan, S Rogers and C McCollum
VII
259 pplication of endoachors in EVAR short neck <10mm
A
Alternative access to control endoleak controversies
267 Alternative access to control endoleaks controversies—transarterial

B Hawthorn, S Ameli-Renani and RA Morgan
275 The transarterial approach for treatment of type II endoleaks

SA Mehta and RG McWilliams
285 lternative access to control endoleaks—para endograft

A
ET Criman and PA Schneider
Technical controversies for open abdominal aortic aneurysm repair
293 The AIDA study—a randomised multicentre three-armed clinical trial

to prevent incisional hernia following abdominal aortic aneurysm open
repair by onlay mesh augmentation
ES Debus, T Kölbel, S Wipper, N Tsilimparis, A Larena-Avellaneda and H
Diener
Peripheral arterial ischaemia controversies
WHETHER to intervene, WHEN to INTERVENE, INTERVENTION METHOD AND

FOLLOW-UP: Controversies on severe aortic bifurcation and iliac occlusive arte-
rial disease
303 What ABPI and toe pressure index tell us about prognosis and how
clopidogrel and statins impact it
M Venermo and M Laivuori
311 overed endovascular reconstruction of the aortic bifurcation

C
P Goverde, K Taeymans, K Lauwers and P Verbruggen
319 Endovascular vs. open treatment of severe aortoiliac occlusive

disease—outcomes of a kissing, self-expanding covered stent for
reconstruction of the aortic bifurcation
S Lepidi, F Squizzato and F Grego
VIII
Endo first vs. open surgery—the controversies and evidence
329 Common femoral and profunda artery disease are best managed by
open surgery
AD Godfrey and CP Shearman
335 ndovascular first for critical limb ischaemia is a concept without

E
evidence
L Meecham, MA Popplewell, S Patel and AW Bradbury
343 Endovascular first for critical limb ischaemia is a concept without

evidence: A vascular surgeon’s perspective
CC Yeh, JC Hnath and RC Darling III
Emerging devices and interventional techniques: Vessel preparation devices
351 reating the superficial femoral artery with a serration balloon catheter
T
L Lee and PA Schneider
357 The use of directional atherectomy prior to drug-coated balloons

RHA Welling, OJ Bakker, GJ de Borst and FL Moll
Drug-coated balloons, stents, drug-eluting stents and bioabsorbable scaffolds
367 I LLUMENATE: European randomised controlled trial two-year results

M Brodmann
373 he potential value of swirling flow—the BioMimics 3D study

T
programme
PA Gaines, T Sullivan, G Ansel, C Caro and T Zeller
Access techniques and peri-interventional imaging
383 The potential value of IVUS-guided superficial femoral artery

interventions—a randomised trial
RB Allan and JI Spark
389 Vector velocity ultrasound—a new ultrasound technique

L Lönn, JB Olesen, JA Jensen, MB Nielsen and KL Hansen
IX
Guidelines, recommendations, and opinions
397 Limb salvage in acute ischaemia due to occlusion of popliteal aneurysm

S Jungi, TR Wyss and J Schmidli
401 The cost of emergency peripheral events for the patient and for the
health service
D Urriza Rodriguez and DPJ Howard
Critical limb ischaemia controversies
411 How to change a service and the stages of changing a service

417 Percutaneous femoropopliteal bypass—the DETOUR I trial

J Mustapha and G Halena
425 Controversies in the local management of diabetic foot ulcers

M Edmonds
Venous and lymphatic controversies
WHETHER to intervene, WHEN to intervene, HOW to intervene:

Outcomes and Follow-up
Imaging section and diagnostic controversies
437 Haemodynamics—objective assessment of venous and lymphatic

function
S Gianesini and J Patel
443 Strain-gauge plethysmography

H Zachrisson, O Nelzén, J Skoog and T Länne
Lymphoedema
451 Surgical treatment of late-stage lymphoedema and advanced

lipoedema
H Voesten and A Lamprou
X
Superficial venous
461 Evidence for cyanoacrylatic ablation

AK Bozkurt and OO Balkanay
469 One extra drop makes a difference in closure rate for endovascular
cyanoacrylate treated saphenous vein ≥8mm in diameter
YC Chan, Y Law, GC Cheung, AC Ting and SW Cheng
477 The pros and cons of endovenous cyanoacrylate

T Hirsch
485 Retrospective review of complications in 577 consecutive cases of

cryolaser and cryosclerotherapy guided by augmented reality
K Miyake, MH Grill and RB Fukushima
491 Reducing hyperpigmentation after sclerotherapy using an

antithrombotic drug
A Gonzalez Ochoa
497 Photodocumentation in aesthetic phlebology

XI
Contributors
A Apruzzi K, MD
Division of Vascular Surgery
Allan RB, DMU, BHIthSc (Hons) “Vita—Salute” University
Finders University and Finders Medical Scientific Institute H
Centre San Raffaele
Adelaide, Australia Milan, Italy
Ameli-Renani S, MBBS, BSc Ardita V, MD

Radiology Department Division of Vascular Surgery
St George’s Hospital “Vita—Salute” University
London, UK Scientific Institute H
San Raffaele
Ancetti S, MD Milan, Italy
Policlinico S Orsola
University of Bologna, Arko FR III, MD
Bologna, Italy Sanger Heart and Vascular Institute
Charlotte, USA
Angelini A, MD
Department of Medico-Diagnostic Division B
University of Padova
School of Medicine, Italy Bachman Nielsen M, MD, PhD, DMSc
Padova, Italy Department of Diagnostic Radiology
University Hospital of Copenhagen
Ansel G, MD Blegdamsvej, Denmark
OhioHealth Heart and Vascular physicians
Columbus, USA Baderkhan H, MD, PhD
Department of Surgical Sciences
Antonello M, PhD, MD Section of Vascular Surgery
Vascular and Endovascular Surgery Uppsala University
Division Uppsala, Sweden
School of Medicine, Italy Bakker OJ, MD/PhD
Padova, Italy Department of Vascular Surgery
Francisucs Gasthuis & Vlietland Hospital
Antonopoulos C, MD, PhD Rotterdam, The Netherlands
Department of Vascular Surgery
“Attikon” Hospital Ball S, MBChb, MRCS
Medical School Academic Surgery Unit
National and Kapodistrian University of University of Manchester
Athens Manchester, UK
Athens, Greece
XII
Ballast JK, BA Blanco C, MD
Sanger Heart and Vascular Institute Vascular Surgery Division
Charlotte, USA Cardiovascular Institute
Hospital Clínic of Barcelona
Balkanay OO, MD, FECTS, FEBVS University of Barcelona
Istanbul University Barcelona, Spain
Department of Cardiovascular Surgery
Cerrahpasa Medical Faculty Böckler D, MD, MHBA
Istanbul, Turkey Department of Vascular and Endovascular
Surgery
Barbante M, MD University Hospital Heidelberg
Vascular Surgery Heidelberg, Germany
Department of Biomedicine and
Prevention Bono Fukushima R, MD
University of Rome Tor Vergata Clinica Miyake
Rome, Italy Centro de Estudos Hiroshi Miyake—CEHiM
Bela Vista, Brazil
Bastos Gonçalves F, MD PhD
Department of Vascular Surgery Bozkurt AK, Professor, MD
Erasmus University Medical Center, Istanbul University
Rotterdam, the Netherlands Department of Cardiovascular Surgery
Department of Angiology and Vascular Cerrahpasa Medical Faculty
Surgery, Istanbul, Turkey
Hospital de Santas Marta,
CHLC, Lisbon, Portugal Bradbury AW, BSc, MBChB (Hons), MD,
MBA, FEBVS, FRCSEd, FRCSEng
Batchelor AJ, MBChb (Hons), BSc (Hons), University Department of Vascular Surgery
MMedSci (Med Ed), MRCS, MAcadMEd Heart of England NHS Foundation Trust
University of Hospitals of Leicester NHS Birmingham, UK
Trust
Leicester, UK Brodmann M
Division of Angiology
Bertoglio L, MD Department of Internal Medicine
Division of Vascular Surgery Medical University Graz
“Vita—Salute” University Graz, Austria
Scientific Institute H
San Raffaele Budtz-Lilly J, MD
Milan, Italy Department of Vascular Surgery
Aarhus University Hospital
Bicknell CD, BM, MD, FRCS Arhus, Denmark
Imperial College London C
London, UK
Cambiaghi T, MD
Bisceglie R, MD
“Vita—Salute” University
Vascular Surgery
Department of Biomedicine and
San Raffaele
Prevention
Milan, Italy
University of Rome Tor Vergata
Rome, Italy
XIII
Caro C Citoni G, MD
Department of Bioengineering Vascular Surgery
Imperial College London, London, UK Department of Biomedicine and
Prevention
Chan YC, MB, BS, BSc, MD, FRCS, FRCS University of Rome Tor Vergata
(General Surgery) Rome, Italy
Division of Vascular & Endovascular
Surgery Coupland AP, BA, MBBS, MRCS
Department of Surgery Academic Section of Vascular Surgery
University of Hong Kong Imperial College London
Pokfulam, Hong Kong London, UK
Cheung GC, BSc, MMedSc Criman ET, MD

Division of Vascular & Endovascular Tripler Army Center
Surgery Honolulu, USA
Department of Surgery
University of Hong Kong D
Pokfulam, Hong Kong
Darling RC III, MD
Chief, Division of Vascular Surgery, Albany
Cheng SW, MB, BS, MS, FRCS
Medical Center Hospital
Director, The Institute for Vascular Health
Surgery
and Disease, Albany Medical Center
Hospital
University of Hong Kong
Albany, USA
Pokfulam, Hong Kong
Davies AH, MA, DM, DSc, FRCS, FHEA,
Chiesa R, MD, Full professor
FEBVS, FACPh
Academic Section of Vascular Surgery
Imperial College London
London, UK
San Raffaele
Milan, Italy
De Borst GJ, MD, PhD
Department of Vascualr Surgery
Cho JS, MB, BS, MRCS
University Medical Center Utrecht
Academic Department of Vascular Surgery
Utrecht, The Netherlands
Guy’s and St Thomas’ NHS Foundation
Trust
Debus ES, Prof, MD, FEBS, FEBVS
King’s College London
Professor and chair
Cardiovascular Division
Department for Vascular Medicine -
St Thomas’ Hospital
University Heart Centre Hamburg
London, UK
University Clinics of Hamburg-Eppendorf
Hamburg, Germany
Chong D, MBBS, MRCS, PhD
The Aortic Team
De Vries JPPM, MD PhD
Vascular Department
Head of Department of Vascular Surgery
Royal Free London NHS Foundation Traut
St Antonius Hospital
London, UK
Nieuwegein, The Netherlands
XIV
Diener H Fenelli C, MD
Department for Vascular Medicine Vascular Surgery
University Heart Center University of Bologna
University Medical Center Bologna, Italy
Hamburg, Germany
Fonio P, MD
Discalzi A, MD Radiology Unit
Vascular Radiology Department of Surgical Sciences
Department of Diagnostic Imaging and University of Turin
Radiotherapy Turin, Italy
Città della Salute e della Scienza di Torino
Turin, Italy Fowler AJ, MB, BS, BSc
Academic Department of Vascular Surgery
Donas KP, Assistant professor, MD, PhD Guy’s and St Thomas’ NHS Foundation
St Franziskus Hospital Trust
Münster, Germany Cardiovascular Division
Draper A, MB, BS, BSc
Academic Department of Vascular Surgery Fronda M, MD
Guy’s and St Thomas’ NHS Foundation Radiology Unit
Trust Department of Surgical Sciences
Cardiovascular Division University of Turin
King’s College London Turin, Italy
E G
Eckstein HH, MD, PhD Gaines P, MB, ChB, FRCP, FRCR
Department of Vascular and Endovascular Sheffield Hallam University
Surgery Sheffield, UK
Klinikum rechts der Isar
Technical University of Munich Gallitto E, MD
Munich, Germany Policlinico S Orsola
University of Bologna,
Edmonds M, MD FRCP Bologna, Italy
Diabetic Foot Clinic
King’s College Hospital Garami Z, MD
London, UK Medical Director
Vascular Ultrasound Lab
Enrico G, MD, PhD Houston Methodist Debakey Heart &
Vascular Surgery Vascular Centre
University of Bologna Houston Methodist Hospital
Bologna, Italy Houston, USA
F Gargiulo M, MD, PhD

Professor of Vascular Surgery
Faggioli GL, MD, PhD, Associate
University of Bologna
professor of Vascular Surgery
Bologna, Italy
Bologna, Italy
XV
Geisbüsch P, MD Grili M, MLIS
Department of Vascular and Endovascular Library of the Medical Faculty Mannheim
Surgery Ruprecht-Karis University
University of Hospital Heidelberg Heidelberg, Germany
Heidelberg, Germany
Grima MJ, MD, MRCS, MSc, ChM
Geroulakos G, MD, PhD, FRCS St George’s Vascular Institute
Department of Vascular Surgery St George’s Hospital NHS Foundation Trust
“Attikon” Hospital London, UK
Medical School
National and Kapodistrian University of Goudeketting, SR, MSc
Athens Department of Vascular Surgery
Athens, Greece St Antonius Hospital
Nieuwegein, The Netherlands
Gianesini G, MD, PhD
University of Ferrara Grover G, BSc (Hons), MBBS MRCS
USUHS University Imperial College London
Bethesda, USA Department of Vascular Surgery
St Mary’s Hospital
Gibbs R, MD FRCS London, UK
Department of Vascular Surgery H
London, UK
Halena G, MD, PhD
Medical University of Gdansk
Godfrey AD, BM, PGCert Medical
Education, FRCS, MD
Vascular Surgery Division
University Hospital Southampton
Medical University of Gdansk
NHS Foundation
Gdansk, Poland
Southampton, UK
Halfen Grill, MD
Gonzalez Ochoa AJ, MD
Clinica Miyake
IMSS
Centro de Estudos Hiroshi Miyake—CEHiM
Sonora, Mexico
Bela Vista, Brazil
Goretti M, MD
Hamady M, MD, FRCR, EBIR
Vascular Surgery
Department of Interventional Radiology
Bologna, Italy
London, UK
Goverde P, MD
Vascular Clinic ZNA
Hansen, LK, MD, PhD
Antwerp, Belgium
Department of Diagnostic Radiology
University Hospital of Copenhagen
Grego F, MD, Professor
Blegdamsvej, Denmark
Vascular and Endovascular Surgery
Division
Hawthorn BR, MBChB, FRCR
Radiology Department
School of Medicine, Italy
St George’s Hospital
Padova, Italy
London, UK
XVI
Hirsch T, MD
Practice for Internal Medicine and Vascular K
Diseases
Kakisis JD, MD, PhD, FEBVS
Vein Competency Centre
Halle, Germany
“Attikon” Hospital
Medical School
Hoeks SE, MD, PhD
National and Kapodistrian University of
Athens
Erasmus University Medical Center
Athens, Greece
Rotterdam, The Netherlands
Khan M, MRes
Howard DPJ, BM, BCH, MA, DPhil
Academic Surgery Unit
(Oxon), FRCS
Institute of Cardiovascular Sciences
University of Manchester and Manchester
John Radcliffe Hospital
University NHS Foundation Trust
Oxford University Hospital NHS
Manchester, UK
Foundation Trust
Oxford, UK
Knappich C, MD
Department of Vascular and Endovascular
Hnath JC, MD
Surgery
Vascular Surgeon, Albany Medical Center
Klinikum rechts der Isar
Hospital
Technical University of Munich
Albany, USA
Munich, Germany
I Kölbel T, MD
Ippoliti A, MD Department for Vascular Medicine
Vascular Surgery University Heart Center
Department of Biomedicine and University Medical Center
Prevention Hamburg, Germany
University of Rome Tor Vergata
Rome, Italy L
Laivouri M, MD
J Department of Vascular Surgery
Jensen JA Helsinki University Hospital
Professor, PhD, Dr Techn University of Helsinki
Technical University of Denmark Helsinki, Finland
Lyngby, Denmark
Lamprou A-AD , MD, FEBVS
Jungi S, MD Centre of Excellence in Lymphovascular
Department of Cardiovascular Surgery Medicine
Inselspital Nij Smellinghe Hospital
Bern University Hospital Drachten, The Netherlands
University of Bern
Bern, Switzerland Länne T, MD, PhD
Department of Medical and Health
Sciences
Department of Thoracic and Vascular
Surgery
Linköping, Sweden
XVII
Larena-Avellaneda A M
Department for Vascular Medicine
Machan K
University Heart Center
Department of Radiology
University Medical Center
University of British Columbia
Hamburg, Germany
Vancouver, Canada
Lauwers K, MD
Majoor-Krakauer D, MD PhD
Vascular Clinic ZNA
Department of Clinical Genetics
Antwerp, Belgium
Erasmus University Medical Center
Law Y, MB, BS, FRCS
Maldonado TS, MD
Surgery
New York University Langone Medical
Center
New York, USA
Pokfulam, Hong Kong
Mani K, MD, PhD, FEBVS
Lepidi S, MD FEBVS
Division of Vascular and Endovascular
Section of Vascular Surgery
Surgery
Uppsala University
Uppsala, Sweden
Medical School
Padova, Italy
McCollum CN, MBChB, MD, FRCS
Professor of Surgery
Lee L, MD
Fort Belvoir Community Hospital
University of Manchester
Fort Belvoir, USA
Manchester, UK
Loftus I, BSc, MB, ChB, MD, FRCS
Mascia D, MD
St George’s Vascular Institute
St George’s Hospital NHS Foundation Trust
London, UK
San Raffaele
Lomazzi C, MD
Milan, Italy
Policinico San Donato University Research
Hospital
Mascoli C, MD
San Donato Milanese
Vascular Surgery
Milan, Italy
Bologna, Italy
Lönn L, MD, PhD, EBIR, SCIR, Professor
Cardiovascular Radiology
Mastracci TM, MD, MSc, FRCSC, FACS,
National Hospital
FRCS
Copenhagen University
Vascular Department
Copenhagen, Denmark
Royal Free London NHS Foundation Traut
London, UK
Lumsden AB, MD
Houston Methodist DeBakey Heart &
Vascular Center
Houston Methodist Hospital
Houston, USA
XVIII
McWilliams RG, MBBCh, FRCR, EBIR Moll FL, MD, PhD
The Royal Liverpool and Broadgreen Department of Vascular Surgery
University Hospitals NHS Trust University Medical Center Utrecht
Liverpool, UK Utrecht, The Netherlands
Meecham L, MBBCh, MRCS Morgan RA, MBChB

University Department of Vascular Surgery Radiology Department
Heart of England NHS Foundation Trust St George’s Hospital
Birmingham, UK London, UK
Mehta AS, MBBS, DNB, FRCR Moulakakis KG, MD, PhD, FEBVS
The Royal Liverpool and Broadgreen Department of Vascular Surgery
University Hospitals NHS Trust “Attikon” Hospital
Liverpool, UK Medical School
National and Kapodistrian University of
Melissano G, MD, Associated professor Athens
Division of Vascular Surgery Athens, Greece
Scientific Institute H Mustapha JA, MD, FACC, FSCAI
San Raffaele St George University School of Medicine
Milan, Italy Advanced Cardiac and Vascular
Amputation Prevention Centers
Melloni A, MD Michigan State University of Osteopathic
Division of Vascular Surgery Medicine
“Vita—Salute” University Grand Rapids, USA
San Raffaele N
Milan, Italy
Naylor AR, MD, FRCS
The Leicester Vascular Institute
Mestres G, MD, PhD
Glenfield Institute
Leicester, UK
Cardiovascular Institute
Nelzen O, MD, PhD student
University of Barcelona
Department of Medical and Health Science
Barcelona, Spain
Department of Thoracic and Vascular
Surgery
Miyake K, MD, PhD
Linköping University
Clinica Miyake
Centro de Estudos Hiroshi Miyake—CEHiM
Bela Vista, Brazil
O
Olesen BJ, MscEng, PhD
Modarai B, PhD, FRCS Technical University of Denmark
Academic Department of Vascular Surgery Lyngby, Denmark
Guy’s and St Thomas’ NHS Foundation
Trust
London, UK
XIX
P Pratesi G, MD
Vascular Surgery
Pakroo N, MB, BS, BSc, MSc Department of Biomedicine and
Academic Department of Vascular Surgery Prevention
Guy’s and St Thomas’ NHS Foundation University of Rome Tor Vergata
Trust Rome, Italy
King’s College London R
London, UK
Riambau V, MD, PhD
Patel AS, PhD, FRCS Vascular Surgery Division
Academic Department of Vascular Surgery Cardiovascular Institute
Guy’s and St Thomas’ NHS Foundation Hospital Clínic of Barcelona
Trust University of Barcelona
King’s College London Barcelona, Spain
St Thomas’ Hospital Riga C, BSc, MBBS, MD, FRCS
London, UK Department of Vascular Surgery
Imperial College
Patel JA, MD London, UK
Vascular Surgery Fellow
Walter Read National Military Medical Righi D, MD
Center Vascular Radiology
Bethesda, USA Department of Diagnostic Imaging and
Radiotherapy
Patel S, BSc, MSc Città della Salute e della Scienza di Torino
Birmingham Clinical Trials Unit Turin, Italy
University of Birmingham
Birmingham, UK Rogers S, BSc (Hons), PgC, AVS
Popplewell MA, MBChB, MRCS Institute of Cardiovascular Sciences
University Department of Vascular Surgery University of Manchester and Manchester
Heart of England NHS Foundation Trust University
Birmingham, UK Manchester, UK
Piazza M, MD Ronellenfitsch U, MD
Vascular and Endovascular Surgery Department of Vascular and Endovascular
Division Surgery
University of Padova University Hospital Heidelberg
School of Medicine, Italy Heidelberg, Germany
Padova, Italy
Ruffino MA, MD, EBIR
Pini R, MD Vascular Radiology
Vascular Surgery Department of Diagnostic Imaging and
University of Bologna Radiotherapy
Bologna, Italy Città della Salute e della Scienza di Torino
Turin, Italy
XX
S Squizzato F, MD
Vascular and Endovascular Surgery
Safron B, MD Division
New York University Langone Health University of Padova
New York, USA School of Medicine, Italy
Padova, Italy
Schmidli J, MD
Department of Cardiovascular Surgery Spark JI, MBChB, MD, FRCS (Eng), FRCS
Inselspital (Gen Surg), PGCert Med US, FRACS
Bern University Hospital (Vasc)
University of Bern Finders University and Finders Medical
Bern, Switzerland Centre
Schneider PA, MD Adelaide, Australia
Hawaii Permanente Medical Group and
Kaiser Foundation Hospital Stella A, MD
Honolulu, USA Professor of Vascular Surgery
Schulz CJ Bologna, Italy
Department of Vascular and Endovascular
Surgery Stolker RJ, MD, PhD
University of Hospital Heidelberg Department of Anesthesiology
Heidelberg, Germany Erasmus University Medical Center
Schuurmann RC, PhD
Department of Vascular Surgery Sullivan TM
St Antonius Hospital Minneapolis Heart Institute
Nieuwegein, The Netherlands Abbott Northwestern Hospital
Minneapolis, USA
Sharrock AE, MBBS, MSc, MRCS, LLB
Department of Military Surgery and Svensjö S, MD,
Trauma Department of Surgery
Royal Centre for Defence Medicine Falun County Hospital
Birmingham, UK Falun, Sweden
Shearman CP, BSc, MBBS, FRCS, MS T

University of Southampton
Southampton, UK Taneva GT, MD, Clinical research fellow
St Franziskus Hospital Münster
Skoog J, MD, PhD Münster, Germany
Sciences Taeymans K, MD
Department of Clinical Physiology Vascular Clinic ZNA
Linköping University Antwerp, Belgium
Linköping, Sweden
Ten Raa S, MD, PhD
Söderberg P, MD Department of Vascular Surgery
Department of Surgery Erasmus University Medical Center
Falun County Hospital Rotterdam, The Netherlands
Falun, Sweden
XXI
Thapar A, FFRCS, PhD, FHEA, PG Cert U
Med Ed
Academic Section of Vascular Surgery Urriza Rodriguez D, MChem, BMBC,
Imperial College London MRCS
London, UK Department of Vascular Surgery
John Radcliffe Hospital
Thorbjørnsen K, MD Oxford University Hospital NHS
Department of Surgery Foundation Trust
Gävle County Hospital Oxford, UK
Gävle, Sweden
V
Ting AC, MB, BS, MS, FRCS Van de Luijtgaarden KM, MD PhD
Division of Vascular & Endovascular Department of Vascular Surgery
Surgery Erasmus University Medical Center
Department of Surgery Rotterdam, The Netherlands
Pokfulam, Hong Kong Van Rijn MJ
Torsello GB, University Professor Erasmus University Medical Center
Münster University Hospital Rotterdam, The Netherlands
St. Franziskus Hospital
Münster, Germany Venermo M, MD, PhD
Torsello GF, MD, BA Helsinki University Hospital
Charité Universitältsmedizin University of Helsinki
Berlin, Germany Helsinki, Finland
Tranoulsee T Verhagen HJM

Department of Radiology Department of Vascular Surgery
University of British Columbia Erasmus University Medical Center
Vancouver, Canada Rotterdam, The Netherlands
Trimarchi S, MD Verbruggen P, MD
Associate Professor of Vascular Surgery Vascular Clinic ZNA
University of Bologna Antwerp, Belgium
Bologna, Italy
Voesten HGJM, MD
Tsillimparis N Centre of Excellence in Lymphovascular
Department for Vascular Medicine Medicine
University Heart Center Nij Smellinghe Hospital
University Medical Center Drachten, The Netherlands
Hamburg, Germany
W
Wanhainen A, MD, PhD
Section of Vascular Surgery
Uppsala University
Uppsala, Sweden
XXII
Welling RHA, BSc Z
University Medical Center Utrecht Zachrisson H, MD, PhD, Associate
Utrecht, The Netherlands Professor
Winther Nicolajsen, MD Sciences
Department of Vascular Surgery Department of Clinical Physiology
Aarhus University Hospital Linköping University
Arhus, Denmark Linköping, Sweden
Wipper S Zeller T, MD, PhD

Department for Vascular Medicine Department of Angiology
University Heart Center Universitäs-Herzzentrum Freiburg – Bad
University Medical Center Krozingen
Hamburg, Germany Bad Krozingen, Germany
Wyss TR, MD
Inselspital
Bern University Hospital
University of Bern
Bern, Switzerland
Y
Yammine H, MD
Sanger Heart and Vascular Institute
Charlotte, USA
Yeh CC, MD
Vascular Surgeon, Albany Medical Center
Hospital
Albany, USA
Yugueros X, MD
Cardiovascular Institute
University of Barcelona
Barcelona, Spain
XXIII
INTRODUCTION
2018 is a very key year of celebration. This series of books began

exactly 40 years ago. The first publisher was Pitman Medical and books
came out some time after the authors convened at the Charing Cross
Symposium. In 1984, when it was time for an atlas, “Vascular Surgical
Techniques”, the first edition was published by Butterworths.
At this point the authors realised that they would be keen to write for a
book provided that the chapters came out rapidly and ideally at the time
that the authors convened. We were lucky that W.B. Saunders agreed to
publish the series despite the fact that the editor was placed in the UK
and not in the USA! He flew the Atlantic to decide that W.B. Saunders
would break the rule and produce this series of textbooks and sell in the
USA and worldwide. At once the impact of the chapters increased and
the authors realised that work could be published within a few months
and the promotion of their work was far greater. As happens, publishers
merge and those individuals responsible for the excellent service were
restrained by new masters.
BIBA Publishing was created in 1999 and the first product was Vascular
News which now reaches a global circulation of 20,000. The publisher
agreed to publish the book and, since that moment, the book has been
available and seen at most vascular meetings in the world. The effect of
this has been for the authors to be extremely keen to write in this series
of books. The large number of chapters in this edition are from invitations
to some of those who will speak at the 40th Charing Cross Symposium to
take place at the end of April 2018. That Symposium is 40 years after the
original one and the book “Progress in Stroke Research 1” was edited by
Roger Greenhalgh and Frank Clifford Rose.
Selected chapters are found under the clear sections of the book:
Controversies —Acute Stroke—Thoracic Aortic—Abdominal
Aortic—Peripheral Arterial Ischaemia—Venous and Lymphatic. The
book is certainly up to date as it was written before the chapters were
spoken to a large audience at the 40th celebration of the Charing Cross
International Symposium to take place in Olympia Grand in the west of
London.
The title of the Symposium includes “40 Years of Looking Forward”.
The series of books are not symposium proceedings. Far from it. These
are chapters preceding the Symposium and the book is the basis of the
presentations that will be delivered at the Symposium. Topics tell their
own story but every year focus either on Controversies, Challenges or
Consensus.
It is hard to focus on particular high spots. Acute Stroke Controversies
include the CCSVI appraisal by Lindsay Machan. In this chapter, essen-
tially, Machan and his co-author dispel the concept that this intervention
affects the natural history of the underlying condition. The patients have
needed to know whether an intervention would alter the natural history of
XXI
their condition. False hopes needed to be corrected and we have the lat-
est information on the subject. It is important for specialists to know that
the procedure should not take place if this gives inappropriate encour-
agement to the patients that they will be cured by intervention. It seems
unlikely that they will be improved but at least it has done no harm.
The Thoracic Controversies section includes presentations on new
thoracic aortic procedures. Perhaps the cutting edge of the whole Charing
Cross Symposium in 2018 is the realisation that the arch of the aorta can
be reconstructed by endovascular means. However, interventions come
at a risk of stroke. This was realised with the transcatheter aortic valve
implantation (TAVI). Cerebral protection devices were introduced to try to
limit this. Chapters in this section relate to information to control cerebral
embolisation. At the meeting, results of the so-called STEP study will be
discussed. Experts share their information on how to eradicate Stroke
from Thoracic Endovascular Procedures. This will be illustrated by an
“aortic live” performance of an endovascular arch reconstruction to
show the audience just what the concerns are and how to minimise the
risks. Unfortunately, in this publication that movie cannot be shown but
will be online after CX.
Amongst the Abdominal Aortic Controversies, a huge area of interest
is in the follow-up results of endovascular aneurysm repair (EVAR). It is
widespread opinion that the original follow-up protocols were suboptimal.
In the Peripheral Arterial Controversies section, a huge controversy
is whether “endovascular first” is the right slogan for management a
critically ischaemic limb. Critical ischaemia was defined in 1981 with an
intention to recognise that, if arterial reconstruction was not performed
successfully, major amputation would follow. In many parts of the world,
“endovascular first” has become a practice but some open surgeons feel
that the surgical open method is not having a fair opportunity. There are
excellent chapters on this topic in the book. Vessel preparation, drug-
coated balloons, stents, drug-eluting stents, bioabsorbable scaffolds all
form part of the answers in peripheral arterial management.
Venous and Lymphatic Controversies focus on how to investigate,
how to intervene, best effect of these conditions. Superficial venous
management has moved very much towards the use of cyanoacrylate
glue occlusion. This can be done without tumescent anaesthesia. Some
have found mild allergies following this procedure and the pros and cons
of the use of cyanoacrylate are discussed in the book.
I am personally extremely grateful to the Faculty of the Charing
Cross Symposium who provided chapters for the book and to the BIBA
Publishing team that has been able to create such an excellent book in
time for the Symposium.
Roger M Greenhalgh
XXII
Acute stroke controversies
Carotid controversies
Debate: Routine completion
assessment is essential after
carotid endarterectomy—
for the motion
“Trust is good, but control is better.”
Vladimir Lenin
Introduction
Carotid endarterectomy has been established as the treatment of choice for patients
with a 50–99% symptomatic stenosis of the extracranial internal carotid artery.
In asymptomatic patients, endarterectomy should be considered if the degree of
stenosis amounts to 60% or more.1
Although there is a multitude of non-randomised and retrospective series, which
in part indicate intraoperative completion studies to be beneficial, there is still a
lack of prospective randomised data.
Due to this shortage of confirmatory trials, intraoperative completion studies
were disregarded for a long time in national and international guidelines.2,3
The recently published 2017 clinical practice guidelines of the European Society
for Vascular Surgery on management of atherosclerotic carotid and vertebral artery
disease mention for the first time that targeted monitoring and quality control
strategies may reduce perioperative stroke or death rates.1
Techniques used as intraoperative completion studies include intraoperative
angiography, intraoperative duplex ultrasound (IDUS), pulsatile wave Doppler
flowmetry, and angioscopy. In the following chapter, we aim to give an overview of
these methods, including their adherent strengths and drawbacks.
Techniques used as intraoperative completion studies

The simplest way to control the result after carotid endarterectomy is digital
palpation. The presence or absence of a pulse indicates a patent or occluded blood
vessel, respectively. Although the character of a pulse can give a hint as to possible
pathologies, this measure is not accurate and documentation is not practical.
According to the German statutory quality assurance database, some form
of intraoperative completion study during elective endarterectomy is executed
in 67% of procedures. Performed in 36%, angiography is the technique most
commonly applied, followed by IDUS and Doppler flowmetry (13% each).
5
Angiography
After reconstruction of the carotid bifurcation, the common carotid artery is

punctured retrogradely by means of an angiocatheter (Figure 1). For better
visualisation of the internal carotid artery and its intracranial branches, it is
advisable to execute an angiogram with the external carotid artery clamped. The
subsequent angiogram is performed with the external carotid artery unclamped.
A major strength of this technique is its wide availability and feasibility, with
little expenditure of extra operating time. The technique is relatively independent
of the administrator; nevertheless, interpretation can be challenging and there are
no officially recognised interpretation criteria to guide the decision on whether
Debate: Routine completion assessment is essential after carotid endarterectomy—for the motion •
intraoperative revision should or should not be performed.

Contraindications are limited to severe renal disease and allergy to iodine-
containing contrast media. Although used frequently in patients with renal
disease, the benefit of peri-interventional administration of sodium saline, sodium
bicarbonate, and acetylcysteine is not proven.4,5
Prophylactic pretreatment with H1 and H2 blockers and steroids can be used
in patients with a previous mild allergic reaction to contrast media. Although
gadolinium can serve as an alternative to iodinated contrast media in the previously
mentioned patient groups, its use comes along with reduced imaging quality.
Carotid angiography has itself been demonstrated to be associated with neurologic
complications.6 In very rare cases, the arterial needle puncture may cause dissection
or dislodgment of atheroma. Furthermore, angiography is associated with a certain
radiation exposure for the patient and the operating personnel.
IDUS
After reconstruction, a “hockey stick” shaped imaging probe is placed directly on
the carotid artery.
With frequencies up to 18MHz, the probes have a penetration depth of about
5mm but a high resolution.
The surgeon is able to perform B-mode, duplex, and pulsatile wave Doppler
ultrasound scans.
A B C
Figure 1: Intraoperative angiography. (A) Angiograms of the carotid bifurcation showing a flawless result; (B) a distal
clamping defect and mobile intima flap; and (C) an occlusion of the internal carotid artery.
6
A B
Figure 2: IDUS. (A) B-mode images of the carotid bifurcation showing a prominent proximal intima step; (B) a mobile
intima flap at the distal reconstruction site; and (C) an intraluminal thrombus in the internal carotid artery.
It is advisable that the investigation follows a standardised workflow. As proposed

by Ascher et al, a transverse B-mode scan of the carotid bifurcation is followed by
longitudinal scans,7 which should involve the proximal and distal intima step—in
particular, the latter is at risk of being elevated by the blood stream (Figure 2).7
Different interpretation criteria have been published. Regarding haemodynamic
criteria, a peak systolic velocity of less than 150cm/sec is usually interpreted as
physiologic.
A velocity ratio, defined as the ratio of the peak systolic velocity in the internal
carotid artery to the peak systolic velocity in the common carotid artery, of <2 is
also interpreted as normal.
A peak systolic velocity exceeding 150cm/sec or a veloctiy ratio of >2 indicates a
moderate stenosis. A severe stenosis is present if the peak systolic velocity exceeds
300cm/sec or if the Vr amounts to more than 3.5.8,9
With respect to morphologic criteria, a lesion is considered pathologic if residual
narrowing exceeds 30%. Furthermore, mobile intima flaps are considered relevant
if longer than 2mm in the internal carotid artery and larger than 3mm in the
common carotid artery.7,10,11
Doppler flowmetry
The flowmetry probe is C-shaped and consists of two ultrasonic transducers on one
side and a reflector on the opposite side of the blood vessel. Both transducers send
an ultrasonic beam upstream and downstream, which are reflected at the opposite
7
side and sensed on the same side of the vessel by a detector. Blood flow advances
or slows the ultrasonic beams depending on their direction and flow is calculated
using the difference between the two signals.12
After carotid endarterectomy, the probe is placed on the common carotid artery
to measure the whole carotid flow or the internal carotid artery and external carotid
artery flow separately by briefly clamping one of both vessels. The internal carotid
artery and external carotid artery flow can also be measured simultaneously.
Additionally, the pulsatility index, which is expressed as the ratio of the flow volume
amplitude to the mean flow volume, serves as an estimate of peripheral resistance.13
Due to the wide variety of flow volume patterns after endarterectomy, there is no
consensus regarding which threshold should indicate the necessity of intraoperative

revision. Therefore, flowmetry is not suitable to detect residual plaques or non-
occluding thrombi.
Angioscopy
With angioscopy, completion control is performed immediately prior to completion
of the reconstruction and, therefore, before blood flow is restored.
After all vessels have been back vented and flushed, the endoscope is inserted and
the lumen of the endarterectomised artery inspected. Naylor et al proclaimed that
intima flaps exceeding 3mm in length should be corrected and all residual thrombi
aspirated.14,15
The fact that angioscopy is performed before restoration of blood flow has
advantages and disadvantages. The major strength is that residual thrombi that
persist after irrigation can be prevented from embolising into the brain.
A drawback is that intima flaps that appear to lie flat against the vessel wall
might lift up as soon as blood flow is restored. Therefore, it is advisable to perform
angioscopy while irrigating the vessel with saline in order to simulate blood stream.
Current evidence
Despite a huge number of retrospective studies and prospective non-controlled case
series, a confirmatory trial to assess a potential benefit of one or another means of
intraoperative completion study is lacking.
Angiography
In a historic study published in 1986, Courbier et al compared their results of
endarterectomy with intraoperative angiography to those without completion
control.16 Angiography was used in the last 100 patients, whereas no angiography
was used in the prior 206 consecutive patients. The authors found that intraoperative
angiography reduced perioperative mortality from 2.9% to 1%, the permanent
stroke rate from 1.9% to 1%, and the temporary stroke rate from 6.3% to 1%.16
More recent trials have not able to obtain results of comparable definitiveness.
A prospective study including 914 endarterectomies published in 2006 did not
find a significant difference in outcomes after routine and selective angiographic
completion control.17
A recently published secondary data analysis of the German statutory quality
assurance database demonstrated for the first time that use of intraoperative
angiography or duplex ultrasound was associated with lower rates of in-hospital
stroke or death under real-world conditions in Germany. Despite the limitations
8
inherent to a retrospective investigation, with 142,074 included patients, the latter
analysis represents the largest series on this topic to date.18
Common limitations applying to most studies addressing the impact of
angiography on clinical outcome after carotid endarterectomy are small patient
numbers and a predominantly retrospective study design. Confirmatory randomised
controlled trials are lacking.
IDUS
The aforementioned limitations equally apply to studies assessing the effect of IDUS
on perioperative event rates after carotid endarterectomy. Although it has been
performed for approximately 30 years now, and despite a multitude of retrospective
studies and small prospective case series, an randomised controlled trial is lacking.
A retrospective study included 9,278 endarterectomy from the NYCAS (New
York Carotid Artery Surgery) trial. Some form of intraoperative completion study
was performed in 3,318 cases, with IDUS used in 585 instances. None of the
techniques showed a significant association with the perioperative stroke rate.19
In a prospective study on 53 patients, IDUS was found to possess the highest
sensitivity and specificity (100% each), followed by angiography (66% and 95.7%)
and flowmetry (16 and 97.8%).20
Despite IDUS presumably being the technique with the highest sensitivity for
detecting minor defects, it is unclear whether correction of these can reduce the
perioperative stroke rate. In fact, it has been shown that there is no significant
relationship between the presence of minor defects in IDUS and restenosis or
occlusion of the arteries assessed.21
The only study showing a significant association of intraoperative duplex
ultrasound with a lower perioperative risk was the aforementioned analysis of the
German quality assurance database. Application of intraoperative duplex ultrasound
was independently associated with lower in-hospital rates of stroke or death, any
stroke, death, and major stroke or death.18

Doppler flowmetry
Regarding intraoperative flowmetry, the evidence is even sparser. A study involving
116 endarterectomies aimed to compare flowmetry with IDUS and angiography.
No correlation between flowmetric results and Intraoperative duplex ultrasound or
angiography was found.12
A retrospective study on 6,115 endarterectomies aimed to assess the effect of
different surgeons’ practice patterns regarding use of completion studies on the
perioperative stroke or death rate.22 Some form of completion study was applied
in 5,554 endarterectomies, with Doppler flowmetry used in 3,520 cases. The
30-day stroke or death rates were significantly lower for surgeons who performed
intraoperative completion studies selectively (1.2%), and higher among those
who applied them routinely (2.4%). However, although trends were similar, this
difference did not maintain statistical significance after risk adjustment.22
In the aforementioned retrospective study of patients included in the NYCAS
study, Doppler flowmetry was used in 2,331 cases and not associated with the
perioperative stroke rate.19
9
Angioscopy
With 1,600 endarterectomies included over a 15-year period, Sharpe et al

reported on the largest cohort of patients undergoing caortid endarterectomy with
intraoperative angioscopic control. A remarkably low 30-day stroke or death rate
of 2.1% was achieved.14
An analysis of 1,305 patients prospectively included in the EVEREST trial
aimed to assess the impact of technical errors on ipsilateral carotid occlusion,
ipsilateral stroke, and the early restenosis rate.23 Angiography was used in 1,004
and angioscopy in 299 patients. Use of angioscopy and angiography did not show
a difference with respect to ipsilateral stroke.23
Conclusion
Retrospective, non-randomised registry data indicate that intraoperative completion
studies after carotid endarterectomy are associated with a lower risk of perioperative
stroke or death.18
Despite the lack of a randomised controlled trial assessing the effect of
intraoperative completion studies on the perioperative outcome of endarterectomy,
the pursuit of perfection of any surgeon should guide his or her action to achieve
the best possible result for the patient. Particularly for less experienced surgeons,
intraoperative completion studies help to discover technical imperfections, and
thus contribute to improving surgical technique and preventing possible sources
of perioperative stroke or restenosis during follow-up. Also experienced surgeons
using completion studies intraoperatively will inevitably detect pathologies that
warrant correction. Although the majority of pathologies might be prevented by a
perfect surgical technique, some of them (e.g. thrombus formation after irrigation
with heparinised saline) will not.
With the number needed to treat for endarterectomy to prevent a stroke at five
years being as high as 6.5 in symptomatic and 20 in asymptomatic patients, one of
the highest priorities must be not to cause any harm.24,25
Therefore, Vladimir Lenin’s famous and often recited quote —“trust is good, but
control is better”—can serve as paradigm for modern carotid surgery, in order to
improve patient safety and reduce morbidity.
10
Summary
• Techniques used as intraoperative completion studies in carotid

endarterectomy include angiography, intraoperative duplex ultrasound,
Doppler flowmetry, and angioscopy.
• Despite a lack of confirmatory randomised controlled trials retrospective
registry data indicate that intraoperative completion studies are beneficial
for the patient.
• To achieve the best possible result, any carotid surgeon should
consider implementing intraoperative completion studies in his routine
armamentarium.
References
1. Naylor AR, Ricco JB, de Borst GJ et al. Management of Atherosclerotic carotid and vertebral artery
disease: 2017 Clinical Practice Guidelines of the European Society for Vascular Surgery (ESVS). Eur J
Vasc Endovasc Surg 2018; 55 (1): 3–81.
2. Ricotta JJ, Aburahma A, Ascher E, et al. Updated Society for Vascular Surgery guidelines for
management of extracranial carotid disease: executive summary. Journal of Vascular Surgery 2011; 54
(3): 832–36.
3. Tendera M, Aboyans V, Bartelink ML, et al. ESC Guidelines on the diagnosis and treatment of peripheral
artery diseases: Document covering atherosclerotic disease of extracranial carotid and vertebral,
mesenteric, renal, upper and lower extremity arteries: the Task Force on the Diagnosis and Treatment
of Peripheral Artery Diseases of the European Society of Cardiology (ESC). European Heart Journal
2011; 32 (22): 2851–906.
4. Subramaniam RM, Suarez-Cuervo C, Wilson RF, et al. Effectiveness of Prevention Strategies for Contrast-
Induced Nephropathy: A Systematic Review and Meta-analysis. Ann Intern Med 2016; 164(6): 406–16.
5. Weisbord SD, Gallagher M, Jneid H, et al. Outcomes after angiography with sodium bicarbonate and
acetylcysteine. The New England journal of medicine 2017. Epub.
6. Derdeyn CP, Moran CJ, Cross DT, et al. Intraoperative digital subtraction angiography: a review of 112
consecutive examinations. AJNR 1995; 16 (2): 307–18.
7. Ascher E, Markevich N, Kallakuri S, et al. Intraoperative carotid artery duplex scanning in a modern

series of 650 consecutive primary endarterectomy procedures. Journal of Vascular Surgery 2004; 39
(2): 416–20.
8. Parsa P, Hodgkiss-Harlow K, Bandyk DF. Interpretation of intraoperative arterial duplex ultrasound
testing. Seminars in Vascular Surgery 2013; 26 (2-3): 105–10.
9. Mays BW, Towne JB, Seabrook GR, et al. Intraoperative carotid evaluation. Archives of Surgery 2000; 135
(5): 525–28.
10. Schanzer A, Hoel A, Owens CD, et al. Restenosis after carotid endarterectomy performed with routine
intraoperative duplex ultrasonography and arterial patch closure: a contemporary series. Vascular and
Endovascular Surgery 2007; 41 (3): 200–05.
11. Mullenix PS, Tollefson DF, Olsen SB, et al. Intraoperative duplex ultrasonography as an adjunct to
technical excellence in 100 consecutive carotid endarterectomies. American Journal of Surgery 2003;
185 (5): 445–49.
12. Winkler GA, Calligaro KD, Kolakowski S, et al. Comparison of intraoperative completion flowmeter
versus duplex ultrasonography and contrast arteriography for carotid endarterectomy. Vascular and
13. Aleksic M, Heckenkamp J, Gawenda M, Brunkwall J. Pulsatility index determination by flowmeter
measurement: a new indicator for vascular resistance? Eur Surg Res 2004; 36 (6): 345–49.
14. Sharpe R, Sayers RD, McCarthy MJ, et al. The war against error: a 15 year experience of completion
angioscopy following carotid endarterectomy. European Journal of Vascular and Endovascular Surgery
2012; 43 (2): 139–45.
11
15. Naylor AR, Sayers RD, McCarthy MJ, et al. Closing the loop: a 21-year audit of strategies for preventing
stroke and death following carotid endarterectomy. European Journal of Vascular and Endovascular
Surgery 2013; 46 (2): 161–70.
16. Courbier R, Jausseran JM, Reggi M, et al. Routine intraoperative carotid angiography: its impact on
operative morbidity and carotid restenosis. Journal of Vascular Surgery 1986; 3 (2): 343–50.
17. Pratesi C, Dorigo W, Troisi N, et al. Routine completion angiography during carotid endarterectomy is not
mandatory. European Journal of Vascular and Endovascular Surgery 2006; 32 (4): 369-73; discussion 74.
18. Knappich C, Kuehnl A, Tsantilas P, al. Intraoperative Completion Studies, Local Anesthesia, and
Antiplatelet Medication Are Associated With Lower Risk in Carotid Endarterectomy. Stroke 2017; 48
(4): 955–62.
19. Rockman CB, Halm EA. Intraoperative imaging: does it really improve perioperative outcomes
of carotid endarterectomy? Seminars in Vascular Surgery 2007; 20 (4): 236–43.
20. Lingenfelter KA, Fuller BC, Sullivan TM. Intraoperative assessment of carotid endarterectomy:
a comparison of techniques. Annals of Vascular Surgery 1995; 9 (3): 235–40.

21. Sawchuk AP, Flanigan DP, Machi J, et al. The fate of unrepaired minor technical defects detected by
intraoperative ultrasonography during carotid endarterectomy. Journal of Vascular Surgery 1989; 9 (5):
671–75
22. Wallaert JB, Goodney PP, Vignati JJ, et al. Completion imaging after carotid endarterectomy in the
Vascular Study Group of New England. Journal of Vascular Surgery 2011; 54 (2): 376–85.
23. Zannetti S, Cao P, De Rango P, et al. Intraoperative assessment of technical perfection in carotid
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24. Rothwell PM, Eliasziw M, Gutnikov SA, et al. Analysis of pooled data from the randomised controlled
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25. Naylor AR. Time to rethink management strategies in asymptomatic carotid artery disease. Nature
reviews Cardiology 2012; 9 (2): 116–24.
12
Debate: Routine completion
assessment following carotid
endarterectomy is essential—
against the motion
Introduction
Completion assessment following carotid endarterectomy is performed to ensure
technical adequacy beyond assessing patency alone, which can be done by handheld
Doppler (or historically, palpation). The types of technical complications looked
for on assessment include intimal flaps and thrombi. Its aim is to reduce the risk of
perioperative stroke and the likelihood of restenosis. There is a long running debate
in the published literature about the necessity of completion assessments and for its
supporters, the type of assessment that should be performed.1 The most commonly
performed intraoperative assessments are arteriography, duplex ultrasonography,
Doppler flowmeter and completion angioscopy.2,3
The debate has resurfaced recently, partly due to the publication of data from the
German quality assurance database that suggests that stroke and mortality rates are
lower if patients undergo completion assessment.4
The aim of this chapter is to explore the rationale and techniques used for
completion assessment and to show by reasoned argument that—other than
intraoperative handheld Doppler patency assessment—its use is unnecessary in
routine practice.
History of completion assessment

From the time that carotid endarterectomy emerged as an operative technique,
technical assessment of operative results has been considered of vital importance.5
The merits of arteriography were assessed by Chino et al in 1988, who found
that the technique was able to detect unacceptable technical errors in 14% of
endarterectomies.6 However, a majority of the errors were identified early in the
study cohort. As operative technique improved over time, fewer technical problems
were identified.
The question for today is whether routine completion assessment should still
be performed by surgeons who perform carotid endarterectomies with better
neurological monitoring (as is possible when performed under regional anaesthesia)
and in units that have a higher case load associated with better outcomes.
13
The need to perform completion assessment
Completion assessment is performed to assess for thrombus formation that

can result in emboli generation or flow limiting defects prior to tissue closure.
Common findings that may prompt re-exploration of an otherwise completed
carotid endarterectomy are the presence of an intimal flap, debris, or residual
atherosclerotic plaque. Other causes include thrombosis, dissection and significant
flow velocity abnormalities that require correction.7
Proponents of routine assessment claim that the detection of such problems
perioperatively followed by timely correction reduces the risk of stroke and
improves clinical outcomes. However, a large number of surgeons either never, or
only selectively, use completion assessment methods.
Types of completion assessment

Debate: Routine completion assessment following carotid endarterectomy is essential—against the motion •
The phrase “completion assessment” does not confer an immediate understanding

of the techniques involved in carrying out the assessment. As has been outlined in
the previous section, the types of abnormalities assessed for are wide-ranging and
each technique used for completion assessment has its own merit.
The most commonly used methods are arteriography, duplex ultrasonography or
the use of a Doppler flowmeter.2 In centres that have trained personnel, angioscopy
using a flexible endoscopic camera—the external diameter of which should be no
more than two thirds the diameter of the vessel lumen—can be used for intra-
arterial visualisation of defects and pathology.8
The challenge with all types of completion assessment is deciding what type and
severity of pathology when identified, should prompt re-exploration and revision
of the newly performed carotid endarterectomy. A consensus has not been reached
in the literature and indications remain subjective.3,9
What proponents will claim

Proponents for completion assessment will call on recent and prior studies to
defend their stance. This section highlights some of the evidence.
Knappich and colleagues have recently published data from the German quality
assurance database that suggests the use of completion angiography (relative risk
[RR], 0.80; 95% confidence interval [CI], 0.71–0.90) or duplex ultrasound (RR,
0.74; 95% CI, 0.63–0.88) were independently associated with lower in-hospital
stroke or death rates following carotid endarterectomy.4 In these data, intraoperative
completion studies were performed in 67% of cases. Naturally, the authors have
used these independent associations to suggest that completion assessment should
become routine and have published acceptable stroke rates in the symptomatic
patient group of 2.5%.4
Other recent data have also been used by authors to support routine completion
assessment.9 In these data 1,179 endarterectomies were studied and although
completion angiography found defects requiring revision in only 6.1% of cases,
carotid plaque length and performing an eversion endarterectomy were found to be
independent predictors of defects been seen on angiography.
Prior to the recent publication of data from the German database, a number of
published studies have suggested a benefit from routine completion assessment.
In 1993, a study was published by Kinney et al reporting that although the
14
30-day morbidity rates were similar whether completion duplex or angiographic
assessment was performed or not, there was a statistically significant increase in
late strokes (30-month follow up) in those patients with restenosis or occlusion of
the internal carotid artery. Restenosis rates were higher in those patients found to
have a residual flow abnormality post-surgery or who did not undergo completion
assessment.10
Other authors also assessed the merit of completion assessment in the “earlier
years” of carotid endarterectomy with the use of a duplex scan 24-hours post
procedure in addition to intraoperative Doppler flow assessment. This study
identified that of those patients that were symptomatic of ischaemic events post
operatively (n=4), three had developed a thrombus demonstrated during duplex
sonography. These thrombi were removed during re-exploration.11
Donaldson et al also published data on the merits of routine completion
angiography. Though combined stroke and transient ischaemic attack rates were low
(2.3%) and may have been impressive at the time, this number is now comparable to
data published from surgeons that do not routinely use completion assessment.12,13
The evidence against completion assessment

Perhaps the most compelling argument against performing completion assessment
comes when the German data are compared with that of the National Vascular
Registry (NVR) in the UK, where routine completion assessment is uncommon.
The 30-day stroke rate across the UK is 1.8%, which makes the 2.5% recorded by
Knappich and colleagues, less impressive.4,13 Furthermore, it is also worth noting
that according to the NVR, 93% of patients received antiplatelet medication
preoperatively and 89% were on a statin. Antiplatelet medication was shown to
reduce the risk of stroke in the German database too (RR, 0.83; 95% CI, 0.71–
0.97) and thus lower stroke rates may not be directly attributable to completion
assessment.
Evidence against completion assessment from other literature is also compelling.
The New England data for 6,115 endarterectomies do not provide assurance that
performing completion assessment (duplex ultrasonography or angiography for this
retrospective cohort) is of value. Those surgeons that performed routine completion
assessments (for >90% of cases) did not have better 30-day stroke/deaths rates
than those surgeons that selectively used completion assessment (2.4% vs. 1.2%
respectively, p=0.05). Even those surgeons that rarely used completion assessment
had better outcomes at 1.7%.7
More compelling data against the use of completion assessment was published
in 2007 from the NYCAS (New York Carotid Artery Surgery) study. Of the 9,278
endarterectomies performed in this retrospective study, 3,318 had at least one form
of completion assessment. No significant differences were seen in in perioperative
stroke rates between the two groups. Nor were there any significant differences
between the modality of completion assessment used.2
In a series of 914 carotid endarterectomies, Pratesi and colleagues studied two
groups: those patients that underwent routine completion assessment and those
that underwent operator dependent selective completion assessment. No statistically
significant differences were observed between the groups in terms of neurological
complications on awakening from anaesthetic or regarding the 30-day stoke and
death rate.14
15
Regarding the notion that performing a completion assessment, identifying
and correcting defects may prevent restenosis, data published have shown that
restenosis occurred in 5.5% of arteries that were free of a postoperative defect one
month following endarterectomy. Thus, it may not follow that a technically good
carotid endarterectomy will prevent restenosis. This is because the development of
intimal hyperplasia is a later event and other factors may influence documented
progression and regression rates.15
Finally, it is difficult to ignore the inherent risk of cerebral ischaemia associated
with revision surgery prompted by completion assessment. Ricco and colleagues
recorded a significantly higher transient ischaemic attack rate in patients that
underwent revision surgery with all events occurring within three hours of surgery.9
The role of angioscopy

In a 21-year effort to reduce the risks associated with carotid endarterectomy,

Naylor et al have published strategies to prevent stroke and death.3 In combination
with preoperative antiplatelet protocols, strict protocol management of post-
operative hypertension and routine transcranial Doppler recordings, Naylor et al
have described methods for successfully reducing peri and postoperative stroke
rates to <1% with the use of intraoperative carotid angioscopy. Routine angioscopy
plays a key role in their strategy and it is employed to detect intimal flaps and
newly formed thrombus. Their policy is to repair intimal flaps >3mm and aspirate
any luminal thrombus from the operative field.
Certainly impressive reductions in postoperative stroke rates are observed across
the 21-year study period, but is unlikely that angioscopy alone has contributed
to stroke reduction. It may however, be used effectively as part of a patient
management protocol that aims to reduce the risk of thromboembolic stroke from
preoperative planning through to postoperative care. It is also worth noting that
Naylor and his group routinely performs carotid endarterectomies under general
anaesthesia with routine arterial shunt use. This is important as the German registry
data demonstrated that performing endarterectomies under local anaesthesia is
independently associated with a lower risk of in-hospital stroke (RR, 0.85; 95%
CI, 0.75–0.95) and the role of angioscopy may be less beneficial in this cohort.4
One of the most compelling arguments for continuing to perform intraoperative
angioscopy is that although with increasing experience the rate of iatrogenic intimal
flap formation reduced, it was still possible for retained thrombus to occur possibly
secondary to bleeding from transected vasa vasorum and thus, angioscopy may play a
key role in identifying and treating a potentially important aetiological process.3,16,17 It
is important to re-emphasise, however, that it may be the pre, intra and postoperative
protocols rather than the intraoperative completion assessment alone that has led to
dramatic stroke reduction in the Naylor data as completion assessment alone with
angioscopy may not be enough to prevent postoperative strokes.18
Conclusion
Reducing the risk of stroke and death following carotid artery surgery is a complex
issue based on a number of factors, including but not limited to, technical success.
There are conflicting reports in the literature about the need for completion
assessment and a common sense approach is required to tackle the issue. Ultimately,
16
performing a carotid endarterectomy is only one vital step in patient management
to ensure a successful outcome and other factors such as optimal blood pressure
control are of vital importance. Outcomes for carotid endarterectomy have
improved over time and are now <2% in the UK, where a majority of surgeons do
not routinely use completion assessment, beyond intraoperative Doppler use.
Regarding more invasive assessments, it could be argued that direct vision trumps
all other techniques when it comes to assessing technical skill and the detection
of intraoperative thrombi, thus angioscopy could confer a greater advantage.
Nevertheless, angioscopy is not commonly used and plenty of surgeons have very
good operative results that highlights the fact that stroke reduction is multifactorial.
As Naylor states, the policies that have contributed to dramatic stroke reduction
in his department that are easily transferable are perioperative dual antiplatelet
use and postoperative hypertension guidelines. The adoption of these methods,
rather than routine completion assessment that has limited proof of efficacy and
blurred lines regarding when to intervene if abnormalities are detected, are likely
to contribute to greater stroke risk reduction.
The sensible approach is, where possible, for experienced operators to perform
carotid endarterectomies, preferably under local anaesthesia, that enables
intraoperative neurological assessment. Following completion of the carotid
endarterectomy, a hand-held Doppler probe should be used to assess flow through
the artery. Should this be satisfactory, the operation should be completed and the
patient only reinvestigated, or re-explored if new neurological deficits occur.
Summary
• Completion assessment is not routinely performed in the United Kingdom and

the national stroke rate is 1.8%.
• There are no agreed criteria to prompt intervention when abnormalities are
detected by any form of completion assessment.
References
1. Ricco JB, Schneider F, Illuminati G, Samson RH. The role of completion imaging following carotid
artery endarterectomy. J Vasc Surg 2013; 57 (5): 1432–39.
2. Rockman CB, Halm EA. Intraoperative imaging: Does it really improve perioperative outcomes of
carotid endarterectomy? Semin Vasc Surg 2007; 20 (4): 236–43.
3. Naylor AR, Sayers RD, McCarthy MJ, et al. Closing the loop: a 21-year audit of strategies for preventing
stroke and death following carotid endarterectomy. Eur J Vasc Endovasc Surg 2013; 46 (2): 161–70.
4. Knappich C, Kuehnl A, Tsantilas P, et al. Intraoperative completion studies, local anesthesia, and
antiplatelet medication are associated with lower risk in carotid endarterectomy. Stroke 2017; 48 (4):
955–62.
5. Quinones-Baldrich WJ, Moore WS. Intraoperative monitoring and use of the internal shunt during
carotid endarterectomy. Int Surg 1984; 69 (3): 207–13.
6. Chino ES, Gwinn BC. The impact of completion arteriography on results and technique of carotid
surgery. Ann Vasc Surg 1988; 2 (4): 326–31.
7. Wallaert JB, Goodney PP, Vignati JJ, et al. Completion imaging after carotid endarterectomy in the
Vascular Study Group of New England. J Vasc Surg 2011; 54 (2): 376–85.
17
8. Pevec WC. Angioscopy in vascular surgery: The state of the art. Annals of Vascular Surgery 1996; 10:
66–75.
9. Ricco JB, Régnault De La Mothe G, et al. Impact of routine completion angiography on the results
of primary carotid endarterectomy: A prospective study in a teaching hospital. European Journal of
Vascular and Endovascular Surgery 2011; 41: 579–88.
10. Kinney EV, Seabrook GR, Kinney LY, et al. The importance of intraoperative detection of residual flow
abnormalities after carotid artery endarterectomy. J Vasc Surg. 1993; 17 (5): 912–23.
11. Cuming R, Blair SD, Powell JT, Greenhalgh RM. The use of Duplex scanning to diagnose perioperative
carotid occlusions. Eur J Vasc Surg 1994; 8 (2): 143–47.
12. Donaldson MC, Ivarsson BL, Mannick JA, et al. Impact of completion angiography on operative
conduct and results of carotid endarterectomy. Ann Surg 1993; 217 (6): 682–87.
13. Watson S, Johal A, Heikkila K, Cromwell D. National Vascular Registry Annual Report 2017. https://
www.vsqip.org.uk/reports/2017-annual-report/ [date accessed 02 February 2018].
14. Pratesi C, Dorigo W, Troisi N, et al. Routine completion angiography during carotid endarterectomy is
not mandatory. Eur J Vasc Endovasc Surg 2006; 32 (4): 369–73.
15. Samson RH, Showalter DP, Yunis JP, et al. Haemodynamically significant early recurrent carotid stenosis:
An often self-limiting and self-reversing condition. J Vasc Surg 1999; 30 (3): 446–52.
16. Sharpe R, Sayers RD, McCarthy MJ, et al. The war against error: A 15 year experience of completion
angioscopy following carotid endarterectomy. Eur J Vasc Endovasc Surg 2012; 43 (2): 139–45.
17. Osman HY, Gibbons CP. Completion angioscopy following carotid endarterectomy by the eversion
technique or the standard longitudinal arteriotomy with patch closure. Ann R Coll Surg Engl 2001; 83
(3): 149–53.
18. Zannetti S, Cao P, De Rango P, et al. Intraoperative assessment of technical perfection in carotid
endarterectomy: a prospective analysis of 1305 completion procedures. Collaborators of the
EVEREST study group. Eversion versus standard carotid endartectomy. Eur J Vasc Endovasc Surg 1999;
18 (1): 52–58.
18
The majority of patients
neither require surveillance
nor reintervention after carotid
stenting/endarterectomy
AR Naylor
Introduction
The management of patients who develop restenoses after either carotid
endarterectomy or carotid artery stenting remains controversial. A number of
meta-analyses have detailed information regarding indications and outcomes
following reinterventions for restenosis,1,2 but none have systematically addressed
whether there is any evidence that restenosis—especially asymptomatic lesions—
are associated with an increased risk of late ipsilateral stroke.
Few guidelines have specifically addressed the management of restenosis after
carotid endarterectomy and carotid artery stenting. In 2011, US society guidelines
observed that “restenosis is generally benign and does not require revascularisation,
except when it leads to recurrent ischaemic symptoms or progresses to preocclusive
severity. Under these circumstances, it may be justifiable to repeat revascularisation,
either by carotid endarterectomy in the hands of an experienced surgeon or by carotid
artery stenting”.3 However, this advice never became a formal recommendation.
Furthermore, in a meta-analysis of non-randomised observational data, Fokkema
et al reported that almost two-thirds of reinterventions for restenoses after carotid
interventions were in patients with an asymptomatic restenosis after carotid
endarterectomy—suggesting that many surgeons and interventionists remained
reluctant not to reintervene on asymptomatic stenoses.4
The 2018 European Society for Vascular Surgery (ESVS) guidelines for the
management of carotid and vertebral artery disease advise that most patients
presenting with a symptomatic 50–99% restenosis should be considered for either
redo endarterectomy or stenting.5 This recommendation was largely based on
evidence supporting primary interventions in patients with symptomatic carotid
disease, as there is little published data for the management of symptomatic
restenoses after endarterectomy.
However, the vast majority of restenoses after endarterectomy (or stenting)
are asymptomatic, and it is this group of patients who have attracted the most
controversy. To address this issue, Kumar et al undertook a systematic review and
meta-analysis of rates of restenosis and late ipsilateral stroke in patients who had
been randomised within various endarterectomy and stenosis studies.6 The reason
why randomised controlled trials were used was that they were prospective, they
tended to be conducted with greater scientific rigour, selection bias is reduced
19
AR Naylor
ESVS Recommendation Class Level

Serial surveillance and reintervention for asymptomatic I C
restenoses >70% is recommended in patients who developed
neurological symptoms during carotid clamping under local
The majority of patients neither require surveillance nor reintervention after carotid stenting/endarterectomy •
anaesthesia, or during balloon inflation (or proximal flow

reversal) during carotid stenting
ESVS Recommendation Class Level

Serial surveillance and reintervention for asymptomatic I C
restenoses >70% is recommended in carotid endarterectomy
patients who developed significant electrophysiological changes
during carotid clamping or whose mean middle cerebral artery
velocities fell below 15 cm/s on transcranial Doppler monitoring
during carotid clamping under general anaesthesia
Table 1: ESVS recommendations for selective surveillance and reintervention following carotid stenting or carotid endarterectomy§
because of the randomisation process, and most endpoints tended to be adjudicated

by independent observers. What made this study unique, however, was that the
principal investigators of the constituent trials were asked to provide previously
unpublished data on the status of the operated or stented internal carotid artery at
the time of the surveillance scan immediately prior to stroke onset. In that way, it
was possible to determine more accurately as to whether a previously asymptomatic
50–99% restenosis was associated with a higher risk of late ipsilateral stroke.
Rates of restenosis after endarterectomy intervention

There were 11 trials (4,249 patients) that reported restenosis rates >70% after any
type of endarterectomy (eversion, traditional, patched, and primarily closed).7–17
Over a mean of just under four years follow-up, the prevalence of restenosis
>70% was 5.8% (95% confidence interval [CI] 4.1-8.2). Five trials (n=1078
patients)12–15,17, reported restenosis rates >70% following patched endarterectomy.
Over a mean of 32 months, the prevalence of restenosis >70% was 4.1% (95%
CI 2.0-8.4).7–11,16 Six trials (2,916 patients) reported that over a mean follow-up
of five years, the prevalence of restenosis >70% in patients undergoing any sort of
endovascular intervention (stenting or balloon angioplasty alone) was 10.3% (95%
CI 6.0–16.4). Five trials (2,716 patients) reported that over a mean follow-up of
just over five years, the prevalence of restenosis >70% was 10% (95%CI 6.0–16.3)
in patients undergoing stenting.7,8,10,11,16
Restenosis and late ipsilateral stroke after intervention

Four trials (n=1,964 patients) reported on rates of late ipsilateral stroke following
carotid stenting.7,8,10,16 Over a mean follow-up of 50 months, only one of 125
stenting patients (0.8%) with an untreated asymptomatic >70% restenosis suffered
a late ipsilateral stroke. Out of 1,839 stenting patients with a 0–69% asymptomatic
restenosis after stenting, 40 (2%) suffered a late ipsilateral stroke (odd ratio [OR]
20
0.87 (95%CI 0.24–3.21); i.e. there was no evidence that a >70% asymptomatic
restenosis after carotid stenting was associated with an increased risk of late
ipsilateral stroke.
Seven trials (n=2,810 patients) reported on rates of late ipsilateral stroke following
stenting 7,8,10,13-15,17. Over a mean follow-up of 37 months, 7/135 endarterectomy
patients (5.2%) with a previously untreated asymptomatic >70% restenosis suffered
a late ipsilateral stroke. By contrast, of 40/2704 endarterectomy patients with a
0-69% asymptomatic restenosis after stenting, 40 (1.5%) had a late ipsilateral
stroke (OR 4.77 [95%CI 2.29-9.92]); i.e. there was a small but significant increase
in the risk of late ipsilateral stroke in patients with a >70% untreated asymptomatic
restenosis.
The implications for clinical practice

The available data would suggest that there is no compelling evidence that stenting
patients benefit from routine ultrasound surveillance and reintervention in those who
develop a >70% asymptomatic restenosis. The vast majority could be reassured and
advised to seek urgent medical assistance should any recurrent symptoms occur. Even
if one did enter all stenting patients into routine surveillance and then reintervene on
everyone with an asymptomatic >70% restenosis, 97% of all late ipsilateral strokes
would still occur in the cohort who did not develop a >70% restenosis.
Whilst the meta-analysis did identify a small but significant increase in late
ipsilateral stroke in endarterectomy patients with an untreated asymptomatic
>70% restenosis, it is unlikely that a policy of reintervening on everyone would
significantly reduce rates of late ipsilateral stroke.
Using the data from the restenosis meta-analysis, about 4% of endarterectomy
patients will develop a restenosis >70% during the course of follow-up. This means
that approximately 1,700 endarterectomy patients would need to undergo serial
duplex ultrasound surveillance in order to identify 100 patients with an asymptomatic
restenosis >70%. Using data from meta-analysis of ipsilateral stroke risks in patients
with/without restenoses, the presence of an untreated, asymptomatic restenosis
>70% would be associated with a 5% risk of late ipsilateral stroke at 37 months.
If one assumes that all then underwent either redo endarterectomy or stenting, a
maximum of five strokes might be prevented. However, about three would suffer
AR Naylor
a perioperative stroke following either stenting or redo endarterectomy,3 meaning

that only about two late ipsilateral strokes might be prevented in the long term.
Moreover, 85% of all late ipsilateral strokes would still occur in patients who had no
evidence of a >70% restenosis. Unless the procedural risks of redo endarterectomy
or stenting can be kept <1% (unlikely), it is neither clinically nor cost-effective to
survey every endarterectomy patient to identify and reintervene on anyone with a
70–99% restenosis.
Understanding who does benefit from surveillance and

reintervention
Notwithstanding the above comments, the 2018 ESVS carotid guidelines do advise
that a small minority of patients do merit entry into an ultrasound surveillance
programme with reintervention for those developing >70% restenoses.5 These
are essentially patients who had evidence of poor collateralisation at the time
21
of endarterectomy or stenting and in whom progression to occlusion might be
AR Naylor
associated with a fatal or disabling stroke. In reality, this will only affect about 10%
of endarterectomy and stenting patients.
Summary
• Historically, the management of restenoses after carotid interventions has

been controversial.
• Symptomatic (50–99%) restenoses should be treated by redo carotid
endarterectomy or carotid artery stenting, with the choice being left to local
experience.
• Recent evidence suggests that the majority of asymptomatic (70–99%)
restenoses are rarely responsible for late ipsilateral stroke if left untreated.
• A small proportion of patients who develop significant 70-99% asymptomatic
restenoses should be offered redo carotid endarterectomy or stenting. These
might include patients who developed neurological symptoms during carotid
cross clamping (under local anaesthesia) or during proximal protection device
deployment (during stenting) or those who developed electrophysiological
or intra-operative blood flow abnormalities, suggesting that they might not
tolerate progression to carotid occlusion.
• The 2018 European Society for Vascular Surgery Carotid guidelines are the first
to provide recommendations on the management of restenoses after carotid
interventions.
References
1. Lattimer CR, Burnand KG. Recurrent carotid stenosis after carotid endarterectomy. Brit J Surg 1997; 84:
1206–19.
2. Bekelis K, Moses Z, Missios S, et al. Indications for treatment of recurrent carotid stenosis. Brit J Surg
2013; 100: 440–47.
3. Brott TG, Halperin JL, Abbara S, et al. 2011 ASA/ACCF/AHA/AANN/AANS/ACR/ ASNR/CNS/SAIP /SCAI/
SIR/SNIS/SVM/SVS guidelines on the management of patients with extracranial carotid and vertebral
artery disease. J Am Coll Cardiol 2011; 57: 1002–44.
4. Fokkema M, Vrijenhoek JEP, den Ruijter HM, et al. Stenting Versus Endarterectomy for Restenosis
Following Prior Ipsilateral Carotid Endarterectomy: An Individual Patient Data Meta-analysis. Ann Surg
2015; 261: 598–604.
5. Naylor AR, Ricco JB, de Borst GJ, et al. Management of atherosclerotic carotid and vertebral artery
Vasc Endovasc Surg 2018; 55: 3–81.
6. Kumar R, Batchelder A, Saratzis A, et al. Restenosis after carotid interventions and its relationship with
recurrent ipsilateral stroke: A systematic review and meta-analysis. European Journal of Vascular and
Endovascular Surgery 2017; 53: 766–75.
7. Mas JL, Arquizan C, Calvet D, et al. EVA-3S Investigators. Long-term follow-up study of endarterectomy
versus angioplasty in patients with symptomatic severe carotid stenosis trial. Stroke 2014; 45: 2750–56.
8. Eckstein HH, Ringleb P, Allenberg JR, et al. Results of the Stent-Protected Angioplasty versus
Carotid Endarterectomy (SPACE) study to treat symptomatic stenoses at two years: a multinational,
prospective, randomised trial. Lancet Neurol 2008; 7: 893–902.
9. Bonati LH, Ederle J, McCabe DJH, et al on behalf of the CAVATAS Investigators. Long-term risk of
carotid restenosis in patients randomly assigned to endovascular treatment or endarterectomy in
the Carotid and Vertebral Artery Transluminal Angioplasty Study (CAVATAS): long-term follow-up of a
randomised trial. Lancet Neurol 2009; 8: 908–17.
22
10. Lal BK, Beach KW, Roubin GS, et al Restenosis after carotid artery stenting and endarterectomy: a
secondary analysis of CREST, a randomised controlled trial. Lancet Neurology 2012; 11: 755–63.
11. Bonati LH, Dobson J, Featherstone RL, et al. Long-term outcomes after stenting versus endarterectomy
for treatment of symptomatic carotid stenosis: the International Carotid Stenting Study (ICSS)
randomised trial. Lancet 2015; 385: 529–38.
12. Mannheim D, Weller B, Vahadim E, Karmeli R. Carotid endarterectomy with a polyurethane patch
versus primary closure: A prospective randomized study. J Vasc Surg 2005; 41: 403.
13. AbuRahma AF, Hopkins ES, Robinson PA, et al. Prospective randomized trial of carotid endarterectomy
with Polytetrafluoroethylene versus collagen-impregnated Dacron (Hemoshield) patching: Late
follow-up. Ann Surg 2002; 237: 885–92.
14. AbuRahma AF, Stone PA, Elmore M, et al. Prospective randomized trial of ACUSEAL (Gore-Tex) vs
Finesse (Hemashield) patching during carotid endarterectomy: Long-term outcome. J Vasc Surg 2008;
48: 99-103.
15. Naylor AR, Hayes PD, Payne DA, et al. Randomized trial of vein versus Dacron patching during carotid
endarterectomy: Long-term results. J Vasc Surg 2004; 39: 985–93.
16. Steinbauer MGM, Pfister K, Greindl M, et al. carotid artery stenting: Results of a prospective, randomized,
single-center trial of carotid artery stenting vs carotid endarterectomy. J Vasc Surg 2008; 48: 93–98.
17. Stone PA, AbuRahma AF, Mousa AY, et al. Prospective randomized trial of ACUSEAL versus Vascu-Guard
patching in carotid endarterectomy. Ann Vasc Surg 2014; 28: 1530–38.
AR Naylor
23
Is there a role for carotid
endarterectomy or
carotid stenting in
preventing dementia?
S Ball and C McCollum
Introduction
Dementia is a progressive neurodegenerative disorder causing severe cognitive
impairment, behavioural changes and dependence on others. Sufferers lose weight,
quality of life, mobility, continence and may ultimately become bed bound.
Overall, 850,000 people have dementia in the UK—with one in 14 aged over
65—and dementia patients costs an estimated £26 billion/year. By 2025, an
estimated one million people will be living with dementia, translating into a 40%
increase in current numbers. Delaying the onset of the condition by five years
could potentially halve the number of dementia patients.1,2
The role of treating asymptomatic carotid artery disease has been widely
researched in relation to stroke prevention but its influence on dementia is less
clear. In this chapter, we review whether there is enough evidence to justify carotid
intervention to prevent dementia.
Background
Alzheimer’s disease and vascular dementia account for more than 80% of
all dementias, with considerable overlap clinically, epidemiologically and
histopathologically. Vascular risk factors are associated with an increased risk of
both but age remains the principal risk factor.
Cognitive decline in stroke patients is well known with a clear link between
stroke and dementia.3–4
As 70% of strokes are ischaemic, with emboli from carotid disease accounting
for the majority, the potential role of carotid disease in the causation of dementia
is obvious.5
Atherosclerotic disease in the carotid arteries is also associated with poorer
cognitive performance.6–8 The link between atherosclerotic disease and dementia is
equally strong for Alzheimer’s disease as it is for vascular dementia.9
Doepp suggested a common vascular pathway in the pathogenesis of both
vascular dementia and Alzheimer’s disease based on similar blood flow velocities
in the middle cerebral arteries but significantly impaired compared to controls.10
The same was true of cerebral blood flow, circulation time and blood flow volume.
25
Altered cerebral blood flow can be secondary to small artery disease, hypoperfusion
• S Ball and C McCollum
or embolism; carotid artery disease may cause the latter two.

Xiang explored the effects of carotid intima-media thickness and stenosis on
cognitive function in 2015 asymptomatic patients aged >65.11 Increased intima-
media thickness and hyperdense plaques were associated with poor cognitive
performance (odds ratio [OR] 1.96 and 4.72 respectively) and were independent
risk factors along with increased age and lower education levels. There was no
difference in cognition between those with normal carotid arteries and those with
mild/moderate stenosis but there was a significant difference between those with
Is there a role for carotid endarterectomy or carotid stenting in preventing dementia?
severe and moderate stenosis. The prevalence of cognitive impairment was higher
in those with left internal carotid artery stenosis, an observation made previously.12
Those with left internal carotid artery stenosis had an OR of 6.7 and 2.6 for
cognitive impairment and decline; an increased risk that persisted after adjustment
for right sided stenosis and vascular risk factors.
Declining cognitive function was associated with increasing intima-media
thickness and plaque index in two studies.13,14
However, it must be recognised that both these measures of early atherosclerotic
disease are likely to progress with increasing age.
A systematic review on carotid intima-media thickness and cognitive impairment
including 20 studies found a significant association in 14 of them.15
Hypoperfusion theory
The term cardiogenic dementia was first coined in 1977 when heart failure was
found to be associated with cognitive decline.16 The possibly overly simplistic
interpretation was that hypoperfusion impairs metabolism, causing amyloid plaques
and neurofibrillary tangles through altered protein synthesis.
The SMART study found severe or bilateral carotid artery stenosis was associated
with progression of brain atrophy, independent of age, sex and vascular risk
factors.17 Patients with large infarcts were excluded, which the authors interpreted
as indicating hypoperfusion. This study triggered a number of papers looking at the
effect of carotid artery stenosis on cerebral haemodynamics and cognition.
Balucani et al found significant differences in cognitive function when patients
with bilateral and unilateral stenosis were compared with those with no carotid
stenosis.18 Impaired cerebrovascular reserve related to the performance of the
relevant cerebral hemisphere. Cerebrovascular reserve was also impaired ipsilateral
to a carotid stenosis.
Balestrini et al evaluated the relationship between severe carotid stenosis,
haemodynamic impairment and cognitive decline.19 Compared to patients with
no stenosis, those with carotid stenosis had an increased probability of developing
cognitive impairment (OR 4.16, P<0.001) and if there was associated haemodynamic
impairment, the risk was markedly higher (OR 14.66; p <0.001).
The RECON (Randomised evaluation of carotid occlusion and neurocognition)
trial assessed whether cognitive function improved following EC-IC bypass compared
to best medical therapy in patients with recent symptomatic carotid occlusion.
While baseline data20 demonstrated that haemodynamic failure was independently
associated with cognitive impairment, the end results demonstrated that EC-IC
bypass was not superior to best medical therapy in improving cognition.20,21
26
Buratti et al performed a prospective three-year study involving patients with bilateral

severe carotid stenosis.22 In patients with bilateral stenosis, the chance of cognitive
decline was significantly associated with impaired cerebrovascular reactivity with the
chance of cognitive decline increasing as cerebrovascular reactivity severity increased.
However, the study was limited as no standardised neuropsychological test was used
and no imaging therefore being unable to elucidate the role of silent infarcts.
Cerebral emboli in dementia

Cognitive impairment frequently prolongs hospital stay following cardiac surgery
and autopsy studies on such patients are consistent with widespread microembolism
to the brain.23,24 This together with the observation that patients with prosthetic
heart valves and those undergoing carotid surgery had cognitive deficits led to the
hypothesis that widespread microembolism to the brain over a period of time leads
to cognitive impairment.24,25 Based on this, we published a series of papers on
the association between spontaneous cerebral emboli, as detected by transcranial
Doppler insonation of the middle cerebral artery, and dementia.24–29 The rate of
cognitive decline also related to the presence and number of cerebral emboli.
However, most patients with dementia did not have significant carotid stenosis and
any link between carotid disease and dementia was weak.27
The published literature records a clear association between multiple micro-
infarcts and dementia with the effect on dementia being driven by multiple cortical
infarcts.30–33 The aetiology of these infarcts is less clear and potentially includes
small vessel disease, intermittent focal ischaemia from marginal brain perfusion,
and cerebral microemboli.30, 32, 34, 35 There is very little in the literature linking
dementia to the severity of carotid disease itself.

Data from the Rotterdam Study on 1,015 randomly selected patients monitored
for a mean of 3.6 years showed silent brain infarcts detected by MRI doubled the risk
of dementia, an increased risk that remained significant even after adjustment for
white matter lesions and subcortical atrophy.36 Patients with infarcts at recruitment
suffered significantly steeper declines in cognition. Cognitive decline was also
greater in those with multiple infarcts and those who developed symptomatic
infarcts during follow-up.
Intervention
Chen reported cognitive function seven days before and three months after carotid
artery stenting demonstrating that those with impaired cognition initially were
significantly improved following stenting.37 There was no similar improvement
in controls where stenting was unsuccessful suggesting that is was not due to a
“practice effect”.
Similar benefits on cognitive function were reported in patients undergoing
stenting for carotid occlusion. Neurocognitive function was significantly improved
at three months but again there was only a small number of patients with no long-
term follow-up.38
Ghogawala et al reported that carotid endarterectomy was more likely to improve
middle cerebral artery blood flow and cognitive function when middle cerebral
artery blood flow was impaired initially.39
27
A systematic review of cognitive performance following carotid artery stenting
and carotid endarterectomy including 32 studies (25 following endarterectomy,

four following stenting and three comparing both) concluded that neurocognition
is not clearly affected.40 Some studies reported improvement and others impairment.
The main limitations in these studies were small numbers, varied follow-up and
the wide range of neuropsychological tests used. The patient population was also
variable; one study focused solely on asymptomatic patients, 10 symptomatic and
the rest a mixture.
Conclusion
There is a clear link between atherosclerotic disease, and dementia and there can be
little doubt that carotid artery disease plays a role. However, there is no adequate
evidence to show that dementia can be prevented or improved by either carotid
endarterectomy or stenting. Carotid artery disease may merely be a marker of the
severity of the underlying generalised atherosclerotic disease with emboli arising
from anywhere within the arterial circulation to the brain.
Summary
• There is a clear link between atherosclerotic disease and dementia, of which

carotid artery disease plays a role.
• There is insufficient evidence to suggest that carotid endarterectomy or
stenting can prevent dementia.
• Further, larger scale studies are needed to determine by what mechanism
carotid artery disease may be related to dementia and the long-term effect
carotid endarterectomy or stenting may have on cognition.
References
1. Demarin V, Zavoreo I, Kes VB. Carotid artery disease and cognitive impairment. Journal of the
Neurological Sciences 2012; 322: 107–11.
2. Dementia UK: Update: Alzheimer’s Society 2014. http://bit.ly/2mPoGN4. [Date accessed 19 January
2018]
3. O’Brien JT, Erkinjuntti T, Reisberg B, et al. Vascular cognitive impairment. Lancet Neurology 2003; 2:
89–98.
4. Desmond DW, Moroney JT, Sano M, Stern Y. Incidence of dementia after ischemic stroke: results of a
longitudinal study. Stroke 2002; 33: 2254–60.
5. Pohjasvaara T, Erkinjuntti T, Ylikoski R, et al. Clinical determinants of poststroke dementia. Stroke 1998;
29: 75–81.
6. Breteler MM, Claus JJ, Grobbee DE, Hofman A. Cardiovascular disease and distribution of cognitive
function in elderly people: the Rotterdam Study. BMJ 1994; 308:1604–08.
7. Hachinski V. Preventable senility: a call for action against the vascular dementias. Lancet 1992; 340:
645–48.
8. Romero JR, Beiser A, Seshadri S, et al. Carotid artery atherosclerosis, MRI indices of brain ischemia,
aging, and cognitive impairment: the Framingham study. Stroke 2009; 40:1590–96.
9. de la Torre JC. Alzheimer disease as a vascular disorder: nosological evidence. Stroke 2002; 33: 1152–62.
10. Doepp F, Valdueza JM, Schreiber SJ. Transcranial and extracranial ultrasound assessment of cerebral
hemodynamics in vascular and Alzheimer's dementia. Neurological Research 2006; 28: 645–49.
11. Xiang J, Zhang T, Yang QW, et al. Carotid artery atherosclerosis is correlated with cognitive impairment
in an elderly urban Chinese non-stroke population. Journal of Clinical Neuroscience 2013; 20: 1571–75.
28
12. Johnston SC, O'Meara ES, Manolio TA, et al. Cognitive impairment and decline are associated with

carotid artery disease in patients without clinically evident cerebrovascular disease. Ann Intern Med
2004; 140: 237–47.
13. Silvestrini M, Gobbi B, Pasqualetti P, et al. Carotid atherosclerosis and cognitive decline in patients with
Alzheimer's disease. Neurobiology of Aging 2009; 30: 1177–83.
14. Komulainen P, Kivipelto M, Lakka TA, et al. Carotid intima-media thickness and cognitive function in
elderly women: a population-based study. Neuroepidemiology 2007; 28: 207–13.
15. Saleh C. Carotid artery intima media thickness: a predictor of cognitive impairment? Frontiers in
Bioscience 2009; 2: 980–90.
16. Dementia C. Cardiogenic Dementia. Lancet 1977; 1(8001): 27–28.
17. Muller M, van der Graaf Y, et al. Carotid atherosclerosis and progression of brain atrophy: the SMART-MR
study. Annals of Neurology 2011; 70: 237–44.
18. Balucani C, Viticchi G, Falsetti L, Silvestrini M. Cerebral hemodynamics and cognitive performance in
bilateral asymptomatic carotid stenosis. Neurology 2012; 79(17): 1788–95.
19. Balestrini S, Perozzi C, Altamura C, et al. Severe carotid stenosis and impaired cerebral hemodynamics
can influence cognitive deterioration. Neurology 2013; 80(23): 2145–50.
20. Marshall RS, Festa JR, Cheung YK, et al. Cerebral hemodynamics and cognitive impairment: baseline
data from the RECON trial. Neurology 2012; 78: 250–55.
21. Marshall RS, Festa JR, Cheung YK, et al. Randomized Evaluation of carotid occlusion and neurocognition
(RECON) trial: main results. Neurology 2014; 82: 744–51.
22. Buratti L, Balucani C, Viticchi G, et al. Cognitive deterioration in bilateral asymptomatic severe carotid
stenosis. Stroke 2014; 45: 2072–77.
23. Moody DM, Bell MA, Challa VR, et al. Brain microemboli during cardiac surgery or aortography. Annals
of neurology 1990; 28:477–86.
24. Voshaar RC, Purandare N, Hardicre J, et al. Asymptomatic spontaneous cerebral emboli and cognitive
decline in a cohort of older people: a prospective study. Int J Geriatr Psychiatry 2007; 22: 794–800.
25. Purandare N, Welsh S, Hutchinson S, et al. Cerebral emboli and paradoxical embolisation in dementia: a
pilot study. Int J Geriatr Psychiatry 2005; 20: 12–16.
26. Purandare N, Voshaar RC, Morris J, et al. Asymptomatic spontaneous cerebral emboli predict cognitive
and functional decline in dementia. Biological Psychiatry 2007; 62: 339–44.
27. Purandare N, Burns A, Daly KJ, et al. Cerebral emboli as a potential cause of Alzheimer's disease and
vascular dementia: case-control study. BMJ 2006; 332:1119–24.

28. Purandare N, Burns A, Morris J, et al. Association of cerebral emboli with accelerated cognitive
deterioration in Alzheimer's disease and vascular dementia. The American Journal of Psychiatry 2012;
169: 300–08.
29. Purandare N, Oude Voshaar RC, McCollum C, et al. Paradoxical embolisation and cerebral white matter
lesions in dementia. The British Journal of Radiology 2008; 81: 30–04.
30. Arvanitakis Z, Leurgans SE, Barnes LL, et al. Microinfarct pathology, dementia, and cognitive systems.
Stroke 2011; 42: 722–27.
31. Sonnen JA, Larson EB, Crane PK, et al. Pathological correlates of dementia in a longitudinal, population-
based sample of aging. Annals of Neurology 2007; 62: 406–13.
32. Troncoso JC, Zonderman AB, Resnick SM, et al. Effect of infarcts on dementia in the Baltimore
longitudinal study of aging. Annals of Neurology 2008; 64: 168–76.
33. Brayne C, Richardson K, Matthews FE, et al. Neuropathological correlates of dementia in over-80-year-
old brain donors from the population-based Cambridge city over-75s cohort (CC75C) study. Journal of
Alzheimer’s Disease 2009; 18: 645.
34. Suter O-C, Sunthorn T, Kraftsik R, et al. Cerebral hypoperfusion generates cortical watershed
microinfarcts in Alzheimer disease. Stroke 2002; 33:1986–92.
35. Schneider JA, Boyle PA, Arvanitakis Z, et al. Subcortical infarcts, Alzheimer's disease pathology, and
memory function in older persons. Annals of Neurology 2007; 62: 59–66.
36. Vermeer SE, Prins ND, den Heijer T, et al. Silent brain infarcts and the risk of dementia and cognitive
decline. The New England Journal of Medicine 2003; 348: 1215–22.
37. Chen YH, Lin MS, Lee JK, et al. Carotid stenting improves cognitive function in asymptomatic cerebral
ischemia. International Journal of Cardiology 2012; 157(1): 104–07.
38. Lin MS, Chiu MJ, Wu YW, et al. Neurocognitive improvement after carotid artery stenting in patients
with chronic internal carotid artery occlusion and cerebral ischemia. Stroke 2011; 42 (10): 2850–54.
39. Ghogawala Z, Amin-Hanjani S, Curran J, Ciarleglio M, et al. The effect of carotid endarterectomy on
cerebral blood flow and cognitive function. Journal of Stroke and Cerebrovascular Diseases 2013;
22:1029–37.
40. De Rango P, Caso V, Leys D, et al. The role of carotid artery stenting and carotid endarterectomy in
cognitive performance: a systematic review. Stroke 2008; 39: 3116–-27.
29
Is protamine reversal of
heparin safe during carotid
endarterectomy?
JD Kakisis, C Antonopoulos, KG Moulakakis and
G Geroulakos
Introduction
Heparin use in vascular surgery is universal, but may lead to severe bleeding.
Unfractionated heparin is a natural polysaccharide as it contains a large number of
linear and polydisperse chains. Its first use as anticoagulant, in humans, occurred in
1935, and it is now used for treating many arterial and venous disorders. Heparin
is capable of interacting with coagulation cascade proteins and also inhibits platelet
function at high concentrations. Its anticoagulation effect comes from three sources:
binding to antithrombin III (ATIII); binding to heparin co-factor 2; and impairing
factor Xa generation. The most profound anticoagulation effect is through binding
to AT-III, which inactivates factors IIa, Xa, IXa, XIa, and XIIa.1
Heparinisation during major vascular procedures in which an arterial clamp is
applied is universal. However, bleeding complications may challenge the use of
heparin during vascular operations. This is mainly due to the fact that only one
third of the drug is able to participate in the major anticoagulant action of heparin
and because heparin contains a heterogeneous mix of molecules. As a result, its
variability is responsible for its unpredictable activity.1
Monitoring for bleeding after heparin use

In order to minimise the unpredictable risk of bleeding with heparin administration
during vascular surgery, many different ideas have been put forward. For example,
the use of activated clotting time (ACT) was introduced in the early 1970s in an
effort to quantify the degree of anticoagulation induced by heparin and, as a result,
to predict bleeding.2 ACT proved to be simple, inexpensive, reliable and more
effective than partial thromboplastin use. By establishing a reliable monitoring of
the level of intraoperative anticoagulation with ACT, reversal of heparin became
rapidly popular.
Protamine sulfate for heparin reversal was approved for medical use in the
USA in 1969. It is a 5-kDa cationic polypeptide derived from salmon sperm that
can bind negatively charged heparin.3 Its main mechanism of action is mediated
through binding to heparin and serves to neutralise the antithrombin-mediated
anticoagulant properties of heparin, with a rapid, concomitant clearing of the
resultant protamine-heparin complex by the reticuloendothelial system.3 Nowadays,
protamine is used in patients who develop significant bleeding complications after
31
heparin administration and to reverse the high concentrations of heparin required
• JD Kakisis, C Antonopoulos, KG Moulakakis and G Geroulakos
for patients undergoing cardiac surgery and cardiopulmonary bypass. Based on

the current instructions for use, one milligram of protamine sulphate neutralises
approximately 100 units of heparin. Because the half-life of heparin is 60–90
minutes when given as an intravenous infusion, the total amount administered
over the previous 2−2.5 hour should be taken into account when calculating the
protamine sulphate dose.4
Two major issues with protamine use during carotid

endarterectomy
Although protamine has been effectively used to reverse heparin during carotid
endarterectomy in cases of expected or ongoing bleeding, two main problems
may be attributed to its use. First, whereas therapeutic ACT values have been
established for cardiac surgery, appropriate anticoagulation for patients undergoing
endarterectomy is not entirely clear and, as a result, when to reverse heparin with
protamine has not been established.2 Second, although widely used for heparin
reversal, protamine has also been posited to be a source of coagulopathy, or “hidden
haemorrhage”, for more than 20 years.5 For these reasons, although administration
of heparin before carotid clamping is routine, its subsequent reversal with protamine
remains controversial—with many surgeons avoiding heparin reversal to minimise
the risk of thrombus formation on the endarterectomised surface of the artery
Is protamine reversal of heparin safe during carotid endarterectomy?
with the consequent risk of stroke. Thus, it is still under investigation whether
protamine neutralisation of heparin is required during endarterectomy.
Evidence from the latest meta-analyses

Two recent meta-analyses addressed the previous issue, evaluating the risks and
benefits of heparin reversal by protamine after endarterectomy.6,7 The study by
Newhall et al calculated relative risks (RRs) in order to summarise the event rates
of the studied outcomes.7 The authors found that the event rates did not differ
significantly between patients who received protamine vs. those who did not for the
following outcomes: stroke (RR 0.84; 95% confidence interval [CI], 0.55-1.29; I2=
5%; nine studies), myocardial infarction (RR, 0.89; 95%CI, 0.53-1.51; I2 = 0%;
three studies), or mortality (RR, 0.9, 95%CI, 0.62-1.29; I2 = 0%; seven studies).
The use of protamine was associated with a significant decrease in major bleeding
complications requiring reoperation (RR, 0.57; 95%CI, 0.39-0.84; I2 = 32%; 10
studies). The authors concluded that the use of protamine following endarterectomy
is associated with a reduction in bleeding complications, without increasing major
thrombotic outcomes, including stroke, myocardial infarction, or death.
Similarly, our synchronous study (Kakisis et al) identified all studies that
evaluated differences in stroke and wound haematoma rates among patients
receiving or not receiving protamine for heparin reversal after endarterectomy.6
Analysis of measured outcomes—namely haematoma, haematoma requiring
reoperation and stroke—was performed per patient, deriving odds ratios (ORs),
absolute risk reduction and numbers needed to treat (NNT). Seven studies were
included in the meta-analysis reporting on 3,817 patients receiving protamine after
endarterectomy and 6,070 patients not receiving protamine for heparin reversal.
Only one study was randomised, three studies were retrospective reviews, one
32
study was prospective, and two were post-hoc analyses of prospectively collected

data. The pooled incidence of wound haematoma in the “no protamine” group was
6% vs. 1.7% in patients who had received protamine, the absolute risk reduction
was 4.3%, and the NNT to prevent one wound haematoma was 23. Concerning
wound haematoma requiring reoperation, the pooled incidence was 3.6% in the
“no protamine” group vs. 1.1% in patients who had received protamine, the
absolute risk reduction was 2.5% and the NNT 40. Consequently, we recorded
a statistically significant reduction both in wound haematoma (OR, 0.36, 95%
CI, 0.21–0.63; p<0.001), as well as in wound haematoma requiring reoperation
(OR, 0.42, 95% CI, 0.22–0.80; p<0.008) after heparin reversal with protamine
in patients undergoing endarterectomy. By contrast, no significant difference was
observed in stroke rates between groups of patients that received and did not receive
protamine (OR, 0.71, 95% CI, 0.49–1.03; p=0.07). The analysis was extended to
include a detailed meta-regression analysis to examine whether the documented
differences were modified by potentially meaningful predictors, namely publication
year, general anaesthesia used, number of patients treated, mean age (years), males,
neurological symptoms, use of patch and use of shunt. Meta-regression analysis did
not reveal any significant effect mediated by the examined modifiers. We concluded
that heparin reversal with protamine seems to reduce the risk of wound haematoma,
without increasing the risk of procedural stroke.

The limitations of the current evidence base
Although both meta-analyses provided enough evidence that reversal with
protamine is both efficient and safe, major limitations exist. In both publications,
the quality of the included studies varied, mainly due to the observational nature
of the eligible studies. Furthermore, the eligible studies spanned over a 20-year
period, which may have introduced a significant temporal trend. This was also
magnified by the fact that improvements in patient selection, medical therapy,
and preoperative management have occurred during this long period. Moreover,
differences among studies in the perioperative use of antithrombotic therapy and
the missing information on the character of the strokes may also have played an
important role. Another important key element is that some eligible studies were
performed in academic centres and others were single-surgeon trials and as a result
might not reflect “real-life” experience. Moreover, outcomes of interest, like “stroke”
and “bleeding” were not always similarly defined among all studies and differences
in operative technique and patient characteristics might have introduced clinical
heterogeneity. Inconsistency among the eligible studies also existed in the use of
wound drains, the reported dose of heparin and protamine, the exact timing of
heparin reversal, the timing of carotid endarterectomy in patients with recent
stroke and the type of anaesthesia used.
Evidence from registries

A review of 10,059 endarterectomy, excluding concomitant coronary bypass, performed
within the Vascular Study Group of New England (VSGNE) from January 2003 to
July 2012, revealed that protamine use increased over time by surgeons participating in
the VSGNE from 43% in 2003 to 62% by 2010.8 The rate of reoperation for bleeding
was 1.44% in patients who did not receive protamine vs. 0.6% in the protamine
33
treated patients, corresponding to a relative risk reduction of 57.2% (p<0.001).
There were no differences in the rate of postoperative myocardial infarction (1.1% vs.
1.09%) and the rate of stroke or death (1.1% vs 1.03%) between protamine treated
and untreated patients, respectively. Surgeons who used protamine routinely had the
lowest reoperation for bleeding rate (0.5%; p<0.001) compared with those using
protamine selectively (1.4%) or rarely (1.5%). There were no differences in the rate of
postoperative myocardial infarction (0.9%, 1.2%, 1.1%; p=0.7) and stroke or death
rates (1.0%, 1.2%, 1.0%; p=0.656) for rare, selective, and routine users of protamine.
Similarly to the meta-analyses, the findings of the VSGNE registry are limited
by the lack of data about heparin and protamine dosing as well as the lack of
information about protamine adverse events.
The need to be aware of the side-effects of protamine

The vascular surgeon and the anaesthetist should be aware of the potentially
deleterious protamine reactions after intravenous administration, including
reduction in myocardial contractility, increased pulmonary artery and venous
pressure, inhibition of platelet aggregation, reduction in platelet number and
prolongation of prothrombin and partial thromboplastin times.9 Interestingly,
protamine administration causes peripheral vasodilatation from histamine release
and hypotension, especially when it is rapidly infused and this should be taken
under consideration, especially when its administration is combined with carotid
de-clamping.10 Among all, the most serious reaction to protamine is anaphylaxis,

characterised by circulatory shock, severe bronchospasm, and occasionally cardiac
arrest.9
Another important issue when using protamine is that appropriate protamine
dosing is crucial. The reason is that protamine in the absence of heparin acts like
an anticoagulant by inhibiting platelet function, coagulation factors (II, V, VII,
VIII, and X), and clot strength as a result of the promotion of fibrinolysis.10 As a
result, overdosing increases the risk of bleeding. This means that, although heparin
is generally neutralised by protamine in a 1:1 protamine to heparin dosing ratio,
the time since heparin administration and the consequent breakdown of heparin
should also be taken into account.10
Critical appraisal of protamine for heparin reversal

Although serious evidence that protamine can be effectively used for heparin reversal
has been provided, many studies and the two powered meta-analyses discussed
above have proposed that further research should be conducted.6,7 Until this
evidence is available, some authors have proposed a more “conservative” approach;
“we recommend the use of protamine in carotid endarterectomy only in patients
with suspected residual heparin levels”.10 Given, however, the typical length of
carotid surgery—normally, less than the half-life of heparin—this strategy will lead
to protamine administration in almost all of the patients.
In any case, it should be acknowledged that heparin is not the only factor to
blame in cases of postoperative bleeding, since several other risk factors have been
recognised including intraoperative hypotension, postoperative hypertension, and
dual antiplatelet therapy, whereas the effect of clopidogrel versus aspirin on the risk
of wound haematoma after endarterectomy remains debatable.6 Similarly, protamine
34
is neither the only important risk factor nor (probably) the most important for

perioperative stroke in patients undergoing carotid endarterectomy. Cerebral
ischaemia during carotid clamping as well as embolism during manipulation of the
carotid artery before clamping, during clamping with a shunt, or after unclamping
as a result either of technical defects or damage from a clamp or a shunt, are the
most probable causes of endarterectomy-related stroke.
Conclusion
There is enough evidence to support the European Society for Vascular Surgery
2017 recommendation that “Protamine reversal of heparin should be considered
to prevent neck haematomas requiring re-exploration”.11 This recommendation,
however, is rightfully rated as Class IIa (weight of evidence/opinion is in favour of
usefulness/efficacy), Level B (data derived from a single randomised clinical trial
or large non-randomised studies), since current data cannot be considered robust
enough to support a stronger recommendation.
Summary
• Protamine administration at the conclusion of carotid endarterectomy remains

controversial with some vascular surgeons supporting the routine use of

protamine to minimise the risk of bleeding, whereas others avoid heparin
reversal for the fear of stroke.
• Meta-analyses of the available studies, summarising data from more than
10,000 patients, reveal that heparin reversal with protamine significantly
reduces the risk of both “wound hematoma” as well as “wound haematoma
requiring reoperation”, without increasing the risk of postoperative stroke,
myocardial infarction or mortality.
• These findings are limited by the fact that they are based on only one
randomised controlled trial, whereas the effect of several other factors should
also be taken into account, e.g. the use of wound drains, perioperative
antiplatelet administration, dose and timing of heparin and protamine
infusion, the timing of endarterectomy in patients with recent stroke, the
choice of anaesthesia etc.
• There is enough evidence to support the ESVS 2018 recommendation
that “Protamine reversal of heparin should be considered to prevent neck
haematomas requiring re-exploration” (Class IIa, Level of evidence B).
• Appropriately powered randomised controlled trials with standardised doses
of heparin and protamine, regular ACT monitoring and well-controlled
confounders are needed to increase the level of evidence of the current
recommendation.
35
References
1. Goldhammer JE, Zimmerman D. Pro: activated clotting time should be monitored during heparinization
for vascular Surgery. J Cardiothorac Vasc Anesth 2018 (in press).
2. Poisik A, Heyer EJ, Solomon RA, et al. Safety and efficacy of fixed-dose heparin in carotid
endarterectomy. Neurosurgery 1999; 45 (3): 434–42.
3. Ni Ainle F, Preston RJ, Jenkins PV, et al. Protamine sulfate down-regulates thrombin generation by
inhibiting factor V activation. Blood 2009; 114 (8): 1658–65.
4. Matthew R, Wilson R, Campbell T. Chapter 23—Hemostasis and anticoagulants. Handbook of
Pharmacogenomics and Stratified Medicine: Academic Press; 2014.
5. Nielsen VG, Malayaman SN. Protamine sulfate: crouching clot or hidden hemorrhage? Anesth Analg
2010; 111 (3): 593–94.
6. Kakisis JD, Antonopoulos CN, Moulakakis KG, et al. Protamine reduces bleeding complications without
Increasing the risk of stroke after carotid endarterectomy: a meta-analysis. Eur J Vasc Endovasc Surg
2016; 52 (3): 296–307.
7. Newhall KA, Saunders EC, Larson RJ, et al. Use of protamine for anticoagulation during carotid
endarterectomy: a meta-analysis. JAMA Surg 2016; 151 (3): 247–55.
8. Patel RB, Beaulieu P, Homa K, et al. Shared quality data are associated with increased protamine use
and reduced bleeding complications after carotid endarterectomy in the Vascular Study Group of
New England. J Vasc Surg 2013; 58 (6): 1518–24.
9. Dorman BH, Elliott BM, Spinale FG, et al. Protamine use during peripheral vascular surgery: a
prospective randomized trial. J Vasc Surg 1995; 22 (3): 248–56.
10. Meesters MI, Boer C. A critical note on protamine use in carotid endarterectomy. J Vasc Surg 2017; 66
(3): 967–8.
11. Naylor AR, Ricco JB, de Borst GJ, et al. Management of atherosclerotic carotid and vertebral artery
Vasc Endovasc Surg 2018 (in press).
36
Cerebral controversies
CCSVI appraisal is
again required
L Machan and T Traboulsee
Introduction
Chronic cerebrospinal venous insufficiency (CCSVI)—described as a combination
of extracranial venous structural and flow anomalies—was proposed as a
contributory factor to the pathogenesis and disabling symptoms in multiple
sclerosis, and subsequently in other conditions including Alzheimer’s disease,
Parkinson’s disease, and Meniere’s disease.1–4 It was postulated that impaired venous
drainage would cause stasis, leading to perivenular iron deposition and triggering
inflammation. This pathogenic hypothesis has not been proven, and some studies
have shown venous narrowings as frequently in healthy volunteers as in multiple
sclerosis participants.5 In the early CCSVI literature, multiple unblinded studies
and case series suggested that venous dilation with or without intravascular stenting
could improve symptoms and modify the disease course in multiple sclerosis and
Meniere’s Disease.1,4,6
The evidence base

More recent sham-controlled studies on angioplasty in patients with multiple
sclerosis have not confirmed findings of the initial trials. In a multicentre Canadian
study, 104 participants were randomised 1:1 to receive balloon or sham venoplasty
of all stenoses and were followed for 48 weeks before crossing over to the alternate
intervention.7 Participants and research staff were blinded to intervention allocation.
Twenty-three sham and 21 venoplasty participants reported at least one adverse
event; one sham (2%) and five (10%) venoplasty participants had a serious adverse
event. The mean improvement in multiple sclerosis quality of life (MSQOL) -54
physical score was +1.3 (sham) and +1.4 (venoplasty) (p=0.95); MSQOL-54 mental
score +1.2 (sham) and -0.8 (venoplasty)(p=0.55). The conclusion of the authors
was that the data do not support the continued use of venoplasty of extracranial
jugular and/or azygous venous narrowing to improve patient reported outcomes,
chronic multiple sclerosis symptoms, or the disease course of multiple sclerosis.
In the BRAVE-DREAMS (Brain venous drainage exploited against multiple
sclerosis), a total of 115 patients underwent a randomised, double-blind, sham-
controlled, parallel-group trial in six multiple sclerosis centres in Italy. Two primary
endpoints were assessed at 12 months: a composite functional measure (i.e.,
walking control, balance, manual dexterity, post-void residual urine volume, and
visual acuity) and a measure of new combined brain lesions on magnetic resonance
imaging, including the proportion of lesion-free patients.8
Of the included 115 patients with relapsing-remitting multiple sclerosis, 76 were
allocated to the percutaneous transluminal angioplasty group and 39 to the sham
group. No serious adverse events occurred. The functional composite measure did
39
not differ between the angioplasty and sham groups (41.7% vs 48.7%; p=0.49).
• L Machan and T Traboulsee
The mean number of combined lesions on magnetic resonance imaging at six to 12

months were 0.47 in the angioplasty group vs. 1.27 in the sham group (p=0 .03;
adjusted p=0.09). The authors’ conclusions were that angioplasty was proven to be
a safe but largely ineffective technique and the treatment cannot be recommended
in patients with multiple sclerosis.
Conclusion
Endovascular medicine suffers from a lack of controlled trials. Two very well
performed studies on angioplasty for CCSVI failed to show a difference vs. sham.
CCSVI appraisal is again required
It is still hoped by some practitioners that a subgroup of patients can be identified

where endovascular therapy can relieve some symptoms. In a disease where a
significant placebo effect can happen, this is a particularly difficult task and to date
has not been discovered.
Summary
• CCSVI was proposed as a contributory factor to the pathogenesis and

disabling symptoms in multiple sclerosis
• Two very well performed studies on angioplasty for CCSVI failed to show a
difference vs. sham.
• It is still hoped by some practitioners that a subgroup of patients can be

identified where endovascular therapy can relieve some symptoms.
References
1. Zamboni P, Galeotti R, Menegatti E, et al. A prospective open-label study of endovascular treatment of
chronic cerebrospinal venous insufficiency. J Vasc Surg 2009; 50: 1348—58.
2. Beggs C, Chung CP, Bergsland N, et al. Jugular venous reflux and brain parenchyma volumes in elderly
patients with mild cognitive impairment and Alzheimer's disease. BMC Neurol 2013; 13: 157.
3. Liu M, Xu H, Wang Y, et al. Patterns of chronic venous insufficiency in the dural sinuses and extracranial
draining veins and their relationship with white matter hyperintensities for patients with Parkinson's
disease. J Vasc Surg 2015; 61: 1511—20.
4. Bruno A, Napolitano M, Califano L, et al. The prevalence of chronic cerebrospinal venous insufficiency
in Meniere disease: 24-Month Follow-up after Angioplasty. J Vasc Interv Radiol 2017; 28: 388–91.
5. Traboulsee AL, Knox KB, Machan L, et al. Prevalence of extracranial venous narrowing on catheter
venography in people with multiple sclerosis, their siblings, and unrelated healthy controls: a blinded,
case-control study. Lancet 2014; 3 83: 138–45.
6. Zagaglia S, Balestrini S, Perticaroli E, et al. Percutaneous transluminal angioplasty for chronic
cerebrospinal venous insufficiency in multiple sclerosis: dichotomy between subjective and objective
outcome scores. Neurol Sci 2013; 34: 2205–10.
7. Traboulsee T, Machan L, Girard M et al. Safety and efficacy of venoplasty in MS: a randomized, double
blind, sham-controlled phase II trial. In press.
8. Zamboni P, Tesio L, Galimberti S. Efficacy and safety of extracranial vein angioplasty in multiple
sclerosis: A randomized clinical trial. JAMA Neurol 2018; 75 (1): 35–43.
40
Quantitative analysis of
embolic filter debris load
during carotid artery stenting
in asymptomatic patients
F Grego, M Piazza, F Squizzato, A Angelini
and M Antonello
Introduction
The rationale for carotid revascularisation in the presence of significant stenosis is
to reduce the risk of stroke. Unfortunately, both carotid endarterectomy and the
endovascular approach (with angioplasty and stenting) are associated with a risk
of periprocedural stroke. Therefore, enormous efforts have been made in refining
techniques to reduce this risk with these procedures.
Stenting is characterised by a non-negligible risk of distal embolisation, derived
from guidewires and catheters manipulation in the aortic arch, navigation through
the carotid stenotic lesion, stent deployment, and ballooning.1,2 For these reasons,
one of the major advances has been the introduction of embolic protection devices
that are designed to capture debris that may potentially embolise further down the
carotid artery.3
However, embolic protection devices do not eliminate the risk of periprocedural
stroke as embolisation may still occur at the beginning of the stenting procedure
during embolic protection device plaque crossing. Microdebris that is not captured
by a filter may also lead to embolisation.
The analysis of the atheroembolic debris captured by a filter may be helpful
in the identification of the plaques that have the strongest risk of embolisation.
Analysis may also help to determine if there is any relationship between the amount
of debris in the filter and the occurrence of a neurological complication during
stenting. These aspects are even more important in patients with asymptomatic
carotid artery stenosis, in which the role of stenting is still debated.
For these reasons, we aimed to investigate the incidence of embolic material
captured in filter of a device during stenting in an asymptomatic patient cohort.
In particular, the quantitative analysis of the debris load was performed to
assess any association between the use of a filter and clinical relevant ischaemic
events and to identify possible correlation with preoperative clinical and
anatomical characteristics.
41
Selection criteria in asymptomatic patients
F Grego, M Piazza, F Squizzato, A Angelini et al
Based on current recommendations, endarterectomy still represents the gold standard

of treatment in patients with asymptomatic stenosis; and in our centre, it is offered
as first-line treatment. 4 Stenosis is, therefore, reserved for patients presenting with
significant “high risk” for open surgery or with hostile neck anatomy (but only in
presence of a suitable anatomy for stenting). This category of patients represents
the 15% of all asymptomatic cases in our experience.
The definition of “high risk” for endarterectomy is based on cardiac, pulmonary,
and kidney comorbidities.4 In this category of patients, a careful stratification of both
neurological risk and anatomical suitability for stenting is mandatory to assess which
type of treatment—between stenting and best medical therapy—is more appropriate
for each specific patient. For this purpose, we include the preoperative imaging
studies—carotid duplex ultrasound, computed tomography (CT) angiogram of the
arch, supra-aortic trunks and intracranial vessels, and cerebral CT.
Carotid duplex ultrasound was performed to assess the grade of stenosis, based on
velocimetry criteria, plaque echolucency and morphological characteristics.5,6 The
Quantitative analysis of embolic filter debris load during carotid artery stenting in asymptomatic patients •
presence of anechogenic plaques represents an exclusion criteria for stenting. Aortic

arch type and quality, carotid angulation and tortuosity as well as carotid plaque
length are evaluated at the preoperative CT scan. Also, a precise morphological
percentage of stenosis can be measured at the CT angiography. The cerebral CT is
used to evaluate the presence of any pre-existing ischaemic lesion.
We consider “at risk” carotid plaques according to the following parameters:
morphologically visible plaque determining >70% stenosis with concomitant
evidence of increased peak of systolic velocity >230 cm/s; any type of carotid
stenosis >70% in presence of contralateral carotid stenosis ≥50%; and any type
of stenosis >80%. Thus, stenting is offered to these patients and best medical
therapy is prescribed to all patients with asymptomatic carotid stenosis ≤70%
and carotid stenosis morphologically between 70% and 80% with peak systolic
velocity <230cm/s.
Stenting in asymptomatic patients

We believe that stenting is justified in high-risk asymptomatic patients because:
• The stenting perioperative stroke risk reported in the literature is extremely
variable (ranging from 1% to 2%, up to 10%), depending on the
analysed cohort7
• On the other hand, in the real-world practice, the benefit of best medical therapy
is not certain, especially because many patients do not apply as required the
“best medical therapy” for several reasons (no compliance, no statin toleration,
allergies, or not-responder to certain antiplatelet or anticoagulant therapy, do
not stop smoking)8,9
Also, it has been demonstrated by the Asymptomatic Carotid Stenosis and Risk
of Stroke (ACSRS) group that asymptomatic carotid stenosis >70%—depending
on the combination of several aspects as age, plaque morphology, smoking history
or previous contralateral transient ischaemia attack/stroke—may be associated with
a predicted stroke-risk at five years of between 5% and >20%.10
For these reasons, in our opinion, the universal benefit of best medical therapy
over stenting is not assured in asymptomatic patients. We believe that appropriate
42
“patient selection” is the key to success when deciding the type of treatment, taking
into account that we should offer a <3% stroke risk. Whichever treatment modality
carries the most advantageous risk–benefit ratio (stroke/no stroke) for specific
patient, should be chosen. Just as no two patients are exactly alike, the risk–benefit
ratio for stenting and best medical therapy are never identical between patients.
Embolic filter debris quantitative analysis

Besides the clinical benefit, embolic protection devices also offer the unique
chance to analyse the atherosclerotic debris captured by the device and this can be
considered an objective measure of embolisation during the procedure. We aimed
to perform a quantitative analysis of the amount of debris captured by filters during
stenting procedures, focusing on asymptomatic patients.3
The technique of embolic filter debris analysis is performed as follows. The filter
is immediately fixed in 10% neutral, buffered formalin just after retrieval in the
operating room. The filter is first gently mechanically separated from the metallic
support to obtain a flattened surface, thus facilitating the measurement of the
percentage of surface occupied by the debris. The obtained membrane is analysed;
images acquired in this configuration are used for the computerised morphometric
analysis with Image-Pro Plus software (Media Cybernetics). The total area of the
filter membrane and the area covered by particulate material are quantified (Figure
1). “Filter load” is defined as the amount of membrane surface occupied by debris,
expressed as percentage of the total area. The software automatically perform
measurements regarding filter surface occupied by the debris.
Figures 1: Example of Angioguard filter (Cordis) free from embolic debris before (A) and after preparation (B) for
embolic filter debris quantitative analysis. Angioguard filter with many athero-thrombus debris attached to the
membrane (C). Opened Angioguard membrane for the calculation of the relationship between total area of the filter
and area occupied from the debris by a dedicated software (D).
43
Figure 2: Frequency density distribution analysis of embolic filter derbis load (%), stratified by complicated vs.
uneventful carotid artery stenting procedures.
With this technique, we analysed a consecutive series of 278 stenting procedures

at our centre. In 198 cases, stenting was performed for patients at “high risk for
endarterectomy” (71%), in 37 (13%) to treat restenosis after endarterectomy, and
was performed in 92 (33%) patients for hostile neck anatomy. Deployment of a
filter was successful in all procedures. The devices used were the Angioguard Rx
emboli capture guidewire system (Cordis) and the SpiderFX embolic protection
device (Medtronic.).
The quantitative filter analysis revealed that debris was present in 74% of cases
(207), meaning there was no evidence of embolic debris in 26% of cases. The mean
debris load was 10±14.7% (median, 1; range 0–80). It was <10% in 203 patients
(73%), between 11% and 20% in 39 patients (14%), between 21% and 30% in
14 patients (5%), and >31% in 22 (8%). The frequency distribution of debris load
is represented in Figure 2.
Clinical relevance of embolic filter debris load

The quantity of debris may not be always directly relate to the occurrence of
adverse clinical events, and its clinical significance is an aspect that remains unclear,
based on the available literature. Our objective was to identify if there was any
relationship between debris quantity and clinical relevance.
In the analysed series, neurological complications included 14 transient ischaemic
attacks (5%), minor strokes (1.4%), and one major stroke (0.4%).4 When we
looked at the cohort of patients with any type of ischaemic neurological event
after stenting (stroke and transient ischaemic attack; n=19), they had a significantly
higher mean debris load compared with patients who did not have an event
(26.7±19% vs. 8.5±13.5%; p<0.001).
44
For this reason, we performed an observational frequency density distribution
analysis of debris load, stratified by complicated vs. uneventful procedures (Figure
2). We identified the presence of a debris load of >12.5% as the optimal cutoff
for the association with perioperative ischaemic events, with a sensitivity of 78%
and a specificity of 77% (area under the curve 0.81, 95% confidence interval [CI]
0.72–0.90).
This means that the correlation between neurologic event and debris quantity
becomes significant once the amount of debris cover more than 12.5% of the filter
surface. These patients represent about 25% of the total study population and
35% of those with any type of debris. Based on these results, this cutoff seems
appropriate to define a “clinically relevant” debris load.
Predictors of clinically relevant filter load

The following step was to identify if there was any anatomical or clinical predictor
of a clinically relevant filter load. We performed a multiple logistic regression, which
showed that age >75 years (odds ratio [OR] 2.56; 95%CI 1.38-4.81; p=0.003),
pre-existing ipsilateral ischaemic cerebral lesions (OR 2.09; 95%CI 1.00-5.11
P=.049), hypoechogenic plaque at the preoperative duplex ultrasound (OR 6.05;
95%CI 2.47-15.71; p<0.001), and plaque length >15mm (OR 1.79; 95%CI 1.02-
3.61; P=.047) were independent predictors of debris load >12.5%. Aortic arch
anatomical characteristics, aortic thrombus, type of stent, post-dilatation, and
other clinical factors were not associated with a clinically relevant debris load.
The concept that hypoechogenic plaques are at higher risk of embolisation has
already been reported by Giannakopoulos, who find that echolucent plaques were
associated to increased presence of embolic material; Malik et al—in their analysis
of 56 filters—showed that embolic potential is increased with heterogeneous and
irregular plaques, while restenosis after endarterectomy is associated with minimal
debris generation.11,12
We also found that a plaque length >15 mm is a predictor of a clinically
significant filter debris load. This result is in line with CREST data showing that
plaques longer than 12.85mm carry a higher perioperative stroke risk (OR 3.42,
95% CI 1.19-9.78); furthermore, a joint effect of the length of the lesion and the
nature of the plaque was demonstrated.13

Another two clinical factors were associated with a clinically relevant debris
load—age >75 years and pre-existing ipsilateral ischaemic cerebral lesions. It has
already been reported in another experience that older patients are at higher risk
of neurological complication during stenting, and this result corroborated by our
finding of a more pronounced embolisation.14 The presence of ipsilateral ischaemic
lesions at the preoperative CT as risk factor for neurological complications, was
described for symptomatic patients with more extensive white-matter lesions,15
but no previous study pointed this focus for asymptomatic patients undergoing
stenting. Our finding, similarly to those identified for symptomatic patients, may
be related to the fact that carotid plaques that have caused previous silent cerebral
infarcts, are more unstable and carry a higher risk of embolisation during the
procedure also in asymptomatic.
45
Improving patient selection
Previous analysis on filters collected after stenting have been published, but they
did not provide information on the correlation between debris load and clinical
relevant ischaemic event after stenting.16–19 This aspect is of interest, especially
when stenting is to be performed in asymptomatic patients, where its application
is still controversial. The identification of anatomical or clinical characteristics that
may define patients at higher risk of real embolisation may improve subselection
and furthermore stratify those who may benefit from medical therapy.
Of note, in the literature, the quantity and the size of embolised debris is reported
to be more pronounced in symptomatic carotid stenosis than in asymptomatic.16,17
Unfortunately, the majority of existing studies on debris merged together these
two completely different subgroups of patients; indeed, the anatomical predictors
of debris identified in these reports may not completely fit with asymptomatic
patient cohorts.
The identification of preoperative risk factors for embolisation should be stressed
instead especially in asymptomatic patients, were the neurologic risk associated
with stenting—in our opinion—must be maintained <2% to obtain a benefit in

terms of stroke risk prevention. For this reason, we included in this study only
asymptomatic patients, and the identification of risk factors for clinically relevant
embolisation may improve subselection and furthermore stratify those who may
benefit from medical therapy.
Summary
• Debris is detectable in most patients undergoing stenting, even if

asymptomatic (74% of cases).
• A debris load covering >12.5% of the filter surface, is associated to a
significantly increased risk of clinically relevant neurological complications
in the perioperative period.
• Age >75 years, pre-existing ipsilateral cerebral ischaemic lesions,
hypoechogenic plaque, and plaque length >15mm are predictors of debris
load >12.5%.
• These clinical and anatomical characteristics should be taken into account
when deciding for the best treatment in patients carrying asymptomatic
carotid stenosis.
References
1. Kastrup A, Nägele T, Gröschel K, et al. Incidence of new brain lesions after carotid stenting with and
without cerebral protection. Stroke 2006; 37 (9): 2312–16.
2. Doig D, Turner EL, Dobson J, et al. Predictors of stroke, myocardial Infarction or death within 30 days
of carotid artery stenting: results from the International Carotid Stenting Study. Eur J Vasc Endovasc
Surg 2016; 51 (3): 327–34.
3. Kastrup A, Gröschel K, Krapf H, et al. Early outcome of carotid angioplasty and stenting with and
without cerebral protection devices: a systematic review of the literature. Stroke 2003; 34(3): 813–19.
4. Ricotta JJ, Aburahma A, Ascher E, et al. Updated Society for Vascular Surgery guidelines for
management of extracranial carotid disease. J Vasc Surg 2011; 54 (3): e1–31.
46
5. Geroulakos G, Ramaswami G, Nicolaides A, et al. Characterization of symptomatic and asymptomatic
carotid plaques using high-resolution real-time ultrasonography. Br J Surg 1993; 80 (10): 1274–77.
6. Timaran CH, McKinsey JF, Schneider PA, et al. Reporting standards for carotid interventions from the
Society for Vascular Surgery. J Vasc Surg 2011; 53 (6): 1679–95.
7. Paraskevas KI, Kalmykov EL, Naylor AR. Stroke/death rates following carotid artery stenting and
carotid endarterectomy in contemporary administrative dataset registries: a systematic eeview. Eur J
8. Ahmad Z. Statin intolerance. Am J Cardiol 2014; 113 (10): 1765–71.
9. Guirgis M, Thompson P, Jansen S. Review of aspirin and clopidogrel resistance in peripheral arterial
disease. J Vasc Surg 2017; 66 (5): 1576–86.
10. Nicolaides AN, Kakkos SK, Kyriacou E, et al. Asymptomatic internal carotid artery stenosis and
cerebrovascular risk stratification. J Vasc Surg 2010; 52 (6): 1486–96.
11. Giannakopoulos TG, Moulakakis K, Sfyroeras GS, et al. Association between plaque echogenicity and
embolic material captured in filter during protected carotid angioplasty and stenting. Eur J Vasc
Endovasc Surg 2012; 43 (6): 627–31.
12. Malik RK, Landis GS, Sundick S, et al. Predicting embolic potential during carotid angioplasty and
stenting: analysis of captured particulate debris, ultrasound characteristics, and prior carotid
endarterectomy. J Vasc Surg 2010; 51 (2): 317–22.
13. Moore WS, Popma JJ, Roubin GS, et al. Carotid angiographic characteristics in the CREST trial were
major contributors to periprocedural stroke and death differences between carotid artery stenting
and carotid endarterectomy. J Vasc Surg 2016; 63(4): 851–57.
14. Hofmann R, Niessner A, Kypta A, et al. Risk score for peri-interventional complications of carotid artery
stenting. Stroke 2006; 37 (10): 2557–61.
15. Ederle J, Davagnanam I, van der Worp HB, et al. Effect of white-matter lesions on the risk of
periprocedural stroke after carotid artery stenting versus endarterectomy in the International Carotid
Stenting Study (ICSS): a prespecified analysis of data from a randomised trial. Lancet Neurol 2013; 12
(9): 866–72.
16. Brightwell RE, Ryder TA, Hamady M, et al. Size and nature of emboli produced during carotid artery
angioplasty and stenting: in vivo study. Int J Surg 2011; 9 (2): 177–82.
17. van Laanen JH, Hendriks JM, Verhagen HJ, et al. Quantity, particle size, and histologic composition of
embolic debris collected in a distal protection filter after carotid angioplasty and stenting: Correlation
with patient characteristics, timing of carotid artery stenting, and procedural details. J Thorac
Cardiovasc Surg 2013; 146 (2): 492–95.
18. Angelini A, Reimers B, Della Barbera M, et al. Cerebral protection during carotid artery stenting:
collection and histopathologic analysis of embolized debris. Stroke 2002; 33 (2): 456–61.
19. DeRubertis BG, Chaer RA, Gordon R, et al. Determining the quantity and character of carotid artery
embolic debris by electron microscopy and energy dispersive spectroscopy. J Vasc Surg 2007; 45 (4):
716–24.
47
Thoracic aortic controversies
Technique and technologies controversies
New thoracic descending
thoracic aortic stent graft
Thoracic endovascular aortic repair

(TEVAR) is the treatment of choice for most thoracic aortic pathologies from
aneurysm to dissection to traumatic injuries.1–3 The Valiant thoracic stent graft
(Medtronic)—a successor to the Talent thoracic stent graft—has been evaluated
and found to be safe and effective in multiple trials for the treatment of thoracic
aortic pathologies, including aneurysm, blunt aortic trauma, and aortic dissection
(acute, subacute, and chronic).4–8
More recently, the Valiant EVO global trial has begun enrolling patients to
evaluate the safety and effectiveness of the new Valiant Navion thoracic stent graft
system (Figure 1).9–10 This stent graft aims to improve outcomes for patients by
addressing some of the problems with existing devices, such as reducing the risk of
trauma to access vessels and to the aorta during deployment.
Potential benefits of a new endoprosthesis

While percutaneous endovascular aortic repair is feasible and safe irrespective
of the size of the introducer sheath and the nature of aortoiliac pathology, early
complications are most often associated with sheath sizes ≥18Fr.11 Unfavourable
iliac artery anatomy—including small calibre iliac artery, tortuosity, or occlusive
disease—limits the passage of the large-diameter delivery sheaths that have
traditionally been required for TEVAR procedures.12–13 The Valiant Navion delivery
system has a lower profile, with up to a 4Fr decrease in sheath size compared with
Valiant Captivia, to facilitate access to small and tortuous iliac anatomy. This may
reduce the risk of access complications and expand the option of femoral access to
patients with small vessels.
Manipulation of the aortic arch has been associated with high rates of stroke
and mortality.14–15 The Valiant Navion thoracic stent graft system has several features
aimed at reducing trauma related to deployment of the stent graft. The lower profile
system reduces the need to drive bulky devices through the aortic arch. Similarly,
tapered tip lengths are reduced by about 1cm compared with the Captivia delivery
system, resulting in a smaller, shorter nosecone. The Valiant Navion stent graft also
uses an optimised multi-filament material—the same used in Endurant grafts (also
Medtronic)—increasing flexibility and allowing grafts to conform more closely to
arch anatomy, even in very steep arches. This increased endograft apposition to
the aortic arch may prevent bird-beak configuration, which has been associated
with adverse clinical events after TEVAR.16 Perhaps most importantly, the proximal
configuration has been changed from the previous generation Valiant Captivia
device. Compared with the Valiant stent graft, the Valiant Navion stent graft
has much shorter proximal struts in the “FreeFlo” component. It also includes a
53
• H Yammine, JK Ballast and FR Arko III
New thoracic descending thoracic aortic stent graft
Figure 1: The Valiant Navion thoracic stent graft system (Image from Medtronic).
proximal “CoveredSeal” configuration with tip capture. Since the proximal zone of
apposition is the site of many complications related to TEVAR, these modifications
might reduce trauma related to TEVAR.17
The Valiant Navion thoracic stent graft system also provides increased sizing
options, expanding the option for TEVAR to a wider range of aortic anatomy. A
smaller, 20mm diameter device is available, expanding options for patients with
smaller aortic size. Lengths up to 225mm are available, potentially reducing the
need to implant more than one device in order to provide adequate coverage. A
longer working length and longer hydrophilic coating length increase the ability to
reach the arch.
Conclusion
The Valiant Navion thoracic stent graft system is currently being investigated in
clinical trials as a premarket device. It has the potential to greatly expand TEVAR to
treat a wider range of aortic morphologies than is presently the case. Future studies
will evaluate the use of the Valiant Navion thoracic stent graft system as another
tool in the vascular surgeon’s arsenal to deal with thoracic aortic pathologies.
54
New thoracic descending thoracic aortic stent graft
Summary
• The Valiant Navion thoracic stent graft system has the potential to greatly
expand access to TEVAR for patients with a wider range of aortic morphology.
• The Valiant Navion delivery system has a lower profile, a smaller, shorter
nosecone, and increased flexibility.
• Compared with the Valiant stent graft, the Valiant Navion stent graft has much
shorter proximal struts in the FreeFlo component. It also includes a proximal
CoveredSeal configuration with tip capture.
References
1. Ranney DN, Cox ML, Yerokun B, et al. Long-term results of endovascular repair for descending thoracic
aortic aneurysms. Journal of Vascular Surgery 2017; 65 (1): e8-9.
2. Fattori R, Montgomery D, Lovato L, et al. Survival after endovascular therapy in patients with type

B aortic dissection: a report from the International Registry of Acute Aortic Dissection (IRAD). JACC:
Cardiovascular Interventions 2013; 6 (8): 876–82.
3. Nienaber CA, Kische S, Rousseau H, Eggebrecht H, et al. Endovascular repair of type B aortic dissection.
Circulation: Cardiovascular Interventions 2013; 6 (4): 407–16.
4. Fairman RM, Tuchek JM, Lee WA, et al. Pivotal results for the Medtronic Valiant thoracic stent graft
system in the VALOR II trial. Journal of Vascular Surgery 2012; 56 (5): 1222–31.
5. Bavaria JE, Brinkman WT, Hughes GC, et al. Outcomes of thoracic endovascular aortic repair in acute
type B aortic dissection: results from the Valiant United States Investigational Device Exemption
Study. Ann Thorac Surg 2015; 100: 802–8.
6. Matsumoto AH, Angle JF, Secic M, et al. Secondary procedures following thoracic aortic stent grafting
in the first 3 years of the VALOR test and VALOR II trials. J Vasc Interv Radiol 2014; 25: 685–92.
7. VIRTUE Registry Investigators. Mid-term outcomes and aortic remodelling after thoracic endovascular
repair for acute, subacute, and chronic aortic dissection: the VIRTUE Registry. Eur J Vasc Endovasc Surg
2014; 48: 363–71.
8. Lim CY. Endovascular repair in acute complicated type B aortic dissection: 3-year results from the
Valiant US investigational device exemption study. The Korean Journal of Thoracic and Cardiovascular
Surgery 2017; 50(3): 137.
9. First patient treated with Medtronic Valiant Evo Thoracic Stent Graft System. http://bit.ly/2GQXDtQ
[Date accessed 5 February 2018]
10. Verzini F. The New Valiant EVO device for TEVAR: What makes it better? LINC 2017.
11. Thomas RP, Kowald T, Schmuck B, et al. Retrospective evaluation of percutaneous access for TEVAR and
EVAR: Time to make it the standard approach? InRöFo-Fortschritte auf dem Gebiet der Röntgenstrahlen
und der bildgebenden Verfahren 2017; 189: 347–55.
12. Van Bogerijen GHW, Williams DM, Eliason JL, et al. Alternative access techniques with thoracic
endovascular aortic repair, open iliac conduit versus endoconduit technique. J Vasc Surg 2014; 60 (5):
1168–76.
13. Vandy FC, Girotti M, Williams DM, et al. Iliofemoral complications associated with thoracic endovascular
aortic repair: frequency, risk factors, and early and late outcomes. The Journal of Thoracic and
Cardiovascular Surgery 2014; 147 (3): 960–65.
14. Melissano G, Tschomba Y, Bertoglio L, et al. Analysis of stroke after TEVAR involving the aortic arch.
European Journal of Vascular and Endovascular Surgery 2012; 43 (3): 269–75.
15. Murphy EH, Stanley GA, Ilves M, et al. Thoracic endovascular repair (TEVAR) in the management of
aortic arch pathology. Annals of Vascular Surgery 2012; 26 (1): 55–66.
16. Ueda T, Fleischmann D, Dake MD, et al. Incomplete endograft apposition to the aortic arch: bird-
beak configuration increases risk of endoleak formation after thoracic endovascular aortic repair 1.
Radiology 2010; 255 (2): 645–52.
17. Peidro J, Boufi M, Hartung O, et al. Complications of the Zone of proximal anchoring after TEVAR: role
of aortic anatomy. Annals of Vascular Surgery 2017; 38: e18–19.
55
TEVAR using a new visceral
manifold device
B Safran and TS Maldonado
Introduction
Thoracoabdominal aortic aneurysms have posed a therapeutic challenge to the
vascular surgeon for decades. Traditionally these aneurysms have been treated with
large and complex open repairs, involving replacement of large segments of aorta
and visceral debranching.1, 2 The operations are high risk, as evidenced by reported
one year mortality rates of up to 31%.3 The perioperative course is often fraught
with complications including bleeding, renal failure and spinal cord ischaemia.3–5
Most patients typically require extended stays in the intensive care unit and only
a small percentage return to their baseline functional status, with approximately
20% being discharged to long-term facilities.6 In recent years, new and innovative
endovascular approaches have been developed to treat complex aneurysms involving
the visceral and renal branches of the aorta.7
In 1991, Parodi et al described the first endovascular repair of an infrarenal
abdominal aortic aneurysm.8 The endovascular approach was initially reserved for
the sickest patients, whose comorbidities posed a prohibitive risk for open repair.
However, as devices improved along with endovascular training, enodvascular
aneuyrsm repair (EVAR) largely came to replace open surgery as the preferred
treatment for most infrarenal aortic aneurysm.9, 10 Similarly, with the development
of new technology, thoracoabdominal aortic aneurysms have become increasingly
amenable to minimally invasive strategies. Examples of such strategies include
hybrid (combined open/endovascular) procedures, fenestrated repairs, and the
use of branched devices. While often less invasive, these novel approaches pose
new and unique challenges of their own. Many of the techniques are non-FDA
approved, some involve specialised back-table modifications, and most are rarely
universally applicable.11 The overarching goal among vascular specialists has been
to develop technology that is off-the-shelf, amenable to all aneurysm types and,
most importantly, safe to use.
Hybrid procedures
The hybrid procedures offer a viable, and arguably less precarious option, compared
with a purely open repair in appropriately selected patients. These procedures consist
of open debranching of the renal and visceral arteries, followed by endovascular
exclusion of the aneurysm.12,13 Despite benefits of avoiding thoracotomy, aortic
cross clamping and the major aortic reconstruction required for open repair,
hybrid procedures still confer substantial morbidity and mortality. In one series
reviewing hybrid operations, the overall long-term endoleak rate was 20.6%, the
reintervention rate was 13.7%, and the overall early and long-term mortality rate
for completed procedures was 15.5%.14 As such, hybrid procedures are typically
57
reserved for high-risk patients who are otherwise unsuitable for endovascular
• B Safran and TS Maldonado
therapy alone. As endovascular technology continues to improve, an increasing

percentage of aneurysms will probably be amenable to a purely endovascular
solution, and hybrid procedures may become obsolete.
Fenestrated devices
The use of a fenestrated stent graft to treat juxta-renal aneurysms in an animal
model was first described by Browne et al in 1999.15 Subsequently, the Zenith
fenestrated stent graft (Cook Medical) became the first commercially available
fenestrated device. The proximal body of this device contains up to three precisely
TEVAR using a new visceral manifold device
located holes (fenestrations) or scallops to accommodate the renal arteries and the
superior mesenteric artery. These must be precisely aligned with the respective vessel
and require custom made devices specific to each patient’s anatomy. Use of the
fenestrated abdominal aortic aneurysm endovascular graft is limited to juxta-renal
aneurysms and as per instructions for use, require a minimum of 4mm infrarenal
seal zone. Nevertheless, fenestrated devices, with up to four fenestrations, have been
used as part of physician-sponsored investigational device exemption protocols and
have shown promising results for treatment of more proximal disease. In a series
from the Cleveland Clinic, of 610 patients undergoing fenestrated repairs for type
IV thoracoabdominal aortic aneurysms (n=349) and juxta-renal aneurysms (n=258),
the eight-year aneurysm related mortality was only 2%—demonstrating the safety
and feasibility of this technique for select anatomy.16 Nonetheless, fenestrated repairs
remain complex and have been associated with complications such as poor renal
perfusion and resultant deterioration in kidney function. Adverse renal events have
been observed in up to 16% of patients without underlying renal dysfunction and
39% of patients with preoperative renal dysfunction, mostly due to postoperative
renal artery stenosis or stent occlusion.17 In practice, the fenestrated repairs require
significant perioperative planning and sizing. Moreover, fenestrated devices are
custom made and can take up to one month for production; thus, these devices
are rarely applicable in the setting of rupture and/or need for an urgent solution.
Branched endografts
Various types of branched endografts have also been used to repair thoracoabdominal
aortic aneurysms in poor surgical candidates. In 2007, Chuter et al reported a
procedural success rate of 100% in a series of 22 patients treated with physician-
assembled branched endografts for repair of complex thoracoabdominal aneurysms.7
While these results are encouraging, physician-assembled devices typically require
sophisticated manufacturing processes. Therefore, they are not widely applicable,
particularly in the emergent setting. The Zenith t-Branch endograft and the Gore
excluder thoracoabdominal branch endoprosthesis (TAMBE device) are designed
to address the need for an off-the-shelf branched device for use in elective and
urgent settings. The t-Branch stent is commercially available only outside the USA
but is restricted to use in aortic centres of excellence, while the TAMBE device is
currently only available in clinical trial.
The Zenith t-branch device is a tubular endograft with four branches that connect
to the coeliac, superior mesenteric and renal arteries via bridging stents (Figure 1).
In 2018, Spanos et al published results of 42 patients who underwent placement
58
A B
Figure 1: (A) The Zenith t-branch

device is a tubular endograft, (B) with
four branches that connect to the
coeliac, superior mesenteric and renal
arteries via bridging stents.

of the Cook t-Branch device for urgent thoracoabdominal aneurysm repairs. They
reported a technical success rate of 93% but noted spinal cord ischaemia in 21%
of patients, renal function impairment in 23% and a 30-day mortality rate of
14%.18 While the t-Branch device appears to offer significant versatility and may
be a feasible option for some patients, one potential limitation is that it requires
adequate working space within the aneurysm to accommodate the endograft as well
as the branches.
In 2014, Patrick Kelly (Sanford Health, Vascular Surgery, Sioux Falls, USA)
developed a novel branched endograft for thoracoabdominal aortic aneurysms that
promises to be fully off-the-shelf, requiring no customisation (Figure 2). The device
is modular and consists of a proximal bifurcated cuff for the thoracic aorta, a visceral
manifold with four branches (two renal arteries, coeliac artery, superior mesenteric
artery), a visceral bypass (for aneurysm exclusion), and an infrarenal bifurcation.
Importantly, this device requires only one measurement for the main body graft
(the proximal seal zone diameter) and does not depend on anatomical alignment,
thus avoiding a common constraint of other endo branch solutions. Additionally,
the procedure is stageable and provides unimpeded flow to the visceral segments
throughout the operation.19
Kelly et al published their results using this physician-assembled endograft on
a series of 14 patients. Three Crawford type II, four type III, four type IV, and
three Type V thoracoabdominal aneurysms were treated. There was no in-hospital,
30-day, or six-month mortality, but there was one case of in-hospital paraplegia,
and two cases of permanent dialysis. Clinical success was observed in 78.6% of
patients and technical success was observed in 85.7% of patients.19
Currently Medtronic, in conjunction with Kelly, has developed a prototype of
the multibranched stent graft system for endovascular treatment thoracoabdominal
aortic aneurysms. This off-the-shelf device is currently undergoing feasibility trials
59
Figure 2: Medtronic prototype of multibranch

stent graft: The graft deployment begins by
placing the thoracic bifurcated graft and visceral
manifold above the “branch vessels.” Next, each
of the branch vessels is stented from a proximal

position with a bridging technique. Once flow has
been secured to each of the involved branches,
the open limb of the proximal compartmentalising
graft can be extended distally, excluding the
diseased segment of vessel.
as part of physician-sponsored investigator device exemption at select centres in

the USA.
Spinal cord ischaemia

Spinal cord ischaemia following endovascular repair for thoracoabdominal aortic
aneurysm is an especially devastating complication. Regardless of approach or
technique, when large segments of thoracoabdominal aorta are covered, patients
are at increased risk of spinal cord ischaemia. A review of 142 consecutive patients
undergoing endovascular repair of thoracoabdominal aortic aneurysm demonstrated
a 16% rate of spinal cord ischaemia with percentage of thoracic aortic coverage
being the only significant risk factor.20 Several techniques have been described to
help mitigate the risks of spinal cord ischaemia.
Beck et al recently published their bundled protocol to help protect against spinal
cord ischaemia. It involves spinal cord drainage, medical management, blood pressure
control and haemoglobin goals. Patients randomised to the protocol were noted to
have a statistically significant decrease in the incidence of spinal cord ischaemia.21
Another technique that may reduce spinal cord ischaemia risk is performing the
repair in a staged fashion to maintain spinal cord perfusion and allow for optimal
collateralisation. In a retrospective review of 87 patients undergoing endovascular
thoracoabdominal aortic aneurysm repair, those who underwent staged repairs were
significantly less likely to develop spinal cord ischaemia.22
Conclusion
Recent technological advancements in endovascular surgery have led to a dramatic
paradigm shift in the management of complex thoracoabdominal aneurysms.
Formerly, the “gold standard”, traditional open repair may soon become the
60
exception, as novel devices are paving the way to safer and less morbid solutions.

Certain risks, especially spinal cord ischaemia, continue to plague physicians
treating patients with thoracoabdominal aortic aneurysm. Despite significant strides
towards advancing the field of endovascular surgery for thoracoabdominal aortic
aneurysms, much work needs to be done to better understand and minimise these
risks. The vascular community should expect an increasing number of innovative
and practical treatment options in the near future.
Summary
• Endovascular repair of thoracoabdominal aortic aneurysms continues to

evolve.

• While hybrid open/endovascular repairs may offer less of a physiologic insult
to patients as they avoid thoracotomy, aortic cross clamping and extensive
aortic repair, they still confer substantial morbidity and mortality.
• A number of branched technologies—including the TAMBE device and
t-Branch—are in development to achieve an “off the shelf” versatile device to
treat most thoracoabdominal aortic aneurysms.
• The t-Branch device has some commercial availability outside the USA, in
select aortic centres of excellence. Early experience has shown good technical
success (up to 93%) in when used for urgent repair of thoracoabdominal aortic
aneurysms, although spinal cord ischaemia and renal impairment remain
significant risks.
• Medtronic, in conjunction with Patrick Kelly, has developed a prototype
of the multibranched stent graft system for endovascular treatment
thoracoabdominal aortic aneurysms that promises to provide a true off the
shelf solution for a variety of thoracoabdominal aortic aneurysms anatomies.
• Spinal cord ischaemia remains a dreaded complication following endovascular
repair for thoracoabdominal aortic aneurysm despite advances in technology
and technique and appears to be largely related to length of aorta covered.
References
1. Kazen UP, Blohme L, Olsson C, Hultgren R. Open repair of aneurysms of the thoracoabdominal aorta.
The Thoracic and Cardiovascular Surgeon 2016; 64 (4): 275–80.
2. Rana MA, Gloviczki P, Duncan AA, et al. Comparison of open surgical techniques for repair of types III
and IV thoracoabdominal aortic aneurysms. Journal of Vascular Surgery 2017. Epub.
3. Rigberg DA, McGory ML, Zingmond DS, et al. Thirty-day mortality statistics underestimate the risk
of repair of thoracoabdominal aortic aneurysms: a statewide experience. Journal of Vascular Surgery.
2006; 43 (2): 217–22.
4. Conrad MF, Ye JY, Chung TK, et al. Spinal cord complications after thoracic aortic surgery: long-term
survival and functional status varies with deficit severity. Journal of Vascular Surgery 2008; 48 (1):47–53.
5. Dayama A, Sugano D, Reeves JG, et al. Early outcomes and perioperative risk assessment in elective
open thoracoabdominal aortic aneurysm repair: An analysis of national data over a five-year period.
Vascular 2016; 24 (1):3–8.
6. Rectenwald JE, Huber TS, Martin TD, et al. Functional outcome after thoracoabdominal aortic aneurysm
repair. Journal of Vascular Surgery 2002; 35 (4): 640–47.
7. Chuter TA, Rapp JH, Hiramoto JS, et al. Endovascular treatment of thoracoabdominal aortic aneurysms.
Journal of Vascular Surgery 2008; 47 (1): 6–16.
61
8. Parodi JC, Palmaz JC, Barone HD. Transfemoral intraluminal graft implantation for abdominal aortic
aneurysms. Annals of Vascular Surgery 1991; 5 (6): 491–99.

9. Greenhalgh RM, Brown LC, Kwong GP, et al. Comparison of endovascular aneurysm repair with open
repair in patients with abdominal aortic aneurysm (EVAR trial 1), 30-day operative mortality results:
randomised controlled trial. Lancet 2004; 364 (9437): 843–48.
10. Prinssen M, Verhoeven EL, Buth J, et al. A randomized trial comparing conventional and endovascular
repair of abdominal aortic aneurysms. The New England Journal of Medicine 2004; 351 (16): 1607–18.
11. Sweet MP, Starnes BW, Tatum B. Endovascular treatment of thoracoabdominal aortic aneurysm using
physician-modified endografts. Journal of Vascular Surgery 2015; 62 (5): 1160–67.
12. van de Mortel RH, Vahl AC, Balm R, et al. Collective experience with hybrid procedures for suprarenal
and thoracoabdominal aneurysms. Vascular 2008; 16 (3): 140–46.
13. Black SA, Wolfe JH, Clark M, et al. Complex thoracoabdominal aortic aneurysms: endovascular
exclusion with visceral revascularization. Journal of Vascular Surgery 2006; 43 (6):1081–89
14. Donas KP, Czerny M, Guber I, et al. Hybrid open-endovascular repair for thoracoabdominal aortic
aneurysms: current status and level of evidence. European Journal of Vascular and Endovascular
Surgery 2007; 34 (5): 528–33.
15. Browne TF, Hartley D, Purchas S, et al. A fenestrated covered suprarenal aortic stent. European Journal
of Vascular and Endovascular Surgery 1999; 18 (5): 445–49.
16. Mastracci TM, Eagleton MJ, Kuramochi Y, et al. Twelve-year results of fenestrated endografts for
juxtarenal and group IV thoracoabdominal aneurysms. Journal of Vascular Surgery 2015; 61(2): 355–64.
17. Haddad F, Greenberg RK, Walker E, et al. Fenestrated endovascular grafting: The renal side of the story.
Journal of Vascular Surgery 2005; 41 (2):181–90.
18. Spanos K, Kolbel T, Theodorakopoulou M, et al. Early outcomes of the t-branch off-the-shelf
multibranched stent-graft in urgent thoracoabdominal aortic aneurysm repair. Journal of Endovascular
Therapy 2018; 25 (1): 31–39.
19. Anderson J, Nykamp M, Danielson L, et al. A novel endovascular debranching technique using
physician-assembled endografts for repair of thoracoabdominal aneurysms. Journal of Vascular
Surgery 2014; 60 (5): 1177–84.
20. Bisdas T, Panuccio G, Sugimoto M, et al. Risk factors for spinal cord ischaemia after endovascular repair
of thoracoabdominal aortic aneurysms. Journal of Vascular Surgery 2015; 61 (6): 1408–16.
21. Scali ST, Kim M, Kubilis P, Feezor RJ, et al. Implementation of a bundled protocol significantly reduces
risk of spinal cord ischaemia after branched or fenestrated endovascular aortic repair. Journal of
Vascular Surgery 2018; 67 (2): 409–23.
22. O'Callaghan A, Mastracci TM, Eagleton MJ. Staged endovascular repair of thoracoabdominal aortic
aneurysms limits incidence and severity of spinal cord ischaemia. Journal of Vascular Surgery 2015; 61
(2): 347–54.e1.
62
Controversies associated with underlying
pathologies, connective tissue disorders, and
dissecting aneurysm
Endovascular repair in
patients with connective
tissue disorders—infrarenal
L Bertoglio, V Ardita, T Cambiaghi, L Apruzzi,
G Melissano and R Chiesa
Introduction
Patients with connective tissue disorders are a peculiar subgroup of aortic patients
because they are younger, they experience syndrome specific comorbidities and
the aortic disease shows greater progression. The most common connective tissue
disorder is Marfan syndrome, and its most common vascular complication is aortic
root aneurysm in which the ascending aorta is involved, followed by the arch and
descending thoracic aorta. Aneurysms of the infrarenal abdominal aorta remain
a rare complication of Marfan syndrome and risk factors for abdominal aortic
aneurysm disease are poorly understood.1
Also non-syndromic, genetically triggered, aortic diseases, such as familial
aortic aneurysms and dissections, are associated to 15–20% of abdominal aortic
aneurysms.1–4 Patients with familial thoracic aortic aneurysm and dissection
are younger at their initial presentation, with greater probability of developing
aneurysmal disease proximal to the infrarenal aorta, bilateral common iliac and
unilateral internal iliac artery aneurysms.5,6
Patients with connective tissue disorders are prone to early development of
aneurysms, dissections, and ruptures, and will often require numerous vascular
interventions over their lifetimes. However, these patients are also prone to
complications from percutaneous access and progressive degeneration of adjacent
arterial segments, which so far, has caused hesitation towards the implementation
of endovascular options for this population. The aim of this chapter is to analyse
the current knowledge, management and role of endovascular repair in patients
with connective tissue disorders, focusing the attention to infrarenal abdominal
aortic aneurysms.
Endovascular treatment of thoracic aortic pathology in

connective tissue disorders
International guidelines state that stent grafting in patients with Marfan syndrome
or any other known connective tissue disorder is not recommended.7–9 Both the
consensus statement of the Society of Thoracic Surgeons and the European Society
of Vascular Surgery guidelines on the diagnosis and treatment of aortic diseases
strongly recommend against endovascular repair in patients with connective
tissue disorders. However, there are a few exceptions: the operative risk has been
deemed truly prohibitive; the endovascular procedure will be performed by a
65
centre experienced in the management of complex aortic disease; if the situation
• L Bertoglio, V Ardita, T Cambiaghi, L Apruzzi, G Melissano and R Chiesa
is emergent and endovascular repair is needed to stabilise the patient as a bridge

to definitive surgical therapy.8,9 These recommendations are based on the lack of
available information on what impact the persistent radial forces of a stent graft
could have on these abnormal and weak aortas. The natural history suggests that
endograft treatment would fail, as the stent grafts fixation zones are prone to
future dilatation under the chronic outward radial force exerted by the grafts.10
Ultimately this leads to loss of seal with consequent development of endoleaks,
device migration or erosion and subsequent need for reintervention to remove the
endograft and repair the aorta.
Concerns for device failure in patients affected by connective tissue disorders are
also the reason why FDA trials for endovascular devices have intentionally excluded
this cohort of patients. Consequently, commercially available stent grafts have not
been investigated for this indication and are thus not approved for the treatment of
thoracic and abdominal aortic disease in patients with connective tissue disorders.
Therefore, the application of endovascular repair in connective tissue disorder
patients falls, a priori, outside the instruction for use.
Despite the lack of clear evidence, selected use of endovascular treatment in
patients with connective tissue disorders has been described in literature in
different aortic segments for a selected subset of patients and with controversial
results.11–16 In 2013 Pacini et al published a systematic review (54 patients from 12
publications; mean age 40.9 years, 75% males) of studies reporting early and mid-
term results of endovascular stent grafting in patients with Marfan syndrome and
type B aortic dissection (20.4% acute dissections).17 The proximal landing zone
for the endovascular grafts was a portion of native aorta in 81% of the cases and a
Endovascular repair in patients with connective tissue disorders—infrarenal
previously implanted aortic graft in 19%. The periprocedural endoleak rate for the
40 patients was 25% (10 patients: seven cases of type I). The endoleak rate went up
to 30.3% when patients who had a previously implanted graft as landing zone were
excluded from analysis. At a follow-up interval of approximately two and a half
years, on average, endoleaks were observed in 17.9% of the 39 hospital survivors,
open surgical operation was required in 12.8%, and a subsequent endovascular
procedure was performed in 17.9%.
Other additional problems associated with the use of endovascular stent grafts in
patients with type B aortic dissection include stent-graft induced new entry-tears
with retrograde aortic dissection and distal lamella ruptures. In a series of 443
patients undergoing endovascular stent grafting for acute, subacute and chronic
type B aortic dissection, reported by Dong et al, 11 patients (2.5%) developed
a retrograde type A dissection.18 Three of the 11 dissections occurred in patients
with known Marfan syndrome. Only six of the 443 patients in this study had
Marfan syndrome and, thus, the incidence of retrograde dissection in these cohort
of patients was 50%. In 2010, Dong et al also reported the occurrence of distal
stent-graft induced new entry tears in 22 (3.4%) out of 650 patients undergoing
endovascular stent grafting for type B dissection with a prevalence of stent graft
induced new entry-tears among Marfan patients of 33.3%.19
Few data are available regarding stent grafting of descending thoracic aneurysms;
however, the european multicentre Medtronic Talent registr reported the short-term
conversion rate to open surgery after endovascular stent grafting of the descending
thoracic aorta. During a median interval of 14 months, 16 out of 421 patients
66
A B C
Endovascular repair in patients with connective tissue disorders – infrarenal

Figure 1: (A) Dissecting type III thoracic abdominal aortic aneurysm with previous descending thoracic and infrarenal
open repair in a Marfan patient who was reoperated through a thoracotomy three times and presented with a frozen
chest. (B) A branched repair was employed to treat his thoracic abdominal aortic aneurysm with proximal and distal
landing within the previous surgical grafts. (C) After three years his left iliac aneurysm was treated with a standard
EVAR with a left iliac branch device. Please note that the EVAR landed proximally within the previous endovascular
and surgical grafts.
required explantation of the device (15 for endoleak and one for retrograde type A
dissection). Five of these 16 patients (31.3%) had Marfan syndrome and Marfan

syndrome was the most significant independent predictor of late conversion
(adjusted hazard ratio 9.97, P=0.008).20 In a series of reoperations for complications
of endovascular procedures, reported by Spiliotopoulos et al, 16 of 45 patients
(35.6%) who had undergone thoracic endovascular aortic repair (TEVAR) also had
a connective tissue disorder (14 Marfan syndrome, 2 Loeys-Dietz syndrome).21
This evidence argues strongly against the routine use of endovascular grafts in
connective tissue disorder patients with thoracic pathology. An exception to this
recommendation are situations in which an endograft can seal within a surgically
placed Dacron graft, especially proximally, preferably both proximally and distally
(i.e. to treat intercostal or visceral patch aneurysms) Figure 1.
The only other reasonable applications for endovascular stent grafting are in
the setting of acute dissection or rupture, where there are clear indications for
emergent intervention as a life-saving effort, or, more rarely, given the young age
and general good health of most Marfan patients, when the risk of open repair is
considered to be prohibitive (Figure 2).
Endovascular treatment of Infrarenal aortic pathology in

connective tissue disorders
Abdominal aortic aneurysm is rarely reported in connective tissue disorders; it is
only the subject of few isolated case reports.22–30 True non-dissecting abdominal
aortic aneurysms as index aortic lesion are extremely rare in Marfan patients,
they occur in relatively young patients (mean age <50 years) and in some patients
tend to rupture or dissect, even if very small in diameter (i.e. 30 mm).29,31 More
commonly, abdominal aortic aneurysms are found in Marfan population during
67
A B C
Figure 2: (A) Dissecting Type IV T abdominal aortic aneurysm in patient with Marfan syndrome and previous emergent
treatment of a complicated (mesenteric ischemia) acute type B dissection treated with TEVAR and multiple bowel
resections. Subsequently, after the index repair, a distal thoracic stent-graft induced new entry-tears was surgically
repaired. Due to his previous surgical history, we treated him with a staged FEVAR with proximal landing within the
thoracic surgical graft: (B) first, an EVAR within the translumen was performed to re-expand the abdominal true lumen;
and, then, (C) the procedure was completed with exclusion of the false lumen with four-vessel fenestrated graft.
follow-up after an initial aortic root aneurysm repair (at a median interval from the
index procedure of 11 years) with a four-fold increased probability of abdominal
aortic aneurysm after root repair.30 Risk factors for distal aneurysmal evolution in
Marfan population seem to include descending thoracic aneurysms, visceral vessels
aneurysms, arterial tortuosity, smoking and family history of abdominal aortic
aneurysms.30
Endovascular aneurysm repair (EVAR) of degenerative abdominal aortic
aneurysm is a valid alternative to open repair in the global population; however,
the use of EVAR for patients with connective tissue disorders is still controversial
and has been reported only in a couple of cases.
Different arguments are held against EVAR for infrarenal pathology in
connective tissue disorder patients. These patients are young with an improved
life expectancy compared with patients in the past, while EVAR seems to perform
poorly in the general population at long-term follow-up (up to 10–15 years).32–34
Moreover, drawbacks specific to connective tissue disorders are present: increased
instability of the proximal aortic neck, lack of intramural thrombus with patency
of inferior mesenteric and lumbar arteries with increased risk of type II endoleak,
iliac pathology with the necessity of hypogastric artery preservation, and vessel
tortuosity especially of the iliac arteries, with possible kinking of the stent graft
landed in this region. These aneurysms can present with isolated dissection of the
infrarenal aorta with multiple re-entries in the iliac arteries jeopardising an effective
and long-lasting exclusion of the aneurysm (Figure 3A).
Two recent investigations evaluated the use of EVAR in patients with familial
abdominal aortic aneurysm.5,32 In both series there was a higher rate of procedure
related complications and secondary interventions in familial abdominal aortic
aneurysm patients when compared to patients with sporadic abdominal aortic
68
A B

Figure 3: (A) Isolated dissecting abdominal aortic aneurysm in a 56-year old Marfan male after an initial root repair
performed seven years earlier. Please note the dissection involvement of both common and hypogastric iliac arteries
with multiple re-entry tears. (B) The patient was treated by means of open repair with aorto bi-iliac repair and bilateral
graft reimplantation of the hypogastric arteries.
aneurysm. Familial abdominal aortic aneurysm patients are at an increased risk

of developing delayed endoleak following EVAR with postoperative imaging
demonstrating type I endoleaks in 6% of the cases and type II endoleaks in 18%,
compared with the 1% and 11 % respectively, found in patients with sporadic
abdominal aortic aneurysm. Most of secondary interventions required were
embolisations of side-branches performed for type II endoleaks and reinterventions
for iliac limb stenosis/occlusion. The authors concluded that EVAR for the general
population represents a safe and effective procedure, on the contrary, patients with
connective tissue disorders need closer surveillance post-EVAR due to the high risk
of complications.
In our centre, we treated all cases (four patients) of isolated abdominal aneurysms
in connective tissue disorder patients with native proximal aortic necks by means of
open repair, with reimplantation of the hypogastric artery when necessary. (Figure
3) In one case with previous infernal open repair, we treated distal progressive iliac
pathology by means of endovascular repair (Figure 1C).
Conclusion
The level of evidence or grade of recommendation on establishing the indications
for endovascular treatment of connective tissue disorders is still limited and need
further investigations. As a general rule, low-risk patients, or those who have not
had several aortic operations, are typically offered open surgical repair, as this
remains the gold standard of treatment, with better long-term outcomes in both
the thoracic and the abdominal segment. However, in selected cases, patients with
connective tissue disorders may benefit from endovascular management, provided
that the indication is given by centres specialised in aortic surgery and that
69
careful evaluation is performed prior to EVAR, to avoid delaying, precluding or
complicating possible open repairs.
Summary
• Abdominal aortic aneurysm in patients with connective tissue disorders

represent a rare disease and few clinical case reports are documented in
literature. Open repair remains the treatment of choice in patients with
connective tissue disorders also for the abdominal aorta.
• Endovascular treatment could be indicated only in cases in which a prosthetic
proximal landing zone is present or as life-saving procedure.
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70
19. Dong Z, Fu W, Wang Y, et al. Stent graft-induced new entry after endovascular repair for Stanford type

B aortic dissection. J Vasc Surg 2010; 52 (6): 1450–457.
20. Ehrlich MP, Nienaber CA, Rousseau H, et al. Short-term conversion to open surgery after endovascular
stent-grafting of the thoracic aorta: the Talent thoracic registry. J Thorac Cardiovasc Surg 2008; 135 (6):
1322–326.
21. Spiliotopoulos K, Preventza O, Green SY, et al. Open descending thoracic or thoracoabdominal
aortic approaches for complications of endovascular aortic procedures: 19-year experience. J Thorac
Cardiovasc Surg 2018; 155 (1): 10-18
22. Yu SC. Marfan’s syndrome with spontaneous pneumothorax and abdominal aortic aneurysm. Int Surg
1976; 61 (1): 30–31.
23. Houston HE. Abdominal aortic aneurysm in Marfan’s syndrome. J Ky Med Assoc 1978; 76 (10): 492–93.
24. Lafferty K, McLean L, Salisbury J, et al. Ruptured abdominal aortic aneurysm in Marfan’s syndrome.
Postgrad Med J 1987; 63 (742): 685–87.
25. van Ooijen B. Marfan’s syndrome and isolated aneurysm of the abdominal aorta. Br Heart J 1988; 59
(1): 81–84.
26. Wolfgarten B, Kruger I, Gawenda M. Rare manifestation of abdominal aortic aneurysm and popliteal
aneurysm in a patient with Marfan’s syndrome: a case report. Vasc Surg 2001; 35 (1): 81–4.
27. Ugwu BT, Ardill W, Yiltok SJ, et al. Marfan’s syndrome presenting with abdominal aortic aneurysm: a
case for vigilance. West Afr J Med 2003; 22 (1): 95–97.
28. Kokotsakis JN, Lioulias AG, Foroulis CN, et al. Combined repair of ascending aortic pseudoaneurysm
and abdominal aortic aneurysm: in a patient with Marfan syndrome. Tex Heart Inst J 2003; 30 (3):
233–35.
29. Takayama T, Miyata T, Nagawa H. True abdominal aortic aneurysm in Marfan syndrome. J Vasc Surg
2009; 49 (5): 1162–65.
30. Hagerty T, Geraghty P, Braverman AC. Abdominal Aortic Aneurysm in Marfan Syndrome. Ann Vasc Surg
2017; 40: 294. e1–294.e6.
31. Niinami H, Aomi S, Tagusari O et al. Extensive aortic reconstruction for aortic aneurysms in Marfan
syndrome. Ann Thorac Surg 1999; 67(6): 1864–87.
32. Ryer EJ, Garvin RP, Thomas B et al. Patients with familial abdominal aortic aneurysms are at increased

risk for endoleak and secondary intervention following elective endovascular aneurysm repair. J Vasc
Surg 2015; 62 (5): 1119–24.
33. Arslan-Kirchner M, von Kodolitsch Y, Schmidtke J. The importance of genetic testing in the clinical
management of patients with Marfan syndrome and related disorders. Dtsch Arztebl Int ; 105 (27): 483–91.
34. Murdoch JL, Walker BA, Halpern BL et al. Life expectancy and causes of death in the Marfan syndrome.
N Engl J Med 1972; 286 (15): 804–08.
71
Sizing matters when it comes
to remodelling and false lumen
thrombosis after TEVAR
Introduction
Initially indicated for use in complicated type B aortic dissection, studies have begun
to suggest that thoracic endovascular aortic repair (TEVAR) may be appropriate for
use in uncomplicated dissections as well.1–3 Results from the international registry of
acute aortic dissection found that TEVAR is associated with lower mortality over a
five-year period compared to medical therapy alone for acute type B aortic dissection.4
Similarly, in patients with stable type B aortic dissection, the INSTEAD-XL trial
found that TEVAR was associated with improved five-year aorta-specific survival
and delayed disease progression compared with medical therapy alone.5 Studies have
identified multiple factors to predict which patients will benefit from endovascular
therapy vs. conservative management, and several have identified the continued filling
of the false lumen as a potential source of complications.6–10 The goal of TEVAR in
uncomplicated type B aortic dissection is to cover proximal entry tears, in order
to eliminate blood flow within the false lumen. In so doing, TEVAR encourages
false lumen thrombosis and aortic remodelling, and may thereby reduce the chance
of aortic degeneration and the need for future complex thoracoabdominal aortic
aneurysm repairs that carry high morbidity and mortality rates.
False lumen thrombosis and aortic remodelling

It is generally accepted that increased aortic diameter is associated with increased
risk of rupture.11,12 A variety of morphological features have been found to be
predictive of aortic growth, including a patent or partially thrombosed false
lumen.8,13,14 Studies have shown that aortic growth rates are higher in patients
with blood flow in the false lumen, and that a partially thrombosed false lumen is
associated with a significantly higher growth rate compared with a false lumen that
is patent or completely thrombosed.15,16 Not only is a partially thrombosed false
lumen associated with aortic growth, but a report from the International Registry
of Acute Aortic Dissection found that partial thrombosis of the false lumen was a
key predictor of mortality in patients with type B aortic dissection.7 In a recently
published study from our group, we found that partial or full thrombosis of the false
lumen was associated with retrograde type A dissection.17 Clearly, inducing false
lumen thrombosis must be a priority in management of type B aortic dissection,
and TEVAR has emerged as a treatment option. Partial or complete thrombosis of
the false lumen along the stented segment has been seen in 90–93% of patients
who undergo TEVAR.5,18
73
B
Sizing matters when it comes to remodelling and false lumen thrombosis after TEVAR •
Figure 1: Preoperative, one month, and one year imaging of type B aortic dissection
treated with TEVAR showing false lumen thrombosis and eventual remodelling within the
treated aorta, and gradual false lumen thrombosis distal to the treated aorta. (A) Aorta at
the level of the carina. (B) Aorta at the level of the coeliac artery.
In addition to inducing false lumen thrombosis, TEVAR encourages aortic

remodelling in type B aortic dissection patients, which is essential to preventing
adverse patient outcomes. In one study, failure to achieve aortic remodelling at six
months postoperatively was the only significant risk factor for late aortic events, and
patients with aortic remodelling had higher rates of freedom from aortic events.19
Another study found that survival was higher in patients with aortic remodelling
compared with those who had no remodelling.9 In general, studies have found that
TEVAR often results in positive aortic remodelling compared with medical therapy
alone, with significant reduction of false lumen diameter and corresponding
increase in true lumen diameter.20,21 In the INSTEAD-XL trial, morphological
remodelling at five years was evident in 79.2% of patients who underwent TEVAR
in addition to optimal medical therapy, as opposed to only 10% of patients who
received optimal medical therapy alone.5
It seems clear that TEVAR can promote false lumen thrombosis and positive
aortic remodelling. However, while total thrombosis of the false lumen within
the treated aorta is seen in 80.6–90% of patients, total thrombosis of the false
lumen below the diaphragm is less frequent (22–76.5%).22–26 While TEVAR can
significantly decrease aortic diameter through the stent grafted segment, it does not
always result in remodelling of untreated segments.27 If complete aortic remodelling
is not achieved, aortic growth due to false lumen patency may continue in the
abdominal aorta even after treatment.9,28 Conrad et al reported that in complicated
type B aortic dissection patients who underwent TEVAR, false lumen patency was
associated with an average of 31% growth of the visceral segment, compared with
a 3% growth in patients with a thrombosed false lumen.10 It appears that aortic
remodelling may only occur within the treated portion of the aorta, and that this
may not occur for all patients.
74
Figure 2: Preoperative and postoperative, one month, and one-year CT angiography with
contrast showing complete aortic remodelling within the treated aorta and continued
aneurysmal degeneration distal to the treated aorta.
To encourage remodelling, treat earlier

Studies have suggested that aortic remodelling is more likely to be accomplished in
acute-onset cases rather than in chronic cases.23,25 This is not to say that TEVAR is
ineffective in chronic type B aortic dissection: it has been reported that aneurysm
diameter reduced or stabilised in 65% of patients after TEVAR.29 However, chronic
type B aortic dissections treated with TEVAR are less likely to have complete

aortic remodelling to the diaphragm level and more likely to have no remodelling
within the treated thoracic aorta when compared with acute-onset cases.24 The
2014 European Society of Cardiology guidelines on the diagnosis and treatment
of aortic diseases suggest that complete aortic remodelling cannot be expected in
chronic cases, due to thickening of the intimal flap.30 While the optimal treatment
in patients with chronic aortic dissection is unclear, a study published in 2017
found that risk of perioperative complications does not appear to increase when
treating chronic dissections.31 Additionally, a review of the Emory aortic database
found that 45.9% of patients who were treated medically for acute uncomplicated
type B aortic dissection later required treatment for complications in the chronic
phase and had poor survival compared to patients who underwent TEVAR.32 With
this in mind, we suggest that treating type B aortic dissections earlier can promote
remodelling and result in improved outcomes.
In addition to being more effective in promoting false lumen regression and aortic
remodelling when performed in the acute phase, TEVAR may cause complications
in the chronic phase due to thickened and stiff intimal flaps. Some studies have
found that oversizing of the distal stent graft may be a significant factor causing
stent graft-induced new entry tears, and that this appears to be more common
in type B aortic dissection that are treated chronically rather than acutely.33–35
However, we have found that the best way to induce remodelling in the distal
thoracic aorta and avoid some of the aforementioned issues is to size the distal graft
to the total aortic diameter in 1:1 fashion.
75
Conclusion
In order to induce false lumen thrombosis and aortic remodelling, we recommend

that distal graft be sized to total aortic diameter. The false lumen is the “problem
child” of type B aortic dissection and treating it early and aggressively might help
lessen complications caused by false lumen patency or partial thrombosis.
Summary
• Aortic growth rates are higher in patients with blood flow in the false lumen.
• A partially thrombosed false lumen is associated with a significantly higher
aortic growth rate compared with a false lumen that is patent or completely
thrombosed.
• A partially thrombosed false lumen is associated with adverse outcomes.

• TEVAR often results in positive aortic remodelling compared with medical
therapy alone.
• Partial or complete thrombosis of the false lumen along the stented segment
is common in patients who undergo TEVAR.
• Aortic remodelling with TEVAR is more likely to be accomplished in acute-
onset cases rather than in chronic cases.
References
1. Elefteriades JA, Lovoulos CJ, Coady MA, et al. Management of descending aortic dissection. Ann
Thorac Surg 1999; 67: 2002–05.
2. Hagan PG, Nienaber CA, Isselbacher EM, et al. The International Registry of Acute Aortic Dissection
(IRAD): new insights into an old disease. JAMA 2000; 283 (7): 897–903.
3. Conway AM, Qato K, Mondry LR, et al. Outcomes of thoracic endovascular aortic repair for chronic
aortic dissections. J Vasc Surg 2017; pii: S0741–5214 (17) 32363–67.
4. Fattori R, Montgomery D, Lovato L, et al. Survival after endovascular therapy in patients with type B
aortic dissection: a report from the International Registry of Acute Aortic Dissection (IRAD). J Am Coll
Cardiol Intv 2013; 6 (8): 876–82.
5. Nienaber CA, Kische S, Rousseau H, et al. Endovascular repair of type B aortic dissection. Circ Cardiovasc
Interv 2013; 6 (4): 407–16.
6. Luebke T, Brunkwall J. Type B aortic dissection: a review of prognostic factors and meta-analysis of
treatment options. AORTA Journal 2014; 2 (6): 265–78.
7. Tsai TT, Evangelista A, Nienaber CA, et al. Partial thrombosis of the false lumen in patients with acute
type B aortic dissection. N Engl J Med 2007; 357 (4): 349–59.
8. Van Bogerijen GH, Tolenaar JL, Rampoldi V, et al. Predictors of aortic growth in uncomplicated type B
aortic dissection. J Vasc Surg 2014; 59 (4): 1134–43.
9. Mani K, Clough RE, Lyons OT, et al. Predictors of outcome after endovascular repair for chronic type B
dissection. Eur J Vasc Endovasc Surg 2012; 43 (4): 386–91.
10. Conrad MF, Carvalho S, Ergul E, et al. Late aortic remodeling persists in the stented segment after
endovascular repair of acute complicated type B aortic dissection. J Vasc Surg 2015; 62 (3): 600–05.
11. Elefteriades JA. Natural history of thoracic aortic aneurysms: indications for surgery, and surgical
versus nonsurgical risks. Ann Thorac Surg 2002; 74 (5): S1877–80.
12. Chaikof EL, Brewster DC, Dalman RL, et al, Upchurch GR, Veith FJ. SVS practice guidelines for the care
of patients with an abdominal aortic aneurysm: executive summary. J Vasc Surg 2009; 50 (4): 880–96.
13. Kamman AV, Brunkwall J, Verhoeven EL, et al. Predictors of aortic growth in uncomplicated type B
aortic dissection from the acute dissection stent grafting or best medical treatment (ADSORB)
database. J Vasc Surg 2017; 65 (4): 964–71.
14. Evangelista A, Salas A, Ribera A, et al. Long-term outcome of aortic dissection with patent false lumen:
predictive role of entry tear size and location. Circulation 2012; 125 (25): 3133–41.
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15. Sueyoshi E, Sakamoto I, Hayashi K, et al. Growth rate of aortic diameter in patients with type B aortic
dissection during the chronic phase. Circulation 2004; 110: II256–61.
16. Trimarchi S, Tolenaar JL, Jonker FH, et al. Importance of false lumen thrombosis in type B aortic
dissection prognosis. J Thorac Cardiovasc Surg 2013; 145 (3 Suppl): S208–12.
17. Yammine H, Briggs CS, Stanley GA, et al. Retrograde type A dissection after thoracic endovascular
aortic repair for type B aortic dissection. J Vasc Surg 2018; 67 (1): e9.
18. Conrad MF, Crawford RS, Kwolek CJ, et al. Aortic remodeling after endovascular repair of acute
complicated type B aortic dissection. J Vasc Surg 2009; 50 (3): 510–17.
19. Watanabe Y, Shimamura K, Yoshida T, et al. Aortic remodeling as a prognostic factor for late aortic
events after thoracic endovascular aortic repair in type B aortic dissection with patent false lumen. J
Endovasc Ther 2014; 21 (4): 517–25.
20. Huptas S, Mehta RH, KÜhl H, et al. Aortic remodeling in type B aortic dissection: effects of endovascular
stent-graft repair and medical treatment on true and false lumen volumes. J Endovasc Ther 2009;
16(1):28–38.
21. Patterson BO, Cobb RJ, Karthikesalingam A, et al. A systematic review of aortic remodeling after
endovascular repair of type B aortic dissection: methods and outcomes. Ann of Thorac Surg 2014; 97
(2):588–95.
22. Resch TA, Delle M, Falkenberg M, et al. Remodeling of the thoracic aorta after stent grafting of type B
dissection: a Swedish multicenter study. J Cardiovasc Surg (Torino) 2006; 47 (5): 503–08.
23. Kusagawa H, Shimono T, Ishida M, et al. Changes in false lumen after transluminal stent-graft
placement in aortic dissections. Circulation 2005; 111(22): 2951–07.
24. Yang CP, Hsu CP, Chen WY, et al. Aortic remodeling after endovascular repair with stainless steel-based
stent graft in acute and chronic type B aortic dissection. Journal of Vascular Surgery 2012; 55 (6):1600–10.
25. Sayer D, Bratby M, Brooks M, et al. Aortic morphology following endovascular repair of acute and
chronic type B aortic dissection: implications for management. Eur J Vasc Endovasc Surg 2008; 36 (5):
522–29
26. Schoder M, Czerny M, Cejna M, et al. Endovascular repair of acute type B aortic dissection: long-term
follow-up of true and false lumen diameter changes. Ann Thorac Surg 2007; 83 (3): 1059–66.
27. Kang WC, Greenberg RK, Mastracci TM, et al. Endovascular repair of complicated chronic distal aortic
dissections: intermediate outcomes and complications. J Thorac Cardiovasc Surg. 2011; 142 (5):1074–83.
28. Sigman MM, Palmer OP, Ham SW, et al. Aortic morphologic findings after thoracic endovascular aortic
repair for type B aortic dissection. JAMA Surgery 2014; 149 (9): 977–83.
29. Scali ST, Feezor RJ, Chang CK, et al. Efficacy of thoracic endovascular stent repair for chronic type B

aortic dissection with aneurysmal degeneration. J Vasc Surg 2013; 58 (1):10–17.
30. Erbel R, Aboyans V, Boileau C, et al. ESC Committee for Practice Guidelines. 2014 ESC Guidelines on
the diagnosis and treatment of aortic diseases: Document covering acute and chronic aortic diseases
of the thoracic and abdominal aorta of the adult. The Task Force for the Diagnosis and Treatment of
Aortic Diseases of the European Society of Cardiology (ESC). Eur Heart J 2014; 35 (41): 2873–926.
31. Miyairi T, Miyata H, Chiba K, et al. Influence of timing after thoracic endovascular aortic repair for acute
type B aortic dissection. Ann Thorac Surg 2017. Epub.
32. Lou X, Chen EP, Duwayri YM, et al. The impact of thoracic endovascular aortic repair on long-term
survival in type B aortic dissection. Ann Thorac Surg 2018; 105 (1): 31–38.
33. Jang H, Kim MD, Kim GM, et al. Risk factors for stent graft-induced new entry after thoracic endovascular
aortic repair for Stanford type B aortic dissection. J Vasc Surg 2017; 65 (3): 676–85.
34. Weng SH, Weng CF, Chen WY, et al. Reintervention for distal stent graft-induced new entry after
endovascular repair with a stainless steel-based device in aortic dissection. J Vasc Surg 2013; 57 (1):
64–71.
35. Pantaleo A, Jafrancesco G, Buia F, et al. Distal stent graft-induced new entry: an emerging complication
of endovascular treatment in aortic dissection. Ann Thorac Surg 2016; 102 (2): 527–32.
77
Radiation controversies
Reduced radiation and
choice of imaging modality
for endoleak detection
and correction
Introduction
Endovascular aneurysm repair (EVAR) is currently the major treatment option for
infrarenal abdominal aortic aneurysms. With the continuous evolution of stent grafts
and endovascular devices, increasingly complex aortic pathologies are being treated
this way. This development demands improved intraoperative assessment of technical
success and prevention of early secondary revisions even in challenging anatomies.
Complications after EVAR

The fundamental randomised trials comparing open repair and EVAR reported a rate
of 6% type I endoleaks in immediate follow-up, with 80% rate of reinterventions,
as confirmed in the DREAM (Dutch randomised endovascular aneurysm repair),
EVAR1 and ACE (Aneurysm de l’aorte abdominale, Chirurgie vs. Endoprothese)
trials. While 14% endoleaks type II with a reintervention rate of 28% were
reported, EVAR-1 revealed up to 26% of reinterventions and a significantly higher
aneurysm-related mortality rate in the EVAR group, mainly due to untreated
endoleaks with secondary sac rupture.1,2 Although a few secondary ruptures occur
after EVAR, most of them can be prevented if the complications leading to the
rupture are identified by optimal surveillance.3
The main cause for early reinterventions and secondary procedures is undetected
type I endoleaks; and for late reintervention, type II endoleaks. Additionally, limb
thrombus, renal artery over-stenting, and limb stenosis occur. Although complex
anatomies and hostile neck are a predictor for reinterventions, complex anatomies
are increasingly treated with an endovascular approach.4,5
On the one hand, secondary procedures after EVAR are associated with higher
mortality, and it is also time-consuming and upsetting for the patient to undergo
a secondary hospital stay and anaesthesia. On the other hand, costs related to
reinterventions for the healthcare system may reduce, and patients with a secondary
intervention may have reduced overall survival.6–8
Therefore, intraoperative approaches for optimal assessment of technical success
are crucial to avoid secondary procedures.
81
Intraoperative endoleak detection with conventional methods
The clinical standard in intraoperative imaging is still digital subtraction angiography

(DSA).9 The main advantages of this widespread technique are availability and
visualisation of flow dynamics. DSA offers high resolution with good image quality
if used on a modern flat panel detector or even a modern portable C-arm.
The number of endovascular procedures is growing steadily, and numerous concerns
have been raised concerning potential hazardous radiation exposure for patients and
healthcare professionals.10 Therefore it became mandatory to apply the “ALARA” (as
low as reasonably achievable) principles to the management of radiation that has
been used in healthcare since the middle of the 20th century. Close adherence to
these principles minimises radiation, firstly by raising awareness, and then by training
employees in personal radiation protection and conscious handling.11
Adjustments that reduce radiation include lower dose levels, shorter X-ray pulses,
Reduced radiation and choice of imaging modality for endoleak detection and correction •
additional beam filtration to reduce scatter radiation, the use of beam collimation,
and avoiding lateral angulations.
Most reductions of radiation (shorter pulses, lower energy) are subject to the laws
of physics and lower the signal to noise ratio, inducing a worsening of image quality.
But with recent developments in image post-processing, it is possible to reduce the
radiation dose while maintaining image quality.12 Philips includes this technique
in the “ClarityIQ” software, while Siemens offers “CARE+CLEAR” protocols and
automatic exposure control. These tools make use of several hardware and software
applications and are often provided in diverse ways in current angiography systems.
These tools include temporal averaging of consecutive images, automatic pixel
shifting to compensate for patient or breathing movement, spatial noise reduction,
and edge and image enhancement.
It is not insignificant that DSA is still the standard, widespread and familiar
tool within the endovascular community for assessment of technical success.
Nevertheless, numerous innovations are being clinically evaluated.
Outlook: Approaches for assessment of technical success

Carbon dioxide (CO2) angiography, for example, is a potential option to avoid
using nephrotoxic iodine contrast agent, but the rheological behaviour of a gas
bears the risk of overestimating endoleaks, and requires user familiarisation with
the changed fluid dynamics. Nevertheless, several advantages come with CO2: no
allergic or toxic reactions, rapid clearance, no dilution in blood, low viscosity, and
visualisation of distal vessels and collaterals.13
Intraoperative contrast enhanced ultrasound (CEUS) has also been suggested for
implantation control, but is not used routinely for intraoperative assessment of
technical success—despite being widely accepted for radiation and contrast agent-
free surveillance after EVAR.14–16
Contrast enhanced cone-beam CT

Vascular hybrid operating theatres offer advanced imaging possibilities and are
increasingly available to endovascular specialists. Therefore, it is now possible to
assess technical success after EVAR with rotational angiography. Modern robot-
mounted flat panel detector angiography systems can perform a semi-circular
acquisition of the region of interest and thus acquire rotational angiographies.
82
Figure 1: The source for this big
endoleak was not clearly seen on DSA;
with cone-beam CT, it was found to be
a lumbar artery.
While these can be difficult to interpret due to the constant rotation of the
acquisition, rotational angiographies still include temporal information of the
blood respectively contrast agent flow of the endovascular reconstruction. Often,
this angiography is not assessed and solely reconstructed as a volume of computed
tomography (CT)-like images.
This so-called contrast-enhanced cone-beam CT offers on-table 3D confirmation
of the intraoperative result and CT-like images in the hybrid operating room. It
enables immediate revision of pathologies while the patient is still on the table,

although offering an image quality comparable to postoperative CT angiography.
All tools available for assessing CT angiography are also available for cone-beam
CT, including multiplanar reconstruction and maximum intensity projections.
Numerous publications give an overview of the evidence for the reliability
of cone-beam CT to assess technical success after EVAR.17–21 It is unanimously
reported in literature that cone-beam CT reliably detects endoleaks, stenoses and
thrombus and is therefore a possible candidate to replace both completion DSA
and early postoperative CT angiography.
An obvious advantage of cone-beam CT is the precise display of anterior or
posterior endoleaks, especially type Ia, that are overlaid by the stent graft and
potentially overlooked in uniplanar DSA. This problem could be solved by
acquisition of completion angiography in an orthogonal projection. However,
while the assessment of proximal type Ib endoleaks also requires retrograde DSA, it
would be necessary to acquire three DSA series for final assessment.
It is even reported that limb stenoses and kinks are underdiagnosed in up to 30%
of the cases assessed only with DSA in one projection.22 Some authors, therefore,
propose two additional series in 45 degrees left anterior and right anterior oblique
projection to assess limb stenoses and kinks. This would result in four angiographies
if a retrograde DSA is performed.
83
Figure 2: Intraoperative workflow

to assess technical success including
intraoperative contrast enhanced
cone beam CT (ceCBCT) as completion
imaging after EVAR.
It is, therefore, possible to suggest that cone-beam CT can assess all pathologies
mentioned above in one single acquisition, omitting repeated angiographies
from different projections. There is a consensus in literature that the findings of
an additional cone-beam CT prompted about 7% of immediate intraoperative
reinterventions during EVAR.17 A relevant proportion of patients benefited from
cone-beam CT identification of intraoperatively detected pathologies, which
potentially inhibited secondary procedures. The early intervention rate in the
mentioned studies was lower compared to investigations without cone-beam CT.
Despite these findings, there is little evidence, and studies are small.
Nevertheless, it is questionable whether cone-beam CT can substitute for
completion DSA as an imaging modality or if it is necessary to combine DSA
and cone-beam CT.18 The Achilles heel of cone-beam CT is the static image and
absence of temporal information. Future developments will include the display of
temporal information in cone-beam CT, offering a 3D CT-like angiography.
The workflow in our institution includes the acquisition of a completion DSA in
deployment angulation. If pathologies require immediate treatment, another DSA
is performed thereafter. When judged satisfactory, we acquire an intraoperative
cone-beam CT to assess for undiagnosed pathologies. If no further treatment is
necessary, the patient is transferred to the recovery room and discharged without
further imaging.
After six weeks, the patient receives a postoperative clinical examination and
ultrasound follow-up and a CT angiography one year after implantation.
The first manoeuvre to repair intraoperative type Ia, Ib or III endoleaks is
ballooning of the involved stent part. If this fails, primarily in hostile necks, we
consider using the Medtronic Aptus Heli-FX EndoAnchor system, which was
evaluated as a good method to improve proximal fixation.23 The proximal extension
with a cuff is reserved for cases with a left landing zone. Distal extension with
84
over-stenting of the internal iliac arteries bears the risk of gluteal claudication or
bowel ischaemia.
Intraoperative cone-beam CT vs. CT angiography

Although being an intraoperative angiography-based imaging modality, cone-beam
CT offers CT-like sliced imaging. Certainly, it is less evolved than CT angiography
and offers lower image quality and lower soft tissue resolution. Over the past few
years, there has been a significant improvement in image quality in CT scans while
radiation dose has been continually reduced. Both imaging modalities offer a high
resolution with submillimetre voxels and it is to be assumed that improvements in
cone-beam CT will further increase image quality while lowering radiation.
Depending on the size of the flat-panel detector, cone-beam CT can cover a
cylindrical volume of 240mm in length and 200mm in diameter. This is sufficient for
assessing a complete abdominal EVAR with iliac side branches; thoracoabdominal
repair is better assessed with a CT angiography scan of the whole aorta.
The acquisition of cone-beam CT causes a higher intraoperative radiation dose
and almost doubles the dose of a standard infrarenal EVAR. The mean dose area
product for one cone-beam CT acquisition is roughly 50 (20–70) Gycm². Lateral
acquisitions especially result in radiation exposure for the operative staff, and
shielding during rotational acquisitions can be quite complex.24 In our clinic, all
staff, therefore, leave the hybrid operating room and the rotational acquisition is
launched remotely.
Various acquisition protocols and hardware set-ups from different manufacturers
are available and result in a broad spectrum of reported radiation dose for cone-
beam CT.17 The different parameters include detector size (a smaller detector results
in a reduction of covered volume and lower radiation dose), frames per acquisition
(lower frame-rate reduces radiation dose but impairs quality) and set dose level per

frame (lower dose results in lower quality). It is no surprise that the reported mean
dose area product for cone-beam CT ranges from 7 to 70 Gycm² with a range from
5 to 130 Gycm².18,19 Of course, the radiation dose for cone-beam CT is higher in
obese patients and image quality is lower. The protocol for balancing image quality
and radiation dose has yet to be determined.
The protocol for cone-beam CT in our institution is a five-second, 200-degree
rotation (180 degrees acquisition and 20 degrees fan angle) with 248 frames, a
system dose of 0.36µGy/f and with a detector size of 300mm by 400mm in portrait
orientation. In a standard Rando Alderson phantom with a BMI of 22kg/m², we
could determine an effective dose of 3.5mSv (ICRP103).25 Applying a fat ring,
raising the BMI to 30kg/m², the effective dose was 5.1mSv.
A multidetector CT angiography (Siemens Somatom Definition Flash with
CARE Dose 4D and Care kV) acquisition of the same 240mm in length as in
ceCBCT results in an effective dose of 2mSv (both for BMI 22kg/m² with a
tube potential of 80kvP and BMI 30 kg/m² and 100kVP). The lower dose of CT
angiography can mainly be explained by the sliced imaging acquisition, where tube
current and potential are modulated for every slice and body region independently,
whereas during cone-beam CT the detector is irradiated per frame until the set
exposure is reached.
85
Figure 4: Comparison of image quality of CT angiography

on the left and cone-beam CT on the right.

Figure 3: 3D reconstruction of a cone-beam CT.
This helps to identify several vessels and to precisely
determine the type of endoleak.
Although a native and, theoretically, a late venous phase acquisition is possible

with cone-beam CT, we do not perform these, as technical success can be assessed
with a single arterial phase cone-beam CT.
We have found that CT angiography theoretically needs less radiation than cone-
beam CT, but in clinical routine the multiphase CT angiography needs significantly
more radiation than the intraoperative single-phase cone-beam CT. A three-phase
CT angiography examination of the entire aorta results in an effective dose of
up to 10.1mSv in the phantom measurements. Considering the same infrarenal
region, CT angiography needs around 50% of the effective dose of cone-beam CT.
Nevertheless, a whole aortic three-phase protocol is about 230% of the effective
dose of cone-beam CT.
Due to intra-arterial contrast injection, the amount of contrast agent is reduced
in a cone-beam CT workflow. In our institution we use 70ml of diluted contrast
agent for cone-beam CT (45ml 300mg I/ml mixed with 25ml of saline) and 90ml
(350mg I/ml) for CT angiography. This means that every cone-beam CT that
replaces CT angiography in our institution reduces the iodine for CT angiography
acquisition by 57% from 31.5g to 13.5g per patient.
The image quality of cone-beam CT is very good for on-table and intraoperative
sliced imaging, though certainly inferior to multidetector CT angiography. Soft
tissue and the aneurysm sac especially are harder to evaluate in cone-beam CT. This
disadvantage is rather theoretical, as every patient receives CT angiography of the
thoracoabdominal aorta to find additional pathologies, and aneurysm shrinkage is
not assessed intraoperatively. Surprisingly, metal artifacts are less severe in cone-beam
CT. Even so, the results are astonishing considering the intraoperative acquisition
and possibility of immediate revision, and an evaluation at our institution revealed
that cone-beam CT image quality is sufficient to detect all relevant pathologies
including endoleaks, stent stenosis and intraluminal thrombus. The image quality
is highly dependent on thorough preparation and execution of the cone-beam CT.
For example, if the pigtail catheter is placed too high, most contrast media drains
into the superior mesenteric artery. Furthermore, the aorta should be in the centre
86
of the volume to avoid fan artefacts and acquisition must be in apnoea, which can
be difficult in loco-regional anaesthesia and non-compliant patients.
The standard in our clinic was changed to completion DSA and routine
intraoperative cone-beam CT for assessment of technical success, and after six
weeks, duplex ultrasound with clinical follow-up. Thereafter, one year follow-up
for infrarenal EVAR is performed with 3-phase CT angiography of the abdominal
aorta for precise measurements of aneurysm shrinkage and assessment of late type
II endoleaks. Afterwards, yearly duplex ultrasound is performed. If cone-beam CT
reveals a type II endoleak, we consider a contrast enhanced ultrasound six months
after implantation.
Conclusion
DSA remains still the valid standard for intraoperative assessment of technical
success. It is widely available and easy to interpret. With innovations in imaging
and image post-processing, the radiation dose for DSA is decreasing. The advantages
include high resolution and temporal information. There is good evidence that
ceCBCT reliably detects pathologies and endoleaks, though whether it can replace
DSA is still in dispute. Currently, additional cone-beam CT can potentially help
to reduce secondary interventions and replace the standard early follow up CT
angiography. If CT angiography is omitted, cone-beam CT reduces contrast agent
use and radiation exposure for the patient.
Summary
• DSA is still the standard for intraoperative endoleak detection.

• Innovative techniques allow reduction of radiation dose while maintaining
image quality.
• DSA offers high resolution, temporal information, is widely accepted and
familiar to interpret.
• Cone-beam CT can help to identify more pathologies intraoperatively and
potentially avoid secondary interventions.
• Cone-beam CT does not yet reach image quality of CT angiography but is
suitable for intraoperative endoleak assessment and can substitute for early
follow-up CT angiography .
• Cone-beam CT reduces in-hospital radiation and contrast agent exposure if
early follow-up CT angiography is omitted.
References
1. Paravastu SC, Jayarajasingam R, Cottam R, et al. Endovascular repair of abdominal aortic aneurysm.
Cochrane Database Syst Rev 2014;1:CD004178.
2. Patel R, Sweeting MJ, Powell JT, Greenhalgh RM. Endovascular versus open repair of abdominal aortic
aneurysm in 15-years' follow-up of the UK endovascular aneurysm repair trial 1 (EVAR trial 1): a
randomised controlled trial. The Lancet 2016; 388 (10058): 2366–74.
87
3. Wyss TR, Brown LC, Powell JT, Greenhalgh RM. Rate and predictability of graft rupture after
endovascular and open abdominal aortic aneurysm repair: data from the EVAR Trials. Ann Surg 2010;
252 (5):805–12.
4. Hobo R, Kievit J, Leurs LJ et al. Influence of severe infrarenal aortic neck angulation on complications
at the proximal neck following endovascular AAA repair: a EUROSTAR study. Journal of Endovascular
Therapy 2007; 14 (1):1–11.
5. Sternbergh WC, Carter G, York JW, et al. Aortic neck angulation predicts adverse outcome with
endovascular abdominal aortic aneurysm repair. Journal of Vascular Surgery 2002; 35 (3): 482–6.
6. van Bochove CA, Burgers LT, Vahl AC, et al. Cost-effectiveness of open versus endovascular repair of
abdominal aortic aneurysm. Journal of Vascular Surgery 2016; 63 (3): 827–38 e2.
7. Sampram ES, Karafa MT, Mascha EJ, et al. Nature, frequency, and predictors of secondary procedures
after endovascular repair of abdominal aortic aneurysm. Journal of Vascular Surgery 2003; 37 (5):930–
37.
8. Hobo R, Buth J, collaborators E. Secondary interventions following endovascular abdominal aortic
aneurysm repair using current endografts. A EUROSTAR report. Journal of Vascular Surgery 2006; 43
(5): 896–902.
9. Eagleton MJ. Intraprocedural imaging: flat panel detectors, rotational angiography, FluoroCT, IVUS, or
still the portable C-arm? Journal of Vascular Surgery 2010; 52 (4 Suppl): 50S–9S.
10. Roguin A, Goldstein J, Bar O, Goldstein JA. Brain and neck tumors among physicians performing
interventional procedures. Am J Cardiol 2013; 111 (9): 1368–72.
11. Kirkwood ML, Arbique GM, Guild JB, et al. Surgeon education decreases radiation dose in complex
endovascular procedures and improves patient safety. Journal of Vascular Surgery 2013; 58 (3): 715–21.
12. Stangenberg L, Shuja F, van der Bom IMJ, et al. Modern Fixed Imaging Systems Reduce Radiation
Exposure to Patients and Providers. Vasc Endovascular Surg 2017:1538574417742211.
13. Sharafuddin MJ, Marjan AE. Current status of carbon dioxide angiography. Journal of Vascular Surgery
2017; 66 (2): 618–37.
14. Ormesher DC, Lowe C, Sedgwick N, McCollum CN, Ghosh J. Use of three-dimensional contrast-
enhanced duplex ultrasound imaging during endovascular aneurysm repair. Journal of Vascular
Surgery 2014; 60 (6): 1468–72.
15. Schmieder GC, Stout CL, Stokes GK, et al. Endoleak after endovascular aneurysm repair: duplex
ultrasound imaging is better than computed tomography at determining the need for intervention.
16. Gray C, Goodman P, Herron CC, et al. Use of colour duplex ultrasound as a first line surveillance tool
following EVAR is associated with a reduction in cost without compromising accuracy. European
Journal of Vascular and Endovascular Surgery 2012; 44 (2): 145–50.
17. Schulz CJ, Schmitt M, Bockler D, Geisbusch P. Intraoperative contrast-enhanced cone beam computed
tomography to assess technical success during endovascular aneurysm repair. Journal of Vascular
Surgery 2016; 64 (3): 577–84
18. Tornqvist P, Dias N, Sonesson B, et al. Intra-operative cone beam computed tomography can help
avoid reinterventions and reduce CT follow up after infrarenal EVAR. European Journal of Vascular and
19. Hertault A, Maurel B, Pontana F, et al. Benefits of completion 3D angiography associated with contrast
enhanced ultrasound to assess technical success after EVAR. European Journal of Vascular and
20. Dijkstra ML, Eagleton MJ, Greenberg RK, et al. Intraoperative C-arm cone-beam computed tomography
in fenestrated/branched aortic endografting. Journal of Vascular Surgery 2011; 53 (3): 583–90.
21. Biasi L, Ali T, Ratnam LA, et al. Intra-operative DynaCT improves technical success of endovascular
repair of abdominal aortic aneurysms. Journal of Vascular Surgery 2009; 49 (2): 288–95.
22. Bianchini Massoni C, Gargiulo M, Giovanetti F, et al. Adjunctive stenting of endograft limbs during
endovascular treatment of infrarenal aortic and iliac aneurysms according to 3-projection completion
angiography. Journal of Endovascular Therapy 2011; 18 (4): 585–90.
23. Jordan WD, Jr., Mehta M, Ouriel K, et al. One-year results of the ANCHOR trial of EndoAnchors for the
prevention and treatment of aortic neck complications after endovascular aneurysm repair. Vascular
2016; 24 (2): 177–86.
24. Resch TA, Tornqvist P, Sonesson B, Dias NV. Techniques to reduce radiation for patients and operators
during aortic endografting. The Journal of Cardiovascular Surgery 2016; 57 (2): 178–84.
25. Steuwe A, Geisbusch P, Schulz CJ, et al. Comparison of Radiation Exposure Associated With
Intraoperative Cone-Beam Computed Tomography and Follow-up Multidetector Computed
Tomography Angiography for Evaluating Endovascular Aneurysm Repairs. Journal of Endovascular
Therapy 2016: 23 (4): 583–92.
88
Deficiencies in operator
behaviour—premature
atypical malignancies in
high-volume operators
Introduction
In recent years, there has been increasing awareness of the possible deleterious
effects of the chronic, low-dose radiation to which interventionalists are exposed
during fluoroscopically-guided procedures. Given the longer operating times
required for increasingly complex endovascular repairs, improving radiation safety
and awareness of risk is a priority.
Radiation exposure during endovascular aneurysm repair

In the 1920s high-end shoe shops routinely X-rayed their customers’ feet, including
children, to assess the fit of the shoe—oblivious to the harmful effects of this
unnecessary exposure. Hindsight may prove that the radiation to which current
endovascular operators are exposed is equally nonsensical, with damaging long-
term health effects. This group of operators are already thought to be at risk of
harm, receiving some of the largest recorded occupational doses of radiation.1
Radiation safety practices and the equipment used to carry out procedures vary.
Hybrid operating theatres incorporating the latest imaging equipment allow the
highest quality imaging for endovascular intervention but, paradoxically, this is at
the cost of increased scatter radiation absorption by the interventionalists. The higher
X-ray energy required for the best quality images means an increase of up to five
times the scatter radiation from hybrid systems compared with a mobile C-arm.2
Endovascular techniques have advanced exponentially over the last decade,
and increasingly complex, longer procedures rely on viewing the aorta in various
projections and using multiple digital subtraction angiography (DSA) runs. We
have previously demonstrated that the majority of radiation exposure during
endovascular aneurysm repair (EVAR) arises from DSA runs, suggesting that the
operator should pay particular attention to minimising the exposure during parts
of the procedure that require DSA.3
Operator behaviours
The main source of radiation exposure to the operator is from scattered radiation after
the main beam reaches the patient’s body. Reducing the level of scatter and shielding
against it is mainly reliant on the safety behaviours instigated by the operator.4
89
European legislation dictates that theoretical and practical training is mandatory
for staff exposed to occupational radiation. There remains much work to be done,
however, with no standard international guidelines for vascular interventionalists.
Radiation safety training programmes and the delivery of this training vary widely
from one country to another.
A 2014 study of vascular trainees reported that 45% of trainees had no formal
radiation safety instruction and only 30% were aware of radiation safety protocols
that should be used for pregnant workers.5 Another study reported that 82%
of trainees had had no formal training, more than two thirds did not use lead
Deficiencies in operator behaviour—premature atypical malignancies in high-volume operators •
goggles and very few knew their previous year’s dose.6 Recent publications suggest
that appropriate education can significantly reduce radiation exposure during
endovascular procedures.7
Radiation safety practices

There are a number of considerations for minimising scatter radiation during
fluoroscopically-guided procedures. All interventionists and support staff should
follow the “ALARA” (as low as reasonably achievable) principles to limit occupational
radiation exposure (fFigure 1). The factors that impact most on radiation exposure
include the following:
Distance
DISTANCE
Doubling the distance
between the operator’s body
and the radiation source will
reduce radiation exposure by
a factor of 4.
SHIELDING
TIME
Maximal lead shielding
is of paramount importance ALARA Reducing the of time
in reducing absorbed dose. of exposure will reduce
This includes lead aprons, radiation exposure and
lead leg shields, mobile lead absorbed dose.
shields and lead glasses.
Figure 1: Illustration of the ALARA principles. Time, distance and shielding are principal factors.
90
The amount of scattered radiation absorbed by the operator decreases by the

inversed squared distance he/she has from the radiation source.8 During DSA runs
and other high radiation scatter-producing manoeuvres, the operator should aim to
maximise their distance between themselves and the patient.
We have recently used real-time dosimetry to monitor the impact of operator
behaviour and factors governing radiation exposure during EVAR. Disappointingly,
operators “stepped back” for <20% of the DSA runs performed. Stepping back
from the table, angulation of the C-arm and source-image intensifier distance were
the strongest predictors of the radiation dose absorbed by the operator during
DSA. This low rate of stepping back from the table could be improved by using
real-time dosimeter technology that incorporates an audible prompt that alerts the
operator to episodes of high radiation exposure. Previous studies have demonstrated
a reduction in operator dose exposure when using such devices. Racadio et al
demonstrated that between a 12-week blinded phase in which doses were measured
but not available to staff and at 17-week un-blinded phase in which staff received
real-time dose data, there were no differences in procedure time, fluoroscopy time,
and patient dose. The median staff dose, however, decreased six-fold from 3.01 to
0.56µSv/min, when staff were aware of their real-time exposure.9
Shielding
The majority of radiation emitted from the X-ray tube is absorbed by the patient’s
tissues, but low-energy photons are most likely to be deflected towards the
operator’s feet and legs. Accordingly, use of appropriately positioned table-mounted
lead shielding is mandatory.10 The additional use of lead leg-shielding appears to
have an additive protective effect.11 Ceiling-mounted lead shields minimise scatter
radiation reaching the head during lateral angulation imaging.12 Phantom studies
have shown that 0.75mm-leaded glasses can independently reduce the radiation
dose to the eye by five–10 fold. Lead-lined caps reduce the effective dose absorbed
by the head. The PROTECT study, measuring doses in 272 interventionalists
wearing barium sulphate-bismuth oxide caps, showed a 10-fold reduction in head

dose.13 Similarly, the BRAIN study demonstrated that barium sulphate–bismuth
oxide caps reduce radiation exposure to the centre of the head by 11-fold and to
the left side of the head 16-fold. Given that brain malignancies have demonstrated
a predilection for the left side in interventionalists, compulsory lead-lined caps
could potentially have a significant impact in reducing deleterious effects.14,15
We have carried out a survey of almost 500 interventionalists around the world
and found that despite the fact that more than 90% were concerned about the
deleterious effects of radiation exposure, >20% did not wear lead goggles and more
than half did not use leg lead shielding. It was encouraging to find that over 60%
of operators wore lead lined caps for head protection.
Time of exposure: Reducing fluoroscopy time and minimising DSA runs are
key for reducing absorbed radiation.
“Last-image hold” and image fusion technologies have reduced reliance on DSA
and ought to be considered as essential by endovascular operators carrying out
complex endovascular repairs on a regular basis. While image fusion is in use in
many hybrid operating theatres, it is not currently considered standard. A recent
study demonstrated that use of fusion imaging during fenestrated aortic repair
leads to significant reductions in total radiation exposure.16
91
Collimation
Collimation reduces the field of view either vertically or horizontally to focus

the image on the area of interest. In doing so, it minimises scatter radiation
and improves the quality of the image. Additionally, it also reduces exposure to
surrounding tissues of the patient as radiation exposure is decreased in proportion
to the reduction of the image size.17
Magnification
Increased magnification results in a moderate drop in image resolution, which
requires an increase in the dose rate. Increasing collimation may mitigate increased
scatter radiation in this circumstance. Modern hybrid theatres with their large
display monitors allow digital zooming, which avoids increased radiation exposure
consequent of using standard magnification.
Angulation
Angulating the C-arm in the left or right anterior oblique position increases the
amount of scattered radiation and should be avoided where possible.18 If it is
necessary to use extreme angulation (>30 degrees), then the duration should be
minimised and with maximal collimation.19
Source to image distance

The distance between the detector, patient and image intensifier must be kept to
a minimum. The X-ray tube output is proportional to the distance between the
tube and the detector. The detector should, therefore, be lowered onto the patient
throughout the procedure.
Risks associated with radiation exposure

The deleterious effects of ionising radiation may be divided into two types:
deterministic or stochastic effects. The severity of deterministic effects increases
as the dose of exposure increases. The physical effects ensue when the burden of
cell death or dysfunction causes functional impairment of the tissue or organ.
Examples include skin erythema/necrosis and cataracts. Stochastic effects, in
contrast to deterministic effects, follow a linear no-threshold principle. This means
that although there is no threshold level for these effects, the risk of an effect
occurring increases linearly as the dose increases. Malignant transformation after
radiation exposure is thought to occur in a stochastic manner.
While currently no reliable data exist on the incidence of radiation-related
adverse biological effects in endovascular operators, several recent publications
have highlighted the significant occupational exposure and malignancy risk for
interventionalists in general. Roguin et al reported 31 cases of brain and neck
cancers, including 17 highly malignant glioblastoma multiforme. In 26 of the
cases, laterality was reported, 85% were left-sided which corresponds to the side
that would have received the highest radiation dose.14
A recent study by an Italian group surveying 466 radiation-exposed and 280
radiation-naive healthcare workers found that, after correcting for age, gender and
health status, skin lesions, cataracts occurred at a significantly higher rate in radiation-
exposed staff. The rate was higher in staff that had a longer history of exposure.20
92
A typical over-lead exposure dose for a complex (fenestrated/branched) EVAR

is around 60µSv which compares with approximately 100µSv and 10,000µSv for a
chest X-ray and CT abdomen/pelvis, respectively. We have recently demonstrated
raised markers of acute DNA damage in operators performing EVAR but it remains
to be seen whether this is linked to a risk of malignant transformation.11 Large
prospective cohorts of radiation-exposed workers need to be studied to demonstrate
an association between chronic low dose radiation exposure and deleterious health
effects, particularly given the likelihood that biological sensitivity to radiation
varies between individuals.
Conclusion
Operators receive substantial doses of ionising radiation over a lifetime carrying out
fluoroscopy-guided interventions. With increasing reliance on endovascular procedures,
promoting a culture that acknowledges radiation safety has become a priority.
Despite being concerned about the ill effects of radiation exposure, operators
remain poor at protecting themselves. It is incumbent on healthcare professionals
to be vigilant when using X-ray guidance and employ steps to reduce their own
and their patients’ doses. Cutting edge endeavours such as use of electromagnetic
guidance that circumvents X-ray use provides hope that one day endovascular
procedures will be carried out without the risk of exposing both patient and
operator to radiation.
Summary
• Endovascular operators performing standard and complex EVAR are at high

risk of receiving potentially harmful doses of occupational radiation exposure.
• Despite growing evidence of the dangers of chronic low dose radiation
exposure, operators remain poor at protecting themselves.

• Education is the key to reducing radiation exposure in endovascular
procedures.
• New technologies including real-time dosimeters may help alert operators to
high risk intraoperative behaviours.
References
1. Abbott A. Researchers pin down risks of low-dose radiation. Nature 2015; 523 (7558):17–18.
2. Kendrick DE, Miller CP, Moorehead PA, K, et al. Comparative occupational radiation exposure between
fixed and mobile imaging systems. J Vasc Surg 2016; 63 (1):190–97.
3. Patel AP, Gallacher D, Dourado R, et al. Occupational radiation exposure during endovascular aortic
procedures. Eur J Vasc Endovasc Surg 2013; 46 (4): 424–30.
4. Haulon S, Hertault A, Sobocinski J, Azzaoui R. How to Reduce Radiation Exposure During EVAR.
Endovasc Today 2015; Supplement (November): 27–31.
5. Bordoli SJ, Carsten CG, Cull DL, et al. Radiation safety education in vascular surgery training. J Vasc Surg
2014; 59 (3): 860–64.e1.
6. Kim C, Vasaiwala S, Haque F, et al. Radiation safety among cardiology fellows. Am J Cardiol 2010; 106
(1): 125–28.
7. Kirkwood ML, Arbique GM, Guild JB, et al. Surgeon education decreases radiation dose in complex
endovascular procedures and improves patient safety. J Vasc Surg 2013; 58 (3): 715–21.
93
8. Vlachos I, Tsantilas X, Kalyvas N, et al. Measuring scatter radiation in diagnostic X rays for radiation
protection purposes. Radiat Prot Dosimetry 2015; 165( 1–4): 382–85.
9. Racadio J, Nachabe R, Carelsen B, et al. Effect of real-time radiation dose feedback on pediatric
interventional radiology staff radiation exposure. J Vasc Interv Radiol 2014; 25 (1): 119–26.
10. Hertault A, Maurel B, Midulla M, et al. Editor’s Choice - Minimizing Radiation Exposure During
Endovascular Procedures: Basic Knowledge, Literature Review, and Reporting Standards. Eur J Vasc
Endovasc Surg 2015; 50 (1): 21–36.
11. El-Sayed T, Patel AS, Cho JS, et al. Radiation Induced DNA Damage in Operators Performing
Endovascular Aortic Repair. Circulation 2017; 117: 029550.
12. Thornton RH, Dauer LT, Altamirano JP, et al. Comparing strategies for operator eye protection in the
interventional radiology suite. J Vasc Interv Radiol 2010; 21 (11): 1703–07.
13. Uthoff H, Quesada R, Roberts JS, et al. Radioprotective lightweight caps in the interventional cardiology
setting: a randomised controlled trial (PROTECT). EuroIntervention 2015; 11 (1): 53–59.
14. Roguin A, Goldstein J, Bar O, Goldstein JA. Brain and neck tumors among physicians performing
interventional procedures. Am J Cardiol 2013; 111 (9):1368–72.
15. Reeves RR, Ang L, Bahadorani J, et al. Invasive cardiologists are exposed to greater left-sided Cranial
Radiation: The BRAIN Study (Brain Radiation Exposure and Attenuation during Invasive Cardiology
Procedures). JACC Cardiovasc Interv 2015; 8 (9):1197–206.
16. Rolls AE, Rosen S, Constantinou J, et al. Introduction of a Team Based Approach to Radiation Dose
Reduction in the Enhancement of the Overall Radiation Safety Profile of FEVAR. Eur J Vasc Endovasc
Surg 2016; 52 (4): 451–57.
17. Haqqani OP, Agarwal PK, Halin NM, Iafrati MD. Minimizing radiation exposure to the vascular surgeon.
J Vasc Surg 2012; 55 (3): 799–805.
18. Albayati MA, Kelly S, Gallagher D, et al. Editor’s choice - Angulation of the C-arm during complex
endovascular aortic procedures increases radiation exposure to the head. Eur J Vasc Endovasc Surg
2015; 49 (4): 396–402.
19. Goldsweig AM, Abbott JD, Aronow HD. Physician and patient radiation exposure during endovascular
procedures. Curr Treat Options Cardiovasc Med 2017; 19 (2): 10.
20. Andreassi MG, Piccaluga E, Guagliumi G. Occupational health risks in cardiac catheterization laboratory
workers. Circ Cardiovasc Interv 2016; 9 (4): 1–9.
94
Stroke from Thoracic Endovascular aortic
Procedures (STEP) controversies
The use of filter protection
in TEVAR patients—lessons
learned from a single-
centre experience
Introduction
Perioperative stroke in thoracic endovascular aortic repair (TEVAR) is a well-
established risk, with reported rates between 3% and 8% as well as associated
early mortality.1,2 Neuroimaging studies have demonstrated a significant burden
of new magnetic resonance imaging (MRI)-detected ischaemic brain injury in
patients undergoing TEVAR, with rates of up to 63–68%.3,4 These lesions have
been associated with an increased risk of future stroke and cognitive decline on
neuropsychometric testing.5 The volume of subclinical embolic infarcts on MRI has
been linked to worse short- and long-term verbal reasoning and memory scores in
carotid revascularisation.6
Transcranial Doppler monitoring studies have demonstrated a significant embolic
burden in both the diagnostic and procedural phases of TEVAR, with maximum
microembolic signals seen during contrast flushing and stent deployment in close
proximity to the supra-aortic vessels.4,7 The nature of these emboli, whether gaseous
or solid, has not been explored thus far.
The putative mechanism of brain injury in TEVAR is disruption of atherosclerotic
plaque into the cerebral circulation through manipulation of large delivery systems
in a diseased aortic arch. With this hypothesis in mind, our centre conducted
a pilot trial of a dual filter cerebral embolic protection system (Sentinel, Claret
Medical) to capture embolic debris and reduce particulate embolisation. We report
on the lessons learnt from this feasibility trial and report the key findings in 10
patients undergoing a TEVAR with embolic protection.
Cerebral embolic protection filter

Anatomical suitability
Sentinel is a 6Fr, 100cm long, steerable sheath comprising two conical filters made of
a 140µm pore biocompatible polyurethane film. It is a 6Fr delivery system inserted
via right percutaneous radial or brachial access. Two filters are then deployed
sequentially at the brachiocephalic and left common carotid arteries to protect the
brain throughout the procedure (Figure 1). Once the procedure is concluded, the
filters are captured and retrieved in reverse order of insertion. Aortic arch anatomy
has to fit the anatomical sizing requirements for the cerebral protection system:
97
A B
The use of filter protection in TEVAR patients—lessons learned from a single-centre experience •
C
Figure 1: (A) The Sentinel cerebral protection system (B)
Proximal landing zones 2, 3 and 4 suitable for the cerebral
protection system. (C) The Sentinel Cerebral Protection System
in-situ with TEVAR. The left subclavian is left unprotected
with the current device, leaving the left posterior circulation
vulnerable to embolisation through the left vertebral artery.
Although, in theory, one filter (proximal) only can be deployed
and retrieved, zones 0 and 1 are generally considered
unsuitable for this device.
the diameter of the origins of the brachiocephalic trunk and left common carotid
artery should range between 9mm and 15mm, and 6.5mm and 10mm, respectively,
without excessive tortuosity or >70% stenotic atherosclerotic disease.
Procedural and safety data

Since September 2015, more than 70 patients underwent various TEVAR procedures
in our unit, with overall anatomical suitability for cerebral embolic protection
device estimated at 59%, according to the manufacturer’s instructions for use. Of
those patients, 16 had cerebral embolic protection devices with 100% technical
success rate—defined as complete navigation, deployment and retrieval of filters.
So far, 10 patients have had complete clinical, radiological and histopathological
analysis and follow-up.
At 30 days, there have been no deaths or major adverse cardiac and cerebrovascular
events, including strokes. All patients underwent a succession of neurocognitive
tests to assess for more subtle cognitive decline for up to six months, and no
significant decline was noted.
The cerebral embolic protection device added a median of seven minutes (IQR
4.6–16) to the procedure, and increased fluoroscopy time by 3.3 minutes (IQR
2.4–3.9). The dose-area-product (mGy.cm2) for the cerebral embolic protection
device was 1824 (IQR 1235–3392) and it increased total procedural radiation by
2.2%. The average contrast volume used increased by 23mls (IQR 24–35). The
SENTINEL and CLEAN-TAVI randomised controlled trials of the device, used
98
Figure 2: Territories of new MRI lesions.
during transcatheter aortic valve implantation (TAVI), reported times of 13 and

18 minutes, respectively, with a similar addition of fluoroscopy time and a 5.8%
increase in radiation dose.8,9 Reduction in time was noted with consecutive cases,
reflecting correlation of navigation with operator experience.
Neuroimaging
There was a marked reduction in number and surface area of new cerebral lesions
on postoperative diffusion-weighted MRI (DW-MRI). The territory, number
and surface area of all new lesions were analysed by two independent, blinded
neuroradiologists. Twenty-three new DW-MRI lesions were noted in seven patients.
The median number of lesions was one (IQR 1–3), and the median surface area
was 6mm2 (IQR 3–16). Figure 2 shows the distribution of the lesions per vascular
territory: 15/23 (65%) were in the posterior circulation, 6/23 (26%) in the anterior
circulation, and 2/23 (9%) were in the temporo-occipital border-zone territory

supplied by either the posterior cerebral artery, or the middle cerebral artery. A
more diseased aortic arch (grade 3 & 4) was associated with an increase in lesions
with a larger diameter ≥3mm (r=0.663, p=0.05), but had no significant impact on
total MRI lesion number or surface area.
The use of the embolic protection device seems to show a reduction in the number
and size of new cerebral lesions, consistent with successful protection of the anterior
circulation when compared to neuroimaging studies published on infarction rate in
unprotected TEVAR. Kalhert et al 3 identified 29 new DW-MRI lesions in 12/19
(63%) patients undergoing TEVAR without protection, mostly in the anterior
circulation (66%), with a median lesion volume of 90mm3. We reported, in a
previous study, a 13% stroke rate in 52 unprotected patients undergoing TEVAR in
our unit, with a 68% silent cerebral infarction rate and median lesion surface area
of 16.5mm2 (IQR 8–171).4 The majority of the small lesions in this pilot study were
noticed in the hindbrain, supplied by the posterior cerebral artery, and of these,
most were in the left hindbrain. This would be consistent with the incomplete arch
protection as the left vertebral is unprotected and therefore embolisation through
the left posterior circulation is still possible. Overall, the device has still managed
to reduce the number and size of total ischaemic burden previously reported. We
are conducting further research to compare cerebral embolisation and ischaemic
99
injury rates in anatomically matched samples to ascertain the absolute benefit of
the device.
Cerebral embolisation
Emboli differentiation
Patients undergoing TEVAR have been shown to have a high number of
microembolic signals. The number of microembolic signals has been reported to
increase the risk of stroke and larger solid emboli (100um), as compared to gaseous
4um, are well recognised to arise from atheromatous plaque to cause blockade
in cerebral microcirculation and manifest as brain injury.7 However, there has
been conflicting evidence in the literature on the role of solid and gaseous emboli
in the development of ischaemic MRI lesions and neurological decline in the
interventional setting, with reports linking both solid and gaseous embolisation to
cerebral injury and cognitive decline.10–12
The nature of emboli in TEVAR has not been explored—in seven of 10
patients trialled with the protection device, dual-frequency transcranial Doppler
was performed of bilateral middle cerebral arteries with Embodop DWL (DWL).
This software insonates simultaneously with 2.0MHz and 2.5MHz frequencies to
differentiate between gaseous and solid emboli, through an automated calculation
of ratios of reflected ultrasound power (Figure 3A).
This is the first time the nature of embolisation has been explored in TEVAR. It
was interesting to note that the highest rate of embolisation occurred during the
deployment of the protection device itself (31.3%), although the majority of these
(95%) were gaseous in origin. Other highest risk phases were stent deployment
(26%) and contrast runs (22%), in keeping with previous studies and clear embolic
“showers” and gaseous clusters could be seen on transcranial Doppler (Figure 3B).
Figure 3A: Trancranial Doppler (Embodop DWL).

Left (solid embolus). Right (gas embolus).
100
Figure 3B: Embolic cluster of microembolic signals.
Histopathology
A total of 19 filters (10 proximal, nine distal) were analysed for debris composition,
particle count and diameter. One patient had one filter deployed and retrieved
due to poor imaging in an emergency case. Debris was captured in 18/19 filters
(95%)—this was similar to the experience reported in TAVI (97%).13 Filters
mostly had a combination of acute thrombus (95%), arterial wall (63%) and
foreign material (32%). The median total number of particles captured was
937 (146–1,687) and an average of 0.54mm2 of embolic material captured per
patient. Filters from emergency patients who were not on prior antiplatelet therapy
showed a trend towards increased surface area and diameter of particles captured.

Embolic protection may have benefit in an emergency situation where optimal
antithrombotic conditions have not been achieved.
Conclusion
The perioperative and longer-term neurological sequelae of TEVAR must be
addressed, and reduction of brain injury with filter based protection appears
encouraging with both a reduction in number and size of new MRI-detected
cerebral injury. The presence of embolic material captures, and the relationship
of an increased number of solid emboli to an increasing total surface area of MRI
lesions certainly supports the conclusion that particulate embolisation is harmful
and a protection filter can help to mitigate that risk. The device can be improved
for full protection and protection of the left subclavian.
The role and relevance of gaseous embolisation in cerebral injury must be further
investigated. Risk was greatest at the stent deployment and contrast run phases and
methods to reduce gas embolisation in these phases must be explored.
101
Summary
• The Sentinel cerebral protection system (Claret Medical) appears to be safe

and compatible with TEVAR with minimal increase in radiation dose and
reduced operator time. There are no reported early complications.
• Capture of embolic material “en route” to the brain, and the reduction in
number and size of new MRI lesions are encouraging findings and filter-based
cerebral protection may be a useful adjunct in protecting the brain in TEVAR.
• The current device does not protect all three supra-aortic trunks, leaving the
left posterior circulation vulnerable to embolisation, and the procedure/device
needs to be modified for complete protection.

• The significant rate of gaseous embolisation and its role in cerebral injury and
mechanisms to reduce it must be further investigated.
References
1. Gutsche JT, Cheung AT, McGarvey ML, et al. Risk factors for perioperative stroke after thoracic
endovascular aortic repair. Ann Thorac Surg 2007; 84: 1195–200.
2. Melissano G, Tshomba Y, Bertoglio L, et al. Analysis of stroke after TEVAR involving the aortic arch. Eur
J Vasc Endovasc Surg 2012; 43: 269–75.
3. Kalhert P, Eggebrecht H, Janosi RA, et al. Silent cerebral ischaemia after thoracic endovascular aortic
repair: a neuroimaging study. Ann Thorac Surg 2014; 98: 53–58.
4. Perera AH, Rudarakanchana N, Bicknell C, et al. Silent cerebral infarction and neurocognitive decline
following thoracic endovascular aortic repair. Br J Surg 2017. Article in press.
5. Vermeer SE, Prins ND, Den Heijer T, et al. Silent brain infarcts and the risk of dementia and cognitive
decline. N Engl J Med 2003; 348: 1215–22.
6. Zhou W, Baughman BD, Soman S, et al. Volume of subclinical embolic infarct correlates to long-term
cognitive changes following carotid revascularization. J Vasc Surg 2016; 65: 686–94.
7. Bismuth J, Garami Z, Anaya-Ayala JE, et al. Transcranial Doppler findings during thoracic endovascular
repair. J Vasc Surg 2011; 54: 364–69.
8. Kapadia SR, Kodali S, Makkar R, et al. Protection against cerebral embolism during transcatheter aortic
valve replacement. SENTINEL Randomized Trial. J Am Coll Cardiol 2017; 69: 367–77.
9. Haussig S, Mangner N, Dwyer MG, et al. Effect of a cerebral protection device on brain lesions
following transcatheter aortic valve implantation in patients with severe aortic stenosis. The CLEAN-
TAVI Randomized Clinical Trial. JAMA 2016; 316: 592–601.
10. Lund A, Nes RB, Ugelstad TP, et al. Cerebral emboli during left heart catheterization may cause acute
brain injury. Eur Heart J 2005; 26: 1269–75.
11. Skjelland M, Krohg-Sorensen K, Tennoe B, et al. Cerebral micro emboli and brain injury during carotid
artery endarterectomy and stenting. Stroke 2009; 40: 230–34.
12. Gerriets T, Schwarz N, Sammer G, et al. Protecting the brain from gaseous and solid micro-emboli
during coronary artery bypass grafting: a randomized controlled trial. Eur Heart J 2010; 31: 360–68.
13. Schmidt T, Akdag O, Wohlmuth P, et al. Histological findings and predictors of cerebral debris from
transcatheter aortic valve replacement: The ALSTER Experience. J Am Heart Assoc 2016; 10: 5 (11).
102
Transcranial Doppler—the
ultimate cerebrovascular
monitoring technique for arch
and supra-arch interventions
Introduction
Transcranial Doppler ultrasound is one of the least understood, rarely used, yet
potentially most valuable tools available for monitoring the cerebral circulation
during invasive procedures of the left heart, aortic arch and carotid circulation. It
has been an integral part of our monitoring system, and is the only tool that provides
real time feedback on cerebral flow and embolisation during the procedures. It is the
“stethoscope for the brain” and is non-invasive, safe and cost-effective in evaluating
the cerebrovascular circulation. Transcranial Doppler shows the direction of blood
flow and velocity in the intracerebral vessels, adding physiological information
to the anatomical images obtained with other imaging modalities. The recent
report by Lansky et al, emphasising the significance of type II stroke (diffusion
weighted MRI lesions in absence of clinical sequelae), has refocused the attention
of the medical device community on the importance of cerebral embolisation as
a complication of invasive procedures. In this chapter, we will describe in basic
terms what transcranial Doppler does, outlining its strengths and weaknesses and
our belief that this is a highly important tool that can be used to refine invasive
procedures by defining “embologenic phases” of the intervention.1
Understanding transcranial Doppler

Trancranial Doppler uses ultrasound (2MHz) to interrogate several of the
intracranial blood vessels. Typically, this is the middle cerebral arteries and anterior
cerebral arteries and rarely the basilar arteries and posterior communicating arteries.
It does this by using a low-frequency ultrasound emitter placed on areas of the
skull known to have thin bony plates that permit the beam to pass into the brain.
The most common windows, which are used are the bilateral temporal windows.
Although these are the most frequently used, windows are absent in up to 20% of
patients. This is the most significant limitation of transcranial Doppler.
Typically the ultrasound beam is directed along the ipsilateral anterior–middle
cerebral artery axis, but frequently crosses the mid line and can detect signal for the
opposite anterior cerebral artery and deeper areas of the opposite middle cerebral
artery. By adjusting the depth of the Doppler signal, an operator interrogates the
pulse wave form from each of these arteries. This will provide information from
103
2 1 2 1
Transcranial Doppler—the ultimate cerebrovascular monitoring technique for arch and supra-arch interventions •
Figure 1: Normal MCA/ACA flow signals from the temporal approach. Schematic courtesy of Debra Liles Canter. (A) PMD
display showing the flow signals from 25–85 mm. (B) The signal at 45–65 mm represents the ipsalateral MCA directed
towards the probe and the cortex. (C) The blue signal at 65–82mm represents the ipsalateral ACA flow directed away from
the probe. (D) The deepest red signal at 82-85 mm represents the contralateral ACA flow directed towards the probe. (E)
The horizontal yellow line at 64mm represents the selected gate for spectral display, which is at the overlapping signals
from the MCA and ACA. (F) The corresponding spectral represents the MCA flow velocity waveform above the zero line. The
ACA waveform is below the zero line and registers a negative velocity since the direction of flow is away from the probe.
The right (G) and left (H) side bars are on either side of the PMD and spectral displays. (I) Schematic of the circle of Willis
with the vessel direction indicated by (1) flow towards the probe and (2) flow away from the probe.
each of these arteries on blood flow direction and blood flow velocity. Immediate
feedback is obtained. Transcranial Doppler ultrasound, therefore, detects:
• Flow velocity
• Flow direction
• Immediate changes in either direction or velocity
Transcranial Doppler can also detect embolisation and is very sensitive, detecting
particles down to 40 microns in diameter. Indeed, this sensitivity has lead to
the negative opinion of many internationalists, “I do not want to know about
this, it has no clinical manifestations”. The obvious retort is, “Explain to me the
good emboli which are going up into the brain”. Emboli detected on Doppler are
referred to as high intensity transient signals and transcranial Doppler provides
both a visual and auditory signal of their presence. Emboli travelling up the carotid
system pass from deep in the brain, either toward the probe via the middle cerebral
artery or away from the probe via the anterior cerebral artery. It takes time for the
emboli to traverse these vascular pathways and results in a distinctive reflection
signal along the X- or time axis. Clearly the Lansky classification has refocused the
argument, which we believe will rejuvenate interest in the method.
Consequently Transcranial Doppler ultrasound can:

• Detect emboli
• Count emboli (semi-quantitatively)
• Demonstrate which pathways the emboli are following: right hemisphere;
left hemisphere; anterior cerebral artery territory; and middle cerebral artery
territory
• Immediately detect when emboli are occurring and what manoeuvres are taking
place in the left heart and arch
104
• Show the absence of emboli during certain phases of the procedure. This
would mean that should the patient awake with an event, then that event did
not occur during the phase with no HITS. This allows the operator or device
engineer to focus on other parts of the procedure.
Transcranial Doppler basics

Since the introduction of transcranial Doppler by Rune Aaslid, the most important
advancement has been the addition of power M-mode Doppler to the single
channel Doppler screen.2 Power M-mode Doppler detects not only the presence
of flow but also its depth, direction, and resistance. The M-mode screen enables
visualisation of intracranial flow signals from depths of between 25mm and 85mm.
All the vessels in line with the focal zone of the probe are captured on the M-mode
display according to their depth (Figure 1).
By scrolling down the M-mode display, one can highlight the selected gate for
spectral display (horizontal yellow line on the power M-mode Doppler display,
Figure 1E). The selected gate displays the spectral waveforms at the bottom of the
transcranial Doppler screen (Figure 1F) with velocity measurements. The spectral
waveforms can be compressed or expanded to display timeframes of between four
and 16 seconds on a single screen.
By convention, the M-mode display is at the top and the spectral display is
at the bottom of the screen. Red colour on the M-mode screen is used for flow
moving towards the probe and blue away from the probe. On the M-mode display,
40–65mm depth corresponds to the location of the M1 segment of the middle
cerebral arter (Figure 1B). The flow pattern is normally continuous throughout
the cardiac cycle and should appear as a relatively homogenous pattern across the
M-mode display corresponding to a low-resistance flow signal.
Figure 2: Normal MCA/ACAs displayed with microembolic signals. Schematic courtesy of Debra Liles Canter. (A) PMD
display with selected gate at 59mm for spectral display. The vertical bright white lines represent microembolic signals
(MES). Emboli are present in the contralateral ACA (the light grey signal at 78–82 mm), the ipsalateral ACA (dark grey
signal at 70–78mm), and the ipsalateral MCA (light grey signal at 55–68mm). Note the backslash slant of the MES as it
travels in the MCA (yellow oval). Since direction of flow is away from the probe, the MES in the ipsalateral ACA (white
oval) have a forward slash shape. (B) The spectral display at 59mm only shows the MES at that depth. Total spectral
MES count: 5. Total PMD MES count:> 10. (C) Schematic showing emboli in the distal MCA.
105
Lumsden AB and Z Garami
Figure 3: Head frame positioning
Once the gate of interest is selected from the power M-mode Doppler, the
corresponding spectral display appears in the lower half of the screen. The saw-
tooth pattern of the waveform reflects the flow velocity changes between systole
and diastole (Figure 1F).
If the anterior cerebral artery is selected (usually at 65–75 mm), flow is expected
to be directed away from the probe (Figure 1C).
On either side of the M-mode and spectral displays are the side bars. On the
left side bar (Figure 1H), information about the target vessel can be entered by
the sonographer. The power setting should be kept between 80 and 100, keeping
the thermal index number under two because of mandated safety regulations. The
right side bar (Figure 1G) shows velocity information from the spectral waveform,
including peak systolic, mean flow, and end-diastolic velocity. From the spectral
velocity measurements, the mean flow velocity and the pulsatility index are
calculated and can be simultaneously displayed on the right side bar. The delta
percentage refers to the percent change from baseline mean flow velocity.
The pulsatility index is an indirect measure of peripheral resistance. Post-stenotic
blunted waveforms have a low-resistance pulsatility index <0.6. Normotensive
patients that are breathing room air should have a pulsatility index of between
0.6–1.2 in all normal diameter vessels. Increased pulsatility index greater than
100% embolus detection clamp release is predictive of perioperative stroke.3
Embolus detection
Transcranial Doppler can detect both gaseous and particulate emboli. We believe
that any emboli passing into the circulation can potentially be hazardous. There is,
in other words, there are no “good” cerebral emboli during a case The minimum
detectable diameter of gaseous emboli has been reported at 10 microns while
particulate emboli can be detected from 40 microns. Based on consensus committee
106
A B Figure 4: (A) Bilateral middle
cerebral artery monitoring during
carotid endarterectomy with
application of shunt. (B) Clamp
applied to the carotid artery (clamp
on) with marked reduction of artery
flow (>50% decrease in mean flow
velocity). (C) Placement of shunt
with restoration of artery flow and
C D associated embolic shower. (D)
Removal of shunt and arterial clamp
with embolic shower.
guidelines, certain technical criteria must be met to qualify as microembolic signals

by transcranial Doppler (Figure 2).4–5
Several observations on microembolic signals can be made based on their Doppler
signature. A microembolic signal recorded on M-mode can be tracked as it moves
through the intracerebral circulation. An embolus travelling up the middle cerebral
artery, for example, will first appear in the proximal portion of the artery on power
M-mode Doppler at 60mm. As the embolus travels, it creates a signature in the
more distal microembolic signal at 40mm (Figure 2A). Additionally, the embolic
signal often has a slight tilt in M-mode that indicates direction. In the M-mode, it
is usually a backslash-shaped signal (“/”). The signatures made by the same embolus
are separated by location as well as by time. Such multiple depth assessments and
signature shapes help to confirm that the tracked object is moving through the
circulation and differentiate signal from artefact.
Bilateral middle cerebral artery monitoring during interventions helps differentiate
and predict the source of embolisation. If microembolic signals are seen on both
the side of the intervention and the contralateral side, the origin of embolus may be
from a central source, e.g., the heart or aorta. Unilateral microembolic signals more
likely result from catheter movement, manipulation or selective injection in the
Figure 5: Unilateral middle cerebral

A B artery monitoring of carotid
endarterectomy showing adequate
artery flow after arterial clamping.
(A) Baseline artery insonation prior
to start of the procedure showing
an elevated pulsatility index in this
patient with chronic hypertension. (B)
Application of carotid artery clamp
C (white arrow) with drop in mean flow
D velocity from 20 to 13. (C) Restoration
of flow velocities within 30 seconds,
demonstrating the adequacy of
collaterals. No shunt was used. (D)
Release of arterial clamp.
107
Figure 6: Contrast injected into right
common carotid artery.

Figure 7: Bilateral middle cerebral

artery monitoring during right carotid
artery stenting. Embolic shower during
carotid stent deployment. The artery
spectral waveform shows minimal
disturbance.
Figure 8: Left Middle cerebral

A B artery showing hyperperfusion after
carotid artery unclamping during
carotid endarterectomy. (A) Clamp
applied to carotid artery (arrows). (B)
Clamp released off carotid artery. (C)
Hyperperfusion phenomenon with
>150% increase in mean flow velocity
from preclamp value (22—52; 236%
C increase). The mean flow velocity
D increase persisted past two minutes
and corrective measures were
taken. (circled % change). (D) After
hyperventilation for several minutes,
the mean flow velocity is reduced.
(circled % change).
108
Figure 9: Bilateral middle cerebral artery monitoring during transcatheter aortic valve implantation (TAVI) : delivery
catheter in the descending aorta (baseline bilateral equal artery signals).
Figure 10: Bilateral middle cerebral artery monitoring during TAVI: delivery catheter passed the arch large vessels, now
in the ascending aorta (left artery signal indicates occlusion after unilateral shower of emboli).
ipsilateral carotid system. However, emboli can cross the midline through collateral
pathways and enter the contralateral middle cerebral artery even with two patent
internal carotid arteries. Over 10% of embolic lesions detected on post-procedural
testing occur on the side contralateral to the intervention.6–7
Case examples
Cerebral hypoperfusion during carotid endarterectomy
After carotid clamp placement, if the mean flow velocity drops below 50% of
baseline (delta% greater than 50%), this suggests that the cerebral hemisphere
cannot recruit adequate collaterals (Figure 4). The distal arterial tree will become
maximally dilated so that the pulsatility index may also decrease. This indicates
the need for shunting. However, after monitoring a carotid endarterectomy with
transcranial Doppler, the experienced Doppler sonographer realises that routine
shunt placement in carotid endarterectomy exposes patients to embolisation both

during shunt insertion and removal. Nevertheless, there is no consensus in the
literature regarding selective vs. routine shunting (Figure 5).
Selective shunting requires cerebral monitoring to determine when shunt
placement is warranted. Several methods have been studied and include: near-
infrared spectroscopy, electroencephalography, somatosensory evoked potentials,
internal carotid artery stump pressure, and transcranial Doppler. Finally, monitoring
interventions in which the conscious patient is treated under local or regional
anaesthesia allows for patient interaction, limited neurological examination, and
can be used in conjunction with other cerebral monitoring methods. 3,8–11
Cerebral hyperperfusion during carotid endarterectomy

Cerebral hyperperfusion by Doppler criteria is defined as a >150% increase in mean
flow velocity from the pre-clamp flow velocity during carotid artery stenting or
endarterectomy. Immediate middle cerebral artery mean flow velocity measurements
109
Figure 11: Bilateral middle cerebral artery monitoring during cardiopulmonary resuscitation
following circulatory arrest at valve placement.
after ballooning or clamp release often show a transient hyperperfusion that

normalises before the end of the procedure. Our technique is to wait two minutes
after correction of stenosis, to allow for restoration of the autoregulatory system.
After two minutes, if signs of hyperaemia still persist, we make the diagnosis of
hyperperfusion and initiate appropriate treatment, i.e., blood pressure management
and hyperventilation.
Carotid artery stenting

Unlike carotid artery endarterectomy, sudden flow velocity and waveform changes
are not generally seen in carotid artery stenting except briefly during balloon
angioplasty. In addition to atherosclerotic emboli, contrast injections in the aortic
arch and the carotid artery allow air bubbles to embolise to the brain and are
detected as microembolic signals by transcranial Doppler. Injection of contrast in
the carotid system appears on Doppler as a bright reflection associated with the
signals (Figure 6).
There are currently several techniques to reduce embolisation during carotid
artery stenting. The most prominent contenders are distal filter wire deployment
and reversal of carotid artery flow. Even when using a distal filter wire, stent
deployment is still associated with distal embolic showers (Figure 7).
Transcatheter aortic valve implantation

Highest emboli count is observed at the device positioning and deployment.
Unilateral signal loss could indicate middle cerebral artery obstruction and stroke,
while bilateral signal loss is indicative of circulatory collapse (Figures 9–11).
Thoracic endovascular aortic repair

Microemboli may also occur during endovascular repair grafting of aortic aneurysm.
The highest microemboli signal counts were generated by the pigtail catheter
110
during the diagnostic phase and by device deployment during therapeutic phase of
the TEVAR (Figure 12).12–21
Conclusion
Transcranial Doppler has many well accepted clinical uses, including vasospasm
detection after intracranial bleeding and detection of intracranial stenoses.8-10
However, it has not yet made the leap into being used to detect flow alterations
or emboli occurring during procedures. For example, during treatment of type
A dissection, bilateral cerebral perfusion is provided by unilateral axillary artery
cannulation. In this situation, emboli are less relevant but flow detection is
crucial. On the other hand, transcatheter aortic valve implantation, carotid
endarterectomies, carotid artery stenting and thoracic endografting are all
associated with flow alterations and are highly emboligenic. Transcranial Doppler
alone provides the operator with immediate feedback on when flow is reduced
and when emboli occur. This is crucial in helping us understand what we refer
to as the “emboligenic” phases of the procedure, and the information is vital to
interventionists and device manufacturers as we strive to reduce the incidence of
type II stroke.
Summary
• Transcranial Doppler represent the ultimate method of cerebrovascular

monitoring during carotid, aortic and valve interventions
• Power M-mode Doppler is a GPS for finding intracranial vessels
• Doppler allows real-time monitoring of microembolic signals and cerebral
blood flow during each phase of the procedure
• Transcranial Doppler is too sensitive is an often heard criticism, but cerebral
emboli are never good — Lanksy has refocused us on cerebrovascular
protection.
• Beyond emboli detection, Doppler also monitors cerebral haemodynamics,
detects malperfusion and intracranial obstruction, i.e. stroke
References
1. Lansky AJ, Messé SR, Brickman AM, et al. Proposed Standardized Neurological Endpoints for
Cardiovascular Clinical Trials: An Academic Research Consortium Initiative. J Am Coll Cardiol 2017;
69 (6): 679–691.
2. Aaslid R, Markwalder TM, Nornes H. Noninvasive transcranial Doppler ultrasound recording of flow
velocity in basal cerebral arteries. J Neurosurg 1982; 57 (6): 769–74.
3. Ackerstaff RG, Moons KG, van de Vlasakker CJ, et al. Association of intraoperative transcranial doppler
monitoring variables with stroke from carotid endarterectomy. Stroke 2000; 31 (8): 1817–23.
4. Georgiadis D, Siebler M. Detection of Microembolic Signals with Transcranial Doppler Ultrasound.
In: Baumgartner RW, editor. Handbook on Neurovascular Ultrasound. Front Neurol Neurosci. Basel,
Karger; 2006. Vol 21, p. 194–205.
5. Basic identification criteria of Doppler microembolic signals. Consensus Committee of the Ninth
International Cerebral Hemodynamic Symposium. Stroke 1995; 26 (6): 1123.
6. Tedesco MM, Lee JT, Dalman RL, et al. Postprocedural microembolic events following carotid surgery
and carotid angioplasty and stenting. J Vasc Surg 2007; 46 (2): 244–50.
111
7. Poppert H, Wolf O, Resch M, et al. Differences in number, size and location of intracranial microembolic
Lumsden AB and Z Garami
lesions after surgical versus endovascular treatment without protection device of carotid artery
stenosis. Neurol 2004; 251 (10): 1198–203.
8. Schutt RC, Bhimiraj A, Estep JD, et al. Deflation Timing Influences Intra-Aortic Balloon Pump-Mediated
Carotid Blood Flow Reversal: A Case Report. Circ Heart Fail 2016; 9 (9): e003474.
9. Tarnoki AD, Tarnoki DL, Giannoni MF, et al. Heritability of central blood pressure and arterial stiffness:
a twin study. J Hypertens 2012; 30 (8):1564–71.
10. Alexandrov AV, Sloan MA, Tegeler CH, et al. Practice standards for transcranial Doppler (TCD)
ultrasound. Part II. Clinical indications and expected outcomes. J Neuroimaging 2012; 22 (3): 215–24.
11. Spencer MP. Transcranial Doppler monitoring and causes of stroke from carotid endarterectomy.
Stroke 1997; 28 (4): 685-91.
12. Rodés-Cabau J, Kahlert P, Neumann FJ, et al. Feasibility and exploratory efficacy evaluation of the Embrella
Embolic Deflector system for the prevention of cerebral emboli in patients undergoing transcatheter
aortic valve replacement: the PROTAVI-C pilot study. JACC Cardiovasc Interv 2014; 7 (10): 1146–55.
13. Chen CI, Iguchi Y, Garami Z, et al. Analysis of emboli during carotid stenting with distal protection
device. Cerebrovasc Dis 2006; 21 (4): 223–28.
14. Garami ZF, Bismuth J, Charlton-Ouw KM, et al. Feasibility of simultaneous pre- and postfilter transcranial
Doppler monitoring during carotid artery stenting. J Vasc Surg 2009; 49 (2): 340–44.
15. Pacchioni A, Mugnolo A, Penzo C, et al. Cerebral microembolism during transradial coronary
angiography: comparison between single and double catheter strategy. Int J Cardiol 2014; 170 (3):
4383–89.
16. Pacchioni A, Versaci F, Mugnolo A, et al. Risk of brain injury during diagnostic coronary angiography:
comparison between right and left radial approach. Int J Cardiol 2013; 167 (6): 3021–26.
17. Estrera AL, Garami Z, Miller CC, et al. Acute type A aortic dissection complicated by stroke: can
immediate repair be performed safely? J Thorac Cardiovasc Surg 2006; 132 (6): 1404–08.
18. Bismuth J, Garami Z, Anaya-Ayala JE, et al. Transcranial Doppler findings during thoracic endovascular
aortic repair. J Vasc Surg 2011; 54 (2): 364–69
19. Garami Z, Lumsden AB. Intra-Operative TCD Monitoring. In: editor: Alexandrov AV, Cerebrovascular
Ultrasound in Stroke Prevention and Treatment. 2nd ed. Hoboken, NJ: Wiley-Blackwell; 2011. p. 214–227.
20. Estrera AL, Garami Z, Miller CC 3rd, et al. Determination of cerebral blood flow dynamics during retrograde
cerebral perfusion using power M-mode transcranial Doppler. Ann Thorac Surg 2003; 76 (3): 704–10.
21. Estrera AL, Garami Z, Miller CC 3rd, et al. Cerebral monitoring with transcranial Doppler ultrasonography
improves neurologic outcome during repairs of acute type A aortic dissection. J Thorac Cardiovasc
Surg 2005; 129 (2): 277–85
112
Juxta-renal (complex abdominal aortic) controversies
Controversies in management
of short, angulated, wide
and challenging aortic
proximal necks—chimney,
FEVAR and open
L Bertoglio, L Apruzzi, D Mascia, A Melloni,
G Melissano and R Chiesa
Introduction
Nowadays, anatomically suitable abdominal aortic aneurysms are preferentially treated
with endovascular aortic repair (EVAR) in the vast majority of centres.1,2 The main
anatomical limitations for EVAR are the proximal aortic neck length, diameter,
angulation and presence of thrombotic apposition. Infrarenal EVAR has been associated
with worse outcomes and more frequent reinterventions in hostile necks.3–5
To overcome these limitations, more complex endovascular techniques have
been proposed for aneurysms with hostile proximal neck features to increase
the applicability of EVAR. In particular, the use of parallel graft techniques and
fenestrated endografts (FEVAR) is now widespread and represents an option for
high-risk surgical candidates.
The aim of this chapter is to illustrate the current advantages and limitations of
possible treatment strategies for aneurysms with hostile proximal necks.
Parallel graft techniques

The “chimney”, “snorkel” and “periscope” techniques (chEVAR) have been proposed
to increase EVAR applicability by relocating the sealing zone more cranially, at the
level of the origin of visceral vessels, thus expanding the indication of standard
EVAR to juxta-renal and pararenal aortic aneurysms. Chimneys and snorkels are
defined as stent grafts deployed in a craniocaudal direction, outside and parallel to
the aortic endograft main body, in order to maintain perfusion from above to renal
or visceral branches during EVAR. Periscopes are instead placed in a caudocranial
direction, perfusing the target vessels from below. First described by Greenberg et
al, chEVAR was suggested as a bailout procedure to restore flow in visceral aortic
side branches unintentionally covered during endograft deployment; nowadays, it
is considered an appealing approach to intentionally cover visceral vessels, while
preserving flow, during complex EVAR.6
115
L Bertoglio, L Apruzzi, D Mascia et al
A B C D
Controversies in management of short, angulated, wide and challenging aortic proximal necks—chimney, FEVAR and open •
Figure 1: Symptomatic short-necked AAA with asymmetric origin of renal arteries (A) treated with a single chimney to
extend the neck length proximally (B). Intraoperative angiography demonstrates successful exclusion of the aneurysm
and patency of the stented renal artery (C and D).
Possible advantages are the off-the-shelf availability in case of urgent repairs,

potentially lower costs and universal applicability with low-profile EVAR devices
for those cases involving small access vessels (Figure 1).7
In a review of the literature, Katsagyris et al reported the results of five studies
comprising 94 patients with juxta-renal aneurysms treated with chEVAR.8 The
30-day mortality rate was 5.3%. The incidence of acute kidney injury was 12%,
while cardiac and pulmonary complications were, respectively, 7.4% and 3.2%.
An early type I endoleak was reported in 10% of cases. The largest worldwide
experience with chEVAR was published in the PERICLES multicentre registry
by Donas et al, with a total of 517 patients: the early mortality rate was 4.9%,
with a 79% survival rate at 17.1 months of follow-up.9 An early type I endoleak
was noted in 3.7% of cases and persisted only in 0.4%. The primary patency of
chimney grafts was 94%.
The main disadvantage of chEVAR is the risk of type I endoleaks secondary
to gutter formation between the parallel grafts (aortic endograft and the renal/
visceral stent grafts). The risk of gutter occurrence is directly proportional to the
number of parallel grafts employed and inversely proportional to the length of
overlap between the aortic endograft and renal/visceral stent grafts. More recently,
to reduce the incidence of gutter leaks, a combination of chimney technique with
endovascular aneurysm sealing (EVAS) has been proposed.10,11 The rationale is to
incorporate the parallel graft into the endobag to obliterate the gutters.
Regardless, the most important limitation of chEVAR is that the configuration
of these parallel grafts can preclude future endovascular reinterventions to fix type
I endoleaks. In the situation of persistent endoleaks or progression of aortic disease
to the proximal sealing zone, proximal relining might not be a feasible option,
not even with custom-made devices, thus leaving open conversion as the only
solution even for high-risk surgical candidates. For these reasons, the application
of chEVAR should be limited to emergent/urgent cases in which patients cannot
wait for a custom-made graft and are unfit for open repair.
116
A B C
Figure 2: Recent improvements with fenestrated endovascular devices can be used to treat complex cases also with
diseased iliac and femoral accesses. (A) Pararenal aneurysm in a patient with previous iliac axis bilateral stenting and
subsequent left iliac occlusion managed by femoral-to-femoral bypass. (B) A new preloaded low-profile device was
employed to address all target vessels through the narrow right iliac access (6mm in diameter) and successfully exclude
the aneurysm (C).15
Fenestrated endovascular repair

Fenestrated and branched devices can be employed to incorporate visceral vessels
into the repair, thus expanding EVAR technology to aneurysms with short landing
zones or involvement of aortic side branches (juxta-renal and pararenal aneurysms).
After the initial report in 1996,12 the development of fenestrated devices customised
to individual patient anatomy allowed the widespread diffusion of these types of
repairs. One major drawback of this technology is the time required for custom-
made endografts, usually six to eight weeks, which limits their application to
elective and stable cases. Another drawback is the requirement for large introducer
sheaths, preventing their application in patients with inadequate access vessels.
However, more recently, off-the-shelf and low-profile fenestrated grafts have been
investigated to address these limitations and increase the clinical applicability of
this technology (Figure 2).13,14
Based on contemporary results from high-volume aortic centres, early and mid-
term outcomes of FEVAR can be comparable to open surgery, when performed by
an experienced team.15,16 Oderich et al reported the outcomes of 42 patients treated
with FEVAR for pararenal aortic aneurysms with no deaths at 30 days and 9% of
acute kidney injury.17 One-year survival was 89±5% with no ruptures or conversion
to open surgery at a mean follow-up of 9.2±7 months.
A systematic review of the literature comparing 364 FEVAR patients to 1,164
open repair patients from 2001 to 2008 showed lower 30-day mortality (1.4% vs.
3.8%) and transient renal failure (14.9% vs. 20%) in the endovascular group.18
Deery et al published their early experience of FEVAR compared to open repair
for complex aneurysms.19 In both groups, the 30-day mortality was 0% and there
was no difference in major adverse events. The one-year survival rate was similar
(100% in the FEVAR group vs. 92% in the open repair group) with higher rates of
graft complications for FEVAR patients during follow-up.
117
Furthermore, a systematic review comparing outcomes of FEVAR to open surgical
repair demonstrated equivalent short-term mortality and renal dysfunction rates,

while FEVAR was associated with higher incidence of long-term renal dysfunction,
lower long-term survival and increased need for secondary interventions, especially
with 3–4 fenestrations designs.20
A recent review by Li et al compared chEVAR with FEVAR: FEVAR demonstrated
better results compared with chEVAR in terms of 30-day mortality (1% vs. 3.8%),
late mortality (5.4% vs. 9.5%), renal impairment or failure (5.5% vs. 21.5%) and
type I endoleaks (3.7% vs. 7.6%).21
Although FEVAR provides an appealing solution for aneurysms with hostile
proximal necks and for juxta-/pararenal aneurysms, it does have its limitations
regarding delivery system size and constructional restraints related to position of
the splanchnic and renal vessels.
Open repair
Open surgical repair is a well-established treatment option for aneurysms with
hostile proximal neck and is widely considered the gold standard for fit patients.2
It provides long-lasting results and few graft-related complications at long-term
follow-up, with 74% survival at five years, a 10% rate of renal injury and only one
aneurysm-related death over 199 patients in a study by Tsai et al.22
A transperitoneal approach can be used to expose the aorta especially when
inter-renal or suprarenal clamping is planned. A retroperitoneal approach through
a left flank incision might be employed to access the more proximal visceral aorta,
although it precludes direct control of the right renal artery. Suprarenal clamping
might be preferred over supravisceral clamping in elective cases, thus eliminating
the need of coeliac trunk and superior mesenteric artery perfusion during surgery;
however, there is no consensus on whether supravisceral clamping carries higher
risk of mortality and morbidity.23,24 Adjunctive procedures on the renal arteries,
including endarterectomy, direct reimplantation, bypass grafting, and stenting are
necessary in 6–16% of cases (Figure 3).25,26
A meta-analysis by Jongkind et al reviewing 21 publications on open repair of
juxta-renal aneurysms showed a perioperative mortality rate of 1.9% (95% CI
1.8–4.6%), which is comparable to standard infrarenal repair. In a more recent
single case series by Ferrante et al of 200 patients, survival estimates were 78% at
five years and 60.5% at 10 years.27,28
Data about the impact of open repair of juxta-renal aneurysms on renal function
are heterogeneous, with a pooled rate of postoperative renal insufficiency of 13.9%,
although permanent dialysis was needed in less than 3% of the cases.24
The absence of a widely accepted definition for renal outcomes after aortic surgery
is a confounding factor and can interfere with the identification of preoperative or
intraoperative risk factors for renal insufficiency.
The role of renal perfusion is still debated as the renal protection attributed
by cold crystalloids and mannitol must be balanced against the possible arterial
damage associated with direct cannulation. A selective use can be suggested in
more complex cases to avoid prolonged kidney ischaemia.29,30
Fit patients should be offered open surgery as a first option; nonetheless, not
all patients are good candidates for open repair, as this procedure may require
prolonged suprarenal aortic clamping with consequent haemodynamic instability.
118
A B C
Figure 3: Pararenal aneurysm treated with open repair with suprarenal clamping (A) and selective bilateral
reimplantation of both renal arteries to the aortic graft with hybrid sutureless graft interposition (B). Postoperative CT
scan (C) demonstrates patent renal vessels at follow-up.
San Raffaele open repair experience

Between 2010 and 2015, 157 patients with complex aneurysm (145 men and 12
women; mean age 72±7 years) underwent open surgical repair at our institute.
In the same time period, 13 patients were treated with endovascular repair with
FEVAR or chEVAR. Fifty (31.84%) of these aortic aneurysms were suprarenal, 66
(42.03%) were pararenal and 41 (26.13%) were juxta-renal.
Elective surgery was performed in 154 (98.1%) cases, while emergency surgery
was required in three (1.9%) cases. Selective renal perfusion with Custodiol
was used predominantly in the suprarenal (90%) and pararenal (75.8%) groups
compared to the juxta-renal group (7.3%). Carrel patch was employed for
visceral artery reimplantation in 74% of the cases in the suprarenal group, and
direct reimplantation was performed in 97% of the cases in the pararenal group.
Interposition of a graft with distal sutureless anastomosis (Gore Hybrid) was used
to reimplant renal arteries in 38% of the suprarenal, 7.6% of the pararenal and
4.9% of the juxtarenal aortic aneurysms. Operative time (238.4±79.9 minutes;
p<0.001) and duration of aortic cross clamping (43.7±14.9 minutes; p=0.009)
were longer in the suprarenal group. Blood loss (27ml; p<0.001) was significantly
higher in the suprarenal group compared to the other groups.

A retrospective analysis of patients (93/157) with adequate preoperative computed
tomography (CT) angiography imaging quality (slice thickness ≤1.5mm) was
performed to evaluate theoretical endovascular feasibility for FEVAR of these cases
managed by open surgery. Patients were then stratified according to the required
theoretical FEVAR design (two, three or four fenestrations): 11 patients (11.8%)
would have required two fenestrations for treatment (2FEN group), 20 patients
(21.5%) would have required three fenestrations (3FEN group), and 62 patients
(66.7%) would have required four fenestrations (4FEN group).31
Patients of the 4FEN group required reimplantation of visceral and renal vessels
more frequently than patients of the 3FEN and 2FEN group (37% vs. 19%;
119
p=0.054). Median operative time was higher in the 4FEN group compared to
the 3FEN and 2FEN group (196±18min vs. 173±32min; p=0.023). Nonetheless,
41.9% of the procedures for 4FEN patients required <180min of operative time.
Aortic cross clamping time was significantly higher in the 4FEN group compared
to the 3FEN and 2FEN (41±4min, 39±8min, and 29±5min respectively; p=0.009).
Blood transfusions more than 500mL were required in 39% of the 4FEN patients,
25% of the 3FEN and 0% of the 2FEN (p=0.031). Intensive care unit stay was
needed in 65% of patients of the 4FEN group, 45% of those of the 3FEN group
and 18% of the 2FEN patients (p=0.011).
Although the surgical management of those patients who would have required a
four-fenestration design is technically more demanding, it is interesting to note that
most of these cases can still be managed with a suprarenal (43%) or infrarenal (21%)
clamping alone (only 36% supravisceral), and with no need of vessel reimplantation
in 63% of the cases. These results are the reason why, in our centre, proximal
abdominal aortic aneurysms (short-necked, juxta-, para- and suprarenal aneurysm)
are still routinely managed by means of open repair in suitable surgical candidates,
while endovascular treatment is reserved only to selected cases of this pathology.
Summary
• Open surgery represents the gold standard for treatment of fit abdominal aortic
aneurysm patients with hostile necks, with better long-term results compared to
endovascular treatment.
• Endovascular strategies (chEVAR or FEVAR) are a less invasive option for patients
deemed unfit for open repair.
• FEVAR, if anatomically feasible, is the alternative option to open repair in high-
risk surgical candidates.
• ChEVAR is an off-the-shelf solution applicable especially in cases of symptomatic
aneurysms or whenever a FEVAR custom-made device is not an option.
References
1. Chaikof EL, Dalman RL, Eskandari MK, et al. The Society for Vascular Surgery practice guidelines on the
care of patients with an abdominal aortic aneurysm. J Vasc Surg 2018; 67: 2–77.
2. Moll FL, Powell JT, Fraedrich G, et al. Management of abdominal aortic aneurysms clinical practice
guidelines of the European society for vascular surgery. Eur J Vasc Endovasc Surg 2011; 41 Suppl 1:
S1–S58.
3. Antoniou GA, Georgiadis GS, Antoniou SA, et al. A meta-analysis of outcomes of endovascular
abdominal aortic aneurysm repair in patients with hostile and friendly neck anatomy. J Vasc Surg 2013;
57: 527–38.
4. Broos PP, Stokmans RA, van Sterkenburg SM, et al. Performance of the Endurant stent graft in
challenging anatomy. J Vasc Surg 2015; 62: 312–18.
5. Giménez-Gaibar A, González-Cañas E, Solanich-Valldaura T, et al. Could preoperative neck anatomy
influence follow-up of EVAR? Ann Vasc Surg 2017; 43: 127–33.
6. Greenberg RK, Clair D, Srivastava S, et al. Should patients with challenging anatomy be offered
endovascular aneurysm repair? J Vasc Surg 2003; 38: 990–96.
7. Massmann A, Serracino-Inglott F, Buecker A. Endovascular aortic repair with the chimney technique
using the ultralow-profile Ovation stent-graft for juxtarenal aneurysms having small iliac access
vessels. Cardiovasc Intervent Radiol 2014; 37: 488–92.
120
8. Katsargyris A, Topel I, Oikonomou K, et al. Comparison of outcomes with open, fenestrated, and
chimney graft repair of juxtarenal aneurysms: Are we ready for a paradigm shift? J Endovasc Ther 2013;
20: 159–69.
9. Donas KP, Lee JT, Lachat M, et al. Collected world experience about the performance of the snorkel/
chimney endovascular technique in the treatment of complex aortic pathologies: The PERICLES
registry. Ann Surg 2015; 262: 546–53.
10. Dijkstra ML, Lardenoye JW, van Oostayen, et al. Endovascular aneurysm sealing for juxtarenal aneurysm
using the Nellix device and chimney covered stents. J Endovasc Ther 2014; 21: 541–47.
11. Youssef M, Zerwes S, Jakob R, et al. Endovascular aneurysm sealing (EVAS) and chimney EVAS in the
treatment of failed endovascular aneurysm repairs. J Endovasc Ther 2017; 24: 115–20.
12. Park JH, Chung JW, Choo IW, et al. Fenestrated stent-grafts for preserving visceral arterial branches
in the treatment of abdominal aortic aneurysm: preliminary experience. J Vasc Interv Radiol 1996; 7:
819–23.
13. Chuter TA. Commentary: From bespoke to off-the-shelf: The t-branch stent-graft for total endovascular
TAAA repair. J Endovasc Ther 2013; 20: 726–27.
14. Farber MA, Eagleton MJ, Mastracci TM, et al. Results from multiple prospective single-center clinical
trials of the off-the-shelf p-Branch fenestrated stent graft. J Vasc Surg 2017; 66: 982–90.
15. Rao R, Lane TR, Franklin JJ, et al. Open repair versus fenestrated endovascular aneurysm repair of
juxtarenal aneurysms. J Vasc Surg 2015; 61: 242–55.
16. British Society for Endovascular Therapy and the Global Collaborators on Advanced Stent-Graft
Techniques for Aneurysm Repair (GLOBALSTAR) Registry. Early results of fenestrated endovascular
repair of juxtarenal aortic aneurysms in the United Kingdom. Circulation 2012; 125: 2707–15.
17. Oderich GS, Ribeiro M, Hofer J, et al. Prospective, nonrandomized study to evaluate endovascular
repair of pararenal and thoracoabdominal aortic aneurysms using fenestrated-branched endografts
based on supraceliac sealing zones. J Vasc Surg 2017; 65: 1249–59.
18. Nordon IM, Hinchliffe RJ, Holt PJ, et al. Modern treatment of juxtarenal abdominal aortic aneurysms
with fenestrated endografting and open repair – a systematic review. Eur J Vasc Endovasc Surg 2009;
38: 35–41.
19. Deery SE, Lancaster RT, Gubala AM, et al. Early experience with fenestrated endovascular compared to
open repair of complex abdominal aortic aneurysms in a high-volume open aortic center. Ann Vasc
Surg 2017; 17: 31125–21.
20. Roy IN, Millen AM, Johnes SM, et al. Long-term follow-up of fenestrated endovascular repair for
juxtarenal aortic aneurysm. Br J Surg 2017; 104: 1020–27.
21. Li Y, Hu Z, Bai C, et al. Fenestrated and chimney technique for juxtarenal aortic aneurysm: a systematic
review and pooled data analysis. Sci Rep 2016; 6: 20497.
22. Tsai S, Conrad MF, Patel VI, et al. Durability of open repair of juxtarenal abdominal aortic aneurysms. J
Vasc Surg 2012; 56: 2–7.
23. Knott AW, Kalra M, Duncan AA, et al. Open repair of juxtarenal aortic aneurysms (JAA) remains a safe
option in the era of fenestrated endografts. J Vasc Surg 2008; 47: 695–701.
24. Shortell CK, Johansson M, Green RM, et al. Optimal operative strategies in repair of juxtarenal
abdominal aortic aneurysms. Ann Vasc Surg 2003; 17: 60–65.
25. Orr NT, Davenport DL, Minion DJ, et al. Comparison of perioperative outcomes in endovascular versus
open repair for juxtarenal and pararenal aortic aneurysms: A propensity-matched analysis. Vascular
2017; 25: 339–45.
26. Maeda K, Ohki T, Kanaoka Y, et al. Comparison between open and endovascular repair for the treatment
of juxtarenal abdominal aortic aneurysms: A single-center experience with midterm results. Ann Vasc
Surg 2017; 41: 96–104.
27. Jongkind J, Yeung, KK, Akkersdijk GJM, et al. Juxtarenal aortic aneurysm repair. J Vasc Surg 2010: 52:
760–77.
28. Ferrante AMR, Moscato U, Colacchio EC, et al. Results after elective open repair of pararenal abdominal
aortic aneurysms, J Vasc Surg 2016; 63: 1443–50.
29. Marrocco-Trischitta MM, Melissano G, Kahlberg A, et al. The impact of aortic clamping site on
glomerular filtration rate after juxtarenal aneurysm repair. Ann Vasc Surg 2009; 23: 770–77.
30. Tshomba Y, Kahlberg A, Melissano G. Comparison of renal perfusion solutions during thoracoabdominal
aortic aneurysm repair. J Vasc Surg 2014; 59: 623–33.
31. Mascia D, Bertoglio L, Kahlberg A, et al. Open repair of proximal abdominal aneurysms classified
according to the equivalent fenestrated endovascular treatment. J Vasc Surg 2017 (under review).
121
Use of EndoAnchors
for elective EVAR
SR Goudeketting, RC Schuurmann and
JPPM de Vries
Introduction
Type Ia endoleak and device migration remain challenges for durable endovascular
aneurysm repair (EVAR). Adequate fixation and sustained sealing of the proximal
part of the endograft within the infrarenal aortic neck are required to prevent such
complications. Fixation and sealing may be hampered by unfavourable infrarenal
neck morphology, including short length (<15 mm), large diameter (>30 mm),
large infrarenal angulation (>60 degrees), reversed taper, and large thrombus load
and calcifications.1 Alternative to angulation, aortic curvature has been identified as
a better predictor for intraoperative, as well as late (>1 year), type Ia endoleaks.2,3
Progressive neck dilatation, mainly due to the radial force of the endograft, may
further increase the risk for neck-related complications post-EVAR.4 These high-
risk patients could benefit from additional antimigration measures during elective
or urgent EVAR.
Heli-FX EndoAnchor system

The Heli-FX EndoAnchor System (Medtronic) was developed to improve sealing
of endografts in the proximal aortic neck and to increase migration resistance. The
system consists of a Heli-FX guide, an applier, and EndoAnchors. The deflecting
guide catheter allows correct positioning of the applier that is used to implant the
EndoAnchors. An EndoAnchor is a helical metallic screw sized 3mm in diameter
and 4.5mm in length. The EndoAnchors can be used prophylactically to optimise
fixation and seal, or therapeutically to treat type Ia endoleaks or migration.5–9 They
can significantly improve the fixation by securing the endograft to the proximal
aortic neck.10,11 Depending on the proximal neck diameter (≤29mm or >29mm),
it is recommended to use at least four or six EndoAnchors, respectively. When
circumferentially deployed, EndoAnchors can approximate the strength of a
surgically hand-sewn anastomosis.8,11 However, to achieve the intended additional
fixation, EndoAnchors should be successfully deployed and penetrate ≥2mm into
the aortic wall.12
In 2017, Medtronic was granted FDA and CE-mark approval for the indication
to treat short aortic neck anatomies (>4mm) and <60-degree infrarenal angulation
with the Endurant II/IIs stent graft system combined with the use of the Heli-FX
EndoAnchor system. This was validated by analysis of a subcohort (70 patients with
4–10 mm neck lengths were treated with Endurant endograft and EndoAnchors) of
the multicentre Aneurysm Treatment using the Heli-FX Aortic Securement System
Global Registry (ANCHOR) database. The study demonstrated an 88.6% technical
123
success rate based on the delivery and deployment of the endograft and successful
• SR Goudeketting, RC Schuurmann and JPPM de Vries
implantation of each EndoAnchor. Type Ia endoleaks were reported in 6.8% and

1.9% of the patients at one-month and 12-month follow-up, respectively. The
overall procedural success rate was 97.1%.13
EndoAnchor deployment technique

The EndoAnchor deployment zone should be critically reviewed on the preoperative
computed tomography (CT) angiography scan. Spiculae of severe mural thrombus
and calcium should be avoided to decrease the risk of EndoAnchor non-penetration
in the aortic wall.7,10 For primary use, as well as revision repair with EndoAnchors,
the main body size of the endograft should not be smaller than the aortic neck
diameter, as the endograft cannot expand further than its maximum diameter.
Therefore, EndoAnchors cannot be used to treat sealing failures due to undersized
endografts (or aortic dilatation during follow-up). In general, gaps between the
endograft and aortic wall of >2mm may preclude good EndoAnchor penetration
due to the limited length of the EndoAnchors.
The C-arm should be positioned perpendicular to the tip of the Heli-FX
endoguide in such a way that thrombus and calcification will be avoided. During
Use of EndoAnchors for elective EVAR
deployment, the Heli-FX applier needs to apply force to the endograft to achieve
apposition. Therefore, the length of the tip of the endoguide should mimic the
aortic neck diameter to be able to gain stability from the contralateral aortic
wall. EndoAnchors should be deployed in a zone close to the proximal edge of
the endograft (the pre-EVAR neck length). During deployment, fluoroscopy
shows a bulging of the endograft because of pushing of the tip of the applier (and
EndoAnchor) against the endograft and aortic wall. This haptic feedback assures
proper EndoAnchor penetration. Figure 1 shows an example of a patient receiving
an Endurant stent graft in combination with EndoAnchors.
Figure 1: Use of EndoAnchors

in combination with an EVAR
procedure. (A) Angiography
of the aortic neck and renal
arteries. An Endurant 32mm
main device is deployed distal
to the left renal artery. (B)
Due to the large angulation
of the infrarenal aorta, three
EndoAnchors are deployed
in the outer curve. The
angiography, however, shows a
small type Ia endoleak (arrow).
(C) Four more EndoAnchors are
deployed to treat the endoleak.
(D) The final angiography
shows patent renal arteries
and the absence of the type Ia
endoleak.
124
ANCHOR database

The prospective, multicentre ANCHOR database was designed to investigate
the real-world use of EndoAnchors in patients undergoing or who underwent
EVAR.5,9,14–17 The registry consists of a primary and revision arm. Patients in the
primary arm are treated both prophylactically as well as therapeutically (treatment
of acute type Ia endoleaks), whereas treatment in the revision arm is therapeutic to
treat migration and/or solve late type Ia endoleaks.
The first results were published in 2014, showing high technical success rates in
patients with mostly challenging anatomy (>96% and >90% in the primary and
revision arm, respectively).9 Adverse events were reported in 61 (19.1%) patients
during the 16±5 months of follow-up, which resulted in 22 (6.9%) aneurysm-
related reinterventions and seven (2%) EndoAnchor-related reinterventions.

Persistent type Ia endoleak and migration were reported in, respectively, 19 (10%)
and zero (0%) patients during 7.1±5.6 months of imaging follow-up. During one
year of follow-up, sac regression (>5mm) was reported in 39% of patients and
sac enlargement (>5mm) was reported in only 2%. There were 5% aneurysm-
related reinterventions and 4% late type Ia endoleaks. There were no reports of
intraoperative type Ia endoleaks, EndoAnchor-related reinterventions or migration
in the prophylactic subgroup.
Similar results were reported at one-year follow-up of 100 patients.16 Most of the
patients (83%) had hostile neck anatomy and on average 5.3±1.8 EndoAnchors were
deployed. The technical success rate was 93%, and adverse events were reported in
21% during an average follow-up of 18±4 months. Reinterventions were aneurysm-
related in 6% of the cases and EndoAnchor-associated in 4% of the cases. At one-year
follow-up, type Ia endoleak was reported in 8%, sac regression (>5 mm) in 40.7%,
and sac enlargement (>5 mm) in only 1.9% of this challenging cohort.
Tassiopoulos et al analysed predictors of early neck dilatation in patients
undergoing EVAR with EndoAnchors.14 Their patient population consisted of
a total of 257, of which 169 (65.8%) were treated prophylactically to prevent
proximal neck complications and 88 (34.4%) were treated for immediate type Ia
endoleaks during primary EVAR. On average, 5.5±1.9 EndoAnchors were deployed.
In the first year following EVAR, aortic neck length and baseline aneurysm sac
diameter were protective against aortic neck dilatation. Additionally, EndoAnchors
had a protective effect on neck dilatation at the usual level of deployment (between
5–10mm from the top of the endograft fabric).
Recently, a propensity matched cohort study was performed with patients treated
with and without EndoAnchors.17 There were 99 matched pairs (ANCHOR vs.
control cohort); the majority of those were classified as hostile necks. A mean
number of 5.3 EndoAnchors were deployed in each of the ANCHOR patients.
Respectively, two and four patients of the ANCHOR and control cohort had a type
Ia endoleak. A Kaplan-Meier survival analysis showed that freedom from type Ia
endoleak was not significantly different at two years. Neck dilatation was observed
in three ANCHOR and eight control patients at two years of follow-up (not
significant). Sac regression was observed in 29 and 25 patients of the ANCHOR
and control cohort, respectively. Sac regression was significantly greater in the
ANCHOR vs. control cohort (53.5±7% vs. 32.3±5.3%, p=0.03). However, sac
regression was less likely if more hostile neck criteria were met.
125
Treatment of short (4–10mm) necks with an Endurant endograft combined
with the use of the EndoAnchors has been recently approved by the FDA and
also received the CE mark. In these short necks, preoperative planning and careful
patient selection remain important, since unintendedly low deployment of the
endograft >3mm below the renal artery orifice has been observed in 26% of elective
EVAR patients.18 This unintended low deployment of the endograft is especially
important in patients with short aortic necks. More importantly, the sealing zone
of the endograft may be minimal in the outer curve of severely angulated necks.
Especially in these patients, it is important to deploy the EndoAnchors in the
first few millimeters below the top of the fabric of the endograft to assure good
penetration of the EndoAnchors in the aortic wall, and to increase the migration
resistance. Moreover, accurate postoperative assessment of the proximal sealing zone
is essential to prevent complications during follow-up.19 The Heli-FX EndoAnchor
System has a short learning curve and EndoAnchors appear to be beneficial against
aortic neck dilatation and to promote sac regression. A high technical success rate
was observed in the treatment of acute and late type Ia endoleaks. EndoAnchors
can significantly increase migration resistance and may be a useful addition to
EVAR to treat or prevent migration and/or type Ia endoleaks.
Conclusion
Hostile neck criteria are associated with early and late aortic neck complications,
such as migration and type Ia endoleak. EndoAnchors are a useful adjunct to
EVAR to treat or prevent migration and/or type Ia endoleaks. The circumferential
deployment of EndoAnchors with good penetration into the aortic wall increases
migration resistance and seems to prevent post-EVAR neck dilatation. EndoAnchors
are an off-the-shelf solution that can be of help to overcome challenging aortic neck
features and to treat type Ia endoleaks. The use of EndoAnchors does not preclude
any further endovascular interventions like chimney cuffs or fenestrated cuffs.
Summary
• The Heli-FX EndoAnchor system increases migration resistance, and is

comparable to a hand-sewn anastomosis.
• EndoAnchors should be deployed in the proximal part of the endograft to
assure good penetration of the EndoAnchors into the aortic wall.
• EndoAnchors are a useful adjunct to EVAR to treat or prevent migration and/or
type Ia endoleaks with a high technical success rate in challenging aortic neck
anatomy.
• Short-neck patients (4–10mm) can be treated with the Heli-FX EndoAnchor
system, but careful patient selection is required as unintended low endograft
deployment occurs in 26% of elective EVAR patients.
• A matched control study showed that EndoAnchors significantly induce
aneurysm sac regression.
126
References

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patients at high risk for late failure of endovascular aneurysm repair. J Endovasc Ther 2017; 24 (3):
418–20.
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endoleak. J Vasc Surg 2016; 63 (3): 596–602.
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neck. J Vasc Surg 2015; 61 (6): 1383–90. e1.
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Endovasc Ther 2015; 22 (2): 163–70.
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aortic aneurysms with an unfavorable neck. J Endovasc Ther 2012; 19 (6): 707–15.

7. de Vries JPPM, van de Pavoordt HDWM, Jordan Jr WD. Rationale of EndoAnchors in abdominal aortic
aneurysms with short or angulated necks. J Cardiovasc Surg 2014; 55: 103–07.
8. Avci M, Vos JA, Kolvenbach RR, et al. The use of endoanchors in repair EVAR cases to improve proximal
endograft fixation. J Cardiovasc Surg 2012; 53 (4): 419–26.
9. Jordan WD, Mehta M, Varnagy D, et al. Results of the ANCHOR prospective, multicenter registry of
EndoAnchors for type Ia endoleaks and endograft migration in patients with challenging anatomy. J
Vasc Surg 2014; 60 (4): 885–892. e2.
10. de Vries JPPM, Jordan WD. Improved fixation of abdominal and thoracic endografts with use of
Endoanchors to overcome sealing issues. Gefässchirurgie 2014; 19 (3): 212–19.
11. Melas N, Perdikides T, Saratzis A, et al. Helical EndoStaples enhance endograft fixation in an
experimental model using human cadaveric aortas. J Vasc Surg 2012; 55 (6): 1726–33.
12. Goudeketting SR, van Noort K, Ouriel K, et al. Influence of aortic neck characteristics on successful
aortic wall penetration of EndoAnchors in therapeutic use during endovascular aneurysm repair. J
Vasc Surg. Accepted for publication Jan 2018.
13. PMA P100021/S063: FDA Summary of Safety and Effectiveness Data. 2017. 1-50 p. https://goo.
gl/6huVJJ [Date accessed 19 February 2018]
14. Tassiopoulos AK, Monastiriotis S, Jordan WD, et al. Predictors of early aortic neck dilatation after
endovascular aneurysm repair with EndoAnchors. J Vasc Surg 2017; 66 (1): 45–52
15. de Vries JPPM, Ouriel K, Mehta M, et al. Analysis of EndoAnchors for endovascular aneurysm repair by
indications for use. J Vasc Surg 2014; 60 (6): 1460–67.
16. Jordan WD, Mehta M, Ouriel K, et al. One-year results of the ANCHOR trial of EndoAnchors for the
2016; 24 (2): 177–86.
17. Muhs BE, Jordan W, Ouriel K, et al. Matched cohort comparison of endovascular abdominal aortic
aneurysm repair with and without EndoAnchors. J Vasc Surg 2017; 1–9. Epub.
18. Schuurmann RCL, Overeem SP, Ouriel K, et al. A semiautomated method for measuring the
3-dimensional fabric to renal artery distances to determine endograft position after endovascular
aneurysm repair. J Endovasc Ther 2017; 24 (5): 698–06.
19. Schuurmann RCL, van Noort K, Overeem SP, et al. Determination of endograft apposition, position, and
expansion in the aortic neck predicts type Ia endoleak and migration after endovascular aneurysm
repair. J Endovasc Ther. Accepted for publication Dec 2017.
127
Use of covered stents for
visceral and aortoiliac injuries
MA Ruffino, M Fronda, A Discalzi, D Righi
and P Fonio
Introduction
Arterial injuries, both spontaneous (bleeding and pseudoaneurysm) and iatrogenic
(rupture, perforations and dissections), are relatively rare but serious conditions
that can be limb-, organ- or life-threatening if not promptly managed.1,2 Although
surgical repair represents the traditional treatment for injured essential arteries,
it is associated with potentially life-threatening complications, especially in an
emergency setting.
Endovascular treatment is an effective and less invasive alternative to surgery.
Depending on the type of vessel and the location of the injury, endovascular
management employs different techniques such as embolisation—performed with
coils, plugs and/or liquid embolic agents—and implantation of covered stents.
As opposed to transcatheter embolisation techniques, the implantation of a stent
graft enables the exclusion of the lesion without the sacrifice of the target vessel,
minimising the risk of ischaemic complications, and should therefore be the
preferred choice when anatomically feasible.
In this chapter, we analyse some technical aspects and the main results of stent-
graft implantation in visceral and aortoiliac arterial injuries reported in the literature.
Visceral arteries
Visceral artery pseudoaneurysms are often related to pancreatitis or iatrogenic
trauma.3,4 Interventional techniques have demonstrated equal or better efficacy
compared with open surgery in controlling active haemorrhage and should be
favoured, in stable patients, due to the high morbidity and mortality associated
with primary operative intervention.5,6 Furthermore, endovascular management of
visceral aneurysms and pseudoaneurysms is more cost-effective and requires less
time in hospital.7,8
Transcatheter embolisation typically consists of placement of coils both distal
and proximal to the pseudoaneurysm to prevent collateral back-filling and loss of
control. Pseudoaneurysms are usually not filled with coils because this could cause
rupture of the fragile wall. Despite its effectiveness, this technique is burdened by
a series of complications, including splenic infarction, coil migration, intestinal
necrosis, and vascular dissection with rates of up to 25%.9–11
Differently from transcatheter embolisation, stent-grafting excludes the aneurysm
preserving the flow through the affected visceral artery and should be performed
especially for the treatment of the proper hepatic artery and main renal artery that
129
• MA Ruffino, M Fronda, A Discalzi, D Righi and P Fonio
A B C
Figure 1: (A) Coeliac trunk stenosis. (B) Acute arterial bleeding after stenting (bare stent). (C)
Final angiogram shows recovery of the lesion after implantation of a 7mm x 37mm balloon-
expandable stent graft (BeGraft Peripheral, Bentley InnoMed).
lack collateral flow, as well as of the coeliac artery and superior mesenteric artery
with inadequate collateral flow (Figure 1).
In the management of all arterial injuries, especially in visceral vessels, a
Use of covered stents for visceral and aortoiliac injuries
preliminary computed tomography (CT) angiography, when feasible, is crucial not

only for the diagnosis of the lesion but also to provide technical information that
is useful for the strategy of the procedure, including best approach (from above
or below), size and length of the stent graft and number of efferent vessels. The
procedure is usually performed under local anaesthesia, using digital subtraction
angiography, through the transfemoral approach—the transaxillary approach may
be used in case the CT scan suggests an easier aneurysm catheterisation using a
cranial rather than a caudal approach.
If possible, a long curved introducer or a guiding catheter (6–9Fr) is placed
at the origin of the involved artery. A preliminary coil (or plug) embolisation
can be performed prior to stent-graft placement to avoid retrograde aneurysm
revascularisation in case of two (or more) efferent vessels.12,13 To achieve exclusion
of the pseudoaneurysm, the stent graft is usually placed along the arterial wall
from which the affected artery originates, determining its devascularisation.
This technique is equally effective for both saccular pseudoaneurysms and artery
stumps following surgery (usually pancreatic). When necessary, post-dilatation can
be performed to better adhere the stent graft to the arterial wall. No oversizing,
or a minimal oversizing, of the stent graft is needed, and both self-expandable
and balloon-expandable stent grafts can be used, depending on technical and
anatomical features. In particular, a balloon-expandable device, more precise but
less adaptable than self-expanding ones, is usually preferred in aneurysms involving
short and rectilinear tracts of the visceral artery or in lesions at the vessel origin
from the aorta.
There is no consensus on the prevention of stent graft thrombosis, but most
authors suggest dual antiplatelet therapy for three to six months followed by
lifelong aspirin (100–300mg/day), starting after the discharge with haemoglobin
level normalisation in active bleeding patients.
The use of coronary balloon-expandable stent grafts in small calibre vessels and the
transaxillary approach may increase the feasibility rate of covered-stent placement.12
130
Venturini et al recently reported technical and clinical success rate of 92%

and 72%, respectively, in a series of 25 visceral pseudoaneurysms treated in an
emergency setting with the placement of a self-expandable covered stent.13 The
periprocedural complication rate was 4%, with splenic artery dissection occurring
in 1/25 patients. The 30-day mortality was 20%, all due to septic shock in patients
with iatrogenic pseudoaneurysms after pancreatic surgery.
In the same study, considering both elective and emergency stent-grafting,
two stent-graft thrombosis occurred, respectively at one and three months, both
asymptomatic and with persisting intrahepatic aneurysm exclusion. The slow
occlusion process due to intimal hyperplasia, in fact, allows time for collateral
formation sufficient to prevent distal ischaemia, leading to a lower risk of ischaemia
than with transcatheter embolisation.14 Out of the remaining patients, the recorded
aneurysm exclusion with stent-graft patency at the follow-up CT imaging was
18/18 (100%) at six months, 12/12 (100%) at 12 months and 7/7 (100%) at 36
months.
When the deployment of a stent graft is not feasible, due to technical or
anatomical conditions, transcatheter embolisation remains a valid alternative in

emergency, especially in splenic artery pseudoaneurysms (with collateral flow from
the short gastric and gastroepiploic arteries), and in the coeliac trunk, proximal
superior mesenteric artery and common hepatic artery lesions (with collateral flow
provided by the pancreaticoduodenal and gastroduodenal arteries).
Aortoiliac injuries
Arterial injuries of the iliac axis, both traumatic and iatrogenic, are relatively
uncommon. They include rupture, perforation, pseudoaneurysm and arteriovenous
fistulae and their incidence is expected to increase due to the growing number of
percutaneous procedures.15,16
In particular, the rate of major complications ranges from 3% to 5% following
transfemoral aortoiliac angioplasty and stenting, and the vast majority is local vascular
problems, e.g. thromboembolic events and dissection, with an incidence of about
0.3–0.4% for perforations and arterial ruptures.17 Other series report an incidence
of iliac rupture or pseudoaneurysm during endovascular interventions of 0.8% and
0.9%.18,19 However, a retroperitoneal haemorrhage from an iliac artery injury may
lead to haemorrhagic shock and death if not diagnosed early and treated promptly.
The treatment of these lesions/defects has shifted, during the last decades, from
emergent surgery to an endovascular approach, and the endovascular approach
became the method of choice and part of the treatment algorithm.20,21
For iatrogenic acute ruptures, the diagnosis is usually made during the procedure,
on the basis of groin and back pain, haemodynamic changes, and observation of
leakage on the arteriogram.18
Temporary haemostasis must be achieved by reinserting the balloon back into the
artery and inflating it until the appropriate covered stent is ready.22–24 It is crucial
that every centre performing endovascular procedures has stent grafts of different
diameters available for such emergencies (Figure 2).18,23 Regarding the type of stent
graft, both balloon-expandable and self-expanding covered stents have advantages
and disadvantages: usually, balloon-expandable stents require a smaller introducer
and allow for a more precise deployment, while self-expandable stent grafts are
more flexible and available in longer lengths.
131
A B
Figure 2: Acute iliac artery rupture during recanalisation of a previously

implanted bare stent (A) successfully treated with a 7mm x 57mm balloon-
expandable stent graft (BeGraft Peripheral, Bentley InnoMed) (B).
Additionally, some authors recommend an aggressive reversal of anticoagulants,

including the use of protamine to reverse heparin, and transfusions of fresh frozen
plasma or platelets as appropriate.22
As for visceral arteries, the endovascular technique (embolisation with coils or
deployment of a stent graft) depends mainly on the type of vessel and the location
of the injury.
Nevertheless, some authors state that in young patients, with long life expectancy,
the long-term outcomes of stent graft placement are unknown and surgery may be
a preferable option.25,26
There are few case series or trials studying the use of devices to treat iliac
artery perforation or rupture. To our knowledge, the biggest series reported in
the literature regarding traumatic peripheral arterial injuries treated with covered
stents (62 patients) showed an immediate technical success of 93.5% (75% in the
subgroup of arteriovenous fistulae), with early and late all-cause mortality rates of
6.5% (one cardiogenic shock, one multiorgan failure and two respiratory arrests)
and 17.7%, respectively (no death was related to the stent graft deployment). The
technical success at six and 12 months, in terms of exclusion of the lesion, was
88.4% and 85.3%, respectively.
The same study reported a rate of early and late adverse events of 14.5% and
6.5%, respectively, and a primary patency at one year of 80.1% for all injury
locations combined (76.4% in the iliac group).27
The comparison with the surgical literature showed a minor rate of operative
and postoperative complications (21.21% vs. 57.70%), procedure-associated early
mortality (9.09% vs. 27.28%), and all-cause late mortality (15.15% vs. 33.86%).
The late complication rate was similar: 6.06% vs. 12.50%, but events were less
severe in the stent graft group.
Many of the complications reported in the literature for surgical repair, such
as disseminated intravascular coagulopathy enteric fistula, evisceration, impotence,
intestinal ischaemia, colon perforation, and haemorrhagic shock did not occur in
the stent-graft group.28–33
132
In 15% of the patients, a surgical bypass was required during the first year; in

this subgroup the stent-graft deployment did not preclude the ability to perform
surgery, permitting an elective intervention with obvious improvement in morbidity
and mortality rates.
In another series of seven acute iliac artery ruptures (five iatrogenic, two due to
iliac artery mycotic aneurysms), Chatziioannou et al reported a technical success of
100% (7/7) after the deployment of nine stent grafts (seven balloon-expandable and
two self-expandable).34 Except for a patient who died at day five due to multiorgan
failure, the primary patency at six months was 100%.
Similar results are reported in two series, of 29 and 12 iatrogenic femoral
pseudoaneurysms (unresponsive to ultrasound-guided compressive therapy) and
arteriovenous fistulae, respectively, with a technical success ranging from 89.7%
and 100% and a primary patency of about 100% at six months and one year.20,26
Even if the natural history of stable pseudoaneurysm and arteriovenous fistulae
is often relatively benign, because of spontaneous resolution, it must be taken into
account that arteriovenous shunts of any degree are badly tolerated by patients
with heart disease. 35,36 Furthermore, a concurrent administration of anticoagulant,

frequent in these patients, can undermine both spontaneous resolution and
ultrasound-guided compressive therapy of pseudoaneurysms.
Conclusion
Endovascular treatment of visceral and iliac arterial injuries, with the implantation
of a stent graft, seems to be safe and effective with a high patency rate during
follow-up. These results need to be confirmed in larger studies.
133
Summary
• Endovascular treatment represents an effective and less invasive alternative to

surgery in arterial injuries and employs techniques such as embolisation and
implantation of covered stents.
• The implantation of a stent graft allows for the exclusion of the lesion
without the sacrifice of the target vessel, minimising the risk of ischaemic
complications, and should therefore be the preferred choice when
anatomically feasible.
• A preliminary CT angiography, when possible, could not only diagnose the
lesion, but also provide technical information for planning, such as the best
approach, measures of the stent graft needed and number of efferent vessels.
• When the deployment of a stent graft is not feasible, due to technical or
anatomical conditions, transcatheter embolisation remains a valid alternative
in an emergency, especially in vascular territories with a good collateral flow.
• An aggressive reversal of anticoagulants, including the use of protamine
to reverse heparin, and transfusions of fresh frozen plasma or platelets as
appropriate, should be taken in account in actively bleeding patients under

antithrombotic therapy.
• Despite there being no consensus on the prevention of stent-graft thrombosis,
dual antiplatelet therapy (for three to six months), followed by lifelong aspirin
(100–300mg/day), is generally recommended (starting after haemoglobin level
normalisation in actively bleeding patients).
• Every centre performing endovascular procedures should have stent grafts
of different sizes available in their storerooms, for the treatment of acute
iatrogenic arterial lesions.
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4. Sanchez Arteaga A, Orue-Echebarria MI, Zarain L, et al. Acute bleeding from pseudoaneurysms
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7. Hogendoorn W, Lavida A, Hunink MGM, et al. Cost-effectiveness of endovascular repair, open repair,
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10. de Perrot M, Berney T, Bühler L, et al. Management of bleeding pseudoaneurysms in patients with
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13. Venturini M, Marra P, Colombo M, et al. Endovascular Repair of 40 visceral artery aneurysms and
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patency. Cardiovasc Intervent Radiol 2017; 41(3): 385–97.
14. Venturini M, Marra P, Colombo M, et al. Endovascular treatment of visceral artery aneurysms and
pseudoaneurysms in 100 patients: covered stenting vs transcatheter embolization. J Endovasc Ther
2017; 24 (5): 709–17.
15. Babu SC, Piccorelli GO, Shah PM, et al. Incidence and results of arterial complications among 16,350
patients undergoing cardiac catheterization. J Vasc Surg 1989; 10 (2): 113–16.
16. Samal AK, White CJ. Percutaneous management of access site complications. Catheter Cardiovasc
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Ann Vasc Surg 2003; 17 (3): 306–14.
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a multicenter trial. Cardiovasc Intervent Radiol 1992; 15 (5): 291–97.
20. Baltacioğlu F, Cimşit NC, Cil B, et al. Endovascular stent-graft applications in latrogenic vascular injuries.
Cardiovasc Intervent Radiol 2003; 26 (5): 434–39.
21. Matsumoto J, Lohman BD, Morimoto K, et al. Damage control interventional radiology (DCIR) in
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Cardiol 2008; 21 (1): 86–99.
23. Formichi M, Raybaud G, Benichou H, Ciosi G. Rupture of the external iliac artery during balloon
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24. Nyman U, Uher P, Lindh M, et al. Stent-graft treatment of iatrogenic iliac artery perforations: report of
three cases. Eur J Vasc Endovasc Surg 1999; 17 (3): 259–63.
25. Onal B, Ilgit ET, Koşar S, et al. Endovascular treatment of peripheral vascular lesions with stent-grafts.
Diagn Interv Radiol 2005; 11 (3): 170–74.
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fistulas: repair with percutaneous implantation of endovascular covered stents. Radiology 2000; 214
(1): 127–31.
27. White R, Krajcer Z, Johnson M, et al. Results of a multicenter trial for the treatment of traumatic
vascular injury with a covered stent. J Trauma 2006; 60 (6): 1189–95.
28. Minato N, Itoh T, Natsuaki M, et al. Isolated iliac artery aneurysm and its management. Cardiovasc Surg
1994; 2 (4): 489–94.
29. Sacks NP, Huddy SP, Wegner T, Giddings AE. Management of solitary iliac aneurysms. J Cardiovasc Surg
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30. Richardson JW, Greenfield LJ. Natural history and management of iliac aneurysms. J Vasc Surg 1988;
8 (2): 165–71.
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33. Giordanengo F, Vandone PL, Trimarchi S, et al. Ruptured aneurysm of the internal iliac artery.
Panminerva Med 1995; 37 (3): 150–54.
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Cardiovasc Intervent Radiol 2007; 30 (2): 281–85.
35. Kresowik TF, Khoury MD, Miller BV, et al. A prospective study of the incidence and natural history of
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and arteriovenous fistulae. J Vasc Surg 1997; 25 (5): 803–08.
135
Predictors of long-term
survival after fenestrated
endovascular aortic repair
Introduction
Fenestrated endovascular aortic repair (FEVAR) is a well-established technique for
the treatment of juxta-renal and thoracoabdominal aortic aneurysms. According to
the UK National Vascular Registry (NVR), 90% of all complex abdominal aortic
aneurysm repairs in 2016 were carried out using endovascular techniques, which
included 590 fenestrated procedures.1 Selection of patients who will benefit from
complex endovascular aneurysm repair in the long term can be challenging. Scoring
systems such as POSSUM and V-POSSUM aim to identify patients at short-term
risk after intervention, but often overpredict mortality and are poor at predicting
morbidity.2–4 Multidisciplinary team decision-making is the accepted standard in
most centres for managing patients with complex aortic conditions, but there is
at times a paucity of evidence supporting decisions made for optimal treatment.
Current evidence suggests that an increasing number of “high-risk” octogenarians
can be safely considered for FEVAR, though this is yet to be confirmed in a
robust prospective fashion.5 Conclusions made from observational studies need to
be carefully balanced against the fact that patients who are judged high-risk for
intervention but survive FEVAR may have a poor long-term outlook by virtue of
their general fitness rather than the procedure itself. It is worth noting that, when
considering intervention on patients in their late seventh and eighth decade, the
average life expectancy for a male aged 65 in the UK is 82 years.6
Long-term survival after infrarenal aneurysm repair

In the EVAR 1 trial, all-cause mortality eight years after endovascular and open
infrarenal aneurysm repair was 53% and 46%, respectively, with a modest statistical
difference between the two.7 The recent meta-analysis of the EVAR 1, DREAM,
OVER and ACE trials describes an overall five-year survival of 73.6%.8 After
aneurysm rupture, coronary heart disease was the leading cause of death amongst
patients enrolled in the EVAR 1 trial at every time point measured, with stroke and
other vascular events also accounting for a large number of the deaths.
In 1984, Hollier et al reported a five-year survival rate of 67.5% amongst 1,112
patients treated with open aortic repair at the Mayo Clinic.9 A recent meta-analysis,
reporting a five-year survival rate of 69% amongst 13,281 patients, suggests that
the long-term survival after aortic aneurysm repair has remained surprisingly
static.10 However, it is likely that we are now treating more complex and frail
patients that may have previously been refused surgery. End-stage renal disease and
chronic obstructive pulmonary disease are strong predictors of long-term survival.11
137
A positive association has also been identified between a preoperative history of
cancer or a cancer diagnosis during follow-up and poor long-term survival.12
Survival after complex endovascular aneurysm repair

A recent systematic review, pooling over 2,362 patients after FEVAR or open
surgical repair, found an equivalent 30-day mortality rate of 4.1% in each group,
with a 55% five-year survival after FEVAR for juxta-renal aneurysms.13 The
GLOBALSTAR registry collated data on the majority of FEVAR procedures (318
procedures) performed between 2007 and 2010 in the UK, with an early mortality
rate of 4%.14
Many studies focus on 30-day mortality, but this should not be considered an
adequate measure of success from a patient’s point of view, for whom surgery to repair
Predictors of long-term survival after fenestrated endovascular aortic repair •
an aneurysm is performed to prolong life. Thirty-day mortality may be an adequate

marker of harm, but not one of longer-term success. The risk of death often doubles
at 90 compared with 30 days after aortic surgery and is a phenomenon that is by
no means restricted to patients undergoing aortic repair, and has been identified in
epidemiological studies of other surgical procedures in the UK.15 This may reflect the
fact that complications develop later than expected, or that improvements in critical
care mean that some patients survive beyond 30 days after surgery but not long
enough to leave hospital.16 For patients and clinicians considering major aortic repair,
accurate survival data are required to enable informed decision-making, including
the cost-effectiveness of complex treatments.
Thirty-day mortality rates from individual series vary between 0% and 6.2%,
with a recent large, monocentric study reporting a 30-day mortality of 3.7% and
five-year survival of 46.2% for over 1,000 fenestrated and branched procedures.17
The latter study identified a number of variables associated with poor long-term
outcomes after complex endovascular aneurysm repair, including advancing age,
congestive cardiac failure, preoperative anaemia, raised heart rate, aneurysm size
and adverse features related to the anatomical characteristics of the aneurysm.17
Complications experienced in the immediate postoperative period are associated
with a more profound impact on long-term survival than any single comorbid
disease alone.18 Coronary artery disease and coronary events have long been
associated with poor outcomes after many types of surgery.9 Acute kidney injury, as
defined by the Kidney Disease: Improving Global Outcomes (KDIGO) consortium,
is a clinically important complication that carries significant mortality risk, and
is a clear predictor of long-term chronic kidney disease.19,20 Renal impairment
is a predictor of long-term outcome with a recent study of 14,475 elective
EVARs suggesting that postoperative renal impairment is a powerful predictor
of mortality.21,22 Paraplegia after FEVAR, associated with the extent of repair and
more common after thoracoabdominal aortic coverage, substantially increases risk
of early death.23–27
The long-term follow-up from the EVAR 1 trial suggested that patients treated
with endovascular repair had higher rates of cancer-related deaths.7 Although far
from proven, there is emerging evidence of biological consequences of medical
radiation exposure.28,29 In a recent cohort of 176 patients treated with EVAR,
the most frequent cause of death was from cancer.12 The current standard for
surveillance after FEVAR is an annual computed tomography (CT) scan, meaning
a large radiation exposure burden for a patient expected to survive a number of
138
years after the procedure. Efforts to develop alternative imaging strategies during

implantation and later surveillance of these grafts should be encouraged.
Our local experience

Between 2008 and 2016, we performed 148 FEVAR procedures for the treatment
of juxtarenal aneurysms. The majority of patients (125 of 148 [84.5%]) were male,
and the average age was 76.4 years (standard deviation [SD] 6.19 years)—44
patients (29.7%) were aged over 80 years. Hypertension was the commonest
comorbidity affecting 103 (69.6%) patients, and 73 (49.3%) patients had a history
of cardiac disease, 24 patients (16.2%) had prior history of cancer. Mean aneurysm
diameter was 64.5mm (SD 9.5mm). Five patients (3.3%) died after 30 days and by
90 days one further patient died representing a 90-day mortality of 4%. Temporal
assessment of the 30-day mortality rate, accepting that numbers are relatively
small, shows a trend towards improvement over time, with the majority of deaths
occurring in our early (pre 2011, 6.5%) compared with late (post 2011, 1.3%)
experience. After multivariable logistic regression analysis (correcting for age,
maximum diameter of abdominal aneurysm, a stroke history and cardiac history)
only diabetes remained significantly associated with 30-day survival (odds ratio
[OR] 9.6 [CI: 1.27–9.60], p=0.03), while chronic kidney disease did not (OR 10.3
[CI: 1.1–237.5], p=0.06). At 90 days, chronic kidney disease was associated with
reduced survival (OR 12.3 [CI: 1.4–273], p=0.04). Twenty one patients (14.2%)
suffered acute kidney injury postoperatively, and only one patient (0.7%) suffered
spinal cord ischaemia.

Ninety three per cent of patients survived to one year, median follow-up was
1,141 days (IQR: 13–3,218 days), Figure 1. The overall five-year survival of patients
undergoing FEVAR for juxta-renal disease was 67%. After Cox proportional
hazards modelling to adjust for additional variables associated with poor outcomes
(including age, maximum aneurysm diameter, stroke history and diabetes history),
only chronic kidney disease was significantly associated with reduced five-year
survival (hazard ratio 2.5, [CI: 1.1–5.7], p=0.03).
Figure 1: Kaplan-Meier analysis of

survival after endovascular repair of
junta-renal aortic aneurysms using
fenestrated stent grafts.
139
As an exploratory analysis, we obtained section 251 support from the
Confidentiality Advisory Group to obtain linked data from the Myocardial

Ischaemia National Audit Project (MINAP). MINAP captures >98% of myocardial
infarctions that present to hospitals across the UK and we provided them with
details of patients treated at our institution to enable longitudinal follow-up of our
patients. Surprisingly, only two patients (1.4%) had suffered a myocardial infarction
after discharge from hospital following FEVAR, and the limited number of events
meant we were unable to explore associations between risk factors and myocardial
infarction. It is important to highlight that in-hospital cardiac complications are
not typically captured by MINAP, and those who die in the community from
sudden death due to cardiac causes will also not be captured by MINAP datasets.
Summary
• In our series, almost two-thirds of those treated by FEVAR for juxta-renal

aneurysms will be alive after five years.
• This is encouraging, particularly given the multiple comorbidities of these
patients and their advanced age. These findings are limited by the relatively
small numbers, especially for early mortality analyses and the fact that these
are single-centre, retrospective data.
• A paucity of high-quality data impacts our current understanding of how best
to implement FEVAR as a treatment for patients with complex aneurysms.
• The onus is on the endovascular community to collate prospective,
multicentre data and, for example in the UK, link these with data held by the
Office for National Statistics to allow meaningful analysis of long-term survival
data related to complex endovascular aneurysm repair.
References
1. VSQIP. National Vascular Registry 2016 Annual Report; November 2016.
2. Tang TY, Walsh SR, Prytherch DR, et al. POSSUM models in open abdominal aortic aneurysm surgery.
Eur J Vasc Endovasc Surg 2007; 34 (5): 499–504.
3. Teixeira IM, Teles AR, Castro JM, et al. Physiological and Operative Severity Score for the enUmeration
of Mortality and Morbidity (POSSUM) system for outcome prediction in elderly patients undergoing
major vascular surgery. J Cardiothorac Vasc Anesth 2017. Epub.
4. Lijftogt N, Luijnenburg TWF, Vahl AC, et al. Systematic review of mortality risk prediction models in the
era of endovascular abdominal aortic aneurysm surgery. Br J Surg 2017; 104 (8): 964–76.
5. Timaran DE, Knowles M, Ali T, Timaran CH. Fenestrated endovascular aneurysm repair among
octogenarians at high and standard risk for open repair. J Vasc Surg 2017; 66 (2): 354–9.
6. Office for National Statistics. Life expectancy at birth and at age 65 by local areas in England and
Wales, 2012 to 2014. 2015; 1–24.
7. Patel R, Sweeting MJ, Powell JT, Greenhalgh RM. Endovascular versus open repair of abdominal
aortic aneurysm in 15-years’ follow-up of the UK endovascular aneurysm repair trial 1 (EVAR trial 1): a
randomised controlled trial. Lancet 2016; 388 (10058): 2366–74.
8. Powell JT, Sweeting MJ, Ulug P, et al. Meta-analysis of individual-patient data from EVAR-1, DREAM,
OVER and ACE trials comparing outcomes of endovascular or open repair for abdominal aortic
aneurysm over 5 years. Br J Surg 2017; 104 (3): 166–78.
9. Hollier LH, Plate G, O’Brien PC, et al. Late survival after abdominal aortic aneurysm repair: influence of
coronary artery disease. J Vasc Surg 1984; 1 (2): 290–9.
140
10. Bahia SS, Holt PJE, Jackson D, et al. Systematic review and meta-analysis of long-term survival after

elective infrarenal abdominal aortic aneurysm repair 1969–2011: 5 year survival remains poor despite
advances in medical care and treatment strategies. Eur J Vasc Endovasc Surg 2015; 50 (3): 320–30.
11. Khashram M, Williman JA, Hider PN, et al. Systematic review and meta-analysis of factors influencing
survival following abdominal aortic aneurysm repair. Eur J Vasc Endovasc Surg 2016; 51 (2): 203–15.
12. Sevilla N, Clara A, Diaz-Duran C, et al. Survival after endovascular abdominal aortic aneurysm repair
in a population with a low incidence of coronary artery disease. World J Surg 2016; 40 (5): 1272–78.
13. Rao R, Lane TRA, Franklin IJ, Davies AH. Open repair versus fenestrated endovascular aneurysm repair
of juxtarenal aneurysms. J Vasc Surg 2015; 61 (1): 242–55.
14. Early results of fenestrated endovascular repair of juxtarenal aortic aneurysms in the United Kingdom.
Circulation 2012; 125 (22): 2707–15.
15. Abbott TEF, Fowler AJ, Dobbs TD, et al. Frequency of surgical treatment and related hospital procedures
in the UK: a national ecological study using hospital episode statistics. BJA Br J Anaesth 2017; 119 (2):
249–57.
16. Pearse RM, Harrison D a, James P, et al. Identification and characterisation of the high-risk surgical
population in the United Kingdom. Crit Care 2006; 10 (3): R81.
17. Beach JM, Rajeswaran J, Parodi FE, et al. Survival affects decision making for fenestrated and branched
endovascular aortic repair. J Vasc Surg 2017. Epub.
18. Khuri SF, Henderson WG, DePalma RG, et al. Determinants of long-term survival after major surgery
and the adverse effect of postoperative complications. Ann Surg 2005; 242 (3): 326–43.
19. Levey AS, de Jong PE, Coresh J, et al. The definition, classification, and prognosis of chronic kidney
disease: a KDIGO Controversies Conference report. Kidney Int 2011; 80 (1): 17–28.
20. Heung M, Steffick DE, Zivin K, et al. Acute kidney injury recovery pattern and subsequent risk of CKD:
an analysis of Veterans Health Administration Data. Am J Kidney Dis 2016; 67 (5): 742–52.
21. Patel VI, Lancaster RT, Mukhopadhyay S, et al. Impact of chronic kidney disease on outcomes after
abdominal aortic aneurysm repair. J Vasc Surg 2012; 56 (5): 1206–13.
22. Zarkowsky DS, Hicks CW, Bostock IC, et al. Renal dysfunction and the associated decrease in survival
after elective endovascular aneurysm repair. J Vasc Surg 2016; 64 (5): 1278–85.e1.
23. Rylski B, Czerny M, Sudkamp M, et al. Fenestrated and branched aortic grafts. Dtsch Arztebl Int 2015;

112 (48): 816–22.
24. Gialdini G, Parikh NS, Chatterjee A, et al. Rates of spinal cord infarction after repair of aortic aneurysm
or dissection. Stroke 2017; 48 (8): 2073–7.
25. Eagleton MJ, Shah S, Petkosevek D, et al. Hypogastric and subclavian artery patency affects onset and
recovery of spinal cord ischemia associated with aortic endografting. J Vasc Surg 2014; 59 (1): 89–94.
26. Berg P, Kaufmann D, van Marrewijk CJ, Buth J. Spinal cord ischaemia after stent-graft treatment for
infra-renal abdominal aortic aneurysms. Analysis of the Eurostar database. Eur J Vasc Endovasc Surg
2001; 22 (4): 342–7.
27. Peppelenbosch N, Cuypers PWM, Vahl AC, et al. Emergency endovascular treatment for ruptured
abdominal aortic aneurysm and the risk of spinal cord ischemia. J Vasc Surg 2005; 42 (4): 608–14.
28. El-Sayed T, Patel AS, Cho JS, et al. Radiation-induced DNA damage in operators performing
endovascular aortic repair. Circulation 2017; 136 (25): 2406–16.
29. Machado R, Ferreira VMD, Loureiro L, et al. Radiation exposure in endovascular infra-renal aortic
aneurysm repair and factors that influence it. Brazilian J Cardiovasc Surg 2016; 31 (6): 415–21.
141
Debate: FEVAR is best
for juxta-renal aneurysm
repair—for the motion
Introduction
Fenestrated endovascular aneurysm repair (FEVAR), first reported in 1999, has
evolved to the extent that it should now be regarded as the treatment of choice for
juxta-renal aortic aneurysms, which account for up to 20% of all abdominal aortic
aneurysms.1–3 Open repair, long considered a gold standard, is now less applicable to
many of the patients that we are asked to consider for intervention. It necessitates
a large physiological stress, frequently compounded by the requirement for bilateral
renal artery cross clamping and the associated organ ischaemia. In the 14 years since
the first series outlining the experience with FEVAR for juxta-renal aortic aneurysm
repair were reported, the technique has gained acceptance globally, and multiple
datasets have confirmed its safety and efficacy, particularly when the proximal extent
of the aneurysm is limited.4–8 Alternative endovascular solutions such as parallel stent
grafting and use of infrarenal stent grafts in combination with EndoAnchors should
be considered as bailout procedures for emergent aneurysms until a larger body of
evidence confirms their efficacy in medium and long term follow-up.
Comparative outcomes after FEVAR and open repair

An early pooled analysis of fenestrated (n=275) and open (n=675) repair of juxta-
renal aortic aneurysms suggested that FEVAR compared favourably with open
repair, with 30-day mortalities of 1.8% and 3.1% respectively (p=NS).9 Rates of
kidney loss were 1.5% and 14.4% for FEVAR and open repair, respectively. A more
recent systematic review of aneurysm repair found a comparable 30-day mortality
rate (4.1%, p=NS) between patients undergoing open repair (n=1575) and FEVAR
(n=751).10 The latter group, however, despite being older with a higher burden
of comorbidities, had a significantly lower major complication rate including
myocardial infarctions, chest infections, ischaemic colitis, pulmonary emboli and
wound problems (16% vs. 25%, p=0.001). New onset renal impairment requiring
dialysis and respiratory complications, in particular, appear to be the Achilles heel
of open repair.11
The GLOBALSTAR registry, collating data on 318 patients from 14 centres
in the UK performing FEVAR for juxta-renal aortic aneurysms, reflected the
aforementioned 4% perioperative mortality rate and demonstrated a primary
technical success rate of 99%, and intraoperative target vessel loss of just 0.6%.
Overall survival was 94%, 91% and 89% at one, two, and three years respectively.12
A more recent analysis of the American College of Surgeons National Surgical
Quality Improvement Program (NSQIP) database identified 535 patients who
143
underwent FEVAR and 1,207 who had open elective repair for abdominal aortic
(but not thoracoabdominal) aneurysms that affected the visceral segment.13

Outcomes for FEVAR were better than open repair with a significantly shorter
length of stay (two vs. seven days; p<0.0001), fewer respiratory complications
(3.0% vs. 19.0%, p<0.0001), lower rate of renal failure requiring dialysis (1.9%
vs. 6.4%, p<0.0001), fewer cardiovascular events (2.2% vs. 5.8%; p=0.001),
less major transfusion requirements (17.4% vs. 50.2%, p<0.0001) and lower
perioperative mortality (2.4% vs. 4.7%; p=0.02). These data have recently been
corroborated by analysis of the American College of Surgeons National Surgical
Quality Improvement Program Targeted Vascular Module, which demonstrated a
lower perioperative mortality (3.4% vs. 6.6%; p<0.05), lower respiratory (1.2% vs.
Debate: FEVAR is best for juxta-renal aneurysm repair—for the motion •
7.6%; p<0.001), cardiac (0.7% vs. 4.3%, p=0.001) and wound (0.2% vs. 3.0%,
p=0.001) complications, shorter length of stay in an intensive care unit (1.0 vs. 4.7
days; p<0.001) and hospital stays (4.1 vs. 11.3 days, p<0.001) as well as reduced
acute kidney injury rate (2.3% vs. 9.5%; p<0.01) and dialysis requirement (1.3%
vs. 6.1%; p<0.001) after FEVAR.14 It is important to acknowledge that 20% of
patients in the open group required clamping above the superior mesenteric artery
during repair.
Contemporary results after FEVAR

The majority of historical datasets that compare FEVAR with open repair for juxta-
renal aortic aneurysms are confounded by the fact that FEVAR patients are older
and have significantly more comorbidities such as renal impairment, cerebrovascular
disease and chronic obstructive pulmonary disease. Despite this, the 30-day
mortality remains comparable.15 Contemporary series are emerging where FEVAR
is used as first line treatment in fit patients, demonstrating excellent results. A
recently published monocentric experience, including 281 FEVAR procedures over
a five-year period for patients with juxta- and supra-renal aneurysms, demonstrated
a 97% technical success rate, a 30-day mortality of just 0.7% and a reintervention
rate of 10% at three years.16 These results have been achieved despite a tendency over
time to use stent grafts incorporating a greater number of fenestrations in an effort
to make the available seal zone longer, and future proof the repair. This increased
complexity does not appear to have made the procedures more hazardous.17 In
fact, the amount of contrast and radiation required to perform the procedures has
decreased over time.18
The FEVAR programme in our institution began in 2007. When the experience
up until 2016 was analysed, we had treated a total of 325 patients, 110 of which
were for juxta-renal aortic aneurysms. There were a greater number of fenestrations
used in FEVAR repairs in the cohort of cases between 2011 and 2016; despite this,
there was a significantly lower incidence of acute kidney injury (32.3% vs. 13.9%;
p=0.03) and a trend towards lower 30-day mortality rate (6.5% vs. 1.3%; p=NS)
compared with the experience between 2007 and 2011.
This evolution of FEVAR encompasses the experience gained by operators, the
ability to better pre-empt and treat complications, development of sophisticated
fenestrated stent grafts and ancillary equipment, improved imaging and the ability
to perform the procedure using a percutaneous approach. The argument that
FEVAR is a highly specialised technique with superior results only achievable in
a few centres is redundant because we must aspire to the best available treatment
144
for each patient, regardless of the logistical requirements. As experience with open

repair declines, the skill set required to repair challenging juxta-renal aneurysms
will diminish and the new generation of endovascular-savvy operators are likely to
innovate towards better and off-the-shelf fenestrated solutions to make this type of
treatment more effective still.
Longer-term results and re-intervention after FEVAR

Longer-term data are emerging related to FEVAR. In our monocentric analysis
of 110 FEVAR cases for juxta-renal aneurysms, we found a five-year survival rate
of 65%. A meta-analysis by Linsen et al suggests that after a follow up of up to
25 months, the all-cause mortality associated with FEVAR is 16%.19 The 12-year
Cleveland Clinic results of fenestrated endografts, used to treat juxta-renal aneurysms
and thoracoabdominal aneurysms, found a 2% aneurysm related mortality after
eight years.20 Haulon recently reported an 82% two-year survival rate after FEVAR
with a patency rate of 97% associated with renal fenestrations.21 The long-term
re-intervention rate associated with FEVAR is approximately 10–12% in meta-
analyses and is required for persistent endoleaks, bleeding, renal artery stenosis and
occlusion.22 Reintervention is an important consideration but, accepting that there
is a paucity of data outlining the effect of re-intervention on the patient’s quality
of life, it should not be viewed as an absolute failure of endovascular treatment. It
should, rather, be viewed as a “second bite at the cherry” and to pre-empt problems,
particularly when performed electively. Surveillance after FEVAR is stringent. It is

unsurprising, therefore, that regular imaging of the aorta, which is not generally
performed after open repair, leads to more re-intervention when compared with
open repair patients. Furthermore, reinterventions such as incisional hernia repair
or adhesional bowel obstruction, which may have a profound effect on the patient’s
quality of life, are not always reported after open repair.
Alternative endovascular solutions

Alternative approaches for the treatment of juxta-renal abdominal aneurysms
include parallel grafts, with the chimney endovascular aortic repair (chEVAR)
being the most common for this type of aneurysm. The chEVAR technique, a
more recent addition to the armamentarium, has the advantage of immediate
availability for symptomatic or ruptured aneurysms.23 A pooled comparison of
542 FEVARs and 158 chimney EVAR procedures performed between 2005 and
2013 for the treatment of aneurysms found that FEVAR is associated with a
lower 30-day mortality (1.1% vs. 3.8%; p=0.05), as well as lower rates of type Ia
endoleak (3.7 vs. 7.6%; p=NS) and all-cause mortality (6.5% vs. 13.3%, P<0.01),
with a similar reintervention rate in both groups at 10–11%.22 The incidence of
renal impairment is higher after chEVAR compared with FEVAR (5.5% vs. 19.6%,
p<0.0001), but very few of these patients in either cohort require dialysis. There
is a relative paucity of follow-up data related to parallel grafts in comparison with
FEVAR, with most reporting single-centre small series. The PERICLES registry,
collating the worldwide experience of 517 aneurysms treated by chimney EVAR,
reported a technical success rate of 97.1% (with 94.1% chimney graft patency) and
30-day mortality of 4.9% (3.7% for elective cases); mortality was, however, 25.1%
by three years of follow-up.24 It must be noted that only 70% of these cases are
145
true juxta-renal abdominal aneurysms, with 25% and 5% classified as suprarenal
and type IV (without involvement of the supradiaphragmatic aorta) respectively.

ChEVAR is hampered by the fact that incorporating more than two target vessels
into the repair increases the chance of failure and gutter leak, limiting the length
of seal that can be achieved or necessitating sacrifice of renal or visceral vessels
which has been shown to have a profound effect on the patient’s prognosis.25 The
“gutters” created by the chimney adjacent to the main stent graft appear to increase
the rate of type I endoleaks with an incidence of up to 14% at the end of the
procedure and a persistent 11% rate during early follow up.26 By comparison, the
type I/III endoleak rate after FEVAR has been shown to be as low as 3%.27 In a
direct comparison between FEVAR and chimney EVAR, Katsargyris et al found a
4.3% proximal type 1 endoleak rate for the former as opposed to 10% for the latter
technique (p=0.002).28
ChEVAR also carries a higher risk of stroke, as unlike standard FEVAR
techniques, it requires access via the aortic arch to place the chimney stent. In
the aforementioned PERICLES study the rate of embolic stroke was 1.7% and it
has been reported that the stroke rate associated with chimney EVAR is 10 times
higher than that for FEVAR (3.2% vs. 0.3%) respectively.24,28
The use of chEVAR for treatment of symptomatic patients or in elective patients
who are poor surgical candidates for open repair and not anatomically suitable
for FEVAR should be carefully considered. The perception that chEVAR is less
challenging than FEVAR may prompt less experienced operators to attempt a
repair, often incorporating multiple target vessels, that is at least as challenging as
a FEVAR.
Endovascular aneurysm sealing with polymer-filled endobags has been used in
combination with parallel grafts to treat juxta-renal aneurysms29 with the theoretical
advantage that the more compliant moulding of the endobags around the chimney
stent will reduce this rate of gutter endoleak. The multicentre ASCEND (Aneurysm
sealing for complex aneurysm: evaluation of Nellix durability) registry of 154
patients investigating the application of parallel grafts in the elective treatment of
juxta-renal aneurysms30 reported a 30-day mortality of 2.8%, one-year all-cause
mortality of 10.2% but an aneurysm-related mortality of 5.7%. Additionally,
despite this novel sealing technique, type Ia endoleak and re-intervention rates at
one year were 4.3% and 10.8% respectively. Although these data confirm proof-of-
concept of this technique, the results of mid- and long-term durability are awaited.
EndoAnchors are an alternative technology for securing a conventional infra-
renal graft into the short, hostile necks of juxta-renal abdominal aneurysms.31 The
STAPLE-1 (21 patients) and STAPLE-2 (154 patients) studies have established the
safety and feasibility of the concept of EndoAnchor use.32,33 The Heli-FX aortic
securement system global registry (ANCHOR) is a prospective, multicentre study
of EndoAnchors used in aneurysms with hostile necks, demonstrating feasibility
and a low endoleak rate in the short term.34 Experience with endovascular
treatment of aneurysms accrued over the past few decades does suggest, however,
that attempting to seal repairs in a compromised neck exposes any technology to a
higher risk of failure in aortas that have already demonstrated a propensity towards
degeneration and dilatation over time.35
146
Conclusion

There is now a large body of comparative evidence demonstrating that FEVAR,
carried out on appropriately selected patients and by practiced operators, is the
best treatment for the majority of juxta-renal aortic aneurysms. A randomised
controlled trial that pits FEVAR against other endovascular and open solutions is
unlikely, not least because many of the interventionists performing FEVAR with
excellent results would not currently have the equipoise required to take part in such
a trial. In the meantime, longer-term results of alternative endovascular solutions
and cohort studies, including the UK complex aneurysm study (UK-COMPASS;
ISRCTN85731188), will be awaited eagerly.
Summary
• FEVAR is now a mature technique for juxta-renal aortic aneurysm repair which
can be performed with a mortality rate of <2%.
• FEVAR should be considered as the treatment of choice for anatomically
suitable patients because: (i) it is minimally invasive (ii) it avoids intra-operative
visceral ischaemia and blood loss (iii) the stent graft and components are
specifically configured to the patient’s anatomy (iv) it does not require aortic
arch access.
• Mid-term follow up data demonstrate that FEVAR affords a durable seal with a

low target vessel loss and component failure rate.
• Similar follow up data is required for other endovascular solutions before they
can be considered as equally effective alternatives.
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abdominal aortic aneurysms repair system. J Vasc Surg 2014; 60: 275–85.
34. Jordan WD, Jr., de Vries JP, Ouriel K, et al. Midterm outcome of EndoAnchors for the prevention of
endoleak and stent-graft migration in patients with challenging proximal aortic neck anatomy. J
Endovasc Ther 2015; 22: 163–70.
35. Schanzer A, Greenberg RK, Hevelone N, et al. Predictors of abdominal aortic aneurysm sac enlargement
after endovascular repair. Circulation 2011; 123: 2848–55.
148
Debate: FEVAR is best for
juxta-renal aneurysmal
repair—against the motion
Introduction
Endovascular repair of juxta-renal aortic aneurysms offers a less invasive alternative,
especially for patients with severe comorbidities deemed unfit or too high-risk
for open repair.1,2 However, the main concern remains with the possibility of
inadequate sealing of the endografts in short neck anatomies. Several techniques
have been proposed as means to deal with this issue.
One option is the fenestrated endovascular aneurysm repair (FEVAR), in which the
used endograft can be custom manufactured based on individual patient aneurysm
and renovisceral vessel morphology.2-5 The Zenith (Cook Medical) endovascular
graft is one of the current products with a CE mark with the corresponding
preclinical and clinical testing, and has the greatest amount of published evidence
among such devices.2-5
Another option is the chimney graft technique—or chimney EVAR (chEVAR)—
in which a covered stent is placed in a parallel fashion to a standard EVAR
abdominal device, thereby creating a conduit that runs outside the aortic main
endograft. The chimney graft maintains blood flow into the purposefully involved
and overstented aortic branches along the sealing zones. Recently, the Endurant
stent graft (Medtronic) received CE approval for use in the chimney technique
with a balloon-expandable covered stent with indication for renal artery placement.
Current evidence on chEVAR shows promising clinical and radiologic results
without significant differences in terms of early mortality, persistent type Ia
endoleak, and postoperative dialysis compared with FEVAR.6-9
In this chapter, we will elaborate on the several reasons that jeopardise FEVAR
as best treatment option for juxta-renal aneurysmal repair.
Clinical reasons
FEVAR devices should be produced and customised specifically for a patient’s
individual anatomy. This production requires a time of more than four weeks.
Consequently, the technique cannot be applied in pathologies such as saccular or
penetrating atherosclerotic ulcers with high risk of rupture, nor in symptomatic or
ruptured cases that require immediate treatment.
To make FEVAR applicable in urgent cases, a novel off-the-shelf fenestrated
endograft (Cook Medical’s p-Branch) has been developed.10-11 However, when
retrospectively evaluating its theoretical anatomical suitability, the p-Branch
configurations (A and B) are not suitable in nearly half of patients.12-13 In that
sense, we evaluated the theoretical application of a p-Branch device in 50 patient
149
cases already treated with chEVAR. Main anatomical limitations for the use of
p-Branch were the clock position of the left renal artery (n=7, 14%), the distance
between the superior mesenteric and left renal artery (A: n=16, 32%; B: n=16,
32%), and significantly narrowed or calcified iliac arteries.13
Nevertheless, the p-Branch endograft remains an investigational device. A
prospective clinical study is warranted to evaluate its actual suitability in-vivo.
Anatomical reasons
FEVAR is an established technique with good mid and long-term results.14,15
However, only a few centres apply this technique on a routine basis due to the
complex anatomical planning, the challenging implantation technique and the
extended intervention time.
Debate: FEVAR is best for juxta-renal aneurysmal repair—against the motion •
While chimney EVAR has an increased applicability even in cases of challenging

iliac and neck anatomies due to the use of low-profile abdominal devices, a
number of technical challenges may cause difficulties during implantation of a
fenestrated device in specific cases. Particularly demanding parts of the procedure
are the catheterisation of steeply angulated or stenotic target vessels through the
fenestrations and subsequent advancement of the 6Fr to 8Fr sheaths. A highly
angulated aortic neck also represents a technical difficulty for exact deployment of
the device in order to have the position of the fenestrations at the orifice of the
renovisceral vessels. Additionally, in patients with calcified, tortuous and elongated
access vessels, the use of a 22Fr sheath for the main body and of large-bore sheaths
through the contralateral iliac artery may be hazardous. In these cases, an additional
invasive procedure such as iliofemoral bypass is needed.
An additional risk of sheath-related lower limb ischaemia, and an obstacle for
complex endovascular repair, exists in patients with stenosed, calcified or occluded
iliac and/or femoral arteries. Recently, Gargiulo’s group reported on the impact of
iliac access complications in FEVAR, and a higher incidence of complications in
a large series from FEVAR cases from Katsargyris et al was observed in the iliac
arteries.16,17 These articles highlight the significant limitation for FEVAR in hostile
iliac arteries.
To overcome most of the described technical difficulties, a new modified
fenestrated device was developed with a preloaded wire for easier catheterisation
of both renal arteries through a delivery system with lower profile: 20Fr instead of
22Fr.18 The results reported in literature have thus far been promising.19,20 However,
a limitation of this device is the use of bridging devices which are compatible with
6Fr sheaths for the renal arteries. Only two balloon expandable covered stents are
currently available over a 6Fr sheath. Firstly, Getinge’s 6mm in diameter and 22mm
in length Atrium Advanta V12/iCAST balloon expandable covered stent, and
secondly Bentley’s 6mm in diameter Begraft stent, which shows the limitation in
renal arteries of more than 6mm diameter. Moreover, the small number of reported
patients and the short-term follow-up including learning curve bias warrant future
studies before this technology can be broadly adopted.19,20
Risk of endograft misalignment and migration

Lala et al21 highlighted the phenomenon of superior mesenteric artery misalignment
in up to a half of the treated patients with stent-free superior mesenteric artery and
150
Figures 1 and 2: show separation and compression of the deployed bridging devices from the
main endograft. This complication is associated with increased mortality risk, especially in case of
involvement of the superior mesenteric artery.
double fenestrations.21 This condition represents the critical threshold needed to

produce symptoms and mesenteric life-threatening complications. Moreover, the
observed cases occurred mainly at six and 12 months, indicating that there are
dynamic changes of the graft over time that potentiates the misalignment. This
stresses the need for mandatory CT follow-up evaluation. At the same time, it
shows the significant limitations of published literature in this context, as one of

the largest published series by Grimme et al reported that only 52% of the patients
had one-year CT follow-up and 11% had a four-year CT follow-up.22
Migration of a fenestrated endograft and fracture of the bridging devices increase
the aortic mortality considerably. Figure 1 and Figure 2 demonstrate compression
and fracture of the bridging device in a fenestrated endograft, highlighting the
importance of radiological imaging. Therefore, profound evaluation of the superior
mesenteric artery outcomes in the fenestrated technology is missing. There is
very scant information about issues such as misalignement of the device in the
superior mesenteric artery and radiological CT angiography-based evidence about
the patency of the artery bridging device. Issues such as fractures or kinking of
these devices are under reported in the literature, despite the fact that a dedicated
bridging device for this indication is still missing.
Limited reproducibility
Chimney EVAR can be used in most endovascular centres with experience of
standard EVAR and renal canulation, as the PERICLES Registry demonstrated.7
However, the use and application of FEVAR for juxta-renal aortic aneurysms require
advanced endovascular knowledge and skills in improved facilities such as a hybrid
room equipped with C-arm. In that sense, FEVAR treatment is currently only
possible in highly specialised volume centres, leaving little opportunity to expand
the use of fenestrated devices in centres outside of this core group consisting of a
few units worldwide.
151
Costs
The customised nature of the FEVAR endograft and the minimum of two or
three bridging stents required for the fenestrations are major factors towards the
significant increase in costs for this technique.23–25 Contrariwise, the chimney
EVAR technique employing a standard EVAR device in adjunction with a covered
or bare metal stent is associated with significantly lower costs. Anecdotal reports
show a difference of 15,000 Euros per patient between a multiple chimney case
vs. FEVAR. A subsequent lifelong surveillance is necessary to evaluate if possible
secondary procedures are similar in both therapeutic options or whether there are
more in the chimney EVAR group, which would minimise the benefit of lower
intraoperative costs.2
Conclusion
Although FEVAR has become the standard endovascular approach for juxta-renal
aortic aneurysms, there are several arguments showing that in specific indications
and patients it seems not to be the best option. In summary, there are several
major arguments for why FEVAR is either not applicable, or associated with high
risk of complications for numerous patients with juxta-renal aortic aneurysms.
These include conditions such as rupture-threatening pathologies requiring urgent
treatment, demanding morphologies of the iliac arteries and aneurysm neck, as
well as the high costs of the procedure. Consequently, FEVAR represents for these
cases either no option, or not the best available option.
Summary
• Delay in customised endograft manufacturing of at least four to eight weeks.

• High cost of procedure.
• Involvement of the superior mesenteric artery either as scallop with a risk of
endograft misalignment and inadvertent coverage of the orifice of the artery
or occlusion of the artery bridging device in case of fenestration.
• Need for anatomically “friendly” conditions for the iliac access and aneurysm
neck.
• Risk of increased mortality in case of migration of the fenestrated endograft
and fracture of the bridging devices.
• Treatment only available in high volume centres with advanced experience
of EVAR/FEVAR and infrastructure, causing centralisation of the expertise.
References
repair of abdominal aortic aneurysms. N Engl J Med 2004; 351: 1607–18.
2. Donas KP, Eisenack M, Panuccio G, et al. The role of open and endovascular treatment with fenestrated
and chimney endografts for patients with juxta-renal aortic aneurysms. J Vasc Surg 2012; 56: 285–90.
3. Qureshi MA, Greenberg RK. New results with the zenith graft in the treatment of aortic aneurysms. J
Cardiovasc Surg 2010; 51: 503–14.
152
4. Verhoeven EL, Vourliotakis G, Bos WT, et al. Fenestrated stent grafting for short necked and juxta-
FEVAR is best for juxta-renal aneurysmal repair—against the motion •

renal abdominal aortic aneurysm: an 8-year single centre experience. Eur J Vasc Endovasc Surg 2010;
39: 529–36.
5. Greenberg RK, Sternbergh 3rd WC, Makaroun M, et al. Intermediate results of a United States
multicenter trial of fenestrated endograft repair for juxta-renal abdominal aortic aneurysms. J Vasc
Surg 2009; 50: 730–37.
6. Amiot S, Haulon S, Becquemin JP, et al. Fenestrated endovascular grafting: the French multicentre
experience. Eur J Vasc Endovasc Surg 2010; 39: 537–44.
7. Donas K, Lee J, Lachat M, et al. Collected world experience about the performance of the snorkel/
chimney endovascular technique in the treatment of complex aortic pathologies: the PERICLES
registry. Ann Surg 2015; 262 (3): 546–53.
8. Donas KP, Eisenack M, Panuccio G, et al. The role of open and endovascular treatment with fenestrated
and chimney endografts for patients with juxta-renal aortic aneurysms. J Vasc Surg 2012; 56: 285–90.
9. Donas K, Torsello G, Piccoli G, et al. The PROTAGORAS study to evaluate the performance of the
Endurant stent graft for patients with pararenal pathologic processes treated by the chimney/snorkel
endovascular technique. J Vasc Surg 2016; 63: 1–7.
10. Resch TA, Dias NV, Sobocinski J, et al. Development of off-the- shelf stent grafts for juxta-renal
abdominal aortic aneurysms. Eur J Vasc Endovasc Surg 2012; 43: 655–60.
11. Kitagawa A, Greenberg RK, Eagleton MJ, et al. Zenith p-branch standard fenestrated endovascular
graft for juxta-renal abdominal aortic aneurysms. J Vasc Surg 2013; 58: 291–300.
12. Mendes B, Oderich G, Reis de Souza L, et al. Implications of renal artery anatomy for endovascular
repair using fenestrated, branched, or parallel stent graft techniques. J Vasc Surg 2016; 63: 1163–69.
13. Schroeder M, Donas K, Stavroulakis K, et al. Anatomical suitability of the Zenith off-the-shelf (p-Branch)
endograft in juxta-renal aortic aneurysms previously treated using the chimney technique. J Endovasc
Ther 2017; 24 (2): 223–29.
14. Mastracci T, Eagleton M, Kuramochi Yuki, et al. Twelve-year results of fenestrated endografts for juxta-
renal and group IV thoracoabdominal aneurysms. J Vasc Surg 2015; 61: 355–64.

15. Verhoeaven E, Vourliotakis G, Bos W, et al. Fenestrated stent grafting for short-necked and juxta-renal
abdominal aortic aneurysm: An 8-year single-centre experience. Eur J Vasc Endovasc Surg 2010; 39:
529–36.
16. Gallito E, Gargiulo M, Faggioli G, et al. Impact of iliac artery anatomy on the outcome of fenestrated
and branched endovascular aortic repair. J Vasc Surg 2017; 66: 1659–67.
17. Katsargyris A, Oikonomou K, Kouvelos G et al. Comparison of outcomes for double fenestrated
endovascular aneurysm repair versus triple or quadruple fenestrated endovascular aneurysm repair in
the treatment of complex abdominal aortic aneurysms. J Vasc Surg 2017; 66: 29–36.
18. Manning BJ, Harris PL, Hartley DE, Ivancev K. Preloaded fenestrated stent-grafts for the treatment of
juxta-renal aortic aneurysms. J Endovasc Ther 2010; 17: 449–55.
19. Bisdas T, Donas KP, Torsello G, Austermann M. Technical assessment of the preloaded fenestrated
stent-graft in the management of pararenal aortic aneurysms. J Endovasc Ther 2013; 20: 461–68.
20. Maurel B, Resch T, Spear R, et al. Early experience with a modified preloaded system for fenestrated
endovascular aortic repair. J Vasc Surg 2017; 65: 972–80.
21. Lala S, Knowles M, Timaran D, et al. Superior mesenteric artery outcomes after fenestrated endovascular
aortic aneurysm repair. J Vasc Surg 2016; 64 (3): 692–97.
22. Grimme F, Zeebregts C, Verhoeven E, et al. Visceral stent patency in fenestated stent grafting for
abdominal aortic aneurysm. J Vasc Surg 2014, 59 (2): 298–306.
23. Osman E, Tan KT, Tse L, et al. The in-hospital costs of treating high- risk patients with fenestrated and
branched endografts. J Vasc Surg 2015; 62: 1457–64.
24. Aiello F, Durgin J, Daniel V, et al. Surgeon leadership in the coding, billing, and contractual negotiations
for fenestrated endovascular aortic aneurysm repair increases medical center contribution margin
and physician reimbursement. J Vasc Surg 2017; 66 :997–1006.
25. Tarride J, Blackhouse G, De Rose G, et al. Should endovascular repair be reimbursed for low risk
abdominal aortic aneurysm patients? Evidence from Ontario, Canada. Int J Vasc Med 2011; 308685.
153
Abdominal aortic controversies
Screening and centralisation of services
Screening for abdominal
aortic aneurysm is cost-
effective and a policy on
2.5–2.9cm aortic diameters
P Söderberg, K Thorbjørnsen, S Svensjö and
A Wanhainen
Introduction
Several large randomised trials on screening for abdominal aortic aneurysm among
elderly men have been shown that screening is effective at reducing aneurysm-
related mortality and that it is cost-effective.1–5 Based on these findings, screening
programmes have been gradually implemented in Sweden and other countries.6–8
Although today’s screening for aneurysms in older men in several countries is
evidence-based healthcare, there are still aspects regarding screening policies that
are not fully understood.8–10
The definition of an aneurysm is not uniform and the most accepted and
simple definition is to use a fixed maximum aortic diameter of ≥30mm, which is
considered to clearly exceed the normal diameter of the aorta. Thus, a fixed aortic
diameter has practical advantages; however, there may be a risk of false positive and
negative results.11
A disputed subgroup is individuals with an aortic diameter of 2.5–2.9cm, termed
subaneurysmal aorta, who fall outside the definition of aneurysm. Therefore, many
screening programmes exclude these individuals from further follow-up, which is
supported by numerous studies, indicating that aneurysm-related death in aortas
<3cm is uncommon.12,13 However, patients with an subaneurysmal aorta do not
represent a normal aorta and recent reports suggest that individuals with an
subaneurysmal have a significant risk of developing “true” aneurysm over time.14,15
Observational studies indicate that more than 50% of subaneurysmal aorta at the
initial scan had expanded to aneurysm after five years.16,17 Furthermore, within
10 years, a considerable number of individuals with subaneurysmal aorta at the
initial scan would reach the threshold for surgical intervention or rupture of an
aneurysm.17–19 The risk factors for aneurysm have been extensively reported in a large
number of population-based studies.20–23 The association between subaneurysmal
aorta and cardiovascular risk factors has been sparsely documented.17
159
Epidemiology
Screening for abdominal aortic aneurysm is cost-effective and a policy on 2.5–2.9cm aortic diameters • P Söderberg, K Thorbjørnsen, S Svensjö and A Wanhainen
The implementation of population-based screening programmes in Europe and the

USA has coincided with a dramatic change in the epidemiology of aneurysm as
well as an alteration in the management of the disease.
Four large randomised controlled trials from the 90s constitute the basis for
implementing population-based screening programmes, and these studies demonstrate
prevalence rates of 4–7.2% for aneurysm with a 40% reduction in aneurysm-related
death.1–4 Since the time of randomisation of these trials, and especially during the
last decade, multiple reports have demonstrated a dramatic decrease in aneurysm
prevalence to 1.5–1.7% among elderly men in some Western societies.5,23 The drop
in prevalence is probably multifactorial but smoking is one of the strongest associated
risk factors in developing an aneurysm, especially in women.24 Smoking rates have
dramatically changed in many Western countries in the last decades and, in Sweden,
reduced smoking rates seem to coincide with declining rates of aneurysm.10 In
addition to smoking, better management of cardiovascular risk factors today has
likely contributed to the drop in the disease incidence.25
The surgical management of aneurysms has changed considerably over the last
two decades, with an increased use of endovascular aneurysm repair (EVAR),which
resulted in lower perioperative mortality, especially in the elderly population.26–28
Also, a general increased longevity in the population has been noted. These
changes could potentially increase an individual’s benefit from early detection of
an unknown aneurysm by screening.
Health economy
The decrease in aneurysm prevalence has rightfully called the emerging screening
programmes into question. This is especially relevant from a health-economic
viewpoint. Low disease prevalence, new treatment options with better outcome
and increased longevity in the population subjected to screening are variables with
monumental impact on the health-economic value of any screening programme.
Recent health-economic studies have thus aimed at taking these dramatic changes
into account when evaluating screening in a modern context. In 2014, a Markov
simulation model study reported that one-time screening of 65-year-old men is still
highly cost-effective when based on the current prevalence of aneurysm, ongoing
actual screening costs, updated costs for aneurysm surgery and postoperative
management as well as updated long-term survival after aneurysm surgery.29 An
incremental cost-effectiveness ratio (ICER) cost per gained quality-adjusted life year
(QALY) of €7,570 with life-time follow-up is well below the often used threshold
of €25,000/£20,000 per gained QALY found in the UK National Institute for
Health and Care Excellence (NICE) clinical guidelines. Furthermore, they report
that one-time screening for aneurysm is cost-effective down to a prevalence rate
of 0.5% with 530 needing to be screened to prevent one death. The absolute risk
reduction was proportionally lower, with lower aneurysm prevalence, but with
prolonged life expectancy and improved aneurysm repair outcome, the life year
saved by each prevented rupture was clinically significant.
Sweden has had a gradual introduction of aneurysm screening of 65-year-old
men. It was initiated in 2006 in Uppsala and achieved full national coverage in
2015. This stepwise introduction, county by county, made it possible to directly
demonstrate the effects of screening, with populations not yet screened serving
160
as controls for the screened population. In a recent report from SASS (Swedish
Aneurysm Screening study group), based on observations of the last 10 years of
implemented screening among 65-year-old men, a 27% decrease in aneurysm
mortality for counties that had screened ≥6 years vs. counties that had screened <4
years was demonstrated.6 A trend towards an even stronger mortality reduction with
prolonged follow-up of screening was also evident. A health-economic evaluation
performed within that study, using a previously validated Markov model updated
with these contemporary observed data, reported an incremental cost-efficiency
ratio of €7,770 per gained QALY, which corroborates previous prognoses.
A report from the ongoing screening programme National Health Service
Abdominal Aortic Aneurysm Screening Programme (NAASP) in the UK
demonstrated an ICER of £7,370 in cost per gained QALY with updated prevalence
rates, costs, surgical outcome and an increased longevity in the population.30 They
assess that NAASP is within the threshold of NICE guidelines (€25,000/£20,000)
per gained QALY down to a prevalence of 0.35%.
Women
The evidence for aneurysm screening in women is insufficient and there is no
reported ongoing population-based aneurysm screening of women in the world.
Due to the modest general representation of female patients in aneurysm studies,
the knowledge is further attenuated. A population-based screening study targeting
70-year-old women in Sweden has demonstrated a prevalence of 0.4% for the
entire screened population where never-smokers displayed a low 0.02% prevalence
but current smokers showed a relative high prevalence (2.1%).31 Follow-up of
the women with screening-detected aneurysms demonstrated that 32% had been
electively repaired after five years, which is in parity with the findings in the large
MASS trial of elderly screened men.32 A recent meta-analysis of contemporary
prevalence of screen-detected aneurysm in women reported a pooled prevalence of
0.7%.33 Women are less likely to be suitable for EVAR than men, and women have
also demonstrated inferior results compared with men after surgery.34 Aneurysms at
any given diameter have a three- to four-fold higher risk of rupture compared with
men and rupture at smaller aneurysm diameter than men.35,36
Due to these discrepancies between men and women, in combination with the
paucity of data in women, the exact risk vs. benefit of identifying aneurysm by
screening in elderly women and performing elective surgery is yet not clear. To
further understand the natural history of aneurysm, more studies are needed.
Screening randomised controlled trials in women are likely not a viable option
due to the low incidence of rupture and the need for very large cohorts in the
attempt to demonstrate significant differences. Well-designed modelling studies
with contemporary epidemiological parameters are more likely to shed light on
this unclear balance of risk vs. benefit.
Targeted screening
A wealth of data for contemporary natural history in elderly men are accumulating
as a result of ongoing screening programmes in many countries and numerous men
are under surveillance for detected aneurysms. Monitoring the findings in these
ongoing screening programmes is of great importance. Further significant changes
161
in the epidemiology of the disease could very well alter cost-effectiveness, making
general population-based screening an inviable option. Targeted screening, as done

today in many countries, towards a group with higher risk of the disease, such as
smokers and/or first-degree relatives, could prove a feasible option.
Prevalence and risk factors of subaneurysmal aortas

In a contemporary population-based aneurysm-screening study with 22,139
65-year old men in middle Sweden, an aortic diameter of 2.5–2.9cm was detected
in 395 men. This represented a prevalence of 1.8%, which is a fairly equal quantity
compared to those with a true aneurysm (1.7%) in the same study.22 The observed
prevalence of screening-detected subaneurysmal aortas in this study in a general
population was marginally inferior to observations done in previous studies.14,15,17
Preliminary (unpublished) data from a prospective population-based cohort
study among 65-year-old males in middle Sweden showed a significant association
between smoking and individuals with an aortic diameter of 2.5–2.9cm, and they
also had higher rates of comorbidity compared with those with an aortic diameter
of <2.5cm had completed a standardised health questionnaire with information on
smoking habits, family and medical history. Based on the maximum aortic diameter
the patients were divided into three groups: 1) normal-aorta group (n=14,129); 2)
SAA group (n=258); and 3) aneurysm group (n=233). Associated risk factors were
compared and analysed between the three groups. The main finding from the study
was that 65-year-old males with subaneurysmal aortas or aneurysm have a very
similar risk factor profile and smoking habits. Smoking is obviously the strongest
independent risk factor in the subaneurysmal aortas (2.8-fold risk) and aneurysm
groups (3.5-fold risk) compared to those with normal aortas.
The natural course of subaneurysmal aortas

A number of studies have demonstrated that a large proportion of aortas with a
diameter of 2.5–2.9cm at screening progress to aneurysm over time.14–18 A Swedish
study showed that 52.5% of 65-year-old males with an subaneurysmal aortas at
the initial screening had developed aneurysms at the re-scan after five years.16 An
observational study, which included 1,696 individuals with subaneurysmal aortas
from eight different centres in Europe, reported that 60% of individuals with
subaneurysmal aortas developed true aneurysms within five years.17 The same study
also demonstrated that 26% of patients under at least 10 years surveillance had
reached an aortic diameter of >5.4cm. A recent long-term follow-up study from
Gloucestershire (UK) showed that about one quarter of men with an subaneurysmal
aortas at age 65 will reach 5.5cm within 15 years.19
MASS, a 13-year follow-up study, showed that the long-term profit of surveillance
was slightly reduced due to ruptures ≥8 years among men initially screened normal
(<3cm). More than 50% of these ruptures occurred among men with an aortic
diameter of 2.5–2.9cm at the baseline screening and argue for offering this group
a re-scan after five years.18
There is, however, only limited evidence regarding the clinical relevance and
cost-effectiveness of surveillance of persons with an subaneurysmal aortas.37 The
fact that this group constitutes a small cohort (<2% of all men screened) means
that such a measure does not require large resources.
162
Conclusion
Taking into account the dramatic change in epidemiology and contemporary
management of aneurysm, ultrasound screening for aneurysm in elderly men still
appears highly cost-effective. Careful monitoring of the findings in the ongoing
screening programmes for elderly men and adapting to the results are crucial. Further
understanding of the natural history of aneurysm in women is of great importance.
Elderly men with screening-detected subaneurysmal aortas and aneurysms have
similar risk-factor profiles. Subaneurysmal aortas tend to expand to true aneurysms over
time and a substantial proportion will reach the threshold for surgical intervention or
rupture at an age when individuals could still profit from elective aneurysm surgery.
These findings support the statement that subaneurysmal aorta appears to be an early
stage of the aneurysmal disease and, therefore, should be treated as such.
Summary
• Population-based ultrasound screening of aneurysm in 65-year-old men is

highly cost-effective with today’s epidemiology.
• Close monitoring of the outcomes of ongoing screening programmes is
recommended.
• Men with subaneurysmal aorta have a similar risk factor profile as men
with an aneurysm, and growing evidence suggests that individuals with
subaneurysmal aortas have a significant risk of developing “true” aneurysm
over time. A considerable proportion of them will reach the threshold for
surgical intervention or rupture.
• This indicates that subaneurysmal aorta is an early stage of aneurysmal
disease and should be treated as such.
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aneurysm (AAA) at age 65. Eur J Vasc Endovasc Surg 2001; 21: 535–40.
14. Hafez H, Druce PS, Ashton HA. Abdominal aortic aneurysm development in men following a “normal” aortic
ultrasound scan. Eur J Vasc Endovasc Surg 2008; 36: 553–58.
15. McCarthy RJ, Shaw E, Whyman MR, et al. Recommendations for screening intervals for small aortic aneurysms.
Br J Surg 2003; 90: 821–6.
16. Svensjo S, Bjorck M, Wanhainen A. Editor’s choice: Five-year outcomes in men screened for abdominal aortic
aneurysm at 65 years of age: a population-based cohort study. Eur J Vasc Endovasc Surg 2014; 47: 37–44.
17. Wild JB, Stather PW, Biancari F, et al. A multicentre observational study of the outcomes of screening detected
sub-aneurysmal aortic dilatation. Eur J Vasc Endovasc Surg 2013; 45: 128–34.
18. Thompson SG, Ashton HA, Gao L, et al. Multicentre Aneurysm Screening Study Group. Final follow-up of the
Multicentre Aneurysm Screening Study (MASS) randomized trial of abdominal aortic aneurysm screening.
Br J Surg 2012; 99: 1649–56.
19. Oliver-Williams C, Sweeting MJ, Turton G, et al. Lessons learned about prevalence and growth rates of
abdominal aortic aneurysms from a 25-year ultrasound population screening programme. Br J Surg 2018;
105: 68–74.
20. Lederle FA, Johnson GR, Wilson SE, et al. Prevalence and associations of abdominal aortic aneurysm detected
through screening. Aneurysm Detection and Management (ADAM) Veterans Affairs Cooperative Study
Group. Ann Intern Med 1997; 126: 441–49.
21. Wanhainen A, Bergqvist D, Boman K, et al. Risk factors associated with abdominal aortic aneurysm: a
population-based study with historical and current data. J Vasc Surg 2005; 41: 390–96.
22. Forsdahl SH, Singh K, Solberg S, Jacobsen BK. Risk factors for abdominal aortic aneurysms: a 7-year
prospective study: the Tromsø Study, 1994-2001. Circulation 2009; 119: 2202–08.
23. Svensjö S, Björck M, Gürtelschmid M, et al. Low prevalence of abdominal aortic aneurysm among 65-year-
old Swedish men indicates a change in the epidemiology of the disease. Circulation 2011; 124: 1118–23.
24. Stackelberg O, Bjorck M, Larsson SC, et al. Sex differences in the association between smoking and abdominal
aortic aneurysm. Br J Surg 2014; 101: 1230–37.
25. Persson SE, Boman K, Wanhainen A, et al. Decreasing prevalence of abdominal aortic aneurysm and changes
in cardiovascular risk factors. J Vasc Surg 2017; 65 (3): 651–58.
26. Mani K, Bjorck M, Wanhainen A. Changes in the management of infrarenal abdominal aortic aneurysm
disease in Sweden. Br J Surg 2013; 100: 638–44.
27. Budtz-Lilly J, Venermo M, Debus S, et al. Editor’s choice: Assessment of international outcomes of intact
abdominal aortic aneurysm repair over 9 years. Eur J Vasc Endovasc Surg 2017; 54: 13–20.
28. Locham S, Lee R, Nejim B, et al. Mortality after endovascular versus open repair of abdominal aortic aneurysm
in the elderly. J Surg Res 2017; 215: 153–59.
29. Svensjo S, Mani K, Bjorck M, et al. Screening for abdominal aortic aneurysm in 65-year-old men remains cost-
effective with contemporary epidemiology and management. Eur J Vasc Endovasc Surg 2014; 47: 357–65.
30. Glover MJ, Kim LG, Sweeting MJ, et al. Cost-effectiveness of the National Health Service Abdominal Aortic
Aneurysm Screening Programme in England. Br J Surg 2014; 101: 976–82.
31. Svensjo S, Bjorck M, Wanhainen A. Current prevalence of abdominal aortic aneurysm in 70-year-old women.
Br J Surg 2013; 100: 367–72.
32. Soderberg P, Wanhainen A, Svensjo S. Five year natural history of screening detected sub-aneurysms and
abdominal aortic aneurysms in 70 year old women and systematic review of repair rate in women. Eur J Vasc
Endovasc Surg 2017; 53: 802–09.
33. Ulug P, Powell JT, Sweeting MJ, et al. Meta-analysis of the current prevalence of screen-detected abdominal
aortic aneurysm in women. Br J Surg 2016; 103: 1097–1104.
34. Mehta M, Byrne WJ, Robinson H, et al. Women derive less benefit from elective endovascular aneurysm
repair than men. J Vasc Surg 2012; 55: 906–13.
35. Lederle FA, Wilson SE, Johnson GR, et al. Immediate repair compared with surveillance of small abdominal
aortic aneurysms. N Engl J Med 2002; 346: 1437–44.
36. United Kingdom Small Aneurysm Trial P. Long-term outcomes of immediate repair compared with
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model. BMJ 2012; 345: e4276.
165
Evidence on patient volume,
outcome and units of trading
for EVAR and open repair
Introduction
The recent decades have seen a steep increase in the frequency of procedures to
treat abdominal aortic aneurysm in many regions of the world. Although open
repair remained the only treatment routinely available up to the end of the 20th
century, in the last 20 years endovascular aneurysm repair (EVAR) has become the
preferred treatment for most vascular surgeons—with open repair being reserved for
selected, often anatomically challenging cases. Given the high absolute frequency
of the procedures and newer evidence that the rupture risk of aneurysms might be
lower than previously assumed,1 the outcome quality of elective aneurysm repair
has become highly important. The same is true for ruptured aneurysms, which
continues to be a potentially fatal condition.
While in the early period after the introduction of the treatments, open repair
and EVAR were conducted mainly at high-volume referral centres, recently, the use
of the techniques has become more widespread. In many health systems, open repair
and EVAR are now also performed at institutions with a relatively low caseload for
both the hospital and the single surgeon. In Germany, 60% of hospitals performing
open repair have a volume of less than five elective cases per year, and 20% of
hospitals performing EVAR have a volume of less than 20 elective cases per year.
Regarding emergency procedures for ruptured aneurysm, 95% of hospitals offering
treatment have a volume of less than five cases per year.2 It must be expected that
in the absence of profound structural changes to health systems, the caseload for
many hospitals regarding open repair will further decrease. A recently published
study that pooled registry data from Australia, New Zealand and nine European
countries showed a decrease in the mean annual volume of open repair per centre—
from 12.9 to 10.6—while for EVAR an increase from 10 to 17.1 cases per centre
was observed.3 A study using the US Nationwide Inpatient Sample showed that the
proportion of hospitals performing at least 25% of aneurysm repair as open repair
fell from 41% in 2007 to 18% in 2011.4
For many surgical procedures, there is high-level evidence that perioperative
outcomes, and specifically mortality, are inversely related to both hospital and
surgeon volume. Examples include colorectal resections, gastrectomy, pancreatic
surgery, oesophagostomy and cardiac surgery.5–8 In some health systems, this has
led to the stipulation of a minimal volume per hospital or surgeon for certain
procedures in order to be reimbursed. In this chapter, we review the available
evidence on the relationship between hospital and surgeon volume and outcome
for open repair and EVAR.
167
Possible mechanisms underlying the volume-outcome
relationship
There are several explanations for how hospital and surgeon volume positively affect
postoperative outcomes. Obviously, the experience of a surgeon, or in other words
the fact that he or she has already encountered a wealth of different challenging
intra- and perioperative situations, should increase the probability to take the right
decisions in such situations. Additionally, since surgery is profound teamwork and
involves not only surgical staff, but also physicians from other disciplines, nurses
etc., the experience of the single team members, and of the team as a whole working
cohesively together, should lead to a better preparedness for difficult situations; to
avert mistakes before they happen, and to cope with complications to mitigate
their sequelae. If one applies this assumption to quality models, this means that a
higher volume is associated with a higher structure and process quality,9 and that
these in turn lead to higher outcome quality. One specific piece in the causal chain
Evidence on patient volume, outcome and units of trading for EVAR and open repair •
might be the so-called “failure to rescue”. This refers to the observation that high-
volume hospitals have a better ability to avert a patient’s death in case of a severe
perioperative complication. Volume- and size-dependent factors such as around-the-
clock availability of all required diagnostic and therapeutic emergency services, and
experience and up-to-date knowledge in all areas important for perioperative care,
might be crucial factors. In fact, a study assessing 20,690 Medicare beneficiaries
undergoing elective aneurysm repair showed that the probability of suffering a
major postoperative complication was only slightly higher in low-volume compared
to high-volume hospitals (odds ratio [OR] 1.18, 95% confidence interval [CI]
1.09–1.27). However, there was a significantly higher likelihood in low-volume
hospitals that a major complication resulted in death of the patient (OR 1.38, 95%
CI 1.16–1.64).10
Evidence for elective open repair

The first studies assessing a possible association between volume and outcome of
open repair for aneurysms were conducted in the USA in the 1980s. They used
variable definitions of what constitutes a “low-volume” and what constitutes a
“high-volume” hospital. Some used predefined thresholds, others quartiles. All of
the studies showed a significantly lower postoperative mortality in high- compared
with low-volume hospitals.11–14 In one study, the postoperative mortality in low-
volume hospitals, treating one to five cases per year, was more than twice as high
as in high-volume hospitals treating more than 38 cases per year (14% vs. 5%).12
In the 1990s and 2000s, large studies comprising data from many hospitals were
conducted both in the USA and other countries. A study including almost 4,000
open repair procedures in the USA showed that hospital volume is a significant
(p<0.001) independent predictor of mortality with mortality rates of 5.5% in low-
volume (<35 cases per year) and 3% in high-volume (≥35 cases per year) facilities.15
A German study including more than 10,000 cases gave a similar picture with
mortality in low-volume hospitals being double than that in high-volume ones
(5.2% vs. 2.6%). In multivariable analysis, however, this result was not statistically
significant (p=0.07). Results also showed a longer operation time, higher amount
of transfused blood, and longer hospital stay in low-volume facilities.16 In 2007, a
systematic review with meta-analysis summarising the hitherto available evidence
was published. It included 421,299 elective aneurysm operations. The weighted
168
Figure 1: A possible mechanism underlying
the volume-outcome relationship, with higher
Volume per facility and volume leading to higher structure and process
individual surgeon quality, and higher process and structure
quality leading to improved outcome.
Process quality
Outcome quality
OR was 0.66 (95%; CI 0.65 to 0.67) in favour of high-volume hospitals at a

cut-off of 43 cases per year.17 More recent studies showed lower mortality in
high-volume facilities, too. Interestingly, one study from England demonstrated
a mortality advantage for up to two years postoperatively for patients operated
in high-volume facilities. This effect was retained even after accounting for early

postoperative mortality differences.18 A recent study, however, did not find a
relationship between hospital volume and outcome in 4,484 patients undergoing
open repair in the USA.19 The latest published study on the topic, which included
all cases of aneuyrsm repair in Germany between 2005 and 2013, showed that
mortality for open repair was 7.6% in the quartile of hospitals with the lowest
volume, while it was 4.5% in the quartile with the highest volume (Figure 2).20
Many studies also evaluated the relationship between individual surgeon volume
and outcomes. Two of the early studies showed that surgeon volume has an effect
on mortality with rates of 9% vs. 4% and 21% vs. 14.7% for low- vs. high-volume
surgeons.12,13 A study including almost 4,000 open repair cases in the USA showed
surgeon volume to be an independent predictor of mortality, which was almost
half for surgeons operating more than 10 open repair cases per year compared
to surgeons operating fewer cases.15 This study also looked at surgeon specialty
and found that open repair, if carried out by a general as compared to a vascular
surgeon, had a 76% higher mortality, whereas no mortality difference was found
between vascular and cardiac surgeons. Interestingly, another study showed that
rather than the individual surgeon’s volume of open repair cases done, a composite
volume of several open vascular procedures predicted mortality on multivariable
analysis.21
A systematic review with meta-analysis including more than 115,000 patients
undergoing open repair yielded a pooled OR of 0.56 in favour of high-volume
surgeons with a threshold identified at 13 cases per individual surgeon annually.22
169
iAAA – Mortality (%)

10%
8%
7.6%
6.8%
6% 5.9%
OAR overall 5.3%
4.5%
4%
3.0%
2% 2.0% 1.7%
EVAR overall 1.7%
1.6%
0%
Q1 Q2 Q3 Q4
iAAA EVAR iAAA OAR
rAAA – Mortality (%)

60%
52.4%
50%
49.4%
45.1%
OAR overall 43.2%
40% 40.0%
38.7%
34.4%
30%
27.0% EVAR overall 27.4%
26.2%
20%
10%
0%
Q1 Q2 Q3 Q4
rAAA EVAR rAAA OAR
Figure 2: Volume-outcome relationship for open repair and endovascular aneurysm repair
(EVAR) of intact and ruptured abdominal aortic aneurysms in a study comprising all cases of
aneurysm repair in Germany between 2005 and 2013 (from Trenner et al20).
A study published thereafter with almost 6,000 patients undergoing open repair
showed low surgeon volume to be associated with postoperative mortality.
In this study, the effect of surgeon volume was stronger than that of hospital
volume, and on multivariable analysis only surgeon volume retained significance
(OR 2, p<0.001).23
In summary, there is robust evidence that both hospital and surgeon volume
have a relevant influence on outcomes after open repair for aneurysm. Patients
who are operated in a hospital and by a surgeon with a higher caseload have a
lower risk of postoperative death. General experience of the surgeon with vascular
procedures as well as specific training of the surgeon also seem to play a role.
170
Which of the mentioned factors plays the strongest role is not fully clear, as some
of the pertinent evidence is inconclusive.
Evidence for elective EVAR

Since EVAR has become a routine treatment for aneurysm, a number of studies
have examined volume-outcome relationship for the procedure. A study comprising
26,750 Medicare patients undergoing EVAR showed an approximately 1.7 times
higher postoperative mortality at hospitals in the lowest quartile vs hospitals in the
highest quartile.24 Interestingly, in this series hospital volume clearly influenced the
choice between open repair and EVAR, with higher volume facilities performing
EVAR relatively more often than lower volume ones. A UK study including 1,645
EVAR cases showed that hospitals performing fewer than eight yearly cases had
mortality rates which were twice as high as in all other hospitals (6.88% vs. 3.02%;
p=0.003). Of note, among the 91 hospitals with an endovascular service included
in the study, 64 performed fewer than eight EVAR cases per year.25 A study assessed
the outcome of 22,830 Medicare beneficiaries undergoing EVAR between 2001
and 2004. It found that adjusted mortality showed a marked decrease between
the first and second quintile of hospital volume, with a smaller decrease over the
subsequent quintiles.26 Another study used the US Nationwide Inpatient Sample
2003–2007 and found no influence of hospital volume on mortality after EVAR in
both univariable and multivariable analyses.23 A recently published study assessing
more than 12,000 patients who underwent EVAR in New York state, USA, from
2000 to 2011 yielded a small but statistically significant mortality difference
between low-volume (1–33 cases per year, 1.6% mortality) and high-volume (>82
cases per year; 1.3% mortality) hospitals.19 The latest published study on the topic,
which included all cases of aneurysm repair in Germany between 2005 and 2013,

showed that mortality for EVAR in the quartile of hospitals with the lowest volume
was 3%, while it was 1.6% in the quartile with the highest volume (Figure 2).20
The relationship between single surgeon caseload and operative outcomes has
also been examined for EVAR. The study using the US Nationwide Inpatient
Sample 2003–2007 also looked at this parameter, finding that surgeon volume
did not independently predict mortality on multivariable analysis.23 Similar results
were found by two recently published studies from the USA, which both failed
to show an association between surgeon volume and postoperative mortality
following EVAR.19,27
In summary, there is ample evidence suggesting an inverse association between
hospital volume and mortality after EVAR. However, in contrast to open repair,
studies did not show an association between single surgeon volume and outcome.
Evidence for treatment of ruptured aneurysms

Absolute mortality rates after emergency treatment of ruptured aneurysms are
much higher than after elective aneurysm repair. Several studies have examined
whether hospital and surgeon volume have a similar association with outcome as
in elective aneurysm treatment. A study comprising nearly 12,000 patients treated
for ruptured aneurysm in the USA and England with both open repair and EVAR
showed that mortality after ruptured aneurysm treatment was higher in hospitals
with a low caseload as well as in smaller hospitals.28 A study using the US Nationwide
171
Inpatient Sample to identify patients who underwent EVAR for ruptured aneurysm
showed a relevant mortality advantage in hospitals with a higher volume of both
elective and emergency open repair and EVAR.29 Another study yielded a 19%
mortality difference (46% vs. 27%) between community hospitals and a tertiary
medical centre in the USA.30 A recently published study, which included all cases
of aneurysm repair in Germany between 2005 and 2013, also included ruptured
aneurysm patients. The study showed that for open repair, mortality was 52.4% in
the quartile of hospitals with the lowest and 38.7% in the quartile with the highest
volume. For EVAR, mortality was 40% and 27%, respectively (Figure 2).20
The role of individual surgeon volume on outcome after ruptured aneurysm
treatment has been assessed only by a few studies. Mortality was inversely associated
with annual surgeon volume for open repair in a Canadian study, but decreases in
mortality beyond six to 10 cases of ruptured aneurysm per year were modest.31 A
study from the USA showed a similar picture, with mortality of 45.4% in surgeons
operating less than 20 elective cases per year and 21.6% in surgeons operating
more cases.32 The only study looking at surgeon volume and outcome after EVAR
found no association.19
In summary, the available evidence shows that for emergency treatment of
ruptured aneurysm there is an inverse association between hospital and surgeon
volume and mortality. For EVAR, the only available study did not show an
association between surgeon volume and outcome.
Conclusion
The available evidence clearly shows that both hospital and individual surgeon
volume are associated with outcome after aneurysm treatment, with facilities and
surgeons with a higher caseload having lower mortality. This association has been
found for both open repair and EVAR in the elective as well as the emergency
setting. The only exception is emergent EVAR for ruptured aneurysm and surgeon
volume, for which there are no sufficient data available to show an association.
The exact mechanisms underlying this association remain speculative and difficult
to prove with currently used study designs. However, it is probable that higher
structure and process quality in high-volume facilities positively affect mortality,
and that “failure to rescue” in smaller institutions has an opposite effect. Based on
these findings, centralisation of aneurysm treatment in high-volume facilities, in
which a sufficient caseload per surgeon is warranted, should be aimed for. A specific
threshold for minimum case numbers per hospital and surgeon cannot be derived
from the studies and probably depends on many setting-specific circumstances. For
treatment of ruptured aneurysms, timely treatment is crucial. Thus, centralisation
172
Summary
• For many surgical procedures, there is a relationship regarding hospital and

individual surgeon volume and outcome.
• The causal link is assumed to be a higher structure and process quality in
facilities treating a larger number of patients. Specifically, “failure to rescue”,
i.e. the inability to avert mortality in case a major complication occurs, might
contribute to a poorer outcome in low-volume settings.
• For elective open repair of aneurysm, there is a large body of evidence
showing an inverse association between hospital and surgeon volume
and mortality.
• For elective EVAR, there is evidence showing an inverse association between
hospital volume and mortality. However, in contrast to open repair, studies did
not show a clear association between single surgeon volume and outcome.
• For emergent treatment of ruptured aneurysm, there is an inverse association
between hospital and surgeon volume and mortality. The exception is
emergent EVAR, for which the one available study did not show an association
between surgeon volume and outcome.
• Centralisation of aneurysm treatment in high-volume facilities, in which a
sufficient caseload per surgeon is warranted, should be aimed for.
of services might be feasible only to a certain extent because access to treatment

within a reasonable time frame must be ensured.
References
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patients unfit for elective repair. J Vasc Surg 2015; 61 (6): 1606–12.
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Registry report from the German Institute of Vascular Healthcare Research (DIGG) of the German
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3. Budtz-Lilly J, Venermo M, Debus S, et al. Editor's Choice - Assessment of International Outcomes of
Intact Abdominal Aortic Aneurysm Repair over 9 Years. Eur J Vasc Endovasc Surg 2017; 54 (1) :13–20.
4. Hicks CW, Canner JK, Arhuidese I, et al. Comprehensive assessment of factors associated with in-hospital
mortality after elective abdominal aortic aneurysm Repair. JAMA Surg 2016; 151 (9): 838–45.
5. Sahni NR, Dalton M, Cutler DM, et al. Surgeon specialization and operative mortality in the United
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6. Birkmeyer JD, Siewers AE, Finlayson EV, et al. Hospital volume and surgical mortality in the United
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11. Katz DJ, Stanley JC, Zelenock GB. Operative mortality rates for intact and ruptured abdominal aortic
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12. Veith FJ, Goldsmith J, Leather RP, et al. The need for quality assurance in vascular surgery. J Vasc Surg
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174
How volume and
endovascular aneurysm
repair impact outcomes for
ruptured abdominal aortic
aneurysm treatment
Introduction
The repair of the ruptured abdominal aortic aneurysms has had an enduring impact
on the history and teaching of emergency surgery.1,2 The notable wrapping of the
aneurysm with cellophane was yet one vain attempt to prevent rupture, leading
Albert Einstein to refuse reoperation, stating, “I want to go when I want. It is
tasteless to prolong life artificially.”3 The statistics regarding outcomes have changed
little over many years, with mortality ranging from 30% to 80%.4,5 Several counter
measures have been taken to minimise the impact of ruptured abdominal aortic
aneurysms, on both individual patients and healthcare systems alike. These include
expanding screening programmes, better secondary medical care including smoking
cessation, and better perioperative anaesthesiology and intensive care.5-7
Despite evidence of a decreased incidence in ruptured abdominal aortic aneurysms,
mortality is still high.5,8 It may be that improvements in perioperative care play a role
in improving the outcomes of treatment, but recent interest in two critical factors—
endovascular aneurysm repair (EVAR) and patient volume —behove further scrutiny.
These two issues are intertwined, and the degree of their interaction has bearing on
their respective impacts, thus encouraging both a separate and composite analysis of
the roles they play in ruptured aneurysm outcomes.
Endovascular aneurysm repair

It is no overstatement that endovascular technology has radically altered abdominal
aortic aneurysm treatment. The welling of single and multicentre analyses regarding
endovascular aneurysm repair (EVAR) was perhaps only matched by the tempo
of expanding use of EVAR across the world.9,10 Four international randomised
controlled trials essentially solidified the evidence that EVAR was now a mainstay
in aneurysm therapy.11-14 Although it may seem inevitable in hindsight, the use
of EVAR in ruptured aneurysms was a profound development in acute vascular
care.15,16 Early reports were positive, with 30‒day mortalities ranging from 0% to
53%, albeit with significant biases.17
175
Figure 1: Percentage
50 of ruptured
44 44
abdominal aortic
40 aneurysms treated
38 with endovascular
34 aneurysm repair
% EVAR 30 (EVAR) for the
Vascunet participating
25 countries in 2013.
20 22
18
13
10 12 12
7
0
ry d d ark ay UK land land den any ralia
ga lan lan m orw e t
Ice itzer Sw Germ Aus
•
n
Hu Fin Zea Den N
w Sw
How volume and endovascular aneurysm repair impact outcomes for ruptured abdominal aortic aneurysm treatment
Ne
A recent analysis from the Vascunet collaboration further documents the growing
use of EVAR for the treatment of ruptures. The rates are still well behind those of
intact abdominal aortic aneurysm treatment, and recent data highlight the variation
between centres and countries (Figure 1).18
In their analysis of almost 10,000 ruptured aneurysms from 2010‒2013, they
found that EVAR was used in approximately 23% of cases. Interestingly, the patients
who underwent EVAR were older and more severely burdened with cardiovascular
and pulmonary disease, yet the perioperative mortality for these patients (17.9%)
was significantly lower than it was for those who underwent open repair (32.1%).
Further analyses are compelling. Figure 2 displays differences between centres which
predominantly treated their ruptured aneurysms with either EVAR or open repair.
50
40 OR=0.38 OR=0.60
Perioperative mortality (%)
p>0.001 p>0.001
30 32.1
29.7
23.0
20
17.9
10
0
AR air R pair
EV re
p VA re
en yE en
ar p
Op im yo
Pr ar
im
Pr
Figure 2: Perioperative mortality from the Vascunet database, 2010-13, for ruptured abdominal
aortic aneurysm repair, based on either EVAR or open repair, as well as for centres, whether they
employed a strategy of primary EVAR (>50%) or primary open repair. The odds ratio is adjusted
for age, patient sex, aneurysm diameter, and the presence or absence of heart disease, pulmonary
disease, cerebrovascular disease, and diabetes mellitus.
176
The issue, as mentioned, for retrospective analyses of ruptured aneurysm
outcomes is the bias of patient selection and haemodynamic stability. These were
somewhat tempered in the IMPROVE (Immediate management of patients with
ruptured aneurysm: Open vs. endovascular repair) trial, which initially showed
no difference in survival between EVAR and open repair.19 The three‒year results,
however, indicate an improved survival for patients who underwent EVAR, and
this was achieved at a lower cost and with a better quality of life.20
Similar to the subsequent studies for intact abdominal aortic aneurysm repair, it should
be anticipated that ensuing analyses of EVAR in ruptured aneurysms will shed light
on patient selection and procedural considerations. These should include information
on age, patient sex, comorbidities, anatomic suitability, and haemodynamic status, as
well as device selection, transfer times, and ascertainment of centres of expertise with
adequate patient volumes, some of which are discussed below.
Volume
The issue of volume and surgical outcomes has several facets, some intuitive,
and others more nuanced and deserving of more discussion. It is not surprising
that experience leads to better results, and this has been shown to be the case
in aneurysm surgery.21,22 The ramifications of this are real. The Leapfrog Group
healthcare quality initiative, for example, was an effort to incorporate “evidence-
based hospital” criteria for patient care and safety.23 A meta-analysis of both
intact and ruptured aortic aneurysms by Holt et al in 2007 brought forth several
important issues, including the independent and additive effects of surgeon and
hospital volume on outcomes. Indeed, higher-volume vascular surgeons operating
in higher-volume hospitals displayed the lowest mortality rates for abdominal
aortic aneurysm surgery.21 The European Society of Vascular Surgery acknowledges
this evidence, stating in their guidelines that abdominal aortic aneurysm repair
should only be performed in hospitals that perform at least 50 elective infra-renal
aneurysm repairs per annum.24 They do not, however, provide recommendations as
to how or who should be performing repairs for ruptured aneurysms, and this is
perhaps reflective of intricate issues which include geography, transfer times, and
the availability of multidisciplinary staff with trained experience, as well as access
to specific technology. In the above-mentioned meta-analysis, Holt et al point out
that rupture repair at lower-volume centres is associated with worse mortality rates,
and they propose that haemodynamically stable patients with a suspected rupture
• C Nicolajsen, K Mani and J Budtz-Lilly
should be transferred to a hospital of expertise. This proposal has been somewhat

challenged, however, by a recent study by Mell et al in their analysis of 4,439
patients with ruptured aneurysms.25 Transfer was associated with a lower operative
mortality, yet overall mortality was increased when one included those patients
who were transferred but did not undergo surgery.
Volume and EVAR

Although the relationship between volume and outcomes after open aortic repair
appears persuasive, an unambiguous relationship between volume and EVAR is not
at hand. In their analysis of over 120,000 Medicare patients who underwent either
EVAR or open repair, Zettervall et al found that surgeon and hospital volume
were strongly associated with mortality after open repair; no such association was
177
shown between EVAR and surgeon volume, while there was a minimal association
between EVAR and hospital volume.26 Similar relationships were reported in the
aforementioned analysis by the Vascunet collaboration.18 That is, while there was a
clear benefit for open repair at centres of high volume, there was no difference of
statistical significance when comparing results for EVAR based on volume, despite
indications of a trend in this direction.
Interpreting these findings should be carried out with caution, and perhaps the
questions they raise are more informative than what the analysis at first glance
reveals. First, although volume of ruptures may be an obvious variable to consider
when considering institutional outcomes, it may be that the number of elective
aneurysms treated with EVAR has an equally important influence. As mentioned
above, centres employing a primary strategy of EVAR for ruptured aneurysms had a
significantly lower overall perioperative mortality (23%) than centres with a primary
strategy of open repair (29.7%). Coupled to this was the significantly greater use
of EVAR in the primary EVAR centres (82%) for their elective aneurysms than in
the primary open repair centres (50.7%). The achievement of favourable outcomes
for ruptured aneurysm treatment would appear to require an overall increase in
the use of EVAR. In other words, some centres were dedicated to EVAR, for
ruptured and intact aneurysms, while other centres had the capability, yet lacked
the organisational capacity or predilection to use EVAR in cases of rupture.
Secondly, if EVAR is indeed superior to open repair in the treatment of ruptured
aneurysms, should all centres adopt this strategy? The guidelines from the European
Society for Vascular Surgery recognise this proposition, pointing out that 24-hour
availability of EVAR requires a significant degree of institutional reorganisation and
dedication.24 On the other hand, if smaller centres can replicate the satisfactory results
of larger centres, perhaps this process is both feasible and gainful. The alternative
would be transfer of patients to larger centres, where the rationale would essentially
be one of institutional capacity to provide this type of service.
Thirdly, if logistical or political contentions prohibit institutional adaptation to a
primary strategy of EVAR for acute ruptures, then prioritisation of higher volume,
or centralisation of services, should nonetheless be pursued. This was also evident
in the Vascunet analysis. Centres of high open aortic repair volume demonstrated
significantly better perioperative mortality (25.3%) than centres of low volume
(36.8%).18
Finally, the improved outcomes from either EVAR or centralisation for ruptured
aneurysms should be considered within the larger context of public healthcare. That
is, centres with high volumes of ruptured aneurysms, prominent use of EVAR, and
laudable outcomes are still failing their population on some level, as it is scarcely
credible to submit that good results for ruptures will ever equal those of timely,
elective repair in centres of high volume. Improved and expedient treatment of intact
aneurysms should be the priority in an effort to reduce the number of ruptures.
An all-important aspect to any retrospective data regarding ruptured aneurysm
outcomes should also be noted. The lack of turn-down rates renders any comparative
analysis problematic, and any interpretation of results should be formed with this
limitation in mind.
178
Conclusion
The evidence for the superiority of EVAR over open repair in the treatment of
ruptured abdominal aortic aneurysms is becoming more persuasive. Whether this is
a result of more widespread experience and expertise, or even improved technology,
the three‒year results from the IMPROVE trial represent an important landmark
in this progression. However important it is, the impact from this trial may not
necessarily be a watershed moment, as it is already clear that many centres are moving
towards EVAR as the primary strategy for treating ruptured aneurysms. This process
is not a simple one, however, as infrastructural and acute service reorganisation is
often required, and one aspect of this process is centralisation of care to centres
of competence. The benefit of higher volumes is well documented in aneurysm
treatment, but the adaptation to fewer centres with greater expertise and access to
technology, such as EVAR, is less well described.27 Future work from prospective
population-based registries such as the Vascunet collaboration and the International
Consortium of Vascular Registries (ICVR) should play a role in this process.
Summary
• Retrospective and randomised control trials have shown EVAR to be superior

to open aortic repair in treating ruptured abdominal aortic aneurysms.
• High patient volume is associated with better outcomes in the treatment of
ruptured abdominal aortic aneurysms, although this relationship with EVAR is
weaker than it is for open repair.
• Improved outcomes for ruptured aneurysm treatment, particularly for EVAR,
are associated with greater volumes of intact aneurysm repairs.
• Reorganisation of vascular surgery services should take into account the
availability and access to EVAR treatment.
References
1. Veith FJ. Historical perspective on the treatment of ruptured abdominal aortic aneurysms. In: Starnes
B, Mehta M, Veith F, editors. Ruptured Abdominal Aortic Aneurysm. Springer, Cham; 2017.1c9.
2. Gerbode F. Ruptured aortic aneurysm: a surgical emergency. Surg Gynecol Obs 1954; 98: 759–64.
3. Cohen J, Graver L. The ruptured abdominal aortic aneurysm of Albert Einstein. Surg Gynecol Obs 1990;
170: 455–58.
4. Bengtsson H, Bergqvist D. Ruptured abdominal aortic aneurysm: a population-based study. J Vasc
Surg 1993; 18: 74–80.
5. Bown MJ, Sutton a J, Bell PRF, Sayers RD. A meta-analysis of 50 years of ruptured abdominal aortic
aneurysm repair. Br J Surg 2002; 89: 714–30.
6. Anjum A, Von Allmen R, Greenhalgh R, Powell JT. Explaining the decrease in mortality from abdominal
aortic aneurysm rupture. Br J Surg 2012; 99: 637–45.
7. Moore R, Nutley M, Cina CS, et al. Improved survival after introduction of an emergency endovascular
therapy protocol for ruptured abdominal aortic aneurysms. J Vasc Surg 2007; 45: 443–50.
8. Kantonen I, Lepantalo M, Brommels et al. Mortality in ruptured abdominal aortic aneurysms. The
Finnvasc Study Group. Eur J Vasc Endovasc Surg 1999; 17: 208–12.
9. Vallabhaneni SR, Harris PL. Lessons learnt from the EUROSTAR registry on endovascular repair of
abdominal aortic aneurysm repair. Eur J Radiol 2001; 39: 34–41.
10. Thomas S, Beard J, Ireland M, Ayers S. Results from the Prospective Registry of Endovascular Treatment
of Abdominal Aortic Aneurysms (RETA): Mid Term Results to Five Years. Eur J Vasc Endovasc Surg 2005;
29: 563–70.
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11. Becquemin J-P, Pillet J-C, Lescalie F, et al. A randomized controlled trial of endovascular aneurysm
repair versus open surgery for abdominal aortic aneurysms in low- to moderate-risk patients. J Vasc
Surg 2011; 53: 1167–73.e1.
12. Prinssen M, Verhoeven ELG, Buth J, et al. A randomized trial comparing conventional and endovascular
13. Greenhalgh RM, Brown LC, Epstein D, et al. Endovascular aneurysm repair versus open repair in
patients with abdominal aortic aneurysm (EVAR trial 1): randomised controlled trial. Lancet 2005; 365:
2179–86.
14. Lederle FA, Freischlag JA, Kyriakides TC, et al. Outcomes following endovascular vs open repair of
abdominal aortic aneurysm: a randomized trial. JAMA 2009; 302: 1535–42.
15. Hinchliffe R., Yusuf S., Macierewicz J., et al. Endovascular Repair of Ruptured Abdominal Aortic
Aneurysm – a Challenge to Open Repair? Results of a Single Centre Experience in 20 Patients. Eur J
16. Resch T, Malina M, Lindblad B, et al. Endovascular Repair of Ruptured Abdominal Aortic Aneurysms:
Logistics and Short-Term Results. J Endovasc Ther 2003; 10: 440–46.
17. Harkin DW, Dillon M, Blair PH, et al. Endovascular Ruptured Abdominal Aortic Aneurysm Repair
(EVRAR): A Systematic Review. Eur J Vasc Endovasc Surg 2007; 34: 673–81.
18. Budtz-Lilly J, Bjorck M, Venermo M, et al. The impact of centralization and endovascular aortic repair
on treatment of ruptured abdominal aortic aneurysms based on international registries: European
Society of Vascular Society, Annual Meeting. Lyon; 2017.
19. IMPROVE trial investigators. Endovascular or open repair strategy for ruptured abdominal aortic
aneurysm: 30 day outcomes from IMPROVE randomised trial. Br Med J 2014; 7661: 1–12.
20. IMPROVE trial investigators. Comparative clinical effectiveness and cost effectiveness of endovascular
strategy v open repair for ruptured abdominal aortic aneurysm: three year results of the IMPROVE
randomised trial. BMJ 2017; 359: j4859.
21. Holt PJ, Poloniecki JD, Gerrard D, et al. Meta-analysis and systematic review of the relationship between
volume and outcome in abdominal aortic aneurysm surgery. Br J Surg. 2007; 94: 395–403.
22. Budtz-Lilly J, Venermo M, Debus S, et al. Editor’s Choice – Assessment of International Outcomes of
Intact Abdominal Aortic Aneurysm Repair over 9 Years. Eur J Vasc Endovasc Surg 2017; 54: 13–20.
23. Milstein A, Galvin RS, Delbanco SF, et al. Improving the safety of health care: the leapfrog initiative. Eff
Clin Pract 2000; 3: 313–16.
24. Moll FL, Powell JT, Fraedrich G, et al. Management of Abdominal Aortic Aneurysms Clinical Practice
Guidelines of the European Society for Vascular Surgery. Eur J Vasc Endovasc Surg 2011; 41: S1–58.
25. Mell MW, Wang NE, Morrison DE, et al. Interfacility transfer and mortality for patients with ruptured
abdominal aortic aneurysm. J Vasc Surg 2014; 60: 553–7.
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27. Gill D, Pigott J, Shalhoub J, Hussain T, et al. Experience of centralization of vascular surgical services at
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180
Generation of high-
performance teams in
emergency aortic surgery—
simulated leadership and
team training is effective
A Sharrock, AJ Batchelder, C Riga and C Bicknell
Introduction
Aortic pathology presenting as an emergency invariably progresses rapidly. Procedures
need to be in place to rapidly diagnose and expediently manage the patient to
maximise their chance of survival. The system is not always set up to ensure this
occurs. It is acknowledged that teams change frequently within the NHS and staff
may have differing levels of clinical experience, especially outside normal office hours.
The opportunity to plan and organise equipment, staff and procedures is removed in
emergency surgery and the logistics of opening an emergency theatre and ensuring kit
and consumables are available can further delay treatment. The surgery itself forms
one step of the patient journey; there is a prolonged pathway between the emergency
department and critical care unit, and each of these steps may cause avoidable and
potentially lethal delays in the hands of an untrained team.
Surgery requires knowledge, technical skills, leadership and team working.
The former are taught and assessed during formal training pathways in the UK.1
Leadership, team working and non-technical skills are critically important in
coordinating a team to act cohesively and effectively in concert. Classical examples
of this are the displays of the Royal Air Force’s aerobatics team, the Red Arrows2
and Formula One pit stop teams, both of whom prepare for the worst while
training for the best performance possible. The importance of slick team working
skills in the crisis scenario was demonstrated on 31st July 1994 during the German
Grand Prix. Jos Verstappen’s pit stop refuelling resulted in the spontaneous ignition
of litres of high pressure fuel when the hose failed to engage with his Benetton
F1 racing car. The pit stop team and Jos were all ignited but were extinguished
four seconds later due to the quick actions of the well-rehearsed team. Jos came
in podium position three weeks later, having escaped with only minor burns to
his face. Team simulation and rehearsal saves lives and the effects of good training
are amplified in emergency or crisis scenarios. Time-critical surgery lends itself
to planning and rehearsal, as errors in leadership and team working may increase
mortality rates directly or through delays. This chapter discusses how simulation
can be used to generate high-performance teams in emergency aortic surgery.
181
Emergency aortic surgery
A Sharrock, AJ Batchelder et al
Despite the aortic screening programme implemented across the UK for males in
their 65th year in 2009, there were 2,761 ruptured abdominal aortic aneurysm
repairs reported in the National Vascular Registry (NVR) between 1 January 2013
and 31 December 2015.3,4 Thoracic aortic aneurysm rupture events were estimated
at approximately three admissions per 100,000 between 1999 and 2010 in those
aged over 75 in the UK, and rates are increasing.5,6 The acute aortic syndromes
including aortic dissection, intramural thrombus and penetrating atherosclerotic
aortic ulcer may also present as an emergency.7 The use of endovascular repair for
ruptured aneurysm increases year on year, and approximately a quarter were repaired
using endovascular means in 2016.4 Endovascular repair is the gold standard for
Generation of high-performance teams in emergency aortic surgery—simulated leadership and team training is effective •
descending thoracic aortic pathology and this technique has halved operative
mortality compared to open repair.8 However, the development and evolution of
endovascular surgery has required considerable technological investment. Over the
years, advancements in surgical technology have undoubtedly improved patient
outcomes; however, this may in itself bring inefficiency and error, including
equipment failure, which has been shown to contribute to a substantial proportion
of reported errors.9
Errors in surgery
In general surgery, adverse events are highest in patients undergoing complex
procedures. Inexperience, communication failure and fatigue were reported to have
respectively contributed to 53%, 43% and 33% of errors in management, of which
33% led to permanent disability and 13% led to death in a large retrospective
series.10 While these figures are high, adverse events in complex arterial and
emergency procedures could be expected to be even greater. Although the majority
of the errors reported by this group occurred in the operating theatre, 27%
occurred preoperatively and 22% postoperatively, demonstrating the error burden
for the entire patient journey and the importance of communication between the
phases of care.
The errors most commonly studied are those in theatre, where the majority occur.
When errors happen during a vascular surgical procedure they are predominantly
non-technical, the majority being related to equipment failure (24%) or errors in
communication (21%).11 Non-technical errors can be divided into the domains of
communication, cooperation, coordination, shared leadership and team monitoring
and assessed on a six-point scale using a tool such as the observational teamwork
assessment for surgery (OTAS).12 Major failures in aortic surgery were associated
with reoperation and were mostly related to communication issues in the 2016
LEAP study.13 Endovascular rather than open repair, thoracic aneurysm rather
than other aortic pathology and unfamiliarity with equipment were all shown to
significantly predict high failure rates. This study sought to define the landscape
of surgical system failures in aortic surgery and suggested that these predictors for
failure may be mitigated through teamwork and leadership training. Additionally,
the LEAP study recommended team simulation, particularly for crisis scenarios.
182
Simulation
Simulation training is established in surgical teaching. It allows for training outside
the operating environment and creates a safe space for the development of technical
skills. Technical simulation has been demonstrated to correlate with quality of
performance in the context of general surgery (laparoscopic cholecystectomy).14
Likewise, simulation training in vascular surgery has been shown to reduce
procedure and fluoroscopy time and improve selection and placement of catheters
and stents.15 Significant improvements in technical skills can be made by junior
vascular surgeons; for example, they may achieve similar competencies to senior
surgeons over the course of six sessions (as shown in one study).16
Non-technical skills may also be improved by simulated practice, and whole
team training in a high-fidelity environment may improve patient outcomes.17
This allows a scenario to be acted out in a safe, controlled environment and
for individuals within a team to gain confidence and understanding in their
role. Team training simulation has been performed effectively in open and
endovascular emergency aortic surgery. Orcamp (Orzone; Figure 1) is an example
of an immersive, high-fidelity, simulated angiography suite which is realistic and
valuable for “enhancing teamwork and patient safety”.18 Scenarios may be selected
to enhance multidisciplinary team training alone or to specifically target those
procedures associated with a higher number of major failures.
Alternatively, a simulator may be used in the operating theatre in conjunction
with other team members to enhance fidelity—“in-situ training”. An inflatable
theatre (Distributed Simulation, Convincis) system has been developed to provide
an enclosed authentic operating environment.19 This provides visual cues to improve
fidelity without the use of limited theatre space in busy hospital environments.
Novel technologies such as Anatomage (Anatomage) interactive virtual dissection
tables have also evolved to facilitate 3D interactive anatomy visualisation.
Generation of high performance teams

High performance teams all require practice. In the NHS, teams are often large and
change frequently, with team members transitioning through different operating
Figure 1: ORCAMP (Orzone)

angiography suite at St Mary's
Hospital, Imperial College, London, UK
183
theatres. Regular simulation training should capture the majority of those who
could be involved in emergency aortic surgery and should ideally include the entire
patient pathway.
A number of methods have been investigated to generate high performance
teams, as summarised in Table 1. Checklists and preoperative briefings are
important elements in the generation of high performance teams. Most widely
publicised is the World Health Organization surgical checklist where significant
error is reduced and there is a significant effect on mortality.20 However, these
checklists should be tailored to the individual environment; for example, equipment
error has been shown to account for almost a quarter of the total errors reported
in a systematic review of surgical error studies.9,21 The policy of incorporating
a preoperative equipment check into the World Health Organization surgical

checklist may be useful in the endovascular environment. Morbi et al (2012) and
Patel et al showed in two separate studies that the adoption of a preprocedural
structured rehearsal was highly effective in reducing errors and inefficiencies
that occurred during minimally invasive surgery.21,22 A multicentre randomised
controlled trial of preprocedural rehearsal of technical and non-technical errors
in live endovascular aneurysm repairs demonstrated a reduction in both major
and minor errors using preprocedural rehearsal.23 This group used a virtual reality
simulator for patient-specific rehearsal and identified improvements in all metrics
studied, including procedural delay, and could easily be implemented for specific
cases. Similarly, Orzone’s high-fidelity simulator has been used for regular team
training at Imperial College London (London, UK) for staff involved in emergency
or elective endovascular surgery. This type of training is useful where the risk of
error is perceived to be higher than normal, such as for training with new pieces
of equipment. The training can also be tailored to the unit, for example following
“serious incident” events. The latter can form the basis of a scenario, so all team
members can learn and reflect on improving future patient care. The utility of
the Orcamp angiography suite for team training has been validated by trainees
and consultant endovascular specialists.18 Improvements in all non-technical skill
domains of communication, cooperation, coordination, shared leadership and team
monitoring were seen when this type of simulation was used in training UK surgical
trainees in thoracic endovascular aortic repair, regardless of training grade.12,24 This
study entailed standardised debriefing of lead operators between two high-fidelity,
fully immersive thoracic endovascular aortic repair simulations, in which the roles
of all other team members were acted and scripted.
The Team Training for Ruptured Aortic Aneurysm Management (TTRAAM)
course has been developed by the Royal College of Surgeons of England to benefit
multiple regional vascular teams throughout the UK. The aim was to improve team
working in the management of all patients with a ruptured aneurysm and cover
the entire assessment and treatment pathway. The impact of this training method
has undergone preliminary review of team attitudes and clinical outcomes, and
data from pilot courses (2012–2013) suggested that trained teams were positively
influenced by the course. In addition to benefits to the team members that attended
the pilot courses, a positive impact was also described for other team members
in the hospital. Significantly, structural pathways for aneurysm management were
developed and new protocols were introduced at many sites.
184
•
Checklists Development of the World Health
Organization surgical/radiological checklist to
include case rehearsal and equipment checks
Preprocedure rehearsal • Mental rehearsal

• Virtual reality patient-specific case rehearsal
Simulation team training High-fidelity virtual reality simulation for:

• Elective cases
• Emergency cases
• High-risk procedures
• Novel procedures
• Learning in response to serious incident
reporting
• Training and reorganisation of entire
pathways of care
Table 1: Evidence-based methods to facilitate generation of high performance teams.
Use of the methods listed in Table 1 the generation of high performance

teams may be affected by other factors such as culture and finance. The culture
of NHS institutions is evolving to support training and improve patient safety
to reduce error. The NHS England Patient Safety Domain supports these efforts
by advocating the use of education in human factors, checklists and teamwork.25
Likewise, training in non-technical skills is increasingly supported within
doctors' training programmes in the UK.26 There is a financial incentive for NHS
institutions to reduce the risk of error. Unpublished data from the LEAP study
suggest that each minor error costs in excess of £50, while major errors without
or with harm each cost over £600 and £2000 respectively.13,27 The factors involved
in accruing costs are calculated from a combination of lost theatre time, the costs
of additional equipment, additional procedures and extra blood products. These
figures are likely to represent an underestimate as they do not take into account the
cost of postoperative complications and extended length of stay. Evidence therefore
exists to support integration of mandatory team training in new technologies and
techniques, updated pathways of care and following serious incidents, and that this
should include both trainees and the entire team responsible for patient care as
standard practice.
Conclusion
Errors occur frequently in surgery, and non-technical errors, including equipment
failure, communication errors and poor leadership, contribute to a significant
proportion of these. Emergency aortic surgery presents a high risk for errors due
to the nature of expedient surgery limiting logistical and surgical planning, as well
as the involvement of staff potentially unfamiliar with the condition, procedure
and equipment. Many of these skills can be taught, refined and assessed, and
training is increasingly supported within institutions and training programmes.
Participation in simulation training may facilitate development of technical and
185
non-technical skills more rapidly than conventional apprenticeship-style training.

The use of high-fidelity simulation has demonstrated a significant improvement in
non-technical skills in surgical trainees and the integration of team training using
these simulators is essential to reduce errors, improve patient safety and develop
high performance teams.
Summary
• Aortic aneurysm rupture has a significant mortality and it is crucial for teams
who treat these patients to work efficiency and effectively.
• Technical and non-technical errors are common in aortic surgery and result in
patient harm.
• Simulation training builds team confidence and improves interaction in a safe,
controlled environment.
• Mental rehearsal and patient-specific rehearsal have been shown to reduce
intraoperative errors.
• High-fidelity immersive simulation recreates the stress of the operating theatre
and is an important training aid.
• Team training is logistically possible and the cost of errors provides a financial
incentive to its universal implementation.
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a global population. N Engl J Med 2009; 360 (5): 491–99.
21. Morbi AH, Hamady MS, Riga CV et al. Reducing error and improving efficiency during vascular
interventional radiology: implementation of a preprocedural team rehearsal. Radiology 2012; 264 (2):
473–83.
22. Patel SR, Gohel MS, Hamady M et al. Reducing errors in combined open/endovascular arterial
procedures: influence of a structured mental rehearsal before the endovascular phase. J Endovasc Ther
2012; 19 (3): 383–89.
23. Desender LM, Van Herzeele I, Lachat ML et al. Patient-specific rehearsal before EVAR: Influence on
technical and nontechnical operative performance. A randomized controlled trial. Ann Surg 2016; 264
(5): 703–09.
24. Sharrock A, Ramjeeawon A, Morbi A et al. Unpublished data. 2018.
25. NHS England. National Safety Standards for Invasive Procedures (NatSSIPs). 2015.
26. RCSEd. Non-Technical Skills for Surgeons (NOTSS) System Handbook. http://bit.ly/2DSjsdW [Date
accessed 26 January 2017]
27. Batchelder A. Multicentre observational study of surgical system failures in aortic procedures and
their effect on patient outcomes—financial analysis of error costs adjusted to 2017.
187
EVAR in women controversies
Risk of abdominal aortic
aneurysm among relatives
of abdominal aortic
aneurysm patients
KM van de Luijtgaarden, F Bastos Gonçalves,
MJ van Rijn, S ten Raa, SE Hoeks, RJ Stolker, D
Majoor-Krakauer and HJM Verhagen
Introduction
Abdominal aortic aneurysm occurs in approximately 6% (range 4–8%) of the male
and 1% (range: 1–2%) of the female population above the age of 55 years, and is
an important cause of mortality in the aged population.1–7 Clinical risk factors for
these aneurysms include age, male gender, smoking and a positive family history.8
Population-based screening programmes targeting the higher risk category of men
over the age of 65 years have demonstrated a reduction in mortality from aneurysm
rupture, and have already been implemented in many Western countries.1–3,5 Recent
data from screening studies in the UK showed, however, an aneurysm incidence
that was lower than expected.9–11 To raise efficacy of these programmes, screening
subpopulations at an especially high risk of having an aneurysm, so called targeted
screening, seems a possible better alternative.
In recent decades, it became clear that familial occurrence of abdominal aneurysm
is high, with up to 20% of the patients having a first degree relative known to be
affected with an aortic aneurysm.12 Therefore, it is important to establish if relatives
of abomdinal aneurysm patients represent a specific high-risk category that may
benefit from targeted screening.
In this chapter, we discuss the current knowledge on gender-specific risk for
developing aortic aneurysms in relatives of abdominal aortic aneurysm patients and
whether we should adjust screening protocols for relatives of such patients.
Genetic background of aneurysm

Familial clustering of abdominal aneurysm disease was first described 30 years
ago, and has since been described at rates around 14%.12,13 Familial abdominal
aortic aneurysm may occur in the genetic aortic aneurysm syndromes, caused by
specific defects in genes involved in the TGF-ß pathway and smooth muscular
cell homeostasis, predominantly affecting the thoracic segment of the aorta.14–17
Approximately 2% of familial and sporadic abdominal aortic aneurysm were caused
by a mutation (TGFBR2, MYH11, and COL3A1) from a diagnostic testing panel
191
KM van de Luijtgaarden, F Bastos Gonçalves, et al
Figure 1: Gender-related risk for relatives of aneurysm patients. (Publication with permission of Vascular
Medicine, SAGE).
Risk of abdominal aortic aneurysm among relatives of abdominal aortic aneurysm patients •
of nine aneurysm genes, which were previously associated with syndromal and non-
syndromal thoracic aneurysms. However, apart from rare overlapping genetic defects
between abdominal aortic aneurysms and thoracic aortic aneurysms, for the majority
of abdominal aortic aneurysms, the major genetic causes remain unknown.18
In familial aneurysms, relatives have an increased risk for aneurysm compared
with the general population. Therefore, similar to the other highly prevalent
hereditary cardiovascular disorders, such as hypertrophic cardiomyopathy and
hypercholesterolaemia, screening of relatives of familial abdominal aortic aneurysm
patients seems logical because it allows early diagnosis and consequently improved
prognosis of relatives.19
Gender-specific risk for relatives

The risk for relatives of aneurysm patients has been established in several studies.
A recent study described a population of 568 aneurysm patients in which 6.4% of
all parents and siblings were reported to have an aortic aneurysm.12 When stratified
for gender, there was a 2.8-fold increase in aneurysm risk for female relatives and
a 1.7-fold increase in risk for male relatives compared with the estimated general
population risks. This corresponded to an absolute risk of 4% for female relatives
and 9.5% for male relatives. Because the general population risk is lower in women
than in men, the increase in risk was higher for female relatives than for male
relatives (Figure 1).
The authors also examined whether gender had an effect on aneurysm risk for
family members.12 They showed that aneurysm was significantly more common
among the relatives of female aneurysm patients as compared with the relatives
of male aneurysm patients, respectively 9% vs. 5.9% (p=0.022). The female and
male relatives of female patients had a 5.5- and two-fold increase in aneurysm
risk, respectively, as compared with the estimated general population risk. This
corresponded to an absolute risk of 7.7% for female relatives and 11% for male
relatives of female aneurysm patients. In families of male aneurysm patients,
risk was 2.4-fold higher for female and 1.6-fold higher for male relatives. This
192
corresponded to an absolute risk of 3.4% for female relatives and 9% for male
relatives of male aneurysm patients (Figure 1).
One in four aneurysm patients have a first-degree relative also diagnosed with
aneurysm. The prevalence of an aneurysm in relatives of aneurysm patients,
irrespective of the presenting patient’s gender, is much higher than the prevalence
in the general population. This is especially the case in females, in which the risk
of developing aneurysms is proportionally much higher. Current data for the risk
for females is relatively scarce, with only five of the 13 family history studies and
two of the 20 studies ultrasound family screening studies reported gender-specific
risks.12 They show, nevertheless, a similar pattern of increased risk for females
developing aortic aneurysm.
Implications for clinical management—the need for targeted

family screening
These findings have important clinical implications. There are large differences in the
approach of screening families for aneurysm in the current international guidelines,
in particular in terms of gender, age and surveillance interval.20–24 These current
guidelines do not use gender-specific risk estimates for relatives of aneurysm nor advise
clinicians to inform patients and their relatives with regard to the risk of developing
aortic aneurysms. The American College of Cardiology/American Heart Association
(ACC/AHA) guideline, for instance, recommends screening of only male relatives,
whereas the European Society for Vascular Surgery (ESVS) guideline recommends
screening of all relatives in patients with a family history of aneurysm.22,25
Considering the significantly increased risk for all relatives, including females,
the current data emphasise the need to focus also on aneurysm risk for female
relatives and to relatives of female aneurysm patients. Targeted family screening of
all (first-degree) relatives of aneurysm patients, irrespective of gender, showed to

already be successful in a Swedish cohort.26
Population screening programmes that have been initiated in several countries,
focusing on the male elderly population, are based on trials showing that screening
of men over the age of 65 years was effective in reducing mortality from aortic
aneurysm rupture.22,27,28–30 However, recent data from these programmes across the
UK, Sweden and USA have shown a lower incidence of abdominal aortic aneurysm
than expected, raising questions on the efficacy of population screening.9–11 Given
the discussions about the cost-effectiveness of nationwide screening programmes,
the current family data suggest that screening for aneurysms in relatives of aneurysm
patients may be a valuable addition or alternative to general population screening.
Another question that remains unanswered is the age threshold to start targeted
family screening. The current European guidelines advise to start screening from
the age of 50 years, and this is based on the finding that 7% of aneurysm patients
worldwide are younger than 60 years and an increase in abdominal aortic diameter
is expected to start several years prior to the average age of presentation.22,31
32
It seems reasonable to advise that relatives should be screened at age 50–55
years, and then repeated at age 65–70 years if negative. If positive, they should
follow the current surveillance recommendations until proven otherwise by future
research. Exceptions should be made for families in which a genetic defect has
been identified and/or patients are diagnosed before the age of 50 years, for whom
tailored screening at earlier age should be considered.
193
Conclusion
Relatives of aneurysm patients have a high risk for developing aneurysms, in

particular the relatives of female patients. The risk for relatives is much higher
in families of aneurysm patients than in the general population. Female relatives
of aneurysm patients have an especially increased risk of developing abdominal
aortic aneurysm. Both male and female relatives of all aneurysm patients should,
therefore, have similar access to screening. Relatives of aneurysm patients are for
now the easiest identifiable high-risk population available for targeted screening.
The new insights in familial risk and family screening for aneurysm are important
to inform aneurysm patients and their relatives and more specifically to allow their
relatives to benefit from screening.
Summary
• The risk for aortic aneurysm in relatives of aneurysm patients is much higher
than that of the general population.
• The absolute risk is highest for male relatives of male or female patients (9%
versus 11%, respectively).
• The relative risk is highest for female relatives of female patients (risk increase
5.5-fold).
• Targeted family screening of both male and female relatives of all aneurysm
patients seems justified to improve early detection of aneurysms.
• We support screening from the age of 50 years.
• Future studies should determine cost-effectiveness of this approach as well its
effect on aneurysm-related mortality.
References
1. Lindholt JS, Juul S, Fasting H, et al. Screening for abdominal aortic aneurysms: single centre randomised
controlled trial. BMJ 2005; 330 (7494): 750.
2. Multicentre Aneurysm Screening Study Group. Multicentre aneurysm screening study (MASS): cost
effectiveness analysis of screening for abdominal aortic aneurysms based on four year results from
randomised controlled trial. BMJ 2002; 325 (7373): 1135.
3. Norman PE, Jamrozik K, Lawrence-Brown MM, et al. Population based randomised controlled trial on
impact of screening on mortality from abdominal aortic aneurysm. BMJ 2004; 329 (7477): 1259.
4. Pleumeekers HJ, Hoes AW, van der Does E, et al. Aneurysms of the abdominal aorta in older adults. The
Rotterdam Study. Am J Epidemiol 1995; 142 (12):1291–99.
5. Scott RA, Wilson NM, Ashton HA, et al. Influence of screening on the incidence of ruptured abdominal
aortic aneurysm: 5-year results of a randomized controlled study. Br J Surg 1995; 82 (8):1066–70.
6. Singh K, Bonaa KH, Jacobsen BK, et al. Prevalence of and risk factors for abdominal aortic aneurysms in
a population-based study : The Tromso Study. Am J Epidemiol 2001; 154 (3): 236–44.
7. Anderson RN. Deaths: leading causes for 2000. Natl Vital Stat Rep 2002; 50 (16): 1–85.
8. Vardulaki KA, Walker NM, Day NE, et al. Quantifying the risks of hypertension, age, sex and smoking in
patients with abdominal aortic aneurysm. Br J Surg 2000; 87 (2): 195–200.
9. Penkar S, Druce S, Ashton HA, et al. Prevalence of screen-detected AAAs in men aged 65 is decreasing;
however, the prevalence of cardiac and respiratory diseases remains significantly higher in this group.
Br J Surg 2011; 98 (1): 1–15.
10. Darwood R, Earnshaw JJ, Turton G, et al. Twenty-year review of abdominal aortic aneurysm screening
in men in the county of Gloucestershire, United Kingdom. J Vasc Surg 2012; 56 (1): 8–13.
194
11. Darwood RJ, Brooks MJ. The impact of decreasing abdominal aortic aneurysm prevalence on a local
aneurysm screening programme. Eur J Vasc Endovasc Surg 2012; 44 (1): 45–50.
12. van de Luijtgaarden KM, Rouwet EV, Hoeks SE, et al. Risk of abdominal aortic aneurysm (AAA) among
male and female relatives of AAA patients. Vasc Med 2017; 22 (2): 112–18.
13. Clifton MA. Familial abdominal aortic aneurysms. Br J Surg 1977; 64 (11): 765–66.
14. Loeys BL, Schwarze U, Holm T, et al. Aneurysm syndromes caused by mutations in the TGF-beta
receptor. N Engl J Med 2006; 355 (8): 788–98.
15. Lindsay ME, Schepers D, Bolar NA, et al. Loss-of-function mutations in TGFB2 cause a syndromic
presentation of thoracic aortic aneurysm. Nat Genet 2012; 44 (8): 922–27.
16. van de Laar IM, Oldenburg RA, Pals G, et al. Mutations in SMAD3 cause a syndromic form of aortic
aneurysms and dissections with early-onset osteoarthritis. Nat Genet 2011; 43 (2):121–26.
17. Renard M, Callewaert B, Baetens M, et al. Novel MYH11 and ACTA2 mutations reveal a role for enhanced
TGFbeta signaling in FTAAD. Int J Cardiol 2013; 165 (2): 314–21.
18. van de Luijtgaarden KM, Heijsman D, Maugeri A, et al. First genetic analysis of aneurysm genes in
familial and sporadic abdominal aortic aneurysm. Hum Genet 2015; 134 (8): 881–93.
19. Hoedemaekers YM, Caliskan K, Michels M, et al. The importance of genetic counseling, DNA
diagnostics, and cardiologic family screening in left ventricular noncompaction cardiomyopathy. Circ
Cardiovasc Genet 2010; 3 (3): 232–39.
20. Hirsch AT, Haskal ZJ, Hertzer NR, et al. ACC/AHA 2005 Practice Guidelines for the management of
patients with peripheral arterial disease (lower extremity, renal, mesenteric, and abdominal aortic): a
collaborative report from the American Association for Vascular Surgery/Society for Vascular Surgery,
Society for Cardiovascular Angiography and Interventions, Society for Vascular Medicine and Biology,
Society of Interventional Radiology, and the ACC/AHA Task Force on Practice Guidelines (Writing
Committee to Develop Guidelines for the Management of Patients With Peripheral Arterial Disease):
endorsed by the American Association of Cardiovascular and Pulmonary Rehabilitation; National
Heart, Lung, and Blood Institute; Society for Vascular Nursing; TransAtlantic Inter-Society Consensus;
and Vascular Disease Foundation. Circulation 2006; 113 (11): e463–654.
21. Chaikof EL, Brewster DC, Dalman RL, et al. SVS practice guidelines for the care of patients with an
abdominal aortic aneurysm: executive summary. J Vasc Surg 2009; 50 (4): 880–96.
S1–S58.
23. Lim LS, Haq N, Mahmood S, et al. Atherosclerotic cardiovascular disease screening in adults: American
College Of Preventive Medicine position statement on preventive practice. Am J Prev Med 2011; 40
(3): 381 e1–10.

24. LeFevre ML, Force USPST. Screening for abdominal aortic aneurysm: US Preventive services task force
recommendation statement. Ann Intern Med 2014; 161 (4): 281–90.
25. Gerhard-Herman MD, Gornik HL, Barrett C, et al. 2016 AHA/ACC Guideline on the Management of
Patients With Lower Extremity Peripheral Artery Disease: Executive Summary: A Report of the
American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines.
Circulation 2017; 135 (12): e686–e725.
26. Linne A, Forsberg J, Leander K, et al. Screening of siblings to patients with abdominal aortic aneurysms
in Sweden. Scand Cardiovasc J 2017; 51 (3): 167–71.
27. Thompson SG, Ashton HA, Gao L, et al. Final follow-up of the Multicentre Aneurysm Screening Study
(MASS) randomized trial of abdominal aortic aneurysm screening. Br J Surg 2012; 99 (12): 1649–56.
28. Duncan JL, Harrild KA, Iversen L, et al. Long term outcomes in men screened for abdominal aortic
aneurysm: prospective cohort study. BMJ 2012; 344: e2958.
29. Earnshaw JJ, Shaw E, Whyman MR, et al. Screening for abdominal aortic aneurysms in men. BMJ 2004;
328 (7448): 1122–24.
30. Spronk S, van Kempen BJ, Boll AP, et al. Cost-effectiveness of screening for abdominal aortic aneurysm
in the Netherlands and Norway. Br J Surg 2011; 98 (11): 1546–55.
31. Bhak RH, Wininger M, Johnson GR, et al. Factors Associated With Small Abdominal Aortic Aneurysm
Expansion Rate. JAMA Surg 2015; 150 (1):44–50.
32. Kent KC, Zwolak RM, Egorova NN, et al. Analysis of risk factors for abdominal aortic aneurysm in a
cohort of more than 3 million individuals. J Vasc Surg 2010; 52 (3): 539–48.
195
EVAR does not have worse
outcomes in women
C Mascoli, C Lomazzi, E Gallitto, R Pini, C Fenelli,
M Goretti, GL Faggioli, A Stella, S Trimarchi
and M Gargiulo
Introduction
Abdominal aortic aneurysms are less common in women than in men, with a 1:4
of predominance, respectively.1 Despite the fact that they are less affected, women
are historically have a worse prognosis.2 Females often present with abdominal
aortic aneurysms at older ages, with underdiagnosed/undertreated comorbidities,
have more challenging anatomy and experience rupture at smaller aneurysm size
than men.3,4 For all these reasons, women are known to have a higher rate of
postoperative complications and mortality following open repair.5 It is less clear
whether this remains true also for female patients undergoing endovascular
aneurysm repair (EVAR).
Over the past two decades, EVAR has been shown to decrease short- and mid-
term morbidity/mortality associated with aneurysm repair. Large randomised
controlled trials—EVAR 1, DREAM ((Dutch randomized endovascular aneurysm
management trial) trial and OVER (Open surgery vs. endovascular repair trial)—
compared EVAR with open repair and showed significantly lower 30-day mortality
(0.5–1.7%) and similar long-term survival.6–8
This benefit has not been equally distributed between genders. Women seem
to not benefit as much as men from the improved outcomes associated with this
less invasive technology. Nevertheless, the small percentage (0.6–9%) of women
in these randomised trials has not permitted adequate gender outcome analysis.4,9
Several theories have been proposed to explain the outcome differences between
men and women, but the cause of this gender disparity following EVAR remains
elusive and no consensus has been reached.
Literature results
A recent systematic review and meta-analysis, by Ulug and colleagues, including
nine studies (52,018 men, 11,076 women) published between 2005 and 2016,
reported that 30-day mortality is higher in women for both elective EVAR (2.3%
vs. 1.4%) and open repair (5.4% vs. 2.8%).10–19 Deery and colleagues, in an analysis
of data from the American College of Surgeons National Surgical Improvement
Program (2011–2014), demonstrated that women undergoing elective repair were
older, had smaller aneurysms, and had a higher 30-day mortality rate after open
repair (8% vs. 4%) and EVAR (3.2% vs. 1.2%) in comparison with men.20 Sidloff
et al analysed data from the UK National Vascular Registry (NVR) for patients
197
undergoing abdominal aortic aneurysm repair between 2010 and 2014 (23,245
• C Mascoli, C Lomazzi, E Gallitto, R Pini, C Fenelli, M Goretti, GL Faggioli, A Stella, S Trimarchi et al
patients, 13% women) and reported an in-hospital mortality rate of 6.9% vs. 4%
(p=0.014) for elective open repair, and of 1.8% vs. 0.7% (p < 0.001) for elective
EVAR in women and men, respectively.21
According to the aforementioned studies, women seem to have worse outcomes
than men when undergoing elective EVAR. All these studies showed that, compared
with open repair, EVAR is associated with considerably lower operative mortality
in both men and women. Ulug and colleagues reported that, even though the odds
ratio for women vs. men has changed little over the years, overall mortality has
decreased since the 2010, especially following EVAR, while the mortality following
open repair in women appears to remain unacceptably high.10 Moreover, there was
a varying amount of heterogeneity in the literature and there are many factors
that might confound the comparison of men and women, such as age, aneurysm
diameter and comorbidities, that were usually inconsistently reported.
Operative mortality is known to increase with age, and women appear to develop
clinically relevant aneurysms at an older age than men, and the prevalence of
this pathology increases rapidly with age, especially in women.22–24 Clinical and
demographic factors might have weight in reducing survival after EVAR and
these data are often under reported in large multicentre studies or meta-analyses.
Gloviczki et al, in a retrospective study on 934 patients (13% women) who
underwent EVAR for infrarenal abdominal aortic aneurysm between 1997 and
2011 at the Mayo Clinic (USA), stratified patients into low/normal-risk or high-
risk categories and analysed the association between surgical risk, female gender,
age, and outcome in asymptomatic patients.25 In this study, in asymptomatic
patients, both in-hospital and 30-day mortality rates were higher in high-risk than
in low/normal-risk patients, while 30-day mortality rates were similar in women
and men (2.8% vs. 0.8%; p 0.09). The authors showed that early and late survival
decreased with advanced age after EVAR, while gender did not significantly affect
30-day and five-year mortality. Similarly, Chang et al also found that advanced age
was an independent predictor of all-cause mortality while female gender did not
affect long-term reinterventions or survival.26
As the majority of studies reported in literature, Gloviczki et al showed an increased
rate of complication and reintervention in female gender, mostly due to lower
EVAR does not have worse outcomes in women
limb ischaemia caused by arterial thrombosis.25 These results refer to procedures

performed between 1997 and 2011, with several generations of endografts.
Aneurysm morphology has been shown to differ between the sexes in several small
cohort studies. At any age, men have larger diameter aortas than women and the
common femoral artery is smaller in women.29,30 Sweet and colleagues reported
that women are more likely to have aortoiliac morphology less suitable for EVAR
due to shorter, more angulated infrarenal necks and small iliac arteries, making
EVAR more challenging.31 The authors reported that only about 70% of men and
40% of women fit the indications for use of current EVAR devices. Old generation
endografts had lower conformability and a higher profile than the new generation
ones, and this could be a plausible explanation for the major complications and
reinterventions in the female sex.
At present, no endografts have been designed specifically for women. The
anatomic challenges of female aortic anatomy are only now beginning to be
addressed by the medical device industry, and preliminary data suggest that the
198
progress in endovascular technology might be the way to increase the proportion of

women suitable for endovascular repair and might reduce the rate of complications
and reinterventions in female gender.10,31,32 Data reported by the current literature
refer to several generations of endografts and several experiences for EVAR, the
poorer short-term outcomes might be the result of technical reasons and are not
representative of new generation endografts.
Results of new-generation devices, which are associated with an increase in
endovascular skills, seem to be encouraging.
Data from GREAT

GREAT (Global registry of endovascular aortic treatment) is a global prospective
observational study that enrolled 5,000 patients treated with a Gore thoracic and
abdominal endograft, from August 2010 to September 2016. We evaluate gender
differences in intra and perioperative outcome after EVAR in elective and acute

aneurysms with a currently commercially available abdominal endograft using
data from the registry. All patients underwent EVAR with Excluder endograft
(Gore) for elective and acute abdominal aortic aneurysms, enrolled in GREAT,
were retrospectively analysed. Preoperative, procedural and perioperative data were
evaluated. Technical success, intraoperative and 30-day mortality, hospital stay,
perioperative procedure-related adverse events and procedure-unrelated serious
adverse events were evaluated. The X2, Fisher’s, and non-parametric tests were used
for bivariate analysis. We identified 3,309 patients (male: 2819 [85%], female: 490
[15%]) who underwent EVAR for elective (3189, male: 85%, female: 15%) and
acute (120, male: 81%, female: 19%) aneurysms. Females were significantly older
(female: 76±9 vs. male: 73±8; p=0.0001) and had lower body surface area (female:
1.75±0.24m2 vs. male: 2.01±0.21m2; p=0.0001). Females had a lower incidence of
coronary artery disease (female: 30% vs. male: 42%, p: 0.0001), but were more
affected by chronic obstructive pulmonary disease (female: 33% vs. male: 23%; p=
0.0001), peripheral arterial disease (female: 25% vs. male: 18%; p=0.0001) and
degenerative connective tissue disease (female: 3.5% vs. male: 1.3%; p=0.003).
Moreover, females had smaller aneurysms (female: 56±12mm vs. male: 58±12mm;
p=0.0001), more severe infra-renal neck angle (female: 37 degree ±25 degree vs.
male: 30 degree ±21 degree; p=0.0001), lower proximal landing zone diameter
(female: 20±4mm vs. male: 22±3mm; p=0.0001) and lower distal landing zone
diameter (female: 10±3mm vs. male: 12±4mm, p;0.0001). The oversizing at the
distal landing zone was significantly higher in females (female: 16% vs. male: 5%;
p=0.0001). There were no differences in technical success (female: 99.8% vs. male:
99.6%; p=0.70), intraoperative (female: 0.2% vs. male: 0%; p=0.14) and 30-day
mortality (female: 1.2% vs. male: 0.6%; p=0.14). Females had longer hospital stay
(female: 9±8 days vs. male: 7±5 days; p=0.01), higher rate of 30-day procedure/
devices unrelated serious adverse event (female: 8.8% vs. male: 6.2%; p=0.04) but
no significant differences in 30-day procedure/devices related serious adverse events
(female: 6.3% vs. male: 4.9%; p=0.22) and 30-day reinterventions (female: 3.1%
vs. male: 2.1%; p=0.18).
In conclusion, according to our results, gender is not associated with worse
EVAR outcomes in terms of technical success, intraoperative and 30-day mortality,
30-day-procedure/devices-related serious adverse events and 30-day reinterventions.
Nevertheless, women have a greater risk of longer hospitalisation and a higher
199
incidence of perioperative EVAR devices/procedure unrelated adverse events. These
results suggest that EVAR, using this new-generation endograft, is safe and effective
in females. Nevertheless, higher attention is needed in the peri-operative period.
Bologna experience
Between 2012 and 2017, all consecutive patients who underwent standard EVAR
for elective aneurysms with currently available endografts were prospectively
collected and retrospectively analysed. Preoperative, procedural and perioperative
data were evaluated. Technical success, intraoperative and 30-day mortality,
hospital stay, perioperative medical and surgical complications were evaluated. The
X2, Fisher’s, and non-parametric tests were used for bivariate analysis. Overall,
489 patients were identified: 453 male (91%) and 45 (9%) female. Females were
significantly older (female: 78±6 vs. male: 74±7; p=0.001), but there were not
significant differences in comorbidities a part of chronic renal failure (40% vs. 22%
in males and females, respectively). There were no differences in abdominal aortic
aneurysm diameter between females and males (56±10 vs. 57±10; p=0.40) at the
time of operation.
There were no differences in terms of technical success (female: 96% vs.
male: 97%; p=0.64), intraoperative adjunctive manoeuvres (female: 33% vs.
male: 26%; p=0.57), intraoperative and 30-day mortality (female: 0% vs. male:
0%; p= not significant and female: 4% vs. male: 1%; p=0.07). There were no
differences in hospital stay (female: 4±3 days vs. male: 5±5 days; p=0.83), 30-day
medical (female: 9% vs. male: 7%; p=76) and surgical (female: 7% vs. male: 2%;
p=0.19) complications.
Conclusion
Women are subjected to intervention at a more advanced stage of the disease (older,
affected by greater comorbidities) and with larger abdominal aortic aneurysms in
proportion to their body mass surface. They often have more hostile anatomies,
characterised by small femoral and iliac arteries with a more advanced peripheral
atherosclerotic pathology and therefore, they are more affected by the size of the
devices. Experiences reported in literature refer to various generations of endografts

and the worst outcomes in female gender might be affected by that.
Experiences with newer generation endografts show better results in terms
of technical success and short-term mortality in women, probably due to the
improvement of procedures/device-related complications. Improvements in devices
such as low-profile size, improved deployment methods, and accuracy of devices
may explain the narrowed gap between men and women in regards to outcomes.
Increased awareness to gender differences along with technological improvement
with the development of design of endografts more suitable for women may
improve the approach and treatment strategies in women.
Larger samples studies referring to new generation endograft are needed for a
proper evaluation of this topic.
200
Summary
• EVAR has been shown to decrease short- and mid-term morbidity/mortality

associated with abdominal aortic aneurysm repair, but this benefit seems not
equally distributed between genders.
• The comparison between genders is affected by great heterogeneity in
the literature with many confounding factors. Age, aneurysm diameter and
comorbidities were usually inconsistently reported in the large multicentre
studies or meta-analyses.
• Data reported in the literature refer to older generation endografts that had
lower conformability and higher profile than the newer generation ones,
and this could be a plausible explanation of the major complications and
reinterventions in the female sex.

• Results of new-generation devices seem to be encouraging, with better results
in females in terms of technical success and 30-day mortality.
• Larger sample studies referring to newer generation endografts are needed for
a proper evaluation of this topic.
References
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2008; 5: 36–43.
2. Norman PE, Powell JT. Abdominal aortic aneurysm: the prognosis in women is worse than in men.
Circulation 2007; 115: 2865–69.
3. Miller M, Byington R, Hunninghake D, et al. Sex bias and underutilization of lipid-lowering therapy in
patients with coronary artery disease at academic medical centers in the United States and Canada.
prospective randomized evaluation of the vascular effects of Norvasc trial (PREVENT) investigators.
Arch Intern Med 2000; 160: 343–47.
4. McPhee JT, Hill JS, Eslami MH. The impact of gender on presentation, therapy, and mortality of
abdominal aortic aneurysm in the United States, 2001-2004. J Vasc Surg 2007; 45: 891–99.
5. Huber TS, Wang JG, Derrow AE, et al. Experience in the United States with intact abdominal aortic
aneurysm repair. J Vasc Surg 2001; 33: 304–10.
randomized controlled trial. Lancet 2004; 364: 843–48.
8. Lederle FA, Freischlag JA, Kyriakides TC, et al. Outcomes following endovascular vs open repair of
abdominal aortic aneurysm: a randomized trial. JAMA 2009; 302: 1535–42.
9. Dillavou ED, Muluk SC, Makaroun MS. A decade of change in abdominal aortic aneurysm repair in the
United States: have we improved outcomes equally between men and women? J Vasc Surg 2006; 43:
230–38.
10. Ulug, P, Sweeting, MJ, von Allmen, RS, and SWAN collaborators. Morphological suitability for
endovascular repair, non-intervention rates, and operative mortality in women and men assessed for
intact abdominal aortic aneurysm repair: systematic reviews with meta-analysis. Lancet 2017; 389:
2482–91.
11. Lowry D, Singh J, Mytton J, Tiwari A. Sex-related outcome inequalities in endovascular aneurysm
repair. Eur J Vasc Endovasc Surg 2016; 52: 518–25.
12. Nevidomskyte D, Shalhub S, Singh N, et al. Influence of gender on abdominal aortic aneurysm repair
in the community. Ann Vasc Surg 2016; published online Aug 26. DOI:10.1016/j.avsg.2016.06.012.
13. Chung C, Tadros R, Torres M, et al. Evolution of gender-related differences in outcomes from two
decades of endovascular aneurysm repair. J Vasc Surg 2015; 61: 843–52.
201
14. Lo RC, Bensley RP, Hamdan AD, et al. Gender differences in abdominal aortic aneurysm presentation,
repair, and mortality in the Vascular Study Group of New England. J Vasc Surg 2013; 57: 1261–68.
15. Mani K, Bjorck M, Wanhainen A. Changes in the management of infrarenal abdominal aortic aneurysm
disease in Sweden. Br J Surg 2013; 100: 638–44.
16. Mehta M, Byrne WJ, Robinson H, et al. Women derive less benefit from elective endovascular aneurysm
repair than men. J Vasc Surg 2012; 55: 906–13.
17. Powell J, Sweeting MJ, Ulug P, et al. Meta-analysis of individual-patient data from EVAR-1, DREAM,
aneurysm over 5 years. Br J Surg 2017; 104: 166–78.
18. Schermerhorn ML, Bensley RP, Giles KA, et al. Changes in abdominal aortic aneurysm rupture and
short-term mortality, 1995–2008: a retrospective observational study. Ann Surg 2012; 256: 651–58.
19. Ramanan B, Gupta PK, Sundaram A, et al. Development of a risk index for prediction of mortality after
open aortic aneurysm repair. J Vasc Surg 2013; 58: 871–78.
20. Deery SE, Soden PA, Zettervall SL, et al. Sex differences in mortality and morbidity following repair of
intact abdominal aortic aneurysms. J Vasc Surg 2017; 65:1006–13.
21. Sidloff DA, Saratzis A, Sweeting MJ, et al. Sex differences in mortality after abdominal aortic aneurysm
repair in the UK. Br J Surg 2017; 104 (12): 1656–64.
22. Grant SW, Sperrin M, Carlson E, et al. Calculating when elective abdominal aortic aneurysm repair
improves survival for individual patients: development of the Aneurysm Repair Decision Aid and
economic evaluation. Health Technol Assess 2015; 19: 1–154.
23. George J, Rapsomaniki E, Pujades-Rodriguez M, et al. How does cardiovascular disease first present
in women and men? Incidence of 12 cardiovascular diseases in a contemporary cohort of 1,937,360
people. Circulation 2015; 132: 1320–28.
24. Ulug P, Powell JT, Sweeting MJ, et al. Meta-analysis of the current prevalence of screen-detected
abdominal aortic aneurysm in women. Br J Surg 2016; 103: 1097–104.
25. Gloviczki P, Huang Y, Oderich GS, et al. Clinical presentation, comorbidities, and age but not female
gender predict survival after endovascular repair of abdominal aortic aneurysm. J Vasc Surg 2015; 61
(4): 853–61.
26. Chang RW, Goodney P, Tucker LY, et al. Ten-year results of endovascular abdominal aortic aneurysm
repair from a large multicenter registry. J Vasc Surg 2013; 58: 324–32.
27. Egorova NN, Vouyouka AG, McKinsey JF, et al. Effect of gender on long-term survival after abdominal
aortic aneurysm repair based on results from the Medicare national database. J Vasc Surg 2011; 54:
1–12.
28. Grootenboer N, Hunink MG, Hendriks JM, et al. Sex differences in 30-day and 50-year survival after
endovascular repair of abdominal aortic aneurysms in the EUROSTAR study. J Vasc Surg 2013; 58:
42–49
29. Sonesson B, Hansen F, Stale H, Lanne T. Compliance and diameter in the human abdominal aorta: the
influence of sex and age. Eur J Vasc Surg 1993; 7: 690–97.
30. Sandgren T, Sonesson B, Ahlgren AR, Lanne T. The diameter of the common femoral artery in healthy
human: influence of sex, age and body size. J Vasc Surg 1999; 29: 503–10.
31. Sweet MP, Fillinger MF, Morrison TM, et al. The influence of gender and aortic aneurysm size on
eligibility for endovascular abdominal aneurysm repair. J Vasc Surg 2011; 54: 931–37.
32. Metha M, Valdes FE, Nolte T, et al. One-year outcomes from an international study of the Ovation
Abdominal Stent Graft System for the endovascular aneurysm repair. J Vasc Surg 2014; 59: 65–73.
202
Internal iliac artery preservation controversies
Establishing evidence for
endovascular aneurysm
repair of the iliac axis:
Data from pELVIS
Introduction
Up to 30% of all abdominal aortic aneurysms extend to the iliac arteries. When
treating an aneurysm, iliac artery aneurysms are usually addressed at the same time.
Nowadays, there are multiple options to treat iliac artery aneurysms. These include
open surgical repair, embolisation and covering of the internal iliac artery, the
bell-bottom technique, the sandwich technique as well as hybrid procedures and
implantation of iliac side branched grafts.
Despite the fact that these endografts have been available for years, there is
currently no sound evidence on their results. This is a chapter on a multicentre,
international registry on the pELVIS (Performance of iliac branched devices for
aneurysms involving the iliac bifurcation) registry.
Indication for treatment of iliac artery aneurysms

Most authors agree on a maximum iliac diameter of >3.5cm for treatment
of isolated iliac artery aneurysms.1 However, most iliac artery aneurysms are
treated in a concomitant fashion when treating aortoiliac aneurysms.2 Moreover,
dilatative degeneration of the iliac arteries secondary to endovascular aneurysm
repair (EVAR)—ultimately leading to a type Ib endoleak—is a common cause for
secondary interventions after EVAR.3
Covering the internal iliac artery in EVAR

Until a few years ago, it was common practice in these cases to extend the coverage
of the common iliac artery into the healthier external iliac artery, thus covering the
internal iliac artery. Additionally, the internal iliac artery was embolised with coils
or plugs to reduce the risk of type II endoleak.
In a review from 2008, Rayt and colleagues reported an incidence of 28% for
buttock claudication when embolising the internal iliac artery prior to EVAR.4 Up
to 16% of the patients had persisting buttock claudication after one year.
Besides erectile dysfunction and lumbar plexopathy, bowel ischaemia can also be
a result of internal iliac occlusion. In 2014, Jean Baptiste and colleagues reported
fatal bowel ischaemia in 2.8% of the patients with an excluded internal iliac artery.5
To avoid these serious complications when treating iliac artery aneurysms by
endovascular means, iliac branched devices were introduced.
205
EVAR preserving the internal iliac artery
Exclusion of the internal iliac artery, for example, by embolising and covering it
with a stent graft is not considered a first-choice treatment option especially in
bilateral disease. This is not only because of the complications associated with this
technique but also because preserving internal iliac blood flow reducing the risk
of spinal cord ischaemia in patients with thoracoabdominal aneurysms—in whom
the internal iliac artery is the main feeder of the lumbar artery collateral network.
Initial results were published by Greenberg and others, reporting on branched
devices for the thoracoabdominal aorta and common iliac artery.6 Greenberg was
one of the pioneers of this technology. In the following years, more reports added to
Establishing evidence for endovascular aneurysm repair of the iliac axis: Data from pELVIS •
the evidence base. Verzini et al compared the use of iliac branch devices to occlusion
and coverage of the internal iliac artery, showing that this technique was connected
to a lower rate of endoleaks and pelvic ischaemic symptoms.7 However, despite this
technology having been in use for a decade, there is still a lack of evidence. Firstly,
the number of patients included in studies is limited. Only recently, results from a
multicentre prospective study on the Excluder iliac branch endoprosthesis (Gore)
were published, evaluating the results in 63 patients.8 Secondly, there is a great
variety of entities treated, with combinations of iliac branch devices and bridging
stents.
The pELVIS registry

To overcome this, nine experienced vascular centres from three European countries
are pooling data in a registry to evaluate long-term results of iliac branch devices.
Since the beginning of enrolment in January 2005, 752 patients have been
included in this registry. A total of 632 aortoiliac and 212 common iliac artery
aneurysms were excluded, implanting 802 Zenith iliac branch devices (Cook
Medical) and 52 Excluder iliac branch endoprotheses (Gore). In 102 cases, patients
were treated bilaterally.
The mean patient age was 71.4 years (range 45–93). Most patients were male
(811, 94.9%). Comorbidities corresponded well to the incidences reported in the
literature, with a high proportion of tobacco use (83%), arterial hypertension
(86.1%), cardiac insufficiency (43%), chronic obstructive pulmonary disease (32%)
and hyperlipidaemia (55%).
Aneurysm diameters were 41.21±18.1mm in the abdominal aorta, and
33.13±12.78mm and 31.12±12.94mm in the right and left common iliac artery,
respectively. Right and left internal artery diameters were 14.87±10.02mm and
16.89±14.01mm, respectively.
As noted above, 802 Zenith iliac branch devices and 52 Excluder iliac branch
endoprostheses were implanted. As bridging stents, balloon-expandable covered
stents were used in 72% of the cases, with the majority being Advanta/iCast
V12 (Maquet) (67% of all cases). In 28% of the cases self-expandable covered
stents were used, with Fluency accounting for 20% of the cases. In 237 cases,
either balloon-expandable or self-expandable stents were relined with bare metal
stents. The group will soon publish results with bridging stents, discriminating
between balloon-expandable, self-expandable and relined bridging stents. The main
endpoints will be primary patency and secondary interventions.
In a recent study, the pELVIS registry collaborators published results of secondary
interventions following EVAR of aortioiliac and common iliac artery aneurysms.9
206
In this study, the authors presented data on 575 patients, reporting a 30-day
reintervention rate of 1.6% and overall reintervention rate of 8.9% in a follow-up
period of about 30 months. Early secondary procedures comprised treatment of
three type I endoleaks by proximal extension.
Typical late complications were related to occluded common/external segment
(30, 4.6%) and internal segment of the iliac device (i.e. the bridging stent graft,
11, 1.6%).
This issue will be addressed in the aforementioned evaluation of bridging stent
grafts as well as in another study on the influence of presence of internal iliac artery
aneurysms and, at the time of writing, soon to be published. The authors will
demonstrate how concomitant internal iliac artery aneurysms worsen the outcomes
of aortoiliac/common iliac artery aneurysms.
In the future, the pELVIS registry will provide long-term data for clinical success
with exclusion of the iliac aneurysm with freedom from type I/III endoleaks and
occlusion of device branches. Secondary endpoints will be technical success,
freedom from reinterventions, freedom from new-onset buttock claudication and/
or colon ischaemia, overall mortality, aneurysm-related mortality, freedom from
iliac aneurysm enlargement as well as fracture or migration of the iliac branch
device or bridging stent.
Conclusion
Although it has been possible to treat iliac aneurysms using branched endograft
technology for more than a decade, we are still at the beginning of generating
the evidence needed. With the pELVIS registry, the investigators will attempt to
answer the main questions related to EVAR of iliac artery aneurysms, including
durability, complications and which devices to use.
207
Summary
• Iliac artery aneurysms are often treated during aortic EVAR.

• Coverage of the internal iliac artery can have deleterious consequences,
especially when performed bilaterally.
• Iliac branch devices aiming at preserving the blood flow to the pelvis have
been available for more than a decade, but evidence on the use of these
devices is still scarce.
• The pELVIS registry has been designed to shed light on long-term durability
of iliac EVAR by the means of externally controlled, retrospective analysis of
prospectively collected data.
• Secondary intervention rates after iliac EVAR are low, with also low rates of
branch occlusions and new-onset buttock claudication.
• Studies on bridging devices, internal iliac artery involvement and others
aspects will soon follow.
References
1. Huang Y, Gloviczki P, Duncan AA, et al. Common iliac artery aneurysm: expansion rate and results of
open surgical and endovascular repair. J Vasc Surg 2008; 47: 1203–10;
2. Farahmand P, Becquemin JP, Desgranges P, et al. Is hypogastric artery embolization during endovascular
aortoiliac aneurysm repair (EVAR) innocuous and useful? Eur J Vasc Endovasc Surg 2008; 35: 429–35.
3. Patel R, Powell JT, Sweeting MJ, et al. The UK EndoVascular Aneurysm Repair (EVAR) randomised
controlled trials: long-term follow-up and cost-effectiveness analysis. Health Technol Assess 2018; 22
(5): 1–132.Rayt HS, Bown MJ, Lambert KV, et al. Buttock claudication and erectile dysfunction after
internal iliac artery embolization in patients prior to endovascular aortic aneurysm repair. Cardiovasc
Intervent Radiol 2008; 31: 728–34.
4. Jean-Baptiste E, Brizzi S, Bartoli MA, et al. Pelvic ischemia and quality of life scores after interventional
occlusion of the hypogastric artery in patients undergoing endovascular aortic aneurysm repair.
J Vasc Surg 2014; 60: 40–9.
5. Greenberg RK, West K, Pfaff K, et al. Beyond the aortic bifurcation: branched endovascular grafts for
thoracoabdominal and aortoiliac aneurysms. J Vasc Surg 2006; 43: 879–86.
6. Verzini F, Parlani G, Romano L, et al. Endovascular treatment of iliac aneurysm: Concurrent comparison
of side branch endograft versus hypogastric exclusion. J Vasc Surg 2009; 49: 1154–61.
7. Schneider DB, Matsumura JS, Lee JT, et al. Prospective, multicenter study of endovascular repair of
aortoiliac and iliac aneurysms using the Gore Iliac Branch Endoprosthesis. J Vasc Surg 2017; 3: 775–85.
8. Donas KP, Inchingolo M, Cao P, et al. Secondary procedures following iliac branch device treatment of
aneurysms involving the iliac bifurcation: The pELVIS Registry. J Endovasc Ther 2017; 24 (3): 405–10.
208
Parallel graft use for internal
iliac artery preservation
C Blanco, G Mestres, X Yugueros and V Riambau
Introduction
Iliac artery aneurysms are associated with an almost 20–30% incidence of abdominal
aortic aneurysms.1–3 Isolated iliac artery aneurysms are uncommon, situated in
70% of cases in the common iliac artery, 20% in the internal iliac artery and 10%
in the external iliac artery.4
Endovascular repair has emerged as a successful treatment of thoracic and
abdominal aortic aneurysms. Nevertheless, the management of aortoiliac aneurysms
remains challenging. The classical treatment of the expansion of aneurysmal disease
into the iliac bifurcation has been to extend the distal sealing to the external
iliac artery with previous embolisation of the internal iliac artery to avoid type
II endoleaks. This procedure requires some anatomical criteria of an external
iliac artery with at least 15mm length of distal straight sealing. Nonetheless, it
is beneficial to preserve at least one internal iliac artery to avoid complications:
buttock claudication (1.6%-56%), colon ischaemia (9%)or erectile dysfunction
(33%, with a 15% persistent symptoms);other rare, but devastating, complications
are spinal cord ischaemia, buttock necrosis or sciatic nerve ischaemia.5–10 Internal
iliac artery preservation is especially significant in young, physically and sexually
active patients, in the presence of contralateral severe hypogastric stenosis or
occlusion, or in cases of impaired collateral circulation from the inferior mesenteric
artery or femoral arteries.11
This chapter provides an updated overview of the different internal iliac artery
preservation techniques, such as bell-bottom, stent grafts or iliac-branched devices,
with special emphasis on the parallel graft technique—also known as the sandwich.
Bell-bottom technique
The so-called bell-bottom technique uses a flared iliac limb stent graft with a large
distal diameter to seal in a wide distal common iliac artery, preserving the patency
of the iliac bifurcation (Figure 1A). Karch et al first reported the use of aortic
extension cuffs implanted into the distal portion of the iliac limb for treatment
of ectatic common iliac arteries with an iliac diameter between 14 and 18mm.12
Excellent mid-term outcomes, in terms of freedom from aneurysmal rupture,
aneurysm-related deaths, and secondary interventions have been reported, but it
has been advocated to be used used only for iliac diameters up to 25mm.13
The advantages of this technique include its high technical success rates (97%),
and good mid-term results with low rates of type Ib endoleaks (2–4%).14,15
Furthermore, as iliac limbs with large diameters are off-the-shelf, the technique
is facile to perform even in emergency settings and it does not augment the
invasiveness of the procedure.
209
Among its disadvantages, we can consider its limitations to treat up to a certain
• C Blanco, G Mestres, X Yugueros and V Riambau
diameter (Medtronic’s Endurant endograft providing iliac limbs and extensions up

to 28mm wide and Cook Medical’s Zenith stent graft employed up to 24mm),
to require at least a 2cm distal landing zone, and to take into consideration the
concerns of long-term durability and renterventions due to further dilatations of
the aneurysmal iliac arteries, stent migrations and type Ib endoleaks.15,17 Mainly
for these reasons, most groups only recommend this technique in older patients,
with shorter life expectancies and with common iliac arteries smaller than 25mm.15
Iliac branch device

Currently, there are three off-the-shelf devices available for this technique: the
Zenith iliac branch endoprosthesis, the Excluder iliac branch endoprosthesis
(Gore) and the E-Iliac stent graft system (Jotec). In spite of the impediments to
this procedure—including higher cost, longer time and increased complexity of
the technique, as well as anatomical requirements and the reduced availability
in emergencies—it is nevertheless deemed the prevailing internal iliac artery
preservation procedure (Figure 1B).
Parallel graft use for internal iliac artery preservation
The Zenith device series are related to an early technical success of 85–100%,
12% of limb occlusions, 50% of them with buttock claudication and 1.6% for
type I and III endoleaks, with internal iliac artery patency rates ranges within
87-98%.18 The Excluder device six months’ results show a comprehensive technical
success rate of 95.2%, 100% external iliac artery patency and 95% for the internal
iliac artery, with no buttock claudication or sexual dysfunction reported.16,19 The
E-iliac stent graft system reported excellent mid-term outcomes in a multicentre
retrospective study with 70 patients. Technical success attained 100%.20 During
A B C
Figure 1: (A) Treatment of an aortoiliac aneurysm with the bell-bottom technique with an Endurant endograft right
iliac limb and an extension of 28mm wide to preserve the internal iliac artery blood flow and a contralateral iliac limb
sealing in the common iliac artery. (B) Treatment of an aortic aneurysm with both aneurysmatic common iliac artery,
with an iliac branch device to preserve right internal iliac artery potency and left internal iliac artery embolisation and
extension into the left external iliac artery. (C) Treatment of a left stent graft limb type Ib endoleak with a femoro-
femoral bypass and a covered stent from the external to the internal iliac artery.
210
a median follow-up period of 12 months, the rates of survival (98.5%), freedom

from occlusion (92.0%), and freedom from endoleaks (87.0%) were comparable to
those of studies of other iliac branch devices.21
Other endovascular procedures to preserve the hypogastric patency are the
deployment of an abdominal bifurcated body into the common iliac artery and the
banana technique, which comprises a retrograde revascularisation with a covered
stent from the external into the internal iliac artery coupled with an aortomonoiliac
stent graft (Figure 1C).
Parallel stent (sandwich) technique

The parallel stent technique, also known as the sandwich, double-barrel or
hypogastric chimney technique, was first described by Lobato in 2008.22 However,
several modifications have now been described. It is a parallel stent technique,
designed to preserve both external and internal iliac arteries during the treatment
of aortoiliac or isolated common iliac artery aneurysms without distal sealing necks

in the common iliac artery. It uses conventional stent grafts (not dedicated for
this purpose) and avoids anatomical limitations related to iliac branch devices.23, 24
Additionally, it represents a more economical solution.
The parallel stent technique is usually performed when other iliac branch devices
are contraindicated: short (<40mm length) and/or tortuous or dissected common
iliac arteries, narrow common iliac artery bifurcations (<16mm), small (<8mm
lumen diameters) and/or short internal iliac arteries (<10mm lengths), or occluded
or too large external iliac arteries.25
The classical sandwich technique could be summarised in the following steps:22
• The main body of the bifurcated (with long ipsilateral limb) stent graft is
inserted through an ipsilateral femoral approach and positioned such that the
distal end of the ipsilateral iliac limb or its extension is 1cm above the internal
iliac artery origin (Figure 2A)
• The ipsilateral internal iliac artery is catheterised through a left brachial access,
through the endograft limb, and an extra stiff guidewire with short floppy tip
(Figure 2B)
Figure 2: Sandwich technique steps: (A) Ipsilateral

iliac extension or limb is deployed 1cm over the iliac
bifurcation. (B) Internal iliac artery is cannulated
from the arm. (C) stent graft is positioned 1cm
inside internal iliac artery and 5–6cm inside the iliac
extension. (D) EIA stent graft is inserted from the groin
in parallel position with the internal iliac artery stent
graft and deployed first. (E) Finally, internal iliac artery
stent graft is deployed and ballooned simultaneously
with the EIA stent graft. (F) Contralateral limb
deployment is performed at the end.
211
Figure 3: (A) Treatment of an aortoiliac aneurysm, treated with a bifurcated Aorfix

endograft, with right contralateral iliac limb sealing in the common iliac artery, and left
ipsilateral limb inside the common iliac artery aneurysm. (B) An additional common iliac
artery extension (20mm) is deployed and via a subclavian approach, the internal iliac
artery is catheterised. (C–D) A 13x100 Viabahn is placed and deployed into the IIA and an
Aorfix iliac extension into the external iliac artery. (E) Good patency of the endograft and
sandwich, without endoleaks, is confirmed in CT angiography.
• Then, a covered, self-expanding stent, through the brachial access, is placed

2cm inside the internal iliac artery, overlapping within the ipsilateral iliac limb
by 6cm (Figure 2C). An iliac limb extension, through the ipsilateral femoral
access, is positioned; the external iliac artery limb extension is deployed first,
followed by the internal iliac artery covered stent (Figure 2D)
• External iliac artery limb extension and internal iliac artery covered stent are
simultaneously re-ballooned (Figure 2E)
• The procedure is completed by the contralateral iliac limb deployment (Figure
2F). For bilateral common iliac artery aneurysms extending to both internal
iliac arteries, steps A to D are repeated
In later descriptions, less internal iliac artery coverage (1cm) and less overlapping
within parallel stents (5cm) have been applied, and a huge variety of endografts
and internal iliac artery covered stents have been used with this technique.23–25
The latest published modification of this technique, recommended the use of
Aorfix endografts (Lombard Medical) with internal iliac artery Viabahn stents
(Gore), and optional reinforcement with bare metal stents inside the Viabahn
ones.26 Compared to the classical technique, the authors advocated a standard
20mm limb landing within the common iliac artery aneurysm, anticipating at least
3cm parallel stents’ overlapping length (half of that initially recommended). As in
the first time, a clear recommendation regarding oversizings was made: a custom-
made, reverse-loaded, contralateral Aorfix limb, 20mm proximal diameter (12mm
distal diameter, 63mm length), was employed as an iliac extender. It means that
inside the 20mm common iliac artery limb, a 20mm external iliac artery limb and
6-8mm internal iliac artery stent are positioned (Figure 3).
212
Published results

Small series with short follow-ups have been published up until now using the
sandwich technique. Lobato reported a cohort of 40 patients with a technical success
of 100%, and a 30-day internal iliac artery stent occlusion rate of 4.2% and 2.5%
for external iliac artery limb occlusions.25 After 12 months’ follow-up, aneurysmal
reduction was observed in 34.8% of the cases and 63% remained stable, with neither
type I, III endoleaks, nor no new internal or external iliac artery stent occlusions.
Other series have reported lower technical success rates and increased rates of early
type III endoleaks between parallel stent graft components: DeRubertis reported
a technical success rate of 88% in 22 patients, with 9% early type III endoleaks
between parallel stent graft components; early limb occlusion occurred in 9% and
the primary patency rates for external and internal iliac artery limbs at six months
were 95% and 88%, respectively.27 Another series of 21 patients treated with the
modified sandwich technique showed 100% technical success, with two type Ib and
one type III intraoperative endoleaks, auspiciously managed.25 After 17.2 months’
follow-up, two occlusions of internal iliac artery stents were reported, with neither

pelvic ischaemic symptoms nor other significant complications.
In spite of the potential advantages of the sandwich technique, and good published
results, there is a clear dearth of rational information on the needed oversizing
between components, and the devices used. Most published articles neither depict
the oversizing nor use external iliac arterty stents of the same diameter of common
iliac artery endograft limbs, with internal iliac artery nominal stents inside, but not
based on any evidence. The most commonly published devices are Aorfix endograts
with Viabahn stents, but a huge variety of devices have been used without any
evidence to buttress them.
Calculating the parallel stent graft oversize and deciding on

parallel stent graft combination: An in vitro study
Endeavoring to elucidate this issue, we performed an in vitro bench model of
common iliac artery aneurysms treated with the sandwich technique.28 Briefly, it
consisted of dissimilar silicon common iliac limbs (10, 12, 14, 16 and 18mm)
into which different external iliac limb devices (16mm Endurant; 12mm Aorfix;
11mm and 13mm Viabahn) and varying internal iliac stent grafts (8mm Advanta
[Atrium Medical]; and 8mm Viabahn) were deployed, simulating an iliac sandwich
procedure to preserve the hypogastric artery. These specific devices and diameters
were selected due to their being the most reported for iliac sandwich procedures.
For the proximal sandwich components, plastic models were selected instead of
standard iliac limbs devices to diminish metallic reverberations and artefacts on
posterior computed tomography (CT) scan evaluations. Those specific diameters
were selected to obtain different oversizings within external and internal iliac
parallel stents.
All those combinations were introduced in a 37-degree C saline bath and kissing
ballooned, simulating in vivo conditions. After that, a CT scan was performed and
axial CT slices were recorded and exported to an external measurement program
(OsiriX Imaging Software v3.8.1, 32 bit, Pixmeo) to analyse them. For every
model, gutter size, parallel stent compression and stent infolding were analysed for
two different observers in order to procure intra- and inter-observer concordance.
213
Figure 4: Comparing gaps, stents

compression and infolding between
different diameter oversizing groups and
with different internal iliac parallel stents
(Viabahn and V12).28
Furthermore, three different parallel stent oversizing methods were also analysed
comparing area oversizing. The most reported method is addition of external iliac
artery limb and internal iliac artery stent graft areas, divided by common iliac
artery device area, calculated as pi x (0.5xd)2. The perimeter oversizing method
uses a theoretical circle perimeter formula pi x diameter: addition of both internal
and external iliac artery perimeters divided by common iliac artery limb perimeter.
Finally, diameter oversizing is an easier and more direct sizing method, that only
uses addition of internal and external iliac artery nominal stent diameters, divided
by common iliac artery limb diameter.
We have seen a very high correlation between all three measuring methods
(diameter oversizing to perimeter oversizing and area oversizing correlation coefficient
0.998 and 0.997 respectively, p<0.001 for both; Spearman’s rho correlation). Thus,
diameter OS was used, as the easiest method to calculate oversizing.
Our results (Figure 4) showed excellent intra- and inter-observer agreements.
Increasing diameter oversizing (<30%, 30-55%, 55-75%, and >75%) led to better
apposition of both parallel stents, reducing gutter area (38.9, 12.2, 5.4, and 2.6
mm2, respectively, p<0.001). However, excessive oversizing increased parallel
stent compression rates (13.5%, 28.9%, 43.9%, and 55.1%, p<0.001), as well as
malpositioning with infolding (0%, 0%, 38%, and 60%, p<0.001).
Regarding material selection, our study did not reveal any noteworthy differences
(p>0.005 for all comparisons) between all analysed devices in terms of gutters,
stent compression or malposition, with the exception of a slight propensity towards
lower infolding (10% vs. 35%, p=0.127), with Viabahn compared with Advanta as
the internal iliac stent.
Therefore, according to our results, some suggestions could be performed in
order to ameliorate and aid in standardising iliac sandwich procedures. On the
214
one hand, a diameter oversizing around 30–55% (addition of internal and external

iliac artery stent diameters, divided by common iliac artery limb diameter), could
be employed to reduce gutters and risks of leaking. Higher oversizings should be
avoided due to higher rates of parallel stent compression and infolding. In fact,
analysing previous published studies, despite not reported, this is the prevailing
oversizing percentage.26
On the other hand, when planning the procedures, the use of simple nominal
stent diameters could be preferred as the easiest way to calculate parallel stent
oversizing, avoiding time-consuming calculations associated with area oversizing
and other methods. Finally, regarding material selection, no clear recommendations
could be obtained.
Conclusion
General consensus agrees that preservation of at least one internal iliac artery is
recommended, whenever feasible. Off-the-shelf iliac bifurcated endografts represent

the first endovascular choice to maintain internal iliac artery flow. Bell-bottom
iliac limbs are related to more mid- to long-term durability concerns. The banana
technique is a good alternative for selected cases with a combination of femoro-
femoral revascularisation. The parallel graft technique has been demonstrated as a
good alternative with acceptable mid-term results. In vitro studies demonstrate that
a 30–55% total oversizing, related to the iliac limb, avoids compression, infolding
and gutter issues. No significant differences in performance have been demonstrated
in vitro among different types of stent graft combinations.
Summary
• Preservation of at least one internal iliac artery is recommended, whenever

feasible.
• Parallel or sandwich technique is a good alternative when iliac branch devices
are not technically possible or available.
• Total internal and external iliac artery stent graft diameters should represent
a 30–55% oversizing related to the iliac limb in order to avoid compression,
infolding and gutter issues.
• zNo clear superiority is identified among different types of stent graft
combinations.
References
1. Sandhu RS, Pipinos II. Isolated iliac artery aneurysms. Semin Vasc Surg 2005; 18: 209–15.
2. Armon MP, Wenham PW, Whitaker SC, et al. Common iliac artery aneurysms in patients with abdominal
aortic aneurysms. Eur J Vasc Endovasc Surg 1998; 15: 255–57.
3. Henretta JP, Karch LA, Hodgson KJ, et al. Special iliac artery considerations during aneurysm
endografting. Am J Surg 1999; 178: 212–18.
4. Bacharach JM, Slovut DP. State of the art: management of iliac artery aneurysmal disease. Catheter
Cardiovasc Interv 2008; 71: 708–14.
5. Bekdache K, Dietzek AM, Cha A, Neychev V. Endovascular hypogastric artery preservation during
endovascular aneurysm repair: a review of current techniques and devices. Ann Vasc Surg 2015; 29:
367–76.
215
6. Bratby MJ, Munneke GM, Belli AM, et al. How safe is bilateral internal iliac artery embolization prior to
EVAR? Cardiovasc Intervent Radiol 2008; 31: 246–53.

7. Verzini F, Parlani G, Romano L, et al. Endovascular treatment of iliac aneurysm: concurrent comparison
of side branch endograft versus hypogastric exclusion. J Vasc Surg 2009; 49: 1154–61.
8. Rayt HS, Bown MJ, Lambert KV, et al. Buttock claudication and erectile dysfunction after internal iliac
artery embolization in patients prior to endovascular aortic aneurysm repair. Cardiovasc Intervent
Radiol 2008; 31: 728–34.
9. Eagleton MJ, Shah S, Petkosevek D, et al. Hypogastric and subclavian artery patency affects onset and
recovery of spinal cord ischemia associated with aortic endografting. J Vasc Surg 2014; 59: 89-94.
10. Oderich GS, Greenberg RK. Endovascular iliac branch devices for iliac aneurysms. Perspect Vasc Surg
Endovasc Ther 2011; 23: 166–72.
11. Geisbusch P, Attigah N, Hyhlik-Durr A, et al. Decision-making and techniques in hypogastric artery
revascularization. J Cardiovasc Surg (Torino) 2013; 54: 71–79.
12. Karch LA, Hodgson KJ, Mattos MA, et al. Management of ectatic, nonanerysmal iliac arteries during
endoluminal aortic aneurysm repair. J Vasc Surg 2001; 33: S33–38.
13. Buckley CJ, Buckley SD. Technical tips for endovascular repair of common iliac artery aneurysms.
Semin Vasc Surg 2008; 21: 31–34.
14. Naughton PA, Park MS, Kheirelseid EA, et al. A comparative study of the bell-bottom technique vs
hypogastric exclusion for the treatment of aneurysmal extension to the iliac bifurcation. J Vasc Surg
2012; 55: 956–62.
15. Torsello G, Schönefeld E, Osada N, et al. Endovascular treatment of common iliac artery aneurysms
using the bell-bottom technique: long-term results. J Endovasc Ther 2010; 17: 504–09.
16. Alvarez Marcos F, Garcia de la Torre A, Alonso Perez M, et al. Use of aortic extension cuffs for preserving
hypogastric blood flow in endovascular aneurysm repair with aneurysmal involvement of common
iliac arteries. Ann Vasc Surg. 2013; 27: 139–45.
17. McDonnell CO, Semmens JB, Allen YB, et al. Large iliac arteries: a high-risk group for endovascular
aortic aneurysm repair. J Endovasc Ther. 2007; 14: 625–29.
18. Karthikesalingam A, Hinchliffe RJ, Holt PJ, et al. Endovascular aneurysm repair with preservation of
the internal iliac artery using the iliac branch graft device. Eur J Vasc Endovasc Surg 2010; 39: 285–94.
19. Schönhofer S, Mansour R, Ghotbi R. Initial results of the management of aortoiliac aneurysms with
Gore Excluder Iliac Branched Endoprosthesis. J Cardiovasc Surg 2015; 56: 883–88.
20. Mylonas SN, Rumenapf G, Schelzig H, et al. A multicenter 12-month experience with a new iliac side-
branched device for revascularization of hypogastric arteries. J Vasc Surg 2016; 64: 1652—59.
21. Loth AG, Rouhani G, Gafoor SA, et al. Treatment of iliac artery bifurcation aneurysms with the second-
generation straight iliac bifurcated device. J Vasc Surg 2015; 62 :1168–75.
22. Lobato AC. Sandwich technique for aortoiliac aneurysms extending to the internal iliac artery or
isolated common/internal iliac artery aneurysms: a new endovascular approach to preserve pelvic
circulation. J Endovasc Ther 2011; 18: 106–11.
23. Ziegler P, Avgerinos ED, Umscheid T, et al. Branched iliac bifurcation: 6 years experience with
endovascular preservation of internal iliac artery flow. J Vasc Surg 2007; 46: 204–10.
24. Pearce BJ, Varu VN, Glocker R, et al. Anatomic suitability of aortoiliac aneurysms for next generation
branched systems. Ann VAsc Surg 2015; 29: 69–75.
25. Lobato AC, Camacho-Lobato L. The sandwich technique to treat complex aortoiliac or isolated iliac
aneurysms: results of midterm follow-up. J Vasc Surg 2013; 57: 26S-34S.
26. Lim CS, Naji Y, Hussain ST, et al. Modified sandwich-graft technique employing Aorfix and Viabahn
stent-grafts to preserve hypogastric flow in cases of complex aortoiliac and isolated common iliac
artery aneurysms Including the internal iliac artery ostium. Eur J Vasc Endovasc Surg 2016; 51: 364–70.
27. DeRubertis BG, Quinones-Baldrich WJ, Greenberg JI, et al. Results of a double-barrel technique with
commercially available devices for hypogastric preservation during aortoiliac endovascular abdominal
aortic aneurysm repair. J Vasc Surg 2012; 34: 892–99.
28. Yugueros X, Mestres G, Pasquadibisceglie S, et al. Parallel-stenting technique in a sandwich
configuration for hypogastric artery preservation during endovascular aneurysm eepair: An In Vitro
study. Ann Vasc Surg 2017; 44: 221–28.
216
Results and follow-up of EVAR
Device labelling is not always
in the patient’s interests
DST Chong and TM Mastracci
Introduction
With recent improvements in endovascular stent grafts for the treatment of aortic
aneurysms, there has been a definitive shift in the management of patients to the
use of endovascular techniques rather than open surgery. Endovascular procedures
are now considered the surgical modality of choice, and are used for patients who
are fit, as well as those who are older or have multiple comorbidities. The initial
experience with first- and second-generation devices for endovascular aneurysm
repair (EVAR) has exposed engineering flaws that have been addressed in later
iterations, based on preclinical tests and post-clinical experience. However, as new
devices have emerged, the clinical world has gained insight into the progressive
nature of aneurysm disease, and some of issues of durability have been attributed to
deteriorating aortic wall. There are anatomical indicators that predict device failure,
such as proximal aortic neck longer than 15mm, infrarenal aortic angulation ≥60
degrees, as well as adequate iliofemoral diameters ≤7mm without circumferential
calcification or severe tortuosity.
Necessarily, device manufacturers publish instructions for use (IFU) that
summarise the boundary conditions in which a specific device can be expected to
perform well. However, these technical guidelines do not address the pathological
deterioration of the aortic wall and the progression of the aortic disease; thus
cannot be misconstrued as clinical guidelines. It is thought that 66% of infrarenal
abdominal aortic aneurysms can be treated with endovascular devices that are
currently available commercially, with men (70%) being more likely than women
(40%) to meet anatomical criteria for endografting; therefore, between 39.3%
and 58.5% of infrarenal aneurysms are treated off-label.1–3 Complex aortic stent
grafts, such as branched and fenestrated devices, have been devised to improve the
durability of endovascular repair in hostile neck anatomy by extending the sealing
zone through a longer portion of aorta, mitigating time-dependent failure, but
their widespread use is limited by cost, experience and regulatory restrictions. This
may leave some clinicians tempted to treat infrarenal aneurysms using devices that
may seem acceptable based on IFU alone, despite the inevitable predictable failure
based on anatomical warning signs. Much has been made about the “off-label” use
of devices in the literature, but using the IFU as a clinical decision-making tool,
whether on- or off-label, does not guarantee long-term clinical success.
Off-label usage of such endovascular devices is unregulated but legal. Starnescalled
off-label usage an “ex post facto liability matter, not a regulatory matter” when
discussing the off-label usage in the context of physician-modified devices, although
his words are applicable too in the context of off-label usage of endovascular stents.4
The idea of liability is when a patient incurs an injury from the use of a medical
device, either due to defectively manufactured stents, defective design of the stents
219
or defectively marketed stents. Therefore, every person or entity that is involved
• DST Chong and TM Mastracci
in the “chain of distribution” can be potentially liable. In these circumstances,

off-label usage can have potential implications, and surgeons and their institutions
can be at risk of civil claims from patients when the device goes wrong. In the UK,
off-label usage is possible but clinicians are advised to inform the patient as part
of the consent process and the importance of documentation.5 This type of usage
happens every day in clinical practice both in Europe and in the USA.6
The aim of this chapter is to discuss the usage of endovascular stents for the treatment
of aneurysm and explore why the outcomes cannot be predicted based on IFU alone.
Device labelling is not always in the patient’s interests
EVAR and hostile anatomy

The implantation of an endovascular stent graft is very dependent on good
apposition of the device with the proximal aortic neck anatomy and distal iliac
anatomy, and this interaction is extremely important as it will determine the long-
term outcome of the device. This apposition is crucial as it excludes blood flow
into the sac and avoids pressurisation of the aneurysm sac. In the absence of this
apposition, endoleaks lead to sac pressurisation and failure of the device.
Initial studies have shown that EVAR could be used in the presence of hostile
neck anatomy outside of IFUs. Hostile neck morphology, in addition to neck
diameter and length, includes severe angulation (>60 degrees), barrel- or conical-
shaped neck, and thrombus lined or circumferentially calcified necks. Studies
looking at hostile anatomy classification for endovascular repair have found that
there is a degree of subjectivity to interpretation but all in all, it is well-known that
hostile aneurysm anatomy does predispose to increase overall mortality.7–9 Off-label
usage, itself, has been highlighted as an independent predictor of sac enlargement
post-EVAR (Figure 1).3
Operating out of IFU-defined anatomy

There has been a mixture of outcomes published, and the impact on mortality for
treatment “outside of IFU” is largely dependent on the stringency and length of
follow-up. Holt et al reported an overall mortality of 40% in a five-year period
with patients treated outside of IFU with no difference in sac expansion or
reinterventions.10 Abbruzesse found that with EVAR performed out of IFU, there
was an 11% increase in aneurysm-related mortality at five years when compared
with 0% with EVAR within IFU.2 Schanzer et al reported a significantly higher rate
of aneurysm sac enlargement in patients who underwent EVAR outside of IFU.3
On the contrary, Mahajan, Walker and Beckerman and colleagues all reported
no differences in all-cause mortality or aneurysm-related mortality in their EVAR
procedures when working to IFU or outside of IFU.11–13 Despite this, there was a
reported 7.7% rate of type I endoleaks, which is slightly higher than that reported
in control groups.13 The majority of these studies looked at a variety of commercially
available stent grafts.
More specifically, the Endurant stent graft system (Medtronic) was developed
in response to users to make stent graft application more relevant in terms of
unfavourable anatomy. Troisi et al looked at the long-term use of the stent comparing
IFU and off-label use.14 They found that there were no differences between the
groups in terms of survival, freedom from any device-related intervention, or
220
Figure 1: The image shows the aortic and iliac
arterial anatomy, which conforms to the IFU that
comes with each commercially available packaged
endovascular stent graft.3 CIA = common iliac
artery, EIA = external iliac artery; and Ca+ =
calcium

freedom from graft thrombosis. When comparing the estimated five-year freedom
from type I endoleak, it was significantly better in the IFU group than in the off-
label group. Further investigation found that female gender and coronary artery
disease were independent predictors, in the off-label group, of poorer survival
outcome. Therefore, they advocated closer monitoring of type I endoleaks, which
can potentially occur during endograft surveillance.
The heterogeneity in the literature might be explained by considering that the
use of stent grafts “on label” is not sufficient to guarantee good long-term clinical
outcomes because the IFU does not take into consideration the physiological
differences that may predispose patients to more rapid progression of disease, and
hence early failure. Although it is important to know the conditions under which
devices are tested, and the conditions in which they perform well technically,
clinicians cannot rely on the IFU for clinical decision-making because the issues
playing the largest role in long-term outcomes likely have more to do with the
patient than the device.
Hostile neck diameter

Studies looking at aortic neck diameters <15mm report higher rates of type Ia
endoleaks of 11–16%.15,16 These figures are significantly higher than the 6.9%
quoted in the control groups.17
221
Hostile iliac anatomy, thrombus load and calcification

There are minimal current published data that look on the long-term outcomes
of hostile iliac anatomy. A thrombus-laden aorta has been shown to be an
independent risk factor that is associated with an increased 30-day mortality.18
Bastos-Gonçalves et al looked at the effect of neck thrombus on outcomes and
found no significant differences in outcome with or without thrombus.19 There
were also no difference in migration, sac expansion, aneurysm-related mortality,
limb thrombosis, renal dysfunction or reintervention between the two comparative

groups of neck thrombus.
Patient selection
Early scepticism about the long-term durability of EVAR made the prevailing
common assumption that this minimally-invasive modality would only be beneficial
in patients who were thought to be unsuitable for open surgery—mainly as EVAR
can be conducted under regional or local anaesthesia and thereby eliminating the
risks of general anaesthesia. In addition to this, EVAR only requires femoral artery
exposure and thereby eliminating the need for a laparotomy.
Technology has moved on to try to further reduce the risk of the EVAR procedure
itself. There have been recent advances in achieving low-profile devices and this has
allowed the development of percutaneous access eliminating even the need for a cut-
down. Percutaneous access has been found to be both feasible and safe, but a recent
comparison with femoral cutdown access has not found any superior outcomes.20, 21
Well-known variables such as congestive cardiac failure, increased age, pulmonary
and renal dysfunction and myocardial ischaemia are independent factors of
preoperative mortality.22,23 Egorova et al found that renal failure, lower extremity
ischaemia, liver disease, female sex, neurological disease, age, hospital volume,
surgeon experience, heart failure and chronic pulmonary disease all increased
30-day mortality in EVAR.23 Despite this, they found that EVAR is safe and
effective in the elderly population, even in those with multiple comorbidities, with
the proportion of patients who are truly unfit for EVAR being small. Interestingly,
patients who present with hostile neck anatomy tend to have higher American
Society of Anesthesiologists (ASA) scores.24,25
Proper patient selection is essential. Younger patients with more hostile neck
anatomy are more likely to have progressive aortic disease that deteriorates over a
shorter duration of time, rendering sealing zones inadequate even with the best graft
design. As well, patients with concurrent but separate aneurysms have demonstrated
their proclivity to aortic wall dilation, and no landing zone is likely safe from
long-term failure. There may be occasions where accepting poor sealing zone, or
a predictable failure, might be in the best interest of the patient—specifically in
the setting of rupture or symptomatic aneurysms when the short-term seal would
be life-saving. In these cases, many would agree that choosing a device that can be
222
converted into a more complex repair, or easily explanted, is likely to be the best

option for the patient.
Postoperative surveillance
Surveillance is mandatory in all cases of endovascular repair, and more vigilance
should be employed in cases where hostile neck anatomy is present. Recently
published guidelines by the Society for Vascular Surgery have recommended
computed tomography (CT) imaging one month postoperatively following EVAR
and, if there are no endoleaks or any other abnormalities seen, then yearly after.26 It
has also been suggested that ultrasound can be used if at one year CT imaging has
shown no endoleaks or other abnormalities. As there has been a higher incidence
of endoleaks, especially type 1 endoleaks in EVAR conducted outside of IFU, there
is a need for tighter surveillance of these cases.
Conclusion

As many studies have shown, off-label use is possible but there is still inconclusive
evidence to support the safety of EVAR in patients with hostile anatomy.27 A recent
systematic analysis conducted on the long-term results found that there were not
enough published data on the subject but advocated tighter surveillance due to the
higher incidence of type I endoleaks.28
It is known that strict adherence to device labelling will limit the number of
patients for whom EVAR would be suitable, and does not guarantee success. Up to
58.5%of patients were found to be treated outside of IFU and this is a substantial
number.3 If strict adherence to the IFU is maintained this would mean that quite
a few patients would require a more complex repair. Strict adherence to device
labelling is not always in the patient’s best interest, and as such, there is no good
clinical evidence to advocate otherwise; any repair should be conducted with
caution and with careful surveillance postoperatively.
Summary
• Early failure of endovascular repair was likely due to design flaws.

• The new generation of devices has much better outcomes in good anatomy.
• Longer-term failure of EVAR can be attributed to the progression of aortic
disease.
• The IFU provided by companies outline the technical parameters for device
implantation but cannot be considered clinical guidance.
• The role of physiology and aortic wall degeneration in the failure of devices
may be inferred by the heterogeneity of long-term durability in patients
treated on and off IFU.
References
1. Carpenter JP, Baum RA, Barker CF, et al. Impact of exclusion criteria on patient selection for endovascular
abdominal aortic aneurysm repair. J Vasc Surg 2001; 34 (6): 1050–4.
223
2. Abbruzzese TA, Kwolek CJ, Brewster DC, et al. Outcomes following endovascular abdominal aortic
aneurysm repair (EVAR): An anatomic and device-specific analysis. J Vasc Surg 2008; 48 (1): 19–28.
after endovascular repair. Circulation 2011; 123 (24): 2848–55.
4. Starnes BW. A surgeon’s perspective regarding the regulatory, compliance, and legal issues involved
with physician-modified devices. J Vasc Surg 2013; 57 (3): 829–31.
5. MHRA. Off-Label Use of a Medical Device 2014. https://goo.gl/tbVEW1 [Date accessed 17 February
2018]
6. Greiner A, Grommes J, Jacobs MJ. The place of endovascular treatment in abdominal aortic aneurysm.
Dtsch Arztebl Int 2013; 110 (8): 119–25.
7. Alsac J-M, Desgranges P, Kobeiter H, Becquemin J-P. Emergency endovascular repair for ruptured
abdominal aortic aneurysms: Feasibility and comparison of early results with conventional open
repair. Eur J Vasc Endovasc Surg 2005; 30 (6): 632–9.
8. Richards T, Goode SD, Hinchliffe R, et al. The importance of anatomical suitability and fitness for the
outcome of endovascular repair of ruptured abdominal aortic aneurysm. Eur J Vasc Endovasc Surg
2009; 38: 285–90.
9. Pitoulias GA, Valdivia AR, Hahtapornsawan S, et al. Conical neck is strongly associated with proximal
failure in standard endovascular aneurysm repair. J Vasc Surg 2017; 66 (6): 1686–95.
10. Holt PJE, Karthikesalingam A, Patterson BO, et al. Aortic rupture and sac expansion after endovascular
repair of abdominal aortic aneurysm. Br J Surg 2012; 99 (12): 1657–64.
11. Mahajan A, Barber M, Cumbie T, et al. The impact of aneurysm morphology and anatomic characteristics
on long-term survival after endovascular abdominal aortic aneurysm repair. Ann Vasc Surg 2016; 34:
75–83.
12. Walker J, Tucker L-Y, Goodney P, et al. Adherence to endovascular aortic aneurysm repair device
instructions for use guidelines has no impact on outcomes. J Vasc Surg 2015; 61: 1151–59.
13. Beckerman WE, Tadros RO, Faries PL, et al. No major difference in outcomes for endovascular aneurysm
repair stent grafts placed outside of instructions for use. J Vasc Surg 2016; 64 (1): 63–74. e2.
14. Troisi N, Torsello G, Weiss K, et al. Midterm results of endovascular aneurysm repair using the Endurant
Stent-Graft according to the instructions for use vs. off-label conditions. J Endovasc Ther 2014; 21 (6):
841–47.
15. AbuRahma AF, Campbell J, Stone PA, et al. The correlation of aortic neck length to early and late
outcomes in endovascular aneurysm repair patients. J Vasc Surg 2009; 50: 738–48.
16. Leurs LJ, Kievit J, Dagnelie PC, et al. Influence of infrarenal neck length on outcome of endovascular
abdominal aortic aneurysm repair. J Endovasc Ther 2006; 13 (5): 640–48.
17. Nissen SE. The DREAM trial. Lancet 2006; 368 (9552): 2049; author reply 2050–51.
18. Kwon H, Han Y, Noh M, et al. Impact of shaggy aorta in patients with abdominal aortic aneurysm
following open or endovascular aneurysm repair. Eur J Vasc Endovasc Surg 2016; 52 (5): 613–19.
19. Gonçalves FB, Verhagen HJM, Chinsakchai K, et al. The influence of neck thrombus on clinical outcome
and aneurysm morphology after endovascular aneurysm repair. J Vasc Surg 2012; 56: 36–44.
20. Krajcer Z, Nelson P, Bianchi C, et al. Percutaneous endovascular abdominal aortic aneurysm repair:
methods and initial outcomes from the first prospective, multicenter trial. J Cardiovasc Surg (Torino)
2011; 52 (5): 651–59.
21. Chen SL, Kabutey N-K, Whealon MD, et al. Comparison of percutaneous versus open femoral cutdown
access for endovascular repair of ruptured abdominal aortic aneurysms. J Vasc Surg 2017; 66: 1364–70.
22. Forbes TL, Steiner SH, Lawlor DK, et al. Risk-adjusted analysis of outcomes following elective open
abdominal aortic aneurysm repair. Ann Vasc Surg 2005; 19 (2): 142–48.
23. Egorova N, Giacovelli JK, Gelijns A, et al. Defining high-risk patients for endovascular aneurysm repair.
J Vasc Surg 2009; 50 (6): 1271–79.
24. Perdikides T, Georgiadis GS, Avgerinos ED, et al. The Aorfix Stent-Graft to treat infrarenal abdominal
aortic aneurysms with angulated necks and/or tortuous iliac arteries: Midterm results. J Endovasc Ther
2009; 16 (5): 567–76.
25. Georgiadis GS, Trellopoulos G, Antoniou GA, et al. Early results of the Endurant endograft system in
patients with friendly and hostile infrarenal abdominal aortic aneurysm anatomy. J Vasc Surg 2011;
54 (3): 616–27.
care of patients with an abdominal aortic aneurysm. J Vasc Surg 2018; 67 (1): 2–77.
57 (2): 527–38.
28. Oliveira-Pinto J, Oliveira N, Bastos-Gonçalves F, et al. Long-term results of outside “instructions for use”
EVAR. J Cardiovasc Surg (Torino) 2017; 58 (2): 252–60.
224
Risk factors for iliac limb
occlusion—one-year data with
latest generation EVAR devices
S Ancetti, E Gallitto, C Mascoli, R Pini, G Faggioli,
A Stella and M Gargiulo
Introduction
Iliac limb patency represents one of the main issues relevant to the follow-up of
patients undergoing endovascular aneurysm repair (EVAR).
The incidence of iliac limb occlusion significantly decreased with endograft
evolution and become relatively uniform from 2004 with the introduction of
second- and third-generation devices.1–3
After endoleaks and graft migration, iliac limb occlusion represents the third
most common reason for reintervention after EVAR.4,5 But unlike the others, there
is often a clear cause for its occurrence and, even more often, these causes were
present and recognisable even before intervention. Iliac limb occlusion probably
represents the most preventable post-EVAR complication.
Risk factors for iliac limb occlusion

Risk factors determining iliac limb occlusion are many and extensively described in
literature. Some of them have been confirmed by many authors; others have been
found significant just in a few works.
These risk factors have been historically divided into two main subgroups:
anatomical and graft related. But, we think that with the introduction of
latest generation devices and the relative homogenisation of their technical
characteristics, it would be more appropriate to define them as anatomical
and procedural.4
In recent works, Taudorf and Carpenter allocate mechanical issues to 83% and
100% of occlusions respectively.3,6 By mechanical, we mean some defect of arterial
wall, endograft surface or vessel’s cross-sectional area that is able to modify blood
flow dynamic, activating coagulation and leading to thrombosis.
Anatomically speaking, aortic bifurcation represents the first key point for
iliac limb patency. Among anatomical risk factors, a calcified, narrow or severely
angulated aortic bifurcation is thought to negatively affect short- and long-term
limb patency.1,2,6–8 Aortic bifurcation has to be large enough to accommodate two
limbs that, together, can easily reach the diameter of the main body as well be soft
and straight enough to not compress or kink the graft so as to cause an outflow
reduction that would affect both limbs and easily evolve to massive endograft
thrombosis.2 According to instructions for use of the majority of the currently
225
available endografts, an aortic bifurcation diameter <18/20mm can negatively
S Ancetti, E Gallitto, C Mascoli, R Pini, G Faggioli, A Stella et al
affect flow through iliac limbs.3

If aortic bifurcation is an important factor to be evaluated for avoiding iliac limb
occlusion, common iliac arteries are crucial, representing the actual distal sealing
zone. The anatomical characteristics of common iliac arteries are demonstrated to
significantly influence limb occlusion rate.9 Mantas et al recently reported their
results with multiple latest generation devices and found that iliac artery angulation
≥60 degrees and iliac perimeter calcification ≥50% may cause graft limb kinking or
stenosis, induce thrombogenicity and predispose to limb occlusion with a five-fold
increase in incidence.2 Moulakakis et al recently confirmed these results on a larger
sample both for monolateral and bilateral limb occlusion.9
A high common iliac artery tortuosity index, intended as the ratio between
the centre lumen line-based length of the common iliac artery from the aortic
bifurcation to the origin of the internal iliac artery and the length of a straight
line between the two landmarks, has also been related to an increased risk of iliac
limb occlusion.3 Excessive and repeated bending, redundancy and severe angulation
of the external iliac arteries in an experimental model can determine graft limb
kinking, twisting and stenosis able to cause a clinically relevant reduction of the
stent graft cross-sectional area and subsequent thrombosis.10 Factors capable of
determining kinking of the endograft are ultimately the most frequently causes of
occlusion reported in literature.11
Risk factors for iliac limb occlusion—one-year data with latest generation EVAR devices •
As referred by Carroccio and colleagues, arterial outflow plays an important role

in the risk of iliac limb occlusion.7 Outflow can be influenced by many different
factors: external iliac arteries diameter, stenosis, calcification and tortuosity and
peripheral arterial obstructive disease.
Faure and colleagues reported their experience, describing a diameter of ≤10
mm, associated with kinking at the level of external iliac arteries, to be a strong
independent predictor of occlusion.11 Equally, Carroccio et al suggested that limb
diameter <14mm negatively affects limb patency.7
Contrary to what is reported by first-generation endograft studies, female gender
seems not to influence iliac limb patency after EVAR, even if recent literature
reports women to have significantly smaller ileofemoral arteries. 2,3,12,13
The presence of haemodynamic external iliac lesions, compromised run-off due
to extensive occlusive peripheral arterial disease (reported in up to 40% of EVAR
patients) or caused by pre-existing or accidental operative dissection can negatively
affect long-term iliac patency as well.4,14–16 Moreover, Karthikesalingam reported
an increased systolic peak velocity inside graft limbs at early postoperative duplex
ultrasound examination was related to an increased risk of limb complications
including iliac limb occlusion.17
It is finally noteworthy that obesity (body mass index >30) has been correlated
with an increased risk of iliac limb occlusion. This could be due to a mechanical
aspect of extrinsic compression exercised by visceral and retroperitoneal fat as well
as the thrombogenicity of fat.3
For procedure-related risk factors, we believe all those factors depend on
suboptimal preoperative planning. Mantas in 2015 and Moulakakis in 2018
reported their experience with the implantation of different brand latest generation
devices and found that an iliac limb oversize >15% in the common iliac arteries
can increase the risk of iliac limb occlusion more than five-fold.9 Fairman and
226
colleagues already described this risk with first- generation devices in 2002,
reporting that with an oversize of 4mm compared with ipsilateral common iliac
artery diameter the incidence of occlusion was increased by 12.12 An excessive
oversize can determine endograft infolding into the iliac lumen and the uneven
surface created by endograft redundancy may lead to turbulent flow and consequent
thrombosis.2,7
Instructions for use violation is reported as a risk factor for iliac limb occlusion in
several studies. In 2008 Abbruzzese et al found that EVAR application outside the
instructions for use of at least one device led to an increased risk of reintervention
in general and limb thrombosis.18 This was confirmed by Mantas in 2015 and
Moulakakis in 2018 with more recent devices.2,9 Device instructions are developed
after model and in vivo testing and are structured to guarantee better results.
Despite good results achieved performing EVAR outside instructions for use it is
of primary importance to learn every endograft characteristic and understand the
limits of each of them.
Finally, many authors proposed the extension of distal sealing in the external
iliac artery as a contributing factor for limb occlusion and many explanations have
been proposed to justify this observation.4,7,11,19– 21 Among these, loss of hypogastric
artery outflow has been suggested to potentially compromise distal runoff.4,7 Others
link this increased risk with the tortuosity between the common iliac and external
iliac arteries, or with the diameter leap between an endograft limb planned to fit
on the common iliac artery and the external iliac artery itself.3,7 These findings are
not confirmed by most recent works that did not prove external iliac arteries to be
a significant factor for inducing iliac limb occlusion.2,9
As already specified, recent studies evidenced no significant difference in terms
of short and long-term patency using different latest generation devices.1 Equally
there is no evidence that endograft material could affect limb patency.22 Only two

aspects of endograft configuration have been found to be significantly correlated
to increased risk of iliac limb occlusion: stent conformation and unsupported
grafts. Demanget and colleagues tested eight different manufacturer graft limbs
in an experimental model. They concluded that stent design strongly influences
endograft mechanical performance and that spiral and circular stents provide
increased flexibility and better adaptation to tortuous iliac anatomies if compared
with Z-stents.10 Fairman et al claim that a difference clearly exists between supported
and unsupported endografts and that the latter are 15 times more prone to develop
kinking and consequent thrombosis.12
Latest generation endografts

In the last 10 years, EVAR has become the preferred method to treat patients with
infrarenal aortic pathology. The endovascular approach demonstrated compelling
results in terms of intraoperative and 30-days mortality, patients’ postoperative
discomfort, discharge times and 30-day morbidity if compared with open surgical
repair. On the other hand, EVAR is associated with life-long surveillance, a more
expensive follow-up as well as a higher reintervention rate of up to 20% within
the first five years.23 Iliac limb occlusion represents the third most frequent cause
of secondary intervention after endoleaks and graft migration.5 Despite small
technical differences, a recent review of publications since 2012 demonstrated that
227
second and third generation EVAR devices have uniform results in terms of limb
patency with an occlusion incidence ranging between 0.4% and 7.7%.22

We reviewed the literature and took into consideration the most recent experiences
with the most-used latest generation endografts, focusing on short-term/one-year
outcomes in terms of iliac limb patency.
Endurant I/II endograft

Endurant (Medtronic) was given the CE mark in July 2008 and as well as being one
of the earliest, it is also one of the most commonly used grafts that is commercially
available. The most recent experiences—Faure’s from ENGAGE (Endurant stent
graft natural selection global postmarket registry) and Donas’ study, both published
in 2015—reported a iliac limb occlusion incidence of 3.4% and 2.1% after >2
years follow-up.11,24 Both authors underline this graft as a reliable tool for EVAR,
even in hostile anatomies. A smaller sample experience with the evolved version,
Endurant II, published by Pecoraro and colleagues in 2016, shows an occlusion
incidence of 1.6% at a mean follow-up time of 22 months.25
Excluder C3
The GREAT (Global registry for endovascular aortic treatment) registry was
established to investigate results of the Excluder C3 endograft (Gore). This graft

showed compelling results in terms of limb patency, with a 30-day reintervention
rate for stenosis/kinking of 0.5% and a 15 months occlusion incidence of 0.7%.26
These results confirm Excluder C3 to be one of the most reliable endografts in term
of limb patency currently available.
Incraft
The performance of latest generation ultra-low-profile (14Fr) Incraft AAA stent
graft system (Cordis) has been evaluated since 2010 within the INNOVATION
trial. This multicentre trial reported a two years’ follow-up limb occlusion rate
of 3.7%.27 Recently, Pratesi and colleagues published the four year follow-up of
INNOVATION trial’s patients and confirmed the Incraft system to be characterised
by low frequency of device-related events in the long term, with a reported slight
increase in iliac limb occlusion if compared with results after one year.28
Ovation
In 2017 Greaves published his experience of using the Ovation stent graft
(Endologix) in hostile anatomies, with a median follow-up of 24 months. There
were no cases of iliac thrombosis and one single case of limb kinking requiring
relining.29 These data confirmed that reported by Metha et al in the Ovation
pivotal study in 2014; as the 14Fr ultra-low-profile system of this endograft and its
particular low-permeability PTFE encapsulated iliac limbs nitinol stent results in
extremely low limb occlusion rate (1.8% at one year) even in severely narrow iliac
anatomies.30
228
Zenith LP/Alpha
Risk factors for iliac limb occlusion—one-year data with latest generation EVAR device •
This second generation endograft (Zenith Flex,Cook Medical) and its 16Fr low-
profile evolution demonstrated similar two‒year limb occlusion rates (Flex 8% vs
low profile 5%) despite low profile endografts being used in more challenging iliac
anatomies.31 Previously, Couchet and colleagues published their experience with
the new low profile endografts reporting no occlusion and just one case of limb
stenosis out of 100 limbs treated at six months follow-up.32 No data have yet been
published on the last released Zenith Alpha abdominal endograft, but preliminary
data from the Alpha Italian Registry, a multicentre experience that collected 274
patients with hostile iliac anatomies, shows an iliac limb occlusion rate of 1.5%
after five months, an improvement over the previous Zenith generation.
Conclusion
Finally, the concept of endovascular aneurysm sealing (EVAS) as an endovascular
treatment option was introduced with the Nellix endograft (Endologix. We did not
take EVAS into consideration in this chapter because it is conceptually different
from standard EVAR devices.
Summary
• Iliac limb occlusion represents the third most frequent cause of reintervention
after EVAR.
• Iliac limb occlusion incidence decreased with endograft evolution and has
become fairly uniform with current different commercially available devices.
• Risk factors for iliac limb occlusion can mainly be divided in anatomical and

procedure related. Graft and material related causes are nearly outdated.
• EVAR success in terms of limb patency is mainly dependent on aorto-iliac
morphology and accurate preoperative planning.
• Anatomical and procedural factors inducing graft limb kinking and stenosis
of the graft limb are proved to determine haemodynamic alterations and
consequent thrombosis.
• The majority of limb occlusion risk factors depend on mechanical reasons.
• Narrow aortic bifurcation, iliac artery angulation ≥60 degree iliac perimeter
calcification ≥50%, compromised distal outflow as iliac limb oversize >15% in
the common iliac arteries are confirmed to be risk factors for limb occlusion.
• Extension of distal sealing in the external iliac artery and instruction for use
violation have been correlated with an increased risk for limb occlusion but
results of different experiences have not been unequivocally proven.
• Last generation devices are characterised by nearly equivalent results in terms
of limb patency, with an iliac limb occlusion rate ranging between 0.4% and
7.7%.
229
References
1. Karanthanos C, Spanos K, Saleptsis V, et al. One Year Outcomes Using Newer Generation Endografts: A
national Multicenter study on real world practice. Ann Vasc Surg 2016; 36: 92–98.
2. Mantas G, Antonapoulos CN, Sfyroeras G et al. Factors predisposing to endograft limb occlusion after
endovascular aortic repair. Eur J Vasc Endovasc Surg 2015; 49: 39–44.
3. Taudorf M, Jensen LP, Vogt KC et al. Endograft limb occlusion in EVAR: iliac tortuosity quantified by
three different indices on the basis of preoperative CTA. Eur J Vasc Endovasc Surg 2014; 48: 527–33.
4. Woody JD, Makaroun MS. Endovascular graft limb occlusion. Sem Vasc Surg. 2004; 17: 262–67.
5. Al-Jubouri M, Comerota AJ, Thakur S et al. Reintervention after EVAR and open surgical repair of AAA:
a 15-year experience. Ann Surg 2013; 258: 652–57.
6. Carpenter JP, Neschis DG, Fairman RM et al. Failure of endovascular abdominal aortic aneurysm graft
limbs. JVS 2001; 33: 296–303.
7. Carroccio A, Faries PL, Morrissey NJ et al. Predicting iliac limb occlusion after bifurcated aortic stent
grafting: anatomic and device related causes. JVS 2002; 36: 679–84.
8. Bianchini Massoni C, Gargiulo M, Giovannetti F et al. Adjunctive stenting of endograft limbs during
endovascular treatment of infrarenal aortic and iliac aneurysms according to 3-projection completion
angiography. J Endovasc Ther 2011; 18: 585–90.
9. Moulakakis KG, Antonopoulos CN, Klonaris C et al. Bilateral endograft limb occlusion after endovascular
aortic repair: predictive factors of occurrence. Ann Vasc Surg 2018; 46: 299–306.
10. Demanget N, Duprey A, Badel et al. Finite element analysis of the mechanical performances of 8
marketed aortic stent-grafts. J Endovasc Ther 2013; 20: 523–35.
11. Faure EM, Becquemin JP, Cochennec F et al. Predictive factors for limb occlusions after endovascular
aneurysm repair. JVS 2015; 61: 1138–45.
12. Fairman RM, Baum RA, Carpenter JP et al. Limb interventions in patients undergoing treatment with
an unsupported bifurcated aortic endograft system: a review of the phase II EVT trial. JVS 2002; 36:
118–26.
13. Tran K, Dorsey C, Lee JT et al. Gender-related differences in ileo-femoral arterial anatomy among
abdominal aortic aneurysm patients. Ann Vasc Surg 2017; 44: 171–78.
14. Becquemin JP, Kelley L, Zubilewicz T et al. Outcomes of secondary intervention after abdominal aortic
aneurysm endovascular repair. JVS 2004; 39: 298–305.
15. Cochennec F, Becquemin JP, Desgranges P et al. Limb graft occlusion following EVAR: clinical pattern,
outcomes and predictive factors of occurrence. Eur J Vasc Endovasc Surg 2007; 34: 59–65.
16. Gallitto E, Mascoli C, Pini R et al. Managing of challenging access. Charing Cross 2017 - Vascular and
Endovascular Consensus Updates 2017. BIBA Publishing: 167–72.
17. Karthikesalingam A, Holt PJ, Hinchliffe RJ et al. Risk of reintervention after endovascular aortic
aneurysm repair. Br J Surg 2010; 97: 657–63.
18. Abbruzzese TA, Kwolek CJ, Brewster DC et al. Outcomes following endovascular abdominal aortic
aneurysm repair (EVAR): An anatomic and device-specific analysis. JVS 2008; 48: 19–28.
19. Urlings TAJ, De Vries AC, de Mol Van Otterloo JC et al. Thromboembolic complications after Zenith
low profile endovascular graft for infrarenal abdominal aneurysms. Cardiovasc Intervent Radiol 2015;
38: 600–05.
20. Maldonado TS, Rockman CB, Riles E et al. Ischemic complications after endovascular abdominal aortic
aneurysm repair. JVS 2004; 40: 703–10.
21. Conway AM, Modarai B, Taylor PR et al. Stent graft limb deployment in the external iliac artery increases
the risk of limb occlusion following AAA repair. J Endovasc Ther. 2012; 19 (1): 79–85.
22. Kouvelos GN, Katsargyris A, Verhoeven E. Limb patency outcomes in contemporary data. Suppl.
Endovascular Today 2015; 12–16.
23. Patel SR, Allen C, Grima MJ et al. A systematic review of predictors of reintervention after EVAR:
Guidance for risk-stratified surveillance. Vasc Endovascular Surg 2017; 51 (6): 417–28.
24. Donas KP, Torsello G, Weiss K, et al. Performance of the Endurant stent graft in patients with abdominal
aortic aneurysms independent of their morphologic suitability for endovascular aneurysm repair
based on instructions for use. JVS 2015; 62: 848–54.
25. Pecoraro F, Corte G, Dinoto E et al. Clinical outcome of Endurant II stent-graft for infrarenal aortic
aneurysm repair: comparison on on-label vs off-label use. Diagn Interven Radiol 2016; 22: 450–54.
26. Verhoeven ELG, Katsargyris A, Bachoo P et al. Real-world performance of the new C3 gore Excluder
stent-graft: 1-year results from the European C3 Module of the Global Registry for Endovascular Aortic
Treatment (GREAT). Eur J Vasc Endovasc Surg 2014; 48: 131–37.
27. Torsello G, Scheinert D, Brunkwall JS et al. Safety and effectiveness of the INCRAFT AAA Stent Graft for
endovascular repair of abdominal aortic aneurysms. JVS 2015; 61:1–8.
230
28. Pratesi G, Pratesi C, Chiesa R et al. The INNOVATION Trial: four-year safety and effectiveness of the
INCRAFT® AAA Stent-Graft System for endovascular repair. J Cardiovasc Surg (Torino) 2017; 58 (5):
650–657.
29. Greaves S, Moore A, Seriki D et al. Outcomes of endovascular aneurysm repair using Ovation stent
graft system in adverse anatomy. Eur J Vasc Endovasc Surg 2017; 1–6.
30. Mehta M, Valdes FE, Nolte T et al. One-year outcomes from an international study of Ovation abdominal
stent graft system for endovascular aneurysm repair. JVS 2014; 59: 65–73.
31. Sobocinski J, Briffa F, Holt PJ et al. Evaluation of the zenith low-profile abdominal aortic aneurysm
stent graft. JVS 2015; 62: 841–7.
32. Couchet G, Maurel J, Sobocinski J et al. An optimal combination for EVAR: Low profile endograft body
and continuous spiral stent limbs. Eur J Vasc Endovasc Surg 2013; 46: 29–33.
231
Reinterventions after
EVAR: “On”and “off”
instructions for use
MJ Grima and I Loftus
Introduction
Since the introduction of endovascular aneurysm repair (EVAR) by Professor
Nicholas Volodos in 1989, the proportion of patients undergoing abdominal aortic
aneurysm repair by endovascular techniques has increased steadily and EVAR is now
performed more frequently than open surgery.1,2 Multiple studies, including the
well quoted randomised trials, have demonstrated that an endovascular approach
permits the repair of aortic aneurysms with a lower perioperative morbidity and
mortality than open repair.3 There is also evidence that patients prefer EVAR over
open surgical repair.4,5 However, the long-term durability of endovascular repair,
in terms of preventing aneurysm expansion and rupture, is still a concern.6 This
concern is higher when aortic endografts are implanted outside of the instructions
for use (IFU) criteria that are provided by the endograft manufacturers, based
largely on the preoperative anatomy of the aorta and access vessels. When faced
with hostile anatomy, the physician, together with the patient, is often faced
with a difficult choice. The options are to proceed with an endovascular approach
but to implant a device outside of the IFU criteria, to opt for a more complex
endovascular repair, open surgical repair, or to adopt a conservative, non-operative
approach, perhaps setting a higher than usual size threshold for intervention.
Description of topic
Whatever the decision taken, the aim of aortic aneurysm repair is to achieve the
durability of an open surgical approach while maintaining the perioperative mortality
and morbidity advantages of minimally invasive surgery. The major contributors to
the long-term durability issues have been the fixation and seal of the aneurysm neck.
Recent data suggest that around 12,000 to 19,000 patients per year who undergo an
EVAR have an unfavourable or hostile aortic neck. This equates to approximately a
third of patients undergoing aneurysm repair every year.7
When faced with unfavourable anatomy, some physicians opt to perform
EVAR outside of the IFU criteria. This decision is usually taken to avoid the
potential higher risks associated with complex EVAR and open surgical repair, for
financial reasons and to avoid time delay awaiting the manufacture of bespoke
endografts. There are also significant anatomical restrictions in terms of the ability
to manufacture bespoke grafts for hostile anatomies. However, there is debate
regarding the suitability of this approach given the documented poorer durability
when placing an endograft outside of the IFU.
233
The critical paper by Schanzer et al serves as a reference regarding long-term
• MJ Grima and I Loftus
results of EVAR outside of IFU.8 In this multicentre observational study, 5,983

patients (58.5%) underwent EVAR outside of IFU and of these, 41% had an
increase in postoperative sac size ≥5mm within five years. However, data could not
be analysed to compare the results of all-cause mortality and/or aneurysm-related
mortality between patients treated within and outside IFU. As a result, the authors
note that despite the large cohort, the study only serves as a starting point for
discussion and debate on this topic rather than implying that physicians should not
treat aneurysm with EVAR outside of IFU.9 This high rate of sac expansion when
Reinterventions after EVAR: “On”and “off” instructions for use
performing EVAR outside of IFU was also documented in an UK single-centre

observational study by Holt et al.10 However, despite a 32% sac expansion rate five
years after EVAR, adverse clinical rates were rare. As a result, the authors questioned
the use of sac expansion as an outcome measure. Furthermore, the result from the
study by Schanzer et al was also challenged by data from the ENGAGE registry.
In this registry of 1,263 patients, although baseline characteristics were similar
between the M2S dataset (used by Schanzer et al) and ENGAGE, only 18.6% of
patients treated outside of the IFU had a sac size increase of ≥5mm (compared to
9.2% patients treated within the IFU criteria) over five years.11
Evidence for the competing views

The risk of continued sac expansion is not the only concerning factor when
considering surgery within or outside of the IFU. It is more of a surrogate marker
of potential endoleak and rupture risk in the longer term (and potential need
for increased surveillance and reintervention). In a study by Leurs et al in 2006,
which analysed the EUROSTAR registry, the authors noted that patients who
had short neck <15mm had a higher rate of type Ia endoleak; however, this did
not translate into higher rates of aortic-related mortality. This observational study
also showed that patients with short aortic necks had significantly higher non-
aortic complications.12 This suggests that these patients underwent EVAR rather
than open surgery or more complex EVAR, because of a higher comorbid burden.
The higher rate of type I endoleaks in patients treated outside of IFU was further
highlighted in a more recent paper by AbuRahma et al.13 This demonstrated that
patients with neck features outside of IFU criteria experienced higher rate of type I
endoleak and higher early reintervention, but also higher all-cause mortality.
The results from the cohort study of 526 patients by AbuRahma et al contrast
with results from a cohort study of 566 patients published in the same year by
Beckerman et al.13,14 In the study by Beckerman et al, there was no difference in
endoleak rates, reintervention rates, aneurysm sac expansion, and aortic rupture
between patients who had EVAR within or outside of the IFU. Yet, in this study,
the most common reason for deviation from the IFU was iliac morphology (463
patients, 41.6%) rather than neck morphology, though similar results were obtained
in the infrarenal neck subgroup analysis. Similarly, in the UK cohort study by Holt
et al, there was no significant difference in reintervention rates between patients
who had EVAR within or outside of IFU criteria with those who did not; however,
all-cause mortality was worse in patients with hostile anatomy (Figure 1).10 The
authors attributed this difference to patient selection, as aneurysm diameter was
larger in patients treated outside of IFU. A larger aortic diameter has also correlated
with higher all-cause mortality in other published studies.15,16
234
Figure 1: Kaplan-Meier analysis of all‐cause mortality after EVAR in patients within or outside endograft
manufacturers’ instructions for use (p=0.012). Citation: British Journal of Surgery; 99 (12): 1657–64.
A recently published review noted that although all-cause and aneurysm-related

mortality rates do not seem to differ significantly in the long term between EVAR
within and outside IFU, short neck aneurysm predispose to higher type I endoleak
rates while necks with severe angulation or high thrombus load do not seem to
cause higher adverse events.17 However, the review article noted that the long-term
results of off-label use of EVAR are seldom published and, as a result, publication
bias may be relevant and hinder our understanding of the true clinical picture.17
Furthermore, a recent study by Chisci et al noted that EVAR outside of IFU criteria
can achieve similar long-term (14 year) results as EVAR in favourable anatomy,
provided that planned perioperative adjunctive interventions are performed to
achieve a more durable solution.18
Given that planned perioperative adjunctive interventions can potentially improve
the overall outcome of EVAR in more hostile aortic anatomies, and given that studies
show that preoperative and postoperative morphology can help with risk prediction
of reinterventions after EVAR, the debate of safety implications of EVAR outside
IFU can potentially guide the development of personalised risk stratification to
identify patients at higher risk of reintervention. We have developed a model (the
St George’s Vascular Institute score), which stratified patients into high- and low-
risk for developing complications using their preoperative aortic sac size and iliac
diameter.19 Meanwhile, Bastos Gonçalves et al showed that patients with early sac
shrinkage, adequate EVAR seal and no endoleak during the first year after EVAR
have low risk of late complications.20,21 This has led to the development of the Long-
term risk stratification for reintervention after EVAR with the Endurant device
(LEAR) surveillance project, where preoperative, intraoperative and postoperative
factors can help with overall risk prediction.22 This may help to identify EVAR
patients who are potentially at high risk for complications and reinterventions, who
235
may benefit from more intensive surveillance with an aim to reduce the risk of late
rupture and longer-term aneurysm-related mortality. Conversely, it may identify

patients who are at such a low risk of reintervention or long-term complications
that they may undergo less intensive surveillance, or ideally be discharged from
surveillance all together. This is some way off, and further studies are needed to
determine whether such risk stratification incorporating specific endograft IFU
criteria, could help guide preoperative planning and postoperative management
(including surveillance) of these patients.
New developments and techniques, and new generation aortic endografts are
increasing patient eligibility for endovascular repair.23 These include the use of
aneurysm sealing technology, parallel graft solutions and the use of endostaples.24–26
However, despite the conflicting global literature and new-generation devices,
recent guidelines by the Society for Vascular Surgery still recommend caution
with the use of devices outside of IFU based on the potential for increased risk
of device migration, delayed type Ia endoleaks, and aneurysm rupture.27 Thus,
caution is advised when offering standard EVAR outside IFU criteria and apart
from adequately informing patients about these potential risks, adherence to
surveillance must be stressed to these patients until further evidence is available
which recommends otherwise.
Summary
• A third of patients undergoing aneurysm repair every year have unfavourable

anatomy and are treated outside of recommended device-specific IFU.
• Studies demonstrate higher rates of sac expansion when performing EVAR
outside of instructions for use.
• There are also studies that have shown higher rate of type I endoleak when
performing EVAR outside of IFU.
• There is conflicting evidence as to whether higher rate of sac expansion and
a potentially higher rate of type I endoleak result in higher aneurysm-related
mortality, but it is clear that post-procedural surveillance, plus timely and
targeted reintervention, are essential in these patients.
• There is a potential role for personalised surveillance programme to improve
EVAR outcomes.
• In the meantime, we need to inform and counsel patients when suggesting
EVAR outside of endograft-specific recommendations.
References
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2010. J Vasc Surg 2014; 59 (6): 1512–7.
2. Waton S, Johal A, Heikkila K, et al. National Vascular Registry: 2016 Annual Report. The Royal College
of Surgeons of England, London; 2016.
236

4. Reise JA, Sheldon H, Earnshaw J, et al. Patient preference for surgical method of abdominal aortic
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12. Leurs LJ, Kievit J, Dagnelie PC, et al. Influence of infrarenal neck length on outcome of endovascular
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J Am Coll Surg 2016; 222 (4): 579–89.
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repair stent grafts placed outside of instructions for use. J Vasc Surg 2016; 64 (1): 63–74. e62.
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results of outside “instructions for use” EVAR. The Journal of Cardiovascular Surgery 2017; 58 (2): 252–60.
18. Chisci E, Guidotti A, Pigozzi C et al. Planned perioperative adjunctive maneuvers make off-label
endovascular aneurysm repair (EVAR) comparable to standard EVAR at a long-term follow-up. J Vasc
Surg 2017; 65 (6): 148S–9S.
19. Karthikesalingam A, Holt PJ, Vidal-Diez A, et al. Predicting aortic complications after endovascular
aneurysm repair. Br J Surg 2013; 100 (10): 1302–11.
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complications after endovascular aortic aneurysm repair. Br J Surg 2014; 101 (7): 802–10.
21. Bastos Goncalves F, van de Luijtgaarden KM, Hoeks SE, et al. Adequate seal and no endoleak on the
first postoperative computed tomography angiography as criteria for no additional imaging up to 5
years after endovascular aneurysm repair. J Vasc Surg 2013; 57 (6): 1503–11.
22. Holt PJ. Risk and clinical surveillance of EVAR – long-term estimation of aortic risk (LEAR). In: Charing
Cross Symposium. London, UK; 2017.
23. Kontopodis N, Papadopoulos G, Galanakis N, et al. Improvement of patient eligibility with the use of
new generation endografts for the treatment of abdominal aortic aneurysms. A comparison study
among currently used endografts and literature review. Expert Rev Med Devices 2017; 14 (3): 245–50.
24. Malas MB, Hicks CW, Jordan WD, Jr, et al. Five-year outcomes of the PYTHAGORAS US Clinical trial of
the aorfix endograft for endovascular aneurysm repair in patients with highly angulated aortic necks.
J Vasc Surg 2017; 65 (6): 1598–1607.
25. Donas KP, Torsello GB, Piccoli G, et al. The PROTAGORAS study to evaluate the performance of the
endovascular technique. J Vasc Surg 2016; 63 (1): 1–7.
26. Schlosser FJ, de Vries JP, Chaudhuri A. Is it time to insert endoanchors into routine EVAR? Eur J Vasc
Endovasc Surg 2017; 53 (4): 458–9.
237
27. Chaikof EL, Dalman RL, Eskandari MK, et al. The Society for Vascular Surgery Practice Guidelines on the
Care of Patients with an Abdominal Aortic Aneurysm. J Vasc Surg 2018; 67 (1): 2–77 e72.
238
Ten-year EVAR follow-
up vs. open repair with
second-generation EVAR
G Pratesi, M Barbante, R Bisceglie, G Citoni and
A Ippoliti
Introduction
In recent decades, the evolution of endovascular techniques has radically
revolutionised the surgical approach to abdominal aortic aneurysms. Endovascular
aneurysm repair (EVAR) has become the first-line treatment for elective repair
of infrarenal abdominal aortic aneurysms expanding the indication in aneurysm
treatment due to the reduction of morbidity and mortality.1 However, few final
assessments of the real benefits of endovascular treatment compared to open repair
have been performed. Recent publication of long-term outcomes of randomised
controlled trials with up to 15-years of follow-up confirmed reinterventions
as the Achilles heel of EVAR, causing a progressive loss of early advantages of
this technique. For these reasons, further investigations on long-term EVAR
performance are mandatory. However, it is not simple to obtain a real comparison
with open repair because the patients are not always comparable (in terms of age
and comorbidities) and the growing experience with new technology in EVAR
(new devices, planning strategies, intraoperative imaging modalities) may lead to
different results. Additional evidence to this analysis may come from dedicated
registries to obtain a close observation of EVAR and clarify the actual durability of
this technique.
Long-term data for EVAR vs. open repair from randomised

controlled trial
The major randomised trials published in the literature in the last two decades
reported a significant advantage of endovascular therapy in the early outcomes
compared to standard open surgery. On the other hand, open surgery is more
effective during follow-up causing the progressive loss of early advantage of EVAR.1
In fact, the perioperative mortality rate is twice in the open group as described in
the EVAR-1 trial and DREAM trial due to higher invasiveness of open repair on
fragile patients.2,3 Nevertheless, additional data analysis for the follow-up after five
years showed that there were no significant differences between the two techniques
in term of overall mortality and aneurysm-related mortality.4 It seems that the
early benefit after EVAR may be lost. The continuous decline of freedom from
secondary procedures after EVAR are showed in EVAR-1 and the DREAM trial due
to endoleak or graft-related complication, whereas secondary procedure after open
repair occurred only sporadically. The OVER trial, on the contrary, did not find an
239
increased rate of secondary intervention after EVAR at mid-term follow-up due to
G Pratesi, M Barbante, R Bisceglie, G Citoni and A Ippoliti
a different classification of secondary procedures in the open group.5 Consequently

patients undergoing EVAR are more inclined to be associated with an increasing
risk of developing aneurysm-related complication during follow-up.
The EVAR-1 trial previously reported aneurysm mortality after intervention up
to 10-years of follow-up, and no differences were noted. However, the problem of
aneurysm sac rupture after EVAR was emerging and doubts on the real durability of
EVAR in the long-term compared to open repair have been raised. Further analysis
has been conducted on the EVAR-1 population to very long-term follow-up and
secondary sac rupture was much more common after EVAR and occurred in any
period after procedure. The importance of close surveillance after EVAR during all
time of follow-up has, therefore, been established.6
When comparing the results of survival from randomised trials to population-
based studies, the overall difference is remarkable. Schermerhorn et al demonstrated
an overall survival rate close to 45% after eight years and similar outcomes were
reported in the Swedish Vascular Registry study at 10 years where the overall
survival rate was 39%. The difference in overall survival between these population-
based studies and randomised trials can be related to the baseline health condition
prior to the surgery.6 These patients are affected by coronary, renal or pulmonary
Ten-year EVAR follow-up vs. open repair with second-generation EVAR •
disease that can be an independent factor for long-term aneurysm-related survival.

Furthermore, the difference in overall survival could also be attributed to the close
follow-up programme in randomised trials. In this way, complications might be
detected at an earlier stage to avoid the degeneration to a major complication.7
In addition to this preliminary consideration about the randomised controlled
trials, there are some variables that are needed to describe the modern decision
process of abdominal aortic aneurysms that outline aily clinical practice. Major
randomised controlled trials are not perfect and can fail to achieve homogeneous
results in terms of mortality, morbidity or reinterventions in the long term.
Anatomy, perioperative risk, expertise of the hospital and physician, and patients’
decisions are some of the factors that must be considered today.8
As well as all these factors, the improvement in device design and sealing
technology is of paramount importance in obtaining durable results in EVAR.
First- and second-generation endografts are included in data collection of major
randomised controlled trials from 1999 and represent today a distortion of real-
world practice. The materials and endovascular management have progressed from
earlier generation stent grafts that are nowadays considered inferior to the currently
available devices. For this reason, randomised controlled trials including early
generation of endografts may underestimate the real advantages of EVAR.
A recent study comparing old and new endografts showed that even though there
does not exist a difference in terms of mortality and long-term outcomes, the use
of the newest stent grafts is associated with a lower rate of conversion, secondary
procedures and aneurysm sac expansion. Increasing experience and the need to use
less invasive techniques to treat aneurysms lead physicians to recommend EVAR
for most of the patients.9 On the other hand, the increased risk of migration,
type 1 endoleak and limb occlusion in patients treated outside the instructions
for use in challenging anatomies require close surveillance after EVAR. Garg et al
demonstrated a great variability in postoperative surveillance, and fewer than half
240
of the patients treated had complete postoperative follow-up as recommended in

the Society for Vascular Surgery (SVS) guidelines.10
Many registries in this way have helped to clarify some fundamental aspect
of EVAR therapy with new devices. The first and the most cited registry is
EUROSTAR.11 More recently, additional data have been published on the basis of
a device-specific multicentre registry to clarify the real performance of single stent
graft in the daily practice with a standardised technique, avoiding any possible bias
related to the graft design, configuration and sealing system. One example is the
ENGAGE registry that aims to collect data from the latest generation Endurant
stent graft (Medtronic) in 80 centres that reported data up to five year of follow-up
so far.12 The ITER registry (Italian excluder registry) is an Italian multicentre single-
device registry aimed to analyse EVAR outcomes using the Excluder endograft
(Gore) with a long follow-up data analysis up to 10-year follow-up and it is the
subject of the present chapter.
Ten-year EVAR follow-up of the multicentre Italian Excluder

Registry
The proportion of abdominal aortic aneurysms treated with a stent graft is
continuously increasing and new stent grafts for performing EVAR are regularly
released. Around 40,000 non-ruptured abdominal aortic aneurysms are treated
every year in the USA alone, with 80% being treated endovascularly.13

Commonly used endografts are subject to regular updates that may have altered
the graft design, structure and performance. Data for these devices are usually based
on post-market surveillance registries, publications with few patients and short
follow-up observation. A recent Cochrane review underlined that no randomised
trials comparing device-specific outcomes of EVAR are actually available.14
Historically, some first generation devices suffered from material fatigue and other
device-related complications after more than five years follow-up.5,6 For this reason,
it seems that registry data have the advantage of being prospectively collected, are
readily available and are able to reflect unselected everyday practice with report
failures in a fast and precise way compared to trials focusing on a single device
performance in similar anatomical conditions. The use of only one device as a
part of a registry could reflect the specific performance of a standardised aneurysm
therapy using EVAR.
ITER is a prospective, unfunded multicentre clinical registry of elective EVAR
using a single device, carried out with the purpose to show early and long-term
performance of the Excluder endograft (Gore). The first publication on five-year
outcomes of the ITER registry on 565 patients showed excellent early outcomes
with a 97.5% technical success, low rate of graft migration, thrombosis and
reintervention at mid-term follow-up.15 At the five-year follow up point, freedom
from reintervention was 86% with no reintervention-related death. The main
reasons for reintervention were endoleak and limb thrombosis. Freedom from any
endoleak was 71%, mainly represented by type II. A notably low risk of limb
thrombosis was observed (1.1% at year five) and freedom from aneurysm-related
death was 97%.15
The low rate of limb thrombosis, migration and reintervention was confirmed
on the 10-year follow-up analysis, carried out on a subgroup of 461 patients
with longest follow-up data available.16 The overall-survival was 62% at 10-years,
241
in line with that reported in the major randomised controlled trials at 10-year
follow-up. One of the major findings of ITER is the 98% freedom from aneurysm-
related death rate, with no aneurysm rupture in the second phase of the study.
Another positive finding of this study is that the freedom from endograft related
complications was 88% at 10-year follow-up, confirming the effectiveness and
durability of this endograft in the long run with only 1.4% limb occlusion rate
and an 80% freedom from reinterventions rate at 10 years.
Furthermore, endograft-related complications were mainly reported in the
early experience and rarely in the long-term follow-up with evidence of statistical
difference between the two periods. These findings support the reliable durability
of EVAR and confirm the effectiveness of the Excluder endograft.16
Current perspectives
Although continuous technological and material evolution has improved endograft
performance with increased EVAR applicability in even more challenging cases,
anatomy is still the main predictor of long-term outcomes. In fact, the presence of
hostile proximal aortic neck anatomy or challenging iliac access vessels represents
a real limitation for EVAR therapy.17 Anatomic suitability for specific standard
endograft is defined by the manufacturer’s instructions for use (IFU). Currently,
IFU have been expanded with endograft improvements allowing for the treatment
of more patients. Obviously, the hostile proximal aortic neck has been clearly
reported to be associated with increased risk of endograft migration and type 1
endoleak.18 The growing use of advanced technology such as fenestrated/branched
endografts or the chimney technique that allow the operator to move the landing
zone more proximally, might definitively solve this problem. Challenging access
vessels play an important role in EVAR feasibility as well—a small iliac and femoral
artery diameter or extensive calcification limit endograft trackability and influence
the technical success of percutaneous access. Calcified common femoral artery is in
fact a well-recognised factor associated with percutaneous EVAR (PEVAR) failure.
The rising interest of pEVAR as part of minimally invasive abdominal aortic
aneurysm treatment led to improvements in closure device systems and operator
learning curve allowing the percutaneous approach to be used in more challenging
cases.19 In order to overcome some of these anatomical limitations, many endografts
have reduced the profile and improved the flexibility of the delivery system. Other
endografts have undergone a radical transformation over the years with changing
sealing systems, stent designs, ultra-thin fabric and delivery systems much more
than a simple “restyling”. Any major change in the sealing concept or in the general
performance of the graft leads to a revolution that must be progressively approved
and tested with appropriate studies and follow-up. For the majority of the newest
endografts, the follow-up period has to be reset due to the changes aforementioned
changes. What we want to underline is that the aim of EVAR to reach the exclusion
of the aneurysm sac can be obtained with different endograft each suitable for
different anatomical situations. Due to technical differences between the newest
endografts, it is difficult to compare their performances in collective studies and
randomised controlled trial.20,21 The Gore Excluder endograft has preserved the
original stent material and design in addition to the sealing concept for more than
15 years. The main improvements were the flexibility and reduction of introducer
sheath profile, as well as the delivery system. Currently, these specific features are
242
fundamental to mark EVAR as minimally invasive technique along with a very

long-term follow-up as showed in ITER.15, 16
Summary
• Endovascular therapy is superior in early outcomes regarding morbidity and

mortality compared with standard open surgery in abdominal aortic aneurysm
treatment
• Randomised controlled trials confirmed reinterventions as the Achilles’ heel of
EVAR and the progressive loss of advantage of EVAR in the mid-term follow-up
• Technological progress of endografts is fast, and randomised controlled trial
results risk to be outdated because of first and second generation of endograft
involvement in the study
• Registries have the advantage to be readily available and reflect unselected
daily practice with results reported in a fast and precise way, focusing on a
single device performance
• ITER registry focused on Gore Excluder endograft performance, analysing
specific outcomes of a standardised abdominal aortic aneurysm therapy using
a single device in the long-term follow-up up to 10 years.

References
repair of abdominal aortic aneurysms, N Engl J Med 2004; 351 (16): 1607–18.
randomised controlled trial, Lancet 2004; 364 (9437): 843–48
3. De Bruin JL, Baas AF, Buth J, et al. Long-term outcome of open or endovascular repair of abdominal
aortic aneurysm, N Engl J Med 2010; 362 (20):1881–89
4. Greenhalgh RM, Brown LC, Powell JT, et al. Endovascular versus open repair of abdominal aortic
aneurysm. N Engl J Med 2010; 362 (20):1863–71.
5. Lederle FA, Stroupe KT, Kyriakides TC, et al. Long-term cost-effectiveness in the veterans affairs open vs
endovascular repair study of aortic abdominal aneurysm: a randomized clinical trial. JAMA Surg 2016;
151 (12): 1139–44.
6. Patel R, Sweeting MJ, Powell JT et al EVAR trial investigators. Endovascular versus open repair of
abdominal aortic aneurysm in 15-years’ follow-up of the UK endovascular aneurysm repair trial 1
(EVAR trial 1): a randomised controlled trial. Lancet 2016; 388 (10058): 2366–74.
7. Schermerhorn ML, Buck DB, O’Malley AJ, et al. Long-term outcomes of abdominal aortic aneurysm in
the Medicare population. N Engl J Med 2015; 373 (4): 328–38
8. Desender LM, Van Herzeele I, Lachat ML, et al. Patient-specific rehearsal before EVAR: Influence on
technical and nontechnical operative performance. A randomized controlled trial. Ann Surg 2016; 264
(5): 703–09.
9. Verzini F, Isernia G, De Rango P, et al. Abdominal aortic endografting beyond the trials: a 15-year
single-center experience comparing newer to older generation stent-grafts. J Endovasc Ther 2014; 21
(3): 439–47.
10. Garg T, Baker LC, Mell MW. Adherence to postoperative surveillance guidelines after endovascular
aortic aneurysm repair among Medicare beneficiaries, J Vasc Surg 2015; 61 (1): 23–27.
11. Harris PL, Buth J, Mialhe C, et al. The need for clinical trials of endovascular abdominal aortic aneurysm
stent-graft repair: the EUROSTAR Project. European collaborators on stent-graft techniques for
abdominal aortic aneurysm repair, J Endovasc Surg 1997; 4 (1): 72–77.
12. Dijkstra ML, van Sterkenburg SM, Lardenoye JW et al. One-Year outcomes of endovascular aneurysm
repair in high-risk patients using the endurant stent-graft: comparison of the ASA classification and
243
SVS/AAVS medical comorbidity grading system for the prediction of mortality and adverse events. J
Endovasc Ther 2016; 23 (4): 574–82.

13. Beck AW, Sedrakyan A, Mao J, et al. International consortium of vascular registries. Variations of
abdominal aortic aneurysm care: a report from the international consortium of vascular registries.
Circulation 2016; 134 (24): 1948–58.
14. Duffy JM, Rolph R, Waltham M. et al, Stent graft types for endovascular repair of abdominal aortic
aneurysms. Cochrane, Database Syst Rev 2013.
15. Pratesi C, Piffaretti G, Pratesi G, et al. ITalian Excluder Registry and results of Gore Excluder endograft
for the treatment of elective infrarenal abdominal aortic aneurysms. J Vasc Surg 2014; 59 (1): 52–27
16. Pratesi G, Piffaretti G, Verzini F et al. Ten-year outcome analysis of the Italian Excluder Registry with the
Gore Excluder endograft for infrarenal abdominal aortic aneurysms. J Vasc Surg 2017. Epub.
17. Egorova N, Giacovelli JK, Gelijns A, et al. Defining high-risk patients for endovascular aneurysm repair.
J Vasc Surg 2009; 50 (6): 1271–79.
18. Antoniou GA, Georgiadis GS, Antoniou SA et al. A meta-analysis of outcomes of endovascular
57 (2): 527–38.
19. Pratesi G, Barbante M, Pulli R et al. Italian percutaneous EVAR (IPER) registry: Outcomes of 2381
percutaneous femoral access sites' closure for aortic stent-graft. J Cardiovasc Surg (Torino) 2015; 56
(6): 889–98.
20. Chaikof EL, Dalman RL, Eskandari MK et al. The Society for Vascular Surgery practice guidelines on the
care of patients with an abdominal aortic aneurysm. J Vasc Surg 2018; 67 (1): 2–77.
21. Pratesi G, Pratesi C, Chiesa R et al, The INNOVATION Trial: four-year safety and effectiveness of the
INCRAFT® AAA Stent-Graft System for endovascular repair. J Cardiovasc Surg (Torino) 2017. Epub.
244
Prediction of less vigorous
follow-up based upon the
first postoperative CT scan
Introduction
Endovascular aneurysm repair (EVAR) is now the primary method for repair of
abdominal aortic aneurysms in many countries, with >80% of intact aneurysm
repairs being performed with EVAR in some hospitals.1,2 Despite the reported
superior short-term outcome, this minimally invasive technique has a downside,
with the risk of incomplete exclusion of the aneurysm sac over time resulting in
continuous pressurisation and, eventually, rupture. 3 An annual post-implantation
rupture rate of approximately 1% has been reported by randomised clinical and
observational trials.4 The major vascular society guidelines recommend annual
follow-up after EVAR to detect adverse events that may result in sac pressurisation
and rupture.5,6 These guidelines are, however, seldom followed in clinical practice,
and lack evidence.7,8 They also result in a significant use of resources. The
development of a stratified routine that tailors the follow-up based on the patient’s
risk for EVAR failure would, therefore, be of importance.
Shortcomings of EVAR surveillance

The effectiveness of EVAR surveillance in preventing aneurysm-related death is not
evident. Studies have reported that compliance to the current follow-up protocols
with annual imaging does not confer any survival benefit.9,10 Additionally, current
follow-up regimens are costly, and they cause significant workload for healthcare
systems and inconvenience for patients. Repeated computed tomography (CT)
results in exposure to radiation and nephrotoxic contrast media. Risk-stratified
follow-up has been discussed to reduce the surveillance burden in patients with low
risk for complications. Several risk factors for developing graft-related complications
have been identified, such as EVAR outside instructions for use (IFU) and the need
for intraoperative adjunct procedures.11 On the other hand, sac shrinkage post-
EVAR, as well as successful exclusion of the aneurysm on the first postoperative
imaging examination has been associated with low risk for EVAR failure. 12
Prediction of EVAR outcome based on the first postoperative

imaging
Troutman et al studied the impact of normal postoperative ultrasound on the late
outcomes after EVAR. Only 2% of patients with normal postoperative ultrasound
developed endoleaks or limb stenosis that required reintervention during three
245
Prediction of less vigorous follow-up based upon the first post-operative CT scan •
Figure 1: Reintervention rate in the low- and high-risk groups post-EVAR, based on assessment of the first
postoperative CT.
Figure 2: Type Ib endoleak in a patient allocated to the high-risk group, (A) detected on CT and (B) visualised with
angiogram. (C) The endoleak was managed by limb extension.
years of follow-up. This is to be compared to 25% of patients with abnormal

initial ultrasound developing an adverse event, p=0.001.13 This study concluded
that surveillance might not be necessary after a normal ultrasound examination
soon after the EVAR procedure. However, ultrasound cannot evaluate the sealing
zone proximally in the aortic neck, or distally in the common or external iliac
arteries. Several studies have shown association between sealing zones and risk
for complications post-EVAR. Sampaio et al demonstrated that the risk of type
I endoleaks decreased by half for each additional 5mm of proximal overlap.14
Goncalves et al studied first postoperative CT scans in 130 patients treated with the
Excluder endograft (Gore). Patients with adequate sealing proximally and distally
and no endoleak on the first postoperative CT had a 98% five-year freedom from
aneurysm-related adverse events, compared to 52% in patients with short sealing
or endoleak.15
246
To validate the aforementioned study, a two-centre cohort study was performed
in Sweden (Uppsala and Gävle hospitals).16 More than 300 patients treated over
the period 2001–2012 were included in this study. Patients were classified into
two groups, based on the result of the first postoperative CT: the low-risk group
(65%) had proximal and distal sealing zone length of ≥10mm and no endoleak,
while the high-risk group (35%) had proximal or distal sealing zone <10mm,
and/or endoleak. Within five years, there were approximately 3% graft-related
complications in the low-risk group vs. 47% in the high-risk group (p<0.001).
Five-year freedom from reintervention was 97% in the low-risk group and 54% in
the high-risk group (p<0.001), Figure 1. A case of type Ib endoleak detected on
the first postoperative CT in a patient that was allocated to the high-risk group and
treated with limb extension is shown in Figure 2.
Thirty per cent of the patients were classified to the high-risk group because of
short sealing, while 50% had an endoleak, and 20% had both short sealing and
endoleak. Three out of four endoleaks were type II. The risk of developing sac
expansion due to type II endoleak was significantly higher in patients in the high-
risk group. This indicates that some of these type II endoleaks may be misclassified
type I endoleaks.
During the follow-up period, 168 imaging examinations were performed per
aneurysm-related complication in the low-risk group, compared to 11 in the high-
risk group. The corresponding number of examinations in Goncalves’ study was 82
for low-risk group and eight for the high-risk group.15
Risk evaluation based on pre- versus postoperative imaging

The association between aortoiliac anatomy (or endografts’ IFU) and the risk of

EVAR complication has been studied extensively. Most of the authors agree that
EVAR in hostile anatomy or outside IFU is associated with higher complication
rates. However, it is relatively usual that the available landing zone is not used
fully during an EVAR procedure, due to maldeployment of the graft. In the
cohort described above, maldeployment (defined as implantation of the EVAR
device >5mm below the lowest renal artery) occurred in approximately 30% of the
patients.15
Therefore, although preoperative imaging is clearly associated with long-term
EVAR outcome, evaluation of the sealing zone on the first postoperative CT may
be a better method for patient stratification for follow-up. An additional benefit
of stratification based on postoperative imaging is the fact that the presence of
endoleaks can be assessed. Although most type II endoleaks are harmless, some may
result in continued sac expansion. Therefore, risk evaluation for EVAR durability
based on postoperative imaging is a more robust criterion than preoperative
anatomical evaluation.
For patients in whom a full exclusion of the aneurysm is achieved with EVAR,
with adequate sealing zones proximally and distally, annual imaging follow-up is not
necessary. These patients are at a very low risk for EVAR complications during the
first five years post-EVAR. As many studies have indicated that EVAR failure may
occur more than five years post-EVAR, it is currently not possible to recommend
a total abolishment of follow-up even in these low-risk patients. Further aortic
degeneration over time exposes the patients to the risk for late endoleaks despite
247
adequate seal initially. Repeat imaging at a five-year interval may serve as a measure
to identify patients in need for more vigorous follow-up over time.
Conclusion
The current follow-up recommendations with annual imaging post-EVAR for all
patients are cumbersome and often not followed in clinical practice. There is a
need for the development of stratified follow-up protocols after EVAR that direct
efforts to patients at risk for EVAR failure, and reduce the burden of follow-up
for patients who are not likely to benefit from annual follow-up. A normal
postoperative CT with adequate sealing zones is a strong predictor of successful

isolation of the aneurysm sac. These patients are at low risk for developing graft-
related complications up to five years after EVAR. More than 60% of the EVAR
patients may be classified as low-risk, and in these patients imaging at a five-year
interval is sufficient post-EVAR. Application of a less vigorous follow-up based
on the first postoperative CT scan would thus significantly reduce the burden of
EVAR follow-up.
Summary
• Patients with adequate seal and no endoleak on the first postoperative

CT scan have a very low risk for EVAR complications up to five years
postoperatively.
• Approximately 60% of EVAR patients can be classified as low-risk for EVAR

failure based on the first postoperative CT scan.
• Subsequent imaging in the low-risk group can be delayed to three to five

years.
• Stratification of follow-up based on the postoperative CT scan is more robust

than basing follow-up on assessment of preoperative aortic anatomy.
References
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International Consortium of Vascular Registries. Circulation 2016; 134 (24):1948–58.
2. Budtz-Lilly J, Venermo M, Debus S, et al. Editor’s Choice – Assessment of international outcomes of
intact abdominal aortic aneurysm repair over 9 years. Eur J Vasc Endovasc Surg 2017; 54 (1): 13–20.
4. Stather PW, Sidloff D, Dattani N, et al. Systematic review and meta-analysis of the early and late
outcomes of open and endovascular repair of abdominal aortic aneurysm. Br J Surg 2013; 100 (7):
863–72.
S1–58.
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7. Patel A, Edwards R, Chandramohan S. Surveillance of patients post-endovascular abdominal aortic
aneurysm repair (EVAR). A web-based survey of practice in the UK. Clin Radiol 2013; 68 (6): 580–7.
8. Garg T, Baker LC, Mell MW. Adherence to postoperative surveillance guidelines after endovascular
aortic aneurysm repair among Medicare beneficiaries. J Vasc Surg 2015; 61 (1): 23–27.
9. Garg T, Baker LC, Mell MW. Postoperative surveillance and long-term outcomes after endovascular
aneurysm repair among Medicare beneficiaries. JAMA Surg 2015; 150 (10): 957–63.
10. Wu CY, Chen H, Gallagher KA, Eliason JL, Rectenwald JE, Coleman DM. Predictors of compliance with
surveillance after endovascular aneurysm repair and comparative survival outcomes. J Vasc Surg 2015;
62 (1): 27–35.
11. AbuRahma AF, Yacoub M, Mousa AY, et al. Aortic neck anatomic features and predictors of outcomes
in endovascular repair of abdominal aortic aneurysms following vs not following instructions for use.
J Am Coll Surg 2016; 222 (4): 579–89.
12. Bastos Goncalves F, Baderkhan H, Verhagen HJ, et al. Early sac shrinkage predicts a low risk of late
complications after endovascular aortic aneurysm repair. Br J Surg 2014; 101 (7): 802–10.
13. Troutman DA, Chaudry M, Dougherty MJ, Calligaro KD. Endovascular aortic aneurysm repair
surveillance may not be necessary for the first 3 years after an initially normal duplex postoperative
study. J Vasc Surg 2014; 60 (3): 558–62.
14. Sampaio SM, Panneton JM, Mozes GI, et al. Proximal type I endoleak after endovascular abdominal
aortic aneurysm repair: predictive factors. Ann Vasc Surg 2004; 18 (6): 621–8.
15. Bastos Goncalves F, van de Luijtgaarden KM, Hoeks SE, et al. Adequate seal and no endoleak on the
first postoperative computed tomography angiography as criteria for no additional imaging up to 5
years after endovascular aneurysm repair. J Vasc Surg 2013; 57 (6): 1503–11.
16. Baderkhan H, Haller O, Wanhainen A, et al. Follow-up after endovascular aortic aneurysm repair can be
stratified based on first postoperative imaging. Br J Surg in press. 2018.
249
Tomographic ultrasound
measures associated
with abdominal aortic
aneurysm growth
Introduction
Abdominal aortic aneurysms are increasingly screen-detected with over 13,000
men with small aneurysms entering surveillance in the UK national aneurysm
screening programme (NAAASP) last year.1 The ability to predict growth would
allow individualised patient care with refined surveillance intervals.
Finite element analysis of aneurysm geometry acquired by computed tomography
(CT) imaging may be able to predict subsequent growth.2 However, as CT exposes
the patient to ionising radiation and nephrotoxic X-ray contrast, it would be
inappropriate for surveillance populations. Standard duplex ultrasound is entirely
safe and reliably measures diameter but cannot be used to analyse geometry. Three-
dimensional (3D) tomographic ultrasound (tUS) may be a novel way to capture
aneurysm geometry for finite element analysis.
Computed tomography
Computer modelling techniques using aneurysm geometry include finite element
analysis and analyses of fluid mechanics.3 Aneurysm volume, length and wall
thickness measured by CT may relate to growth and possibly to rupture risk.4–6
Ultrasound
Standard duplex is considered to be entirely safe but measures aneurysm diameters
approximately 2–5mm smaller than CT.7–9 As ultrasound was used to measure
aneurysms in the UK Small Aneurysm Trial and the Multicentre Aneurysm Screening
study, the indication for repair is based on diameter measured by ultrasound.10–11
Duplex measurement in two planes enables measurements of diameter, distensibility,
pulsatility, aneurysm and luminal thrombus cross-sectional areas.
Aneurysm diameter and growth has been widely studied. Meta-analyses describe
growth rates of 0.12cm/year and 0.35cm/year for aneurysms of 3.5cm and 4.5cm
diameter, respectively, with an average increase in growth rate of 0.59mm/year for
every 0.5cm increase in diameter (95% CI, 0.51–0.66).12,13
Distensibility describes the increase in volume caused by pulse pressure.14
Although real-time aortic volume and pressure measurements are not feasible,
standard duplex has been used to estimate distensibility using equations for pressure
251
strain elastic modulus and stiffness with reported intraobserver variabilities of
21.1% and 17.6%, respectively.15 Previous research suggests a negative association

between distensibility and growth but a positive one with risk of rupture.16–18
Pulsatility describes the increase in diameter or volume during systole and may
be more clinically relevant than distensibility.
Intraluminal thrombus measured as the cross-sectional surface area is associated
with a minor increase in growth rates.19–21
3D ultrasound (tUS)
Tomographic ultrasound (Piur imaging) requires only one sweep of the duplex
transducer to produce a 3D image, whereas standard duplex requires multiple
sweeps for the ultrasonographer to build up a mental image of the aneurysm. Thr
Tomographic ultrasound measures associated with abdominal aortic aneurysm growth •
modality, like CT, creates a 3D image that can be rotated, viewed from any angle
and analysed for data for geometry including radius of curvature.22 We have shown
that tUS may be a practical, safe and reliable alternative to CT for finite element
analysis and modelling fluid dynamics.23
Tomographic ultrasound uses electromagnetic tracking to capture every
ultrasound reflection from the area of interest. The tracking system can be attached
to any standard duplex system enabling ultrasound reflection to be orientated in
space (Figure 1). Specialist software is used for multiplanar reconstructions of the
entire image to produce the 3D image needed to measure aneurysm geometry
including diameter, area, volume, length, luminal thrombus and wall thickness.
Various 3D ultrasound measures (not tUS) have been shown to reduce the error
in diameter measurement compared with CT.24–26 3D ultrasound systems can
directly measure aneurysm volumes accurately, with strong correlations between CT
and 3D ultrasound (r=0.93, p<0.0001; and r=0.76, p<0.0001 in two studies).27,28
We explored whether tUS measures of aneurysm geometry were associated with
aneurysm growth rate in 128 patients in our aneurysm surveillance programme.
Figure 1: Piur tUS combines information from the duplex ultrasound system (left) and the sensors on the transducer
(right) to produce multiplanar reconstruction.
252
Patients

Consecutive patients (n=128) with small aneurysms, in which the growth rate had
already been measured for at least two years, were recruited from the surveillance
clinic at the University Hospital of South Manchester.
Methods
The aneurysm was imaged using the Mindray Resona 7 (Mindray) duplex ultrasound
with the addition of tUS for 3D image production. An experienced vascular scientist
acquired the images, after which all research measures were reported and calculated
by a different blinded vascular scientist to measure interobserver variability. Blood
pressure was recorded (supine) with a sphygmomanometer.
Maximum systolic and minimum diastolic inner-to-inner anterior-posterior
diameters were measured within a single cardiac cycle. Aneurysm diameter, area,
volume, length, luminal thrombus volume and wall volume were measured.
Pulsatility, distensibility and wall thickness were then calculated.
Pulsatility was calculated using the following formula:
Pulsatility (cm)=maxiumum systolic diameter-maximum diastolic diameter
Distensibility comprised of pressure strain elastic modulus (Ep) and stiffness (β)
that were calculated:
133.3(BP systolic – BP diastolic)

Ep (105 Nm-2)= ([Dmax systolic-Dmax diastolic]/Dmax diastolic)
naural logarithm(BP systolic/BP diastolic)

β (arbitary units)= ([Dmax systolic-Dmax diastolic]/Dmax diastolic)
Analysis
For the measurement of aneurysm, thrombus and wall volumes, the effective length
and, therefore, start and end of volume measurement were determined by the
diameter of the aorta. The start and endpoints of what was considered aneurysm
(as opposed to normal adjacent aorta) was determined by 1.5 times the normal
aortic diameter.
Tomographic ultrasound reconstructions were angle-corrected to avoid oblique
measurements. The ImFusion Suite software (ImFusion) was used to calculate
volumes/areas through segmentation. Segmentation is the process of drawing
around the outer surface, inner surface or luminal surface of free-flowing blood
in 1mm slices from the start to end of the aneurysmal aorta (Figure 2). This was
performed to calculate aneurysm, thrombus and wall volumes. Aneurysm and
thrombus cross-sectional area were measured at maximum inner-to-inner anterior-
posterior diameter. Wall thickness was measured in millimetres at the point of
maximal diameter.
Statistical analysis
Wall and thrombus volumes/area were corrected for aneurysm volumes/areas.
Pulsatility was corrected for systolic diameter.
253
Figure 2: Segmentation of the aneurysm
wall represented by an inner lumen

(aneurysm sac area) and outer wall
Figure 3: Correlation between diameter (cm) with growth

rate (cm/year). Diameter significantly correlates with
aneurysm growth (r=0.43, p<0.0001).
Figure 4: Correlation between volume (cm3) with growth

rate (cm/year). Volume significantly correlates with
aneurysm growth (r=0.46; p<0.0001).
Figure 5: Correlation between wall volume to aneurysm

ratio (this ratio was used to correct wall volume for
aneurysm volume) with growth rate (cm/year). Wall volume
significantly negatively correlates with aneurysm growth
(r=-0.43; p<0.0001).
254
Pearson’s (normally distributed data) or Spearman’s (non-normally distributed

data) correlation coefficient was used to assess intra-/interobserver variability and
the relationship between growth and ultrasound characteristics. A multivariate
linear regression model was used for diameter, volume and wall volume to assess
for independent association with growth.
Tomographic ultrasound relates to growth

Tomographic ultrasound imaging for geometry was undertaken in 128 aneurysm
surveillance patients of mean age 77.8 years with 97 men and 31 women. The
overall mean growth rate over the previous two years was 0.20cm/year with growth
rates of 0.12cm/year, 0.23cm/year and 0.30cm/year for small (3–4.4cm), medium
(4.5–5.4cm) and large (more than 5.5cm) aneurysms, respectively.
Wall thickness measured by standard duplex had poor intraobserver agreement.
The intraobserver agreement on all tUS measures was better than r=0.70.
Interobserver variability for systolic and diastolic diameter showed agreement of
r=0.97 with mean differences of -0.06cm and 0.13cm, respectively (less than the
interobserver variability of 0.3cm for standard ultrasound).29
Diameter and area

As expected, growth correlated closely with diameter (r=0.43) (Figure 3) and area
(r=0.42) (p<0.001).
Volume
Growth correlated more closely with volume (r=0.46, p<0.001) (Figure 4) than
diameter or area. Volume measured by tUS correlated closely with cross-sectional
area multiplied by length (r=0.97, p<0.001).

Wall volume
Measuring wall thickness using standard duplex proved unreliable, but wall volume
(corrected for volume) inversely related to growth (r=-0.43, p<0.001) (Figure 5).
wall volume did not relate to pulsatility (r=0.10, p=0.35).
Multivariate analysis of diameter, volume and wall volume

Diameter alone (r2adjusted=0.18, p<0.001) was independently associated with
growth. This association was improved by adding wall volume (r2adjusted=0.22,
p<0.001). However, the addition of aneurysm volume to wall volume and diameter
(r2adjusted=0.21, p<0.001) weakened the association suggesting that volume and
diameter are dependent variables.
Luminal thrombus volume

Aneurysm growth correlated weakly with thrombus volume (corrected for volume)
(r=0.27, p=0.015) and thrombus area (corrected for aneurysm area) (r=0.27,
p=0.0022). Again, the volume of thrombus did not influence pulsatility (r=-0.08,
p=0.49)
Pulsatility and distensibility

Pulsatility, strain distensibility and elastic distensibility all failed to correlate
significantly with growth with r=-0.05, p=0.56, r=0.09, p=0.35 and r=0.09; p=0.32
respectively.
255
Conclusion
Aneurysm growth most strongly related to volume and inversely to wall volume.
Tomographic ultrasound, which is inexpensive, quick and entirely safe, has proven
to be a novel modality for measuring geometry with reproducible and accurate
results. A surveillance programme that uses volume and wall volume may more
accurately identify patients at risk of rapid growth and potentially rupture.
Summary
• The number of patients with aneurysms entering surveillance in our national

screening programme is rising rapidly.
• CT can be used to capture geometry but the cumulative risks of ionising

radiation and nephrotoxic contrast prohibit its use in surveillance patients.
• If tUS measures of geometry predict growth, we will be able to use these
measures to develop individual patient management strategies.
• Growth was found to relate most closely to volume and inversely with wall
volume measured by tUS.
References
1. Public Health England. Abdominal aortic aneurysm screening: 2015 to 2016 data. England: Gov.uk;
2016.
2. Abeera A, Rizwan A, Alberto S, Matthew W. Can we predict abdominal aortic aneurysm (AAA)
progression and rupture by non-invasive imaging?—A systematic review. Int J Clin Med 2011; 2 (4):
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3. Morris PD, Narracott A, von Tengg-Kobligk H, et al. Computational fluid dynamics modelling in
cardiovascular medicine. Heart 2016; 102 (1): 18–28.
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with baseline volume and increasing finite element analysis-derived rupture risk. J Vasc Surg 2016; 63
(6): 1434–42.
5. Shang EK, Nathan DP, Woo EY, et al. Local wall thickness in finite element models improves prediction
of abdominal aortic aneurysm growth. J Vasc Surg 2015; 61 (1): 217–23.
6. Sacks MS, Vorp DA, Raghavan ML, et al. In vivo three-dimensional surface geometry of abdominal
aortic aneurysms. Ann Biomed Eng 1999; 27 (4): 469–79.
7. Chiu KW, Ling L, Tripathi V, et al. Ultrasound measurement for abdominal aortic aneurysm screening: a
direct comparison of the three leading methods. Eur J Vasc Endovasc Surg 2014; 47 (4): 367–73.
8. Manning BJ, Kristmundsson T, Sonesson B, Resch T. Abdominal aortic aneurysm diameter: a
comparison of ultrasound measurements with those from standard and three-dimensional computed
tomography reconstruction. J Vasc Surg 2009; 50 (2): 263–68.
9. Vidakovic R, Feringa HH, Kuiper RJ, et al. Comparison with computed tomography of two ultrasound
devices for diagnosis of abdominal aortic aneurysm. Am J Cardiol 2007; 100 (12): 1786–91.
10. Ashton HA, Buxton MJ, Day NE, et al. The Multicentre Aneurysm Screening Study (MASS) into the
effect of abdominal aortic aneurysm screening on mortality in men: a randomised controlled trial.
Lancet 2002; 360 (9345): 1531–39.
11. Powell JT, Brown LC, Forbes JF, et al. Final 12-year follow-up of surgery versus surveillance in the UK
small aneurysm trial. Br J Surg 2007; 94 (6): 702–08.
12. Powell JT, Sweeting MJ, Brown LC, et al. Systematic review and meta-analysis of growth rates of small
abdominal aortic aneurysms. Br J Surg 2011; 98 (5): 609–18.
13. Bown MJ, Sweeting MJ, Brown LC, et al. Surveillance intervals for small abdominal aortic aneurysms –
a meta-analysis. JAMA 2013; 309 (8): 806–13.
14. Van’t Veer M, Buth J, Merkx M, et al. Biomechanical properties of abdominal aortic aneurysms assessed
by simultaneously measured pressure and volume changes in humans. J Vasc Surg 2008; 48 (6): 1401–07.
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15. Wilson KA, Lee AJ, Hoskins PR, et al. The relationship between aortic wall distensibility and rupture of

infrarenal abdominal aortic aneurysm. J Vasc Surg 2003; 37 (1): 112–17.
16. Wilson K, Whyman M, Hoskins P, et al. The relationship between abdominal aortic aneurysm wall
compliance, maximum diameter and growth rate. Cardiovasc Surg 1999; 7 (2): 208–13.
17. Molacek J, Baxa J, Houdek K, et al. Assessment of abdominal aortic aneurysm wall distensibility with
electrocardiography-gated computed tomography. Ann Vasc Surg 2011; 25 (8): 1036–42.
18. Long A, Rouet L, Bissery A, et al. Compliance of abdominal aortic aneurysms evaluated by tissue
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19. Golledge J, Wolanski P, Parr A, Buttner P. Measurement and determinants of infrarenal aortic thrombus
volume. Eur Radiol 2008; 18 (9): 1987–94.
20. Brunner-Ziegler S, Hammer A, Seidinger D, et al. The role of intraluminal thrombus formation for
expansion of abdominal aortic aneurysms. Wien Klin Wochenschr 2015; 127 (13–14): 549–54.
21. Behr-Rasmussen C, Grondal N, Bramsen MB, et al. Mural thrombus and the progression of abdominal
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27. Arsicot M, Lathelize H, Martinez R, et al. Follow-up of aortic stent grafts: comparison of the volumetric
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257
Application of EndoAnchors
in EVAR short neck <10mm
Endovascular options for short infrarenal necks

About 20% of patients with infrarenal abdominal aortic aneurysm have neck
morphology that is unsuitable for standard enodovascular aneurysm repair (EVAR)
due to severe angulation, large diameter, or short neck length.1–4 Endovascular
alternatives that are available for unsuitable neck morphology include parallel
“chimney” stent grafting (chEVAR) and repair using fenestrated grafts (FEVAR).5
While the technique is associated with low rates of type Ia endoleaks, FEVAR is
limited to necks with infrarenal angulation less than 45 degrees and is not widely
available.6 Also, because grafts must be custom-made, the delay before a device
is ready precludes the urgent use of FEVAR. Parallel stent grafting, on the other
hand, involves the use of off-the-shelf stent grafts, allowing for quick intervention.
Although technical success of chEVAR is reported to be 98–100%, the procedure
is complex and may result in the development of the infamous gutter leaks.7–10
It also worth noting that both chEVAR and FEVAR carry a risk to visceral and
renal perfusion, especially if reintervention is required. While these techniques
provide less invasive repairs for patients with abdominal aortic aneurysms, they
have significant risks that decrease the durability of repairs.
Open repair remains a more durable option for repair of abdominal aneurysms
compared to EVAR, because it does not hold the same risk for concerning
complications such as endoleaks, graft migration, or late rupture.11–13 Nonetheless,
not all patients can withstand an open repair, and endovascular options have
marked benefits for patients.14 Heli-FX EndoAnchors (Medtronic) offer an off-the-
shelf endovascular technology that engages native aortic tissue to create a fixation
that has strength comparable to an open surgical anastomosis, augmenting the
proximal seal by securing an endograft to the vessel wall.15 By virtue of being
an endovascular technique that essentially simulates open surgical repair, use of
EndoAnchors in EVAR may provide a solution that is less invasive and simpler for
patients with short infrarenal necks.
EndoAnchors
The ANCHOR registry (Aneurysm treatment using the Heli-FX EndoAnchor
System global registry) has been enrolling EVAR patients since 2012 to evaluate
the safety and effectiveness of EndoAnchors in augmenting the fixation of stent
grafts to the aortic wall. In patients who underwent EndoAnchor placement for a
first-time EVAR and also in those who underwent a revision to treat a proximal
neck complication, results have been positive.16–18 Despite treating hostile neck
anatomy, studies have noted aneurysm shrinkage, low incidence of type Ia endoleak,
and no ruptured aneurysms up to one year after treatment with EndoAnchors.19
259
A C
B
Application of EndoAnchors in EVAR short neck <10mm
Figure 1: (A) Preoperative 3D of infrarenal aneurysm with a short, highly

angulated neck. (B) Intraoperative angiography of infrarenal neck. (C) Postoperative
angiogram showing complete exclusion of aneurysm sac with successful
EndoAnchor placement in the infrarenal neck.
Recently, the FDA approved an expansion of the indication to include their use
in conjunction with Endurant (Medtronic) or Endurant II/IIs stent grafts for
infrarenal neck lengths ≥4mm and <10mm.20 Use of EndoAnchors in EVAR for
short necks less than 10mm appears promising, and results from an evaluation of
the device in the short neck cohort will provide further insight into its safety and
efficacy for this aortic morphology.
Benefits and risks

Use of EndoAnchors in EVAR may reduce endoleak rates, reducing risk for
rupture.21 Rates of type I endoleaks as low as 0.6% after EndoAnchor have been
reported despite being used in hostile necks.16,22 EndoAnchors give clinicians the
additional advantage of being able to address type Ia endoleaks intraoperatively.
Using EndoAnchors in EVAR allows clinicians to avoid manipulations or
interventions involving renovisceral vessels by permitting stent grafts to be deployed
below the renal arteries even in short necks, thereby preserving perfusion. Primary
patency of renovisceral vessels is statistically similar in FEVAR and chEVAR, around
97% in FEVAR and 88%–96% in chEVAR.23–25 Studies of FEVAR and chEVAR
have found rates of postoperative renal impairment to be between 5.5% and 30%
for these procedures, with rates generally higher after chEVAR.5,7,26–27 In studies
of EndoAnchor patients, on the other hand, the highest rate of postoperative
260
renal complication is reported to be 5%, and most studies have not reported any

procedure-related renal complications.17
When choosing type of endovascular repair, it is important to consider potential
need for reintervention. A meta-analysis of chEVAR and FEVAR range found
reintervention rates were similar between the two types of repair, at 10% and
13.6%, respectively, compared with reintervention rates of 3.8%–5.6% in studies
of EndoAnchors.16,18,28 Reintervention following chEVAR or FEVAR may also be
complex and costly, due to the involvement of visceral and renal vessels as well as the
intricacy of maneuvering among the multiple grafts involved. Use of EndoAnchors
preserves all other ancillary and future EVAR options for patients, simplifying any
further interventions and allowing future use of proximal cuff, chEVAR, FEVAR,
or open repair.
Compared to traditional EVAR, use of EndoAnchors does represent a longer and
costlier repair. However, their use in patients with short neck anatomy is much less
costly than FEVAR or chEVAR, which both require additional devices, sheaths,
and catheters. Implantation of EndoAnchors is also relatively quick, around 15
minutes, reducing radiation exposure.29

Patient selection
Since EndoAnchors function by enhancing the seal between the stent graft and the
native aorta, it is necessary that patients have at least some neck below the renal
arteries. In patients with juxta-renal or pararenal aneurysms who do not have any
infrarenal neck, it will still be necessary to consider some alternative endovascular
Figure 2: Intraoperative imaging of EndoAnchor placement.
261
strategy to preserve flow to the renal and/or visceral arteries and provide an
adequate proximal seal. EndoAnchors are contraindicated in necks with excessive

calcification or thrombus since these impede the penetration of the device into
the aortic wall. Careful evaluation of neck morphology is necessary to determine
appropriate use of EndoAnchors, because some anatomic characteristics are
predictive of type Ia endoleak after EVAR with EndoAnchors.30 EndoAnchors are
indicated with Medtronic, Gore Excluder, Cook Zenith, and are contra-indicated
with Endologix grafts.
Technical application of technique

EndoAnchors are usually deployed after the standard EVAR procedures have been
completed. After the main EVAR device is recaptured and removed, a 16Fr sheath
is introduced to seal the arteriotomy and pushed all the way up to above the EVAR
flow divider. We prefer a dry-seal sheath. The obturator is removed and the Aptus
sheath is introduced and parked just above the renal arteries. Feeding the delivery
sheath through another larger sheath can ease concern regarding tortuosity while
deploying EndoAnchors, since it allows clinicians to torque the device through the
sheath without impacting the surrounding graft or vessels. Once the sheath is in
place, the wire and obturator are removed, and the stapling device is introduced.
This can be done off fluoroscopy, as there is a white marker to tell you when to
stop. We prefer to start a little higher than the desired area of placement, then start
deflecting the sheath and bringing the whole thing down until it is perpendicular
to the stent graft. In patients with more severe neck angulation, a contralateral
approach can facilitate proper positioning. We place the staples as proximally as
possible on the endograft (within the first 5mm) to simulate open repair
To get adequate fixation, it is necessary to maintain a 90-degree sheath position.
Once deployment has begun, it should be possible to see the stent graft moving
and feel the force of the stent graft pushing back on the catheter. The stapler is
pushed out, and gentle pressure is kept while firing the stapler. If the placement
of the EndoAnchor is satisfactory and it has clearly penetrated the stent graft,
the forward button is pushed one more time to ensure that it is secured prior to
releasing it. If the anchor position is not appropriate after the first firing attempt,
it is possible to recapture the endostaple by pushing the back button. Once the
placement of the EndoAnchor is complete, the sheath is straightened, and the
stapler removed to be reloaded with another staple. The recommended minimum
number of EndoAnchors is four in necks ≤29mm, and six for neck diameters
30–32mm.21 We prefer to place at least six staples. In terms of sizing, we usually
use the 22mm heli-FX in necks that are 18–28mm in diameter, and the 28mm
heli-FX for necks that are 28–32mm.
Conclusion
Abdominal aortic aneurysm with a short infrarenal neck is a complex morphology
whose best options for treatment are still being evaluated for short-term outcomes
and long-term durability. EndoAnchors may provide an endovascular option that is as
durable as open surgical repair and has fewer complications than FEVAR or chEVAR.
262
Summary
• Endovascular techniques for treating short infrarenal necks include parallel

chEVAR and repair using FEVAR).
• Use of EndoAnchors in EVAR is an endovascular technique that simulates open
surgical repair.
• EndoAnchors may provide benefits by reducing endoleak rates, avoiding
potential complications involving the renal arteries, and preserving future
endovascular options if reintervention is required.
• Careful evaluation of the infrarenal neck is required to ensure success of
EndoAnchor implantation.
• EndoAnchors may provide an endovascular option that is as durable as open
surgical repair and has fewer complications than FEVAR or chEVAR.

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264
Alternative access to control endoleak
controversies
Alternative access to control
endoleaks controversies—
transarterial
B Hawthorn, S Ameli-Renani and RA Morgan
Introduction
Endoleaks are the most common complication following endovascular aneurysm
repair (EVAR), requiring costly long-term surveillance and prompt reintervention
to prevent aneurysm rupture in some cases. Defined as persistent blood flow
within the aneurysm sac, endoleaks can be classified by the source of persistent
blood flow, which determines their clinical significance and influences subsequent
management. The vast majority of these complications can be treated successfully
with endovascular techniques and without the need for open surgery.
Type I endoleak
Type I endoleaks are encountered in up to 10% of patients following EVAR.1 They
are defined as a failure to create or maintain an adequate seal between the endograft
and the vessel wall, allowing blood to flow into the aneurysm sac. This can occur
at the proximal (type Ia) or distal (type Ib) attachment sites and may be detected
immediately following deployment of the endograft (primary) or during follow up
(secondary). Primary endoleaks occur as a result of an undersized or malpositioned
endograft, while secondary endoleaks are thought to be a consequence of endograft
migration or continuing aortic neck dilatation.
Primary endoleaks are more common with adverse aortic aneurysm anatomy. For
example, aneurysms with necks that are short (<15mm in length), wide (>28mm
in diameter) or severely angulated (>60 degrees) are more likely to develop this
complication following endograft deployment.2
Because there is direct pressurisation of the aneurysm sac by the aorta, there is a
risk of subsequent sac expansion and eventual rupture. There is, therefore, a general
consensus on the need for early reintervention for type I endoleaks.3
Standard endovascular treatment of type I endoleaks

The aim of treatment is to improve the seal between the endograft and the aortic
wall. Initially, balloon angioplasty of the proximal endograft can be performed. If
this fails to improve the seal, a large calibre balloon-expandable metal stent can
be deployed inside the endograft to increase its radial force. Aortic cuffs are used
to extend the length of the endograft proximally in case of a malpositioned or
undersized endograft results in inadequate proximal coverage.4
267
Figure 1: 81 year old male presenting
• B Hawthorn, S Ameli-Renani and RA Morgan
with a proximal type 1 endoleak: (A)

sagittal CT angiogram image shows an
endoleak adjacent to the posterior aspect
of the proximal endograft; (B) a reverse
angled catheter is positioned with its
tip in the endoleak entrance and an
“endoleakogram” accurately confirms the
size and morphology of the endoleak
cavity. Contrast also opacifies an exiting
lumbar vessel; (C) following placement
of a microcatheter in the inferior recess
of the endoleak cavity, embolisation is
performed with detachable coils and
Onyx; (D) post-embolisation, there is
complete filling of the endoleak cavity
with Onyx. Follow-up Duplex scan 15
months post-embolisation shows no
evidence of endoleak recurrence.
Alternative access to control endoleaks controversies—transarterial
Percutaneous transcatheter embolisation

In cases that are unsuitable for—or are refractory to—standard management,
transcatheter embolisation of the endoleak is an alternative treatment method that
is safe and feasible in most cases. The aim of treatment is to occlude arterial flow
within the perigraft space and, thereby, halt direct pressurisation of the sac. One
of the main indications for this alternative approach is adverse aortic anatomy (e.g.
type Ia endoleak with proximal landing zone dimensions that are unsuitable for
an aortic cuff). Type Ib endoleaks can usually be managed by balloon angioplasty
to increase apposition of the iliac limb to the artery wall or by extending distal
endograft coverage, and only rarely require embolisation.
Endoleak embolisation is performed via a femoral approach using local anaesthesia
at the puncture site and conscious sedation. A long access sheath (6Fr, 45cm)
is inserted into the aorta, with its tip just below the proximal end of the graft,
and a reverse shape curved catheter is used to engage the endoleak entrance (the
communicating space between the aorta and the endoleak cavity). A microcatheter
is advanced co-axially through the parent catheter into the endoleak cavity. At this
point, an “endoleakogram” is performed to better define the size and morphology
of the cavity and guide subsequent embolisation. Embolisation can be achieved
with a wide range of embolics but in our experience, is best performed initially
with detachable coils to form a “scaffold” within the cavity prior to use of a liquid
embolic agent such as ethylene vinyl alcohol copolymer (Onyx, Medtronic). Liquid
embolic agents are essential to achieve complete occlusion of the endoleak cavity
and avoid potential recurrence.
A wide endoleak entrance (e.g. >15mm) is an unfavourable anatomical
characteristic for embolisation due to the potential for reflux of liquid embolic
268
material into the aorta and consequent risk of non-target embolisation. A large

endoleak cavity (>30ml) is also considered unfavourable due to the large volume of
embolic material required and lesser probability of achieving complete occlusion.
Conversely, very small endoleak cavities are difficult to treat successfully. In such
cases, embolisation is often deferred until surveillance scans demonstrate more
favourable endoleak anatomy.5 Embolisation of type 1a endoleaks has been shown
to be a safe and feasible treatment option in patients who are unsuitable for standard
treatment methods. We have recently published mid-term outcome data for our
cohort of 25 embolisation cases.5 Embolisation using Onyx with or without coils
was technically successful in all cases. During the average follow-up time of 311
days, seven patients developed recurrent endoleak. Endoleak recurrence was more
common when embolisation was performed using Onyx alone than when using
coils and Onyx together.
Type II endoleak
Type II endoleaks are the most common type of endoleak following EVAR,
occurring in 10–30% of patients.10,11 They occur as a result of retrograde flow in
a patent aortic side-branch into the aneurysm sac, most commonly the inferior
mesenteric and lumbar arteries. There is usually low flow via small calibre
anastomotic connections and the aneurysm sac is, therefore, not directly pressurised

by the aorta. The majority of aneurysms with associated type II endoleaks will
remain stable or decrease in size, and feeding vessels may thrombose spontaneously.
Consequently, there is no need for expeditious treatment of type II endoleaks and
most operators advocate intervention only if there is an enlarging sac diameter (≥
5mm) on surveillance imaging.12,13
In cases with an expanding sac size, it is important to exclude an occult type
I or type III endoleak disguised as a type II. In such cases, opacifed aortic side
branches may simply be acting as exit vessels rather entrance vessels. If computed
tomography (CT) imaging is inconclusive, catheter aortography (sometimes
combined with cone-beam CT) can be used to confirm the source of an endoleak
and help plan access for embolisation.
Transarterial embolisation
Transarterial embolisation is the basis of treatment for type II endoleaks, and the
purpose of intervention is to occlude the endoleak cavity and feeding vessels. The
specific embolisation technique depends on the anatomy of the feeding arteries.
Transarterial embolisation of the dominant feeding vessel is the most commonly
employed approach. This technique requires a navigable route from the vessel origin,
via collaterals to the feeding vessel and endoleak cavity. The technical success of
this approach is limited if the responsible feeding vessel cannot be cannulated or if
a viable path to the endoleak cavity cannot be found.14‒16
Retrograde filling via the inferior mesenteric artery can usually be treated by
catheterising the superior mesenteric artery and navigating through the arc of Riolan
or other middle colic and marginal artery branches. This technique is performed
under conscious sedation via femoral access, with local anaesthesia administered at
the access site. A long access sheath (6Fr, 45cm) is placed with its tip just below
the origin of the superior mesenteric artery. A reverse shape curved catheter is
used to engage that artery and an angiogram is performed to confirm filling of
269
the endoleak cavity and to provide an arterial map for access to the cavity. Over a
wire, the parent catheter is advanced as far as possible into the middle colic artery
before a microcatheter is used to negotiate through the arterio-arterial anastomosis
and into the inferior mesenteric artery and endoleak cavity. In our practice, as with
type I endoleaks, embolisation is best performed with a combination of detachable
coils to form a “scaffold” within the cavity prior to use of a liquid embolic agent.
A liquid embolic agent is useful for accomplishing complete occlusion of the
endoleak cavity.17,18
Type II endoleaks arising from lumbar arteries can be treated by accessing
iliolumbar branches arising from the internal iliac artery. A short 6Fr access
sheath is placed in the ipsilateral femoral artery and an angled catheter is used
to catheterise the internal iliac artery. After angiography, a microcatheter is used
to navigate through the ascending iliolumbar artery, into the lumbar artery and
into the endoleak cavity. These vessels are tortuous and small in calibre, making
this technique challenging, with a lesser probability of successfully accessing
the endoleak. If the endoleak cavity cannot be accessed, it may be feasible to
successfully embolise the endoleak by injecting a low viscosity Onyx (Onyx 18)
from a more proximal location. The low viscosity Onyx may flow gradually into
the endoleak cavity. However, proximal embolisation of the iliolumbar artery itself
without occlusion of the endoleak cavity usually results in recurrence developing as
a result of other collateral vessels, which may supply the endoleak cavity.
Good technical and clinical success rates have been widely reported for this
technique. The short- and mid-term technical and clinical results are respectable
in most series. However, from the limited data available, some studies report less
favourable long-term results. One cohort of 95 patients treated with embolisation
(predominantly transarterial but including some other techniques) showed 81.5%
freedom from aneurysm sac expansion at one year but a significant decrease in this
figure to 43.7% at five years, with an associated increase in the number of repeat
embolisation procedures required.19
The high failure rate reported after transarterial embolisation may in part be
due to failure to completely occlude the endoleak cavity and may reflect the
shortcomings of earlier techniques (e.g. performing embolisation using coils alone
without liquid embolic agents, or embolisation of the feeding vessels without
occlusion of the endoleak cavity).
As previously mentioned, transarterial access via the dominant feeding vessel
may not always be possible. In such cases, other techniques may achieve access to
the endoleak cavity for embolisation.
Transiliac para-endograft embolisation

This is a novel technique for treatment of type II endoleaks that cannot be accessed
by a standard approach. This technique offers the advantage of avoiding general
anaesthesia and can be performed in the same session as an attempt at conventional
transarterial embolisation. Prior CT imaging is reviewed initially, to specifically
assess the degree of apposition between the distal aspect of each of the endograft’s
iliac limbs and the artery wall. The area with least apposition between the iliac limb
and the artery wall is targeted for access. The technique is performed via ipsilateral
retrograde femoral access and a short 6Fr sheath is inserted with its tip just distal to
the end of the iliac limb. An angled catheter and a straight hydrophilic guidewire
are used to gain access into the para-endograft space and are then advanced
270
superiorly between the graft and the artery wall until they enter the aneurysm sac.

Standard catheter and wire manipulations are used until there is blood flow from
the catheter, confirming access into the endoleak cavity. A microcatheter is inserted
coaxially through the parent catheter and an “endoleakogram” is performed to
assess the cavity anatomy and to plan subsequent embolisation. A liquid embolic
agent is used to completely fill the endoleak cavity and may or may not reflux into
the feeding arteries.
Coppi et al published their experience and outcomes using the transiliac para-
endograft approach in 2014. In 16 of 17 attempts, the aneurysm sac was successfully
accessed using this technique. They reported one case of intraoperative type Ib
endoleak as a complication of para-endograft access using a 9Fr sheath.20 In this
author’s experience, para-endograft access with a 4/5Fr catheter alone or a 6Fr sheath
is technically sufficient and minimises the risk of procedural type IB endoleaks.21
Direct percutaneous puncture of the aneurysm sac

Direct percutaneous puncture of the aneurysm sac is performed under general
anaesthesia.22 Prior CT imaging is initially reviewed to plan the approach to the
endoleak cavity with reference to fluoroscopic landmarks. Access is usually via a
left posterolateral trans-lumbar approach to avoid inadvertent injury to the inferior
vena cava. Under fluoroscopic guidance, a 20G Chiba needle is advanced until there
is brisk, pulsatile blood flow through the needle, indicating a satisfactory position

within the endoleak cavity. An angiogram is performed to depict the anatomy of
the endoleak and plan subsequent embolisation. A super stiff guidewire is inserted
and the Chiba needle is exchanged for a 6Fr short sheath and 4/5Fr catheter. If
possible, the feeding vessels are selectively catheterised and embolised. In any case,
the endoleak cavity is embolised completely using a liquid embolic agent.
Figure 2: 84-year-old male

presenting with type II endoleak
and significant sac expansion. The
endoleak arises from a lumbar
artery and is not amenable
to transarterial embolisation.
(A) Cone-beam CT aortogram
demonstrates an endoleak at the
right posterolateral aspect of the
aneurysm sac; (B) “Endoleakogram”
performed after fluoroscopically-
guided right translumbar puncture
of the endoleak using a Chiba
needle. This confirms the size and
morphology of the endoleak cavity
and the feeding lumbar artery; (C)
the needle is exchanged for a 6Fr
sheath and 5Fr catheter over a stiff
wire; and (D) post-embolisation
with detachable coils and Onyx
there is complete filling of the
endoleak cavity. Follow up Duplex
scan at three months post-
embolisation shows no evidence of
endoleak recurrence.
271
A systematic review of 32 studies, comprising a total of 393 interventions for
type II endoleaks, compared outcomes for direct sac puncture and transarterial
embolisation. It found that direct sac puncture had a higher success rate (81%
vs. 62.5%), fewer cases of endoleak recurrence (19% vs 35.8%) and a lower
complication rate (0% vs 9.2%) when compared with transarterial embolisation.23
However, this review includes data from non-randomised, retrospective studies
using a variety of techniques and embolic agents. Its overall conclusion, which is
that direct sac puncture is more effective than transarterial embolisation, is open
to question.
Transcaval embolisation
Embolisation of type II endoleaks has also been performed using a transcaval
approach. Transcaval access is achieved using an angled tip catheter and an angled
sheathed needle (e.g. transjugular intrahepatic portosystemic shunt [TIPS] or
transjugular liver biopsy set) to penetrate the inferior vena cava wall and enter
the endoleak cavity. This method is not commonly practised and there is limited
published data. Mansueto and colleagues have published outcomes for a small
cohort of 12 patients treated using a transcaval approach.24 The procedure was
technically successful in 11 of 12 attempts. At one year follow up, no recurrent
endoleak was present and sac diameter was reduced in 10 of 11 patients.
Surgery is generally a treatment of last resort and is rarely required unless the
above techniques have failed to control the endoleak. Surgical options include
laparoscopic clipping of the lumbar or inferior mesenteric arteries, surgical fixation
of the endograft to the aortic wall or open aneurysmectomy.25
Type III endoleak

Type III endoleak is a relatively uncommon complication. The incidence of this
complication is significantly higher with first and second generation endografts
(12.7%) when compared to modern third generation endograft designs (1.2%).26
Adverse aortic anatomy, such as severe angulation of the neck or iliac components
may increase the risk of subsequent type III endoleak.4
The endoleak results from a structural defect within the endograft; in type IIIa
endoleaks, blood flows from the aorta into the aneurysm sac via a space between
disconnected modular components, whereas type IIIb endoleaks result from a tear
in the graft material. As with type I endoleaks, expeditious treatment is required
because there is direct pressurisation of the aneurysm sac by the aorta and a risk of
subsequent sac expansion and eventual rupture.
Type III endoleaks are treated by deploying a new endograft or cuff within the
pre-existing graft, thereby sealing the structural defect.
Type IV endoleak
This phenomenon is observed following initial endograft deployment at the time
of completion angiogram and is related to the porosity of some older endograft
designs. Type IV endoleaks are rarely encountered now but are self-limiting and do
not require intervention.
272
Type V endoleak

Type V endoleak, also referred to as “endotension” can be defined as an increase
in aneurysm sac size in the absence of an identifiable endoleak. This is a poorly
understood but largely historical entity relating to a specific older generation
endograft design.
Summary
• An understanding of the mechanism and dynamics of each type of endoleak is

important in deciding the need for intervention.
• Endovascular techniques are the mainstay of treatment for endoleaks with
surgery reserved as an option of last resort.
• Percutaneous transcatheter embolisation of type I endoleaks is a safe and
feasible alternative treatment if standard therapeutic options are unsuitable or
have failed.
References
1. Van Marrewijk C, Buth J, Harris PL, et al. Significance of endoleaks after endovascular repair of

abdominal aortic aneurysms: The EUROSTAR experience. J Vasc Surg 2002; 35 (3): 461–73.
2. Chen J, Stavropoulos SW. Management of Endoleaks. Semin Intervent Radiol 2015; 32(3):259–64.
3. Green N, Sidloff D a., Stather PW et al. Endoleak after endovascular aneurysm repair: Current status.
Rev Vasc Med 2014; 2 (2): 43–47.
4. Rosen RJ, Green RM. Endoleak management following endovascular aneurysm repair. J Vasc Interv
Radiol 2008; 19 (6 Suppl): S37–S43.
5. Ameli-Renani S, Pavlidis V, Morgan RA. Early and midterm outcomes after transcatheter embolization
of type I endoleaks in 25 patients. J Vasc Surg 2017; 65 (2): 346–55.
6. Golzarian J, Struyven J, Abada HT, et al. Endovascular aortic stent-grafts: transcatheter embolization of
persistent perigraft leaks. Radiology 1997; 202 (3): 731–34.
7. Golzarian J, Maes EB, Sun S. Endoleak: Treatment options. Tech Vasc Interv Radiol 2005; 8 (1 SPEC. ISS.):
41–49.
8. Henrikson O, Roos H, Falkenberg M. Ethylene vinyl alcohol copolymer (Onyx) to seal type 1 endoleak.
A new technique. Vascular 2011; 19 (2): 77–81.
9. Eberhardt KM, Sadeghi-Azandaryani M, Worlicek S, et al. Treatment of type I endoleaks using
transcatheter embolization with onyx. J Endovasc Ther 2014; 21 (1): 162–71.
10. Nevala T, Biancari F, Manninen H, et al. Type II endoleak after endovascular repair of abdominal aortic
aneurysm: effectiveness of embolization. Cardiovasc Intervent Radiol 2010; 33 (2): 278–84.
11. Warrier R, Miller R, Bond R, et al. Risk factors for type II endoleaks after endovascular repair of
abdominal aortic aneurysms. ANZ J Surg 2008; 78 (1-2): 61–63.
12. Ozdemir BA, Chung R, Benson RA, et al. Embolisation of type 2 endoleaks after endovascular aneurysm
repair. J Cardiovasc Surg (Torino) 2013; 54 (4): 485–90.
13. Chung R, Morgan RA. Type 2 Endoleaks Post-EVAR: Current Evidence for Rupture Risk, Intervention
and Outcomes of Treatment. Cardiovasc Intervent Radiol 2015; 38 (3): 507–22.
14. Hongo N, Kiyosue H, Shuto R, et al. Double coaxial microcatheter technique for transarterial aneurysm
sac embolization of type II endoleaks after endovascular abdominal aortic repair. J Vasc Interv Radiol
2014; 25 (5): 709–16.
15. Abularrage CJ, Patel VI, Conrad MF, Schneider EB, Cambria RP, Kwolek CJ. Improved results using Onyx
glue for the treatment of persistent type 2 endoleak after endovascular aneurysm repair. J Vasc Surg
2012; 56 (3): 630–36.
16. Aziz A, Menias CO, Sanchez LA, et al. Outcomes of percutaneous endovascular intervention for type II
endoleak with aneurysm expansion. J Vasc Surg 2012; 55 (5): 1263–67.
17. Martin ML, Dolmatch BL, Fry PD, Machan LS. Treatment of type II endoleaks with Onyx. J Vasc Interv
Radiol 2001; 12 (5): 629–32.
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18. Chung R, Morgan R. Technical Note: “Remote” Transarterial Embolisation Technique of Lumbar Artery
Type 2 Endoleaks with Onyx. EJVES Extra 2014; 27 (4): e32–33.

19. Sarac TP, Gibbons C, Vargas L, et al. Long-term follow-up of type II endoleak embolization reveals the
need for close surveillance. J Vasc Surg 2012; 55 (1): 33–40.
20. Coppi G, Saitta G, Coppi G, et al. Transealing: a novel and simple technique for embolization of type 2
endoleaks through direct sac access from the distal stent-graft landing zone. Eur J Vasc Endovasc Surg
2014; 47 (4): 394–401.
21. Ameli-Renani S, Pavlidis V, Mailli L,et al. Transiliac Paraendograft Embolisation of Type 2 Endoleak: An
Alternative Approach for Endoleak Management. Cardiovasc Intervent Radiol 2016; 39 (2): 279–83.
22. Baum RA, Carpenter JP, Golden MA, et al. Treatment of type 2 endoleaks after endovascular repair
of abdominal aortic aneurysms: Comparison of transarterial and translumbar techniques. J Vasc Surg
2002; 35 (1): 23–29.
23. Sidloff DA, Stather PW, Choke E, et al. Type II endoleak after endovascular aneurysm repair. Br J Surg
2013; 100 (10): 1262–70.
24. Mansueto G, Cenzi D, Scuro A, et al. Treatment of type II endoleak with a transcatheter transcaval
approach: results at 1-year follow-up. J Vasc Surg 2007; 45 (6): 1120–27.
25. Jouhannet C, Alsac J-M, Julia P, et al. Reinterventions for type 2 endoleaks with enlargement of the
aneurismal sac after endovascular treatment of abdominal aortic aneurysms. Ann Vasc Surg 2014; 28
(1): 192–200.
26. Maleux G, Poorteman L, Laenen A, et al. Incidence, etiology, and management of type III endoleak
after endovascular aortic repair. J Vasc Surg 2017; 66 (4): 1056–64.
274
The transarterial approach for
treatment of type II endoleaks
SA Mehta and RG McWilliams
Introduction
Endoleak is defined as persistent blood flow within an aneurysm after endovascular
aneurysm repair (EVAR). Endoleaks are classified into five types depending on
the source of perfusion—type II endoleak relates to aneurysm perfusion through
patent branch vessels and is further divided into type IIa (single patent branch)
or IIb (two or more patent branches), which are also known as communicating
type II endoleaks; type II is the most common type of endoleak. In a recent
meta-analysis, a pooled prevalence of 22% was seen across 45 studies with a total
of 36,588 participants.1 This chapter will deal with endovascular approaches to
type II endoleak treatment post-EVAR for abdominal aortic and iliac aneurysms,
specifically the transarterial route to embolisation through arterial collaterals and
access to the sac using a peri-graft approach.
Transcollateral approach
Anatomy
Large patent lumbar arteries and the inferior mesenteric artery are the aortic
branches that are the most commonly affected by type II endoleaks. Less commonly
seen sources include the median sacral artery and accessory renal arteries.
Treatment of type II endoleaks entails embolisation of the patent component
of the aneurysm sac as well as occlusion of the feeding vessel. Treatment of type
IIb endoleaks ideally entails occlusion of all inflow and outflow branches, though
this is often not possible. Successful treatment of type IIa endoleaks is sometimes
possible with coil embolisation of the patent single aortic branch at the level of the
aneurysm without additional embolisation of the endoleak cavity.
Inferior mesenteric artery

The most common approach to an inferior mesenteric artery endoleak is through
the superior mesenteric artery via the Arc of Riolan, which connects the middle
colic branch of the superior mesenteric artery to the left colic branch of the inferior
mesenteric artery.
An alternative arterial anastomosis involves the superior rectal artery, which is
a terminal branch of the inferior mesenteric artery. This vessel anastomoses with
the middle rectal (from the anterior division of the internal iliac artery) and the
inferior rectal branch of the internal pudendal artery (itself a branch of the anterior
division of the internal iliac artery).
275
• SA Mehta and RG McWilliams
The transarterial approach for treatment of type II endoleaks
Figure 1: (A/B) Consecutive frames from superior mesenteric artery angiographic run showing inferior mesenteric
artery endoleak due to collateral flow through the arc of Riolan; (C) arteriogram demonstrates the collateral pathway
between the lateral and median sacral arteries contributing to a type II endoleak; and (D) inadvertent selective
catheterisation of the inferior rectal artery (*) via the middle rectal artery.).
While not typically used as an alternative route for inferior mesenteric artery
embolisation, it is important to remember this pelvic arterial communication can
be inadvertently catheterised when attempting to select the lateral sacral to median
sacral pathway
Lumbar arteries
The target vessels are usually the third and fourth lumbar arteries. These may arise as
paired vessels from the dorsal surface of the aorta, or the fourth lumbar arteries may
arise as a common trunk sometimes in combination with the median sacral artery.
The most common route to the lumbar arteries is through the iliolumbar artery. This
arises from the posterior division of the IIA in 96.3% of cases.2 The deep circumflex
iliac branch of the distal external iliac artery may provide another route to a lumbar
endoleak via its anastomoses with the iliolumbar and fourth lumbar arteries.
276
Figure 2: (A) Oblique CT reconstruction showing the origin of the iliolumbar artery (*); (B) Tube angulation during
embolisation is based on the CT anatomy, allowing rapid demonstration of the iliolumbar (*) artery.).
Preoperative scrutiny of the computed tomography (CT) images is invaluable to

understand the anatomy and position of the iliolumbar artery and determine the
tube angulation required to demonstrate it and the catheter combinations required
for a successful procedure.

Median sacral artery
The median sacral artery arises as a single branch from the posterior surface of the
aorta just above the bifurcation. This vessel anastomoses with the iliolumbar artery
as well as with lateral sacral branches of the posterior division of the internal iliac.
It may arise from a common stem with the fourth lumbar arteries.
Figure 3: (A–C) Axial images from enhanced CT scan showing endoleak supplied by a hypertrophied median
sacral artery. The anastomosis with the lateral sacral artery is clearly demonstrated; (D) angiographic image
shows the lateral to median sacral anastomosis which supplies the endoleak.
277
Catheterisation of the median sacral artery is possible via the anastomosis with
the lateral sacral branch of the internal iliac artery. This possible route should be
looked for when a hypertrophied median sacral artery is the source of an endoleak.
Percutaneous access to superior gluteal artery

The superior and inferior gluteal arteries arise from the posterior division of the
internal iliac artery. These vessels course through the greater sciatic notch to leave
the pelvis, travelling along the superior and inferior borders of the pyriformis
muscle.3 Accessing these vessels will allow retrograde cannulation of the internal
iliac artery and its branches, and can be used to treat type II endoleaks following
stent grafting across an aneurysmal internal iliac artery. Puncturing the vessel
beyond the greater sciatic notch avoids the chance of injury to other vascular or
nervous structures in this region. The puncture itself has been described by various
techniques, including open surgery, ultrasound and CT guidance and under
fluoroscopic control.3–6 Haemostasis has been achieved with coil embolisation of
the vessel entry point, or by injecting gel foam slurry into the sheath tract, both
along with manual compression.
Procedure planning
It is crucial to study the preoperative CT angiography in detail to identify the
arterial anatomy. The CT angiography will identify the ideal tube angulation
required to profile the origins of target vessels, which can help to reduce procedure
time and improve success rates. The angle of vessel take-off will also allow proper
hardware selection, as certain catheter shapes may be more conducive to quick
vessel cannulation. One study has reported on the use of dual-phase cone beam
CT and automatic vessel detection software in embolisation for type II endoleaks
in 10 patients.7 It found that dual-phase cone beam CT detected the endoleak
and automatic vessel detection identified the feeding branch in all cases. This
study suggested the utility of automatic vessel detection in cases with complex and
challenging anatomy.
Very often the procedure is performed with a triple co-axial method using a long
sheath, particularly for the superior mesenteric artery, with a 4Fr catheter selectively
cannulating the middle colic artery. Negotiating the 4Fr catheter far into this vessel
increases stability and frees greater length of the microcatheter, which may sometimes
be required to negotiate the tortuous anastomotic pathways to reach the endoleak
nidus. Commonly used devices include the 2.4–2.7 Fr Progreat (Terumo) and the
2.4–2.8 Fr Renegade (Boston Scientific). Smaller devices such as the Echelon-14
(Medtronic) may be used, but will not allow the use of 0.018” coils.
Peri-graft approach
This technique, also known as transealing, involves advancing a sheath or catheter
between the wall of the common iliac artery and the graft limb to reach the endoleak
nidus.8 As described by Coppi et al, aneurysms with sealing zones in the external
iliac arteries are not suitable for this approach due to the risk of dissection with or
without rupture. A catheter is placed against the lip of the iliac limb of the device,
278
Figure 4: (A, B) Peri-graft angiogram demonstrates endoleak lumbar artery inflow and accessory left
renal artery outflow.

and a wire forced into the space between the graft and the vessel wall. This wire is
advanced up to the nidus and is followed by a 5–6 Fr sheath. Aspiration of blood
confirms position within the nidus. The sheath can then be used to introduce a
suitable catheter to perform the embolisation.
Coppi et al have described the use of a Piton GC catheter (Medtronic).8 A
robotic catheter such as the Magellan (Hansen Medical) may be used as a bailout
device where available when standard devices are unsuccessful.9 Following sac
embolisation, the limb used for access is ballooned and an angiogram performed to
exclude types I and III endoleaks.
Coppi et al reported technical success in 16 of 17 cases (94.1%). One patient
(5.9%) required an iliac limb extension for a type Ib endoleak post-transealing.
One major complication (5.9%) was seen involving colon ischaemia caused by
embolisation through the inferior mesenteric artery requiring bowel resection and
permanent stoma.8
Choice of embolic agent

Over the years different workers have used various materials for endoleak
embolisation, including N-butyl cyanoacrylate (NBCA) glue, coils and Onyx
(Medtronic) either alone or in combination.
Coil embolisation alone, using either pushable or detachable coils, has been used
for endoleak treatment. In selected patients who have only a single vessel providing
inflow and outflow, type IIA endoleak, coil embolisation of the culprit vessel itself
without any specific treatment for the nidus can prove to be successful.
However, in a study published by Baum et al, 16 of 20 (80%) transarterial
inferior mesenteric artery endoleaks that underwent coil embolisation failed over
time. Interestingly, 13 of these patients had a negative CT angiography with
resolution of the endoleak at 30 days, which reappeared on subsequent follow-up.10
Sarac et al reported that use of coils alone resulted in more secondary procedures.11
NBCA glue has long been used in treatment of type II endoleaks, both as a single
agent and in conjunction with other embolics. NBCA polymerises upon contact
279
Figure 5: (A, B) Type IIA endoleak treated by embolisation of the stem of the inferior
mesenteric artery; (C, D) Pre-embolisation ultrasound image showing patent echo poor cavity
which thrombosed following embolisation.
with any ionic solution, including blood. Use of NBCA requires flushing the
microcatheter thoroughly with dextrose solution to prevent device blockage. NBCA
polymerises much more rapidly than Onyx and, after delivery, the microcatheter is
pulled back rapidly from the site of embolisation to prevent adherence to the glue
cast. Use of multiple doses requires multiple microcatheters, which can be achieved
using the triple co-axial method described above.
Onyx is a liquid embolic agent consisting of ethylene vinyl alcohol (EVOH)
copolymer dissolved in dimethyl sulfoxide (DMSO) which is an organic solvent. It
is available in different concentrations, for use in differing vascular beds. Onyx-18
(6%) EVOH is less dense and is preferred for thinner tortuous vessels. Onyx-34
(8%) EVOH is more viscous and can be used to create a plug to contain the
embolic agent. Upon contact with the blood stream, DMSO washes away and the
Onyx starts to polymerise. Onyx should only be used with DMSO compatible
microcatheters. Once the microcatheter has reached a stable and satisfactory
position, it is flushed with a volume of DMSO equivalent to its dead-space.
Onyx is then injected slowly through the microcatheter. If the procedure is being
performed under local anaesthesia or conscious sedation, it is important to let the
patient know to expect some pain when the DMSO hits the blood stream. Onyx
should be injected slowly under fluoroscopic, roadmap or angiographic control. It
is important to be aware of the screening time and patient and operator radiation
280
doses during these procedures, as often they involve significant tube angulation and

magnification. The use of close beam collimation and decreasing fluoroscopy and
DSA frame rates is suggested.
Abularrage et al reported 68 interventions in 51 patients with persistent type II
endoleaks and sac expansion.12 Onyx showed a 91% long term success rate (10 of
11 patients) compared with 23% (9 of 40 patients) for coils and NBCA used in
initial treatment. However, there was no difference in success rates when multiple
secondary interventions were required (50% vs 50%).
Complications
The treatment of type II endoleak is associated with a low rate of complications.
Sarac et al reported mesenteric ischaemia in two patients, with individual cases of
access site pseudoaneurysm, renal perforation, aspiration pneumonia, multisystem
organ failure, catheter sepsis, lumbar plexopathy (from excess NBCA glue
overflowing into lumbar collateral vessels) and severe acute claudication in a review
of 140 procedures.11 Haulon et al in a study of 18 patients reported one case of
asymptomatic thrombosis of the mesenteric arch of the mesocolon. Three of 18
patients developed low back pain without neurological signs, which resolved with

simple analgesia.13
Outcomes
The transarterial route has historically been the standard technique for endoleak
management, and is still widely practised today. However, several studies have
shown the translumbar route to have higher success rates with shorter procedure
times. Baum et al compared 33 angiographically proven type II endoleaks in 19
patients, treated with either transarterial (20) or translumbar (13) embolisation.
Sixteen of 20 inferior mesenteric artery embolisations showed persistent type II
endoleaks at six month follow-up CT angiography, compared to one failure in the
translumbar cohort.10 Nine patients that failed with the transarterial approach had
subsequent translumbar treatment. In every case the inferior mesenteric artery was
occluded; however, the aneurysm was being perfused through additional lumbar
feeders. In comparison, 12 of 13 (92%) translumbar cases had a durable result.
They postulated that type II endoleaks behave like arteriovenous malformations,
and therefore embolisation of only the feeding vessel is less likely to achieve
durable clinical success. It is to be noted that this study used only coil embolisation
without the use of liquid embolics which are more prevalent today.
Several workers have questioned the need for intervention in type II endoleaks.
Hajibandeh et al reviewed the literature to identify the evidence supporting
continued surveillance or aggressive treatment in these cases. They concluded that
current evidence is heterogeneous and based largely on retrospective case series.
However, at present a conservative approach may be appropriate in cases without
sac expansion, as 35–75% of T2EL resolve spontaneously.14
One large multicentre registry retrospective review evaluated outcomes in 1,736
patients post-EVAR, 474 (27.3%) of whom developed type II endoleaks. They
found that patients managed conservatively for these had similar aneurysm-related
outcomes compared to patients who underwent reintervention.15
281
Sidloff et al conducted a systematic review which included 32 non-randomised
retrospective studies totalling 21,744 EVAR cases with 1,515 type II endoleaks.
Only 14 patients (0.9%) with isolated type II endoleaks developed an abdominal
aortic aneurysm rupture, over a third of whom (6) did not have sac expansion.
They also found that translumbar treatment had a higher clinical success rate (81
vs. 62.5%), lower recurrence (19% vs. 35.8%) and a lower complication rate (0%
vs. 9.2%).16
Summary
• The commonest sources of type II endoleaks are patent inferior mesenteric

Transarterial approach for treatment of type II endoleaks
and lumbar arteries. Understanding the collateral and anastomotic pathways

allows treatment of these endoleaks via a transarterial approach.
• Percutaneous access to the superior gluteal artery is a described treatment for
internal iliac artery aneurysm endoleak.
• Transealing embolisation is a potential treatment option in selected cases.
• Careful and detailed preoperative procedure planning, based on the CT
angiography, guides catheter selection and helps to reduce procedure time
and radiation dose.
• While multiple embolic agents have been used historically, Onyx has been
shown to have a high success rate.
• The translumbar approach may result in greater clinical success rates.
• Not all type II endoleaks require treatment, with a large proportion resolving
spontaneously.
References
1. Guo Q, Du X, Zhao J, et al. Prevalence and risk factors of type II endoleaks after endovascular aneurysm
repair: A meta-analysis. PloS one 2017; 12 (2): e0170600.
2. Chen RS, Liu YX, Liu CB, et al. Anatomic basis of iliac crest flap pedicled on the iliolumbar artery.
Surgical and radiologic anatomy. SRA1999; 21 (2): 103–07.
3. Magishi K, Izumi Y, Tanaka K, et al. Surgical access of the gluteal artery to embolize a previously
excluded, expanding internal iliac artery aneurysm. Journal of Vascular Surgery 2007; 45 (2): 387–90.
4. Herskowitz MM, Walsh J, Jacobs DT. Direct sonographic-guided superior gluteal artery access for
treatment of a previously treated expanding internal iliac artery aneurysm. Journal of Vascular Surgery
2014; 59 (1): 235–37.
5. Kabutey NK, Siracuse JJ, Gill H, et al. Percutaneous transgluteal coil embolization of bilateral internal
iliac artery aneurysms via direct superior gluteal artery access. Journal of Vascular Surgery 2014; 60
(1): 226–29.
6. Werner-Gibbings K, Rogan C, Robinson D. Novel Treatment of an Enlarging Internal Iliac Artery
Aneurysm in Association with a Type 2 Endoleak via Percutaneous Embolisation of the Superior
Gluteal Artery through a Posterior Approach. Case Reports in Vascular Medicine 2013: 861624.
7. Ierardi AM, Pesapane F, Rivolta N, et al. Type 2 endoleaks in endovascular aortic repair: cone beam CT
and automatic vessel detection to guide the embolization. Acta radiologica (Stockholm, Sweden: 1987.
2017:284185117729184.
8. Coppi G, Saitta G, Gennai S, et al Transealing: a novel and simple technique for embolization of type
2 endoleaks through direct sac access from the distal stent-graft landing zone. European Journal of
Vascular and Endovascular Surgery 2014; 47 (4): 394–401.
9. Schwein A, Chinnadurai P, Bismuth J. Iliac Limb Perigraft Access with Robotic Catheter Assistance for
Type 2 Endoleak Embolization. Annals of Vascular Surgery 2017; 38: 317.e5–7.
282
10. Baum RA, Carpenter JP, Golden MA, et al. Treatment of type 2 endoleaks after endovascular repair

of abdominal aortic aneurysms: comparison of transarterial and translumbar techniques. Journal of
11. Sarac TP, Gibbons C, Vargas L, et al. Long-term follow-up of type II endoleak embolization reveals the
need for close surveillance. Journal of Vascular Surgery 2012; 55 (1): 33–40.
12. Abularrage CJ, Patel VI, Conrad MF, et al. Improved results using Onyx glue for the treatment of
persistent type 2 endoleak after endovascular aneurysm repair. Journal of Vascular Surgery 2012; 56
(3): 630–36.
13. Haulon S, Tyazi A, Willoteaux S, et al. Embolization of type II endoleaks after aortic stent-graft
implantation: technique and immediate results. Journal of Vascular Surgery 2001; 34 (4): 600–05.
14. Hajibandeh S, Ahmad N, Antoniou GA, Torella F. Is intervention better than surveillance in patients
with type 2 endoleak post-endovascular abdominal aortic aneurysm repair? Interactive Cardiovascular
and Thoracic Surgery 2015; 20 (1): 128–34.
15. Walker J, Tucker LY, Goodney P, et al. Type II endoleak with or without intervention after endovascular
aortic aneurysm repair does not change aneurysm-related outcomes despite sac growth. Journal of
16. Sidloff DA, Stather PW, Choke E, et al. Type II endoleak after endovascular aneurysm repair. The British
Journal of Surgery 2013; 100 (10): 1262–70.
283
Alternative access to control
endoleaks—para endograft
ET Criman and PA Schneider
Introduction
Since its inception, endovascular aneurysm repair (EVAR) has brought with it a
unique host of mechanical challenges and complications. Endoleak remains the
most prevalent and vexing of these. There is general consensus that type I, type III,
and type IV endoleaks mandate repair because they leave the aneurysm sac exposed
to arterial pressure. Type II endoleaks are the most commonly observed subtype,
complicating an estimated 10–25% of endovascular aortic graft placements.1 Since
these result from back-bleeding branch vessels that typically do not approach
systemic arterial pressure, they may be safely observed, with the majority of patients
requiring no intervention. While work has been done to identify preoperative risk
factors for the development of a type II, we are as yet unable to predict which
patients with these endoleaks will ultimately require another intervention.2 In this
chapter, we will discuss the treatment of complex type II endoleaks after EVAR and
detail several different approaches while elaborating on a “transfemoral/around the
graft” (TAG) approach to gain access to the aneurysm sac.
Description of the topic

It should be stressed at the outset of this discussion that most chronic type II
endoleaks do not require treatment. In a cohort of 136 patients with this type
of endoleak, Abularrage et al demonstrated a 67% freedom from reintervention
at five years, and this clinical observation has been corroborated by numerous
other groups. 2 While most do not require treatment, those that fail to resolve
or demonstrate interval enlargement may place the patient at risk for rupture
or change in aneurysmal morphology, potentially leading to the development of
high pressure endoleaks (e.g. type I or III endoleaks). Extrapolating from standard
guidelines indicating aneurysm repair, the general threshold for consideration of
intervention is enlargement of more than 0.5mm over six months. Suggesting that
there is no universal approach to address this challenge, a number of endovascular,
transvascular, percutaneous, and surgical approaches have been proposed. These
approaches fall within three broad categories: embolisation of the feeding vessel;
surgical ligation of the feeding vessel; and obliteration of the aneurysm sac.3
Embolisation of the feeding vessel

The transarterial approach uses selective catheterisation to access, via collateral
circulation, the inferior mesenteric artery (via the superior mesenteric artery) and
the lumbar arteries (via the internal iliac artery). This requires favourable anatomy
(e.g. an intact Arc of Riolan or marginal artery from superior mesenteric to inferior
285
mesenteric artery cannulation) and a working familiarity with microvascular
• ET Criman and PA Schneider
catheters to traverse the collateral systems. If the patient’s anatomy is unfavourable

and this endovascular approach is not feasible, CT-guided, percutaneous approaches
to the endoleak sac have demonstrated success in addressing endoleaks. This
approach is particularly successful for type II endoleaks emanating from more
superior lumbar arteries. This technique requires a patient that can tolerate prone
positioning, a skilled interventionalist, and to be performed under CT guidance. It
has an increased incidence of infection compared with transarterial approaches but
may be more effective.4
Surgical ligation of the feeding vessel

Alternative access to control endoleaks—para endograft
Both laparoscopic and open approaches have been proposed for surgical ligation,
and range from laparoscopic ligation of the inferior mesenteric artery to open
transperitoneal sacotomy with graft preservation and ligation of culprit vessels,
to open conversion, to a standard graft.5,6 As alternative endovascular approaches
become more widely used, the aforementioned surgical ligation approaches appear
to be on the decline due to the morbidity associated with these procedures and
the need for general anaesthesia. Nevertheless, surgical ligation remains in the
armamentarium of surgeons practising endovascular techniques as an option of last
resort should other less invasive interventions fail.
Obliteration of the aneurysm sac

Obliteration of the aneurysm sac has been proposed by using a variety of approaches
and techniques. Percutaneous, transcaval, and retrograde arterial endovascular
approaches have been proposed using embolisation adjuncts such as glue, thrombin
slurries, and coils. Percutaneous embolisation of the sac is accomplished as described
above for selective treatment of lumbar vessels. Transcaval embolisation uses a
catheter introduced into the inferior vena cava to puncture the adjacent aneurysm
sac and place an embolising agent. This approach, while technically demanding,
has been demonstrated to be both safe and effective.7 It may useful in cases where
other approaches have failed. Endovascular obliteration of the aneurysm sac was
first described as a prophylactic means of preventing type II endoleak by Zanchetta
et al.8 Using a treatment catheter placed deliberately outside the endograft at
the time of graft deployment, they were able to instill fibrin glue into the newly
excluded sac. The group was able to demonstrate a reduction in the incidence of
type II endoleaks using this approach. This work was expanded upon by Ronsivalle
et al who prophylactically performed sac “thrombinisation” at the time of endograft
placement in a series of several hundred patients, with an associated reduction in
the incidence of type II endoleaks and no documented morbidity associated with
the procedure.9
Prophylactic instillation of glue, thrombin slurry, and/or embolisation coils into
an excluded aneurysm sac is not without associated cost or morbidity. Piazza et al
analysed the cost associated with each prophylactic embolisation, and from their
data it is not clear whether this approach and its associated reduction of type II
endoleak was able to offset the expense associated with the added intervention.10
Coppi et al describe an incidence of colon ischaemia, and spinal cord injury from
embolisation of glue and/or coils into the lumbar arteries is also thought to be
286
possible. 11 Introduction of coils or glue at the time of endograft placement may

also complicate postoperative surveillance, with scatter artifact on computerised
tomography making the diagnosis and localisation of a type II endoleak more
challenging.3
While much of the feasibility work on sac embolisation has been done in the
prophylactic setting, Quinones-Baldrich et al took this approach a step further and
expanded it to include patients who had persistent type II endoleaks after endograft
placement.12 They used a transfemoral, retrograde “inside the artery but outside the
endograft” approach to perform sac obliteration in select patients with an excellent
rate of technical success. This technique offers several advantages over those described
above and is discussed in more detail below. We have adopted this approach and it is
part of our workflow for patients requiring treatment of type II endoleak.
Transfemoral/around the graft approach

This technique is referred to variously as TAG, “transealing,”and “perigraft arterial
sac embolisation” (PASE). 11,12 Despite the lack of standardised nomenclature, the
procedure is generally understood to include the following steps:

1. With the patient in the supine position and using local anaesthesia and/or
monitored anaesthesia care, obtain femoral artery access with sheath support
on the side of interest. Coppi et al note that in the majority of cases (76%),
a small gap could be detected between the iliac limb and artery wall on pre-
operative CT angiography. If no gap was detected, the side with the shortest
iliac limb was chosen11
2. Introduce an angled, hydrophilic catheter with stiff tip pointed at the graft
edge
3. Gently push with a hydrophilic guidewire until embedded behind the graft
limb
4. Advance catheter behind the graft limb and then into the aneurysm sac.
5. Perform saccography and use this to guide treatment using coils, glue, or
another haemostatic adjunct (e.g. fibrin or thrombin)
6. Perform completion arteriography of the iliac limb to exclude the presence of
a new type I or type III endoleak. Be prepared to angioplasty the graft limb to
ensure seal and to extend graft limb or reline as needed.
This technique is systematically illustrated in Figure 1. There are some key technical
considerations with this procedure. Retrograde access to the sac by going around
the graft risks creation of a high pressure endoleak (type 1 or type III). The surgeon
must be prepared for graft extension or relining as indicated. With this in mind,
the iliac limb must be of such a length that it may be safely extended if necessary.
It should be noted that Coppi et al excluded patients with external iliac landing
zones because of concern about rupture/dissection.11 As with the other approaches
to sac obliteration, there is a risk of colonic or spinal cord ischaemia in addition to
the standard risks of arteriography (e.g. access site complication, contrast-induced
nephropathy, and other complications of endovascular intervention). Transfemoral/
around the graft technique offers several advantages over those described above.
First, it borrows heavily from other familiar techniques in endovascular surgery
(e.g. sub-intimal passage and traversal of chronic total occlusions). Second, it
allows the surgeon to access the aneurysm sac using comparatively larger treatment
287
A B
C D
Figure 1: Transfemoral/around the Graft—illustrated: (A) Sheath in true lumen with catheter traversing the left
common iliac artery landing zone to enter the previously excluded aneurysm sac. Saccography demonstrating type II
endoleak from lumbar vessels. Note previously coiled inferior mesenteric artery. (B) Coils and occluders within culprit
lumbar artery and aneurysm sac. (C) Repeat angioplasty of traversed left iliac artery landing zone to secure the
endograft limb seal. (D) Completion angiography demonstrating no type IB or type III endoleak.
catheters than other approaches described above. It also lends itself to occlusion of
low lumbar arteries that are often difficult to address with percutaneous transarterial
approaches. In limited series, outcomes appear to be comparable to alternative
approaches to sac obliteration as described above.11,12 This approach tends to work
best if the inferior mesenteric and lumbar arteries are already coiled, and may
be combined with concurrent transarterial embolisation. We view this as one of
several options for accessing the sac, not necessarily better or worse an option than
the others mentioned. It is not yet clear in which patients this is the first choice for
access. We have typically used it as a second or third choice.
Conclusion
Chronic type II endoleak remains a vexing problem in the field of EVAR. While
common, these types of endoleaks can often be safely observed and do not require
another intervention. While prophylactic aneurysm sac obliteration has been
demonstrated in several series to be effective, it remains controversial because
it unquestionably adds cost and operative risk to the index procedure. When
intervention is indicated by an enlarging aneurysm sac and radiographic evidence
of an endoleak, sac obliteration using the transfemoral/around the graft technique
appears to be a reasonable option.
288
Summary
• Type II endoleaks complicate an estimated 10–25% of endovascular

graft placements but the majority may be observed and do not require
intervention.
• Consideration for intervention should be given in cases of aneurysmal sac
growth.
• A variety of endovascular, percutaneous, and surgical approaches may be
used to occlude feeding vessels and/or obliterate the aneurysm sac to suit
the individual patient and his/her anatomy.
• No single approach has demonstrated superiority over the others and each
has unique advantages/disadvantages.
• The transfemoral/around the graft method represents a user friendly means of
performing sac obliteration in select circumstances and may be more effective
when combined with other modalities.

References
1. Veith FJ, Baum RA Ohki T, et al. Nature and significance of endoleaks and endotension: summary of
opinions expressed at an international conference. J Vasc Surg 2002; 35: 1029–35.
2. Abularrage CJ, Crawford RS, Conrad MF, et al. Preoperative variables predict persistent type 2 endoleak
after endovascular aneurysm repair. J Vasc Surg 2010; 52 (1): 19–24.
3. Barleben A, Inui T, Owens E, et al. Intervention after endovascular aneurysm repair: Endosalvage
techniques including perigraft arterial sac embolization and endograft relining. Semin Vasc Surg 2016;
29( 1-2): 41–49.
4. Larzon T and Fujita S. Type II endoleak: a problem to be solved. J Cardiovasc Surg (Torino) 2014; 55
(1): 109–18.
5. Ho P, Law WL, Tung PH, et al. Laparoscopic transperitoneal clipping of the inferior mesenteric artery
for the management of type II endoleak after endovascular repair of an aneurysm. Surg Endosc 2004;
18: 870.
6. Maitrias P, Belhomme D, Molin V, et al. Obliterative endoaneurysmorrhaphy with stent graft
preservation for treatment of type ii progressive endoleak. Eur J Vasc Endovasc Surg 2016; 51: 38–42.
7. Giles KA, Fillinger MF, DeMartino RR, et al. Results of transcaval embolization for sac expansion from
type II endoleaks after endovascular aneurysm repair. J Vasc Surg 2015; 61 (5): 1129–36.
8. Zanchetta M, Faresin F, Pedon L, et al. Fibrin glue aneurysm sac embolization at the time of
endografting. J Endovasc Ther 2005; 12: 579–82.
9. Ronsivalle S, Faresin F, Franz F, et al. Aneurysm sac ‘thrombinization’ and stabilization in EVAR: a
technique to reduce the risk of type II endoleak. J Endovasc Ther 2010; 17: 517–24.
10. Piazza M, Frigatti P, Scrivere P, et al. Role of aneurysm sac embolization during endovascular aneurysm
repair in the prevention of type II endoleak-related complications. J Vasc Surg 2013; 57: 934–41.
11. Coppi G, Saitta G, Coppi G, et al. Transealing: A Novel and Simple Technique for Embolization of Type
2 Endoleaks Through Direct Sac Access From the Distal Stent-graft Landing Zone. Eur J Vasc Endovasc
Surg 2014; 47 (4): 394–401.
12. Quinones-Baldrich W, Levin ES, Lew W, Barleben A. Intraprocedural and postprocedural perigraft
arterial sac embolization (PASE) for endoleak treatment. J Vasc Surg 2014; 59: 538–41.
289
Technical controversies for open abdominal aortic
aneurysm repair
The AIDA study—a
randomised multicentre
three-armed clinical trial to
prevent incisional hernia
following abdominal aortic
aneurysm open repair by
onlay mesh augmentation
ES Debus, T Kölbel, S Wipper, N Tsilimparis,
A Larena-Avellaneda and H Diener
Introduction
Incisional hernia is a common complication following midline abdominal incision
with a prevalence of 12.8% after two years.1–4 Age, male sex, chronic obstructive
pulmonary disease, corticosteroid therapy, obesity (body mass index >30kg/
m2), smoking or presence of diabetes are the major confounders influencing the
prevalence of incisional hernia.10 Open repair of abdominal aortic aneurysm deems
to be the highest risk factor, leading to an even higher incidence of incisional
hernia. Pooled adjusted risk factors have shown a 2.9 up to 5.4-fold risk for
developing this type of hernia following aortic hernia surgery with a midline
incision.5,6 Mechanisms of extracellular matrix remodelling and imbalance between
connective tissue degrading enzymes and their inhibitors, which cause inflammatory
responses, have been described.5 Additionally, collagen defects caused partly by a
dysregulation between collagen type I and III are supposed to be causative reasons.1,7
The reported incidence of incisional hernia post abdominal aortic aneurysm repair
with midline incision varies between 10% and 37% and can even arise up to 69%
after five years.1,8–11,12 Incisional hernias can cause persistent pain, have impact on
the patient’s quality of life, and include the risk of incarceration.13,14 The repair of
incisional hernia also represents a high economic burden for the healthcare system
of the society and healthcare facilities, which was estimated in France to be 6451€
(range 4731–10170€) in a multicentric cost analysis among a large panel of 51
French hospitals.15 Additionally, the recurrence rate after repair of incisional hernia
is as high as 37% with a reoperation rate of 8% within the following four years.16,17
Therefore prevention of incisional hernia as the major obstacle following open
abdominal aortic aneurysm repair should be aimed for. Although most aneurysm
repairs today are performed by endovascular means, open repair still plays a role.
293
In 2015 the European Hernia Society published their guidelines and recommended
• ES Debus, T Kölbel, S Wipper, N Tsilimparis, A Larena-Avellaneda and H Diener
prophylactic mesh augmentation based on studies published until 2013, but with
little evidence.2
Since then, several randomised clinical trials and meta-analyses were published,
revealing significant benefits of prophylactic mesh insertion after midline laparotomy
for aneurysm repair and other indications for general surgery.
Methods
A literature search using Pubmed and Medline between 2013 and 2017 was
performed (final search day: Dec 30th 2017). Search items were prophylactic
mesh, abdominal aortic aneurysm repair, and incisional hernia. Of 104 studies,
only randomised prospective clinical trials and meta-analyses were included in this
narrative survey.
Results and discussion

The included studies have shown that heterogeneity, and especially among studies
with prophylactic mesh insertion following abdominal aortic aneurysm repair, are
rare, and the best position for placement of a prophylactic mesh remains unclear.18–20
Several meta-analyses for preventing incisional hernia were published in 2017 and
all of them showed a significant benefit by using a prophylactic mesh, but the
data were heterogeneous due to indication of laparotomy and its risk factors.18–20
Additionally, the operative techniques and suture material used were not identical
in the studies, making them a challenge to compare, although they all point in a
similar direction. Only six studies revealing abdominal aortic aneurysm surgery
were included.9,21–25 In four studies, the mesh was placed retro-muscularly in a
sub-lay technique, and one in a preperitoneal position.2,21–23,26 Only four of them
The AIDA study
were randomised controlled trials and the remaining investigations were cohort
studies.2,21–24 One randomised controlled trial augmented the fascia with a mesh,
in onlay technique, and found significant differences after three years (p<0.001),
but in this study a biological mesh was used and the number of patients was low.24
However, all these data result in a significant reduction of incisional hernias. A
recently published study in the Lancet compared closing the midline incision with
single suture technique vs. prophylactic mesh placement in onlay techniques or
sublay technique in high risk patients.26 This trial included 150 patients following
aneurysm surgery and showed a significant reduction of incisional hernia using a
prophylactic mesh in onlay technique (p=0.008) and in sublay technique (p=0.03)
compared to suturing alone.
There is only one trial that compared sublay vs. onlay mesh augmentation in
patients following abdominal aortic aneurysm surgery, which reported no significant
differences (16% and 19% respectively).26 Muysoms et al observed no incisional
hernia in the mesh-augmented reinforcement group in sublay position after two
years, whereas the cumulative incidence of incisional hernias after primary surgery
wall of the midline was 17% (10 of 58) at 12 months and 28% (17 of 58) after 24
months.9 Nevertheless, onlay mesh augmentation is easy to learn and to perform,
which may be of special importance since vascular surgeons are not generally
trained in mesh augmentation for hernia repair, in contrast to general surgeons. In
294
general, dissection and closure in sublay augmentation takes longer than onlay, and
The AIDA study

retromuscular placement of mesh requires more specific experience.2,26
The AIDA study is the only multicentre randomised controlled study in
abdominal aortic aneurysm using onlay mesh augmentation showing a significant
reduction of incisional hernias.27 Here, a polypropylene mesh was used. This mesh
is a monofilament, lightweight, large-pore sized, polypropylene mesh designed to

reduce amount of polymer material but still providing significant reinforcement
to the abdominal wall. Out of 104 patients, 33 to 36 were randomised in each of
the three groups. After 12 months, 4.55% of the patients with mesh augmentation
developed an incisional hernia, whereas 21.74% and 18.18% of patients
undergoing midline abdominal closure with two different running sutures had one.
Wound healing disorders occurred in 15.19%. Notable differences occurred in the
formation of seromas, which were exclusively found in the mesh group (19.23%),
with four patients needing revision, by preserving the mesh.27
A 5cm overlap on both sides and 2.5cm at the proximal and distal edges as
recommended and evident in hernia repair were performed. The PRIMA (Primary
mesh closure of abdominal midline wound) trial used the same mesh but opted
for a smaller overlap of 3cm to avoid further dissection of the wound in order not
to induce more wound morbidity, due to the fact that there is no fascia defect. In
contrast to the AIDA study, meshes were fixed by glue. The incidence of incisional
hernia in the PRIMA trial performing onlay mesh augmentation was higher than
in AIDA, but there were more patients included in the only group.
The risk of detected bias in systemic reviews and the published meta-analysis has
already been described. Additionally, in some studies no blinding was described.
Closure of a primary midline incision, however, can involve the use of various
different suture materials and techniques. A continuous monofilament suture in
a single layer technique is generally recommended. A suture length-to-wound
length ratio of at least 4:1 is of major importance for the prevention of wound
complications.2 The risk of wound dehiscence is low with a ratio higher than four.
The distance between the bites should be no more than 2–2.5cm. The peritoneum
is not generally recommended for suturing. Millbourn et al have demonstrated
a small bite technique, where the wound is closed with a single suture running
technique, taking bites of 5–8mm of the fascia and stitches every 5mm, which
resulted in fewer incisional hernias and surgical site infections.28 In the STITCH
(Small bites vs. large bites for closure of abdominal midline incisions) trial by
Deerenberg et al, 560 patients were randomised comparing a small bite technique
of 5mm every 5mm compared to a large bite technique of more than 10mm
every 10mm closing a midline incision after abdominal surgery. They found a
significant hernia reduction in the small bite group (n=13%) vs. the large bite
group (incisional hernia n=21%) after one year follow up. A smaller size of suture
material (USP 2/0) and needle size (31mm) together with a higher ratio of suture
length to wound length were associated with these results.29 Besides the risk factors,
the time of follow-up is also important. Most incisional hernias occur between 12
and 36 months after surgery. Fink et al reported an incidence of hernia of 12.6% in
the first year, which increased significantly to 22.4% after three years. A minimum
of two years follow-up is recommended.4 Additionally, wound healing disorders
may play a role and occurred in 13 patients (13%) of the AIDA trial. Notable
differences were visible in formation of seromas which were exclusively found in
295
the mesh group, which are caused by the onlay technique. Occurrence of seromas
was also described in other preventional mesh augmentation studies, also in the
sublay mesh techniques.10,18–20 The latter one also found seromas only in onlay or
preperitoneal position but not in sublay position, and use of polypropylene mesh
increased seroma risk only in the onlay position (relative risk = 2.77; p=0.04). In
PRIMA, significantly more seromas after onlay mesh augmentation were detected
(18.1%) compared with primary suture (4.7%) and sublay mesh augmentation
(7%). Apart from a significant incidence of seroma formation, no other differences
were observed when a prophylactic prosthetic mesh was used. The formation of
seroma, however, did not result in substantially weaker outcomes as well as in our
study and onlay mesh did not increase surgical site infection or mesh infection.
Whereas in the AIDA study, no meshes had to be removed, 6% of meshes had to
be removed in the PRIMA trial (sublay mesh augmentation) because of infection.
In a small study by Herbert to prevent hernias using sublay mesh technique,
four meshes (25% of study population) had to be extracted because of infection
(n=3) or persistent seroma (n=1).30 Bali et al have shown a significant reduction
of hernias after implantation of bovine pericardium meshes for reinforcement of
the fascia after abdominal aortic aneurysm surgery.24 Nevertheless, they also have
observed postoperative formation of seromas in 10%.2,20 If there is an advantage
in using bovine pericardium for onlay mesh augmentation, this must be controlled
in further, larger studies. A systemic review of literature using a biologic mesh for
hernia prevention by Muyosoms found limited, poor quality evidence to support
the use of biologic meshes.9 No studies have compared non-absorbable meshes
and synthetic meshes directly, and a trial comparing non-absorbable and biologic
meshes in closures of laparotomies might be necessary.9
The AIDA study
Conclusion
Patients following abdominal aortic aneurysm surgery revealed a significant benefit
of preventional mesh augmentation in onlay or sublay technique. Prophylactic
mesh augmentation, therefore, may become mandatory in the future. Onlay mesh
augmentation is easy to perform and does not need a specific surgical training
for fascia dissection like sublay mesh augmentation, and shows similar or better
results, although there are a higher number of seromas observed. Rate of wound
and surgical side-infections is higher following sublay augmentation, however.
Because of the prophylactic nature of this study, a number of patients will receive a
mesh, which may not be clinically indicated. However, the literature suggests that
these patients would still have the possibility of have a late recurrence due to their
propensity to abdominal wall defects. The risk to the patients by adding a mesh to
their procedure is nevertheless acceptable. Preventive mesh augmentation should
be included in future guidelines on abdominal aortic aneurysm repair, warranting
a high level of evidence.
296
The AIDA study
Summary
• Open repair for abdominal aortic aneurysm following midline laparotomy is

often associated with incisional hernia.
•

Preventive mesh augmentation of the abdominal wall has proven to
significantly reduce the incidence of incisional hernia following midline
laparotomy for aneurysm repair.
• Sublay mesh augmentation is similarly effective as onlay technique.
• Onlay mesh augmentation is easy to perform and does not need a specific
surgical training for fascia dissection.
• The incidence of postoperative seroma is higher using onlay technique.
However sublay mesh implantation is associated with higher rate of wound
infections, due to more extensive preparation. Preventive mesh augmentation
using alloplastic material is therefore recommended for open abdominal aortic
aneurysm repair and should be included in future guidelines.
References
1. Bosanquet DC, Ansell J, Abdelrahman T, et al. Systematic Review and Meta-Regression of Factors
Affecting Midline Incisional Hernia Rates: Analysis of 14,618 Patients. PLoS One 2015; 10 (9):
2. Muysoms FE, Antoniou SA, Bury K, et al. European Hernia Society guidelines on the closure of
abdominal wall incisions. Hernia 2015; 19 (1): 1–24
3. Raffetto JD, Cheung Y, Fisher JB, et al. Incision and abdominal wall hernias in patients with aneurysm
or occlusive aortic disease. Vasc Surg 2003; 37 (6):1150–54.
4. Fink C1, Baumann P, Wente MN,et al. Incisional hernia rate 3 years after midline laparotomy. Br J Surg
2014; 101 (2): 51–54.
5. Antoniou George A, Georgiadis George S, et al. Abdominal aortic aneurysm and abdominal wall
hernia as manifestations of a connective tissue disorder. J Vasc Surg 2011; 54 (4):1175–81.
6. Takagi H, Sugimoto M, Kato T, et al. Postoperative Incision Hernia in Patients with Abdominal Aortic
Aneurysm and Aortoiliac Occlusive Disease: A Systematic Review. Eur J Vasc Endovasc Surg 2007; 33
7. Muysoms FE, Dietz UA. Prophylactic meshes in the abdominal wall. Chirurg 2017; 88 (Suppl1):34–41.
8. Gruppo M., Mazzalai F., Lorenzetti R. et al. Midline abdominal wall incisional hernia after aortic
reconstructive surgery: A prospective study. Surgery 2012; 151: 882–88.
9. Muysoms FE1, Detry O, Vierendeels T et al. Prevention of Incisional Hernias by Prophylactic Mesh-
augmented Reinforcement of Midline Laparotomies for Abdominal Aortic Aneurysm Treatment: A
Randomized Controlled Trial. Ann Surg 2016; 263 (4): 638–45.
10. Timmermans L, de Goede B, Eker HH et al. Meta-analysis of primary mesh augmentation as prophylactic
measure to prevent incisional hernia. Dig Surg 2013; 30 (4–6): 401–09.
11. Musella M, Milone F, Chello M, et al. Magnetic resonance imaging and abdominal wall hernias in aortic
surgery. J Ant Coll Surg 193: 392–95.
12. 10Sami Alnassar, Mohammed Bawahab, Ahmed Abdoh, et al. Incisional hernia postrepair of abdominal
aortic occlusive and aneurysmal disease: five-year incidence. Vascular 2012; 20 (5): 273–77
13. van Ramshorst GH, Eker HH, Hop WC, et al. Impact of incisional hernia on health-related quality of life
and body image: a prospective cohort study. Am J Surg 2012; 204: 144–50
14. Rogmark P, Petersson U, Bringman S, et al. Quality-of-life and surgical outcome 1 year after open and
laparoscopic incisional hernia repair: PROLOVE—a randomized controlled trial. Ann Surg 2016; 263:
244–50.
15. Gillion JF, Sanders D, Miserez M, Muysoms F.The economic burden of incisional ventral hernia repair: a
multicentric cost analysis. Hernia 2016; 20 (6): 819–30.
16. Burger JW, Luijendijk RW, Hop WC, et al. Long-term follow-up of a randomized controlled trial of
suture versus mesh repair of incisional hernia. Ann Surg 2004; 240: 578–83.
17. Al Chalabi H, Larkin J, Mehigan B, McCormick P. A systematic review of laparoscopic versus open
abdominal incisional hernia repair, with meta-analysis of randomized controlled trials. Int J Surg 2015;
20: 65–74.
297
18. Wang XC, Zhang D, Yang ZX, et al. Mesh reinforcement for the prevention of incisional hernia formation:
a systematic review and meta-analysis of randomized controlled trials. J Surg Res 2017; 209: 17–29.
19. Payne R, Aldwinckle J, Ward S. Meta-analysis of randomised trials comparing the use of prophylactic
mesh to standard midline closure in the reduction of incisional herniae. Hernia 2017; 21 (6): 843–53.
20. Borab ZM, Shakir S, Lanni MA, et al. Does prophylactic mesh placement in elective, midline laparotomy
reduce the incidence of incisional hernia? A systematic review and meta-analysis Surgery 2017; 161
(4): 1149–63.
21. Rogers M, Mc Carthy R, Earnshaw JJ Prevention of Incisional Hernia after Aortic Aneurysm Repair. Eur
J Vasc Endovasc Surg 26 (5): 519–22.
22. O’Hare JL, Ward J, Earnshaw JJ Late results of mesh wound closure after elective open aortic aneurysm
repair. Eur J Vasc Endovasc Surg 33: 412–13
23. Bevis PM, Windhaber RA, Lear PA, et al. Randomized clinical trial of mesh versus sutured wound closure
after open abdominal aortic aneurysm surgery. Br J Surg 2010; 97 (10): 1497–502
24. Bali C, Papakostas J, Georgiou G, et al. A comparative study of sutured versus bovine pericardium mesh
abdominal closure after open abdominal aortic aneurysm repair. Hernia 2015; 19 (2): 267–71.
25. Timmermans L, Eker HH, Steyerberg EW et al . Short-term results of a randomized controlled trial
comparing primary suture with primary glued mesh augmentation to prevent incisional hernia. Ann
Surg 2015; 261 (2): 276–81.
26. Jairam AP, Timmermans L, Eker HH, et al. PRIMA Trialist Group. Prevention of incisional hernia with
prophylactic onlay and sublay mesh reinforcement versus primary suture only in midline laparotomies
(PRIMA): 2-year follow-up of a multicentre, double-blind, randomised controlled trial. Lancet 2017; 390
(10094): 567–76.
27. Diener H, Eckstein HH, Wenk H, et al. Prevention of Incisional Hernia after Abdominal Aortic Aneurysm
Repair (AIDA study). Eur J Vasc Endovasc Surg 2016; 52: 412
28. Millbourn D, Cengiz Y, Israelsson LA Effect of stitch length on wound complications after closure of
midline incisions:a randomized controlled trial. Arch Surg 144:1056–59
29. Deerenberg EB, Harlaar JJ, Steyerberg EW, et al. Small bites versus large bites for closure of abdominal
midline incisions (STITCH): a double-blind, multicentre, randomised controlled trial. Lancet 2015; 386:
1254–60.
30. Herbert GS, Tausch TJ, Carter PL: Prophylactic mesh to prevent incisional hernia: a note of caution. Am
J Surg 2009; 197: 595–98.
The AIDA study
298
Peripheral arterial
ischaemia controversies
WHETHER to intervene, WHEN to INTERVENE,
INTERVENTION METHOD AND FOLLOW-UP:
Controversies on severe aortic bifurcation and iliac
occlusive arterial disease
What ABPI and toe pressure
index tell us about prognosis
and how clopidogrel
and statins impact it
Introduction
One of the most important challenges in public healthcare is identifying the
population that is most at risk of cardiovascular disease and preventing them from
having cardiovascular events. At present, the aim of primary prevention programmes
is to modify risk factors such as hypertension, dyslipidaemia and cigarette smoking;
secondary prevention focuses on reducing the risk of further events in individuals
with symptomatic cardiovascular disease.1
The key issues are to distinguish the people at risk among the “healthy”
population—to find the patients with asymptomatic atherosclerosis that will
potentially develop severe cardiovascular or cerebrovascular disease—and to focus
primary prevention on these individuals as well as managing secondary prevention
in patients after they have had an event.
Several markers have been evaluated as tools for predicting patients at increased
risk; for example, carotid artery intima-media thickness, carotid plaques, aortic
calcification and the ankle-brachial index (ABI). In addition to these markers,
scoring systems using cardiovascular risk factors, such as blood pressure, cholesterols,
diabetes mellitus and cigarette smoking, have been evaluated;the Framingham risk
score being the most well-known scoring system.2,3
The role of the ABI

ABI (the ratio of systolic blood pressure in the ankle to that in the arm), which has
traditionally been used in vascular practice to assess foot perfusion and the severity
of limb ischaemia, is inexpensive, quick and easy to measure.
Cross-sectional studies have shown that it is also an indicator of generalised
atherosclerosis; low values have been associated with higher rates of concomitant
coronary and cerebrovascular disease and with cardiovascular risk factors.4, 5 Also,
population cohort studies have shown that a low ABI is related to an increased
mortality (total and cardiovascular), and increased rates of myocardial infarction
and stroke. The association between ABI and mortality is not linear: both low
and high values correlate with increased cardiovascular mortality in a U-shaped
fashion.5,6 This is due to the fact that in patients with crural atherosclerosis, the
medial layer of the arterial wall becomes medial sclerotic and stiff and this causes
303
falsely high ABI-values. This so-called pseudohypertension tends to be more
common among diabetic patients.

In addition to ABI, toe pressures are widely used in the evaluation of foot
perfusion. As toe pressure measurements require specialised equipment, they are
usually limited to the special healthcare and the vascular laboratory. As digital
arteries are usually free from medial sclerosis, toe pressure is a more reliable measure
of foot perfusion than is the ABI in patients with medial calcinosis. The relationship
between cardiovascular mortality and toe pressure as well as the prognostic value
of toe pressure in predicting outcome has been less well studied compared with the
ABI. In some recent studies, a linear correlation between the toe brachial index and
What ABPI and toe pressure index tell us about prognosis and how clopidogrel and statins impact it •
the risk of cardiovascular death has been distinguished.7
ABI, toe pressure and cardiovascular mortality

In a systematic review, Heald and colleagues analysed the studies on the ABI and the
risk of cardiovascular morbidity and mortality (including coronary heart disease,
myocardial infarction and stroke).1 Out of 680 citations and 50 full-text articles,
they eventually included 11 studies, comprising a total of 44,590 participants. The
cutoff level for low ABI was 0.9. The pooling of the results gave an estimated
age and sex adjusted relative risk (RR) of 2.35 (95% CI 1.66–3.32) for all-cause
mortality, 3.34 (95% CI 2.12–5.28) for cardiovascular mortality, 2.13 (95% CI
1.54–2.94) for coronary heart disease (fatal and non-fatal events combined) and
1.86 (95% CI 1.43–2.42) for fatal and non-fatal events combined.
The Framingham risk score has been the standard for predicting cardiovascular
mortality and morbidity. However its accuracy has been criticised: it tends to
overestimate risk in low-risk populations and under-estimate risk in high-risk
populations.3 In a meta-analysis, Fowkes and colleagues analysed whether the
ABI provided information on the risk of cardiovascular events and mortality
independently of that of the Framingham risk score risk score and, thus, could be
used to improve risk prediction.8 After a search of MEDLINE and EMBASE, they
identified 16 population cohort studies; overall, these studies included 25,000 men
and 23,000 women with 480,000 person years follow-up. A low ABI (≤0.90) was
associated with twice as high 10-year overall mortality, cardiovascular mortality
and major coronary event rate compared with the overall rate in each Framingham
category. Therefore, ABI increased the accuracy of the Framingham risk score.
Although definitely useful, ABI measurement has certain limitations; for example,
in patients with severe aortoiliac stenosis or even occlusion with a good collateral
arteries, the ABI can be normal despite significant atherosclerosis. Furthermore,
medial sclerosis may mask even a significant atherosclerotic disease with a normal
ABI. It has been suggested that as many as nearly half of the patients with
asymptomatic lower limb arterial disease may have normal resting ABI.9,10 Fowkes
et al state that in the original ABI studies, patients had advanced atherosclerosis.
Usually toe arteries are free of medial sclerosis and, therefore, toe pressure are
more reliable in diabetic patients.
While not as many as studies have been performed on the value of toe
pressures than they have for the value of the ABI, there are a few publications.
In a retrospective study, Wickström and colleagues studied the association of
ankle pressure and the ABI as well as of toe pressure and the toe brachial index
with cardiovascular mortality, overall mortality and amputation-free survival in
304
732 patients with symptomatic lower extremity arterial disease. Cardiovascular
mortality, overall survival and amputation-free survival were poorest among patients
with toe pressure <30mmHg, toe brachial index <0.25, ABI>1.3 and ankle pressure
>250mmHg. In a multivariate analysis, both toe brachial index and toe pressure
were significantly associated with all three endpoints. The hazard ratios (HR) for
cardiovascular mortality, overall mortality and amputation free survival were 2.84
(95% CI 1.75-4.61), 2.05 (95% CI 1.44-2.92) and 2.13 (1.52-2.98) respectively,
compared to patients with toe pressure ≥50. The corresponding hazard ratios for
toe brachial index =0.25 compared to toe brachial index ≥0.50 were 3.68 (95% CI
1.48-9.19), 2.53 (1.35-4.74) and 2.47 (1.38-4.40), respectively. Both toe pressure
and toe brachial index were better in predicting the endpoints than was ABI and
ankle pressure.11
Clopidogrel
Antiplatelet medication is used to prevent limb-related and general cardiovascular
events; aspirin is traditionally used in this prevention. Two trials, however, have
not found benefit from aspirin compared to placebo in patients with asymptomatic
lower extremity arterial disease. In symptomatic patients, aspirin protects against
major cardiovascular events.12,13
Clopidogrel adds an antithrombotic effect but at the same time, increases the risk
of bleeding. A CAPRIE (Clopidogrel versus aspirin in patients at risk of ischaemic
events) trial post-hoc analysis on the patients with lower extremity arterial disease
showed a significant reduction in cardiovascular mortality at three years in the
clopidogrel group compared to the aspirin group (hazards ratio [HR] 0.76 [95%
CI 0.64–0.91]) and major cardiovascular events (HR 0.78 (95% CI 0.65–0.93),
with similar benefit in the subgroup of lower extremity arterial disease patients
with diabetes.14
A fresh Cochrane update included randomised controlled trials with 34,000
participants comparing the use of aspirin plus clopidogrel with aspirin plus placebo
or aspirin alone in individuals with coronary disease, ischaemic cerebrovascular
disease, peripheral arterial disease, or at high risk of atherothrombotic disease
included.15 There was no difference in the effectiveness of aspirin plus clopidogrel
in preventing cardiovascular mortality (RR 0.98, 95% CI 0.88 to 1.10), and no
evidence of a difference in all-cause mortality (RR 1.05, 95% CI 0.87 to 1.25).
However, the risk of fatal and non-fatal myocardial infarction was lower with
clopidogrel plus aspirin compared to aspirin plus placebo or aspirin alone (RR
0.78, 95% CI 0.69 to 0.90). The risk of fatal and non-fatal ischaemic stroke was
also reduced (RR 0.73, 95% CI 0.59 to 0.91). The risk of major bleeding was
higher with clopidogrel plus aspirin compared to aspirin plus placebo or aspirin
alone (RR 1.44, 95% CI 1.25 to 1.64). In conclusion, the expected number of
myocardial infarctions and strokes to be prevented per 1,000 patients in 12 months
was 12 and 23 respectively, but nine major bleeds and 33 minor bleeds would be
caused during a median follow-up period of 10.5 and six months.
The 2017 European Society for Cardiology and European Society for Vascular
Surgery guidelines on the diagnosis and treatment of peripheral arterial diseases
recommends single antiplatelet therapy only if lower extremity arterial disease
patients are symptomatic or have undergone revacularisation. Clopidogrel is the
preferred drug in such patients.16
305
Statins
There is a strong theoretical background according to which lipid lowering drugs

are useful in atherosclerotic disease. The Class I recommendation to use statins to
reduce low-density lipoprotein (LDL) to <100mg/dL in all patients with peripheral
arterial disease materialised largely from the HPS (Heart Protection study) in
2002.17 This study randomised 20,500 patients with coronary disease, vascular
disease, or diabetes to receive 40mg simvastatin daily or placebo for five years.
Statin use was associated with a reduction in fatal and non-fatal cardiovascular
events, regardless of baseline cholesterol levels. Furthermore, in a later publication
an analysis of 6,748 patients with lower extremity arterial disease showed 24%
reduction in the first occurrence of a major vascular event (myocardial infarction,

stroke, or revascularisation) and the reduction rate was higher in patients who had
lower extremity arterial disease than those who did not.18
A Cocrane review (2007) of 18 randomised controlled trials compared lipid-
lowering therapy with placebo or usual treatment for at least 90 days in patients
with lower extremity arteria disease.19 The only type of drug for which consistent,
clear evidence of a beneficial effect on total cardiovascular events, total coronary
events and stroke was available, was statins. The pooled data showed a significantly
lower risk of a cardiovascular event among those taking statins when compared
with placebo (odds ratio [OR], 0.74; 95% CI, 0.67-0.82; p<0.001). The greatest
evidence was with simvastatin in individuals with a blood cholesterol level of at
least 3.5mmol/litre.
In a matched-cohort pair study of 5,480 asymptomatic patients with a low ABI
but no history of cardiovascular disease patients who took statins had fewer major
adverse cardiac events (20 events/ 1000 person-years) than those who did not
take statins (25/1000 person-years). The respective overall mortality was 25/1000
patient years for statin users and 30/1000 patient years for non-users.20
The 2017 European Society for Cardiology and European Society for Vascular
Surgery Guidelines on the Diagnosis and Treatment of Peripheral Arterial
Diseases recommends statins in all patients with peripheral arterial diseases (IA).
Furthermore, the recommendation is to reduce LDL cholesterol to <1.8mmol/l or
decrease it by 50% is baseline values are 1.8–3.5mmol/l (IC).16
Our experience
At Helsinki University Hospital, we have included the ABI-data in our vascular
registry since 1990. We extracted 6,800 patients with a total of 25,000 ABI
measurements from the registry. Using the patients’ personal identity codes, we
were able to get the date and cause of death from the Statistics Finland. Survival
was associated with ABI the highest mortality being among patients with medial
sclerotic ABI of >1.3. We found a clear correlation between toe pressure and survival
(Figure 1). In a subgroup of patients (n=250) who had normal ABI (0.9-1.3), almost
one in four patients had toe pressure<50mmHg. Among these patients, mortality
was strongly associated with toe pressure value and the survival was lowest among
patients with toe pressure <30mmHg. We were also able to extract information
on clopidogrel and statin-medication purchased for these patients from the Social
Insurance Institution of Finland. In this material, there was a clear association
between the medications and long-term survival and this was seen in all ABI and
toe pressure groups (Figure 2).
306
Figure 1: A clear
correlation between toe
pressure and survival was
found.
Figure 2: There was a

clear association between
the medications and
long-term survival, which
was seen in all ABI and toe
pressure groups.

Conclusion
People with lower extremity arterial disease have increased risk for cardiovascular
mortality and cardiovascular events. This risk can be predicted with ABI and
toe pressure values. Statin medication is indicated in all patients who have ABI
less than 0.9 or higher than 1.3, or toe pressure less than 50mmHg regardless
patient’s symptoms. Antiplatelet therapy is indicated in patients with symptomatic
lower extremity arterial disease. There is no evidence for benefit on antihrombotic
medication in asymptomatic patients with lower extremity arterial disease but
in symptomatic patients antithrombotic medication decreased cardiovascular
mortality and morbidity. In case of antithrombotic medication, together with
decreased risk for cardiovascular events, increased risk of bleeding must be taken
into consideration. If a patient has normal ABI but toe pressure is decreased, the
cardiovascular risk burden is increased and they should have similar prevention
than patients with ABI<0.9. In vascular surgical patients, statin and clopidogrel
medication seem to decrease overall mortality and the biggest effect is achieved
when both medications are used.
307
Summary
• The association between the ABI and mortality is not linear: both low and
hight values correlate with increased cardiovascular mortality in a U-shaped
fashion.
• ABI may be misleading. For example, in severe aortoiliac stenosis with a good
collateral arteries, the ABI can be normal despite significant atherosclerosis.
Furthermore, medial sclerosis may mask even a significant atherosclerotic
disease with a normal ABI.
• It has been suggested that nearly half of all patients with asymptomatic lower
limb arterial disease, may have normal resting ABI.
• Toe pressure is a more reliable measure of foot perfusion than is ABI in
patients with medial calcinosis.
• There is an inverse association between toe pressure and the risk of
cardiovascular events and cardiovascular death.
• Statin medication decreases the mortality and is recommended to all patients
who have lower extremity arterial disease.
• Single antiplatelet therapy is recommended if patients with lower extremity
arterial disease are symptomatic or have undergone revacularisation.
• If a patient who have normal ABI, toe pressure is decreased, the cardiovascular
risk burden is increased and they should have similar prevention than patients
with ABI<0.9.
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309
Covered endovascular
reconstruction of the
aortic bifurcation
P Goverde, K Taeymans, K Lauwers and P Verbruggen
Introduction
Open surgical repair, in the literature, is still the recommended approach for managing
extensive aortoiliac occlusive disease (described as any stenosis or occlusion from the
distal aorta to the common femoral artery). The standard treatment, especially for
TASC-II C and D lesions, is aortobifemoral or aortobiiliac bypass grafting. In recent
years, however, endovascular treatment has become more important. Studies have
shown that endovascular treatment results in shorter mean hospital stay and fewer
complication rates compared with traditional open surgical revascularisation.1,2
Initially, the kissing balloon technique was used as an endovascular approach for
treating lesions in the aortoiliac bifurcation. Long-term results for this technique
were rather disappointing due to elastic recoil and dissections.3 The next step was
the introduction of the kissing-stent technique, with two stents protruding in the
lumen of the distal aorta. An important disadvantage of this configuration was
residual vascular space outside the kissing stents, which led to flow perturbations
and possibly causing thrombus formation and neointimal hyperplasia.4
To overcome the different histological, biomechanical and haemodynamic
disadvantages with the bare kissing stent technique, and to achieve better long-
term patency rates, Goverde developed (in 2008) a new technique. The first
technical report of the covered endovascular reconstruction of the aortic bifurcation
(CERAB) was published in 2013. With this technique, the aortoiliac bifurcation is
reconstructed with a minimum of three covered stents, mimicking the anatomical and
physiological situation.5
In this chapter, we will describe how it is done, why covered stents are used for
the reconstruction and what the benefits are of this configuration. We will also
share our own clinical experience and three-year results.
How to use the CERAB technique

Access to both common femoral arteries is achieved either percutaneously or by
surgical cutdown of the vessel and two medium-length introducer sheaths are
placed (9Fr and 7Fr); after this, 5,000–7,500 units of heparin are administered.
The next step is recanalisation of the aortoiliac lesion (stenosis or occlusion)
in either an endoluminal or subintimal way. Depending on the lesions type and
location, different approaches and techniques can be used. After recanalisation of
both aortoiliac axes and aortic intraluminal guide wire placement, the 9Fr introducer
sheath is placed above the proximal margin of the aortic lesion. Through this
sheath, a balloon-expanded, polytetrafluoroethylene (ePTFE) covered stent (mostly
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12mm) is introduced and expanded in the distal aorta approximately 15mm to
• P Goverde, K Taeymans, K Lauwers and P Verbruggen
20mm above the bifurcation (Figure 1A). After expansion, this stent is flared with
a larger balloon, with a diameter adapted to the aortic diameter (mostly 16mm).
The marker of this postdilatation balloon is placed about 15mm to 20mm proximal
to the distal stent margin (Figure 1B). After optimal positioning and complete
expansion, the distal aortic stent part becomes funnel-shaped. Subsequently, two
iliac covered stents are placed, in a kissing-stent configuration, in this distal conic
segment (Figure 1C) and simultaneously inflated (Figure 1D). Both covered stents
should make a very tight connection with the aortic stent, as if were they moulded
together, simulating a neobifurcation. This new bifurcation mimics the normal
anatomy and should have comparable haemodynamics to that of an aortobifemoral
prosthesis or “flow splitter” of an endovascular aneurysm repair (EVAR) prosthesis
(Figures 1E and 1F).
Operators need to ensure they go from healthy to healthy tissue, so sometimes
extensions are needed. The introducers are then removed and the puncture sites can
then be closed, using regular vascular closure devices (i.e. StarClose and/or ProGlide,
Abbott). In the case of a hybrid intervention, a concomitant endarterectomy of
the common femoral and/or external iliac artery can be performed, to ameliorate
the outflow; this can be done either before or after the endovascular part. Post
Covered endovascular reconstruction of the aortic bifurcation
procedure, the patients (e.g. the case example in Figure 2) received standard
statin treatment and dual antiplatelet therapy for six months, which is followed by
aspirin monotherapy.
A B C
D E F
Figure 1: (A) CERAB technique: expansion of a 12mm covered stent in the distal aorta; (B) postdilatation and creation
of distal conic segment of the aortic stent; (C) placement of two covered stents in the iliacs; (D) simultaneous inflation
of the kissing covered stent configuration; (E&F) creation of covered neo-bifurcation with optimal haemodynamics
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A B
Figure 2: (A) Aorto-uni-iliac occlusion and subocclusive stenosis treated with contralateral
approach, reversal of the wire & predilatation; (B) final result with a CERAB in place.
The need for covered stents

One of the most important benefits of using covered stents is the ability to
immediately solve intraprocedural complications such as flow limiting dissections
and perforations.6

We use ePTFE balloon-expandable stent grafts for the reconstruction because
these stents can be postdilated with a few millimetres after deployment. Therefore,
you can create tailor-made reconstructions—flaring them to a diameter that
is adapted to the patients vessel diameter and, thus, avoid diameter mismatch..
Another benefit is the “dog-bone” inflation pattern because thrombotic debris is
trapped between the stent and vessel wall, thereby preventing or minimising distal
embolisation. The ePTFE balloon-expandable stent grafts that we use provide an
easy and accurate deployment and have an optimal radial force.
The ePTFE coverage could also serve as a mechanical barrier between the intimal
hyperplasia and the arterial lumen, which, consequently, could reduce the risk
of restenosis and improve patency rates. An additional benefit may be that this
layer can prevent the migration of macrophages into the vascular wall, which are
normally attracted by proinflammatory mediators secreted by the damaged vessel
wall and which induce inflammation and thereby restenosis.7
The most important trial showing a benefit in the use of covered stents is
COBEST (Covered vs. balloon expandable stent trial). In this study, 125 patients
with severe aortoiliac occlusive lesions (168 iliac arteries overall) were randomly
assigned to receive either a balloon-expandable covered stent or a bare metal stent.
After a 12-month follow-up period, investigators Mwipatayi et al found similar
outcomes between groups for the treatment of TASC-II A and B lesions. However,
for TASC-II C and D lesions, the covered stents were associated with significantly
better results compared with the bare metal stents regarding both patency and
clinical outcome.8 Also, the recently published five-year data for COBEST showed
an enduring patency benefit using covered compared with bare metal stents in the
treatment of TASC-II C and D lesions.9
Initially, the CERAB technique was mostly performed using Advanta V12 stents
(Maquet Getinge). However, due to manufacturing problems, the large diameter
Advanta V12 stents are now no longer available. Therefore, at present, we use
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A B
C D
Figure 3: (A) In vitro reconstructed CERAB configurations with Advanta V12 & V12 LD (Maquet
Geting); (B) with LifeStream balloon expandable vascular covered stent (Bard); (C) with
BeGraft peripheral stent graft system and BeGraft aortic (Bentley); (D) as alternative with the
body of an AFX endovascular abdominal aneurysm system (Endologix).
Begraft peripheral and Begraft Aortic (Bentley) and LifeStream (Bard) devices for
this indication.
As not every stent is always available, we tested—in vitro and in vivo—different
stent configurations to see if it was possible to build a CERAB. The Advanta V12
covered stent was the first to be intensively tested, followed by the LifeStream
stent. Both devices are made from 316L stainless steel and have a double layer
of ePTFE, with a porosity of 100–120µm for the Advanta V12 and of 10–40µm
for LifeStream. The two stents can be postdilated by at least 2mm without any
consequences. In the majority of cases, we use a 12mm diameter stent as the aortic
stent; this is either, if available, with the Advanta V12 LD or the LifeStream
device—both can be safely dilated up to 16mm (depending on the size of the
native distal aorta) Figure 3A and Figure 3B. Another possibility is the newer
BeGraft peripheral and aortic stent graft system (Bentley), which is a L605 cobalt-
chromium stent with a single external ePTFE layer and with a porosity of 102+/-
25µm. It can also be slowly postdilated to a larger diameter. One of the benefits
of the large diameter BeGraft aortic stent is that it is available in different lengths
and diameters up to 24mm (can be postdilated to 28mm) Figure 3C. If no larger
covered stents are available, a main body of the AFX endovascular aneurysm system
(Endologix) can be used as an alternative to reconstruct the aortic bifurcation with
or without extensions into the iliac arteries (Figure 3D)
Understanding the correct configuration

Groot Jebbink et al et al developed a biphasic flow model and a phantom model
of the abdominal aorta and aortoiliac bifurcation. In these models, different
configurations, used to treat aortoiliac lesions, could be compared regarding
flow disturbances. Four different configurations were tested: one bare metal self-
expanding kissing stent configuration; one kissing stent configuration with covered
balloon-expandable stents; and two CERABs with different positions of the iliac
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stents in the distal conic segment of the aortic stent. Different investigations were

performed (colour photographs, X-ray photographs, computed tomography [CT]
scanning and endoscopic imaging) and the results showed multiple differences
between the configurations regarding stent conformation, mismatch area and
volume or death space, triggering flow disturbances. The lowest radial mismatch
was found in the CERAB technique. Particle image velocimetry was also performed
in the biphasic model after dye injection, under continues and pulsatile flow. The
CERAB configuration had the most laminar flow without recirculation and kissing
stent configuration created turbulent flow with recirculation.10
In another study, in vivo geometry of kissing stent and CERAB were compared
by comparing anatomical characteristics on postoperative CT angiography. The
results showed a 16-fold higher mismatch area in the kissing stent group than
in the CERAB group. Mismatch volumes showed even larger differences. These
results not only confirm the above mentioned results of the in vitro study, but also
show that the in vitro results were largely underestimated. This radial mismatch or
protrusion mismatch could lead to flow perturbations and thrombus formation,
jeopardising patency of the stent configurations.4
These tests support the benefit of CERAB configuration in ameliorating
haemodynamics after aortoiliac bifurcation reconstruction and in this way

improving long-term patency.
Our clinical experience

Between February 2009 and July 2016, we treated 130 patients (69 male and
61 female) in two centres with the CERAB technique. The majority of lesions
(89.2%) were classified as TASC-II D. Median follow-up was 23.5 months (range
0–67 months).
The technical success rate was 96.9%. The remaining 3.1% were cases in which
the lesion could not be crossed. Most procedures were performed by bilateral
percutaneous access of the common femoral arteries (n=87; 66.9%). In 33.1%
of cases a surgical cutdown of either one or both femoral arteries was performed.
Brachial access was necessary in two procedures.
The mean procedure time was 152.7 ± 88 minutes. In 10.8% of the cases, there
were procedural complications, including unintentional dissection, arterial rupture
or thrombosis and all of them were solved during the initial procedure without any
further consequences. Median hospital stay was two days (range one to 76 days);
54.1% of the patients stayed in hospital for one to two days; 29.5% of the patients
stayed three to five days; and 6.8% were admitted for longer than five days.
At three weeks after the procedure, there were two cases of early thrombosis of
the CERAB. However, both were successfully treated; one by thrombectomy, and
the other by thrombolysis. The 30-day mortality rate was 0%.
Clinical improvement, expressed as an increase of at least one Rutherford
category, at six weeks follow-up was 86.7%. The median Rutherford category
changed from 3 (min: 1, max: 6) preoperative to a median of 0 (min: 0, max:
5) postoperative (P<.05). At 24 and 36 months the median Rutherford category
was 0 (min: 0, max: 6) and 0 (min: 0, max: 6), both significantly different with
respect to the preoperative staging. The ABI significantly improved from 0.65 ±
0.22 preoperatively to 0.88 ±0.15 after the procedure (P<0.05). At 24 and 36
months the ABI was respectively 0.97 ±0.14 and 0.99 ±0.14.
315
Limb salvage rate at one-year was 98.1% and 96.9% at three year follow-up. The
overall survival at one and three-year FU was 93.0% and 87.9%, respectively. The
primary patency outcome was very promising with 86.2% after 12 months, 83.9%
after 24 months and 82.1% after 36 months.11
Conclusion
Diffuse distal aortoiliac occlusive disease, especially the TASC-II C and D lesions,
are in literature still recommended to be treated with open surgery. However, with
the availability of different covered stents, the CERAB technique is an alternative
solution for the endovascular treatment of these challenging lesions. The technique
can be performed as a completely percutaneous approach or as a “hybrid” procedure,
combined with open surgical procedures such as endarterectomy.
Our three-years results are very promising with low complication rates and
short mean hospital stay combined with sustained clinical benefit and long-term
patency rates.
Summary
• Golden Standard/advice for treatment of TASC-II D aortoIliac occlusive disease

(AIOD) is still open surgery
• Endovascular interventions are now gaining more and more importance as a
valuable and safe solution in dealing with TASC-II C & D AIOD
• CERAB provides a feasible and durable technique, that mimics the native
aortoiliac bifurcation
• In vitro testing showed better results with the CERAB configuration regarding
geometry and flow dynamics compared to the more traditional interventional
options
• This technique can be done completely percutaneously through a 7 & 9Fr
sheat or as a hybrid procedure
• The CERAB reconstruction can lower hospital/ICU stay and the
rehabilitation period
• There is still a need for dedicated devices that can facilitate the intervention
and reduce procedure costs
References
1. Sabri S, Choudhri A, Orgera G, et al. Outcomes of covered kissing stent placement compared with bare
metal stent placement in the treatment of atherosclerotic occlusive disease at the aortic bifurcation. J
Vasc interv radiol 2010; 21: 995–1003.
2. Powell RJ, Rzucidol EM. Aortoiliac disease: endovascular treatment. Cronenwett Jl, Johnston KW,
editors. rutherford’s Vascular surgery, seventh edition. Philadelphia, Pa: saunders; 2010.
3. Vandeweyer D, Verbist J, Bosiers M, et al. Review choice of stent in iliac occlusive disease. Interventional
Cardiology 2011; 3: 373–79.
4. Groot Jebbink E, Ter Mors G, Slump C, et al. In vivo geometry of the kissing stent and covered
endovascular reconstruction of the aortic bifurcation configurations in aortoiliac occlusive disease.
Vascular 2017; 25 (6): 635–41.
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5. Goverde P, Grimme F, Verbruggen P, et al. Covered endovascular reconstruction of aortic bifurcation

(CERAB) technique: a new approach in treating extensive aortoiliac occlusive disease. J Cardiovasc
Surg (Torino) 2013; 54 (3): 383–87.
6. Elsner M, Auch-Schwelk W, Britten M, et al. Coronary stent grafts covered by a polytetrafluoroethylene
membrane. Am J Cardiol 1999; 84: 335–38: A8.
7. Marin ML, Veith FJ, Cynamon J, et al. Effect of polytetrafluoroethylene covering of Palmaz stents on
the development of intimal hyperplasia in human iliac arteries. J Vasc Interv Radiol 1996; 7: 651–56.
8. Mwipatayi BP, Thomas S, Wong J, et al. Covered versus balloon expandable stent trial (COBEST)
cinvestigators. A comparison of covered vs bare expandable stents for the treatment of aortoiliac
occlusive disease. J Vasc Surg 2011; 54: 1561–70.
9. Mwipatayi BP, Sharma S, Daneshmand A, et al. Durability of the balloon-expandable covered versus
bare-metal stents in the covered versus balloon expandables trial (COBEST) for the treatment of
aortoiliac occlusive disease. J Vasc Surg 2016; 64: 83–94.
10. Groot Jebbink E, Grimme FA, et al. Geometrical consequences of kissing stents and the covered
endovascular reconstruction of the aortic bifurcation configuration in an in vitro model for
endovascular reconstruction of aortic bifurcation. J Vasc Surg 2015; 61 (5): 1306–11.
11. Taeymans K, Groot Jebbink E, Holewijn S, et al. Three-year outcome of the covered endovascular
reconstruction of the aortic bifurcation technique for aortoiliac occlusive disease. J Vasc Surg 2017. Epub.
317
Endovascular vs. open
treatment of severe
aortoiliac occlusive disease—
outcomes of a kissing,
self-expanding covered
stent for reconstruction of
the aortic bifurcation
S Lepidi, F Squizzato and F Grego
Introduction
In severe aortoiliac occlusive disease, including Trans-Atlantic InterSociety
Consensus II (TASC II) lesions types C and D, aortobifemoral bypass grafting is
still considered the gold standard of treatment due to its long-term patency rates
(up to 90% at five years)—although it is associated with a non-negligible morbidity
and mortality.1,2 Because of the improvements in endovascular technology and
techniques, as well as in health-related quality of life, endovascular therapy has
been replacing open repair as primary treatment of aortoiliac occlusive disease for
both focal and advanced lesions in many cases.3,4 Two major vascular societies now
recommend an endovascular-first strategy for aortoiliac occlusive disease if it does
not compromise subsequent surgical options.5,6
This approach has been reflected at our centre, but, initially, endovascular
therapy was mainly indicated for high-risk patients and aortobifemoral bypass was
reserved for younger, fitter patients who could tolerate the procedure. Therefore,
with increasing experience, endovascular therapy is increasingly considered to be
the first-line treatment in all groups of patients. This relates to the evidence of low
complication rates and the possibility of performing a second-line aortobifemoral
bypass without any additional risks.
Endovascular reconstruction of the aortic bifurcation

In the subgroups of TASC C and D lesions, involving both iliac arteries and/
or the aortic bifurcation, the typical endovascular approach is the kissing stent
technique.7,8 Although the kissing stent is a straightforward technique, different
types of stents (such as balloon-expandable and self-expanding stents, with or
without fabric covering) and different technical approaches (the use pre- and
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post-dilatation of the occlusive lesions; stenting of the distal aorta, a separate stent
Endovascular vs. open treatment of severe aortoiliac occlusive disease—outcomes of a kissing, self-expanding covered stent for reconstruction of the aortic bifurcation
in the distal aorta with kissing stents inside) have been employed.9
Covered stents carry the potential advantage of a lower rate of in-stent restenosis.
In the prospective, randomised COBEST (Covered vs. balloon expandable stent
trial), covered balloon-expandable stents demonstrated better primary patency rates
than did bare metal stents in TASC C and D lesions.10 However, the trial was not
designed to include merely kissing stents. Sabri et al performed a retrospective
single-centre comparison between covered and. uncovered balloon-expandable
stents for the treatment of aortoiliac occlusive disease using the kissing technique.11
The authors reported significantly better primary patency rates at one and two
years for covered stents (92% and 92%, respectively) as compared to bare metal
stents (78% and 62% respectively); p=0.023 for the comparison. Regardless of any
potential patency advantages, covered stents may also provide a safety margin in the
treatment of complex common iliac and aortic lesions where rupture, dissections
and embolisation are possible complications. On the other hand, bare metal stents
are generally characterised by a lower profile, lower costs, and may be deployed
over the iliac bifurcation, without compromising the internal iliac artery patency.
Theoretically, heavily calcified lesions or ostial lesions favour the use of balloon-
expandable stents, which have greater radial strength and resistance to crush. That
they can be precisely deployed may be another potential advantage. However,
balloon-expandable stents are more rigid compared with self-expanding stents
and they conform less well to the aortic wall, especially in cases of tortuous
anatomy or in long lesions extending to the external iliac artery. Grimme et al
recently reported the results of balloon-expandable covered stents in the treatment
of aortoiliac occlusive disease involving the aortic bifurcation using the kissing
stent configuration.12 Goverde et al have described an interesting new approach or
the treatment of extensive aortoiliac occlusive disease—the covered endovascular
reconstruction of aortic bifurcation (CERAB) technique.13 This approach consists
of the use of three covered balloon-expandable stents to reconstruct the aortic
bifurcation: one delivered in the distal aorta and expanded in a tapered fashion;
and the other two deployed subsequently in a parallel fashion going from the
distal part of the tapered aortic stent to both common iliac arteries. However,
this technique may be disadvantaged by the need for a fixed length of distal aorta
stenting, the irreproducible expansion in the tapered fashion in a calcified aorta
and the delivery of the first stent in the distal aorta without concomitant iliac
stenting—which may result in an unprotected rupture of a calcified plaque at the
level of the aortic bifurcation.
Beyond these general considerations, there is no clear evidence on the best type of
stent and technique to be recommended, since the vast majority of published studies
are small single-centre retrospective analyses, without any comparison group.7
Kissing self-expanding covered stents

At our institute, we have preferentially adopted self-expanding covered stents to
reconstruct the aortic bifurcation in the kissing configuration. The adaptability of
self-expanding stents to calcific irregular atherosclerotic lesions in aortic bifurcation
may provide an advantage over the more rigid balloon expandable stents in terms
of long-term patency, whereas ePTFE covering provides protection against possible
serious intraoperative complications such as arterial rupture, dissection and distal
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thromboembolism. The flexibility of these stents may represent an important
advantage in cases of long lesions extending into the external iliac artery, which
is characterised by a more pronounced tortuosity and mobility compared to the
common iliac artery. Furthermore, as compared to balloon expandable stents, self-
expanding covered stents are commercially available in longer lengths (up to 25cm
in Viabahn, Gore) and a single stent may provide the treatment of long aortoiliac
lesions involving the entire length of the external iliac artery. This aspect acquires
a particular importance considering that our approach to treating iliac obstructive
lesions is based on stent deployment from healthy-to healthy vessel, mimicking an
“endo” aortobifemoral grafting.
Operative technique of kissing stents using self-expanding

covered stents
Local anaesthesia with conscious sedation, epidural or general anaesthesia are
provided, depending on the planned procedure complexity.
Bilateral femoral access is always obtained: percutaneous or open in case of
concomitant common femoral artery endarterectomy or anterior wall heavy
calcifications. Lesion crossing is first attempted from the retrograde femoral
access (Figure 2A) and, in case of failure, from an antegrade contralateral iliac or
left brachial artery access. Hydrophilic or specialty guidewires (0.018 or 0.035
inch) along with support catheters are used to cross the lesion intraluminally or
subintimally. Small (3–5mm diameter) non-compliant balloons are used to predilate
the site of occlusion (Figure 2B). A long and adequate-calibre introducer is inserted
over the wire bilaterally to advance the stent through the lesion.
Two self-expanding covered stents are then deployed simultaneously in a parallel
fashion from the same aortic level (at least 1.5cm above the aortic bifurcation) to
both iliac arteries distally (Figure 1). Post-dilatation of stents is performed with
Figure 1: (A) Preoperative 3D CT image showing extensive calcific TASCII D lesions in aortoiliac
occlusive disease. (B) Schematic drawing of parallel self-expanding covered stents from the distal
aorta to both iliac arteries covering the entire length of the occlusive lesions.
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Figure 2: Intraoperative images during the kissing self-expanding covered stents procedure. (A) Preoperative
angiography showing the occlusion of both common iliac arteries and severe stenosis of both external iliac arteries.
(B) After guidewire crossing, the lesions are predilated using kissing small-diameters balloons. (C) After self-expanding
covered stents delivery, the stents are post-dilated using appropriate-size balloons.
Figure 3: Kaplan-Meier curves of primary patency for the self-expanding covered stents group (dotted curve) and the
aortobifemoral group (dashed curve).
balloons 1mm smaller than graft diameter (Figure 2C) and a final angiogram
performed. For long lesions involving external iliac arteries, longer self-expanding
covered stents or additional overlapping covered or uncovered stents are deployed
to treat the entire lesion. In most cases, the internal iliac artery is preoperatively
occluded and a self-expanding covered stent covering the internal iliac artery
origin is placed; otherwise, a self-expanding bare metal stent is used to preserve the
patency of this vessel.
322
Common femoral artery open endarterectomy and patch angioplasty with
autologous great saphenous vein is associated in cases of common femoral artery
stenosis greater than 50%.
After the procedure, all patients are prescribed aspirin at a dose ranging from
81mg to 325mg and clopidogrel at 75mg daily, with dual antiplatelet therapy
continued for at least six weeks.
Kissing self-expanding covered stents vs. aortobifemoral

bypass
The aim of our study was to compare endovascular therapy using kissing self-
expanding covered stents with open repair using aortobifemoral grafting, in patients
presenting with extensive aortoiliac occlusive disease lesions (classified as TASC II
C and D involving both iliac arteries and/or the aortic bifurcation). A retrospective
review of all patients admitted to our institution for aortoiliac occlusive disease
between January 2009 and December 2016 was carried out. Patients were classified
into two groups: those who received a self-expanding PTFE-covered stent and
those who received aortobifemoral grafting.
During the study period, 100 consecutive patients were treated (50 with
aortobifemoral grafting and 50 self-expanding covered stents). Patients were similar
regarding symptoms at presentation (Rutherford category). Patients included in the
self-expanding covered stents group had a significantly higher perioperative risk,
measured as Society for Vascular Sugery (SVS) sum score (1.00±0.53 vs. 0.79±0.46;
p=0.047), SVS cardiac score (1.11±0.91 vs. 0.58±0.70; p=0.001) and American
Society of Anaesthesiologists (ASA) score (3.00±0.00 vs. 2.91±0.28; p=0.025).
Aortoiliac lesions of self-expanding covered stents group were classified as TASC II
C in 23 patients (46%) and TASC D in 27 (54%), whereas the aortobifemoral group
had a significantly higher number of TASC D lesions, being eight (16%) patients
classified as TASC C and 42 (84%) as TASC D (p=0.002). In the self-expanding
covered stents group, the mean number of stents per limb was 1.42±0.58, with a
mean length of coverage of 9.1±4.4cm. The same type of stent was always used on
each patient, Fluency (Bard/ now BD) were placed in 46 limbs and Viabhan (Gore)
in 54. Thirty-four limbs required additional procedures in the external iliac arteries:
a PTFE-covered stent was implanted in 16 cases (Fluency in nine limbs and Viabahn
in seven) and a bare metal stent (Easy Flype; Alvimedica) in 16.
Endovascular therapy was characterised by a significantly shorter length of
hospitalisation (4.1±5.6 days vs. 9.5 ± 5.2 days; p<0.001) and ICU stay (0±0.1
days vs. 2.5±1.1 days; p<0.001). Postoperative mortality was not observed for both
groups and major cardiac or respiratory adverse events rates were similar between
the two groups. The aortobifemoral group had a significantly higher cumulative
surgical complication rate (5% vs. 14%; p=0.023).
The Kaplan-Meier estimates of five-year primary patency were 88.8% (95%
CI, 78–99) and 89.8% (95% CI, 80–100) for the aortobifemoral and the self-
expanding covered stents group respectively (p=0.485) (Figure 3). Secondary
patency (aortobifemoral 100%, self-expanding covered stents 98.3%; p=0.301)
and limb salvage rates (aortobifemoral 100%, self-expanding covered stents 98.6%;
p=0.334) did not show any differences between groups.
The Cox proportional hazards model demonstrated that, among all clinical
and anatomical variables, Rutherford category was the only predictor of patency
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(hazards ratio [HR] 3.04, 95%CI 1.31–7.05; p=0.01), and this result was
confirmed by the multiple logistic regression model (odds ratio [OR] 2.76, 95%CI
1.25–6.38; p=0.02). The type of procedure (endovascular vs. open surgical), TASC
classification and SVS score were not significantly associated with patency.
Discussion
Several studies have been published on the outcomes of kissing stents for aortoiliac
occlusive disease treatment, with varying results. A systematic review has been
recently published by Groot Jebbink et al.9 The majority of the studies analysed in
this review presented retrospective single-centre data on aortoiliac occlusive disease
patients showing mixed preoperative clinical and anatomical characteristics and
treated with various type of stents and techniques. The pooled data from these
studies show an overall technical success rate of 98.7%, a complication rate of
10.8% and a primary patency at 12, 24 and 60 months of 89.3%, 78.6% and 69%
respectively.
Factors reported to affect patency include the presenting symptoms, anatomical
characteristics, protrusion length of the stents inside the aorta, a systematic pre-
and/or post-dilatation, crossing position of the stent, stent characteristics, and
post-interventional medications. No comparative data are available for assessing
outcomes of stent types—except for a retrospective single-centre comparison by
Sabri et al.11 They investigated covered vs. uncovered balloon-expandable stents and
reported significantly better (p=0.023) primary patency rates at one and two years
for covered stents (92% and 92%, respectively) as compared to bare metal stents
(78% and 62% respectively).
Besides the lack of comparative studies, only a few reports present the results of
uniform types of stents, since many published studies combine the results of balloon-
expandable and self-expanding stents, making impossible any comparison.8,14–17
Considering only series using similar types of stent, a five-year primary patency of
82% was reported in self-expanding bare metal stents by Houston et al, although a
much lower rate of 64% was reported more recently by Moon et al.18,19 Concerning
balloon-expandable bare metal stents, a two-year primary patency of 86.8% was
reported by Scheinert et al, although a much lower rate of 62% was observed in
the comparative study of Sabri et al.7,11 Grimme et al recently reported the results
of kissing balloon-expandable covered stents with a primary patency of 75.3% at
four years.12 The outcomes of 130 patients (89% TASC II D lesions) treated by the
CERAB technique were recently published, showing a three-year primary patency
of 82%.20
In the present series, 50 aortoiliac occlusive disease patients (46% TASC II C
and 54% TASC II D lesions) treated by kissing self-expanding covered stents were
evaluated over a longer follow-up (32±18 average months) and showed a five-year
primary patency of 89.8%, equivalent to the control group of aortobifemoral
patients (88.8%).
In our experience, although the overall number of TASC II D lesions were
significantly higher and comorbidity scores significantly lower in the open repair
group, the Cox proportional hazards and the multiple logistic regression results were
weighted for TASC classification and SVS score, that were not significantly associated
to patency with the Rutherford category being the only predictor of patency.
324
Severe aortoiliac occlusive disease lesions (TASC II C or D) frequently involve the
external iliac arteries and common femoral artery. In external iliac artery occlusive
disease, flexible, self-expanding stents are recommended because of the motion these
vessels undergo and the potential for kinking and crimping of balloon-expandable
stents placed in this location. In the present series, the mean length of coverage of
9.1±4.4cm. Self-expanding covered stents are currently available in longer lengths,
having the potential advantage to avoid zones of stent overlaps.
Conclusion
This is the first report on the results of self-expanding covered stent delivered in the
kissing configuration for treatment of severe aortoiliac occlusive disease involving
the aortic bifurcation. The kissing self-expanding covered stents technique of severe
aortoiliac occlusive disease lesions presented an excellent primary patency, equal
to aortobifemoral at five years. Self-expanding covered stents patients showed a
significant lower hospital and intensive care unit stay, as well as lower surgical
complications compared to aortobifemoral. Although self-expanding covered stents
presented significantly less advanced TASC lesions and greater total SVS comorbidity
score, multivariate statistical analyses showed that the only independent predictor
of primary patency was the preoperative clinical presentation.
Summary
• The kissing stents technique represents the endovascular approach of choice

to treat aortoiliac obstructive lesions involving the aortic bifurcation.
• Self-expanding covered stents are flexible, conformable and available in long
lengths, able to adapt to the often calcific, irregular and long atherosclerotic
lesions in this area, and to prevent complications like arterial rupture and
distal thromboembolism.
• In our experience, the five-year primary patency rate of kissing self-expanding
covered stents for the treatment of TASC C–D lesions is 90%, similar to
aortobifemoral bypass, although with shorter length of hospitalisation
and lower cumulative surgical complication rate.
• Clinical presentation, classified as Rutherford category, was the only
independent predictor of patency.
References
1. Norgren L, Hiatt WR, Dormandy JA, et al. Inter-society consensus for the management of peripheral
arterial disease (TASC II). J Vasc Surg 2007; 45 Suppl S:S5–67.
2. Indes JE, Pfaff MJ, Farrokhyar F, et al. Clinical outcomes of 5358 patients undergoing direct open
bypass or endovascular treatment for aortoiliac occlusive disease: a systematic review and meta-
analysis. J Endovasc Ther 2013; 20: 443–55.
3. Bosch JL, van der Graaf Y, Hunink MG. Health-related quality of life after angioplasty and stent
placement in patients with iliac artery occlusive disease: results of a randomized controlled clinical
trial. The Dutch Iliac Stent Trial Study Group. Circulation 1999; 99: 3155–60.
4. Upchurch GR, Dimick JB, Wainess RM, et al. Diffusion of new technology in health care: the case of
aorto-iliac occlusive disease. Surgery 2004; 136: 812–18.
325
5. Conte MS, Pomposelli FB, Clair DG, et al. Society for Vascular Surgery practice guidelines for
atherosclerotic occlusive disease of the lower extremities: management of asymptomatic disease and
claudication. J Vasc Surg 2015; 61 (3 Suppl): 2S–41S.
6. Aboyans V, Ricco JB, Bartelink MEL, et al. 2017 ESC Guidelines on the Diagnosis and Treatment of
Peripheral Arterial Diseases, in collaboration with the European Society for Vascular Surgery (ESVS).
Eur J Vasc Endovasc Surg 2017. Epub ahead of print.
7. Scheinert D, Schröder M, Balzer JO, et al. Stent-supported reconstruction of the aortoiliac bifurcation
with the kissing balloon technique. Circulation 1999; 100: II295–300.
8. Björses K, Ivancev K, Riva L, et al. Kissing stents in the aortic bifurcation--a valid reconstruction for
aorto-iliac occlusive disease. Eur J Vasc Endovasc Surg 2008; 36: 424–31.
9. Groot Jebbink E, Holewijn S, Slump CH, et al. Systematic review of results of kissing stents in the
treatment of aortoiliac occlusive disease. Ann Vasc Surg 2017; 42: 328–36.
10. Mwipatayi BP, Thomas S, Wong J, et al. Covered versus balloon expandable stent trial (COBEST) co-
investigators. A comparison of covered vs bare expandable stents for the treatment of aortoiliac
11. Sabri SS, Choudhri A, Orgera G, et al. Outcomes of covered kissing stent placement compared
with bare metal stent placement in the treatment of atherosclerotic occlusive disease at the aortic
bifurcation. J Vasc Interv Radiol 2010; 21: 995–1003.
12. Grimme FA, Spithoven JH, Zeebregts CJ, et al. Endovascular treatment of occlusive lesions in the aortic
bifurcation with kissing polytetrafluoroethylene-covered stents. J Vasc Interv Radiol 2015; 26: 1277–84.
13. Goverde PC, Grimme FA, Verbruggen PJ, et al. Covered endovascular reconstruction of aortic
bifurcation (CERAB) technique: a new approach in treating extensive aortoiliac occlusive disease. J
Cardiovasc Surg (Torino). 2013; 54 (3): 383–87.
14. Rzucidlo EM, Powell RJ, Zwolak RM, et al. Early results of stent-grafting to treat diffuse aortoiliac
15. Dorigo W, Piffaretti G, Benedetto F, et al. A comparison between aortobifemoral bypass and aortoiliac
kissing stents in patients with complex aortoiliac obstructive disease. J Vasc Surg. 2017; 65: 99–107.
16. Sharafuddin MJ, Hoballah JJ, Kresowik TF, et al. Kissing stent reconstruction of the aortoiliac bifurcation.
Perspect Vasc Surg Endovasc Ther 2008; 20: 50–60.
17. Yilmaz S, Sindel T, Golbasi I, et al. Aortoiliac kissing stents: long-term results and analysis of risk factors
affecting patency. J Endovasc Ther 2006; 13: 291–301.
18. Houston JG, Bhat R, Ross R, et al. Long-term results after placement of aortic bifurcation self-expanding
stents: 10 year mortality, stent restenosis, and distal disease progression. Cardiovasc Intervent Radiol
2007; 30: 42–47.
19. Moon JY, Hwang HP, Kwak HS, et al. The results of self-expandable kissing stents in aortic bifurcation.
Vasc Specialist Int 2015; 31: 15–19.
20. Taeymans K, Groot Jebbink E, Holewijn S, et al. Three-year outcome of the covered endovascular
reconstruction of the aortic bifurcation technique for aortoiliac occlusive disease. J Vasc Surg 2017 Epub.
326
Endo first vs. open surgery—the controversies and
evidence
Common femoral and
profunda artery disease are
best managed by open surgery
Introduction
Atherosclerotic disease of the common femoral artery and the femoral bifurcation
is often seen as a continuum of arterial disease. The common femoral artery and
its bifurcation are critically important in preservation of the lower limb arterial
tree. This is evidenced by the rapid onset of limb threatening ischaemia when
thrombotic or thromboembolic occlusion of the vessel occurs.
The transition towards minimally invasive procedures, demand for rapid return
to normal function, and reduced hospital bed occupancy continue to drive the
endovascular options for intervention—when comparable outcomes to open
procedures exist. However, while these technologies continue to rapidly evolve in
most arterial beds, their routine use in the common femoral artery and femoral
bifurcation has not been developed with as much enthusiasm. This chapter examines
the current evidence for treatment of the common femoral artery and its branches,
including the profunda femoris (deep femoral) artery.
Background
Patients with mild common femoral artery disease often present with mild
claudication affecting the thigh and lower leg. However, as the arterial disease
worsens, involving the inflow and outflow vessels, symptoms may progress to life-
style limiting claudication and critical limb ischaemia. Diagnosis of common femoral
artery and bifurcation pathology involves a thorough history, clinical examination
and non-invasive vascular investigations (ankle-brachial indices and arterial duplex
ultrasound). In patients in whom intervention is planned, vascular imaging—such
as magnetic resonance (MR) or computed tomography (CT) angiography—add
value in delineating the concomitant proximal and distal arterial disease and aid
planning any intervention.1
Typically, common femoral artery lesions are treated with endarterectomy
with selective patch repair, particularly for severe disease. This approach is
relatively simple and allows access to carry out concomitant procedures such as
iliac angioplasty or profundaplasty that is often required in patients with critical
limb ischaemia who have more than one level of disease. However, such surgical
treatments involving the common femoral artery and bifurcation are associated
with significant morbidity rates, particularly groin wound complications.
Angioplasty with or without stenting forms the foundation of endovascular
practice and these interventions continue to have improving technical success and
patency rates. Recent developments, such as plaque debulking strategies (atherectomy
329
catheters) and bioabsorbable scaffolds, may offer alternatives to traditional
surgical procedures like endarterectomy.2 However, the use of traditional stents in

highly flexible regions—e.g. the common femoral artery and its bifurcation—are
often considered to dispose to stent fracture and failure, particularly non-self-
expanding stents.
Evidence for surgery

Long-term patency rates of common femoral artery and bifurcation endarterectomy
reach 96% at seven years, with freedom from further revascularisation and survival
of 79% and 80% respectively.3 When the profunda femoris is involved in multilevel
Common femoral and profunda artery disease are best managed by open surgery •
disease, adding profundaplasty to bypass revascularisation has been shown

to improve long-term outcomes for both aortoiliac and infrainguinal
revascularisation techniques.1,4
Profundaplasty for profunda femoris or deep femoral artery ostial disease,
without femoropopliteal reconstruction in the setting of concomitant superficial
femoral artery occlusion, has been shown to play a role in the management of
severe claudication and critical limb ischaemia. In a recent study, profundaplasty,
with bovine pericardium patch repair, resulted in an overall 80% clinical success
rate—with claudication patients faring better than those with critical limb
ischaemia.5 Such procedures have been shown to provide valuable limb-salvage in
patients considered to be at high operative risk and/or who are unlikely to have
a successful distal bypass.1 Similarly, where major limb amputation is inevitable,
revascularisation of the profunda femoris is considered essential for below-the-knee
stump healing and preservation of the knee joint resulting in an enhanced degree
of functional rehabilitation.6
Data suggest that one in five patients (21.6%) who undergo femoral or bifurcation
surgery have a complication that may include wound infection, sutural aneurysm,
haematoma, lymphocele formation or nerve injury.1,7 Operative mortality has been
reported as high as 3.4%.6 Predictors of mortality include age, non-independent
pre-operative functional status, dialysis use, emergency treatment and high
American Society of Anesthesiologists (ASA) grade (4 and above) .
Evidence for endovascular treatment

Several reports of successful endovascular treatment of the profunda femoris and
femoral bifurcation exist. Isolated profunda femoris angioplasty has been shown to
be safe and effective in improving claudication walking distance in the setting of
long segment superficial femoral artery occlusion.1 Similarly, a series of 31 patients
with profunda femoris ostial stenosis (62% with concomitant superficial femoral
artery occlusion) had technical success of profunda femoris angioplasty alone in
90%, with an in-hospital limb salvage rate of 94% and a 71% cumulative event-
free survival rate at 34 months.8 However, 69% of patients required additional
endovascular interventions to the inflow and or outflow vessels.
Furthermore, considerable reservations remain about stenting the common
femoral artery.1 Due to its position, stent fracture due to flexion-extension
movements of the hip is a concern—particularly around the use of stiffer balloon-
expandable stents. Placing a stent in the common femoral artery restricts its use
as a future access vessel for cardiovascular investigations treatments (“metal jacket
330
phenomena”). Due to calcification, often bilaterally, access to the vessel lumen can
prove a challenge.
Focal common femoral artery disease is a relatively uncommon situation
in patients with critical limb ischaemia. It is more frequent in patients with
claudication, but the majority of these patients should be managed by cardiovascular
risk modification and supervised exercise. This limits the number of patients
who require revascularisation with common femoral artery disease suitable for
endovascular treatment alone. However, the current evidence discussed below
suggests, that in selected patients stenting is an acceptable option in thecommon
femoral artery.1
In a series of 27 consecutive patients (33 limbs) who underwent femoral
bifurcation endovascular intervention with stent placement, only one stent fracture
was seen in a patient who had a balloon-expandable stent.9 The others, with self-
expandable stents were fracture free over a median 23 months (common femoral
artery, n=19; profunda femoris, n=4; superficial femoral atery ostia n=2; and bypass
graft anastomosis, n=8). At three years, 83% of the vessels remained patent.
The role of endovascular treatment of common femoral artery and bifurcation
disease was further explored in a retrospective analysis of 360 consecutive
procedures,10 42.2% of which required inflow and or outflow procedures. After
balloon angioplasty, 36.9% of cases required stenting based on suboptimal
radiological appearance. Procedural failures (greater than 30% residual stenosis
on final angiography) were 7.2% with a combined complication rate of 6.4% at
30 days. At 12 months, data were available for 87.5% of cases, demonstrating
restenosis (greater than 50%) and target lesion revascularisation in 27.6% and
19.9% of cases respectively.
In a more focused study by the same group, 97 patients with focal common

femoral artery atherosclerotic disease (11 occlusive) from a screened pool of 516
underwent endovascular revascularisation with angioplasty.11 Stent placement was
reserved for suboptimal angiographic appearance that was identified in 38.1%
cases. Procedural success was 91.8%, with cumulative vascular complications of
7.2% at 30 days. At 12 months, restenosis (greater than 50%) and target lesion
revascularisation rates were 19.5% and 14.1% respectively.
Reports continue to emerge regarding the role of primary endovascular
atherectomy devices (directional or orbital laser).12–17 While concerns surrounding
embolic debris and restenosis with this strategy exist, atherectomy catheters have
been shown to reduce the role of traditional femoral endarterectomy and are devoid
of local wound complications associated with open surgical practice.6,18 In a series
report of 250 patients (579 lesions) who underwent infra-inguinal atherectomy
with or without adjunctive measures, the 18-month primary and secondary
patency rates for patients with claudication was 58% and 83% respectively. Larger
prospective multicentre trials will be necessary to assess the clinical value of these
procedures.19
Evidence for new technologies

In a single-centre, randomised controlled trial of bioabsorbable scaffold implantation
compared to surgery for patients with common femoral artery atherosclerotic lesions
in 80 patients, treatment was technically successful in 97.5%. Thirty-day and one-
year primary patency rates were 92% and 80% compared to 100% and 100% for
331
endarterectomy respectively (p<0.05); with secondary stent patency at one year
reaching 84%. Surgical site infection following surgery occurred in seven patients
compared to none in the group treated with bioabsorbable scaffolds (p=0.002).
Decalcification of heavily calcified common femoral artery and its bifurcation
using a Cavitron ultrasonic surgical aspirator (Dentsply Sirona) has recently been
reported as a hybrid procedure in combination with a vein patch angioplasty,
providing an alternative to traditional endarterectomy.20 While reported as being
feasible, in a series of 13 interventions (in 12 patients), there was one arterial
wall perforation and one wound infection requiring reintervention. In follow-up
imaging, all treated vessels confirmed patency albeit in a limited mean follow-up of
six months (one to 13 months).
Conclusion
A recent literature review of isolated atherosclerotic stenosis of the common femoral
artery identified seven surgical and four endovascular studies for analysis.21 Primary
patency was consistently higher with surgery as was target lesion revascularisation.
While survival was comparable between the groups, complications were higher in
those undergoing surgery (6-45% vs. 4.1–26%) with at least one complication in
7.9% of patients.22
Based on the current evidence available, patients who are able to tolerate
open surgery, do not have a hostile groin (current or past infection or imbedded
prosthetic material) and are not morbidly obese, should preferably undergo open
revascularisation as clinically indicated.23
Summary
• The common femoral artery and its bifurcation are critical segments of the
lower-limb arterial tree.
• Revascularisation of the profunda femoris in isolation may be beneficial for
patients with critical limb ischaemia or undergoing major limb amputation.
• Determining the presence of significant supra and infra-inguinal disease is
essential in planning intervention and maintaining clinical outcomes.
• Currently there are limited data available to support endovascular treatment
of isolated disease or as a continuum of atherosclerosis in the common
femoral artery and bifurcation as first-line treatment.
• Endovascular therapy is a potential consideration in those unable to tolerate
open surgery, or in those with a hostile groin.
• Large randomised controlled trials of surgery vs. endovascular treatments with
long-term clinical outcome date are required.
References
1. Thatipelli M, Misra S. Management of common femoral artery and bifurcation diseases. Vascular
Disease Management 2010; 7 (1): 27–30.
2. Yongquan G, Lianrui G, Lixing Q, et al. Plaque excision in the management of lower-limb ischemia of
atherosclerosis and in-stent restenosis with the SilverHawk atherectomy catheter. Int Angiol 2013; 32
(4): 362–67
332
3. Ballotta E, Gruppo M, Mazzalai F, et al. Common femoral artery endarterectomy for occlusive disease:
an 8-year single-center prospective study. Surgery 2010; 147 (2): 268–74.
4. Malone JM, Moore WS, Goldstone J. The natural history of bilateral aortofemoral bypass grafts for
ischemia of the lower extremities. Arch Surg 1975; 110 (11): 1300–06
5. Savolainen H, Hansen A, Diehm N, et al. Small is beautiful: why profundaplasty should not be forgotten.
World J Surg 2007; 31 (10); 2058–61.
6. Towne JB, Rollins DL. Profundaplasty: Its role in limb salvage. Surgical clinics of North America 1986;
66 (2): 403–14
7. Nguyen BN, Amdur RL, Abugideiri M, et al. Postoperative complications after common femoral
endarterectomy. J Vasc Surg 2015; 61 (6):1489–94.
8. Silva JA, White CJ, Ramee SR, et al. Percutaneous profundaplasty in the treatment of lower extremity
ischemia: results of long-term surveillance. J Endovasc Ther 2001; 8 (1): 75–82.
9. Stricker H, Jacomella V. Stent-assisted angioplasty at the level of the common femoral artery
bifurcation: midterm outcomes. J Endovasc Ther 2004; 11 (3):281–86.
10. Bonvini RF, Rastan A, Sixt S, et al. Endovascular treatment of common femoral artery disease: medium-
term outcomes of 360 consecutive procedures. J Am Coll Cardiol 2011; 58 (8): 792–98.
11. Bonvini RF, Rastan A, Sixt S, et al. Angioplasty and provisional stent treatment of common femoral
artery lesions. J Vasc Interv Radiol 2013; 24 (2): 175–83.
12. Das T, Mustapha J, Indes J, et al. Technique optimization of orbital atherectomy in calcified peripheral
lesions of the lower extremities: the CONFIRM series, a prospective multicenter registry. Catheter
Cardiovasc Interv 2014; 83: 115–22.
13. Dave RM, Patlola R, Kollmeyer K, et al. Excimer laser recanalization of femoropopliteal lesions and
1-year patency: results of the CELLO registry. J Endovasc Ther 2009; 16: 665–75.
14. Korabathina R, Mody KP, Yu J, et al. Orbital atherectomy for symptomatic lower extremity disease.
Catheter Cardiovasc Interv 2010; 76: 326–32.
15. Laird JR, Zeller T, Gray BH, et al. Limb salvage following laser-assisted angioplasty for critical limb
ischemia: results of the LACI multicenter trial. J Endovasc Ther 2006; 13: 1–11.
16. Zeller T, Krankenberg H, Steinkamp H, et al. One-year outcome of percutaneous rotational
atherectomy with aspiration in infrainguinal peripheral arterial occlusive disease: the multicenter
pathway PVD trial. J Endovasc Ther 2009; 16: 653–62.
17. Zeller T, Rastan A, Sixt S, et al. Long-term results after directional atherectomy of femoro-popliteal
lesions. J Am Coll Cardiol 2006; 48: 1573–78.

18. TASC Steering Committee. An update on methods for revascularisation and expansion of the TASC
lesion classification to include below-the-knee arteries: A supplement to the Inter-Society Consensus
for the Management of Peripheral Arterial Disease (TASC II). Journal of Endovascular Therapy 2015; 22
(5): 663–77.
19. McKinsey JF, Zeller T, Rocha-Singh KJ, et al. Lower extremity revascularisation using directional
atherectomy: 12-month prospective results of the DEFINITIVE LE study. JACC Cardiovasc Interv 2014;
7: 923–33.
20. Maeda S, Nakamura T. Decalcification of a heavily calcified common femoral artery and its bifurcation
with a Cavitron Ultrasonic Surgical Aspirator. EJVES Short Rep 2016; 34: 5–8.
21. Halpin D, Erben Y, Jayasuriya S, et al. Management of Isolated Atherosclerotic Stenosis of the Common
Femo ral Artery: A Review of the Literature. Vasc Endovascular Surg 2017; 51 (4): 220–27.
22. Siracuse JJ, Gill HL, Schneider DB, et al. Assessing the perioperative safety of common femoral
endarterectomy in the endovascular era. Vasc Endovascular Surg 2014; 48 (1): 27–33.
23. Stern JR, Bernhard VM. (2017) In the Patient with Profunda Artery Disease, Is Open Revascularisation
Superior to Endovascular Repair for Improving Rest Pain? In: Skelly C, Milner R. (eds) Difficult Decisions
in Vascular Surgery. Difficult Decisions in Surgery: An Evidence-Based Approach. Springer, Cham.
333
Endovascular first for
critical limb ischaemia is a
concept without evidence
L Meecham, MA Popplewell, S Patel and AW
Bradbury
Introduction
Despite a lack of “Level 1” evidence from randomised controlled trials
indicating durable clinical superiority over vein bypass, best endovascular
treatment is increasingly used to treat infrainguinal peripheral arterial disease in
patients presenting with critical limb-threatening ischaemia. The reasons for this
probably include:
• The attractiveness to patients and their physicians of perceived reduced
periprocedural morbidity and mortality
• The perception that a best endovascular treatment-first revascularisation
strategy is, therefore, likely to be associated with less resource use, at least in
the short term
• The fact that, in many countries, peripheral arterial disease is increasingly
treated by physicians who cannot offer surgical intervention
• The relentless marketing of endovascular devices by industry.
Although practice varies considerably, in the UK and many other countries,

plain balloon angioplasty, with the use of “bailout” bare metal stents where
post- plain balloon angioplasty angiographic appearances and/or flow are
considered to be unacceptable, is still widely considered to be the current
endovascular standard of care. This is because newer endovascular technologies,
in particular drug-coated balloons and drug-eluting stents, have not been shown
to produce superior clinical outcomes and are associated with significantly
increased procedural costs. In this chapter we make the argument that an
endovascular-first revascularisation strategy for critical limb-threatening ischaemia
has no evidence base.
Femoropopliteal disease
The only randomised controlled trial to have compared a bypass surgery-first with a
plain balloon angioplasty-first revascularisation strategy in patients presenting with
chronic limb-threatening ischaemia due to infrainguinal disease is the UK NIHR
HTA-funded BASIL (Bypass versus angioplasty in severe leg ischaemia) trial.1
Considering the trial cohort of 452 patients as a whole, BASIL showed that in
patients who lived more than two years, overall and amputation-free survival were
better following randomisation to bypass surgery than to plain balloon angioplasty.
335
Around 75% of the interventions in BASIL were in the femoropopliteal segment
• L Meecham, MA Popplewell, S Patel and AW Bradbury
and about 25% of the bypasses were performed using prosthetic grafts. When
femoropopliteal bypass surgery (n=128) is compared to femoropopliteal plain
balloon angioplasty (n=183) within the BASIL trial, overall and amputation-free
survival were non-significantly better in those patients randomised to bypass
surgery. This difference is more pronounced for vein bypass but still statistically
non-significant. However, both freedom from reintervention (76.6% vs. 65.6%,
hazards ratio [HR] 1.59, p=0.036) and major adverse limb events (71.1% vs
59.6%, HR 1.51; p=0.041) were significantly better following bypass surgery
(Figure 1). However, proponents of a best endovascular treatment-first approach to
critical limb-threatening ischaemia often point to the fact that BASIL patients were
randomised between 1999 and 2004 and argue that, were the trial to be repeated
using modern endovascular techniques and technologies, a different result in favour
of best endovascular treatment would be obtained. To examine this claim, we have
compared the outcomes following femoropopliteal plain balloon angioplasty in
BASIL with those observed in our unit following femoropopliteal best endovascular
treatment a decade later (2009–2014). Although technical success rate improved
somewhat (87% vs. 83%, not significant), overall and amputation-free survival
Endovascular first for critical limb ischaemia is a concept without evidence
Figure 1: Major adverse limb events in patients undergoing femoropopliteal bypass surgery and femoropopliteal plain
balloon angioplasty in the BASIL trial.
Figure 2: Amputation-free survival after femoropopliteal plain balloon angioplasty in the BASIL trial (1999–2004) and
in our vascular unit a decade later (2009–2014).
336
were significantly worse in the contemporary series (Figure 2). Therefore, claims

that the femoropopliteal BASIL trial data are no longer relevant to current vascular
practice are not supported by reality. Best endovascular treatment enthusiasts will
then argue that had drug-coated balloons and drug-eluting stents been available,
the BASIL trial would have reported in favour of best endovascular treatment.
However, this is also a specious argument. While industry sponsored studies have
reported improved anatomical outcomes with drug-coated balloons and drug-
eluting stents in patients with intermittent claudication, these devices have not
been shown to result in improved walking distances and there are virtually no data
in patients with critical limb-threatening ischaemia.2–12 Thus, all of the recently
published systematic reviews and meta-analyses have recommended randomised
controlled trials to investigate the role of drug-coated balloon and drug-eluting
stents in patients with critical limb-threatening ischaemia.13–16 The data for other
endovascular technologies such as atherectomy and stent grafts are even less
convincing.17–20
Looking to the future, the UK NIHR HTA-funded BASIL (Balloon vs. stenting
in severe ischaemia of the leg) 3 trial is currently randomising 861 critical limb-
threatening ischaemia patients deemed suitable for femoropopliteal endovascular
intervention to either plain balloon angioplasty plus bare metal stents, or drug-
coated balloon plus bare metal stents, or primary drug-eluting stents.21 The primary
endpoint is amputation-free survival. However, the investigators are collecting a
wide range of secondary clinical endpoints, patient reported outcomes measures
(PROMs), health-related quality of life (HRQL), and health economic data for

cost-utility analysis. A further argument often advanced by those advocating a best
endovascular treatment-first revascularisation strategy is that it is a “free-shot”;
in other words, if best endovascular treatment is unsuccessful then the patients
can have bypass surgery. However, once again, the reality is very different from
the endovascular “hype”. Thus, in BASIL, amputation-free survival in patients
undergoing secondary bypass surgery after failed plain balloon angioplasty
was significantly worse than those who underwent bypass surgery as their first
randomised treatment (40% vs. 60% at seven years; p=0.04) (Figure 3). Other
investigators have found the same.22,23 In summary, therefore, while the results
of further randomised controlled trials are awaited, the evidence we have already
Figure 3: Amputation-free survival in patients in the BASIL trial following bypass as their first procedure and following
bypass after failed endovascular intervention.
337
clearly indicates that critical limb-threatening ischaemia patients who are suitable
for femoropopliteal vein bypass should have vein bypass in preference to best
endovascular treatment as their first revascularisation procedure.
Infrapopliteal disease
At present, there are no published trials comparing infrapopliteal bypass surgery
and best endovascular treatment in patients with critical limb-threatening ischaemia
and so the arguments rehearsed above in respect of femoropopliteal disease
apply equally well, arguably even more so, below the knee. With regard to plain
balloon angioplasty, most of the available data describe anatomical as opposed to
clinical outcomes and derive from uncontrolled case series or the control arms
of industry-funded drug-coated balloon and drug-eluting stents studies. A recent
meta-analysis reported a pooled primary technical success of 91%, a primary
patency of 63%, and mortality and major amputation rates of around 15% in
6,769 patients undergoing infrapopliteal plain balloon angioplasty. The authors
concluded that these outcomes were suboptimal.24 With regard to drug-eluting
Figure 4: Overall survival following infrapopliteal vein bypass and plain balloon angioplasty in the BASIL-1 trial.
Figure 5: Time to cessation of rest pain following infrapopliteal vein bypass and plain balloon angioplasty in the
BASIL-1 trial.
338
Figure 6: Amputation-free survival following infrapopliteal bypass in the BASIL-1 trial (1999–2004) and in a
contemporary series from our own unit (2009–2014).
stents, several industry-funded studies have reported better anatomical outcomes

(primary patency, restenosis, target lesion revascularisation), and some also better
clinical outcomes (improved wound healing, reduction in event-free survival) when
compared to plain balloon angioplasty or primary bare metal stent.25–27 However,
the results of such studies should be interpreted with caution due to short follow
up (typically six to 12 months) and the heterogeneity of the techniques and
devices used in the active and control arms.28 As noted above, most drug-coated

balloon studies have been performed in patients with intermittent claudication
with limited femoropopliteal disease. Only two trials have reported drug-coated
balloon outcomes in the infrapopliteal segment. In the DEBATE-BTK trial, where
132 critical limb-threatening ischaemia patients were randomised to drug-coated
balloon angioplasty or to plain balloon angioplasty in a single centre, the use of a
drug-coated balloon was associated with better wound healing, reduction in binary
restenosis and lower rates of reocclusion.29 However, the much larger, multicentre
IN.PACT DEEP trial, where 352 patients were randomised to drug-coated balloon
angioplasty or plain balloon angioplasty, was stopped early as the amputation rate
in the drug-coated balloon arm was 2.4 times higher.30 Furthermore, drug-coated
balloon use was not associated with any anatomical advantage. Vein bypass using
ipsilateral great saphenous vein is associated with five-year patency and limb salvage
rates of 50–70% and 74–95% restrictively and is still considered by many vascular
surgeons to be the standard of care in patients with critical limb-threatening
ischaemia who require infrapopliteal intervention.31 However, advocates of a best
endovascular treatment-first revascularisation strategy for infrapopliteal disease
point to increased morbidity and mortality rates with femoro-distal vein bypass
when compared with infrapopliteal best endovascular treatment and the poor
results observed with prosthetic grafts below the knee. A recently published analysis
of 104 patients randomised in the BASIL trial to infrapopliteal vein bypass or
infrapopliteal plain balloon angioplasty reported a trend towards better amputation-
free survival (HR=0.68, 95% CI: 0.42–1.10, p=0.1), overall survival (HR=0.60,
95% CI: 0.36–1.02; p=0.06) (Figure 4) and time to wound healing (HR 1.69,
95% CI: 0.88–3.26) with vein bypass. Vein bypass patients also demonstrateda
significantly quicker relief of ischaemic rest pain (Figure 5).32
339
As already discussed, proponents of a best endovascular treatment-first
revascularisation strategy often claim that infrapopliteal BASIL-1 outcome data

are no longer relevant given subsequent advances in endovascular technologies
and techniques. However, as with femoropopliteal disease, this assertion is not
evidence-based. Indeed, despite an increase in immediate technical success (73%
to 91%), clinical outcomes following infrapopliteal plain balloon angioplasty
performed in our unit between 2009 and 2014 are no better than those reported
after infrapopliteal plain balloon angioplasty performed between 1999 and 2004
in the BASIL trial (Figure 6). Other investigators have reported similar findings,
casting serious doubt on the appropriateness of offering infrapopliteal endovascular
treatment to patients who could have distal vein bypass.33 Looking to the future, the
UK NIHR HTA-funded BASIL-2 trial is currently randomising up to 600 critical
limb-threatening ischaemia patients who require an infrapopliteal intervention
to a vein bypass-first or a best endovascular treatment-first revascularisation. The
primary and secondary endpoints are the same as for BASIL-3 described earlier.
Conclusion
At the present time, there are three publicly-funded randomised controlled trials,
BASIL-2 and BASIL-3 in the UK and the NIH-funded BEST-CLI in the USA,
randomising different subgroups of critical limb-threatening ischaemia patients to

either a bypass surgery-first or a best endovascular treatment-first revascularisation
strategy.21,34,35 The trial investigators have co-operated closely so that it will
be possible eventually to perform an individual patient data meta-analysis of
over 3,000 patients. In the meantime, the authors respectfully submit the only
reasonable, logical and unbiased conclusion that can be drawn from the data we
have already is that:
1. Patients presenting with critical limb-threatening ischaemia due to
femoropopliteal and/or infrapopliteal disease, and who can have a vein bypass
should have a bypass.
2. Outside of a randomised controlled trial, an endovascular-first revascularisation
strategy should be reserved for patients who cannot have a vein bypass.
340
Summary
• The current “Level 1” evidence base does not support an endovascular-first

revascularisation strategy in either the femoropopliteal or the infrapopliteal
arterial segment.
• Results from industry funded studies regarding drug eluting technology
have demonstrated improved anatomical outcomes in selected groups of
patients who are mostly claudicants. Results are yet to show a translation into
improved clinical, cost-effectiveness or HRQL outcomes.
• The data that we have suggests that if patients have a life expectancy greater
than two years, have suitable autologous venous conduit and are fit for
surgery, they would probably be best served with a vein bypass as their first-
revascularisation procedure.
• Ongoing randomised trials (BASIL-2, BASIL-3 and BEST-CLI) are due to report
outcomes on >3000 patients with CLTI undergoing revascularisation and will
better inform evidence-based revascularisation
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2. Werk M, Albrecht T, Meyer DR, et al. Paclitaxel-coated balloons reduce restenosis after femoro-popliteal
angioplasty: evidence from the randomized PACIFIER trial. Circ Cardiovasc Interv 2012; 5 (6): 831–40.
3. Rosenfield K, Jaff MR, White CJ, et al. Trial of a paclitaxel-coated balloon for femoropopliteal artery disease. N
Engl J Med 2015; 373 (2): 145–53.
4. Scheinert D, Duda S, Zeller T, et al. The LEVANT I (Lutonix paclitaxel-coated balloon for the prevention of
femoropopliteal restenosis) trial for femoropopliteal revascularization: first-in-human randomized trial of
low-dose drug-coated balloon versus uncoated balloon angioplasty. JACC Cardiovasc Interv 2014; 7 (1): 10–19
5. Zeller T, Beschorner U, Pilger E, et al. Paclitaxel-coated balloon in infrapopliteal arteries: 12-month results
from the BIOLUX P-II Randomized Trial (BIOTRONIK'S-First in Man study of the Passeo-18 LUX drug releasing
PTA balloon catheter vs. the uncoated Passeo-18 PTA balloon catheter in subjects requiring revascularization
of infrapopliteal arteries). JACC Cardiovasc Interv 2015; 8 (12): 1614–22
6. Tepe G, Laird J, Schneider P, et al. Drug-coated balloon versus standard percutaneous transluminal angioplasty
for the treatment of superficial femoral and popliteal peripheral artery disease: 12-month results from the
IN.PACT SFA randomized trial. Circulation 2015; 131 (5): 495–502.
7. Tepe G, Schnorr B, Albrecht T, et al. Angioplasty of femoral-popliteal arteries with drug-coated balloons:
5-year follow-up of the THUNDER trial. JACC Cardiovasc Interv 2015; 8 (1 Pt A): 102–8.
8. Fanelli F, Cannavale A, Corona M, et al.The “DEBELLUM” – lower limb multilevel treatment with drug eluting
balloon – randomized trial: 1-year results. J Cardiovasc Surg (Torino) 2014; 55 (2): 207–16.
9. Werk M, Langner S, Reinkensmeier B, et al. Inhibition of restenosis in femoropopliteal arteries: paclitaxel-
coated versus uncoated balloon: femoral paclitaxel randomized pilot trial. Circulation 2008; 118 (13): 1358–
65.
10. Dake MD, Ansel GM, Jaff MR, et al. durable clinical effectiveness with paclitaxel-eluting stents in the
femoropopliteal artery: 5-year results of the Zilver PTX Randomized Trial. Circulation 2016; 133 (15): 1472–83;
11. Duda SH, Bosiers M, Lammer J, et al. Drug-eluting and bare nitinol stents for the treatment of atherosclerotic
lesions in the superficial femoral artery: long-term results from the SIROCCO trial. J Endovasc Ther 2006; 13
(6): 701–10.
12. Duda SH, Pusich B, Richter G, et al. Sirolimus-eluting stents for the treatment of obstructive superficial
femoral artery disease: six-month results. Circulation 2002; 106 (12): 1505–09.
13. Cassese S, Ndrepepa G, Liistro F, et al. Drug-coated balloons for revascularization of infrapopliteal arteries: A
meta-analysis of randomized trials. JACC Cardiovasc Interv 2016; 9 (10): 1072–80.
341
14. Baerlocher MO, Kennedy SA, Rajebi MR, et al. Meta-analysis of drug-eluting balloon angioplasty and drug-
• L Meecham, M A Popplewell, S Patel and AW Bradbury
eluting stent placement for infrainguinal peripheral arterial disease. J Vasc Interv Radiol 2015; 26 (4): 459–73.
15. Sarode K, Spelber DA, Bhatt DL, et al. Drug delivering technology for endovascular management of
infrainguinal peripheral artery disease. JACC Cardiovasc Interv 2014; 7 (8): 827–39.
16. Katsanos K, Spiliopoulos S, Karunanithy N, et al. Bayesian network meta-analysis of nitinol stents, covered
stents, drug-eluting stents, and drug-coated balloons in the femoropopliteal artery. J Vasc Surg 2014; 59 (4):
1123–33.
17. Laird JR Jr, Yeo KK, Rocha-Singh K, et al. Excimer laser with adjunctive balloon angioplasty and heparin-
coated self-expanding stent grafts for the treatment of femoro-popliteal artery in-stent restenosis: Twelve-
month results from the SALVAGE study. Catheter Cardiovasc Interv 2012; 80: 852–59.
18. Regine R, Catalano O, De Siero M, et al. Endovascular treatment of femoropopliteal stenoses/occlusions with
a SilverHawk directional atherectomy device: Immediate results and 12-month follow-up. Radiol Med 2010;
115: 1208–18.
19. Garcia L, Jaff MR, Metzger C, et al. Wire-interwoven nitinol stent outcome in the superficial femoral and
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20. Lammer J, Zeller T, Hausegger KA, et al. Heparin-bonded covered stents versus bare-metal stents for complex
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arterial disease. J Am Heart Assoc 2013; 2 (6): e000345.
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lower extremity chronic limb-threatening ischemia. J Vasc Surg 2017; 66 (2): 466–75
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infrapopliteal arterial disease: systematic review and meta-analysis. Circ Cardiovasc Interv 2016; 9: e003468.
25. Bosiers M, Scheinert D, Peeters P, et al. Randomized comparison of everolimus eluting versus bare-metal
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55 (2): 390–98.
26. Scheinert D, Katsanos K, Zeller T, et al. A prospective randomized multicentre comparison of balloon
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Circulation 2013; 128 (6): 615–21.
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randomized trial. J Am Coll Cardiol 2014; 64 (15): 1568–76.
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Ischaemia of the Leg (BASIL) Trial. Eur J Vasc Endovasc Surg 2017; 54 (2): 195–201.
33. Patel SD, Biasi L, Paraskevopoulos I, et al. Comparison of angioplasty and bypass surgery for critical limb
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342
Endovascular first for critical
limb ischaemia is a concept
without evidence: A vascular
surgeon’s perspective
Introduction
Critical limb ischaemia is a diagnosis that represents a broad spectrum of disease,
ranging from rest pain to profound ischaemia with extensive gangrene and foot
sepsis. Unfortunately, with such a wide range of symptoms, there are multiple and
conflicting treatment modalities. It seems antithetical to invoke one modality as
the treatment of choice while leaving others for failure of endovascular therapy.
This becomes particularly important when one considers the incidence and cost
of critical limb ischaemia. The incidence of critical limb ischaemia has been
estimated upwards of 1,000/1,000,000 per year in industrialised countries, and
this may increase due to the prevalence and increase of risk factors such as diabetes,
smoking, and other metabolic syndromes.1–3
Also, providing care for patients with critical limb ischaemia is associated with
an almost US$10 billion cost per year throughout the world—US$3 billion of
which is in the USA.4–6 When looking at options for treating patients with critical
limb ischaemia, one needs to find a modality to account for the diagnosis as well
as multiple other factors. Factors that necessitate consideration include anatomy,
extent of disease and degree of tissue destruction, life expectancy, and availability
of autogenous conduit for reconstruction. The goal should be to provide enough
nutrient flow as directly as possible to the affected area to allow healing, maximise
quality of life, and provide limb salvage. The optimal techniques should be
durable, cost-effective, and minimise reintervention. We struggle to believe that
one technology, no matter how improved and how advanced, will be the panacea
for all patients with critical limb ischaemia.
Approach to decision-making for patients presenting with

critical limb ischaemia
The wide breadth of indications for critical limb ischaemia may direct the vascular
surgeon towards one therapy. Patients presenting with rest pain or minor tissue
loss may require only an incremental improvement in blood flow to alleviate their
ischaemic symptoms. Conversely, patients presenting with extensive tissue loss, foot
sepsis, and/or profound ischaemia, however, would require much more. Since most
patients presenting with critical limb ischaemia have multilevel occlusive disease,
one needs to first alleviate the inflow disease before the outflow disease is addressed.
343
The vast majority of patients can be treated by endovascular means or by hybrid
techniques involving inflow, angioplasty and stenting and femoral endarterectomy

or distal bypass. Also, patients presenting with femoral bifurcation disease as well
as superficial femoral artery disease can be treated by ileofemoral endarterectomy
and superficial femoral artery stenting in order to improve distal nutrient flow.
Unfortunately, many of the patients presenting with critical limb ischaemia have
significant manifestations from their long-term diabetes, smoking, hyperlipidaemia
and hypertension. These patients tend to have a distribution of disease that
is infrainguinal and specifically infrageniculate. Although there have been
improvements in techniques in endovascular therapies, such as retrograde pedal
access, drug-coated balloons and re-entry devices, this still remains an area in
which distal bypasses have shown increased durability, higher nutrient flow and
Endovascular first for critical limb ischaemia is a concept without evidence: A vascular surgeon’s perspective •
better limb salvage. This finding has been substantiated by data in both past and
more recent studies.7–10
This begs the next question, “What type of venous conduit does the patient have
in order to potentially undergo distal arterial reconstruction?” A duplex exam of
the greater saphenous, small saphenous, basilic and cephalic veins are important
to be able to discuss openly with the patient what their options and expectations
should be for wound healing, limb salvage and reintervention. One can logically
and intelligently discuss with a patient regarding an endovascular first approach,
especially a very aggressive endovascular first approach, when the operator knows
they are limited in conduit and that their other open surgical options are scarce.
Lastly, many have written that endovascular failures are most consistently seen
in patients with long, extensive calcified lesions, especially in diabetics with poor
runoff.7 In the initial angiogram, those patients with adequate conduit, long
occlusive lesions and poor runoff who present with significant gangrene, foot sepsis
or profound ischaemia are probably better suited to initial bypass than endovascular
therapy. Also, one must consider longevity of the patient and the patient’s current
physical status and quality of life. Although we have impressive technology, those
patients who are non-ambulatory and have a short lifespan who present with a poor
quality of life and profound ischaemia, may be better suited to primary amputation
or allowed to live symbiotically with their gangrene. With that said, I think it is
very important to get the input from the family and the patient and have a full
evaluation of the options outlined to them. Although historically we have seen
that there is a 50% mortality in critical limb ischaemic patients over a two-year
period, there have been other randomised trials reported in the last decade that
have shown that a two-year survival in excess of 70% can be seen in patients who
receive treatment.11–14
Why an “endo-first” for all patients is not the right approach

Endovascular treatment has advanced with smaller catheters and devices are more
steerable so that now almost all arteries down to the foot can be opened with
minimal morbidity and low mortality. However, there are not only significant
limitations of the technique, but there are also sequelae that may worsen the short
and even long-term results for patients with critical limb ischaemia.
Since the development of the Intersocietal Consensus for the management of
peripheral arterial disease (TASC II) from 2007, there has been little consensus
between those who perform solely interventional techniques and those who have the
344
option of interventional and open surgical procedures in how to treat patients with
critical limb ischaemia.1 In the original TASC II paper, TASC C & D lesions were
considered best served with operative therapy; however, in the more recent update,
which reflects a perceived improvement in endovascular therapy, the guidelines
have seemingly been pushed towards a more endovascular-first therapy.15–18
Schermerhorn et al has demonstrated that an endovascular-first approach
was associated with less early morbidity, but not mortality and had a potential
loss of approximately 9% of outflow with decreased patency of the secondary
procedures.19–22 This is corroborated in other studies and also demonstrated a
decrease in limb salvage. Although there are a few prospective randomised trials,
the most quoted is the BASIL (Bypass vs. angioplasty in severe leg ischaemia) trial.
As seen from the first and second publication, these studies revealed that 70% of
the patients who survived past the initial two-year period in bypass first approach
were associated with a higher overall survival and, although not statistically
significant, had an improved amputation-free survival. This was especially apparent
when subgroup analysis demonstrated the superiority of vein over prosthetic in
the outcomes of patients who received surgical reconstruction.23 Also, although
endovascular therapy was less expensive in the first year, the cost became equivalent
over the three-year period. Thus it should be noted that the conclusions for this trial
are that patients predicted to live more than two years and had a usable vein should
usually have bypass surgery first. If the patient is expected to live fewer than two
years and those without usable vein should have balloon angioplasty as the primary
procedure. Similarly, Barshes et al developed a framework for evaluation of value
and cost effectiveness in the management of critical limb ischaemia. In this study,
they demonstrated that the cost of initial bypass with subsequent endovascular
revisions was roughly half that of an endovascular-first procedure. However, this
cost was mitigated in those patients who had small ulcers, thus demonstrating that
endovascular first may be better suited for those patients with small ulcers or rest
pain that need the smaller incremental increase in blood flow.
Even more recently, the BEST-CLI (Best endovascular vs. best surgical therapy
for patients with critical limb ischemia) trial is now trying to answer many of
the questions that we have posited in comparing peripheral intervention to open
surgical reconstruction. Hopefully, this trial, as well as the BASIL II and BASIL
III trials, will help answer questions regarding the comparative effectiveness of
endovascular options against open surgical therapy, especially in light of evolving
technologies, such as drug-coated balloon and drug-eluting stents. This will help us
not only in outcomes, such as patency, wound healing, and limb salvage, but also
would be very important when one looks at the entire longitudinal cost of these
procedures.
The patients suited to an “open-first” approach

Our group has performed over 15,000 infrainguinal reconstructions over the past
40 years. Despite being a primarily endovascular-first group, we still reserve bypass
for selected patients. Our rationale has been that those patients with significant
foot sepsis, tissue loss and extensive arterial occlusive disease who have a usable
venous conduit may do better with an aggressive surgical approach as opposed
to an endovascular-first approach with potential for lessening of their tissue loss.
Currently we see a 3:1 ratio in endovascular to primary open bypass reconstruction
345
but follow patients in both arms closely to make sure the primary endpoints such
as wound healing, increased perfusion as judged by noninvasive studies, as well

as aggressive necrotic tissue removal for early ambulation and wound healing. We
evaluated our results over a two year period from 2008 to 2010 with 1,316 bypasses
and primary endovascular procedures performed on 844 limbs and found by using
a “balanced” approach reserving bypass for those patients with severe gangrene,
sepsis and extensive occlusive disease we could generate a combined limb salvage
rate of endo and open patients of 93% at two years.24 Many times it is a misnomer
to say it is bypass first therapy in the sense that many of these patients have had
interventions by other endovascular specialists such as cardiologists, interventional
radiologists, and other vascular surgeons and now present to us prior to amputation.
With that said, distal reconstruction, primary or secondary, has become somewhat
of a lost art in many institutions.

Many have been appropriately concerned about the early postoperative
complications that can ensue with either primary infrainguinal reconstruction
such as wound complications or vein harvest complications, swollen legs and
groin infections secondary to lymphatic leak, or poor hygiene. However, looking
historically at the data derived from many institutions that performed infrainguinal
reconstruction when conceded the five-year limb salvage rates for those reported
studies are below 90% at five years.25,26 This is in contradistinction to the current
data for endovascular therapy where many of the two-year limb salvage rates
are in the high 70% to low 80%. One could argue that we are taking on more
difficult patients with endovascular therapy or could equally argue that these
patients are referred for amputation without consideration of open surgical
therapy. Interestingly as amputation rates have decreased as shown by Goodney
et al, unfortunately close to 60% of patients who receive amputations have not
had any preceding endovascular or open procedures. I would argue that not only
do we have a problem with people receiving the wrong therapy; many patients are
still being deprived of any therapy. We are getting closer to having pre procedure
algorithms based on objective data such as the lower extremity grading system
(LEGS) to guide initial treatment of those patients with critical limb ischemia as
well as the Wound, Ischemia, and foot Infection (WIfi) criteria.27,28 It has been
shown numerous times that the initial financial impact of open surgical therapy
is greater than endovascular therapy; however, I think it is incumbent upon us
to look at the longitudinal cost, especially with the identification that multiple
endovascular procedures tend to be needed in order to achieve reasonable limb
salvage and wound healing.
Conclusion
The choice of initial therapy should not be based on the surgeon’s or
interventionalist’s skillset, market forces, or patient desire. Our goal as physicians is
to appropriately diagnose and offer the best, most durable cost-effective treatment
for our patients that will improve their quality of life, increase their chance of the
wound healing and preservation of their limb and offer the least mortality. This
can only be accomplished by databased decision making process where we use all
technology available to us; medical therapy, observational therapy, endovascular
therapy, and open surgical reconstruction. There is still much work to be done to
provide objective data for not only the physicians performing these procedures, but
346
more importantly to provide informed consent for our patients and their families
when they present with these profoundly difficult problems.
Summary
• A balanced approach to patients with critical limb ischemia will maximise limb
salvage
• Patients with good venous conduit and significant tissue loss may benefit from
primary bypass as opposed to an endo first approach
• Physicians treating critical limb ischemia need to have technical skills for
endovascular and open distal reconstruction
References
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long infrapopliteal lesion in diabetic patients with critical limb ischemia: are TASC II recommendations
suitable? A population-based cohort study. Int J Low Extrem Wounds 2012; 11: 277-85.
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14. Allie DE, Hebert CJ. Critical limb ischemia: a global epidemic. A critical analysis of current treatment
unmasks the clinical and economic costs of CLI. Eurointervention 2001; 1: 75–84.
15. Gerhard-Herman MD, Gornik HL, Barrett C, et al. 2016 AHA/ACC guideline on the management of
patients with lower extremity peripheral artery disease: executive summary: a report of the American
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Cardil 2017; 69: 1465–508.
16. Forbes JF, Adam DJ, Bell J, Fowdes FG, Gillespie I, Raab GM et al. Bypass versus angioplasty in severe
ischaemia of the leg (BASIL) trial: health-related quality of life outcomes, resource utilization, and cost-
effectiveness analysis. J Vasc Surg 2010; 51: 43S–51S.
17. Conte M. Bypass versus angioplasty in severe ischaemia of the leg (BASIL) and the (hope for) dawn of
evidence-based treatment of advance limb ischemia. J Vasc Surg 2010; 51: 69S-75S.
347
18. Iida O, Soga Y, Yamauchi Y, et al. Anatomical predictors of major adverse limb events after infrapopliteal
Endovascular first for critical limb ischaemia is a concept without evidence: A vascular surgeon’s perspective • CC Yeh, JC Hnath and RC Darling III
angioplasty for patients with critical limb ischaemia due to pure isolated infrapopliteal lesions. Eur J
19. Darling JD, McCallum JC, Soden PA, Korepta L, Guzman RJ, Wyers MC, et al. Results for primary bypass
versus primary angioplasty/stent for lower extremity chronic limb-threatening ischemia. J Vasc Surg
2017; 66 (2): 466–75.
20. Darling JD, Bowdewes TCF, Deery SE, Guzman RJ, Wyers MC, Hamdan AD et al. Outcomes after first-
time lower extremity revascularization for chronic limb-threatening ischemia between patients with
and without diabetes. J Vasc Surg 2017; S0741-5214.
21. Bodewes TCF, Darling JD, Deery SE, O’Donnell TFX, Pothof AB, Shean KE, et al. Patient selection and
perioperative outcomes of bypass and endovascular intervention as first revascularization strategy for
infrainguinal arterial disease. J Vasc Surg 2018; 67 (1): 206–16.
22. Shean KE, Soden PA, Schermerhorn ML, Zettervall SL, Deery SE, Darling JD et al. Lifelong limb
preservation: A patient-centered description of lower extremity arterial reconstruction outcomes. J
Vasc Surg 2017; 66 (4): 1117–22.
23. Bradbury AW, Adam DJ, Bell J, et al. Bypass versus angioplasty in severe ischaemia of the leg (BASIL)
trial: Analysis of amputation free and overall survival by treatment received. J Vasc Surg 2010; 51:
18S–31S.
24. Darling RC III, Mehta M, Roddy SP, Chang BB, Kreienberg PB, Paty PSK, et al. Distal bypass in the
endovascular first era: Is there still a need for open surgery? (Abstract) J Vasc Surg 2011; 54 (3): 922.
25. Shah DM, Darling RC III, Chang BB, Fitzgerald KJ, Paty PSK, Leather RP. Long term results of in situ
saphenous vein bypass: Analysis of 2058 cases. Ann Surg 1995; 222: 438–48.
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infrainguinal reconstructions. J Vasc Surg 1996; 21: 403–12.
27. Mills JL, Conte MS, Armstrong DG, et al. Society for Vascular Surgery Lower Extremity Guidelines
Committee. The Society for Vascular Surgery Lower Exgtremity Threatened Limb Classification System:
risk stratification based on wound, ischemia, and foot infection (Wifi). J Vasc Surg 2014; 59 :220–34.
28. Taylor SM, Kalbaugh CA, Gray BH, Mackrell PJ, Langan EM, Cull DL, et al. The LEGS Score: A proposed
grading system to direct treatment of chronic lower extremity ischemia. Ann Surg 2003; 237 (6): 812–18.
348
Emerging devices and interventional techniques:
Vessel preparation devices
Treating the superficial
femoral artery with a
serration balloon catheter
Introduction
We treat patients with lower extremity occlusive disease to achieve the critical
outcome of durable arterial lumen gain to improve tissue perfusion. Endovascular
techniques to dilate an artery started with Charles Dotter and device and technique
refinement continues to this day.1 The tools and armaments for vascular specialists
to seek reliable lumen gain are diverse, often costly, and unfortunately, not always
successful.2–4 We have made strides with the tools and techniques to treat more
complex lesions. In an evolving scenario, serratoplasty using the Serranator PTA
serration balloon catheter (Cagent Vascular) is a simple and cost-effective solution.
Concept
The concept of serration is common in everyday experience. Shark teeth, bread
knives, and paper tablets use serration technology and benefit from the mechanical
advantages that serrations provide. Granite and marble is quarried using serration
engineering to use the minimal amount of force to control fracture planes. A
tomato is precisely cut using a serrated knife allowing a simple motion to generate
the desired focal plane of disruption. The principle behind the development is that
serrated material is more responsive to directed energy (Figure 1).
The Serranator’s mechanism of action enables predictable and controlled lumen
expansion along the serrated lines with minimal injury. Serrations are ubiquitous in
devices and products and in engineering for buildings and other structures. Once
a serration is produced, similar to a fault line, any energy that is applied tends to
preferentially flow along that line. This has now been applied to atherosclerotic
plaque in the superficial femoral artery (Figure 2).
The Serranator Alto PTA serration balloon catheter treats superficial femoral
artery and popliteal lesions, using an over-the-wire nylon semicompliant balloon
dilatation catheter with four embedded serrated metal strips designed to perform
percutaneous transluminal angioplasty in the peripheral vasculature. The serrated
strips are designed to create linear, interrupted scoring along the endoluminal
surface during balloon angioplasty. The metal serrated strips allow focal precise
application of force that achieves maximal lumen gain with the least amount of
barotrauma. The device sizes are 4mm, 5mm and 6mm in diameter with 40, 80
and 120mm lengths. The device is compatible with an 0.018 inch guidewire and a
6Fr sheath. Serranator provides the possibility of less injury associated with dilation
of a complex superficial femoral artery or popliteal lesion.
351
Treating the superficial femoral artery with a serration balloon catheter •
Figure 1: Serrated material is more responsive to directed energy. Serration enables predictable and controlled
lumen expansion along the serrated lines with less injury than uncontrolled balloon expansion. After the
serration is produced, similar to a fault line, energy that is applied tends to preferentially flow along that
serrated line.
Figure 2: The Serranator Alto PTA serration balloon catheter treats superficial femoral artery and popliteal
lesions, using an over-the-wire balloon dilatation catheter with four embedded serrating metal strips. The
serrated strips create linear, interrupted scoring along the endoluminal surface.
Clinical evidence
The PRELUDE study, led by principal investigator Andrew Holden, was conducted
in study centres in New Zealand and Europe.5 The primary objective was to
evaluate the technical feasibility of the Serranator device. Safety was defined as a
composite of major adverse events and periprocedural death, assessed at 30 days
post procedure. Efficacy was the rate of device success, defined as the achievement
of successful delivery, balloon inflation/deflation, device retrieval with a final
diameter stenosis of <50% by visual assessment at the intended target site using
only the Serranator device. A key secondary objective was to assess the feasibility of
using optical coherence tomography (OCT) and intravascular ultrasound (IVUS)
in a subset of patients to evaluate the serration.
The study enrolled 25 patients, of which 80% were male. Twenty (80%) of the
lesions treated were in the superficial femoral artery and five (20%) were in the
popliteal arteries. One patient had an inflow artery treated prior to Serranator. The
average lesion length was 4.65cm (1.52–9.77) and the reference vessel diameter was
5.05mm (3.96–6.12). There was 100% technical success with the device (n=25).
352
Figure 3: The serration effect

can be demonstrated with
intravascular ultrasound. The
serration effect is marked by
arrows.

The acute angiographic results demonstrated lumen gain from a prediameter
stenosis of 88% (59–100%), to 23% (13–29%) post Serranator use. Of note is
that 32% (n=8) of the lesions were chronic total occlusions and 56% (n=14) had
moderate-to-severe calcification as determined by an angiographic core lab. There
were no flow limiting dissections. One bailout stent (4%) was placed after treatment
of a chronic total occlusion. In the subset of patients (n=10) who underwent post
Serranator OCT or IVUS imaging, all showed a serration effect (Figure 3).
All images were analysed by a core lab. To date, 24 patients have returned for
the 30-day follow-up, all of whose treated arteries are patent per the core lab.
There were no target lesion revascularisations, and no serious or major adverse
events related to using the device. Clinical experience so far suggests that highly
complex lesions such as occlusions or heavily calcified lesions may be treated with
the Serranator. Some of these features are demonstrated in Figures 4 and 5, which
are cases from the PRELUDE Study.
Vessel preparation
The need for improved lesion preparation devices is becoming apparent in the
era of drug-coated balloon angioplasty.6–8 The Serranator is an ideal, cost-effective,
adjunctive technology that may be an ideal bridging device. For instance,
Serratoplasty facilitates controlled lumen gain in complex lesions, and in theory
it could allow drug-coated balloon technologies to have full effacement and drug
apposition along the lumen mitigating the risk of drug-coated balloon-related
barotrauma; therefore allowing the maximum drug to wall apposition and lowering
dissection risk. The serration creates focal points of intimal disruption along
which the expansile force of the angioplasty balloon is propagated. Additionally, a
single preclinical porcine study in bilateral superficial femoral artery and profunda
353
Figure 4: Highly calcified distal
A B superficial femoral artery lesion.

The figure shows a pre- and post-
Serranator image of a complex,
eccentric, highly calcified
lesion of the distal superficial
femoral artery. Standard balloon
angioplasty is only occasionally
successful with this type of lesion.
(A) shows pretreatment reference
vessel diameter of 6.12mm;
94.59% stenosis; lesion length of

30.04mm and severe calcification.
(B) shows post-treatment residual
stenosis of 24.07% and no
dissection.
Figure 5: This figure

A B demonstrates treatment of a
popliteal artery occlusion with
the Serranator with minimal
residual stenosis and a type B
dissection (per core lab). (A)
shows pretreatment reference
vessel diameter of 4.19mm;
100% stenosis; lesion length
of 54.28mm and mild or no
calcification. (B) shows post-
treatment residual stenosis of
20.23% and type B dissection.
arteries compared drug uptake after use of the Serranator followed by a drug-
coated balloon vs. plain balloon angioplasty followed by a drug-coated balloon. The
animal was kept alive for seven days. Ten arterial tissue samples were analysed by
an independent laboratory. The preliminary data demonstrated a 2.8 times greater
paclitaxel drug uptake (micrograms/mm2) in per mm length and 2.7 times greater
total paclitaxel uptake in the Serranator samples.9 These data suggest that serrations
may also serve as microchannels into the artery wall for the drug.
This device may also be useful as a post-atherectomy adjunctive technology.
Regardless of debulking or compliance modification platforms, post-atherectomy
angioplasty is critical for maximising outcomes and lumen gain, especially
354
A B
Figure 6: Use of the Serranator in tortuous, small calibre anatomy. (A) shows a cadaver study showing a 2.5mm X
40mm device inserted retrograde into the anterior tibial artery, passed into the peroneal artery and inflated. (B) shows
a different cadaver study showing the Serranator passed into the pedal arch.
in those focal areas that atherectomy did not fully address. The arterial lumen
post-atherectomy is also at significant risk of further injury given recent plaque
modifications with additional interventions. The radiation, expense, and risk of
atherectomy warrants the best feasible durable lumen gain, which might make
the argument for the additional plaque modification of the low barotrauma

Serranator technology.
There is future applicability for the development of the Serranator in the
infrapopliteal arteries. A recent cadaver study reveals data forn a 2.5mm X 40mm
device that is inserted retrograde into the anterior tibial artery and tracked to the
peroneal artery and inflated. The device is able to track through tortuous, small
calibre anatomy, including the pedal arch (Figure 6).
Conclusion
Serration technology is apparent in multiple real-world venues and permits the
direction of energy along the serrated line. Serranator permits this process in the
superficial femoral artery. The highly morphologically variable plaque present in
the superficial femoral artery may be prepared for success by the Serranator. Early
results from the PRELUDE study suggest that the Serranator can provide the acute
lumen gain required to achieve success with lower extremity revascularisation.
355
Summary
• There is a need for better endovascular techniques and vessel preparation

devices
• Serranator Alto PTA Serration Balloon Catheter uses the well-known principle
of serrations to dilate a diseased vessel
• The serrated strips embedded on the outside of the balloon are designed
to create linear, interrupted scoring along the endoluminal surface during

balloon angioplasty
• Serranator enables predictable and controlled lumen expansion along the
serrated lines with minimal injury
• Serrated material is more responsive to directed energy
• The PRELUDE study successfully demonstrates the safety and effectiveness of
the Serranator device
• The Serranator may be an ideal adjunctive therapy when used prior to drug-
coated balloons or stents or in combination with atherectomy
References
1. Dotter C and Judkins M. Transluminal treatment of arteriosclerotic obstruction: description of a new
technic and a preliminary report of its application. Circulation 1964; 30: 654–670.
2. Laird, J. Limitations of percutaneous transluminal angioplasty and stenting for the treatment of
disease of the superficial femoral and popliteal arteries. Journal of Endovascular Therapy 2006; 13 (2):
S II30–40.
3. Nguyen B, et al. Late outcomes of balloon angioplasty and angioplasty with selective stenting for
superficial femoral-popliteal disease are equivalent, Journal of Vascular Surgery 2011; 54(4) 1051–57.
4. AT Hirsch et al. National health care costs of peripheral arterial disease in the Medicare population.
Vascular Medicine 2008; 13: 209–15.
5. CSR-0182, Cagent Vascular PRELUDE interim study internal report 2017.
6. Armstrong E and Brodmann M. Vessel preparation and plaque modification of infrainguinal lesions.
Endovascular Today 2017; 6 (9).
7. Garcia, L. Does vessel preparation still matter in DCB era? Presentation at LINC 2017.
8. Fanelli F, et al. Calcium assessment and impact on DEB. Cardiovasc Intervent Radiol 2014; 37: 898–907
9. Cagent Vascular 15-RP-1002Rev01
356
The use of directional
atherectomy prior to
drug-coated balloons
RHA Welling, OJ Bakker, GJ de Borst and FL Moll
Introduction
The recent European guideline on peripheral arterial disease states that there is
Class IIb evidence (i.e. the usefulness or efficacy is less well-established by evidence
or opinion) to support the use of drug-coated balloons in femoropopliteal occlusive
lesions. This recommendation for patients with intermittent claudication or severe
chronic limb ischaemia is based on level A data (i.e. data derived from multiple
randomised clinical trials or meta-analyses) for short (<25cm) de novo lesions.1
Drug-coated balloons provide the benefits of antiproliferative drugs, without the
need for an implanted drug-eluting stent—which is itself associated with late stent
thrombosis. In 2016, sirolimus became the first drug after paclitaxel to be approved
for use in these balloons. Sirolimus, also known as rapamycin, was previously
unsuccessful as a balloon coating due to its molecular instability, slow uptake and
its inability to achieve long-term tissue retention. With the use of nano-capsules,
however, these problems have been addressed.2,3
Drugs from the “-limus family”—sirolimus, everolimus and zotarolimus—inhibit
the mammalian Target Of Rapamycin (mTOR), stopping the cell cycle before
DNA replication, which results in a cytostatic effect.4 The safety and efficacy of
sirolimus-coated balloons in coronary lesions has recently been reported, and is
currently being assessed for femoropopliteal lesions.3 Paclitaxel works mostly in the
mitosis phase of the cell cycle, impairing centrosomes and disrupting microtubules.
This disturbance in cells that are almost ready to divide, induces apoptosis, which
is the basis for paclitaxel’s cytotoxic effect.
Even though paclitaxel-coated balloons have shown superiority to plain balloon
angioplasty in peripheral arterial disease, most trials have excluded severely calcified
lesions.5–7 Effectiveness in these lesions remains disappointing, and additional
debulking might be the key to ensuring lesion patency. The concept of atherectomy
was first presented by American cardiologist John Simpson.8 During a 1982 autopsy,
he used a pleural biopsy needle to remove a plaque from an atherosclerotic coronary
artery. The evolved endovascular version was granted a premarket approval in 1990,
and now almost 30 years later, atherectomy has become an established alternative
in both coronary and peripheral interventions.
The DEFINITIVE LE trial, a multinational prospective single-arm study to
evaluate the effectiveness of directional atherectomy in 800 patients, reported high
treatment successes and a low bailout stent rate of just 3%.9 However, in studies
comparing atherectomy to balloon angioplasty, no significant improvement in
long-term patency has been found.10,11 It is thought that by combining drug-coated
357
balloons and atherectomy clearing out a smooth new lumen, it is possible to achieve
• RHA Welling, OJ Bakker, GJ de Borst and FL Moll
more homogenous balloon-vessel contact, higher drug accumulation and deeper

vessel wall penetration.12 This should lead to both high technical success rates and
improved long-time patency, even in severely calcified lesions.
Observational data for combined procedures

In the common femoral artery, the use of endovascular therapies has been limited,
as surgical endarterectomy is a relatively easy procedure with excellent long-term
patency.13 However, surgical endarterectomy is not without complications and these
include wound infections and lymph fistulas.14 Two recent single-centre registries
analysed the efficacy of combined atherectomy and drug-coated balloon treatment.
The first reported on 47 patients treated with a drug-coated balloon of whom 21
had vessel preparation with directional atherectomy.15 The comparison between the
two groups favoured atherectomy, but the difference in outcomes between groups
did not reach statistical significance. A second registry included only patients with
grade three calcification of the artery (calcifications on both sides of the lumen >1
cm in length).16 All 30 patients treated with directional atherectomy and drug coated
Use of directional atherectomy prior to drug-coated balloons
balloons achieved technical success. Bailout stenting was required in three patients,
and at one year, a revascularisation procedure was required in two (6.7%) patients.
A similar prospective registry for grade three calcifications in the femoropopliteal
segment included 30 patients.17 In this study, patients were treated for lesions
under 15cm in length with directional atherectomy and drug-coated balloon.
The intervention was successful in all patients without any procedural adverse
events. Target lesion revascularisation was required three patients, and all patients
experienced an improvement in Rutherford class.
Another study of drug-coated balloons in the femoropopliteal segment compared
28 patients pretreated by orbital atherectomy with 61 who were not.18 Patients
treated with atherectomy more often had a calcium circumference ≥180 degrees
(83% vs. 43%), higher calcium grade 3–4 (83% vs. 42%) and more often calcium
lengths of ≥5cm (78% vs. 38%). Despite this difference in calcium burden, there
was no difference in primary patency or 12-month revascularisation. Furthermore,
lesions that underwent atherectomy were less likely to need bailout stenting
(18% vs. 39%). A third observational study investigated the effect of different
treatments after directional atherectomy.19 One-third of patients (n=29) were
treated with drug-coated balloons, while two-thirds of patients (n=60) were treated
with standard balloon angioplasty. Long lesions were treated in this study; on
average, these were 153mm in the drug-coated balloon group and 180mm in the
balloon angioplasty group. In-stent restenosis was treated in 27 (30%) and 36
(40%) lesions, respectively. Technical success was achieved in all patients, and at
12 months, freedom from restenosis was significantly higher in the drug-coated
balloon group (84.7% vs. 43.8%). To control for selection bias in this retrospective
study, the authors used inverse propensity weighting in a multivariable cox model
and this resulted in a hazard ratio of 0.28 in drug-coated balloon for restenosis-risk.
A final registry focused solely on lesions in the popliteal artery. The popliteal
artery is subjected to additional mechanical forces due to the mobility of the knee
joint, which influences stent complications and restenosis ratios.20 Among the
included patients, 41 underwent directional atherectomy followed by drug-coated
balloon inflation, while in 31 other patients, only the drug-coated balloon inflation
358
was inflated. Lesions were on average 42mm and 47mm, and were situated in the

P2 segment in most patients (73% and 68%). Technical success did not differ
significantly (93% vs. 84%, p=0.24), but at one year follow-up, primary patency
rates were significantly higher with atherectomy plus drug-coated balloon inflation,
than with drug-coated balloon inflation alone (82% vs. 65%, respectively).
DEFINITIVE AR—a randomised pilot study

The DEFINITIVE AR (Directional atherectomy followed by a paclitaxel-coated
balloon to inhibit restenosis and maintain vessel patency)—a pilot study of anti-
restenosis treatment study—is the only randomised controlled trial to assess the
effect of directional atherectomy before drug-coated balloon.21 In this study,
lesions between seven and 15cm in the femoropopliteal segment were pretreated
with directional atherectomy in 48 patients, while in 54 others no debulking was
performed. Lesions in the atherectomy group were longer compared with the drug-
coated balloon-only group (112.3mm vs. 96.6mm; p=0.05), but other characteristics
did not differ significantly. Technical success was higher in the atherectomy group
(89.6% vs. 64.2%) and fewer patients required adjunctive therapy such as bailout
stenting or post dilatation (6.3% vs. 37.0%). One-year primary patency did not

reach a statistically significant difference (82.4% vs. 71.8%; p=0.41). A post-
hoc analysis of angiographic patency showed a trend towards an advantage for
atherectomy (95% vs. 68.8%) in lesions longer than 10cm. The authors could
not find a significant difference in functional outcomes between the two groups,
and postulate that the overall lack of statistical power is most likely a result of the
limited cohort size in this pilot study.
Severely calcified lesions, defined as fluoroscopic dense calcifications extending >5
continuous centimetres, were excluded from randomisation, but were treated with
the atherectomy plus drug-coated balloon combination in a separate analysis arm
(n=19). Technical success was achieved in 85.4% of patients, without any clinically
relevant adverse events. Patency at 12 months was 68.8%, as measured with duplex
Vessel No. of Technical One-year

Segment patients Success primary patency
Observational
Stravoulakis 2017b CFA 21 95% 88%
Cioppa 2017 CFA 30 100% 90%
Cioppa 2012 Fempop 30 100% 90%
Foley 2017 Fempop 28 98% 77%
Kokkinidis 2017 Fempop (ISR) 112 98% 87%
Stavroulakis 2017 Popliteal 41 93% 82%
Randomized controlled trial
Gandini 2013 SFA (ISR) 24 100% 67%
Zeller 2017 Fempop 48 90% 85%
Procedural and one-year results of combined atherectomy and drug-coated balloon treatment.
CFA: Common femoral artery, SFA: superficial femoral artery, fempop: femoropopliteal segment, ISR: in-stent restenosis.
359
ultrasound. Surprisingly, no clinically driven target lesion revascularisation was
required in this complex subgroup of patients.
Treatment of in-stent restenosis

The treatment of in-stent restenosis poses a different challenge for endovascular
debulking. Calcium is rare in these lesions, with over 50% of the neointimal volume
made of collagen and proteoglycans.22 Not only does this make the lesion more
“spongy” and unsusceptible to balloon dilation due to strong recoil, it also makes
it harder for mechanical atherectomy devices to remove the plaque. Simultaneously,
there is an increased risk of stent disruption, stent fractures or even cutter head
entrapment.23 The EXCITE ISR (Excimer laser randomized controlled study for
treatment of femoropopliteal in-stent restenosis) trial investigated the efficacy of
excimer laser atherectomy before balloon angioplasty in 250 patients with in-stent
restenosis in the femoropopliteal segment.24 Procedural success, freedom from
target lesion revascularisation and 30-day major adverse events, all favoured the
use of excimer laser. As a result, laser atherectomy is, at the moment, the only
atherectomy device approved by the US Food and Drug Administration for the
treatment of in-stent restenosis.

A small single-centre randomised trial investigated the additional benefit of drug-
coated balloon inflation after laser atherectomy in in-stent restenosis, comparing 24
patients with the combination treatment with 24 patients treated by drug-coated
balloon inflation only.25 All patients were classified as having Rutherford class 4
or 5 lesions, and an in-stent occlusion in the superficial femoral artery. Lesions
were on average 20mm. Technical success was achieved in all patients, but target
lesion revascularisation was required in 16.7% of the laser plus drug-coated balloon
inflation patients, vs. 50% in the drug-coated balloon inflation -only group. Limb
salvage rates at one year were also better in the laser plus drug-coated balloon
inflation group (66.7% vs. 54.2%).
A larger retrospective study of 112 patients, showed similar results favouring
the combined use of laser atherectomy and drug-coated balloon inflation (n=62)
over laser atherectomy and balloon angioplasty (n=50).26 Patients treated with a
combination of laser and drug-coated balloon inflation required less bailout stenting
(31.7% vs. 58%), had a better freedom from target lesion revascularisation (72.5%
vs. 50.5%) and, in a subgroup of patients with in-stent occlusion, experienced
improved freedom from one-year reocclusion.
Aneurysmal degeneration
The adjunctive use of drug-coated balloons appears to be of benefit for most
de novo lesions and in-stent restenosis. However, a potential complication has
not yet been addressed: aneurysmal degeneration. This may occur after minor
vessel wall injuries caused by atherectomy cannot heal due to the inhibition of
the healing response by the paclitaxel. In the 41 patients who were treated by
directional atherectomy and drug-coated balloon inflation for isolated popliteal
lesions, three popliteal aneurysms (7%) were found on follow-up exams.20 One of
these popliteal arteries had a diameter over 2.5cm and required a stent graft in the
degenerated segment.
360
Aneurysm formation is not uncommon after atherectomy; the DEFINITIVE LE

trial reported aneurysms in 0.4% of patients, 30 days after directional atherectomy.9
Surprisingly however, no other study in either the peripheral or coronary vessels
has reported an increased incidence of aneurysms after atherectomy combined with
drug-coated balloon inflation.27 Moreover, the DEFINITIVE AR study explicitly
denounces the occurrence of aneurysm formation.21 The only available animal
study on atherectomy followed by drug-coated balloon inflation also did not detect
any signs of aneurysm formation.28
Conclusion
Current knowledge about the combined usage of drug-coated balloon inflation s
after atherectomy is based on several prospective and retrospective observational
studies. The combined treatment was technically successful in a high percentage of
cases (89.6–100%, in patients who often had long and calcified lesions). One-year
primary patency rates were also high (77–90%). For comparison, the DEFINITIVE
LE study that treated 800 patients with only directional atherectomy showed
12-month primary patency rates of 78% in claudicants and 71% in patients with
critical limb ischaemia.9

At the moment, the available studies suggest that atherectomy prior to drug-
coated balloon use is safe and effective in the long term, even in severely calcified
lesions and in-stent restenosis. However, several hurdles are yet to be overcome.
The studies discussed here all report atherectomy success after a residual stenosis
of less than 30%. However, drug uptake is reduced by presence of any atheroma
or calcium.12 The DEFINITIVE AR study confirmed the importance of reduced
residual stenosis and showed a significant correlation with 12-month patency.21 On
the other hand, being too rigorous in the atherectomy might cause severe vessel
injury, and this in turn can lead to restenosis in itself. For now, it is not known to
what extent the atherectomy has to be performed.
Due to the observational quality of most studies and the lack of statistical
significance from the DEFINITIVE AR pilot study, the superiority of a mechanical
and pharmacological combination remains uncertain. Furthermore, the studies
reported here have only used directional or orbital atherectomy, leaving the possible
beneficial effects of rotational atherectomy and laser atherectomy for de novo lesions
unknown. The possible adjunctive effect of drugs from the “-limus family” instead
of the cytotoxic paclitaxel also remains to be investigated. Until the combination of
mechanical and pharmacological lesion treatment has been assessed in sufficiently
powered randomised studies, the promising results presented here should thus be
interpreted with care.
361
Summary
• Atherectomy prior to the use of drug-coated balloons is safe in longer and

calcified lesions.
• Atherectomy increases procedural success and the adjunctive use of drug-
coated balloons increases long-term patency.
• Current knowledge is based on primarily observational studies and requires
adequately powered randomised-controlled trials to show superiority.
References
1. Aboyans V, Ricco J-B, et al. 2017 ESC Guidelines on the diagnosis and treatment of peripheral arterial
diseases, in collaboration with the European Society for Vascular Surgery (ESVS). Eur J Vasc Endovasc
Surg. Epub.
2. Granada JF, Tellez A, Baumbach WR, et al. In vivo delivery and long-term tissue retention of nano-
encapsulated sirolimus using a novel porous balloon angioplasty system. EuroIntervention 2016; 12
(6): 740–47.
3. Cortese B, di Palma G, Latini RA, et al. Immediate and short-term performance of a novel sirolimus-
coated balloon during complex percutaneous coronary interventions. The Fatebenefratelli sirolimus
coated-balloon (FASICO) registry. Cardiovasc Revascularization Med 2017; 18 (7): 487–91.
4. Wessely R, Schömig A and Kastrati A. Sirolimus and paclitaxel on polymer-based drug-eluting stents.
J Am Coll Cardiol 2006; 47 (4): 708–14.
5. Schroeder H, Werner M, Meyer D-R, et al. Low-dose paclitaxel–coated versus uncoated percutaneous
transluminal balloon angioplasty for femoropopliteal peripheral artery disease clinical perspective.
Circulation 2017; 135 (23): 2227–36.
6. Laird JR, Schneider PA, Tepe G, et al. Durability of treatment effect using a drug-coated balloon for
femoropopliteal lesions. J Am Coll Cardiol 2015; 66 (21): 2329–38.
7. Scheinert D, Duda S, Zeller T, et al. The LEVANT I (Lutonix paclitaxel-coated balloon for the prevention
of femoropopliteal restenosis) trial for femoropopliteal revascularization. JACC Cardiovasc Interv 2014;
7 (1): 10–19.
8. Simpson JB. How atherectomy began: A personal history. Am J Cardiol. 1993; 72 (13): E3-E5.
9. McKinsey JF, Zeller T, Rocha-Singh KJ, et al. Lower extremity revascularization using directional
atherectomy: 12-month prospective results of the DEFINITIVE LE study. JACC Cardiovasc Interv 2014;
7 (8): 923–33.
10. Janas A, Milewski K, Buszman P, et al. Long term outcomes of percutaneous lower-extremity arterial
interventions with balloon angioplasty versus atherectomy-propensity score matched registry. Postep
w Kardiol Interwencyjnej 2016; 12 (1): 85–86.
11. Dattilo R, Himmelstein SI, Cuff RF. The COMPLIANCE 360° trial: A randomized, prospective, multicenter,
pilot study comparing acute and long-term results of orbital atherectomy to balloon angioplasty for
calcified femoropopliteal disease. J Invasive Cardiol 2014; 26 (8): 355–60.
12. Tzafriri AR, Garcia-Polite F, Zani B, et al. Calcified plaque modification alters local drug delivery in the
treatment of peripheral atherosclerosis. J Control Release. 2017; 264: 203–10.
13. Nishibe T, Maruno K, Iwahori A, et al. The role of common femoral artery endarterectomy in the
endovascular era. Ann Vasc Surg 2015; 29 (8): 1501–07.
14. Gouëffic Y, Della Schiava N, Thaveau F, et al. Stenting or surgery for de novo common femoral artery
stenosis. JACC Cardiovasc Interv 2017; 10 (13): 1344–54.
15. Stavroulakis K, Schwindt A, Torsello G, et al. Directional atherectomy with antirestenotic therapy vs
drug-coated balloon angioplasty alone for common femoral artery atherosclerotic disease. J Endovasc
Ther 2018; 25 (1): 92–99
16. Cioppa A, Stavroulakis K, Schwindt A, et al. Combined use of directional atherectomy and drug-coated
balloon for the endovascular treatment of common femoral artery disease: immediate and one-year
outcomes. EuroIntervention 2017; 12 (14): 1789–94.
17. Cioppa A, Stabile E, Popusoi G, et al. Combined treatment of heavy calcified femoro-popliteal lesions
using directional atherectomy and a paclitaxel coated balloon: one-year single centre clinical results.
Cardiovasc Revascularization Med 2012; 13 (4):219–23.
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18. Foley TR, Cotter RP, Kokkinidis DG, et al. Mid-term outcomes of orbital atherectomy combined with

drug-coated balloon angioplasty for treatment of femoropopliteal disease. Catheter Cardiovasc Interv
2017; 89 (6): 1078–85.
19. Sixt S, Carpio Cancino OG, Treszl A, et al. Drug-coated balloon angioplasty after directional atherectomy
improves outcome in restenotic femoropopliteal arteries. J Vasc Surg 2013; 58 (3): 682–86.
20. Stavroulakis K, Schwindt A, Torsello G, et al. Directional atherectomy with antirestenotic therapy vs
drug-coated balloon angioplasty alone for isolated popliteal artery lesions. J Endovasc Ther 2017; 24
(2): 181–88.
21. Zeller T, Langhoff R, Rocha-Singh KJ, et al. Directional atherectomy followed by a paclitaxel-coated
balloon to inhibit restenosis and maintain vessel patency twelve-month results of the DEFINITIVE AR
study. Circ Cardiovasc Interv 2017; 10 (9): pii e004848.
22. Gandini R, Del Giudice C. Synergistic strategy of laser atherectomy and drug eluting balloon
angioplasty for treatment of in-stent restenosis in the superficial femoral artery. Lasers in Cardiovascular
Interventions 2015: 181–90.
23. Vandenberg JC. Laser synergism with drug eluting balloon for treatment of in-stent restenosis in the
lower extremities. Lasers in Cardiovascular Interventions 2015: 171–79.
24. Dippel EJ, Makam P, Kovach R, et al. Randomized controlled study of excimer laser atherectomy
for treatment of femoropopliteal in-stent restenosis: initial results from the EXCITE ISR trial. JACC
Cardiovasc Interv 2015; 8 (1 Pt A): 92–101.
25. Gandini R, Del Giudice C, Merolla S, Morosetti D, Pampana E, Simonetti G. Treatment of chronic SFA
in-stent occlusion with combined laser atherectomy and drug-eluting balloon angioplasty in patients
with critical limb ischemia: a single-center, prospective, randomized study. J Endovasc Ther 2013; 20
(6): 805–14.

26. Kokkinidis DG, Hossain P, Jawaid O, et al. Laser atherectomy combined with drug-coated balloon
angioplasty is associated with improved 1-year outcomes for treatment of femoropopliteal in-stent
restenosis. J Endovasc Ther 2017; 25 (1): 81–88.
27. Rissanen TT, Uskela S, Siljander A, et al. Percutaneous coronary intervention of complex calcified
lesions with drug-coated balloon after rotational atherectomy. J Interv Cardiol 2017; 30 (2): 139–46.
28. Tellez A, Dattilo R, Mustapha JA, et al. Biological effect of orbital atherectomy and adjunctive paclitaxel-
coated balloon therapy on vascular healing and drug retention: early experimental insights into the familial
hypercholesterolaemic swine model of femoral artery stenosis. EuroIntervention 2014; 10 (8): 1002–08.
363
Drug-coated balloons, stents, drug-eluting stents
and bioabsorbable scaffolds
ILLUMENATE: European
randomised controlled
trial two-year results
M Brodmann
Introduction
Drug-coated balloons are becoming a widely accepted and the preferred first-line
therapy for the treatment of femoropopliteal disease in patients with claudication.
As such, there is a continued effort and investment by the industry to evolve
drug-coated balloon therapy and improve the safety and efficacy of these devices
through optimisation of the coating characteristics. The goals of the modern drug-
coated balloon are to maximise drug transfer to the target lesions while minimising
systemic drug loss. Due to differences in coatings and drug transfer capabilities,
robust clinical evidence is required for each drug-coated balloon; clinical data from
one drug-coated balloon cannot be generalised to another.
Critical components of a drug-coated balloon

Drug-coated balloons are not simply angioplasty balloons dipped in paclitaxel. The
performance of a drug-coated balloon is dependent on the balance of multiple
factors, including the right coating morphology, excipient and drug dose. Currently,
all commercially available drug-coated balloons use paclitaxel as the active drug.
Paclitaxel is hydrophobic, meaning it does not bind to aqueous media, such as
blood, but it is lipophilic and naturally captured by the fatty tissue constituents
after direct contact with the vessel wall.
Paclitaxel morphology on the balloon surface can range from amorphous to
crystalline. Having an optimal mix of both, along with the correct excipient, is
essential for an effective drug-coated balloon. Amorphous paclitaxel promotes
coating durability during device handling and during transit through the vasculature
towards the target lesion. It is also transferred more quickly to the vessel wall.
However, evidence suggests that amorphous drug does not stay resident in the
vessel wall at therapeutic levels for as long as crystalline paclitaxel.1 Preclinical
data show crystalline paclitaxel dissolves into the tissue slowly for sustained release
over time and remains at therapeutic levels beyond the 30-day restenotic cascade.
However, a coating that is too crystalline is more brittle and flaky, increasing loss
during handling and downstream embolisation. Figure 1 demonstrates the different
pharmacokinetic properties of different paclitaxel morphologies.
The excipient is another critical component. Excipients help facilitate and
maximise paclitaxel adherence to the balloon during tracking and transfer from the
balloon to the arterial wall during inflation. The type and amount of excipient are
important design considerations that ensure that the paclitaxel is not excessively
and prematurely lost before the drug-coated balloon reaches the target lesion.
367
ILLUMENATE: European randomised controlled trial two-year results • M Brodmann
Figure 1: Serrated material is more responsive to directed energy. Serration enables predictable and controlled
lumen expansion along the serrated lines with less injury than uncontrolled balloon expansion. After the serration
is produced, similar to a fault line, energy that is applied tends to preferentially flow along that serrated line.
The Stellarex DCB

The Stellarex DCB (Philips) was designed to carefully balance the critical factors
described earlier and has been proven safe and effective in a series of robustly
conducted clinical trials.2–5 The dose of paclitaxel is low, at 2µg/mm2. However,
the coating consists of the optimal mixture of both amorphous and crystalline
paclitaxel morphologies, merging the characteristics of both. Animal study data
have indicated the formulation creates a durable coating that minimises drug
loss during insertion and transit to the treatment site and provides optimal drug
transfer with drug resident at a therapeutic dose throughout the 30-day restenotic
window. The excipient on this drug-coated balloon is polyethylene glycol.
Durability demonstrated in a randomised clinical trial

The ILLUMENATE European randomised controlled trial (EU RCT) was the first
randomised study of the Stellarex DCB following the promising early results of the
ILUMENATE First-in-Human study. 2,3 Importantly, the study employed blinded,
independent core laboratories to analyse duplex ultrasound images (VasCore)
and Angiograms (SynvaCore). Additionally, there were 100% monitoring of
data, an independent and blinded clinical events committee and a data safety
monitoring board.
Eligible patients had moderate to severe claudication, or ischaemic rest pain
(Rutherford class 2, or 4) with angiographic evidence of >70% stenosis within the
superficial femoral artery and/or popliteal artery, one or two de novo or restenotic
lesions with cumulative length from 30mm to 200mm. Patients will be followed for
five years. Follow-up visits include clinical assessments, functional status, adverse
events, medication compliance, and duplex ultrasound examination of patency
(through three years).
The primary safety endpoint was a composite of freedom from device- and
procedure-related death through 30 days post-procedure and freedom from target
limb major amputation and clinically driven target lesion revascularisation through
368
12 months post-procedure. The primary effectiveness endpoint was primary patency
ILLUMENATE: European randomised controlled trial two-year results

at 12 months, defined as an absence of target lesion restenosis as determined by
a duplex ultrasound peak systolic velocity ratio ≤2.5 and freedom from clinically-
driven target lesion revascularisation.
Patients were randomised to treatment with a drug-coated balloon (222 patients,
254 lesions) or an uncoated percutaneous transluminal angioplasty balloon (72
patients, 79 lesions) following successful predilatation. The patients were well-
matched with similar baseline characteristics. Per angiographic core lab assessment,
the mean lesion length was 7.2cm in the drug-coated balloon group and 7.1cm
in the percutaneous transluminal angioplasty group (p=0.878), and 19.2% and
19% (p=0.97) of lesions were total occlusions, respectively. Severe calcification was
present in 13% of lesions in the drug-coated balloon group and 10% of lesions in
the percutaneous transluminal angioplasty group. Predilatation was performed in
all but one lesion (in the percutaneous transluminal angioplasty group) and bailout
stents placed in 15% of lesions in the drug-coated balloon group and 11% of
lesions in the percutaneous transluminal angioplasty group (p=0.38).
One-year outcomes
As previously published, the primary safety endpoint was met and superiority was
demonstrated; freedom from a primary safety event was 94.1% (193/205) with drug-
coated balloon and 83.3% (50/60) with percutaneous transluminal angioplasty, for
• M Brodmann
a difference of 10.8% (95% CI: 0.9–23%).2 The primary effectiveness endpoint
was primary patency at 12 months and this endpoint was met as well. Additionally,
superiority of Stellarex over percutaneous transluminal angioplasty was achieved
(83.9% [188/224] vs. 60.6% [40/66], p<0.001).
The primary patency rate per Kaplan-Meier estimate was 89% for Stellarex vs.
65% for percutaneous transluminal angioplasty (log-rank; p<0.001), the highest
published one-year primary patency rate in any drug-coated balloon randomised
Figure 2: Primary patency by Kaplan-Meier estimate was significantly higher in the drug-coated balloon group as
compared to the percutaneous transluminal angioplasty group through two years (75.2% vs. 61.2%, log-rank p=0.004).
369
trial. As expected, the higher patency rate resulted in clinically-driven target lesion
• M Brodmann
revascularisation rates that were significantly lower in the drug-coated balloon

group (5.9% vs 16.7%; p=0.014).
Importantly, functional and quality-of-life outcomes were similar between
groups with a significantly lower rate of revascularisations in the drug-coated
balloon cohort. A similar percentage of patients in both groups had improvements
in ankle-brachial index (83.9% and 76.8%), Rutherford classification (89.2% and
86.2%) and walking distance (77.1% and 72.1%).
Two-year outcomes
Recently, the two-year data of the trial were presented.6 Primary patency through
two years remained significantly higher in the drug-coated balloon group at
75.9% (145/191 lesions), in comparison to 61% (36/59 lesions) for percutaneous
transluminal angioplasty (difference 14.9%; 95% CI: 1.1–28.7%; p=0.025).
Similarly, the primary patency Kaplan-Meier estimates at 730 days showed
sustained treatment effectiveness at 75.2% for the drug-coated balloon group vs.
61.2% for the percutaneous transluminal angioplasty group (log-rank through 24
months p=0.004; Figure 2). Importantly, this is the first time a low-dose drug-
coated balloon has demonstrated a statistically significant treatment effect at
two years.
The rate of clinically-driven target lesion revascularisations through the end of
the two-year follow-up window (790 days) was 12.1% for drug-coated balloon
vs. 30.5% for percutaneous transluminal angioplasty (p<0.001). The treatment
effect, or difference between groups, was not only maintained at two years but also
increased in magnitude. The difference between groups was 10.8% at one year and
went up to 18.4% at two years.
Clinical and functional improvements over baseline were sustained and remained
similar between treatment groups. However, as noted earlier, the percutaneous
transluminal angioplasty group required significantly more revascularisations to
maintain these levels (30.5% in the percutaneous transluminal angioplasty arm vs.
12.1% in the drug-coated balloon arm; p<0.001). Rutherford-Becker classification
was improved from baseline for 87.8% of drug-coated balloon patients and
84.9% of percutaneous transluminal angioplasty patients at 24 months. Distance
walked, as measured by the six-minute walk test or treadmill test, improved for
74.2% of drug-coated balloon patients and 66.7% of percutaneous transluminal
angioplasty patients at 24 months. An improvement in the walking impairment
questionnaire (WIQ) composite score at 24 months was seen in 82.1% of drug-
coated balloon patients and 94.7% of percutaneous transluminal angioplasty
patients, and improvements in ankle-brachial index at 24 months were achieved for
78.7% of drug-coated balloon patients and 83.3% of percutaneous transluminal
angioplasty patients.
Conclusion
The ideal drug-coated balloon is one that maintains a high treatment effect while
minimising the drug dose and potential embolisation and thereby minimises any
possible downstream effects. The sustained outcomes observed in this trial are
similar to the outcomes obseved in the IN.PACT SFA trial at two years, which were
achieved with a higher dose (3.5µg/mm2) drug-coated balloon.7 A subsequently
370
developed low-dose (2µg/mm2) drug-coated balloon failed to show a significantly

higher patency at two years compared to percutaneous transluminal angioplasty.8
The differences in trial outcomes across these three different drug-coated balloons,
with different coatings, validates the importance of coating characteristics and
drug-coated balloon design.
For the first time, the ILLUMENATE EU RCT trial demonstrated the durability
of the biological effect of a low-dose drug-coated balloon in humans. Prior to this
trial, the sustainaibility of the biologcial effect from low-dose drug-coated balloons
was not supported beyond 12 months based on randomised data. The implications
of these findings are important as they may support the use of this technology in
new areas and could help expand the therapeutic options of current-generation
drug-coated balloon technologies.
Summary
• Drug-coated balloons are becoming a widely accepted and preferred

first-line therapy for the treatment of femoropopliteal disease in patients
with claudication.
• Drug-coated balloons performance is dependent on the balance of multiple
factors (e.g. coating morphology, excipient and drug dose).
• M Brodmann
• The active drug on all commercially available drug-coated balloons is
paclitaxel, but the dose differs by manufacturer and ranges from 2µg/mm2
to 3.5µg/mm2.
• Potential benefits of lowering the drug concentration include a reduction
in the potential for vessel wall toxicity and distal embolisation following
balloon inflation.
• The ILLUMENATE EU RCT trial assessed the Stellarex low-dose drug-coated
balloon. Significantly higher patency rates were observed at both one and
two years in the Stellarex cohort compared with the uncoated angioplasty
balloon group.
• Stellarex is the first low-dose drug-coated balloon to demonstrate a
statistically significantly higher patency rate at two years as compared to
treatment with an uncoated angioplasty balloon.
References
1. Granada JF, Stenoien M, Buszman PP, et al. Mechanisms of tissue uptake and retention of paclitaxel-
coated balloons: impact on neointimal proliferation and healing. Open Heart 2014; 1 (1): e000117.
2. Schroeder H, Werner M, Meyer DR, et al. Low-dose paclitaxel-coated versus uncoated percutaneous
transluminal balloon angioplasty for femoropopliteal peripheral artery disease: One-year results of
the ILLUMENATE European Randomized Clinical Trial (Randomized trial of a novel paclitaxel-coated
percutaneous angioplasty balloon). Circulation 2017; 135 (23): 2227–36.
3. Schroeder H, Meyer DR, Lux B, et al. Two-year results of a low-dose drug-coated balloon for
revascularization of the femoropopliteal artery: Outcomes from the ILLUMENATE first-in-human study.
Catheter Cardiovasc Interv 2015; 86 (2): 278–86.
4. Schroë H, Holden AH, Goueffic Y, et al. Stellarex drug-coated balloon for treatment of femoropopliteal
arterial disease-The ILLUMENATE Global Study: 12-Month results from a prospective, multicenter,
single-arm study. Catheter Cardiovasc Interv 2017. Epub.
371
5. Krishnan P, Faries P, Niazi K, et al. Stellarex drug-coated balloon for treatment of femoropopliteal
• M Brodmann
disease: Twelve-month outcomes from the randomized ILLUMENATE Pivotal and Pharmacokinetic
Studies. Circulation 2017; 136 (12): 1102–13.
6. Brodmann M. ILLUMENATE European Randomized Trial: 2-year results paper presented at: VIVA; Sep
13, 2017, 2017; Las Vegas, NV.
femoropopliteal lesions: 24-month results of IN.PACT SFA. J Am Coll Cardiol 2015; 66 (21): 2329–38.
8. Lutonix 035 Drug Coated Balloon PTA Catheter Instructions for Use (DW5190-01r7).
372
The potential value of
swirling flow—the BioMimics
3D study programme
PA Gaines, T Sullivan, G Ansel, C Caro and T Zeller
Introduction
Medical advances in the treatment of femoropopliteal artery disease over the last
decade reflect the on-going fight to maintain patency; and that battle is important
for a number of reasons. Patency has a clear effect upon the clinical success of
treating both claudication and critical limb ischaemia; revascularisation to maintain
patency adds risk to the patient and costs to the healthcare provider.
Lumen loss after endovascular intervention has separate mechanisms depending
upon whether it is early or late.1 Immediately after angioplasty, particularly in
bulky and calcified disease, there may be immediate recoil or dissection. Over
the ensuing months, there is a fibrotic adventitial response known as late negative
remodelling, and an inflammatory response that leads to vascular smooth muscle
cell proliferation, extracellular matrix formation and the development of neointimal
hyperplasia. When the combination of remodelling and hyperplasia is excessive, it
is referred to as restenosis.
The accepted treatment for recoil and flow limiting dissection observed at the
time of intervention, and to prevent the late constrictive effect of late negative
remodelling, is to place a stent. Such an intuitive solution has resulted in clear
benefit when compared with simple angioplasty.2,3 The more difficult problem of
limiting restenosis now has two solutions that may be complementary—drugs and
imparting swirling flow.
Using swirling flow to benefit intervention in the

femoropopliteal artery
It is clear that the distribution of atherosclerosis and the tendency of an artery to
develop restenosis varies throughout the human arterial system; the femoropopliteal
artery has both a high prevalence of atherosclerosis and a high tendency to develop
restenosis. Part of the reason for the variable distribution of native arterial disease
was explained in a 1969 Nature article, which drew attention to the relationship
between high wall shear stress and a reduced tendency towards atherosclerosis.4
We all recognise that normal arterial blood flow is laminar. Less well known is
that the normal pattern in the aorta and proximal branches is also spiral—referred
to as swirling flow.5 Wall shear stress can be thought of as the velocity of blood
against the internal wall of the vessel. Swirling flow increases wall shear stress when
compared with non-swirling flow, resulting in a reduced propensity to develop
atherosclerosis when exposed to well recognised risk factors. Blood flow in the
373
• PA Gaines, T Sullivan, G Ansel, C Caro and T Zeller
B
The potential value of swirling flow—the BioMImics 3D study programme
Figure 1: (A) A computational fluid dynamics model of swirling flow showing it becoming dampened in the iliac
arteries, resulting in straight laminar flow in the superficial femoral artery; (B) a CFD model of high wall shear stress
in the iliac arteries (as a consequence of swirling flow) and low wall shear stress in the superficial femoral artery. The
graph on the left shows a scale of wall shear stress from low (pathogenic) to high (protective) reproduced from Malek
AM, et al. JAMA 1999; 282: 2035–42.
superficial femoral artery is naturally less swirling—hence, the high prevalence of

native disease (Figure 1).
Less well recognised is the effect of wall shear stress on the tendency to develop
restenosis. Animal studies have shown that areas of low wall shear stress predicts the
development of neointimal hyperplasia in grafts and stents.6 Treating the superficial
femoral artery of peripheral arterial disease patients with straight nitinol stents has
been shown to impair wall shear stress.7 Evaluation of coronary stents in humans
showed that the pattern of restenosis is determined by the distribution of wall shear
stress.8,9
These observations led to the development of a self-expanding stent with a helical
centreline that is capable of inducing swirling flow (Figure 2). The ability of this
stent to reduce restenosis was first tested in a porcine model in which a straight stent
was placed in one carotid artery and a helical stent in the other of the same animal.
The study demonstrated that the helical centreline stent deformed the artery into
a helix and generated swirling flow; that the swirling flow significantly reduced the
development of neointimal hyperplasia (NIH) (Figure 3); and that a correlation
between the degree of curvature and the reduction in NIH was established.
The BioMimics 3D stent was subsequently tested in the first randomised controlled
trial to directly compare two nitinol stents in the femoropopliteal segment.10 The
MIMICS trial was a multicentre, core-lab controlled, prospective, randomised trial
374
Figure 2: BioMimics 3D stent.
in which the BioMimics 3D stent was compared with a conventional straight stent
control (Lifestent, Bard) in 76 patients with symptomatic occlusive disease of the
superficial femoral and proximal popliteal arteries. Conventional radiographs and
angiography confirmed that the BioMimics 3D stent imparts non-planar curvature
to the diseased artery. Compared with the straight stent control the BioMimics 3D
stent had significantly better primary patency through two years (Figure 4). There
was no change in clinically driven target lesion revascularisation in the BioMimics
3D arm between 12 and 24 months whereas there was a three-fold increase in

clinically-driven target lesion revascularisation in the straight stent control arm
over the same time period; a significant difference between the two stents (Figure
5).
The complementary effect of swirling flow and drug coated

balloons
Current drug coated balloons use paclitaxel, a powerful antiproliferative drug, to
address the biological mechanisms leading to restenosis. The drug is combined
with an excipient to provide uniform dosage and rapid transfer. Variations in the
excipient, formulation and dosage of the paclitaxel results in the different behaviour
of the individual drug-coated balloon.
The pivotal trials showed improved performance over simple angioplasty but
this was in a well-defined set of lesions and the importance of that in terms of
Figure 3: Thirty-day histology of a straight nitinol stent (left) and the same stent with a 3D helical shape (right) in a
porcine carotid model. Overall, in 10 animals studied, there was a 45% reduction in neointimal thickness (p<0.001).
375
Figure 4: Kaplan-Meier survival estimate from loss of patency (MIMICS Study).

generalisability of the value of drug-coated balloons deserves some attention.11–15

Severe calcification and an inability to completely pre-dilate the lesion were
exclusions in these studies and effectively removed those lesions from any analysis.
Furthermore, since only 12–26% of lesions were total occlusions this non-calcified,
simple disease was unlikely to recoil after angioplasty—resulting in a bailout stent
rate of only 2.5–7%. When the same drug-coated balloons are used in more
routine clinical practice, and documented within the Global Registries, the lesion
patency and clinically driven target lesion revascularisation rates remain good.16,17
This is because these more clinically generalisable cohorts are in fact measuring
the outcome of drug-coated balloon plus stent. This everyday disease is more
complex than those recruited to the pivotal trials resulting in an average stent rate
Figure 5: Kaplan-Meier estimate of survival from clinically driven target lesion revascularisation between one and two
years (MIMICS Study).
376
of 28-35.5%. The stent rate is clearly related to both lesion length and the chronic

total occlusion rate. In IN.PACT Global for instance, when the length of lesion
exceeds 25cm, the stent rate is 53%, and in total occlusions the stent rate is 47%.17
The Kaplan-Meier survival estimates from the pivotal trials demonstrate that
the improvement in patency and reduction in clinically driven target lesion
revascularisation over simple angioplasty occur between six and 12 months, but
after this time the Kaplan Meier curves are the same.18 This trend is seen also in
the global registries.16,17
It is clear that there are limitations to the use of drug-coated balloons in the
femoropopliteal segment: a “drug-coated balloon-only” approach is not appropriate
to clinical practice outside pivotal trials. While the bailout stent rate was low
in the pivotal trials the global registries demonstrate that a much higher use of
stents is required to maintain high patency and low rates of clinically-driven target
lesion revascularisation.
Loss of patency is a combination of recoil, late negative remodelling and
restenosis. Drug-coated balloons alone clearly do not provide the scaffolding that
a stent can to overcome the recoil and remodelling. Indeed, drug-coated balloons
appear to have been tested in an environment that would avoid likely recoil; lesions
were short and both calcified lesions and lesions that demonstrated recoil after the
initial pre-dilatation were excluded in the pivotal trials.
The antiproliferative effects are necessarily time limited and yet contemporary
data show that loss of patency due to restenosis in the femoropopliteal segment
occurs out to three to four years.19 Something other than the drug is required to

affect these late events.
It would appear, therefore, that in common clinical practice, a stent is required in
a significant proportion of drug-coated balloon-treated lesions. If a stent is used to
support a drug-coated balloon, it would appear sensible to use a device with good
outcomes that would not only provide the scaffolding that drug-coated balloon-
only therapy lacks, but could also extend the period of low clinically driven target
lesion revascularisation past the initial 12 months when drug-coated balloons are
effective. The BioMimics 3D stent was seen in a randomised clinical trial to have
a better patency and a reduced clinically-driven target lesion revascularisation rate
when compared with a straight nitinol stent. Furthermore, as there was no clinically
driven target lesion between 12 and 24 months in the BioMimics 3D arm of the
randomised controlled trial, this suggests that the use of a proven drug-coated
balloon and BioMimics 3D might be the ideal combination.
Continuing the BioMimics programme

The clinical validation of swirling flow as a key component in a combined approach
to limit restenosis is continuing across a range of studies in the BioMimics
clinical programme. Following on from MIMICS, MIMICS-2 is a prospective,
multicentre, interventional study designed to evaluate the safety and effectiveness
of BioMimics 3D in the treatment of patients with symptomatic femoropopliteal
disease. The study is being conducted under a USA Food and Drug Administration
(FDA) investigational device exemption (IDE), with Japanese Pharmaceuticals
and Medical Devices Agency (PMDA) concurrence under the “Harmonisation By
Doing” initiative, in order to provide safety and effectiveness data that are intended
377
to support marketing applications for BioMimics 3D in both the USA and Japan.
One-year primary endpoint outcomes will be announced imminently.

Additionally, MIMICS-3D is an ongoing prospective, multicentre, observational
registry evaluating the safety, effectiveness and device performance of
BioMimics 3D within a real-world clinical population in a minimum of 500
patients across Europe.
This combined clinical database of over 1000 cases is intended to provide
significant validation of the unique helical shape of BioMimics 3D and the clinical
benefits of swirling flow.
Summary
• Swirling flow increases walls shear stress, resulting in a reduced propensity to

develop atherosclerosis and restenosis.
• Treating the superficial femoral artery of peripheral arterial disease patients
with straight nitinol stents has been shown to impair wall shear stress.
• BioMimics 3D is a self-expanding stent with a helical centreline capable of
inducing swirling flow and increasing wall shear stress.

• When compared with a straight stent control in a randomised clinical trial
the BioMimics 3D stent had significantly better primary patency through two
years and no clinically driven target lesion revascualrisation between 12 and
24 months.
• The global registries demonstrate that a much higher use of stents is required
to maintain high patency and low rate of clinically-driven target lesion
revascularisation rates than was shown in the “drug-coated balloon only”
approach of the pivotal trials.
• Drug-coated balloons alone do not provide the scaffolding that a stent can to
overcome the recoil and remodelling that lead to loss of patency.
• The antiproliferative effects of drug-coated balloons are necessarily time-
limited and contemporary data show that loss of patency due to restenosis in
the femoropopliteal segment occurs out to three to four years.
• If a stent is used to support a drug-coated balloon, it is desirable to use a
device with good outcomes that provides the scaffolding that drug-coated
balloon only therapy lacks, and that can also extend the period of low
clinically-driven target lesion revascularisation past the initial 12 months when
drug-coated balloons are ineffective.
• Available data suggest that the use of a proven drug-coated balloon and
BioMimics 3D might be the ideal combination.
References
1. Jukema JW, Verschuren JJ, Ahmed TA, Quax PH. Restenosis after PCI. Part 1: pathophysiology and risk
factors. Nat Rev Cardiol 2011; 9: 53–62.
2. Laird JR, Katzen BT, Scheinert D, et al. Nitinol stent implantation vs. balloon angioplasty for lesions in
the superficial femoral and proximal popliteal arteries of patients with claudication: three-year follow-
up from the RESILIENT randomized trial. J Endovasc Ther 2012; 19: 1–9.
378
3. Schillinger M, Sabeti S, Loewe C, et al. Balloon Angioplasty versus implantation of nitinol stents in the

superficial femoral artery. N Engl J Med 2006; 354: 1879–88.
4. Caro CG, Fitz-Gerald JM, Schroter RC. Arterial wall shear and distribution of early atheroma in man.
Nature 1969; 223: 1159–60.
5. Caro CG, Doorly DJ, Tarnawski M, et al. Non-planar curvature and branching of arteries and non-planar
flow. Proc R Soc Lond 1996; 452: 185–97.
6. LaDisa JF, Olson LE, Molthen RC, et al. Alterations in wall shear stress predict sites of neointimal
hyperplasia after stent implantation in rabbit iliac arteries. Am J Physiol Heart Circ Physiol 2005; 288:
H2465–75.
7. Schlager O, Zehetmayer S, Seidinger D, et al. Wall shear stress in the stented superficial femoral artery
in peripheral arterial disease. Atherosclerosis 2014; 233: 76–82.
8. Sanmartín M, Goicolea J, García C, et al. Influence of shear stress on in-stent restenosis: in vivo study
using 3D reconstruction and computational fluid dynamics. Rev Esp Cardiol 2006; 59: 20–27.
9. Wentzel JJ, Whelan DM, van der Giessen WJ, et al. Coronary stent implantation changes 3-D vessel
geometry and 3-D shear stress distribution. J Biomech 2000; 33 :1287–95.
10. Zeller T, Gaines PA, Ansel GM, Caro CG. Helical Centerline Stent Improves Patency: Two-Year Results
From the Randomized Mimics Trial. Circ Cardiovasc Interv 2016; 9: pii: e002930.
11. Tepe G, Laird J, Schneider P, et al. Drug-coated balloon versus standard percutaneous transluminal
angioplasty for the treatment of superficial femoral and/or popliteal peripheral artery disease:
12-month tesults from the IN.PACT SFA randomized trial. Circulation 2014; 131 (5): 495–02.
femoropopliteal lesions: 24-Month Results of IN.PACT SFA. J Am Coll Cardiol 2015; 66: 2329–38.
13. Scheinert D, Schulte KL, Zeller T, et al. Paclitaxel-releasing balloon in femoropopliteal lesions using a
BTHC excipient: twelve-month results from the BIOLUX P-I randomized trial. J Endovasc Ther 2015; 22:
14–21.
14. Schroeder H, Meyer DR, Lux B, et al. Two-year results of a low-dose drug-coated balloon for
revascularization of the femoropopliteal artery: outcomes from the ILLUMENATE first-in-human study.
Catheter Cardiovasc Interv 2015; 86: 278–86.

15. Rosenfield K, Jaff MR, White CJ, et al. Trial of a Paclitaxel-coated balloon for femoropopliteal artery
disease. N Engl J Med 2015; 373: 145–53.
16. Scheinert. LINC 2016 presentation. Latest results from the Levant Global registry on challenging, real
world lesion including long lesions, CTOs and ISR & lesions learned from Levant II
17. D Scheinert. VIVA 2016 presentation. Strengths and weaknesses of DCBs: Insights from the Global
Registries
18. Laird JR et al. Durability of treatment effect using a drug-coated balloon for femoropopliteal lesions
24-month results of IN.PACT SFA. JACC 2015; 66: 2329–38.
19. Iida O, Uematsu M, Soga Y et al. Timing of the restenosis following nitinol stenting in the superficial
femoral artery and the factors associated with early and late restenoses. Catheter Cardiovasc Interv
2011; 78: 611–17.
379
Access techniques and peri-interventional imaging
The potential value of IVUS-
guided superficial femoral
artery interventions—a
randomised trial
Introduction
Intravascular ultrasound (IVUS) imaging provides fundamentally different
information to that provided by angiography. Because it uses high-frequency
ultrasound to acquire a 360-degree cross-sectional image, it produces high-
resolution imaging of the entire vessel without dependence on contrast media
opacification or radiation. In contrast to angiography, which is limited to displaying
a two-dimensional “lumenogram”, IVUS can assess the wall structures and plaque
morphology and more accurately measures arteries compared to angiography,
particularly when the lumen is irregular or eccentric.1–4
IVUS imaging has been widely investigated in coronary artery imaging and
has been shown to improve a range of outcome measures.5–7 It has been much
less extensively investigated in peripheral artery applications and data comparing
results for angiography and IVUS in the femoropopliteal arteries are scarce with
no prospective studies.
There are two retrospective studies comparing results for angiography and IVUS.
Iida et al analysed a multicentre endovascular registry and found that the use of
IVUS was associated with significantly higher rates of primary patency rate and
freedom from reintervention.8 Unfortunately, in this study, IVUS was performed
in less than 25% of cases with a bias against IVUS use in patients with poorer
prognosis. Additionally, there was a lack of data for the IVUS findings and on
how IVUS influenced changes in treatment. In the second study, an analysis
of the US Nationwide Inpatient Sample database showed that the use of IVUS
was associated with reduced post-procedural complications and amputations.9
This study was limited by the low level of detail provided by the database and
a lack of information for reporting standard endovascular endpoints. There are
also comparative retrospective data from the iliac arteries reporting higher primary
patency with the use of IVUS,although how this relates to treatment of the
femoropopliteal arteries is unclear. 10
This limited evidence suggests that IVUS may improve outcomes; however,
better quality data are required and prospective studies comparing outcomes for
angiographic and IVUS guidance are essential. With this in mind, we initiated the
first randomised controlled trial to investigate if routine use of IVUS, as an adjunct
to angiography, results in improved outcomes.
383
IVUS trial details
Method
In this single-centre randomised controlled trial, patients were eligible for enrolment
if they had severe claudication or critical limb ischaemia (Rutherford class 3–5)
with femoropopliteal artery lesions suitable for endovascular treatment. Patients
were randomised using 1:1 allocation into control or treatment groups. In the
control group, the surgeon had access to angiography findings alone whereas in the
The potential value of IVUS-guided superficial femoral artery interventions—a randomised trial •
treatment group the surgeon had access to both angiography and IVUS imaging.
Patients were followed after treatment for two years with clinical and duplex
ultrasound assessment. The primary outcome measures were primary patency and
freedom from clinically driven target lesion revascularisation. The target sample
size was set at 150 patients (75 in each group). The study was approved by the
Southern Adelaide Clinical Human Research Ethics Committee in accordance with
the “National Statement on Ethical Conduct in Human Research” (2007) and is
registered with the Australian New Zealand Clinical Trials Registry.11,12
Angiography and IVUS were performed in all cases prior to endovascular
intervention being undertaken. The treatment plan after initial angiographic imaging
was recorded and randomisation was then performed. If the patient was randomised
to the control group IVUS was performed but not made available to the surgeon.
If the patient was randomised to the treatment group, IVUS imaging was available
to the surgeon, and the treatment plan, based on both the angiographic and IVUS
images (and any change to the initial plan), was recorded. The endovascular treatment
was then performed. Completion angiography and IVUS images were obtained at
the conclusion of the treatment. The completion IVUS images were withheld in the
control group and available in the treatment group.
Angiography was performed following standard departmental protocols. IVUS
images were acquired with a Volcano S5 IVUS system (Philips Volcano) using
continuous imaging acquisitions during automated or manually pullback as
described previously.13 Bookmarks recorded every centimetre during pullback,
enabled verification of the position within the artery and estimation of lesion
length.
Measurements were obtained of reference vessel diameters, stenosis diameters
and lesion length using angiographic quantitative vessel analysis software and
the IVUS system quantification software. Stenosis estimation was obtained
using the minimum diameter and the maximum reference vessel diameter. Stent
lumen diameters were measured as previously described to allow quantification of
stent expansion and apposition.13 A significant measurement difference between
modalities was defined as a vessel diameter ≥0.5mm or lesion length ≥20mm.
Results
Preliminary results of 92 patients with up to two years of follow-up are currently
available, with 45 cases randomised to the control group (angiography alone)
and 47 cases to the treatment group (angiography and IVUS). The mean age of
patients was 74 years, with 58 males and 34 females and clinical presentations of
severe claudication (Rutherford class 3) in 56 patients and critical limb ischaemia
(Rutherford class 4–5) in 36 patients. The mean IVUS lesion length was 145mm
(SD=90mm) and the lesions were predominately TASC A–C (A=22, B=39, C=26
384
Figure 1: Primary patency at
two years.
Figure 2: Freedom from

clinically driven target lesion
revascularisation at two years.

and D=5) including 52 stenoses, 28 occlusions and 12 restenoses. There were no
significant differences in patient demographics, risk factors and lesion characteristics
between the two groups, confirming adequate randomisation.
There was a disagreement in one imaging finding between angiography and
IVUS in 48 patients and in two imaging findings in 19 patients, making a total of
86 occasions of disagreement of findings in 67 patients (73% of cases). By far the
most common disagreements were in lesion length (39 cases) and reference vessel
diameter (31 cases) with IVUS revealing generally longer lesions (mean lesion
length: angiography=112mm, angiography and IVUS=145mm; p=0.042) and larger
reference vessel diameter (angiography=5.1 mm, angiography and IVUS=5.6mm,
p=0.001). Overall, there was no significant difference in the percentage stenosis
estimate between IVUS and angiography, and there was a clinically significant
difference in stenosis (defined as a difference that would alter the decision to treat)
in only three cases. Differences in post-treatment appearances were seen in 13 cases
(10 dissections and three cases of stent under expansion or malapposition).
385
A change of treatment occurred in 37 of 47 cases in the treatment group (79%).
The length of the treatment zone was increased in 17 cases (drug-coated balloon
angioplasty in eight cases and stenting in nine cases), the balloon size was changed
in 11 cases (increased in 10 and decreased in one), the length of treatment and the
balloon size were both increased in one case, the type of treatment was changed
in three cases, the stent size was increased in one case, and there was additional
treatment performed after initial completion imaging in four cases (reangioplasty
to two dissections and two stents).
Vessels were treated with plain balloon angioplasty in six cases, drug-coated
balloon in 55 cases, bare metal stents with or without drug-coated balloon in
22 cases, drug-eluting stents in five cases and covered stents in four cases. Vessel
preparation with adjunctive atherectomy was performed in 16 cases. There was
no difference in treatment methods between the randomisation groups (Pearson
chi-square=1.509, p=0.912).
Kaplan-Meier survival analysis for results up to two years showed primary
patency of 59.5% for angiography and 78.3% for angiography and IVUS
combined (p=0.048) (Figure 1) and freedom from clinically driven target lesion
revascularisation of 78.6% for angiography and 89.1% for angiography and IVUS
(p=0.126) (Figure 2).
Figure 3: DSA image of an occluded

superficial femoral artery prior to treatment
with IVUS images.
Treatment plan after initial angiography
was to treat an 80mm length of vessel.
IVUS imaging revealed significant disease
beyond this zone resulting in treatment to be
extended by 50% to 120 mm of the vessel.
Short dashed line=lumen, long dashed
line=external elastic lamina.
Figure 4: DSA and IVUS measurement of

vessel lumen in distal SFA/P1 segment of
popliteal artery DSA image of quantitative
vessel analysis measurement = 6.1mm. IVUS
measurement at same part of vessel, mean
lumen diameter = 6.75mm. Treatment plan
changed with plain balloon and DCB increased
from 6mm to 7mm.
386
Discussion
This is the first randomised controlled trial to assess the impact of IVUS imaging
on outcomes in peripheral endovascular interventions. These preliminary findings
confirm that using IVUS in addition to angiography improves primary patency up
to two years post-treatment. Also, there is a trend toward a reduction in clinically-
driven target lesion revascularisation with IVUS imaging.
The results of this study confirm that angiography tends to underestimate lesion
length and vessel lumen and is in agreement with previous studies that have reported
the superiority of IVUS over angiography for a range of imaging parameters.
The improvement in primary patency is likely to be related to the ability of IVUS
to more precisely measure lesion length (Figure 3) and vessel size (Figure 4). In this
patient population, drug-coated balloon angioplasty was by far the most common
treatment, comprising 60% of all cases. A drug-coated balloon is primarily a drug
delivery system, and its therapy is dependent on the adequate delivery of paclitaxel
to the entire lesion. This can be compromised if the balloon is undersized and
therefore not fully apposed to the intima, or if less than the full length of the lesion
is treated.14,15 The most common treatment changes due to IVUS findings were an
increase in balloon size and an increase in length of treatment, and the more precise
delineation of vessel size and disease extent provided by IVUS allowed the treating
surgeon to optimise drug-coated balloon deployment and drug delivery. Adequate
plain balloon dilatation prior to drug-coated balloon use is another important key
factor for optimal treatment. The increase in balloon size and length of treatment
due to IVUS are likely to have resulted in more effective pre-drug-coated balloon
dilatation and may have contributed to the better outcomes in the treatment group.
The most common change in treatment related to stenting was an increase in
the length of the stent used, again due to the longer length of disease revealed by
IVUS. This resulted in fewer instances of significant plaque adjacent to stent edges
on completion imaging. In general, longer length of stenting and larger stent sizes
are considered to increase the risk of restenosis; however, there was no evidence of

this in this study. The number of cases stented in this study was relatively small and
a larger trial specifically comparing stenting results with angiography and IVUS
would be beneficial.
Even though disagreement in post-treatment dissection appearances occurred in more
than 10% of cases, this resulted in additional treatment in only two cases. Although
dissections tended to look more severe with IVUS, the relative lack of changes to
treatment probably reflects uncertainty about the significance of IVUS dissection
findings in relation to angiographic assessment and a preference to avoid bailout
stenting, if possible. This is an area that would also benefit from further research.
387
Conclusion
These results suggest that the routine use of IVUS in femoropopliteal interventions
improves primary patency. This is likely to be due to better sizing of vessels and
more complete treatment of lesions.
Summary
•
This is the first randomised controlled trial undertaken to compare

angiography and combined IVUS- and angiography-guided peripheral
endovascular interventions.
• Preliminary two-year results show that adding IVUS to standard angiographic
guidance significantly improves primary patency.
• Secondary findings include disagreement in imaging information between
angiography and IVUS and a change in treatment plan in over 70% of cases.
References
1. Cooper BZ, Kirwin JD, Panetta TF, et al. Accuracy of intravascular ultrasound for diameter measurement
of phantom arteries. J Surg Res 2001; 100: 99–105.
2. Arthurs ZM, Bishop PD, Feiten LE, et al. Evaluation of peripheral atherosclerosis: A comparative analysis
of angiography and intravascular ultrasound imaging. J Vasc Sur 2010; 51: 933–9.
3. 3. morphology in normal subjects and patients with coronary artery disease. Circulation 1991; 84:
1087–99.
4. Tabbara M, White R, Cavaye D, Kopchok G. In vivo human comparison of intravascular ultrasonography
and angiography. J Vasc Surg 1991; 14: 496–504.
5. Casella G, Klauss V, Ottani F, et al. Impact of intravascular ultrasound-guided stenting on long-term
clinical outcome: A meta-analysis of available studies comparing intravascular ultrasound-guided and
angiographically guided stenting. Catheter Cardiovasc Interv 2003; 59: 314–21.
6. Cho Y-K, Hur S-H. Practical application of coronary imaging devices in cardiovascular intervention.
Korean Circ J 2015; 45: 87–95.
7. Singh V, Badheka AO, Arora S, et al. Comparison of in-hospital mortality, length of hospitalization,
costs, and vascular complications of percutaneous coronary interventions guided by ultrasound
versus angiography. Am J Cardiol 2015; 115: 1357–66.
8. Iida O, Takahara M, Soga Y, et al. Efficacy of intravascular ultrasound in femoropopliteal stenting for
peripheral artery disease with TASC II class A to C lesions. J Endovasc Ther 2014; 21: 485–92.
9. Panaich SS, Arora S, Patel N, et al. Intravascular ultrasound in lower extremity peripheral vascular
interventions: Variation in utilization and impact on in-hospital outcomes from the Nationwide
Inpatient Sample (2006–2011). J Endovasc Ther 2016; 23: 65–75.
10. Buckley CJ, Arko FR, Lee S, et al. Intravascular ultrasound scanning improves long-term patency of iliac
lesions treated with balloon angioplasty and primary stenting. J Vasc Surg 2002; 35: 316–23.
11. 2007. National Statement on Ethical Conduct in Research Involving Humans. Canberra: NHMRC.
12. ACTNRN12614000006640. Australian Clinical Trials; 2014. https://goo.gl/PchAxj [Date accessed 20
February 2018]
13. Spark J, Allan R. When a flexible stent is used with intravascular ultrasound. In: Greenhalgh R, editor.
Vascular and Endovascular Consensus Update 2017. London: Biba Medical 2017. ISBN: 978-0-9570419-
6-7. p303–8.
14. van den Berg JC. Drug-eluting balloons for treatment of SFA and popliteal disease – A review of
current status. Eur J Radiol 2017; 91: 106–15.
15. Mustapha JA, Diaz-Sandoval LJ, Saab F. The drug-coated balloon: Not just a balloon. Cath Lab Digest
2014.
388
Vector velocity ultrasound—a
new ultrasound technique
L Lönn, JB Olesen, JA Jensen, MB Nielsen
and KL Hansen
Introduction
Ultrasound blood flow estimation is a well-established technique to assess
haemodynamic conditions of the cardiovascular system. Being noninvasive and
repeatable, ultrasound is the preferred method when examining blood flow. Most
commercially available ultrasound systems can detect flow through three different
modes, spectral, power, and colour Doppler—each with their unique set of
advantages.
All three Doppler modes have a common denominator; they are incapable of
detecting blood flow perpendicular to the direction of the emitted ultrasound beam.
This prohibits the possibility of studying complex flow phenomena in different
vessel geometries (Figure 1).1–5
Over the last three decades technical research has focused on the 1D limitation
of the current ultrasound scanners.3,6–16 These methods have been categorised as
vector flow imaging techniques, providing both the velocity and direction of blood
flow in large fields of view independent of the insonation angle. Essentially, this
Figure 1: A vortex in the carotid bulb

during the late systole of a healthy
volunteer obtained in long axis view
with vector flow imaging. Reprinted
with permission from Reprinted with
permission from IEEE (Ultrasonics,
Ferroelectrics, and Frequency Control)
389
tool is not limited by the position of the ultrasound probe, and vector flow imaging
L Lönn, JB Olesen, JA Jensen, MB Nielsen and KL Hansen
detects not only the blood movement that runs parallel to the ultrasonic beam, but
also the perpendicular shift. Some methods can also detect the out-of-scan-plane
flow component.
Despite the introduction of these new vector flow imaging techniques, only one
commercially available scanner currently displays vector flow imaging in real-time
(BK5000; BK Ultrasound), though other companies are starting to advance in the
field too, e.g. Mindray Medical, Toshiba, and GE Healthcare. Results obtained
using the BK Ultrasound system will be presented in the remainder of the chapter,
along with examples of a few of the applications. The chapter concludes with a
brief look to the future, where ultrasound is used for 3D flow estimation.
Unambiguous flow estimation using ultrasound

The current 1D blood flow estimation technique detects the velocity component
in the direction of the insonifying beam. However, vessels that run parallel to the
skin surface, make this component the least important one to study (Figure 2). To
achieve an acceptable insonation angle below 60 degrees, the beam or the transducer
•
can be tilted. However, even with an acceptable insonation angle, complex blood
Vector velocity ultrasound—a new ultrasound technique
flow is a challenge to visualise with conventional techniques as multiple angle

corrections in each frame would be necessary.4 Blood flow in the cardiovascular
system is mainly pulsatile and complex with transitory vortices, therefore, vector
velocity estimation is necessary for a comprehensive understanding of dynamics.
Detection of 2D flow patterns allows alternative measures to be obtained with
new insonation windows. This has been shown in the portal vein, in which vector
flow imaging was more precise than spectral Doppler regardless of insonation angle
for velocity estimation.17
Figure 2: Blood flow in the common carotid artery perpendicular to the insonifying ultrasound beam is found with
conventional colour flow mapping (A), and the 2D vector velocity estimation technique (B). Area (A) reveals that the
conventional method is incapable of detecting the actual flow, while (B) shows the 2D vector flow estimation approach
with an unambiguous vector velocity map of the blood flow with indication of direction and magnitude. The figure is
acquired with permission from BK Ultrasound, Denmark.
390
Figure 3: (A) Systolic flow obtained in long-axis view for two patients. Recording of a patient with a healthy aortic
valve, (B) whereas the flow from a diseased valve is shown in. (C) Figure shows the same patient as in (B) after aortic
valve replacement. LV: left ventricle; AA: ascending aorta. Reprinted with permission from Elsevier (Ultrasound in
Medicine and Biology).
• L Lönn, JB Olesen, JA Jensen, MB Nielsen and KL Hansen

A new marker for assessing a diseased aorta
Complex flow phenomena in and around the heart is a competitive research field.
Previous studies with vector flow imaging have examined the flow patterns of
the normal and stenotic aortic valve (Figure 3). Among the findings was shown
that flow complexity can be quantified with vector flow imaging, which could be
applicable in stenosis assessment.5,18
Volume flow estimation using vector flow imaging

MRI volume flow estimation or thermo-dilution techniques are used in a wide range
of clinical applications.19 In ultrasound, volume flow estimation by conventional
Doppler systems is impaired by the necessary assumptions of a fixed flow angle and
a rotationally symmetric flow profile.20 Vector flow imaging can provide an estimate
independently of the restrictions found in conventional Doppler systems. Recent
papers showed significantly improved precision for flow rate estimation with vector
flow imaging when compared with ultrasound dilution technique, the conventional
Figure 4: Vector flow imaging of an arteriovenous fistula. (A) Figure shows an in vivo example of a stenosed fistula
with complex flow and reduced flow rate, while (B) presents the same fistula after balloon dilatation with a more
laminar flow and increased flow rate. Courtesy of KL Hansen (MD)
391
Figure 5: Changes in
intravascular pressure
along a streamline found
using 2D flow estimation
in the carotid bifurcation
of a healthy volunteer.
The pressure is plotted
along the course of the
streamline. Reprinted
with permission from
IEEE (IEEE Proceedings)
invasive method for volume flow estimation in patients with arteriovenous fistula
(Figure 4).21,22
Noninvasive pressure gradient estimation

2D blood flow estimation allows for more than the visualisation of flow. The new
advancement provides blood flow dynamics enabling features such as estimation of
vascular pressure gradients.23 Pressure gradients are used in the diagnostic assessment
of flow constrictors. At present, pressure gradients are measured through means of
endovascular catheters that rely on ionising radiation for guidance and positioning.
Figure 6: 3D vector flow gives full access to the blood flow in all planes within the scan region. The
left part shows a full volume representation of the carotid flow, with streamlines indicating the flow
trajectories. Next to this are three cross-sectional views. Courtesy of the Alexandra Institute, Denmark.
392
To overcome the concerns related to such minimally invasive procedures, vector

flow imaging is suggested as an alternative for mapping intravascular pressure
gradients (Figure 5).
The future of vector flow imaging is in 3D

2D flow estimation can visualise the complex blood flow movement in the
cardiovascular system. But knowledge regarding the out-of-plane flow component
is still lacking. With 3D flow estimation, all types of complex flow can be studied
independently of the examiners.24,25 Flow features such as the vortex ring formation
in the ventricles of the heart, or the shear stress along the vessel walls could be
detected through 3D flow (Figure 6).
Summary
• Vector flow techniques, with their many advantages over conventional

Doppler techniques, are powerful alternatives for blood flow evaluation.

• Vector flow imaging can visualise complex flow; refine the classic flow
parameters; and introduce new flow parameters and insonation windows.
• These factors will reduce operator dependency, improve the logistical work
flow for users and the diagnostic accuracy for patients.
References
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carotid artery with vector flow ultrasound. Ultrasound Med. Biol 2014; 40 (11): 2700–06.
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vector flow imaging. IEEE Trans. Ultrason., Ferroelec., Freq. Contr 2016; 63 (6): 842–53.
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14. Jensen JA, Nikolov SI, Yu A, Garcia D. Ultrasound vector flow imaging I: sequential systems. IEEE Trans
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dynamics. Ultrasound Med Bio 2013; 39(6).
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for estimation of peak velocity in the portal vein. Ultrasound Med Biol 2018; 44 (3): 593–601
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(8): 1607–17.
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Biomedical Engineering; 2006.
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transesophageal echocardiography and pulmonary artery thermodilution are not interchangeable.
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ultrasound vector volume flow. J Vascul Access 2016; 17 (6): 483–88.
22. Hansen PM, Olesen JB, Pihl MJ, et al. Volume flow in arteriovenous fistulas using vector velocity
ultrasound. Ultrasound Med Biol 2014; 40 (11): 2707–14.
23. Olesen JB, Villagomez-Hoyos CA, Dechau NM, et al. Non-invasive Estimation of Pressure Changes using
2-D Vector Velocity Ultrasound: An Experimental Study with In-Vivo Examples. IEEE Trans Ultrason
Ferroelec Contr 2018; 99: 1-1. .
24. Holbek. S, Hansen KL, Bouzari H, et al. Common carotid artery flow measured by 3D ultrasonic vector
flow imaging and validated with MRI. Ultrasound Med Biol 2017; 43 (10).
25. M. Correia, J. Provost, M. Tanter, M. Pernot. 4D ultrafast ultrasound flow imaging: in vivo quantification
of arterial volumetric flow rate in a single heartbeat. Phys Med Biol 2016; 61 (23): L48–61.
394
Guidelines, recommendations, and opinions
Limb salvage in acute
ischaemia due to occlusion
of popliteal aneurysm
Introduction
Popliteal artery aneurysms are rare, with an estimated prevalence of approximately
1% in men aged 65–80 years.1 The most dreaded complication is aneurysm
thrombosis leading to acute limb ischaemia.2 Preceding the event of acute ischaemia,
silent peripheral embolism from an aneurysm often leads to chronically occluded
crural vessels. Decades ago, Lilly and colleagues described arterial anatomy below
popliteal aneurysms to be distinctly abnormal in 90% of patients. Eighty-six
percent of patients with severe ischaemia had only a single-vessel runoff.3 These
chronically occluded crural vessels make revascularisation challenging and explain
the high amputation rates in the setting of acute limb ischaemia due to popliteal
aneurysm of up to 36%.4 Every effort should be undertaken to achieve limb salvage
since older patients with major amputation experience a low functional outcome.5
Contemporary large series addressing outcome after surgery for acutely thrombosed
popliteal aneurysms are not available.
Diagnosis of popliteal aneurysms in acute limb ischaemia

Initially, assessing the clinical status—including evaluation of motor function,
sensory function, and the arterial and venous Doppler signal—is important to
estimate the risk of extremity loss according to Rutherford.6 Diagnosis or exclusion
of a popliteal aneurysm is essential in acute limb ischaemia, because this has a
significant impact on the optimal therapy. Duplex ultrasound is readily available
and can provide information about the inflow and the outflow situation (Figure
1). Furthermore, the quality of the great saphenous vein for bypass material can be
assessed. Additional diagnostic tools can be chosen depending on the availability, but
should not delay urgent revascularization in cases of severe ischaemia. Alternatively,
computed tomography (CT) angiography is useful because it provides crucial
information on the inflow situation, vessel calcification, extent of thrombosis, and
patency of outflow arteries (Figure 2).
Surgical approach
The gold standard to treat acute limb ischaemia due to popliteal aneurysm is
open bypass surgery.7 The patient is placed in a supine position to get access to
the common femoral, the superficial femoral, the above-the-knee and below-the-
knee popliteal artery, and the crural arteries. If no preoperative CT angiography
has been performed, we perform an intraoperative angiography to assess in- and
397
A B
Figure 1: (A) Ultrasound diagnosis of a thrombosed distal superficial femoral artery in the setting of acute limb
ischaemia. (B) A completely thrombosed popliteal artery aneurysm of 3.47cm was the reason for this.
Limb salvage in acute ischaemia due to occlusion of popliteal aneurysm •
outflow. If a suitable outflow artery is identified, we proceed to bypass. Autologous

bypass material is preferably used. The site of the proximal anastomosis is either the
superficial femoral artery via a medial approach or the common femoral artery via a
longitudinal inguinal approach, in cases of superficial femoral artery aneurysms. A
below-the-knee medial approach, according to Szilagyi, is used to expose the distal
popliteal, the tibial and the fibular arteries.8 When inflow and outflow arteries are
identified, the vein is harvested. We perform an angioscopy guided valvulotomy
and use the vein in a non-reversed fashion, especially for longer bypasses. This
preserves the larger proximal vein diameter for the proximal (i.e. larger) arterial
anastomosis, hence reducing calibre mismatch. Intraoperative quality control is
performed with Doppler flow measurements and
angiography of the bypass and the anastomoses
(Figure 3). Importantly, the aneurysm should be
excluded with ligation. Nevertheless, aneurysms
can still grow through collaterals, and this might
lead to a secondary intervention.
When no suitable target vessel is identified,
exploration and balloon catheter thrombectomy
is performed to establish a bypass target. Intra-
arterial thrombolysis may be helpful in this
situation. When balloon catheter thrombectomy
is not possible, direct embolectomy of the
distal tibial artery at the level of the ankle may
be helpful to establish a bypass target. When
no revascularisation is achievable, conservative
Figure 2: Coronary reconstruction of a CT angiogram in the setting of

acute limb ischaemia revealed bilateral popliteal artery aneurysms with
complete aneurysm thrombosis on the left.
398
treatment with prostacyclin and heparin is started. Demarcation is awaited to

determine the level of amputation.
After revascularisation, the patient is anticoagulated with acetylsalicylic acid
and warfarin. We continue oral anticoagulation for a minimum of three months.
In cases of severely compromised outflow, which is often the case in the setting
of acute limb ischaemia due to popliteal aneurysm, lifelong anticoagulation with
warfarin is prescribed.
A systematic review presented limb salvage rates of 74% at five years after
acute limb ischaemia due to popliteal aneurysm. Excellent five years secondary
patency rates of 80% have been published.9 This is remarkable, considering the
limited outflow. In an elective setting, popliteal artery aneurysm can be treated
with a very low mortality and morbidity and high patency rates of bypass or
interposition grafts.7
Endovascular approach
In the literature, a complete endovascular approach has been described in the
setting of acute limb ischaemia due to popliteal aneurysm. This can either consist of
catheter-directed thrombolysis with repeated angiographies and selective stenting.
Direct stenting of a thrombosed popliteal aneurysm in patients with a least one
open outflow vessel without preoperative thrombolysis has also been reported. The
largest series included only six patients.10 Primary and secondary patency rates are
lower compared to bypass surgery.

This approach may be justified in
selected high-risk patients unsuitable
for surgery.
Role of preoperative
thrombolysis
The role of preoperative thrombolysis is
controversial in the setting of acute limb
ischaemia due to popliteal aneurysm. In
a recent systematic review, limb salvage
rates were unchanged after preoperative
thrombolysis compared to patients who
did not undergo thrombolysis.9 Five-year
primary and secondary patency rates
were not superior after thrombolysis.9
However, the included surgical series
reported the extent of acute ischaemia
only in 122 of 895 patients. Neurologic
deficits (Rutherford category IIb and III)
Figure 3: (A) Intraoperative angiography after GSV bypass

from the superficial femoral artery to the below-the-knee
popliteal artery. (B) The outflow is severely compromised
with a single-vessel runoff via the fibular artery.
399
are indicators for emergency revascularisation.11 Thus, preoperative thrombolysis may only
lead to a better outcome in patients with less severe ischaemia. These patients have per
se better outcomes regarding limb salvage. According to the available data, preoperative
thrombolysis has no benefit and may lead to a delay in revascularisation. Therefore, it
cannot be recommended in the setting of acute limb ischaemia due to popliteal aneurysm.
Summary
• Diagnosis of a popliteal aneurysm in the setting of acute limb ischaemia

is crucial.
• In severe ischaemia, rapid transfer to the operating theatre is important and

should not be delayed by excessive diagnostics. A CT angiography is useful
when readily available.
• Revascularisation in acute limb ischaemia due to thrombosed popliteal
aneurysm is challenging due to chronically occluded crural vessels.
• Preoperative thrombolysis is not recommended.
• Revascularisation with open bypass surgery is the treatment of choice.
• Good limb salvage rates and excellent bypass patency can be achieved.
References
1. Trickett JP, Scott R a P, Tilney HS. Screening and management of asymptomatic popliteal aneurysms.
J Med Screen 2002; 9: 92–93.
2. Ravn H, Björck M. Popliteal Artery Aneurysm with Acute Ischemia in 229 Patients. Outcome after
Thrombolytic and Surgical Therapy. Eur J Vasc Endovasc Surg 2007; 33 (6): 690–95.
3. Lilly MP, Flinn WR, McCarthy WJ, et al. The effect of distal arterial anatomy on the success of popliteal
aneurysm repair. J Vasc Surg 1988; 7 (5): 653–60.
4. Vermilion BD, Kimmins SA, Pace WG, Evans WE. A review of one hundred forty-seven popliteal
aneurysms with long-term follow-up. Surgery 1981; 90 (6): 1009–14.
5. Schoppen T, Boonstra A, Groothoff JW, et al. Physical, mental, and social predictors of functional
outcome in unilateral lower-limb amputees. Arch Phys Med Rehabil 2003; 84 (6): 803–11.
6. Robinson WP, Belkin M. Acute limb ischemia due to popliteal artery aneurysm: A continuing surgical
challenge. Semin Vasc Surg 2009; 22 (1): 17–24.
7. Huang Y, Gloviczki P, Noel AA, et al. Early complications and long-term outcome after open surgical
treatment of popliteal artery aneurysms: Is exclusion with saphenous vein bypass still the gold
standard? J Vasc Surg 2007; 45 (4): 706–16.
8. Szilagyi D, Schwartz R, Reddy D. Popliteal arterial aneurysms: Their natural history and management.
Arch Surg 1981; 116 (5): 724–28.
9. Kropman RHJ, Schrijver AM, Kelder JC, et al. Clinical outcome of acute leg ischaemia due to
thrombosed popliteal artery aneurysm: Systematic review of 895 Cases. Eur J Vasc Endovasc Surg 2010;
39 (4): 452–57.
10. Fargion A, Masciello F, Pratesi G, et al. Endovascular treatment with primary stenting of acutely
thrombosed popliteal artery aneurysms. Ann Vasc Surg 2017. Epub.
11. Rutherford RB, Baker JD, Ernst C, et al. Recommended standards for reports dealing with lower
extremity ischemia: Revised version. J Vasc Surg 1997; 26 (3): 517–38.
400
The cost of emergency
peripheral events for
the patient and for
the health service
Introduction
Vascular disease is the leading cause of death and disability worldwide.1–3 Peripheral
arterial disease has a poor prognosis, and has been neglected in terms of research,
early detection and primary prevention.4–7 The paucity of contemporary research
is despite the growing evidence for simple, cost-effective primary and secondary
prevention strategies in at-risk groups—including antiplatelet, statin, and
antihypertensive therapy, smoking cessation and supervised exercise programmes.8–10
Recent estimates put the cost of vascular disease to the US and European healthcare
systems at US$196 billion and €106 billion respectively.11,12 Clearly more needs to
be done to prevent, diagnose and treat peripheral arterial disease. In this chapter,
we will summarise the findings of the OXVASC (Oxford Vascular) study, which
assessed the costs of peripheral arterial disease at an individual patient level and at
a healthcare system level.
OXVASC
The OXVASC study was designed to ascertain all acute peripheral arterial disease
events presenting to medical attention, irrespective of age, in a population of
92,728 in Oxfordshire, UK, from 2002 onwards.13 This study has enabled the
determination of incidence, outcome, risk factors, long-term prognosis, and
calculation of both acute and long-term healthcare costs after index events.
For the purpose of the OXVASC study, the following three acute events were
measured—acute limb ischaemia, acute visceral ischaemia, and critical limb
ischaemia.14 Acute limb ischaemia was defined as an arterial event of sudden onset
and less than two weeks in duration, resulting in symptomatic limb ischaemia.5
Severity of ischaemia was graded as per the Rutherford classification.15 Acute
visceral ischaemia was defined as an acute arterial event of sudden onset and less
than two weeks in duration resulting in critical limb ischaemia. This essentially
included all patients whose symptoms had been present for greater than two weeks,
with ischaemic rest pain and/or tissue loss to warrant urgent hospital admission,
and whose symptoms were thought to be secondary to large or small vessel
arterial disease.14
OXVASC was developed to provide accurate population-based data on the
incidence, outcome, risk factors, and current levels of primary and secondary
401
The cost of emergency peripheral events for the patient and for the health service •
Figure 1: The terms “normotensive” and “non-diabetic” refer to no diagnosis of hypertension or diabetes made prior
to event.
prevention for peripheral arterial disease. This enables the creation of strategies to
improve prevention, calculation of risk stratification, and will provide clinicians with
evidence to inform patients about risks and prognosis. By assessing the financial
impact of peripheral arterial disease on the healthcare system, OXVASC aims to
compare costs with other common conditions, inform health service provision, and
guide future research into peripheral arterial disease.
Incidence
Critical limb ischaemia is the most common type of acute peripheral arterial disease
episode, with an incidence in the population of 22/100,000/year (Figure 1). The
respective incidences of acute limb ischaemia and acute visceral ischaemia are less
than half of critical limb ischaemia—10 and 8 per 100,000 population per year.
402
Incidence rates for all event types increase steeply with age: 60% of events occur
at age ≥75 years and over 25% at ≥85 years. Age at event is significantly higher for
women than for men for all types of event.
Previous published work has largely used hospital episode statistic (HES) coding
data for identification of peripheral arterial disease events and interventions.16–19
However, OXVASC has shown, particularly in the UK, that the accuracy of HES
coding to be very poor for this group of conditions, with less than half of peripheral
arterial disease events correctly identified (49%) and many non-peripheral arterial
disease events are incorrectly classified (Figure 2).14
Impact on individuals
Patient independence was measured using a modified Rankin Scale, before and after
the acute peripheral arterial disease event. The majority of participants, over 60%,
were found to be independent (defined as modified Rankin Scale ≤ 2) prior to the
index event. However, only a quarter were found to be alive and independent at six
months, and barely above 10% at five-years post-index event.14
Patients presenting with critical limb ischaemia or acute limb ischaemia as an
acute event are at a significant risk of future limb loss. OXVASC data show that
amputation-free survival is lower within the first three months, from the index
event, in patients presenting with acute limb ischaemia compared with those with
critical limb ischaemia (59.1% vs. 75.5%; p=0.001). However, at five years post-
event, the risk of limb loss becomes greater in patients with critical limb ischaemia:
27.1% compared with 36.7%.14 Overall, survival rates at 30-days and five-years
was lowest in patients presenting with acute visceral ischaemia (28.2% and 24.4%)
in comparison to those presenting with acute limb ischaemia (75.3% and 55.9%)

or critical limb ischaemia (92.6% and 70.8%) [Figure 3].14
Healthcare costs
Despite the poor prognosis associated with peripheral arterial disease, there has been
little research into the economic impact of peripheral arterial disease on healthcare
systems. OXVASC found that the mean five-year total hospital costs after the index
peripheral arterial disease event were £27,165 (95% confidence intervals: £23,709
Figure 2: The efficacy of routine coding (hospital discharge, hospital death, and primary care death coding) in
identifying ischaemic peripheral arterial events as compared to OXVASC ascertainment.
403
Figure 3: Five-year rates of major amputation, amputation-free survival, and overall survival for incident acute
peripheral arterial events by subtype with numbers at risk.
to £30,620). The large majority were due to inpatient hospital stays, costed at
£23,707 (87%). The costs were also shown to vary significantly depending on the
type of peripheral arterial disease event. Acute limb ischaemia patients incurred
mean total costs over five years of £18,390 (95% confidence intervals [CI]:
£11,885 to £24,896), acute visceral ischaemia patients incurring costs of £7,765
(95% CI: £4,506 to £11,023), and critical limb ischaemia patients incurring costs
of £37,658 (95% CI: £32,772 to £42,544; p<0.0001). Independent of the type
of index peripheral arterial disease event, the large majority of expenditure were
incurred in the first year alone: acute limb ischaemia £11,790(64%); acute visceral
ischaemia £5,033 (65%); and critical limb ischaemia £23,604 (63%).
404
Univariate analysis was carried out to assess baseline predictors of five-year
hospital costs following index peripheral arterial disease event. This analysis showed
that patients with history of peripheral arterial disease prior to their acute event
incurred significantly higher hospital costs (£33,328 vs. £20,895, p=0.0004),
as did patients with diabetes mellitus (£45,114 vs. £19,850; p<0.0001) and
hyperlipidaemia (£33,878 vs. £21,293; p=0.0003). Age and previous history of
heart failure were also found to be significant predictors of reduced overall costs
over five-years, which could be explained by higher case fatality rates. We also
observed that current smokers at the time of the index event were significantly
more likely to incur lower costs (reduced by £12,708, p=0.008) than non-smokers.
Due to the OXVASC methodology and the simultaneous ascertainment of all
acute vascular events in the same population, it is feasible to compare healthcare
costs for different vascular conditions.14 The mean five-year hospital costs after
stroke and transient ischaemic attack were £18,435 and £13,500, in comparison to
£27,165 after peripheral arterial disease event (p<0.00001). Even when comparing
for severe stroke (£19,044), costs after peripheral arterial disease were considerably
and significantly higher (p=0.011). Despite higher mortality rates than from stroke,
the increased costs after peripheral arterial disease are in part explained by the
higher rates of surgical procedures in these patients. Multivariate analysis shows
that peripheral arterial disease interventions significantly increased costs in the first
five years post-event. For example an above-knee amputation increased care costs
by £20,115. As stroke has been previously shown to be more costly than acute
myocardial infarction for the healthcare system, one could infer that critical limb
ischaemia is the most expensive cardiovascular event—alas, with the least amount
of research funding and resources focused on improving its prevention.20–21

Premorbid identification
Given the high impact of acute peripheral arterial disease events, it is important
that we consider potential prevention strategies with an aim to identify patients
at-risk in order to initiate intervention and attempt to prevent or delay index event
occurrence. In OXVASC, the majority of patients (77.2%) had documented prior
vascular disease—peripheral arterial disease was noted to be the most common type
in patients presenting with critical limb ischaemia (70.8%). Almost all patients
(96.8%) that presented with peripheral arterial disease had known vascular risk
factors. Patients presenting with critical limb ischaemia were far more likely to
have three or more risk factors for atherosclerosis (hypertension, smoking, diabetes
mellitus, hyperlipidaemia, and male sex) than patients presenting with acute limb
ischaemia or acute visceral ischaemia (61.9%; 44.9%; and 39.8%; p=0.001).14
Compared to the underlying study population, known hypertension (relative risk
[RR] 2.75, 95% CI: 1.95–3.90; p <0.001), ever-smoking (RR 2.14, 95% CI:
1.37–3.34; p <0.001), and diabetes (RR 3.01, 95% CI: 1.69–5.35; p<0.001) were
associated with peripheral arterial disease events.14 Mean age at index event was
highly correlated with the number of atherosclerotic risk factors, where patients
with >3 risk factors had an event approximately eight years younger than those with
<2 risk factors (p=0.007).14 Prior diagnosis of atrial fibrillation was most common
in patients presenting with acute limb ischaemia or acute visceral ischaemia and
less prevalent in patients with critical limb ischaemia (38.7%; 37.2%; and 20.8%;
p=0.001).14
405
Despite the high prevalence of cardiovascular risk factors and known arterial
disease, only a moderate proportion of patients were on antiplatelet (54.4%),

statin (44.5%) and anti-hypertensive therapy (69.7%). In patients who had been
commenced on antihypertensives, more than 50% of subsequent blood pressure
readings still exceeded 140/90mmHg.14 In patients with index cardio-embolic
events (23.6%), the majority had documented diagnosis of atrial fibrillation
prior to the event. However, less than 15% were anticoagulated despite a large
majority (>80%) having CHA2DS2VASC score ≥222 without contraindication
for anticoagulation.14
Prognostic indicators at index presentation

Severity of ischaemia on admission with peripheral arterial disease was predictive
of 30-day amputation or death as well as one-year mortality for all event types.14
In cases of acute limb ischaemia, male sex, renal dysfunction and prior coronary
artery disease were independently predictive of 30-day amputation or death, while
age and renal dysfunction was predictive of one-year mortality. In acute visceral
ischaemia, age and hypertension were predictive of one-year mortality. In patients
with critical limb ischaemia, prior heart failure and renal dysfunction were predictive
of one-year mortality. Thirty-day amputation-free survival could be stratified in
critical limb ischaemia depending on severity on presentation—100% for rest
pain only (Rutherford 4), 83.7% for minor tissue loss (Rutherford 5), and 41.7%
for major tissue loss (Rutherford 6).14 In acute limb ischaemia and critical limb
ischaemia, diabetes mellitus was predictive of both short and long-term risk of limb
loss, suggesting more aggressive early intervention may be recommended in these
patients. Finally, acute visceral ischaemia has the highest one-year mortality of all
acute vascular events, yet many of these events would be prevented by appropriate
anticoagulation therapy for at-risk patients with atrial fibrillation.
Conclusion
The clinical and financial burden of peripheral arterial disease at the individual
and healthcare system level are substantial. There are high rates of mortality and
poor functional outcome, despite advances in open and endovascular intervention
to prevent life or limb loss. The majority of patients have known vascular disease
and multiple treatable risk factors, yet premorbid control is poor despite readily
available medical therapy with a strong evidence-base supporting its use. More
needs to be done in primary and secondary care to identify and manage patients
with peripheral arterial disease to prevent emergency life-threatening presentations.
It is time to close the stable doors before the proverbial horse bolts.
406
Summary
• Peripheral arterial disease is a global pandemic with poor prognosis.

• It has been neglected in terms of research, early detection and primary
prevention.
• The costs for the individual (death and disability) and health care system are
substantial (acute peripheral arterial disease presentations require multiple
emergency interventions, prolonged hospital and community care, at great
cost).
• Most patients suffering emergency events have known prior vascular disease
and multiple treatable risk factors, yet premorbid intervention and risk factor
control are poor.
• More needs to be done in primary and secondary care to identify and manage
patients with peripheral arterial disease to prevent emergency life-threatening
presentations.
References
1. Lozano R, Naghavi M, Foreman K, et al. for the Global Burden of Disease Study. Global and regional
mortality from 235 causes of death for 20 age groups in 1990 and 2010: a systematic analysis for the
Global Burden of Disease Study 2010. Lancet 2012; 380 (9859): 2095–28.
2. Murray CJ, Vos T, Lozano R, et al. for the Global Burden of Disease Study. Disability-adjusted life years
(DALYs) for 291 diseases and injuries in 21 regions, 1990-2010: a systematic analysis for the Global
Burden of Disease Study 2010. Lancet 2012; 380 (9859): 2197–23.
3. Wang H, Dwyer-Lindgren L, Lofgren KT, et al. for the Global Burden of Disease Study. Age-specific

and sex-specific mortality in 187 countries, 1970-2010: a systematic analysis for the Global Burden of
Disease Study 2010. Lancet 2012; 380 (9859): 2071–94.
4. Hirsch AT, Criqui MH, Treat-Jacobson D, et al. Peripheral arterial disease detection, awareness, and
treatment in primary care. JAMA 2001; 286 (11): 1317–24.
5. Norgren L, Hiatt WR, Dormandy JA, et al. Inter-Society Consensus for the Management of Peripheral
Arterial Disease (TASC II). J Vasc Surg 2007; 45 Suppl S: S5–67
6. Tomson J, Lip GY. Peripheral arterial disease: a high risk - but neglected - disease population. BMC
Cardiovasc Disord 2005; 5 (1): 15.
7. Jaff MR. Why patients know more about cars than peripheral artery disease. Circulation 2014; 130:
1778–79.
8. Anderson JL, Halperin JL, Albert NM, et al. Management of patients with peripheral artery disease
(compilation of 2005 and 2011 ACCF/AHA guideline recommendations): a report of the American
College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines.
Circulation 2013; 127: 1425–43.
9. Board JBS. Joint British Societies' consensus recommendations for the prevention of cardiovascular
disease (JBS3). Heart 2014; 100 Suppl 2: ii1-ii67.
10. Perk J, De Backer G, Gohlke H, et al., European Association for Cardiovascular P, Rehabilitation and
Guidelines ESCCfP. European Guidelines on cardiovascular disease prevention in clinical practice
(version 2012). The Fifth Joint Task Force of the European Society of Cardiology and Other Societies on
Cardiovascular Disease Prevention in Clinical Practice (constituted by representatives of nine societies
and by invited experts). European Heart Journal 2012; 33: 1635–701.
11. Mozzafarian D, Benjamin EJ, Go AS, et al. Heart disease and stroke statistics – 2016: A report from the
American Heart Association. Circulation 2016; 133: e38-e360.
12. Leal J, Luengo-Fernandez R, Gray A. Economic Costs. In: Nichols M, Townsend N, Scarborough P, et al.
European Cardiovascular Disease Statistics 2012. European Heart Network, Brussels, European Society
of Cardiology, Sophia Antipolis.
13. Rothwell PM, Coull AJ, Silver LE, et al.; Oxford Vascular Study. Population-based study of event-rate,
incidence, case fatality, and mortality for all acute vascular events in all arterial territories (Oxford
Vascular Study). Lancet 2005; 366: 1773–83.
407
14. Howard DPJ, Banerjee A, Fairhead JF. et al. A population-based study of incidence, risk factors, outcome
and prognosis of ischaemic peripheral arterial events: implications for prevention. Circulation 2015;
132 (19): 1805–15.
15. Rutherford RB, Baker JD, Ernst C, et al. Recommended standards for reports dealing with lower limb
peripheral arterial occlusion. J Vasc Surg 1997; 26: 517–38.
16. Farrell B, Godwin J, Richards S, Warlow C. The United Kingdom transient ischaemic attack (UK-TIA)
aspirin trial: final results. J Neurol Neurosurg Psychiatry 1991; 54: 1044–54.
17. Hirsch AT, Hartman L, Town RJ, Virnig BA. National health care costs of peripheral arterial disease in the
Medicare population. Vascular Medicine 2008; 13: 209–15.
18. Peacock JM, Keo HH, Duval S, et al. The incidence and health economic burden of ischemic amputation
in Minnesota, 2005-2008. Pre Chronic Dis 2011; 8: A141.
19. Currie CJ, Morgan CLL, Peters JR. The epidemiology and cost of inpatient care for peripheral vascular
disease, infection, neuropath, and ulceration in diabetes. Diabetes Cae 1998; 21: 42–48.
20. C Nicholson G, Gandra SR, Halbert RJ, Richhariya A, Nordyke RJ. Patient-level costs of major
cardiovascular conditions: a review of the international literature. Clinicoecon Outcomes Res 2016;
8: 495–506.
21. Hallberg S, Gandra SR, Fox KM, et al. Healthcare costs associated with cardiovascular events in patients
with hyperlipidemia or prior cardiovascular events: estimates from Swedish population-based register
data. Eur J Health Econ. 2016; 17 (5): 591–601.
22. National Institute for Health and Care Excellence. Atrial fibrillation: management. London: NICE; 2014.
408
Critical limb ischaemia controversies
How to change a service
and the stages of
changing a service
“Superior doctors prevent the disease, mediocre doctors treat the disease before evident,
inferior doctors treat the full-blown disease.” 1
Introduction
After initial training, most surgeons develop an area of clinical interest in which
they become expert and strive to gain the best results for their patients with
conditions that fall within this area of interest. However, after a period of surgical
enthusiasm, they usually realise that many more factors, other than their technical
ability, influence outcome. Awareness of the condition in the population and
amongst other non-specialist clinicians, timeliness of referral and the resources to
follow-up patients will affect the outcome for the patient, often more so than the
technical success of the vascular intervention.
Many surgeons now realise that unless all of these factors are addressed and
optimised, it is unlikely that they will see an improvement in surgical outcomes and,
therefore, they set about trying to improve the service. With increasing pressures on
healthcare budgets across the world and competing needs of a burgeoning, ageing
population, securing adequate resources for a service can prove daunting—many
become disillusioned and frustrated with the attempt to implement change and
give up.
This chapter describes the observed stages of change that have occurred in diabetic
foot care in the UK—a service intimately linked to vascular surgery and an example
of how relatively small changes in service configuration can make highly significant
changes in patient outcomes with financial and operational efficiency. However,
bringing about change (improvement) has been slow and still has a long way to
go. The chapter outlines our experiences, observations and service improvement
principles, which may aid others understand what the obstacles to implementing
service change exist and how to overcome them.
Stage 1: Recognition of the problem

In healthcare, recognition that a problem is developing is often slow and insidious.
That the world faces a diabetes pandemic has been recognised for years, but the
consequences of the complications of the condition seem to have escaped notice to
all but a few. It is estimated that there are 3.6 million people living with diabetes
in the UK, plus another 1 million who are undiagnosed. This figure will reach 5
million by 2025. Putting this into a global context, there are currently 422 million
people with diabetes—8.5% of the population.2 This results in an estimated annual
411
incidence of 90,000 foot ulcers and 9,900 amputations in the UK and up to 26
• AD Godfrey and CP Shearman
million foot ulcers worldwide.3

Although the St Vincent’s Declaration, the first issued in 1989, strongly advocated
the need to improve care for people with diabetes, little attention was paid to
it until recently. However, awareness has grown as the cost of this problem has
taken hold. In 2005, the International Diabetes Foundation and the International
Working Group on the Diabetic Foot suggested that 85% of amputations in people
with diabetes were potentially preventable.4
Stage 2: Enthusiasm
Even with a problem as large and threatening to the populations’ health as discussed,
How to change a service and the stages of changing a service
unless enthusiasts are prepared to tackle the problem, little is likely to be changed
or implemented. Diabetic foot complications have generally not been an attractive
area in which doctors choose to work. The scale of the problem and perceived
lack of therapies available have often led to a nihilist attitude to the problem.
However, over the past two decades, a number of diabetic physicians around the
world have championed the cause of the diabetic foot and gained the recognition
as a problem that must not be ignored, but importantly, one that with the correct
service configuration and resources can significantly improve for patients.
The prevalence of diabetes in patients with vascular disease has meant that
vascular surgeons, even if not directly involved with foot care, cannot escape the
management of the increasing numbers of patients with diabetic foot complications.
The need to understand how diabetes, the circulation and the implication of
surgical interventions in this population group has become essential. Although
revascularisation procedures are currently a main stay of treatment, vascular
surgeons have realised that many patients can avoid the need for these treatments
if managed appropriately in the early stages of their disease. Surgical enthusiasm
has contributed to large international meetings such as DFCon in the USA, The
International Symposium on the Diabetic Foot in the Netherlands and Ilegx at the
Charing Cross symposium to name but a few.
Stage 3: Knowledge
While emotive pleas for extra funding may occasionally be successful in a high
profile areas such as childhood cancer, with so many competing healthcare needs
and a finite budget, hard evidence is needed to convince those responsible for
commissioning healthcare that supporting a condition will bring benefit to the
patients suffering from it. Historically, high-quality evidence supporting surgical
interventions has been poor and has led to many procedures being challenged or not
made widely available. However, surgeons and patients undergoing treatment are
increasingly becoming engaged in high quality research demonstrating the clinical
efficacy, or not, of the therapies available. Evidence of clinical efficacy is obviously
essential to justify the use of a particular therapy in a patient. Yet this alone is not
enough to justify its use; the cost-effectiveness of the treatment must also be taken
into account. Many surgeons find cost-effectiveness an uncomfortable concept
and do not feel that it is their role to make judgements on the applicability of a
clinically proven treatment. However, in all publically funded healthcare systems,
the cost-effectiveness of a therapy is bound to have a bearing of its adoption.5
412
Since the work of Paul Brand in the 1950s and 60s in leprosy that signposted the

underlying mechanisms of diabetic foot complications, published literature in the
field has increased from 0.7% of PubMed listed articles between 1980 and 1988 to
2.7% between 1998 and 2004. Knowledge of why complications occur and how
to manage and prevent them is now advanced.5 The cost of our current methods
of managing the condition are not effective and exorbitantly costly consuming
0.6–0.7% of the total NHS budget.6
Stage 4: Implementation
Ideally, national policy towards managing a condition will bring about benefits
widely and most rapidly. Early evidence from Finland showed a reduction in
major amputations that was related to better access to services.7 However, the
implementation of change in services has been localised and somewhat patchy.
Individual services have been able to show amputation reductions of approximately
70% and to save money for the local health economy. Many, however, have then
failed due to lack of continued support and amputation rates have increased
once again.6
The development of International and National Guidelines such as the

International Federation of Diabetes in 2015 and National Institute for Health
and Clinical Excellence (NICE) guidelines in 2011 and 2015 should have driven
change.8,9 The message of the guidelines was simple and indicated that people
with diabetes should have regular foot checks and if they develop problems, be
seen early by a member of a diabetic foot care team. While in many areas of the
uptake of these guidelines has been good, in many others they have largely been
ignored. In the last National Diabetes Audit of 2015, 31% of hospitals in England
had no diabetic foot service and 58% of people admitted to hospital with new or
established foot ulcers were not examined within 24 hours.10 This is reflected in the
continuing wide variation in amputation rates for people with diabetes depending
on where they live.
In 2012 vascular surgery became an independent speciality in the UK with its
own curriculum for training vascular surgeons. For the first time, management
of the diabetic foot was made explicit, ensuring that all future vascular surgeons
would be exposed to, and learn how to manage diabetic foot complications in
a multidisciplinary team setting. This was mirrored in the Provision of Vascular
Service Document of 2015, produced by the Vascular Society of Great Britain
and Ireland that gave advice to healthcare commissioners on how services should
be provided.11
Stage 5: Persistence
With such good evidence of clinical efficacy, cost effectiveness and simple guidelines
to follow it might be expected that beneficial change would result. Disappointingly,
this is often not the case. The short-term financial constraints, compounded by the
pressure of other priorities, distract a stretched healthcare system from the project.
This is often the stage that clinicians become frustrated after all their previous work
and give up.
However, patient led groups—if engaged in the process—can be amazingly
forceful in ensuring work continues. In the UK, Diabetes UK has run a number
413
of publicity programmes (Putting Feet First) illustrating the plight of people with
diabetes and foot complications. These have been recognised by the national media,
as have publications that explore regional, unit specific amputation rates and the
variability within. Strong public and media campaigns have resulted in the areas
with the worst results forcing a change in the service provided. Politicians can also
be strong advocates of change at this time. Some with diabetes themselves, or the
support of people with diabetes in their constituencies, lead groups or committees
to pressurise government to adopt policies such as the NHS Cardiovascular Disease
Outcomes Strategy to reduce death and amputation in people with cardiovascular
disease (including those with diabetes).12 This approach also resulted in an All-
Parliamentary Group report on saving limbs and saving lives.13
Stage 6: Litigation
Litigation in UK healthcare is becoming a massive burden on healthcare costs. In
2015–2016 it reached £1.4 billion that could otherwise be spent on healthcare.14
Diabetic foot complications are a significant proportion of this amount. Failure to
diagnose, or to refer and treat in a timely fashion, resulting in avoidable amputation
causes unnecessary suffering and disability for the patient and is quite reasonably
likely to result in compensation. While litigation can be an uncomfortable
experience for all involved, ironically, it can be a powerful catalyst for change. Not
many organisations that lose an expensive case and pay compensation fail to take
action, implementing changes to prevent the same occurrence. Of course, it would
be far better for the patient if this lesson did not have to be learnt repeatedly,
but different healthcare organisations frequently forget the lessons learnt, acting as
individual silos, reducing the open culture of learning which we all strive towards.
Conclusion
The best results for surgical outcomes in people with diabetic foot complications
occur in well-structured, organised multidisciplinary teams that encompass both
the community and hospital care. Screening, early detection and correction of
problems is the key to good outcomes. Achieving this—despite strong evidence of
better outcomes for patients, matched with cost savings for the healthcare system—
can be surprisingly difficult. Evidence of clinical efficacy and cost benefit combined
with simple solutions, enthusiasm, persistence and patient support are likely to
bring about change. If not, ultimately lawyers will!
414
Summary
• There is a problem that needs to be characterised.

• Expert enthusiasts should promote the need to improve care.
• High quality evidence for the benefit of change must be established.
• Implementation of changes including guidelines with patient and professional
advocacy.
• Persistence and lobbying when initial attempts do not succeed
• Identify poor outcomes including those that come to litigation.
References
1. Huangdi Neijing (2600BCE). https://en.wikipedia.org/wiki/Huangdi_Neijing [Date accessed 14
February 2018]
2. World Health Organization. Diabetes.
3. Diabetic Foot Ulcers and their recurrence. N Engl J Med 2017; 376: 2367–75.
4. International Diabetes Federation. Time to Act: diabetes and foot care. International Diabetes

Federation, Brussels. 2005.
5. National Institute for Health and Clinical Excellence. Judging whether public health interventions offer
value for money. http://bit.ly/2F1fa26 [Date accessed 14 February 2018]
6. Diabetes UK. Foot care for people with diabetes: the economic case for change. http://bit.ly/2F1knqC
[Date accessed 14 February 2018]
7. Winell K, Niemi M, Lepantalo M. The national hospital discharge register data of lower limb
amputations. Eur J Vasc Endovasc Surg 2006; 32: 66–70.
8. The International Working Group on the Diabetic Foot. Prevention and management of Foot Problems
in Diabetes. http://www.iwgdf.org/files/2015/website_development.pdf [Date accessed 14 February
2018]
9. National Institute for Health and Clinical Excellence. Diabetic foot problems: prevention and
management. https://www.nice.org.uk/guidance/ng19 [Date accessed 14 February 2018]
10. National Diabetes Audit, 2015-16 Report 2a: Complications and Mortality (complications of diabetes).
http://bit.ly/2srbAvD [Date accessed 14 February 2018]
11. Vascular Society of Great Britain and Ireland. The provision of services for patients with vascular
disease 2015. http://bit.ly/2HdPBeZ [Date accessed 14 February 2018]
12. Gov UK. Improving cardiovascular disease outcomes: strategy. http://bit.ly/2F2SGh4 [Date accessed
14 February 2018]
13. All-Party Group on Vascular and Venous Disease. Saving limbs and saving lives: Patient access to
technologies for the diagnosis and treatment of peripheral arterial disease. http://appgvascular.org.
uk/reports [Date accessed 14 February 2018]
14. NHS Litigation Authority Annual report and accounts 2015/16. http://bit.ly/2HcGJGm [Date accessed
14 February 2018]
415
Percutaneous femoropopliteal
bypass—the DETOUR I trial
J Mustapha and G Halena
Introduction
Peripheral arterial disease affects more than 200 million people worldwide—and
its prevalence continues to increase as “baby boomers” enter high-risk age groups.1
With estimates of more than 20% of the population projected to age into the 65
and over cohort by the year 2050, peripheral arterial disease is a growing epidemic
with staggering social and economic costs.2
Disease of the femoropopliteal arterial segment is the most common cause
of intermittent claudication.3 Once this disease progresses to lifestyle-limiting
claudication or, even further, to critical limb ischaemia, physicians will generally
consider revascularisation to be mandatory. Endovascular interventions are now
reported to be even more common than bypass surgery in the treatment of
this disease.4 From the patient’s perspective, the possibility of avoiding general
anaesthesia, prolonged hospital stays—as well as complications such as wound
infection, haemorrhage, or nerve injury—is compelling. But, while a number
of endovascular techniques have improved outcomes and broadened the field of
treatable patients, certain comorbidities and lesion architecture do not immediately
lend themselves to safe, minimally-invasive solutions that provide durable patency.
Unmet need in treatment of long lesions

Short- to mid-length lesions can be successfully treated with standard endovascular
technologies such as balloon angioplasty, drug-coated balloons, and stents. In
clinical trials, these technologies have proven safe and effective for revascularisation
in short, diseased arteries. For long occlusions, especially those greater than 20cm,
additional challenges remain.
Long lesions have historically been treated with open femoropopliteal bypass
surgery (fem-pop bypass). Open bypass surgery has the benefit of long-term
durability; however, open surgery of any kind is linked with a number of
complications that can negatively affect patient quality-of-life or device/procedure
patency. Open fem–pop bypass specifically is associated with complications that
contribute to a 30-day morbidity rate of 37%.5
Currently, minimally-invasive technologies are being used to treat these longer
lesions; however, they have yet to demonstrate the same durability as open surgery.6
Even with advanced skills, acute technical success does not translate into durable,
long-term patency. These procedures are time-consuming, often requiring the use of
many devices, and are plagued with re-treatments, generating a financial burden for
the healthcare system as well as frustration for the patient and treating physician.
Ultimately, many of these patients progress to open bypass surgery or amputation.
417
All of these factors distill into one simple but serious conclusion: there is an
• J Mustapha and G Halena
unmet need in endovascular approaches to the treatment of long-segment superficial

femoral artery disease, as an ever-growing number of patients are not able to
benefit from the durability of an open surgical bypass due to age and cardiovascular
comorbidities. For patients with long-segment femoropopliteal disease, the optimal
treatment path remains unclear.
The novel DETOUR procedure

An innovative new therapy, the DETOUR procedure may be the solution to this
unmet need. Enabled by PQ Bypass’ proprietary DETOUR system—the Torus
Percutaneous femoropopliteal bypass—the DETOUR I trial
stent graft, DETOUR crossing device, and DETOUR snare—a pathway is created
originating in the superficial femoral artery, crossing into and travelling through
the femoral vein, and then returning into the popliteal artery, completely bypassing
the diseased part of the vessel (Figure 1). Variables affecting long-term patency and
procedure times such as chronic total occlusion and diffuse calcification are instead
made irrelevant by the pathway created by a series of overlapping Torus stent
grafts, creating a fully endovascular, fem–pop bypass. Unlike existing technologies,
which merely create a channel through the disease, the DETOUR procedure is an
innovative and unique solution designed to provide the durability and patency of
open bypass surgery, through a minimally-invasive approach.
Figure 1: Schematic of the DETOUR procedure. Figure 2: Long occlusion of the patient’s right
superficial femoral artery. Total lesion length
exceeded 25cm.
418
Figure 3: Angiography performed during a redo Figure 4: Follow-up duplex Doppler scan of the graft at 24
intervention on the patient’s contralateral limb months demonstrating flow through distal junction (where the
18 months after the PQ bypass procedure. The graft leaves the deep vein and re-enters the popliteal artery).

endovascular conduit (white arrows) remains
patent without any signs of restenosis. Black star
marks the passage of the conduit from the deep
femoral vein back to the landing zone in the
popliteal artery (black arrow).
Case study of the DETOUR system

A 60-year-old woman with bilateral superficial femoral artery disease was treated
with a DETOUR procedure in November 2015 for a 25cm long occlusion of her
right superficial femoral artery (Figure 2). The procedure was performed under
local anaesthesia, was discharged home the following day, and noticed immediate
improvement and no claudication in her right limb. During the observation
period in the study, her left (contralateral) limb also required treatment twice. The
left superficial femoral artery was initially treated with stenting of the proximal
portion and balloon angioplasty of a mid- superficial femoral artery lesion. Twelve
months after this procedure she had to undergo a redo procedure on the left as she
developed a mild in-stent restenosis in the proximal superficial femoral artery and
haemodynamically significant restenosis in the middle portion of the superficial
femoral artery. This time a drug-coated balloon was used to treat in-stent restenosis
and another stent was implanted in the middle portion of her superficial femoral
artery. As the procedure was performed using a contralateral approach, completion
angiography demonstrated patent percutaneous bypass on the right with no signs
of restenosis at 18 months after implantation (Figure 3). The patient completed the
24 months follow up in December 2017 with primary patency of 100% of her index
limb and two interventions for potentially less complex superficial femoral artery
disease in the contralateral limb. No deep venous thrombosis was detected, and her
ankle brachial index was one in the limb receiving the DETOUR procedure. The
follow-up duplex Doppler scan confirmed the patency of the DETOUR procedure
(Figure 4) and freedom from deep venous thrombosis (Figure 5).
419
Figure 5: Doppler scan at 24 months of the deep femoral vein demonstrating venous return and no deep venous
thrombosis in the vein around the graft. Notice the 7mm distance between the graft and the vein wall.
Detailed technique
Fully percutaneous femoropopliteal bypass has been performed in more than
100 patients, mainly in the DETOUR I trial. From a lesion perspective, the key
requirements included a short (1cm) proximal superficial femoral artery stump (no
longer a requirement in the upcoming DETOUR II trial) and a good-quality P1
segment of the popliteal artery, which is needed as a landing zone for the distal
stent graft. The adjacent deep femoral vein is used as a pathway for the stent graft
bypass. To avoid interaction and compression of the stent graft within the calcified
superficial femoral artery, crossing into the deep venous system is performed from
the proximal first 3–4cm of the superficial femoral artery. Later, the re-entry from
vein to popliteal artery is created above the upper margin of the patella.
The procedure starts by accessing the posterior tibial vein using ultrasound. After
placing a sheath and performing venography to confirm the patency and diameter
of the deep venous system, a contralateral arterial access with an 8-F Flexor Balkin
sheath (Cook Medical) is performed. A through-and-through access is established
for extra support, which is needed for crossing into and out of the venous system.
After performing the crossing from the proximal superficial femoral artery into
the deep vein and back into the popliteal artery with the PQ crossing device, two
or three overlapping Torus stent grafts are implanted, creating an endovascular
bypass. At least 3–4cm of the graft are placed in the popliteal artery to ensure
adequate anchoring. A larger overlap between stent grafts in the deep femoral vein
is required to prevent the stent grafts from decoupling.
Health economic implications of the DETOUR procedure

Patients with lifestyle limiting claudication or critical limb ischaemia typically
have fem-pop lesions longer than 15cm which, in contrast to short to mid-length
420
lesions, do not fare well as with existing treatments, resulting in substantial financial

burden for the health system.
While shorter, less complex lesions are easily treated with endovascular
approaches, more complex lesions, such as those with long chronic total occlusions,
are associated with costly index procedures. Procedure cost is driven by both the
length of procedure time and the large volume of specialised devices used to try to
cross and treat these lesions. Even with these specialised tools, approximately 20%
of chronic total occlusions are impossible to cross leaving physicians and patients
with less than desired alternatives.
Regarding readmissions, surgical revascularisation has the benefit of long-term
durability (patency); however, it is associated with complications that contribute
to a 30-day morbidity rate of 37% and 30-day readmission rate of 24%, the third-
highest rate of any diagnosis-related group, behind only congestive heart failure and
psychoses.7 Because existing endovascular approaches for complex lesions have yet
to demonstrate the same durability as open surgery, they are associated with costly
re-treatment procedures. A recent study reported that 30-day readmission rates for
inpatient endovascular interventions in the US were 17.6%. Twenty one percent of
these patients underwent a subsequent peripheral arterial revascularisation or lower

extremity amputation and procedure costs were as high as US$386,428.7
DETOUR, a minimally-invasive procedure with expected durability similar
to open bypass surgery, is designed to mitigate healthcare costs associated with
existing treatments by reducing the need for costly equipment and by reducing the
occurrence of post-procedural complications that result in costly readmissions and
high mortality rates.
Existing and future trials

The DETOUR system has been successfully studied in DETOUR I, an
international, multicentre, single arm, prospective trial, in 78 patients/81 limbs.
The DETOUR I study’s six-month data were presented by Dierk Scheinert at the
2017 Leipzig Interventional Course. During this initial study interval, no cases
of deep venous thrombosis were detected. Primary patency was 84.7% and all
patients reported improvement in claudication, defined as a shift from Rutherford
class 3 or 4 to either Rutherford class 0 or class 1. These data reflect a unique
and innovative approach toward the treatment of long (>25cm) superficial femoral
artery occlusions.
PQ Bypass will continue to build upon the existing body of evidence, announcing
in late 2017 that it received conditional approval of its investigational device
exemption (IDE) from the US Food and Drug Administration (FDA) to initiate
the pivotal DETOUR II clinical trial. As the first-ever pivotal trial for percutaneous
femoropopliteal bypass, DETOUR II will evaluate the safety and effectiveness of
the DETOUR system in up to 292 patients with lower limb ischaemia due to long
atherosclerotic lesions (>15cm) in the superficial femoral artery.
DETOUR II is a prospective, single-arm, global multicentre trial and will be
conducted at up to 40 sites to enable the collection of safety and effectiveness data
in support of a pre-market approval (PMA) submission to the FDA. Additionally,
to demonstrate health economic outcomes, the trial includes a prospective
economic study designed to collect data related to the costs associated with treating
peripheral arterial disease in the study population. An economics core lab will lead
421
the collection of quality-of-life outcome measures (collected at baseline, 30 days, six
and 12 months), and procedural and follow-up costs, including rehospitalisations,

through 24 months.
Conclusion
Patients affected by peripheral arterial disease suffer from lifestyle limiting pain
that modern medicine cannot always treat, given the currently approved therapy
options. The proportion of undertreated patients living with severe claudication
grows even larger, further impacting their quality-of-life. There is an existing
pattern in medicine demonstrating a paradigm shift from lifesaving but traumatic
and expensive treatments to minimally-invasive, patient-focused solutions. With

an ever-increasing population suffering from peripheral arterial disease, the next
logical step in the evolution of vascular medicine is to draw this principle into the
treatment of severe femoropopliteal lesions. The DETOUR system and associated
procedure may be this next evolutionary stepping stone in the age of value-
based care, offering a new, minimally-invasive, high-quality, and cost-effective
revascularisation treatment solution.
Summary
• Peripheral arterial disease affects millions of lives worldwide, and that

population is continuing to increase.
• Evidence indicates that while shorter lesions demonstrate durable patency
with traditional endovascular therapies, long lesions require open surgical
bypass to reach the same patency.
• Open surgical bypass is associated with complications leading to a 30-day
morbidity rate of 37% and 30-day readmission rate of 24%.
• Fully percutaneous femoropopliteal bypass (DETOUR procedure) offers a new,
minimally-invasive, high-quality revascularisation option for patients suffering
from severe femoropopliteal lesions.
• The DETOUR Procedure uses a specialty crossing device and landing platform
to lay a series of proprietary stent grafts beginning above the lesion in the
SFA, crossing into the femoral vein, and then re-entering the popliteal artery.
• Early clinical results indicate that the DETOUR procedure has patency
equivalent to open bypass surgery using a minimally-invasive approach.
• The DETOUR Procedure is currently under investigation in the US IDE study
DETOUR II.
References
1. Overview of classification systems in peripheral artery disease. Semin Intervent Radiol 2014; 31: 378–88
2. World Population Ageing 1950-2050. http://bit.ly/2F1ZETL [Date accessed 13 February 2018]
3. Tadros RO, Vouyouka AG, Ting W, et al. A review of superficial femoral artery angioplasty and stenting.
J Vasc Med Surg 2015; 3: 183.
4. Goodney PP, Beck AW, Nagle J, et al. National trends in lower extremity bypass surgery, endovascular
interventions, and major amputations. J Vasc Surg 2009; 50 (1): 54–60.
422
5. van de Weijer MA, Kruse RR, Schamp K, et al. Morbidity of femoropopliteal bypass surgery. Semin Vasc

Surg 2015; 28 (2): 112–21.
6. Srowiec SM, Davies MG, Eberly SW, et al. J Vasc Surg 2005; 41 :259–78.
7. Secemsky, E, Schermerhorn, M, Carroll, B, et al. Readmissions after revascularization procedures for
peripheral arterial disease. Ann Intern Med 2018; 168 (2): 93–99.
423
Controversies in the
local management of
diabetic foot ulcers
M Edmonds
Introduction
Local treatment of the diabetic foot ulcer is controversial. Most studies have been
carried out in diabetic neuropathic feet with very few studies in the two entities
of the diabetic ischaemic foot—that is the purely ischaemic foot or the ischaemic
foot associated with neuropathy, namely the “neuroischaemic” foot. However, over
the last 20 years, there has been an ever-increasing preponderance of ischaemic/
neuroischaemic ulceration which is now more common than the neuropathic
ulceration.1 Analysis conducted at the Diabetic Foot Clinic, King's College
Hospital (London, UK) indicated that the prevalence of neuroischaemic ulcers has
been rising since the 1990s from approximately one-third of patients to more than
50%; therefore, they have developed into the most common aetiology of diabetic
foot ulcers.2 Recent large European cohort studies of patients with diabetes and
foot ulcers confirm that at least half are of neuroischaemic or ischaemic origin.3–5
All ischaemic feet should have vascular investigations and, if indicated, undergo
revascularisation. However, this chapter will concentrate on the local management
of diabetic foot ulcers, in particular discussing the evidence for the management
of the ischaemic/neuroischaemic foot ulcer (which, henceforth, will be referred
to as the neuroischaemic foot ulcer). It will consider controversies in dressings,
debridement, negative pressure wound therapy and skin grafting.
Dressings
Until recently, published guidelines concluded that there was no firm evidence
that any dressing is better or worse than any other.6–8 A recent Cochrane review
also concluded that there was no evidence to support the effectiveness of any one
type of protective dressing over any other for treating diabetic foot ulcers. 9 These
reviews commented that most dressing studies were of poor quality. Additionally,
most studies included neuropathic feet and not neuroischaemic feet.10 In view of
the paucity of acceptable studies, the International Working Group of the Diabetic
Foot together with the European Wound Management Association, published a
guideline to support improved trial design.11 Recently, randomised controlled studies
have been carried out—embracing key points in this guideline and replicating real-
world conditions; in particular, neuroischaemic ulcers and mild infections.
425
Effectiveness of sucrose octasulphate in the treatment of
• M Edmonds
neuroischaemic ulcers
Recently, a study investigating the effectiveness of sucrose octasulphate dressing
in the treatment of neuroischaemic ulcers was performed to a high standard. It
incorporated a double-blind design, a control dressing, masking to treatment
allocation, independent randomisation, good standard of care in active and control
Controversies in the local management of diabetic foot ulcers
groups, and the wound closure primary endpoint was analysed in the intention-
to-treat population.12 The delay in healing of the neuroischaemic ulcer has been
related to excess of matrix metalloproteases, which destroy the components of the
extracellular matrix and damage the growth factors and their receptors that are
essential for healing.13–16
The potassium salt of sucrose octasulfate has been shown to inhibit matrix
metalloproteases.17 As these metalloproteases are the main enzymes involved in
extracellular matrix degradation, their inhibition will result in a reduction of
proteolytic destruction of essential extracellular matrix components.18 Also, the
potassium salt of sucrose octasulfate, due to its high charge density, has been shown
to interact with growth factors and thus restore their biological functions.19,20
Recently, a two parallel-group, randomised, double-blind clinical trial (the
Explorer study) was carried out in 43 specialised diabetic foot clinics.21 Diabetic
patients with a non-infected neuroischaemic foot ulcer were randomly assigned
(1:1) to either a treatment dressing containing sucrose octasulphate or control
dressing (the same advanced wound dressing without sucrose octasulfate), together
with good standard of care, for a 20-week period. After 20 weeks, wound closure
took place in 34 patients (30%) in the control group and in 60 patients (48%) in
the treatment group (adjusted odds ratio 2·60 [95% confidence interval, CI, 1·43
to 4·73]; p=0·002). The sucrose octasulfate dressing, compared with an advanced
dressing, reduced the estimated time-to-reach wound closure in neuroischaemic
foot ulcers; mean time to closure was 180 days (95% CI 163 to 198) in the control
group and 120 days (95% CI 110 to 129) in the treatment group (p=0·029) without
affecting the safety profile. In addition to this evidence, a favourable benefit-risk
ratio of sucrose octasulphate had previously been established through clinical
studies in leg ulcer with venous and mixed/arterial aetiologies, when compared to
advanced wound dressing and to protease modulating dressing.22,23.
The efficacy of a two layer system—EDX110—generating

nitric oxide in clinically infected ulcers and moderate
ischaemic ulcers
Infection is a strong predictor of delayed healing in diabetic patients with
neuroischaemic ulcers.24 EDX110 consists of a non-adherent contact layer, and
an absorptive hydrogel secondary layer. Nitric oxide is generated when the two
layers are placed in contact and applied to the wound, and it plays a crucial role
in maintaining the microvascular supply and infection control in the skin, and its
absence in diabetes is a compounding factor in poor ulcer healing.25,26 The role
of nitric oxide in ulcer healing involves three recognised elements: vascular, as it
influences blood vessel vasodilatation and stimulates angiogenesis; inflammatory,
as it influences the host immune response;and antimicrobial as it demonstrates
potent, broad spectrum antimicrobial activity.27–29
426
The ProNOx1 study was a multicentre, prospective, observer-blinded, parallel

group, randomised controlled trial of a nitric oxide -generating wound treatment vs.
current standard of care dressings in diabetic foot ulcers.30 As a primary outcome,
EDX110 was as safe as standard of care dressings. EDX110 administration resulted
in a significantly greater percentage area reduction of ulcer compared to standard
of care dressings (p=0.016). The percentage of foot ulcers demonstrating >50%
percentage area reduction at four weeks additionally showed a significant difference
in favour of EDX110 (p=0.03).
Debridement
Although debridement is accepted as a useful local treatment, evidence for it is
sparse. In a subgroup analysis of cases from a randomised control trial of a separate
intervention, healing at 12 weeks was more likely following a more vigorous
debridement as assessed from wound images retrospectively.31
Sharp debridement
Sharp debridement with a scalpel is the preferred method in neuroischaemic ulcers.
Only very cautious debridement should be performed if the foot is very ischaemic
• M Edmonds
(ankle brachial pressure index < 0.5).
Debridement by larval therapy

An alternative method of debridement of ulcers in the neuroischsaemic foot is
larval therapy. The larvae of the greenbottle fly can remove moist, slimy slough,
atraumatically and rapidly; although, this method of debridement is not
without controversy.32,33
Larval debridement therapy has been shown to decrease significantly time to
healing of diabetic foot wounds, in non-ambulatory patients with peripheral arterial
disease and also to decrease risk of amputation.34 A recent review of debridement
methods suggested that larval therapy may improve outcomes when compared to
autolytic debridement with a hydrogel.35 A study using a complex non-randomised
cohort reported significant effect on the appearance of the wound at two weeks.36
However, a further paper reported no difference in either healing or amputation
rates between those treated with larval therapy and a control group.37 Furthermore,
others do not recommend larvae in ischaemic ulcers as they may exacerbate or
cause severe pain. The mechanism is not fully understood but may be due to the
relatively low pH (pH 7.2) of the secretions from the larvae, which can exacerbate
local tissue damage.1
Negative pressure wound therapy

In this technique, a vacuum pump applies negative pressure through a tube and
foam sponge which are applied to the ulcer over a dressing and sealed in place with
a plastic film to create a vacuum. Exudate from the wound is sucked along the tube
to a disposable collecting chamber. The negative pressure wound therapy (NPWT)
stimulates granulation of the wound and improves vascularity.
There have been two large randomised controlled trials investigating NPWT. In
2005, 162 patients with postoperative wounds, following partial foot amputation,
were enrolled into a 16-week, 18-centre, randomised clinical trial. A TcPO2
427
>50mmHg or toe pressure >30mmHg was used as inclusion criteria, to exclude
• M Edmonds
patients with critical ischaemia. More patients were healed in the negative pressure
group than in the control group (43 [56%] vs. 33 [39%], p=0.040). The rate of
wound healing, based on the time to complete closure, was faster in the NPWT
group than in controls (p=0.005).38
A second randomised controlled trial involving 342 patients showed a reduced
time to closure and an increased incidence of healing by 16 weeks in the NPWT

group compared with a group treated with advanced moist wound therapy. Again,
patients were required to have an adequate perfusion as assessed by a dorsum
transcutaneous oxygen test ≥30 mmHg, ankle-brachial index values ≥0.7 and ≤1.2
with toe pressure ≥30 mmHg, or Doppler arterial waveforms that were triphasic
or biphasic at the ankle of the affected leg.39 In empiric, clinical practice, NPWT
has been useful in the neuroischaemic foot—although randomised controlled trial
evidence, so far, has been obtained in mainly neuropathic feet. A recent Cochrane
review indicated that further definitive evidence is needed to confirm its specific
role in diabetic foot ulceration.40
Skin grafting
Split-thickness skin graft (STSG) placement has also been used as a primary means
of healing wounds in the diabetic foot. In a retrospective study of the outcome
of skin grafting in 94 patients, of whom 66 (70.2%) had diabetes, including 13
who were dialysis-dependent, 65 (69.1%) patients experienced complete graft take
and healing; also, 18 (19.1%) required revision, five (5.3%) of whom ultimately
required major limb amputation.41 NPWT was used as an adjunct to prepare the
wound bed before grafting and postoperatively to bolster the STSG. Those feet
that were ischaemic had perfusion corrected before STSG placement. Also, the
authors evaluated whether revascularisation before STSG affected wound healing
compared with patients who did not require revascularisation. Thirty-seven patients
had a revascularisation procedure before undergoing STSG. Overall, there was no
difference in outcomes in patients who did and did not require revascularisation
before STSG. The results of this study suggested that STSG is an effective method
for management of wound healing.
Conclusion
Although local management of diabetic foot ulceration is controversial, there
is now evidence that sucrose octasulphate dressings are efficacious in healing
the neuroischaemic foot ulcer. Larval therapy is also useful in debriding the
neuroischaemic foot ulcer. NPWT has proved beneficial in mainly postoperative
wounds and EDX110 may be useful in both neuropathic and neuroischaemic-
infected ulcers.
428
Summary
• At least half of diabetic foot ulcers are neuroischaemic or ischaemic in origin.

• Sucrose octasulfate dressings significantly increase wound closure rate and
reduce the estimated time-to-reach wound closure in diabetic neuroischaemic
foot ulcers.
• EDX110, a nitric oxide generating dressing, improved healing, as measured by
significantly reducing the ulcer area, in clinically infected ulcers and moderate
ischaemic ulcers.
• Sharp debridement is recommended in neuroschaemic ulcers but larval
therapy may also be useful.
• Negative pressure wound therapy can be worthwhile in the
postoperative wound.
• Split skin grafting can be used on wounds in neuroischaemic feet which
should be preferably revascularised before the procedure.
• M Edmonds
References
1. Ndip A, Jude EB. Emerging evidence for neuroischemic diabetic foot ulcers: model of care and how to
adapt practice. Int J Low Extrem Wounds 2009; 8 (2): 82–94.
2. Armstrong DG, Cohen K, Courric S, et al. Diabetic Foot Ulcers and Vascular Insufficiency: Our Population
Has Changed, but Our Methods Have Not. Diabetes Sci Technol 2011; 5 (6): 1591–95.
3. Jeffcoate WJ, Chipchase SY, Ince P, et al. Assessing the outcome of the management of diabetic foot
ulcers using ulcer-related and person-related measures. Diabetes Care 2006; 29: 1784–87.
4. Prompers L, Huijberts M, Apelqvist J, et al. High prevalence of ischaemia, infection and serious
comorbidity in patients with diabetic foot disease in Europe. Baseline results from the Eurodiale study.
Diabetologia 2007; 50: 18–25.
5. Gershater, MA, Löndahl, M, Nyberg, P, et al. Complexity of factors related to outcome of neuropathic
and neuroischaemic/ ischaemic diabetic foot ulcers: a cohort study. Diabetologia 2009; 52 (3):
398-407.
6. Lavery LA, Davis KE, Berriman SJ, et al. WHS guidelines update: Diabetic foot ulcer treatment guidelines.
Wound Repair Regen 2016; 24: 112–26
7. Schaper NC, Van Netten JJ, Apelqvist J et al. International Working Group on the Diabetic Foot.
Prevention and management of foot problems in diabetes: a Summary Guidance for Daily Practice
2015, based on the IWGDF Guidance Documents. Diabetes Metab Res Rev 2016; 32 (suppl 1): 7–15.
8. Game FL, Apelqvist J, Attinger C, et al. for the International Working Group on the Diabetic Foot
(IWGDF). Effectiveness of interventions to enhance healing of chronic ulcers of the foot in diabetes: a
systematic review. Diabetes Metab Res Rev 2016; 32 (suppl 1): 154–68.
9. Wu L, Norman G, Dumville JC et al. Dressings for treating foot ulcers in people with diabetes: an
overview of systematic reviews. Cochrane Database Syst Rev 2015; 7: CD010471
10. Jeffcoate WJ, Bus SA, Game FL, et al. for the International Working Group on the Diabetic Foot (IWGDF).
Reporting standards of studies and papers on the prevention and management of foot ulcers in
diabetes: required details and markers of good quality. Lancet Diabetes Endocrinol 2016; 4: 781–88.
11. Carter MJ, Fife CE, Walker D, et al. Estimating the applicability of wound care randomized controlled
trials to general wound care populations by estimating the percentage of individuals excluded from a
typical wound care population in such trials. Advances in Skin & Wound Care 2009; 22: 316-24
12. Game F. Treatment strategies for neuroischaemic diabetic foot ulcers. Lancet Diabetes Endocrinol 2017
Epub.
13. Lazaro JL, Izzo V, Meaume S, Davies AH, et al. Elevated levels of matrix metalloproteinases and chronic
wound healing: an updated review of clinical evidence. J Wound Care 2016; 25: 277–87.
14. Ren Y, Gu G, Yao M, et al. Role of matrix metalloproteinases in chronic wound healing: diagnostic and
therapeutic implications. Chin Med J (Engl) 2014; 127: 1572–81.
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15. Liu Y, Min D, Bolton T, et al. Increased matrix metalloproteinase-9 predicts poor wound healing in
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diabetic foot ulcers. Diabetes Care 2009; 32: 117–19.

16. Menghini R, Uccioli L, Vainieri E, et al. Expression of tissue inhibitor of metalloprotease 3 is reduced in
ischemic but not neuropathic ulcers from patients with type 2 diabetes mellitus. Acta Diabetol 2013;
50: 907–10.
17. White R, Cowan T, Glover D. Supporting evidence-based practice: a clinical review of TLC healing
matrix (2nd edition). MA Healthcare Ltd, London, 2015.
18. Lazaro JL, Izzo V, Meaume S, et al. Elevated levels of matrix metalloproteinases and chronic wound
healing: an updated review of clinical evidence. J Wound Care 2016; 25: 277–87.
19. Volkin DB, Verticelli AM, Marfia KE, et al. Sucralfate and soluble sucrose octasulfate bind and stabilize
acidic fibroblast growth factor. Biochim Biophys Acta 1993; 1203: 18–26.
20. Kulahin N, Kiselyov V, Kochoyan A, et al. Dimerization effect of sucrose octasulfate on rat FGF1. Acta
Crystallogr Sect F Struct Biol Cryst Commun 2008; 64: 448–52.
21. Edmonds M, Lázaro-Martínez JL, Alfayate-García JM, et al. Sucrose octasulfate dressing versus control
dressing in patients with neuroischaemic diabetic foot ulcers (Explorer): an international, multicentre,
double-blind, randomised, controlled trial. Lancet Diabetes Endocrinol 2017. Epub.
22. Meaume S, Truchetet F, Cambazard F, et al. A randomized, controlled, double-blind prospective
trial with a Lipido-Colloid Technology-Nano-OligoSaccharide Factor wound dressing in the local
management of venous leg ulcers. Wound Repair Regen 2012; 20: 500–11.
23. Schmutz JL, Meaume S, Fays S, et al. Evaluation of the nano-oligosaccharide factor lipido-colloid
matrix in the local management of venous leg ulcers: results of a randomised, controlled trial. Int
Wound J 2008; 5: 172–82.
24. Prompers L, Schaper N, Apelqvist J, et al. Prediction of outcome in individuals with diabetic foot
ulcers: focus on the differences between individuals with and without peripheral arterial disease. The
EURODIALE Study. Diabetologia 2008, 51 (5): 747–55.
25. Witte MB, Barbul A. Role of nitric oxide in wound repair. Am J Surg 2002; 183: 406–12.
26. Schwentker A, Vodovotz Y, Weller R, et al. Nitric oxide and wound repair: role of cytokines. Nitric Oxide
2002; 7: 1–10.
27. Ziche M, Morbidelli L. Nitric oxide and angiogenesis. J Neurooncol 2000; 50: 139–48.
28. Tucker A, Cooke ED, Pearson RM, et al. Effect of a nitric oxide generating system on microcirculatory
blood flow in the skin of patients with Raynaud’s Syndrome. Lancet 1999; 35: 1670–75.
29. Guzik J. Nitric oxide and superoxide in inflammation and immune regulation. J Physiol Pharmacol
2003; 54: 469–87.
30. Rajbhandari S. The ProNOx1 Study – Can a nitric oxide wound treatment system improve clinical
outcomes in DFUs compared to standard of care. Presentation at Diabetic Foot Study Group Meeting,
Oporto September 2017
31. Steed DL. Foundations of good ulcer care. Am J Surg 1998; 176 Suppl 2a: 20S-25S]
32. Wolff H, Hansson C. Larval therapy--an effective method of ulcer debridement. Clin Exp Dermatol 2003;
28 (2): 134–37.
33. Rayman A, Stansfield G, Woollard T, et al. Use of larvae in the treatment of the diabetic necrotic foot.
Diabetic Foot 1998; 1: 7–13.
34. Armstrong DG, Salas P, Short B, et al. Maggot therapy in "lower-extremity hospice" wound care: fewer
amputations and more antibiotic-free day. J Am Podiatr Med Assoc 2005; 95 (3): 254–57.
35. Edwards J, Stapley S. Debridement of diabetic foot ulcers. Cochrane Database Syst Rev 2010; 1:
CD003556. doi:10.1002/14651858 35 .
36. Sherman RA. Maggot therapy for treating diabetic foot ulcers unresponsive to conventional therapy.
Diabetes Care 2003; 26: 446–51.
37. Paul AG, Ahmad NW, Ariff AM, et al. Maggot debridement therapy with Lucillia cuprina: a comparison
with conventional debridement in diabetic foot ulcers. Int Wound J 2009; 6: 39–46.
38. Armstrong DG, Lavery LA, Diabetic Foot Study Consortium. Negative pressure wound therapy after
partial diabetic foot amputation: a multicentre, randomised controlled trial. Lancet 2005; 366: 1704.
39. Blume PA, Walters J, Payne W, et al. Comparison of negative pressure wound therapy using vacuum-
assisted closure with advanced moist wound therapy in the treatment of diabetic foot ulcers: a
multicenter randomized controlled trial. Diabetes Care 2008; 31: 631.
40. Dumville JC, Hinchliffe RJ, Cullum N, et al. Negative pressure wound therapy for treating foot wounds
in people with diabetes mellitus. Cochrane Database Syst Rev 2013; CD010318.
41. Rose, DO, Giovinco, N Mills JL, et al. Split-thickness skin grafting the high-risk diabetic foot J Vasc Surg
2014; 59: 1657–63.
430
Venous and lymphatic
controversies
WHETHER to intervene, WHEN to intervene, HOW to
intervene: Outcomes and Follow-up
Imaging section and diagnostic controversies
Haemodynamics—objective
assessment of venous and
lymphatic function
Introduction
Veins and lymphatics represent a perfect example of a delicate synergy, for which, in
physiological conditions, the interconnection between the two systems guarantees
the lower limb drainage homeostasis. At the same time, in case of pathological
failure, such tight interconnection presents the downside of having the venous
system incompetence potentially affecting the lymphatics function and vice versa.1
Lee’s group demonstrated the vicious circle created by lymphoedema potentially
impairing venous drainage, which in turn can aggravate the same lymphatic stasis.2
Moreover, the damage of the lymphatics inside the vein media leads to a lipid
accumulation that is responsible for an inflammation that can further damage the
lymphatics surrounding the same vein adventitia.3 Venous ulceration is associated
with lymph oozing and collectors damage.4,5 At the same time, both in deep venous
thrombosis and post-thrombotic syndrome, a lymphatic network alteration has
been reported. Indeed, in these conditions, the subfascial lymphatic drainage is
reduced, while the prefascial drainage is increased, with the exception of recurrent
cellulitis cases.6 Especially in cases of lower extremity oedema, this inter-relationship
between veins and lymphatics must be addressed in the objective assessment.
Venous function objective assessment

Venous function is widely assessed by Doppler ultrasound scanning in an easy, fast
and reliable way. While colour mode gives only qualitative information regarding
the flow direction, the spectral analysis is able to provide an objective measurement
of the venous flow haemodynamics.
Of course, several limitations affect Doppler ultrasound analysis. First of all, it is
an operator dependent investigation and, as has been demonstrated by assessments
on the arterial side, the same detection of haemodynamic parameters—such as
peak systolic velocity and resistance index—have been affected by a significant
inter and intra-observer variability.7,8 Moreover, the scanning is limited to a vein
segment, thus leading to the possible missed evaluation of other involved veins
tracts. Despite these limitations, recent investigations pointed out the importance
of combining the assessment of these Doppler ultrasound parameters with
endothelial biosignalling. Indeed, the physical force generated on the venous wall
by haemodynamics is translated into a biochemical signal influencing the same
venous pathophysiology. In particular, endothelial derived platelet growth factor
release has been demonstrated to directly correlate with reflux time and inversely
with resistance index.9
437
At the same time, venous reflux suppression is associated with 14 cytokines
decrease, among which endothelial growth factor, platelet derived growth factor
and RANTES are potential candidates as biomarkers.10 Furthermore, Doppler
ultrasound allows an objective assessment of venous haemodynamics whenever
reporting the flow changes during the reflux elimination test.
This diagnostic manoeuvre consists of compression of the incompetent varicose
veins with a single finger, while assessing the evoked flow on the saphenous axis
above the finger compression. The digit compression mimics the ligation or
Haemodynamics—objective assessment of venous and lymphatic function •
ablation of the incompetent tributary, in order to preoperatively test the effect

of the procedure. If case the reflux is not suppressed by the digit compression, a
treatment of the incompetent saphenous trunk is indicated (Figure 1).11
Perforating veins haemodynamics represent a challenging topic of investigation.
Despite their fundamental role in communicating between the superficial and
deep venous systems, their assessment is limited by the Doppler ultrasound sample
volume angle and steering, moreover providing the analysis of a single spot of the
generally tortuous vessel. A recently developed Doppler ultrasound software allows
a multi-gate quality Doppler profile analysis which is the result of a simultaneous
assessment of 256 sample volumes along all the perforating vein, independently by
the vessel tortuosity. In this way, quality Doppler profile analysis is able to provide
data regarding the net flow direction inside perforating veins.
The use of this software pointed out how the definition of perforating vein
incompetence by simple measurement of the outward flow could not be always
reliable. Indeed, the sensitivity in detecting a net outward flow of an outward flow
lasting more than 500msec at the traditional single gate analysis resulted to be
just 13.9%. At the same time, the specificity in detecting a net inward flow of an
outward flow lasting less than 500msec at the single gate analysis, was 96.4%.12
Even if now mainly substituted by Doppler ultrasound in venous diagnostics,
strain gauge, photo and air plethysmography demonstrated to be valuable devices
in providing objective assessment of venous haemodynamics. Venous refilling time,
Figure 1: Reflux elimination test: (A) Great saphenous vein reflux involving also an incompetent tributary. (B) Digit
compression of the incompetent tributary and great saphenous vein reflux disappearance because of the pressure
gradient suppression. (C) Despite the digit compression on the incompetent tributary, great saphenous vein is still
refluxing, thus indicating the presence of another pressure gradient feeding the reflux.
438
measured by photo or air plethysmography, is a useful parameter in determining the

haemodynamic significance of femoral valve incompetence and in the measurement
of the outcome of saphenous ablation.13–15
Air plethysmography allows an objective demonstration of the changes after
varicose vein surgery (great saphenous and short saphenous vein stripping, external
banding valvuloplasty), by reporting an improvement of the venous volume, venous
filling index, residual volume fraction and ejection fraction.16 In recent days, the
same plethysmographic parameter improvement have been demonstrated following
also both endovenous laser and radiofrequency ablation.17,18
A new plethysmographic parameter called venous drainage index (opposite of
the venous filling index) was recently validated in its use for assessing the effects
of obstructions or stenosis of the lower limb venous drainage.19 Indeed, air
plethysmography demonstrated to be a practical, cost-effective, reliable tool for the
diagnosis of haemodynamically significant chronic venous obstruction.20 Recently,
iliofemoral venous drainage impairment has gathered progressive attention in the
scientific world dealing with lower limb chronic venous disease.21
Innovative diagnostic devices such as intravenous ultrasound are surely useful in
the clinical management of the disease, but provide just an imaging support rather
than quantitative haemodynamics data. In particular, intravascular ultrasound
seems to be promising in guiding stent implantation and catheter-based procedures
from the common femoral to the inferior vena cava.22,23
Lymphatics function objective assessment

Assessing objectively the lymphatic system has represented a challenge for many
years of clinical lymphology. Lymphoscintigraphy using isotopic contrast agents
is lacking resolution in outlining the same lymphatic anatomy. Moreover, tracing
the clearance from the injection site to lymph nodes can be useful in assessing the
lymphatic function, but with a limited accuracy. Lymphangiography using iodine
oil agent could visualise the lymphatics but it is no longer in use because of the
potential severe side effects. Magnetic resonance imaging (MRI) presents some
fundamental advantages compared with lymphoscintigraphy: in particular, a higher
spatial and temporal resolution together with a possible 3D reconstruction.24
Among the several contrast agents tested in the last few years, gadobenate
dimeglumine demonstrated good performances in visualisation of the lymphatics
visualisation and in the assessment of the functional status of the lymph flow.25 A
significant delay in lymph transport can be detected in the affected channels. This
diagnostic technique highlights lymph node impairment together with collectors’
dilation and tortuosity. Moreover, identification of subcutaneous fat deposition,
water displacement and fibrosis detected during the investigation allow the staging
of the lymphatic impairment.26 Near infra-red imaging using indocyanine green
as fluorescent tracers demonstrated the efficacy of manual lymphatic therapy
in increasing lymph flow without any radiation exposure with a relatively high
resolution in real time, with the only limitation of the imaging depth.27
Venous and lymphatics global function evaluation

Objective assessment of lymphatic drainage in case of venous haemodynamics
impairment with no primary damage of the same lymphatic structures can be
439
challenging. Sub- or intracutaneous injection of radiotracer can show normal
findings at routine lymphoscintigraphy. Even an increased lymphatic flow can be

detected, leading to the wrong conclusion of a perfectly functioning lymphatic
drainage, while in reality a pathological overload of the system is developing fed by
impaired venous haemodynamics.
Ultrasonography plays a fundamental role in detecting both direct signs of venous
haemodynamics alteration and indirect signs of lymphatics impairment. Indeed,
in particular high frequency probes can detect not only skin and subcutaneous
thickness, but also subcutaneous findings such as hyperechoic areas within a normal
adipose tissue, anechoic areas in the contest of lymphatic lakes or a homogeneous
hyperechogenicity. Even if not quantitative, these qualitative data suggest a possible
lymphatic involvement and allow a lymphostasis grading.28 Recently, the literature
showed the possible role of ultrasound in differentiating also a dependent oedema
from a secondary lymphoedema, pointing out the lymphatic component in the
subcutaneous involvement.29,30
An objective assessment of venous and lymphatics drainage must begin with a
clinical suspect. Taking into consideration from the inability to pinch a fold of skin
of the foot between the assessor fingers (Kaposi-Stemmer sign), to all the clinical
signs of potential lymphatics involvement is mandatory. 31
Unknown unknowns: The need of further investigations

Venous and, even more, lymphatic haemodynamics represent one of the most
intriguing topics in vascular medicine. Indeed, the current description is based
on laws of Newtonian physics that apply to an ideal system. Nevertheless, venous
and lymphatic vessels are not ideal conduits, as our blood and lymph are not ideal
fluids.32 Future investigations should aim both to the design of more reliable lump
models and to the in vivo validation of the related haemodynamics concepts.
In particular, considering the fundamental Poiseuille law for which a pressure
gradient is needed in order to generate a flow, direct and indirect assessments of
pressure values related to fluid motion should be performed. In this aspect, Bauer
investigation is particularly interesting, pointing out the possible use of strain-gauge
plethysmography as a possible non-invasive means to indirectly measure peripheral
lymph flow by correlating the pressure decrease at the end of the venous congestion
plethysmography with the related interstitial fluid removal. Unfortunately, the
progressive abandon of plethysmography diagnostics has limited investigations on
this topic.33
Interestingly, Raju demonstrated that stenting of iliac vein stenosis can lead
to phlebo-lymphedema relief, despite a normal clearance of radionuclide at the
lymphoscintigraphy.34
These data suggest the need of further investigations addressed to specifically
identify the lymphatic and the venous component interested in the different kind
of oedema, to focus on specifically addressed diagnostic and treatment protocols.
Lower limb venous volume variation represents one of the most commonly used
outcome measures in venous and lymphatics drainage assessment, with water
plethysmography being the gold standard for data collection.35
At the same time, lower limb volumetry is an absolute value that is unable
to provide data regarding the localisation of the fluid accumulation. Moreover,
advanced stages of lymphoedema are accompanied by variable grades of fibrosis,
440
thus making the same volume variation a parameter of relative significance. New

investigations should be addressed to identify an assessment method providing
objective data regarding fluid localisation and mobilisation.
Last but not least, future studies should provide also further clues in the
identification of biomarkers correlating haemodynamics forces with biochemical
signalling, so offering an objective measurement of venous and lymphatics function.
Conclusion
Having vein and lymphatics experts gathering together to focus on evidence-based
science is mandatory in order to move towards a real science reporting objective
data in haemodynamics to provide accurate assessments and therefore optimal
patient care.
Summary
• Venous and lymphatic systems are tightly interconnected, potentially

balancing each other in physiological conditions, but also impairing one other
in cases of functional overload.
• Venous haemodynamics can be objectively assessed by Doppler ultrasound,
correlating flow parameters with endothelial biochemical release.
• A multi-gate Doppler analysis allows for net flow direction assessment into

perforating veins, questioning the actual definition of incompetence.
• Plethsymography still represents a valid device in lower limb haemodynamics
objective evaluation.
• Magnetic resonance lymphography and near infra-red imaging with
indocyanine green are useful diagnostic techniques in lymphatics anatomy
and function evaluation.
• In vivo validation of the modern haemodynamics pathophysiology is needed.
• Collaboration among vein and lymphatics experts is mandatory in the
objective assessment of lower limb haemodynamics investigation.
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442
Strain-gauge plethysmography
H Zachrisson, O Nelzén, J Skoog and T Länne
Introduction
Chronic venous disease is a common clinical condition with a prevalence of
30–40%.1,2 Clinical signs include a wide spectrum, ranging from minor telangiectasias
to more severe stages of venous disease with varicose veins and obstruction,
which can lead to oedema, eczema, lipodermatosclerosis, and ultimately ulcers.3
Duplex ultrasound is considered to be gold standard in the diagnosis of chronic
venous disease and provides diagnostic information on presence and anatomical
distribution of the disease.3,4 However, although duplex is useful in assessing reflux
in individual vein segments, it does not permit an overall quantification of venous
function. In particular, these days, when a number of new treatment options have
emerged, there is increasing interest in functional diagnostics that can quantitatively
describe the haemodynamic significance of the anatomic abnormalities identified
by duplex ultrasound.5,6 Such additional information may in some cases be crucial
for the proper selection of patients for venous intervention/surgery. Alternatives for
non-invasive global testing of venous function include strain gauge, photo, and air
plethysmography, which all have been suggested to provide quantitative information
about whole limb venous haemodynamics.4 In this chapter, we elaborate how
strain-gauge plethysmography can be useful as a possible complement to duplex
ultrasound in venous insufficiency.
Strain-gauge plethysmography is a non-invasive method to measure alterations in
limb volume. Since bone, adipose tissue, muscle, and skin have a relatively constant
volume in limbs, rapid changes in limb volume can be attributed to changes in
blood volume.7 The strain-gauge is most often placed around the calf or foot and
as the circumference of the limb is changed during various test manoeuvres, the
corresponding rapid changes in stretch of the strain-gauge can be translated into
changes in blood volume.5,8 Strain-gauge plethysmography has predominantly been
used to evaluate venous reflux and venous obstruction. In this chapter, we will
mainly focus on venous reflux. To identify abnormal reflux in the lower limb, volume
changes are examined in the standing position during and after activation of the
muscle pump. The principle is that blood is expelled during muscle contractions (i.e.
the volume of the limb decrease) and that the veins are refilled with blood during
muscle relaxation (i.e. the volume of the limb increase). If valvular incompetence is
present, the increase in volume occurs faster compared with the volume increase in
patients with normal valve function (Figure 1). The time taken in seconds for 50%
(T50) and 90% (T90) of the venous volume to be refilled, as well as the volume
required to refill 100% of the venous volume (expelled volume) are commonly used
parameters. Although the relationship between plethysmographic reflux parameters
and clinical severity of the venous disease has varied across studies,6,9,10 there are
443
• H Zachrisson, O Nelzén, J Skoog and T Länne
Figure 1: Schematic illustration of strain-gauge plethysmography during exercise (knee bends) and quiet standing
following exercise. (A) Normal venous valve function. During exercise (e.g., knee bends) the muscle pump is activated
and forces venous blood in the proximal direction, i.e., the volume decrease. Following exercise, the patient is standing
quietly and the veins are refilled with blood, i.e., the volume increase. (B) Abnormal venous valve function. Damage to
the valves leads to rapid refill by retrograde venous flow.
indications that decreased venous filling times (T50 and T90) are correlated with
higher C class (CEAP classification), as well as more specific values, such as skin
changes.5,10 Lattimer et al suggest that venous refilling times might provide a
better assessment of clinical severity and stratification of patients, according to
the stage of the disease, compared with expelled volume.10 Further, by combining
strain-gauge plethysmography with application of cuffs occluding the superficial
veins it has been suggested that the global components of superficial and deep
venous reflux can be separated from each other.8,11 This in an important question
because a correct description of the two components might, for example, help
to distinguish those patients with mixed venous insufficiency who would improve
their haemodynamic venous function and benefit from intervention/surgery.
Selective superficial venous occlusion

Plethysmographic assessment of venous reflux with cuff application has been used
to differentiate superficial from deep venous incompetence.11–13 However, the lack
of consensus regarding the use of compression cuffs for selective occlusion of
the superficial veins has contributed to conflicting results regarding the utility of
compression cuffs in the assessment of venous reflux.11,14,15 Zachrisson et al developed
a method to achieve selective occlusion of the superficial veins using a standardised
cuff occlusion model.12 This system consists of a proximal cuff (3x40cm) placed
on the calf just below the tibial condyles and a distal cuff (3x30cm) placed on the
ankle just above the malleoli. The supine position (legs 30cm above heart level)
was used for selective superficial vein occlusion (60mmHg proximal calf cuff,
30mmHg ankle cuff). Inflation pressures were derived, and the hydrostatic vein
pressure was corrected for when using ascending phlebography and strain-gauge
plethysmography. (Figure 2). The efficacy of the system to occlude superficial veins
444
Figure 2: Strain-gauge plethysmography with superficial venous occlusion. Arrangement of patient, calf cuff, ankle
cuff, and strain gauge for lower extremity venous plethysmography.
without affecting deep veins has been validated by ascending phlebography.8 Thus,
dynamic measurement with strain-gauge plethysmography in combination with
selective superficial venous occlusion seems to provide an important complement
to duplex ultrasound given its possibility to quantify venous refilling rates and thus
help to distinguish between the superficial and deep haemodynamic components of
venous incompetence (Figure 3).8
Strain-gauge plethysmography and selective superficial

venous occlusion
Dynamic measurements of volume changes with plethysmographic methods may
provide accurate quantitative information about whole limb venous haemodynamics
and abnormalities in the reflux phase.5,11,13,16 Together with a uniform method for
selective occlusion of the superficial veins, the importance of plethysmography
as a clinical complement to duplex ultrasound seems to increase. However, the
clinical application of strain-gauge plethysmography has so far showed variable
method variability and the issue of selective superficial occlusion is crucial.
Recent studies have presented confidence intervals around 10–18% for dynamic
measurement,which seems acceptable and also better than earlier investigations
with similar techniques. 5,8,13 By using our cuff occlusion model with selective
superficial occlusion, Nelzén et al found that reflux parameters such as T50 and
T90 were markedly improved in patients with superficial insufficiency compared
to measurements without superficial occlusion.8 These results correspond to
previous finding by Skeik et al.11 Further, the study by Nelzén et al compared
the results of preoperative reflux parameters from strain-gauge plethysmography
445
Figure 3: Representative tracings of preoperative strain gauge plethysmography without and with superficial venous
occlusion in a patient with superficial venous insufficiency. (A) Preoperative measurement without superficial
venous occlusion demonstrate that the times required for 50% (T50) and 90% (T90) of venous refilling were four
and 11 seconds, respectively. (B) Preoperative measurement with superficial venous occlusion demonstrate that the
times required for 50% (T50) and 90% (T90) of venous refilling were 20 and 39 seconds, respectively. A significant
improvement of reflux parameters are seen during superficial venous occlusion. (Ekman Biomedical Data, Sweden).
during standardised superficial venous occlusion with postoperative outcome

measurements one month after successful radio frequency ablation and found that
it was possible to predict the results of the venous intervention using strain-gauge
plethysmography with superficial occlusion. Prediction of venous function could
be of importance in assessing the probability of good outcome after intervention/
surgery, as well as to evaluate the importance of reflux pathways identified by
duplex ultrasound—especially in patients with mixed insufficiency. Moreover,
in a study investigating 54 patients undergoing treatment for great saphenous
vein insufficiency, duplex ultrasound and strain-gauge plethysmography with
standardised superficial vein occlusion were performed before and one month after
treatment with either radiofrequency ablation or high ligation and stripping.17
Both treatment groups showed significant improvement of plethysmographic reflux
measurements preoperatively. Postoperative duplex ultrasound revealed technically
successful treatments in all patients except one. However, postoperative strain-
gauge plethysmography showed significant improvement in reflux parameters
during superficial venous occlusion indicating remaining reflux pathways. The
question of recurrences is an important question and the progression of the disease
over time may be very important. These findings indicate that significant venous
incompetence may occur one month postoperatively due to remaining pathways
of venous reflux. Postoperative investigation by duplex ultrasound alone may show
obliterated segment of intervention, but accessory venous incompetence within
non-treated venous segments and perforators may occur.
446
Finally, patients with outflow obstruction and/or stenosis such as May-Turner
syndrome may show poor increase of venous reflux after superficial vein occlusion.
The haemodynamic significance of outflow obstruction may not easily be
answered by duplex ultrasound alone, and the site and anatomical extent of the
obstruction have only a weak correlation to the clinical symptoms.6 Venous outflow
plethysmography and/or radiological methods may in these cases be valuable
as a complement to duplex ultrasound of the iliac veins in the diagnosis of
outflow obstruction.6
Conclusion

Additional plethysmographic evaluation of venous disease may serve as a valuable
complement to duplex ultrasound—especially in complex cases with mixed deep
and superficial incompetence—during postoperative follow up or in cases with
possible proximal outflow obstruction. A combined functional investigation
quantifying both reflux and obstruction as an integrated haemodynamic assessment
has recently been shown to correlate well with the clinical severity of the disease
and may be a further step into functional diagnostics.6 However, prospective studies
including repeated measurements after interventions in larger patient populations,
as well as in patients with combined superficial and deep venous incompetence,
needs to be performed to further validate the clinical application of strain-gauge
plethysmography with superficial venous occlusion.
Summary
• Plethysmographic measurements provide quantitative information on whole

limb haemodynamics.
• Strain-gauge plethysmography with standardised superficial venous occlusion
appears to be a reliable method for identifying significant venous reflux and
predict outcome of venous intervention.
• Strain-gauge plethysmography may improve diagnostics and serve
as a valuable complement to duplex ultrasound in complex cases of
venous disease.
• Larger studies are needed to validate the combination of duplex ultrasound
and strain gauge plethysmography in clinical practice.
References
1. Brown CM, Hainsworth R. Assessment of capillary fluid shifts during orthostatic stress in normal
subjects and subjects with orthostatic intolerance. Clinical Autonomic Research 1999; 9 (2): 69–73.
2. Maurins U, Hoffmann BH, Losch C, et al. Distribution and prevalence of reflux in the superficial and
deep venous system in the general population--results from the Bonn Vein Study, Germany. J Vasc
Surg 2008; 48 (3): 680–87.
3. Wittens C, Davies AH, Baekgaard N, et al. Editor's Choice - Management of Chronic Venous Disease:
Clinical Practice Guidelines of the European Society for Vascular Surgery (ESVS). Eur J Vasc Endovasc
Surg 2015; 49 (6): 678–737.
4. Eberhardt RT, Raffetto JD. Chronic Venous Insufficiency. Circulation 2014; 130 (4): 333–46.
5. Rosfors S, Persson LM, Blomgren L. Computerized venous strain-gauge plethysmography is a reliable
method for measuring venous function. Eur J Vasc Endovasc Surg 2014; 47 (1): 81–86.
447
6. Nicolaides A, Clark H, Labropoulos N, et al. Quantitation of reflux and outflow obstruction in patients
Strain-gauge plethysmography • H Zachrisson, O Nelzén, J Skoog and T Länne
with CVD and correlation with clinical severity. Int Angiol 2014; 33 (3): 275–81.
7. Abu-Halimah SJ, Marston W. Plethysmographic Techniques in the Diagnosis of Venous Disease. In:
AbuRahma AF, editor. Noninvasive Vascular Diagnosis: A Practical Textbook for Clinicians. Cham:
Springer International Publishing 2017: 525–33.
8. Nelzen PO, Skoog J, Lassvik C, et al. Prediction of post-interventional outcome in great saphenous vein
incompetence: The role of venous plethysmography with selective superficial vein occlusion. Eur J
9. Danielsson G, Norgren L, Jungbeck C, Peterson K. Global venous function correlates better than
duplex derived reflux to clinical class in the evaluation of chronic venous disease. Int Angiol 2003; 22
(2): 177–81.
10. Lattimer CR, Kalodiki E, Azzam M, Geroulakos G. Reflux time estimation on air-plethysmography may
stratify patients with early superficial venous insufficiency. Phlebology 2013; 28 (2): 101–08.
11. Skeik N, Kalsi H, Wysokinski WE, et al. Predicting superficial venous incompetence with strain gauge
plethysmography. Phlebology 2012; 27 (3): 135–40.
12. Zachrisson H, Volkmann R, Bergerheim T, Holm J. Selectivity of superficial vein occlusion at the ankle
and calf level: a methodological study in healthy volunteers. Clin Physiol 1998; 18 (1): 55–60.
13. Volkmann E, Falk A, Holm J, et al. Effect of varicose vein surgery on venous reflux scoring and
plethysmographic assessment of venous function. Eur J Vasc Endovasc Surg 2008; 36 (6) :731–37.
14. Rooke TW, Heser JL, Osmundson PJ. Exercise strain-gauge venous plethysmography: evaluation of
a "new" device for assessing lower limb venous incompetence. Angiology 1992; 43 (3 Pt 1): 219–28.
15. Harada RN, Katz ML, Comerota A. A noninvasive screening test to detect "critical" deep venous reflux.
J Vasc Surg 1995; 22 (5): 532–37.
16. Christopoulos DG, Nicolaides AN, Szendro G, et al. Air-plethysmography and the effect of elastic
compression on venous hemodynamics of the leg. J Vasc Surg 1987; 5 (1): 148–59.
17. Nelzén O, Skoog J, Länne T, Zachrisson H. Residual reflux despite technical successful treatment of
Great Saphenous Vein Incompetence? 39th Charing Cross Symposium; London 2017.
448
Lymphoedema
Surgical treatment of
late-stage lymphoedema
and advanced lipoedema
Introduction
Lymphoedema is defined as the abnormal accumulation of interstitial fluid in
the early stage and as the abnormal accumulation of fibro-adipose tissues in the
late stage. In primary lymphoedema, the cause is congenital malformation of the
lymphatic system; in secondary, the cause is lymphoedema injury after surgery,
radiotherapy, infection or trauma is the cause.
Both primary and secondary lymphoedemas result in accumulation of protein-
rich lymphatic fluid, leading to proliferation of adipocytes and deposition of
collagen fibers in the extracellular matrix and around collecting lymphatics. In
the late stage, this ends in non-pitting hyper-trophied fatty tissue and scar tissue
formation.1
Lymphoedema an occur unilaterally or bilaterally in men. In contrast to this,
lipoedema only occurs in women and presents exclusively as a bilateral symmetrical
progressive accumulation of subcutaneous fat in the lower trunk, legs and sometimes
arms—typically without involvement of feet or hands.2,3
Patients may complain of pain and tenderness and sustain easy bruising. Extensive
extremity and trunk adiposity seems to be refractory to weight loss. Lipoedema
is generally categorised in stages, as described by Strößenreuther, and types, as
described by Schrader.4
The biology of the disease is poorly understood, resulting in limited treatment
options for diagnosed patients, which at best ameliorate the symptoms of
lipoedema. The absence of diagnostic tools and the lack of public and medical
awareness adds to the stigma associated with weight gain. Approximately 50% of
lipoedema patients have an elevated body mass index, making the differentiation
between lipoedema and obesity difficult. Additionally, large accumulations of
subcutaneous fat depositions can give rise to mechanical compression of previously
functional lymphatic structures, leading to a mechanical insufficiency and over
time to secondary lymphoedema in an extremity with lipoedema.
For this reason, we divided this chapter into surgery of advanced lymphoedema
and surgery of advanced lipoedema.
Lymphoedema
Although the gold standard in lymphoedema is non-operative compression therapy,
surgery is inevitable in advanced late-stage lymphoedema. Historically, two different
types of surgery have been tested: reconstructive surgery to restore lymph transport
capacity and reductive surgery by volume difference reduction.
451
Reconstructive surgery
For many years, different types of venous anastomosis, lympho-venous-lymphatic

transplants, lympho-venous-lymphatic transplants and different forms of lymph
vessel or lymph gland transplantation have been tried.5,6 The lasting effect of this
reconstructive surgery in the treatment of lymphoedema of the extremities has
never been proven.7
Not only is standardisation of patient selection lacking, but many measurement
methods mentioned are also not validated. Most studies are retrospective, with
primary and secondary lymphoedema mixed in the same study.
Although performed and studied for more than 30 years, reconstructive surgery
Surgical treatment of late-stage lymphoedema and advanced lipoedema •
never gained popularity as the treatment of choice for non-treatable lymphoedema.8

There are several reasons for this:
• Excess arm or leg volume difference in late stage non-pitting lymphoedema is
caused by massive hypertrophy of subcutaneous adipose tissue and scar tissue
formation. Restoring lymph transport will, therefore, never result in removing
surplus adipose tissue
• In case of any substantial difference in volume of two extremities, the
maximum amount of volume difference reduction by any type of reconstructive
surgery mentioned in the literature is not enough to get a good functional or
cosmetic result
• In early stages (pitting) lymphoedema responds very well to compression
garments, making preventive reconstructive surgery not indicated.
Reduction surgery background

Charles’ Procedure is a historically radical excision approach followed by skin grafts
from the removed surgical specimen. The result is “second hand skin” with dangers
Figure 1: Secondary arm lymphoedema at start and end of procedure
452
of skin breakdown, weeping blisters, erysipelas, fibrotic scar tissue formation and

extremely poor cosmetic results resulting in redo surgery or amputation.
Sistrunk, Homans and Miller introduced longitudinal excision techniques,
resulting in volume difference reduction in combination with local tissue
advancement. However, the rest of the skin has the same inferior quality as the
pathological skin which has been removed.
Reduction surgery in arms and legs

The only proven surgical method to reduce volume difference completely in
extremities is circumferential suction-assisted lipectomy in combination with
lifelong wearing of measured-to-fit compression garment.9 In end stage, non-
pitting lymphoedema of arm or leg, all suprafascial adipose tissue is removed by
suction assisted lipectomy, resulting in more than 100% reduction of volume
difference.8,10 The result is an arm or leg that is permanently smaller in volume than
the non-treated extremity—provided the patient is willing to wear measured-to-fit
compression garments 24 hours a day for the rest of their life (Figures 1 and 2).
Surgical reduction of midline lymphoedema in men

Lymphoedema of the external genitals—or midline lymphoedema—can be a very
challenging problem. In advanced cases, men are forced to pass urine in a plastic
bag; sexual intercourse is impossible. Midline bandaging is technically difficult,
and the best results are obtained with bandaging, special trousers and skincare
in a combined treatment period before and after surgical resection, which can be

quite extensive.11
The testicles are being temporarily moved out of the way; the urethra is identified
and protected by an indwelling catheter; surplus pathologic tissue is excised
Figure 2: Secondary leg lymphoedema before and three months after reduction.
453
Figure 3: Reduction surgery midline men before and three months after reduction.
subsequently followed by surgical closure of skin over the testicles.12 Split skin
covering the shaft of the penis is technically and functionally not difficult. After
the wound has healed, in most cases, passing urine in the typical male posture and
sexual intercourse may be possible again.
End-stage midline lymphoedema in women

Common phenomena include weeping blisters that leak lymph fluid in the genital
area and provoking erysipelas and subsequently more lymphoedema.
Excellent results can be obtained by electrocoagulation of these blisters. Within
several weeks, soft tissue scar formation will result in complete stop of leakage,
giving good cosmetic and functional results.
Axillary or inguinal seroma formation

Lymphorrhoea after axillary or inguinal lymph node dissection can occur for a
prolonged period of time. Lengthening the period between punctures in combination
with local compression often suffices to produce a clean axilla or groin In refractory
cases, patients are admitted for suctioning fluid out by puncture in combination
with use of fibrin glue combined with local compression and immobilisation by
sling or bedrest.
During the period of admission, 0.1mg octreotide is given subcutaneously three
times a day. Octreotide is a hormone with general antisecretory effects, having
been used to control lymphorrhoea in thoracic duct injury and after radical neck
dissection.13 Large persistent collections of lymph cysts not reacting to this regime
can be excised. When lymphorrhoea in an ulcer causes leaking, lymph ducts can be
ligated after identification by indigo carmine.
454
Elephantiasis nostras verrucosa
Surgical treatment of late-stage lymphedema and advanced lipoedema •

In legs with lymphoedema, lack of compression may in time result in wart-like
severe papillomatosis on the back of the toes or distal foot (elephantiasis nostras
verrucosa) provoking recurrent erysipelas attacks. Papillomatosis of feet responds
very well to surgical shaving, in which surplus tissue is removed until pinpoint
bleeding is observed. 14 Wound healing takes another four to six weeks until made-
to-measure garments with toe caps are worn.
At least 20% of all leg lymphoedema patients have problems with locomotion
being forced to use ill-fitting shoes with different sizes between the two feet.
Any improvement of range of motion—even a small procedure as a shaving of
papillomatosis—will enhance venous foot pump effectivity and lymph transport
capacity of the afflicted leg.
Amputation: A last resort

Although even in lymphoedematous legs of patients with paralysis, e.g. spina
bifida, the results of reduction surgery are quite rewarding. Sometimes deformity
can be so extreme with open defects and recurrent attacks of erysipelas can be so
debilitating that lower leg amputation is the only option to save a patient’s life.
The role of urgent surgery in extremities of people who have lymphoedema

Common surgical problems encountered are wrist fracture, “trigger finger”, carpal
tunnel syndrome or severe shoulder function impairment by scar tissue formation
and contracture of the axilla. In planning emergency surgery, it is important to

respect the anatomy of the lymphatic vessels and preferably use old incisions already
present. Lymph vessels in the extremities are mainly located in the epifascial region;
practically speaking, deeper lymphatics are of no consequence.
The superficial subcutaneous collectors roughly follow the course of the major
cutaneous veins of the skin. Anastomotic branches between adjacent collectors offer
different escape routes for trapped lymph fluid in case a single collector is blocked
e.g. by a surgical incision, erysipelas or late effect of radiotherapy. Moreover,
Figure 4: Reduction surgery in advanced lipoedema before and three months after reduction
455
different body parts have separate drainage systems that are connected with only a
few anastomoses. The borders between these areas are called “lymphatic watersheds”
and are particularly susceptible to oedema following damage to the lymphatics. In
case of a lymph blockage, the collateral lymph circulation between these watersheds
initiates a lymphatic backflow toward the dermis. The goal of compression is the
restoration of the original flow.
The significant contribution of physical therapy in treatment of lymphoedema
is based on the fact that exercise can increase the lymph transport capacity more
than 10 times. It is important to bear in mind that generally speaking there is
no active lymph pump, and transport largely depends on external enhancement
by mechanical compression caused by arterial pressure pulsations, arteriolar

vasomotion, intestinal smooth muscle contractions and motility, skeletal muscle
contraction and skin tension.15 In addition to this, lymphoedema may delay wound
healing after surgery by negative interference with the inflammatory response as
the lymph fluid may slow down microvascular circulation and venous return by
filling interstitial spaces, while cellular access to oxygen and nutrients as well as the
discharge of toxins and inhibitory factors from tissues may be interrupted.
In the presence of swelling, reduction of a fracture can be obtained by external
fixation. In contrast to the amount of literature on wound healing in lymphoedema,
little is written on fracture healing. An experimental study in rats demonstrated
delay in callus formation.15 After prolonged time to ensure good consolidation, the
lymphoedema problem still remains to be managed.
Although ulnaropathy is the most common nerve problem in healthy persons,
carpal tunnel syndrome, i.e. compression of the median nerve, is seen in up to
28% of lymphoedematous arms. Good results can be obtained when patients
are bandaged before and after carpal tunnel release. Surgical correction of any
impairment of hand, arm or shoulder function such as trigger finger or contracture
of the axilla may enhance lymph transport capacity enormously.
In leg lymphoedema, varicose veins, fractures, arthritic joints, skin tumours, and
infected ingrown toenails can occur. All these conditions can be treated by surgery
without lymphoedema deterioration, provided a good pre- and postoperative
compression treatment is carried out in a multidisciplinary setting.
Lipoedema
Conservative treatment of lipoedema
In lymphoedema and in lipoedema, conservative treatment is the gold standard—
e.g. a functional approach in terms of compression therapy and physical exercise to
help oedema reduction, enabling the patient to cope with this condition in everyday
life.16 Increasing muscle power and the patient becoming more active, combined
with healthy lifestyle, are an essential part of this treatment. The latter is, however,
often hard to achieve due to the debilitating nature of lipoedema. Effect of therapy
can be assessed by measuring muscle strength of the quadriceps as a guideline for
overall condition. The need for oedema volume reduction however is secondary to
the need for restoring functionality and providing methods to objectively monitor
this chronic condition.17,18
456
Surgery of advanced lipoedema

As lipoedema is not recognised in the international classification of diseases, health
insurance companies do not reimburse treatment unless lymphoedema is also
present. Patients referred to our centre are mostly “end stage III”, often presenting
with impaired locomotion caused by extreme anatomical deformation, lymph stasis
and suffering from extensive comorbidity in the presence of obesity.
The indication for surgery in advanced lipoedema is:
• Occurrence of secondary lymphoedema
• Severe impairment of locomotion
• Negative synergy occurring between lipoedema and other diseases such as
multiple sclerosis and rheumatic arthritis
• Referral by centres of excellence for example as lipoedema prevents urgent
knee joint replacement
Surgical debulking methods used are suction assisted lipectomy, longitudinal

excision of lumps, three-dimensional reconstruction or a combination of these.
The goal of this approach is to restore functionality, reduce risk of erysipelas, pain
and swelling and improve the physical appearance and the quality of life.
Surgery in these patients is quite challenging with over 50% presence of severe
comorbidity such as diabetes, sleep apnoea, thyroid malfunction and a mean body
mass index of 47kg/m2.
With an intensive care unit and a multidisciplinary approach, surgery can be
carried out without mortality or severe morbidity.

Conclusion
Patients with advanced stage III lipoedema can be treated surgically in a
multidisciplinary approach with good results at the cost of temporary complications
and no mortality.
Summary
• In lymphoedema and lipoedema, conservative treatment is the gold standard.

• In advanced non-pitting lymphoedema reduction, surgery has been proven to
reduce volume difference effectively and permanently provided the patient is
willing to continually wear garments.
• In advanced non-pitting lymphoedema, reconstructive surgery is not
successful in removing hypertrophic adipose tissue.
• In early (pitting) lymphoedema preventive reconstructive surgery is not
indicated, as compression suffices.
• Emergency surgery in the presence of lymphoedema can be carried out safely
with use of anatomical landmarks and old incisions.
• In advanced lipoedema reduction surgery can be lifesaving.
• Surgery of advanced lymphoedema or lipoedema requires a multidisciplinary
approach in a centre of excellence.
457
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37 (7): 985–91.
17. Halk AB, Damstra RJ. First Dutch guidelines on lipoedema using the international classification of
functioning, disability and health. Phlebology 2016; 32 (3): 152–59.
18. Schmeller W, Hueppe M, Meier-Vollrath I. Tumescent liposuction in lipoedema yields good long-term
results. Br J Dermatol 2012; 166 (1): 161–68.
458
Superficial venous
Evidence for cyanoacrylatic
ablation
AK Bozkurt and OO Balkanay
Introduction
The methods of intervention available for the treatment of venous disease have seen
dramatic growth in the last 20 years. Surgery, which has traditionally been seen as
the first-line management, is now being replaced by minimally invasive techniques
with reported benefits of improved early quality of life, less morbidity and faster
recovery times, allowing an earlier return to normal activities. These advantages
have led to a rapid increase in the use of endovenous techniques and a significant
decrease in the use of high ligation and stripping.1,2 Ten-month data of The
Vascular Quality Initiative Varicose Vein Registry clearly reflect an increased use of
endovenous methods in the USA, where 89.1% of the procedures are performed
with endovenous laser ablation or radiofrequency ablation.3
Non-thermal, non-tumescent techniques

Endothermal techniques require injection of tumescent anaesthesia around the
vein, which can cause severe discomfort. Also, neurological complications such
as paraesthesia are another limiting factor. Thus, non-thermal, non-tumescent
techniques have gained popularity. Ultrasound-guided foam sclerotherapy is a
viable, cheap, non-thermal endovenous ablation technique with moderate closure
rates. Newer non-thermal ablation techniques such as mechanical occlusion with
chemical assistance (MOCA) and cyanoacrylate ablation can be performed without
tumescence injection during the endovenous ablation.4,5
Cyanoacrylate
Cyanoacrylate has been used as an adhesive in medicine with various chemical
derivatives since the 1960s—to treat nerve lesions, wound closure, gastrointestinal
bleeding, and arteriovenous malformations—with no signs of toxicity.6,7 Treating
refluxing saphenous veins with cyanoacrylate ablation is the most recent
development in non-tumescent, non-thermal ablation, which overcomes even
some of the limitations of foam and MOCA.2,8 Neither MOCA nor cyanoacrylate
ablation cause paraesthesia, but (unlike MOCA) cyanoacrylate ablation does
not have a dose limit—allowing the simultaneous treatment of several veins in
the same session. Additionally, cyanoacrylate ablation does not require medical
compression stockings after the intervention. The mechanism of the cyanoacrylate
is simple: plasma and blood stimulates polymerisation and leads to closure
of the target vein. Cyanoacrylate glue triggers an inflammatory reaction in the
vessel wall causing fibrosis and occlusion. Wang et al demonstrated that when
461
cyanoacrylate mixed with lipiodol was injected into rabbit veins, the vessels were
• AK Bozkurt and OO Balkanay
obliterated immediately.9
Cyanoacrylate ablation
Almeida et al published the results of a two-year clinical follow-up of 38 patients
who underwent treatment of their symptomatic varicose veins with cyanoacrylate
glue.5 They found an occlusion rate of 92% at 24 months. Venous Clinical Severity
Score (VCSS) improved in all patients from a mean of 6.1±2.7 at baseline to
2.7±2.5 at 24 months (p<0.001). Furthermore, patients had no significant side-
effects or complications, or had deep vein thrombosis or pulmonary embolism.
However, Proebstle showed that the first eight of 38 (21%) patients had post-
Evidence for cyanoacrylatic ablation
ablation thrombus extension through the saphenofemoral junction.10 Further

modification of their technique with the first cyanoacrylate injection located 5cm
from the saphenofemoral junction seemed to have eliminated any further post-
ablation thrombus extension. In the eSCOPE trial, 70 great saphenous veins in
70 patients were treated, and follow-up to one year was completed in 60 (86%)
patients. Life-table occlusion rates were 98.6% at two days, 95.7% at three months
and 94.3% at six months. Phlebitis occurred in six cases (8.7%).11
In a randomised non-inferiority trial of cyanoacrylate ablation vs. radiofrequency
ablation (VeClose trial), patients with symptomatic great saphenous vein
incompetence were randomised to cyanoacrylate ablation (n=108) with the
VenaSeal system (Medtronic) or to radiofrequency ablation (n=114) with the
ClosureFast system (Medtronic). The trial has enrolled 242 patients (20 roll-in
and 222 randomised) at 10 study sites, and will follow these patients out to 36
months. Three-month closure rates were 99% for cyanoacrylate and 96% for
radiofrequency ablation. At day three, less ecchymosis in the treated region was
present after cyanoacrylate compared with radiofrequency ablation (p<0.01). The
authors reported that cyanoacrylate ablation was found to be non-inferior to
radiofrequency ablation for the treatment of incompetent great saphenous veins at
month 3 with less post-procedure ecchymosis.12 The VeClose study also indicated
that this is an easy technique to learn, with first-time operators in a roll-in study
achieving 100% (n=19) complete occlusion by the third month, compared with
95.4% (n=103) of radiofrequency ablation closures.13 There is a more notable
learning curve when using adhesive closure in the saphenofemoral junction.13 In
month 12, the complete occlusion rate was almost same in both groups (97.2%
in the cyanoacrylate and 97% in the radiofrequency ablation group). A trend
toward greater freedom from recanalisation in the cyanoacrylate ablation group
(p=0.08) was reported. Quality of life scores improved equally with both groups.14
For the same patient group, Kolluri reported a closure rate of 94.3% (n=87) in
the VenaSeal group and a rate of 94% (n=84) for the radiofrequency group at 24
months and both treatments maintained this improvement through 24 months.
Similarly, the Aberdeen Varicose Vein Questionnaire (AVVQ) results revealed
that patients showed statistically significant improvement over time, but with no
difference between the treatment groups. There were three adverse events reported
in the VenaSeal group between 12 and 24 months, all of “uncertain cause” in the
form of erythema in the medial thigh at both 12- and 24-month endpoints.15
Recently Gibson et al reported mid-term results of VeClose trial: at three years,
complete closure rates were 94.4% for VenaSeal and 91.9% for radiofrequency.16
462
In the WAVES trial, the use of cyanoacrylate ablation for the treatment of 48

great saphenous veins, 14 accessory saphenous veins, and eight small saphenous
veins (up to 20mm in diameter) was evaluated. Procedural pain was mild and
all treated veins had complete closure by duplex ultrasound at one month. The
revised VCSS improved to 1.8 ± 1.4 (p<0.001) and the AVVQ score to 8.9 ± 6.6
(p<0.001) at one month. Phlebitis in the treatment area or side branches
occurred in 10 patients (20%) and completely resolved in all but one patient (2%)
by one month.17
The one-year results of a prospective comparative study of another cyanoacrylate
glue (VariClose) vs. endovenous laser ablation for the treatment of venous
insufficiency have been reported by Bozkurt et al.18 This system differs from VenaSeal
in several aspects. Firstly, it is a low viscosity cyanoacrylate that provides immediate

polymerisation and a sealing effect in fewer than five seconds.18 Polymerisation is
composed of three stages as defined by Kailasnath and Chaloupka in an explanted
pig carotid artery model: 1) fast polymerisation stage with increasing tensile forces
for approximately 10 seconds; 2) second stage with stable tensile force for up to
one minute; and 3) final polymerisation stage with fast and logarithmic expanding
of tensile force.19 Polymerisation time may differ according to the cyanoacrylate
ablation type, formulisation, intravascular salt and blood levels. This system is
based on low viscosity and faster polymerisation time of cyanoacrylate compared
to the higher viscosity and slower polymerisation in the VenaSeal. A total of 310
patients were treated with cyanoacrylate or laser ablation. Operative time was
shorter (15±2.5min vs. 33.2±5.7min, p<0.001), and periprocedural pain was less
(3.1±1.6 vs. 6.5±2.3, p<0.001) in cyanoacrylate ablation group compared to the
laser group. Ecchymosis at the third day was also significantly less in cyanoacrylate
ablation group (p<0.001). Temporary or permanent paraesthesia occurred in seven
patients in the laser group and in no patients in the cyanoacrylate ablation group
(p=0.015). One, three, and 12 months’ closure rates were 87.1%, 91.7%, and 92.2%
with laser and 96.7%, 96.6%, and 95.8% with cyanoacrylate ablation, respectively.
The closure rate at the first month was significantly better in the cyanoacrylate
ablation group (p<0.001). Although there was a trend of better closure rates in
cyanoacrylate ablation patients, this difference did not reach statistical difference at
six and 12 months (p=0.127 and p=0.138, respectively). Both groups had significant
improvement in VCSS and AVVQ postoperatively (p<0.001), but there was no
significant difference in VCSS and AVVQ between the groups at months one, six,
and 12. Only a slightly better well-being trend was noted in the cyanoacrylate
ablation group in terms of AVVQ scores (p=0.062).
Koramaz el al conducted a retrospective comparison of 339 patients. The
12-month total occlusion rates in the cyanoacrylate and laser ablation groups
were 98.6% and 97.3%, respectively (p=0.65). VCCS declined significantly with
no difference between groups. There were fewer adverse events after cyanoacrylate
compared with laser ablation (pigmentation, p≤0.002; phlebitis, p≤0.015).20 Yasim
et al also reported early results of a retrospective study using VariClose. One
hundred and eighty patients with varicose veins due to incompetent saphenous
veins were treated (great saphenous veins in 169 patients and small saphenous veins
in 11 patients). Procedural success was 100%, and recanalisation was not observed
in any of the patients in a mean follow-up time of 5.5 months. The average VCSS
was 10.2 before the procedure and decreased to 3.9 after three months (p<0.001).21
463
The same group recently reported mid-term results and 168 patients available for
follow-up for 30 months were included. Ablation rates were 100% at the third
month, 98.3% at the sixth month, 96.6% at one year, and 94.1% at 30 months.
No complication was reported.22 Results of three other groups were also reported,
with similar prospective cohort series using cyanoacrylate glue.23–25
With no tumescent anaesthesia, this approach causes a low amount of pain and
no nerve damage, and requires no additional devices. There have been concerns
over histotoxicity, and the fact that implants take years to be reabsorbed. Phlebitis-
like skin reactions have been reported in the literature, at a rate of up to 20%.26
Acrylates are known to cause allergic reactions. The generalised skin affections
observed after varicose treatment are hives and itching, which is typical for
histamine dependency—a type I allergy. This can be treated using steroids and
anti-histamines. Skin changes like these are seen in 1–2% of cases.
Specific circumstances
Small saphenous vein
Small saphenous vein reflux accounts for about 15% of varicose veins. Untreated
varicose veins may sometimes lead to ulceration of the leg, which is difficult
to manage. Traditionally, treatment was restricted to surgery or conservative
management, and since the 1990s, endovenous thermal ablation has been a
popular choice. The small saphenous vein lies in its own saphenous compartment,
and in the distal two-thirds of the lower leg—the distance between the vein and
the sural nerve is <5mm in 90% of the legs. Also, in the saphenopopliteal region,
the average shortest distance between the small saphenous vein and the tibial
nerve is 4.4mm, and in 20% of patients, this distance is <1mm. Thus, at the
saphenopopliteal region, the tibial nerve and in the distal two-thirds of the lower
leg, the sural nerve is at risk during endovenous thermal ablation due to the short
distance to the small saphenous vein.27 In a study, the sonographic anatomy of
sural nerve demonstrated anatomical variations in 44.3% of patients. The sural
nerve may become epifascial at a higher point than usual in many cases, and the
classical believe of protection of the nerve inside the deep fascia of the upper calf,
may be unreliable.28 Thus, endovenous laser ablation of the small saphenous vein
is associated with a significantly higher incidence of sensory disturbance compared
with laser ablation of the great saphenous vein.29
In order to investigate and compare the anatomical success rates and complications
of the treatment modalities for small saphenous vein incompetence, a systematic
literature search was performed. The search found 49 articles (five randomised
controlled trials and 44 cohort studies) reporting on the different treatment
modalities: surgery (n=9), laser (n=28), radiofrequency (n=9), foam sclerotherapy
(n=6), and MOCA (n=1). The pooled anatomical success rate was 58% for surgery
in 798 small saphenous veins; 98.5% for laser in 2,950; 97.1% for radiofrequency
in 386; and 63.6% for foam sclerotherapy in 494. One study reported results of
MOCA, with an anatomical success rate of 94%. Neurological complications were
most frequently reported after surgery (mean 19.6%) and thermal ablation (laser:
mean 4.8%; radiofrequency: mean 9.7%). Endovenous thermal ablation (laser/
radiofrequency) should be preferred to surgery and foam sclerotherapy in the
treatment of small saphenous vein incompetence. Although data for non-thermal
464
techniques in small saphenous veins are still sparse, the potential benefits, especially

the reduced risk of nerve injury, might be of considerable clinical importance.30
There is no doubt that endovenous glue ablation will increasingly become the first-
line treatment for patients with symptomatic superficial venous reflux specifically
in patients with small saphenous vein reflux.
Concomitant phlebectomy
In a review, Hager et al collected data from eight clinical comparative studies
of combined saphenous ablation and phlebectomy vs. staged procedures:
three randomised prospective studies, two prospective comparisons, and three
retrospective reviews. Eventually, 30% to 60% of patients may require treatment
for varicosities and that may increase up to 80% for advanced cases. The authors

concluded that combined treatment of saphenous incompetence and symptomatic
varicosities results in better short-term and better to equivalent long-term patient
outcomes.31 Certainly, there are patients who prefer not to have varicosities treated
if this is not absolutely needed and, therefore, the patient’s preference should
be considered. Kokkosis and Schanzer evaluated anatomical and clinical factors
favouring the performance of saphenous ablation and microphlebectomy as a
single-stage procedure. Patients with more severe varicosities were more likely to
require a secondary procedure and should be considered for a one-stage approach.32
Interestingly, there is growing evidence that the rate of secondary procedure rates is
lower following endovenous glue ablation than with endothermal ablation.16
Conclusion
In a recent paper, Vos et al reported a systematic review and meta-analysis of
MOCA and cyanoacrylate ablation techniques for the great saphenous vein.33
Procedural success was reported in three of eight cyanoacrylate ablation studies and
was 100% in all three studies. A pooled analysis of seven studies showed an overall
anatomical success rate at six months of 94.8% (95% CI, 92.0–97.6%).The pooled
anatomical success at 12 months of four studies was 89% (95% CI, 84.2–93.9%).
Of the studies on cyanoacrylate ablation, three reported the AVVQ score, and all
reported a significant reduction in mean AVVQ score compared with baseline. The
most reported complications after cyanoacrylate ablation were thrombophlebitis
(0.5–18%), hyperpigmentation (1.6–3%), deep vein thrombosis (0–3.5%), access
site infection or cellulitis (1.4–3%), and ecchymosis or haematoma (1.4–1.6%).
Nerve injury or paraesthesia was rare (0–2%). Bozkurt and Yilmaz reported 4.5%
paraesthesia, 3.2% temporary and 1.3% permanent, and this occurred only in the
laser group.
The occlusion rates of current endovenous treatments are as good as those of
high ligation/stripping; side-effects and complications are relatively rare, and the
convalescence period is short. N-butyl cyanoacrylate-based vein sealing systems
are fast and effective treatment options for the management of incompetent
saphenous veins and do not involve tumescent anaesthesia, compression stockings,
paraesthesia, burn marks, or pigmentation. However, long-term follow-up data for
cyanoacrylate ablation are still lacking.
465
Summary
• Non-thermal ablation techniques such as MOCA and cyanoacrylate ablation

can be performed without tumescence injection during the endovenous
ablation.
• The mechanism of cyanoacrylate is simple: plasma and blood stimulate
polymerisation and lead to closure of the target vein.
• Cyanoacrylate ablation does not require medical compression stockings after
the intervention.
•
Endovenous glue ablation will increasingly become a first-line treatment for

patients with symptomatic superficial venous reflux specifically in patients
with small saphenous vein reflux.
• N-butyl cyanoacrylate-based vein sealing systems are fast and effective
treatment options for the management of incompetent saphenous veins.
• Long-term follow-up data for cyanoacrylate ablation are still lacking.
References
1. Van der Velden SK, Lawaetz M, De Maeseneer MG, et al. Predictors of recanalization of the great
saphenous vein in randomized controlled trials 1 year after endovenous thermal ablation. Eur J Vasc
Endovasc Surg 2016; 52 (2): 234–41.
2. Proebstle T, van den Bos R. Endovenous ablation of refluxing saphenous and perforating veins. Vasa
2017; 46 (3): 159–66.
3. Obi AT, Sutzko DC, Almeida JI, et al. First 10-month results of the Vascular Quality Initiative Varicose
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clinical trial. Phlebology 2012; 27 (2): 67–72.
5. Almeida JI, Javier JJ, Mackay E, et al. First human use of cyanoacrylate adhesive for treatment of
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10. Proebstle T. Status of cyanoacrylate glue for saphenous ablation. In: Presented at the International
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11. Proebstle TM, Alm J, Dimitri S, et al. Twelve-month follow-up of the european multicenter study on
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12. Morrison N, Gibson K, McEnroe S, et al. Randomized trial comparing cyanoacrylate embolization and
radiofrequency ablation for incompetent great saphenous veins (VeClose). J Vasc Surg 2015; 61 (4):
985–94.
13. Kolluri R, Gibson K, Cher D, et al. Roll-in phase analysis of clinical study of cyanoacrylate closure for
incompetent great saphenous veins. J Vasc Surg Venous Lymphat Disord 2016; 4 (4): 407–15.
14. Morrison N, Gibson K, Vasquez M, et al. VeClose trial 12-month outcomes of cyanoacrylate closure
versus radiofrequency ablation for incompetent great saphenous veins. J Vasc Surg Venous Lymphat
Disord 2017; 5 (3): 321–30.
15. Kolluri R. In: Two-year outcomes of the VeClose pivotal trial. Presented at the VEITHsymposium. New
York, USA: 15–19 November 2016.
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16. Gibson K, Khilnani N, Schul M, et al. American College of Phlebology Guidelines – Treatment of

refluxing accessory saphenous veins. Phlebology 2017; 32 (7): 448–52.
17. Gibson K, Ferris B. Cyanoacrylate closure of incompetent great, small and accessory saphenous veins
without the use of post-procedure compression: Initial outcomes of a post-market evaluation of the
VenaSeal System (the WAVES Study). Vascular 2017; 25 (2): 149–56.
18. Bozkurt AK, Yılmaz MF. A prospective comparison of a new cyanoacrylate glue and laser ablation for
the treatment of venous insufficiency. Phlebology 2016; 31 (1 Suppl): 106–13.
19. Kailasnath P, Chaloupka JC. Quantitative assessment of polymerization-binding mechanics of
cyanoacrylates: model development and validation. Am J Neuroradiol 2002; 23 (5): 772–78.
20. Koramaz İ, El Kılıç H, Gökalp F, et al. Ablation of the great saphenous vein with nontumescent n-butyl
cyanoacrylate versus endovenous laser therapy. J Vasc Surg Venous Lymphat Disord 2017; 5 (2): 210–15.
21. Yasim A, Eroglu E, Bozoglan O, et al. A new non-tumescent endovenous ablation method for varicose
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22. Eroglu E, Yasim A, Ari M, et al. Mid-term results in the treatment of varicose veins with N-butyl

cyanoacrylate. Phlebology 2017; 32 (10): 665–69.
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30. Boersma D, Kornmann VN, van Eekeren RR, et al. Treatment modalities for small saphenous vein
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31. Hager ES, Ozvath KJ, Dillavou ED. Evidence summary of combined saphenous ablation and treatment
of varicosities versus staged phlebectomy. J Vasc Surg Venous Lymphat Disord 2017; 5 (1): 134–7.
32. Kokkosis AA, Schanzer H. Anatomical and clinical factors favoring the performance of saphenous
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33. Vos CG, Ünlü C, Bosma J, et al. A systematic review and meta-analysis of two novel techniques of
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2017; 5 (6): 880–96.
467
One extra drop makes a
difference in closure rate for
endovascular cyanoacrylate
treated saphenous vein
≥8mm in diameter
YC Chan, Y Law, GC Cheung, AC Ting and SW Cheng
Introduction
Cyanoacrylate glue is a liquid adhesive that has been used in humans to treat
varicosities and was first used in endoscopic intravenous injections of peptic
varicosities.1 Although this non-thermal office-based endovenous treatment modality
does not require tumescence anaesthesia, safety and effectiveness in closure rates are
important clinical outcomes.2 The VenaSeal closure system (Medtronic) received
the CE mark in September 2011 and was approved by the US FDA in February
2015. It is now being used clinically to treat trunkal reflux in the USA, Europe,
Asia, Australia, and Canada.
Almeida et al studied 38 patients who were treated with VenaSeal
cyanoacrylate. At 36 months, 27 of the 29 patients were available for follow-up
and the great saphenous vein occlusion rate was 94.7%. In this study,
great saphenous vein with diameters of <3mm or >12mm in any segment
were excluded.3
The VeClose trial was a multicentre randomised controlled, investigational device
exemption (IDE) study that was conducted in 10 centres in the USA. Enrolment
was completed in September 2013 with 222 patients (108 were randomised
to receive VenaSeal cyanoacrylate and 114 were randomised to be treated with
radiofrequency ablation). At the three-month follow-up point, closure rates were
99% for cyanoacrylate and 96% for radiofrequency ablation.4 In this study, the
mean diameter of the proximal great saphenous vein was 6.3mm (3–12mm). In the
same cohort of patients, after the three-month follow-up visit, approximately 41%
of patients in both groups had one or more adjunctive therapies to treat visible
varicosities and incompetent tributaries.5 Twelve months into the study, closure
rates were statistically the same with a complete occlusion rate of 97.2% in the
VenaSeal group and 97% in the radiofrequency group.5
469
Predictors of recanalisation following cyanoacrylate
YC Chan, Y Law, GC Cheung, et al
treatment of great saphenous veins at our institution

We have been using the VenaSeal system at our institution to treat patients with
incompetent great saphenous veins since September 2014, and was the first centre
in Asia to use this treatment modality (local Institutional Review Board approval:
reference UW 15–212). Our pilot study assessing the safety and efficacy of VenaSeal
for the treatment of symptomatic incompetent great saphenous veins included a
total of 57 legs in 29 consecutive patients with duplex-proven saphenofemoral
junction/great saphenous vein incompetence between September 2014 and October
2015.6 We preferentially chose bilateral cases because of cost. The average maximum
diameter of the long saphenous vein in the treatment zone as determined by pre-
One extra drop makes a difference in closure rate for endovascular cyanoacrylate treated saphenous vein ≥8mm in diameter •
operative duplex ultrasound with the patient in the supine position was 7.1mm
(range 3.9–11.4mm). On day seven, all the great saphenous veins were successfully
obliterated. At one week, one month, six months, and 12 months postoperatively,
the closure rates remained high at 100%, 95.3%, 90.3%, and 78.5%, respectively.
Our definition of complete closure of the saphenous vein was defined as Doppler
ultrasound non-compressibility/absence of flow signal along the entire treated
saphenous vein segment with no discrete segments of patency exceeding 5cm as
read by a qualified specialist vascular ultrasonographers.7 There were no cases of
total recanalisation, but partial recanalisation (defined as any further recanalisation
compared to previous scans) occurred in seven legs during follow-up. The closure
rates were not as good as in the VeClose trial, and binary logistic regression showed
that a mean great saphenous vein diameter ≥8mm was a significant independent
predictor of recanalisation (odds ratio 13.3, 95% CI 2.08–85.41; p=0.006). The
mean diameter of great saphenous vein was defined as the average of diameters
of great saphenous vein for each leg at three levels: proximal thigh 1cm from the
saphenofemoral junction, mid-thigh, and distal thigh above knee with the patient
in the supine position. Closure rates of those VenaSeal-treated great saphenous
veins <8mm remained high at 100%, 93.1%, 93.1%, and 93.1% at one week,
one month, six months and 12 months postoperatively, respectively. Closure rates
for great saphenous veins ≥8mm were 90.9%, 90.9%, 68.2%, and 34.1% at one
week, one month, six months and 12 months, respectively (log-rank test; p=0.006).
Other factors such as treatment length of great saphenous veins and preoperative
clinical score (CEAP) were not statistically significant predictors of recanalisation.
In our follow-up study with 108 legs in 55 consecutive patients with incompetent
great saphenous veins treated with VenaSeal (including those from our pilot study),
the median average diameter of the great saphenous veins in the treatment zone
was 6.6mm (range 2.3–11.4mm); 6.6mm was the median of all mean diameters
of great saphenous veins measured with the patient in the supine position.8 Again,
it was demonstrated that preprocedure great saphenous vein diameter was a
significant predictor of closure. Closure rates of great saphenous veins <6.6 mm
were 100%, 100%, 100%, and 90% at one week, one month, six months, and
12 months postoperatively; for great saphenous veins ≥6.6mm, closure rates were
93.8%, 82.3%, 76.2%, and 58.6% at one week, one month, six months, and 12
months postoperatively (log-rank test; p=0.002). The pattern of recanalisation was
commonly from the saphenofemoral junction downwards, involving previously
closed great saphenous veins.
470
Modification of technique of endovenous VenaSeal for great
saphenous veins ≥8mm in diameter
The VenaSeal device is a disposable, single-use system for administering
cyanoacrylate. Each device is packed in a clear sterile plastic tray containing
all items needed for cyanoacrylate ablation, except for a micropuncture set for
percutaneous venous access using the Seldinger technique. The set consists of a
gun-shaped disperser handle, a small container with 5cc of the specially formulated
N-butyl-2-cyanoacrylate, two Luer Lock syringes with blunt needles for aspirating
the glue, a 7Fr introducer/dilator sheath, and a 5Fr delivery catheter.6,8,9
The endovenous procedures have been described before.6,8 Briefly, all the patients
had the same procedural protocol and the procedures were performed as outpatient
day cases in the minimally invasive surgical centre under local anaesthesia in the
presence of an anaesthetist. Percutaneous ultrasound-guided puncture of the great
saphenous vein was performed using a micropuncture set (Angiodynamics). The
0.035-inch proprietary guidewire was passed to the saphenofemoral junction and
then exchanged to the proprietary 5Fr long sheath. The proprietary guidewire and
the long sheath were from the VenaSeal set. The VenaSeal cyanoacrylate was prepared
and attached to the delivery catheter. With the patient in head-down position,
the tip of the 5Fr introducer sheath/cyanoacrylate catheter was advanced to the
saphenofemoral junction and positioned 4cm distal to the saphenofemoral junction
under ultrasound guidance. With occlusive compression at the saphenofemoral
Figure 1: (A) Diagrammatic representation of “normal protocol”, which was applied to all great saphenous veins before
we modified our protocol, and currently applied to mean great saphenous vein diameter <8mm; (B) modified “extra-
drop protocol”, which is now applied to mean great saphenous vein diameter ≥8mm.
471
Figure 1: (A) Diagrammatic representation of “normal protocol”, which was applied to all great saphenous veins before
we modified our protocol, and currently applied to mean great saphenous vein diameter <8mm; (B) and modified
“extra-drop protocol”, which is now applied to mean great saphenous vein diameter ≥8mm.
level by the ultrasound probe, cyanoacrylate was injected endovenously with two
injections of 0.09mL given 1cm apart at this location followed by a three-minute
period of local compression and then repeated at 3cm intervals with 30-second
ultrasound probe compression sequences until the entire length of the target vein
was completed. Each complete trigger pull will deliver 0.09ml of VenaSeal into the
vein. Great saphenous vein obliteration and the lack of deep vein thrombosis (with
compressibility) were confirmed by duplex ultrasound intraoperatively. Small stab
avulsions of varicosities under local anaesthesia were performed simultaneously in
all patients. Our study protocol with the catheter starting point at 4cm from the
saphenofemoral junction and compression at the saphenofemoral junction was
different from the US instructions for use with the catheter tip 5cm from the
saphenofemoral junction and compression at 2–2.5cm.9 Patients were discharged
after the procedure from the vascular ward on the same day.
With the observation that great saphenous veins with larger diameters tend to
recanalise from the saphenofemoral junction downwards, and with reference to
the results of the WAVES study, we have decided to modify our protocol slightly
for great saphenous veins with mean preoperative diameter of ≥8mm.10 The
WAVES study was a single-centre, multiple-investigator, single-arm prospective
study investigating the use of VenaSeal in patients with symptomatic venous
reflux disease, in which addition of VenaSeal volume (0.1 ml) was permitted for
(unspecified and undefined) larger diameters of veins at the treating physician’s
discretion. Our modified protocol used one extra complete trigger pull delivering
an additional 0.09ml of VenaSeal at the proximal great saphenous vein for veins
472
with mean diameter ≥8mm, while those with <8mm diameters had our normal
protocol (Figure 1). All other procedures were conducted in the same fashion.
We began adopting the “extra-drop” protocol on 21 July 2016, and for this
subgroup of treated legs (n=48), the follow-up period was shorter. All patients
underwent serial clinical and duplex ultrasound examinations at one week and at
one, six, 12, 24, 36 and 48 months after the procedure. The primary endpoint was
procedural success rate with obliteration of the great saphenous vein, lack of deep
vein thrombosis, and lack of clinical recurrence of varicose veins.
Closure rates were dated back to the latest duplex ultrasound scan, with a median
duplex follow-up period of 12.5 months (range 0–38). There were 157/173 (91%),
141 (82%), 68 (39%), 42 (24%), and 14 (8%) legs that passed the one-, six-, 12-,
24-, 36-month follow-up points. The follow-up for great saphenous veins that were
treated with the extra-drop protocol had a median follow-up of 6.5 months (range
0–13.6). The Kaplan-Meier curve for closure rates for treated great saphenous veins
Figure 3: (A) Graphic representation of the Venous Clinical Severity Score and (B) Aberdeen Varicose Vein
Questionnaire, comparing those legs with great saphenous vein diameter ≥8mm treated with “normal protocol”, and
≥8mm treated with “extra-drop protocol”.
473
(our cohort of 88 patients, 173 leg, unpublished results) is shown in Figure 2.
The mean length of the great saphenous vein stump in closed veins at one week
and six months (as measured with duplex from the saphenofemoral junction to
the obliterated great saphenous veins) was 2.18cm, 2.95cm, 2.07cm and 2.33cm,
4.59cm, 2.74cm in great saphenous veins <8mm diameter, n≥8mm diameter-
normal protocol; and n≥8mm diameter-“extra-drop” protocol, respectively, and
none of the patients developed deep vein thrombosis. Thrombus extension from
the great saphenous vein to the deep vein appeared in four, two, and three legs,
respectively, and, therefore, the “extra-drop protocol” did not predispose to
development of post-procedure deep vein thrombosis.
Venous Clinical Severity Score and Aberdeen Varicose Vein Questionnaire
were routinely filled out preoperatively, and at one month, six months, one year
and two years postoperation. Figure 3 shows the trend of average questionnaire
findings comparing the “normal protocol” vs. “extra-drop protocol” for those great
saphenous veins ≥8mm. Baseline severity was comparable, and initial response to
glue treatment was positive with a general decreasing trend of scores. However,
there was a resurge after one year for the available data in the “normal protocol”,
corresponding to the duplex ultrasound finding of greater incidence of recanalisation.
Mean questionnaire scores for “extra-drop protocol” were significantly lower at six
months (Student’s t test p=0.036) (Figure 3).
Conclusion
Contemporary published literature and our experience has shown that VenaSeal
cyanoacrylate is safe and effective in closing great saphenous veins. We have shown
that great saphenous vein diameters of ≥8mm6 and ≥6.6mm8 were statistically
significant predictors for late recanalisation, although the precise mechanism for
this remains unclear. The pattern of recanalisation in the great majority seemed to
be from the saphenofemoral junction downward and not segmental recanalisation
of the treated great saphenous vein, which mostly closed at one week. In three
legs, recanalisations were detected on the one-year follow-up duplex scan: two were
from the mid-thigh to the lower thigh, and one was at the mid-thigh at the level
of a perforator. With the modified “extra-drop” protocol for great saphenous veins
≥8mm, we have improved the closure rates (Figure 2C), and this new protocol
has a closure rate that was not statistically different to that of great saphenous
veins <8mm (Figure 2D). Additionally, this extra drop did not predispose the
development of thrombus extrusion into the deep vein or to deep vein thrombosis.
Durability and effectiveness will be tested over time.
474
Summary
• Contemporary published literature and our experience have shown that

VenaSeal cyanoacrylate is safe and effective in closing great saphenous veins.
• In our experience, larger great saphenous vein diameters of ≥8mm and
≥6.6mm were statistically significant predictors for late recanalisation, and the
great majority seemed to be from the saphenofemoral junction downward.
• Our modified “extra-drop” protocol has improved the closure rates for great
saphenous veins ≥8mm and did not predispose the development of thrombus
extrusion into the deep vein or deep vein thrombosis.
References
1. Labenz J, Börsch G. Bleeding gastric and duodenal varicose veins: endoscopic embolisation using
tissue adhesives. Dtsch Med Wochenschr 1992; 117 (34): 1274–77.
2. Chan YC, Ting AC, Yiu WK, Cheng SW. Cyanoacrylate superglue to treat varicose veins: truly office
based and minimally invasive? Eur J Vasc Endovasc Surg 2013; 45 (2): 1767–67.
3. Almeida JI, Javier JJ, Mackay EG, et al. Thirty-sixth-month follow-up of first-in-human use of
cyanoacrylate adhesive for treatment of saphenous vein incompetence. J Vasc Surg Venous Lymphat
Disord 2017; 5 (5): 658–66.
985–94.
5. Morrison N, Gibson K, Vasquez M, et al. VeClose trial 12-month outcomes of cyanoacrylate closure
versus radiofrequency ablation for incompetent great saphenous veins. J Vasc Surg Venous Lymphat
Disord 2017; 5 (3): 321–30.
6. Chan YC, Law Y, Cheung GC, et al. Cyanoacrylate glue used to treat great saphenous reflux: Measures
of outcome. Phlebology 2017; 32 (2): 99–106.
7. Khilnani NM, Grassi CJ, et al. Multi-society consensus quality improvement guidelines for the
treatment of lower-extremity superficial venous insufficiency with endovenous thermal ablation from
the Society of Interventional Radiology, Cardiovascular Interventional Radiological Society of Europe,
American College of Phlebology, and Canadian Interventional Radiology Association. J Vasc Interv
Radiol 2010; 21: 14–31.
8. Chan YC, Law Y, Cheung GC, Cheng SW. Predictors of recanalization for incompetent great saphenous
veins treated with cyanoacrylate glue. J Vasc Interv Radiol 2017; 28 (5): 665–71.
9. VenaSeal IFU Protocol. VenaSeal Sapheon Closure System: SP-101 Instructions for use (PT-10843-02
Rev D) 2014-06; 1–84
VenaSeal System (the WAVES Study). Vascular 2017; 25 (2): 149–56.
475
The pros and cons of
endovenous cyanoacrylate
T Hirsch
Introduction
Treating varicose veins using endovenous thermal techniques—in particular laser
and radiofrequency ablation—has emerged as an effective alternative to surgical
treatment, which consists of stripping and high ligature. Even though these
thermal methods are very gentle and patient-friendly, they still present risks and
side-effects. The risk of damaging peripheral and motor nerves is lower than with
open surgery; however, a risk is still present in the context of heat exposure and
tumescent anaesthesia.
Acrylate adhesion is a non-thermal method for treating saphenous varicose
veins. It has a lower risk of nerve lesions and is able to compete in terms of its
effectiveness. This chapter highlights the available data for this method of treatment
and discusses its special technical aspects and pitfalls.
Adhesion of saphenous varicose veins expands the portfolio

of endovenous methods
Introduced in 2011, one of the latest techniques for treating varicose veins involves
the closure of saphenous varicose veins through embolisation with cyanoacrylate.1
The VenaSeal system (Medtronic) was approved and has been on the market in
Germany since 2012. The system, originally developed by the start-up Sapheon,
was approved by the FDA in 2015 and has been used in the USA ever since.
Another system that uses cyanoacrylate to close diseased saphenous veins was
developed in Turkey (VariClose, Biolas).
The kits of these systems contain all of the devices needed to perform
the treatment. No other additional equipment is needed apart from a high-
performance ultrasound machine. As with thermal methods and conventional
vein surgery, the quality of the pre- and perioperative diagnostics determines the
treatment success of the adhesive method. The use of a (minimum) 12MHz linear
probe is recommended.
The acrylate adhesive needs to come in contact with blood in order to polymerise.
This prevents it from adhering to the catheter. An adhesive with a particularly
high viscosity was developed for the VenaSeal system and can be applied safely
and accurately.
Two-step closure
After preparing the guidewire, sheath with dilator and delivery gun, treatment begins
by closing the saphenous vein near the level of the junction. Under ultrasound
guidance the treatment catheter is inserted over a 180cm-long guidewire up to
the saphenofemoral or saphenopopliteal junction. In order to avoid displacing the
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adhesive into the deep vein system, the sonic head is used to completely close the
• T Hirsch
treated vein proximally to the catheter tip through external compression before the
first dose of precisely 0.09ml of adhesive is administered by the delivery gun. The
next dose of adhesive is dispensed at a distance of 1cm. After applying the adhesive,
the treated area must be compressed for three minutes until the polymerisation
The pros and cons of endovenous cyanoacrylate
process is completed. For safety reasons the manufacturer advises maintaining a

distance of 5m from the catheter tip to the deep vein system. The visibility of the
catheter tip is enhanced in the sonogram by fine air channels.
In a second step, the saphenous vein is closed by withdrawing the catheter along
the vein, stopping every 3cm to dispense a dose of cyanoacrylate. Thirty seconds of
compression is required each time the adhesive is released. As a guide, 1.53ml of
adhesive is used to treat a 45cm-long vein segment (Figure 1).
No heat is administered apart from the slight release of energy from the
exothermal polymerisation reaction. This makes tumescent anaesthesia redundant.
The procedure produces little to no pain.
As venepuncture represents the only potential form of trauma, the risk of nerve
damage is very low. This makes the method particularly suitable for treating
the small saphenous vein, which is otherwise difficult to treat thermally due to
its proximity to the intersecting sural nerve. Moreover, the method provides
an endovenous treatment option for patients in whom tumescent anaesthesia
is contraindicated due to an allergy to local anaesthetics and for patients with
cardiac arrhythmia whose antiarrhythmic treatment would interact with aminoamide
local anaesthetics.
Once the cyanoacrylate polymerises, the varicose vein is immediately and
permanently closed. This means the patient can resume every type of activity
immediately after the treatment. When only the saphenous veins are treated,
compression stockings do not necessarily have to be worn.
The method is very easy to learn if the user already has experience in treating
varicose veins with endovenous techniques. Kolluri et al found in a study that the
Figure 1: As the catheter is withdrawn, ultrasound is used to monitor the application of 0.09ml of N-butyl-
cyanoacrylate every 3cm. The catheter tip can be clearly identified as a star shape in the ultrasound image.
478
success rate and safety data were comparable between the first-time users of the

system and users with more experience.2
Cyanoacrylate—superglue with a long history of medical

applications
Cyanoacrylate has been used in medicine for decades in different chemical
derivatives. In the 1960s methyl 2-cyanoacrylate was introduced to repair nerve
lesions.3 Isobutyl 2-cyanoacrylate (IBCA) was initially used to close wounds
during surgery until N-octyl-cyanoacrylate was introduced in 1996. The latter is
still being widely used today.4 N-butyl 2-cyanoacrylate (NBCA) has been used
intravascularly since 1989 to treat, for example, acute gastrointestinal bleeding,
and for embolisation of vascular deformities and malignant tumours.5 This active
ingredient is also used to treat varicose veins.
NBCA has exhibited good tissue compatibility in thousands of patients since its
• T Hirsch
introduction. In contrast to the previously used short-chain compounds (methyl-
and ethyl cyanoacrylate), today’s longer-chain derivatives (N-butyl-cyanoacrylate
and N-octyl-cyanoacrylate) produce few histotoxic inflammatory reactions in vitro
and in animal testing.6–9 Clinical investigations reinforce these observations.10 The
length of resorption is in direct correlation with chain length.
Non-thermal acrylate adhesion—a competitive form of

varicose vein treatment
There is an abundance of registry data for non-thermal acrylate adhesion despite its
short period of use and the fact that it was not approved in the USA until 2015.
The feasibility study on cyanoacrylate adhesion for the VenaSeal system identified
a closure rate of 92%.11 Proebstle et al confirmed these findings in a European
multicentre study. The remarkable aspect about this study was that it consequently
ignored the treatment of tributaries. At the time of inclusion, 1.4% of the treated
legs were free of visible varicose veins and 41.4% were free of varicose veins three
months after the saphenous varicose veins were closed.12
In the only randomised controlled study currently available (VeClose, FDA
approval study), Morrison et al compared acrylate adhesion with radiofrequency
ablation (ClosureFast, Medtronic). At the two-year follow-up, the patient group
treated with VenaSeal had a tendentially higher closure rate of 94.3% than the
radiofrequency ablation comparison group (94%). Both study arms exhibited
comparable results with regard to clinical improvement. The Venous Clinical
Severity Score (VCSS) at the time of inclusion was 5.6 (±2.6) for radiofrequency
ablation and 5.5 (±2.6) for acrylate adhesion. After six months it was 1.6 (±1.9)
for radiofrequency ablation and 1.5 (±1.8) for acrylate adhesion with a persisting
effect.13 The currently unpublished three-year data also confirm these findings.
In a current publication on the use of cyanoacrylate with the Biolas VariClose
system, the Turkish working group of Çalık et al describes a closure rate of 97.2%
after six months (215 treated saphenous veins).14
So far, there has been no case of nerve damage resulting from acrylate adhesion
of varicose veins. In animal trials, the polymerised acrylate has never been
detected outside the adventitia, which indicates that the inflammatory reaction
is not strong enough to damage the nerves and surrounding tissue.1 The studies
479
found no incidence of paraesthesia or hyperpigmentation. Based on the author’s
own observations, a general absence of hyperpigmentation cannot be confirmed.
• T Hirsch
Hyperpigmentation is particularly observed after treating very superficial and

extrafascial vascular segments.
Special technical aspects and pitfalls

One technical limitation of vein adhesion is that the manufacturer requires a safety
distance of 5cm from the saphenofemoral or saphenopopliteal junctions. This does
not correspond to the generally recognised principle, at least in Germany, that the
saphenous vein stump should be as short as possible. It should be noted that there
is a lack of reliable data substantiating a higher rate of long-term non-recurrence
for a short or completely absent stump.
The long safety distance serves to prevent adhesive from entering the deep vein
system. Since the adhesive is visible in the ultrasound, a shorter stump is also
feasible; however, this requires somewhat of a learning curve.
A particularly organised approach is required when multiple saphenous veins are
to be treated in one session. The treatment system has to be prepared in a specific
way (aspiration of the adhesive in the treatment catheter, cleaning of the catheter
tip, etc) and the consumption of the adhesive needs to be calculated.
In addition to the special technical aspects, it should be taken into account
that the polymerised acrylate is, in principle, an implant that, like a stent, suture
material and staples, is encapsulated and endothelialised. The metabolic degradation
of the material occurs very slowly as indicated by sonographic images taken over a
period of 12 months (Figure 2).2
Individual cases of transient inflammatory reactions and eosinophilic vasculitis
have been published, whereby inflammatory processes also play a role in vessel
obliteration.15,16 Thrombophlebitis has been observed in connection with all
saphenous vein treatment methods. This applies to stripping/high ligation, as well
as thermal and non-thermal endoluminal methods, and its cause can be found
in the remaining tributaries. The slightly painful localised reddening that has
been detected after acrylate adhesion cannot be attributed to thrombophlebitis
in the narrow sense. Instead it is the result of the histotoxic reaction described
Figure 2: The polymerised adhesive (highly reflexive structure in the centre of the vein with acoustic shadow) is an
intravenous implant that can take several years to resorb.
480
• T Hirsch
Figure 3: A painful redness is experienced by 10–15% of patients several days after the procedure. It is
an expression of the histotoxic effect of the cyanoacrylate used to treat the saphenous vein.
above. This transient irritation can be observed in every fifth patient during the
postoperative phase and is described in all available studies (Figure 3).17 There
is, however, terminological discrepancies in these studies when it comes to
interpreting this side-effect. It has been described as “phlebitis”, “painful redness”
and “thrombophlebitis”. The patient should always receive information before the
procedure about this painful phenomenon, which occurs only latently.
Contact-related allergic reactions have been repeatedly reported in various
professional groups (beauticians, nail designers, dental technicians) in connection
with the handling of acrylate adhesives. A link to medical use has been identified
by various case studies when it is used to close wounds.18–20 This is based on the
predication of it being a type IV allergic reaction. Sensitisation occurs through
the acrylate monomer (no longer the inert polymer) that binds to keratin in
the skin. Mediating dendritic cells, which are only present in the cutis, trigger a
contact allergy characterised by hives and rashes.21 No case studies can be found
in the literature describing this in the context of an intravascular application of
cyanoacrylate derivatives, something which has been performed for decades,
for example, to treat gastric bleeding and intracranial aneurysms. This could be
explained by the fact that the acrylate monomer is inserted directly into the vessel
through a catheter. When applied correctly, there should be no contact to the
immune-mediated cells in the skin.
In the course of varicose vein treatment, isolated cases of temporary urticarial
efflorescence have been observed, which respond to anti-histamines and steroids.
Only one case can be found in the literature, described by Kathleen Gibson as part
of the WAVES study.22 Since the symptoms do not correspond to a typical type
IV allergy, the author is of the opinion that there needs to be a discussion on the
481
alternative mechanisms triggering this allergic reaction. In every case, the patient’s
• T Hirsch
allergy history should be touched upon in the preoperative discussion with the
patient as an existing allergy to acrylates and suspicious events in the patient’s
history represent an absolute contraindication for the method.
Summary
• Acrylate adhesion of saphenous varicose veins exhibits an efficacy on par with

thermal methods but with minimal invasiveness.
• The procedure has few side-effects and is safe and easy to learn. The risk of
nerve damage is much lower than thermal methods due to the absence of
tumescent anaesthesia.
• A painful, localised reaction that is frequently observed in the early
postoperative phase and the risk of an allergic reaction to the implant should
be discussed with the patient in preparation for the procedure.
• Acrylate adhesion of saphenous varicose veins constitutes a useful add-on to
the established methods. It is attractive to many patients due to the special
areas of application mentioned above and because it is a gentle procedure.
References
1. Almeida JI, Min RJ, Raabe R, et al. Cyanoacrylate adhesive for the closure of truncal veins: 60-day swine
model results. Vasc Endovasc Surg 2011; 45: 631–35.
2. Kolluri R, Gibson K, Cher D, et al. Roll-in phase analysis of clinical study of cyanoacrylate closure for
incompetent great saphenous veins. J Vasc Surg Venous Lymphat Disord 2016; 4 (4): 407–15.
3. Johnson GW, Smith GW. Effect of methyl cyanoacrylate on the central nervous system: A preliminary
evaluation in nerve anastomosis. Surg Forum 1963; 14: 414–16.
4. Trott AT. Cyanoacrylate tissue adhesives. An advance in wound care. JAMA 1997; 277 (19): 1559–60.
5. Brothers MF, Kaufmann JC, Fox AJ, Deveikis JP. n-Butyl 2-cyanoacrylate-substitute for IBCA in
interventional neuroradiology: Histopathologic and polymerization time studies. Am J Neuroradiol
1989; 10 (4): 777–86.
6. Sohn JJ, Gruber TM, Zahorsky-Reeves JL, et al. Comparison of 2-ethyl-cyanoacrylate and 2-butyl-
cyanoacrylate for use on the calvaria of CD1 mice. J Am Assoc Lab Anim Sci 2016; 55 (2): 199–203.
7. Toriumi DM, Raslan WF, Friedman M, et al. Histotoxicity of cyanoacrylate tissue adhesives. A
comparative study. Arch Otolaryngol Head Neck Surg 1990; 116 (5): 546–50.
8. Nitsch A, Pabyk A, Honig JF, et al. Cellular, histomorphologic, and clinical characteristics of a new octyl-
2-cyanoacrylate skin adhesive. Aesthetic Plast Surg 2005; 29 (1): 53–58.
9. Vinters HV, Galil KA, Lundie MJ, et al. The histotoxicity of cyanoacrylates. A selective review.
Neuroradiology 1985; 27 (4): 279–91.
10. Leggat PA, Smith DR, Kedjarune U. Surgical applications of cyanoacrylate adhesives: A review of
toxicity. ANZ J Surg 2007; 77 (4): 209–13.
11. Almeida JI, Javier JJ, Mackay EG, et al. Two-year follow-up of first human use of cyanoacrylate adhesive
for treatment of saphenous vein incompetence. Phlebology 2015; 30 (6): 397–404.
12. Proebstle T, Alm J, Dimitri S, et al. The European multicenter cohort study on cyanoacrylate
embolization of refluxing great saphenous veins. J Vasc Surg Venous Lymphat Disord 2015; 3 (1): 2–7.
985–94.
14. Çalık ES, Arslan Ü, Ayaz F, et al. N-butyl cyanoacrylate in the treatment of venous insufficiency-the
effect of embolisation with ablative polymerisation. Vasa 2016; 45 (3): 241–46.
15. Quinn JC, Mittal N, Baisre A, et al. Vascular inflammation with eosinophils after the use of n-butyl
cyanoacrylate liquid embolic system. J Neurointerv Surg 2011; 3 (1): 21–24.
482
16. Wang YM, Cheng LF, Li N. Histopathological study of vascular changes after intra-arterial and

intravenous injection of N-butyl-2-cyanoacrylate. Chin J Dig Dis 2006; 7 (3): 175–79.
17. Hirsch T. Non-thermal endovenous treatment: Acrylate adhesion of varicose saphenous veins.
Phlebologie 2017; 46: 143–147.
18. Leggat PA, Kedjarune U, Smith DR. Toxicity of cyanoacrylate adhesives and their occupational impacts
for dental staff. Ind Health 2004; 42 (2): 207–11.
19. Studer M, Pouget-Jasson C, Waton J, et al. How testing allergic contact dermatitis from
octylcyanoacrylate tissue glue (Dermabond®). Revue Francaise d’Allergologie 2010; 50: 75–6.
20. Bowen C, Bidinger J, Hivnor C, et al. Allergic contact dermatitis to 2-octyl cyanoacrylate. Cutis 2014;
94 (4): 183–86.
21. Calnan CD. Cyanoacrylate dermatitis. Contact Dermatitis 1979; 5: 165–67.
VenaSeal System (the WAVES Study). Vascular 2016; 25 (2): 149-56.
• T Hirsch
483
Retrospective review
of complications in 577
consecutive cases of cryolaser
and cryosclerotherapy guided
by augmented reality
Introduction
Liquid sclerotherapy is recommended as the method of choice for ablation of
telangiectasias and reticular varicose veins (C1) (Grade 1B).1 Cryolaser and
cryosclerotherapy (CLaCS) is a new procedure that has been developed since 1999
and, in the last few years, has gained relevance; at present, CLaCS has adepts in more
than 20 countries. It is the synergy of transdermal laser selective photothermolysis
and injection sclerotherapy by dextrose 75%. Dextrose 75% is the most common
sclerosing agent used in Brazil and the choice of 35.34% of Brazilian vascular
surgeons.2 CLaCS is performed on telangiectasias and their causative feeder veins,
or on reticular veins up to 1.5mm (internal diameter by ultrasound).
The CLaCS technique employs the following features: (1) augmented reality
visualisation of the feeder veins; (2) application of transdermal laser energy to the
feeder veins and overlying telangiectasias; (3) injection of a sclerosant in the feeder
vein and surface telangiectasias; and (4) skin temperature protection and numbing
of the skin with application of a flow of cold air throughout the procedure.3–5
Dextrose 75% sclerotherapy is the targeted osmotic ablation of telangiectasias and
varicose veins by intravenous injection of a hypertonic dextrose solution. Dextrose
75% destroys the venous endothelium immediately after thermal transdermal vein
wall damage. The purpose of CLaCS is to achieve sclerosis with the least possible
amount of thrombosis.
Our group has been using the synergy of light and dextrose 75% for over two
decades.6,7 Since 2005, we have been using a protocol that we named “CLaCS
guided by augmented reality”. The results are impressive (Figure 1) and that is the
reason why many vascular surgeons are using it.
The aim of this review is to evaluate the complications of the CLaCS procedure.
The CLaCS procedure

The files of all 577 patients were electronically reviewed by keywords. Patients were
treated by CLaCS at the same clinic and by the same physician from August 2011
to November 2016.
Inclusion factors:
485
K Miyake, MH Grill et al
Retrospective review of complications in 577 consecutive cases of cryolaser and cryosclerotherapy guided by augmented reality •
Figure 1: Lateral view of the right thigh. Patient with telangiectasias and reticular veins and no axial reflux, CEAP 1
and Score 6 (Score 9–1).8,9 Prior treatment with augmented reality and showing some feeder veins. Control photo after
three years (the patient was treated with five CLaCS sessions).
• Female patients complaining about leg telangiectasias (spider veins or thread

veins)
• Patients should not have complaints of pain and/or swelling
• Fitzpatrick10 skin type 1–5
• CEAP 1.
Exclusion factors:
• Reflux in saphenous veins
• Reflux in perforant veins
• Feeder veins with more than 1.5mm internal diameter measured by ultrasound
in standing position
• Fitzpatrick skin type 6.
CLaCS protocol:
• The first step in the CLaCS protocol is photodocumentation
• The skin cooling device is set on maximum power. Cold air temperature varies
from -5 degrees Celsius to -20 degrees Celsius and the skin generally cools
from 33 degrees Celsius to 5–15 degrees Celsius. If the skin gets white and
icy, it means it is freezing and the skin cooling device should be set to a lower
power setting11,12
• Transdermal laser (Harmony Long Pulse 1064nm, Alma Lasers) is used to
perform the first damage on the telangiectasias and feeder veins.13 ND:Yag
1064nm, 6mm spot size and long pulse are used
• The laser is set to 70J/cm2 and 15msec if the skin is light or not tanned.
• Fluence is lowered to 60J/cm2 or 50J/cm2 if the patient complains about
pain, the Fitzpatrick classification is high (4 or 5) or the patient is tanned
• The same setting is used to treat telangiectasias, feeder veins and reticular veins.
• The augmented reality device used (VeinViewer, Christie Medical) is set and
the feeder veins under the telangiectasias are projected in a rectangular area
486
Retrospective review of complications in 577 consecutive cases of cryolaser and cryosclerotherapy guided by augmented reality
Figure 2: Photodocumentation showing a complication. A female patient, Fitzpatrick 2, was treated with CLaCS under
sedation due to pain. During the procedure, the air cooling device stopped working and the right foot was treated with
no cooling while another air cooling device was initialised. Redness was noted minutes after. In minutes, small blisters
were observed. It is important to note that the patient had a hypochromic area near the ankle prior to treatment. The
six-month follow-up is shown on the photo at the bottom right.
(75mm x 60mm). An average of 30 laser shots are delivered with one to

three passes on telangiectasias and feeder veins. Then, injection sclerotherapy
with dextrose 75%, a 3ml syringe and a 27G needle is performed. Injection
sclerotherapy is also performed under skin cooling.
• 2–3mm cotton balls are placed on the sites of injections with adhesive tape.
Patients are advised to remove the cotton balls after two hours.
• No compression stockings or bandages are recommended.
• Sun exposure and exercises are allowed on the following day.
• The recommended interval between sessions is 30 days and the average session
duration is one hour.
Complications
The incidence of complications was as follows: pigmentation 1.35%, skin burn
0.19% (Figure 2) and matting 0.06%. More severe complications have not been
observed since the creation of CLaCS. The technique has been performed in
•
approximately 3,000 patients since 1999, with no cases of anaphylaxis, large tissue
necrosis, skin ulcer, visual disturbances, headache, migraine, stroke or transient

ischaemic attack.
The CLaCS technique was developed by synergising well-known methods that
had “medium power” on sclerotherapy. One of the goals was to create a method
that was free of or had very few complications. Dextrose 75% is free of allergens
and its viscosity protects the reflux to the capillary system that may cause skin
ulcers after sclerotherapy.14
In 2016, we evaluated the volume of dextrose per shot—this was an internal
evaluation to help teaching and has not been published yet. Seventy two consecutive
CLaCS sessions were evaluated and the average number of laser shots per session
487
was 478 (35–1,659 laser shots). The average session duration was 45 minutes and
the average injected volume was 4.75ml. That means that a typical CLaCS session
has 400–500 laser shots and uses 0.01ml per laser shot.
It is important to remember that all transdermal laser manufacturers’ protocols
suggest almost twice the amount of energy that we use. We prefer to use less
energy and “cook” the vein with more passes. This concept was based in a study
we performed in 1999 and that unfortunately was rejected by all medical journals
we submitted it to. We investigated anatomopathological aspects to demonstrate
the effect of the 1064nm ND:Yag laser on reticular veins. Laser shots were applied
to a 5cm segment before surgical removal by crochet hook. At naked eyes, it was
difficult to conclude that the veins had been damaged. Lasered and non-lasered
segments were sent for a blinded, independent, anatomopathological haematoxylin
and eosin analysis. No skin damage was observed. Endothelial hypertrophy
demonstrated vein damage (varicose vein) in control or lasered segments. Lasered
venous segments presented intercellular oedema in all cases, whereas no control
segment showed that change (p=0.0046). Eight out of eight lasered venous segments
showed lesions of elastic fibre in the media endothelial vesicles, while none of the
control venous segments presented similar lesions (p=0.01431). We concluded that
selective venous thermolysis was successfully achieved with the 1064nm ND:Yag
applied to small varicosities.12,15–18
CLaCS is a private treatment and, therefore, patients need to pay for the
procedures from their own pockets. It is an aesthetic treatment and is as private as
an aesthetic dermatological treatment or an aesthetic plastic surgery. Most of the
phlebological procedures worldwide are financed by government healthcare systems
or insurance companies. That means the price is fixed and low. This low cost directs
physicians to focus on quantity and not necessarily on quality. If the physician
spends time pursuing better diagnosis with augmented reality, for instance, or
performing photodocumentation, he/she will not receive a higher payment. On
the other side, if patients are unhappy with the result, as they did not pay from
their own pocket, they will not come back to complain. They will search for
another doctor on the healthcare system list or believe that there is no treatment
for the aesthetic lesions. Unfortunately, it is common to see patients who receive
prescription of medications that promise improvements on the vein walls, and
recommendation for compression stockings—and due to the lack of a successful
aesthetic treatment they will cover their legs for the rest of their lives.
In Brazil, it is a whole different scenario. Women began to increasingly expose
their legs in the 60s. Mini-skirts, bikinis, shorts and the tropical weather led
women to ask Brazilian vascular surgeons to search for a better treatment. At that
point, private aesthetic phlebology was born. When the vascular surgeon spends
15 minutes to take photos and organise them, he/she needs to charge for that.
Thorough photodocumentation and investment in treatment mean payment must
come from the patient’s pocket—that is aesthetic phlebology. This is positive
because we, as physicians, do not have to deal and negotiate with huge corporations
and/or the government. Private medicine is a niche where the physician becomes
a businessman and he/she needs to commit to the result, the follow-up and the
“after-sales” service. Yes, we provide a service and need to have a commitment to
the result.
488
Photodocumentation is not complicated but you need to have discipline and
Retrospective review of complications in 577 consecutive cases of cryolaser and cryosclerotherapy guided by augmented reality
follow some protocols. Fortunately, you do not need a huge investment. CLaCS
requires the following equipment, which sums up to £70,000–150,000 depending
on the models used. We recommend that the “phlebosuite” (a complete aesthetic
phlebology procedure room) should have:
• Duplex ultrasound
• Augmented reality
• Photodocumentation
• ND:Yag Long Pulse 1064nm 6mm spot size transdermal laser
• Skin air cooling device.
Conclusion
When treating veins with aesthetic purposes, it is imperative to avoid complications.
Therefore, it is recommended to pursue standardised procedures that yield
no complications.15,16 The CLaCS technique was never compared to injection
sclerotherapy and we encourage those who have equipoise with the two techniques
to design comparative studies. We believe that, at present, it is more important to
evaluate the complication rate with these techniques, as there is a huge potential
clinical benefit that will impact patients’ quality of life. Asymptomatic but
unpleasantly looking legs affect women worldwide with an incidence that is much
greater than we would expect.
Summary
• CLaCS (Cryolaser and cryosclerotherapy) is a new procedure that has been

developed since 1999 and, in the last few years, has gained relevance. It is
the synergy of transdermal laser selective photothermolysis and injection
sclerotherapy by dextrose 75%.
• We reviewed 577 patients treated between August 2011 and November 2016
and found the following complications: pigmentation in 1.35% of the cases,
skin burn in 0.19% and matting in 0.06%.
• CLaCS is an aesthetic treatment and is as private as an aesthetic
dermatological treatment or an aesthetic plastic surgery.
• Private medicine is a niche where the physician becomes a businessman
and he/she needs to commit to the result, the follow-up and the
“after-sales” service.
•
•
When treating veins with aesthetic purposes, it is imperative to avoid

complications. Therefore, it is recommended to pursue standardised
procedures that yield no complications.
References
1. Gloviczki P, Comerota AJ, Dalsing MC, et al. The care of patients with varicose veins and associated
chronic venous diseases: clinical practice guidelines of the Society for Vascular Surgery and the
American Venous Forum. J Vasc Surg 2011; 53 (5 Suppl): 2S–48S.
2. Figueiredo M, Figueiredo M F. Survey about liquid sclerotherapy of lower limb varicose veins. J Vasc
Surg 2013; 12 (1): 10–15.
489
3. Miyake RK, Zeman HD, Duarte FH, et al. Vein imaging: A new method of near infrared imaging, where
a processed image is projected onto the skin for the enhancement of vein treatment. Dermatol Surg
2006; 32 (8): 1031–38.
4. Miyake K. Prevalence of small varicosities among patients with or without telangiectasias on the lower
limbs estimated by augmented reality examination. Int Angiology 2013; 32 (5) (Suppl 1): S124.
5. Miyake RK. Fatores preditivos da lesão cutânea por luz intensa pulsada. (Tese de Doutorado). São
Paulo: Faculdade de Medicina da Universidade de São Paulo, 1999. 47 p.
6. Miyake RK, Miyake H, Kauffman P. Skin temperature measurements during intense pulsed light
emission. Dermatol Surg 2001; 27 (6): 549–54.
7. Miyake RK, Miyake H. PhotoDerm VL on darker skin. In: Proceedings. Annual Congress – North
American Society of Phlebology. Washington DC, 1996; 10.
8. Miyake K. Case report of 195 patients classified by duplex scanning and augmented reality, and
treated by cryo-laser & cryo-sclerotherapy: Results and complications. Int Angiol 2013; 32 (5) (Suppl
1): S153.
9. Miyake K. Laser treatment of reticular and subcuticular veins. In: Greenhakgh RM. Vascular and
Endovascular Challenges Update. London: BIBA Publishing; 2016. 555–62.
10. Fitzpatrick TB. Soleil et peau. J Médicine Esthétique 1975; 2 (7): 33.
11. Miyake RK, Duarte FH, Kikuchi R, Fidelis RJR. Pain reduction using cooled forced air at -20°c during
laser and sclerotherapy. Annals of American Society of Laser in Medicine Surgery; Dallas: 2002.
12. Miyake RK, Duarte FH, Fidelis RJR, Miyake H. New leg veins air cooled treatment using 1064nm laser
combined with scleroterapy. Technique description and one year follow up. Las Med SCI 2003; 18: 522.
13. Miyake RK, Miyake H, Telles MA, et al. Avaliação anatomopatológica do efeito do laser “Vasculight”
(1.064 nm) sobre microvarizes. Resumos. XXXIII Congresso Brasileiro de Angiologia e Cirurgia Vascular;
1999; Belo Horizonte: SBACV; 1999. 60.
14. Miyake RK, King JT, Kikuchi R, et al. Role of injection pressure, flow and sclerosant viscosity in causing
cutaneous ulceration during sclerotherapy. Phlebology 2012; 27 (8): 383–89.
15. Morrison N, Cavezzi A, Bergan J, Partsch H. Regarding “Stroke after varicose vein foam injection
sclerotherapy.” J Vasc Surg 2006; 44 (1): 224–25.
16. Forlee MV, Grouden M, Moore DJ, Shanik G. Stroke after varicose vein foam injection sclerotherapy. J
Vasc Surg 2006; 43 (1): 162–64.
490
Reducing hyperpigmentation
after sclerotherapy using
an antithrombotic drug
A Gonzalez Ochoa
Introduction
Telangiectasia and reticular veins are common, affecting 50% of women by
the age of 50 years. In men, the epidemiology is more difficult to assess since
men tend to be less concerned about the condition in the initial stages, seeking
medical treatment only when there is a presence of varicose veins or if they are
very symptomatic. Although in most cases telangiectasias and reticular veins are
not a life-threatening disease, they do affect quality of life and can significantly
affect self-confidence and cause patients to feel older and less attractive. They can
also limit simple recreational situations such as going to the beach or a public
pool. Some sources assert that telangiectasia and reticular veins are the number one
cosmetic concern for women in the USA.1–5
Chemical sclerotherapy is the most effective and widely used method of treatment
for telangiectasia. With the correct technique, it is a simple procedure that enables
rapid return to daily activities and has low cost. It is usually well tolerated by
patients, requiring no anaesthesia.
Many patients seek treatment a few days or weeks before an event or trip with
the hope that they can look great for their special occasion. The reality is that
their legs are likely to look a bit worse before they look better. Even with mild
agents and a good technique, the treatment has some side-effects, which can be an
important issue in a procedure that is undertaken mostly for cosmetic reasons.3,6,7
Sclerotherapy
Chemical sclerotherapy is the most widely used method because of its low technical
complexity, rapid return to daily activities, and low cost. It is almost painless,
requiring no anaesthesia, with discomfort being related to venepuncture and
drug infusion. This therapy uses a variety of chemical agents, and the currently
available sclerosants are categorised according to their mechanism of action into
hyperosmolar agents (e.g. hypertonic glucose and hypertonic saline), detergent
agents (e.g. polidocanol and sodium tetradecyl sulfate), and chemical irritants (e.g.
chromated glycerin) that primarily promote irritation, dehydration, and destruction
of the endothelial cells, resulting in elimination of the vein.8,9
Hyperpigmentation
Hyperpigmentation is a brownish discoloration of the skin. The incidence
of transient hyperpigmentation ranges from 10% to 30% with spontaneous
491
A Gonzalez Ochoa
A B
Reducing hyperpigmentation after sclerotherapy using an antithrombotic drug •
Figure 1: (A) Initial varicose vein and (B) One-month after treatment.
resolution after six months in 70% of cases. Permanent pigmentation, which is

defined as staining after one year, affects 1–2% of patients. Its onset is gradual
after the treatment session with a peak at 6–8 weeks. It is caused by the migration
of melanin pigment to the skin and by the deposition of haemosiderin in the
dermis. Perivascular fragmentation of red blood cells occurs after fragmentation by
macrophages. The intracellular fragments in the macrophage cytoplasm are further
compartmentalised into haemoglobin containing globules. Evidence suggests that
the incidence of hyperpigmentation is most likely to occur with increased vessel
diameter, higher and stronger agent concentrations (e.g. polidocanol vs. chromated
glycerin), lack of postoperative compression, and post-treatment sun exposure.
Thrombosis and hyperpigmentation

The incidence of residual thrombi is in direct relation with the diameter of the
treated target vessel, usually less 10% in telangiectasia, 30% in reticular veins and
up to 80% in varicose veins.
Superficial thrombophlebitis after sclerotherapy is reported at a frequency
of 4–7.5%. It occurs primarily after treatment of larger varicose veins and is
manifested by an area of erythema, heat, and tenderness over an indurated venous
segment. This usually develops within a few weeks of treatment and involves the
treated area or a venous segment proximal or distal to the injection site. In case
of post sclerotherapy superficial thrombophlebitis, assessment should be made to
understand the involvement of the proximal saphenous veins and concomitant
deep vein thrombosis.
Persistent thrombi are thought to cause “perivenulitis”. The “perivenulitis”
favours extravasation of red blood cells through a damaged endothelium or by
an increase in permeability of treated endothelium. Thus, the development of
492
Reducing hyperpigmentation after sclerotherapy using an antithrombotic drug
Figure 2: Software-treated area.
post sclerotherapy hyperpigmentation is influenced by the extent of endothelial

destruction with resultant inflammation and extravasation of red blood cells.10–17
Sulodexide effect
•
Sulodexide is a highly purified mixture of glycosaminoglycans composed of low
A A Gonzalez Ochoa
molecular weight heparin (80%) and dermatan sulphate (20%). For a long time
it was considered a “minor” antithrombotic agent and, like other heparin-like
substances, has gained renewed interest especially during the last decade. In fact,
after oral administration, sulodexide displays new biological properties, such as
the ability to regulate endothelium blood cell interactions, counteract vascular
inflammatory and proliferative changes, and protect and restore structures and
functions of the injured endothelium, all this while maintaining, to a mild degree,
those inherent antithrombotic and profibrinolytic activities.18–24
With the hypothesis that residual thrombosis is the primary cause of
hyperpigmentation, we researched the effect of using a medication with
antithrombotic effect in combination with sclerotherapy. The objective is to
reduce or prevent the formation of these residual thrombi and therefore reduce
the incidence of hyperpigmentation without increasing the risk of even minor
haemorrhagic complications and still reaching the desire effect of vein clearance.
In a prospective, randomised fashion, 104 patients with telangiectatic, reticular
or varicose veins that were candidates for sclerotherapy were analysed from
December 2016 to May 2017. Patients were divided in two groups: sulodexide and
control. The sclerosant agent used was Aethoxysklerol (lauromacrogol 400) from
Kreussler Pharma, in concentration according to vein diameter as recommended.
We normally use a 3ml syringe with a 30G needle for veins smaller than 2mm with
0.5ml maximum sclerosing volume per injection site and 27G in larger veins with
2ml maximum sclerosing agent per site; no more than 10ml in total per session.
In the sulodexide group, patients were given the same treatment protocol of
sclerotherapy plus: 25mg bid oral dose beginning on the day of first evaluation and
493
continue during the three months of follow-up, usually beginning the sclerotherapy
A Gonzalez Ochoa
treatment in less than seven days after first visit. In patients who wanted to begin
treatment immediately a single intravenous dose of 50mg was given followed by a
conventional oral dose of 25mg bid.
After one month, photographic control was taken (Figure 1). The variables
taken for analysis were: area of hyperpigmentation, area of vein disappearance,
presence of haematoma or ecchymosis, skin tone intensity of hyperpigmentation.
Using computer software, the area of detected hyperpigmentation was marked and
compared with the initial area of treatment and a percentage of affected areas was
given (Figure 2). The same method was used to evaluate vein disappearance. Using
the Von Luschan’s scale, a numeric value was given to area of pigmentation, taking
the area of darker tone present for the record. The photograph was also analysed by
two blind evaluators. The average of the three results was the one taken for analysis.
No more sclerotherapy was performed near the zone of hyperpigmentation until
the next check-up at three months, when the same parameters were taken.
Continuous variables were expressed as mean (SD) or median values, and
categorical variables were expressed as absolute and relative frequencies. The Student
t test or the nonparametric Mann-Whitney test was used to compare continuous
variables. The Fisher exact test or the X2 test was used to compare categorical
variables. Groups were compared using the Goodman test for multinomial
populations. The level of significance was set at less than 5% (p<0.05).
Results
Baseline demographic characteristic in control group vs. sulodexide group show:
mostly female gender (94 vs. 92%); median age (years) 40.3 vs. 43.1 years;
Hispanic ethnicity in 87% vs. 78%; previous varicose vein surgery in 12 vs .17%
and Fitzpatrick skin type III and IV in 57 v.s 72% and body mass index median
24.3 vs. 31.4 with no statistical difference between both groups except regarding
body mass index which was higher in the sulodexide group (p=0.003).
The baseline vein disease in the control group vs. sulodexide group show:
telangiectasia (%) 82 vs. 79; reticular veins (%) 51 vs. 46; varicose veins (%) 70
vs. 56; 5 or more segments involve (%) 62 vs. 70 with no significant difference
between the two groups.
In the therapeutic endpoints results: hyperpigmentation was present in the
control group vs sulodexide at one month (%) 22.4 vs. 13.7 (p=0.001) and at three
months 8.9 vs 3.5 (p=0.04). Vein clearance (%) 40 vs. 40 at one month and 77
vs. 76 at three months with no significant difference and no mayor complications
in either group
Conclusion
The value of sclerotherapy as a therapeutic method for removing unwanted blood
vessels is unquestionable, but the technique is not free of adverse effects. Since
it is mostly used with a cosmetic purpose, the aesthetic result is very important
in a patient population that most of the time has an expectation of immediate
vein disappearance.
The benefit of early thrombectomy to reduce the incidence of residual
pigmentation has been reported,25 but it is still painful for the patient and it must
494
be done in the early weeks for the thrombus to be correctly removed; since it is not
Reducing hyperpigmentation after sclerotherapy using an antithrombotic drug

widely covered by healthcare systems, the cost of extra consultation must be taken
into account.
We believe formal anticoagulation would probably help limiting the formation
or residual thrombosis; however, this would pose a higher risk of other minor
complication such as bleeding, haematoma and ecchymosis in a population that
normally is very physically active. Using a mild antithrombotic drug, we managed
to significantly reduce the incidence of hyperpigmentation without increasing this
risk of major bleeding.
There have been studies focusing on the use of phlebotonics and other drugs,
trying to reduce the inflammation response in patients treated with sclerotherapy
and laser vein ablation,26,27 but these did not focus on reducing thrombosis and
pigmentation in the initial phase. There has been some focus on the treatment of
permanent hyperpigmentation with laser after one year of the initial treatment.28
We believe these results will spark interest in this field. More research is needed
to confirm these finding.
Summary
• Although in most cases telangiectasias and reticular veins are not a life-
threatening disease, they do affect quality of life.
• Chemical sclerotherapy is the most effective and widely used method of
•
treatment for telangiectasia. It is a simple procedure, which enables rapid
A Gonzalez Ochoa
return to daily activities and has low cost.
• The incidence of transient hyperpigmentation ranges from 10% to 30%
with spontaneous resolution after six months in 70% of cases. Permanent
pigmentation affects 1–2% of patients.
• With the hypothesis that residual thrombosis is the primary cause of
hyperpigmentation, we researched the effect of using sulodexide in
combination with sclerotherapy.
• When comparing sulodexide and control groups, the sulodexide group
showed a significant reduction in the presence of pigmentation at one and
three months, with no presence of major side-effects or complications related
to the medication.
• Using a mild antithrombotic drug, we managed to significantly reduce the
incidence of hyperpigmentation without increasing this risk of major bleeding.
References
1. Gloviczki P, Comerota AJ, Dalsing MC, et al. The care of patients with varicose veins and associated
chronic venous diseases: Clinical practice guidelines of the Society for Vascular Surgery and the
American Venous Forum. J Vasc Surg 2011; 53: 2S–48S.
2. Watson JJ, Mansour A. Cosmetic sclerotherapy. J Vasc Surg Venous and Lymphat Disord 2017; 5: 437–45.
3. Pappas PJ, Lakhanpal S, Nguyen KQ, Vanjara R. The Center for Vein Restoration Study on presenting
symptoms, treatment modalities, and outcomes in Medicare-eligible patients with chronic venous
disorders. J Vasc Surg Venous and Lymphat Disord 2018; 6: 13–24.
495
4. Kaplan RM, Criqui MH, Denenberg JO, et al. Quality of life in patients with chronic venous disease: San
A Gonzalez Ochoa
Diego population study. J Vasc Surg 2003; 37: 1047–53.

5. Lohr JM, Bush RL. Venous disease in women: Epidemiology, manifestations, and treatment. J Vasc Surg
2013; 57: 37S–45S.
6. Murad MH, Coto-Yglesias F, Zumaeta-Garcia M, Elamin MB. A systematic review and meta-analysis of
the treatments of varicose veins. J Vasc Surg 2011; 53: 49S–65S.
7. Bertanha M, Sobreira ML, Pinheiro Lúcio Filho CE, et al. Polidocanol versus hypertonic glucose for
sclerotherapy treatment of reticular veins of the lower limbs: Study protocol for a randomized
controlled trial. Trials 2014; 15: 497.
8. Bertanha M, Jaldin RG, Moura R, et al. Sclerotherapy for reticular veins in the lower limbs: A triple-blind
randomized clinical trial. JAMA Dermatol 2017; 153 (12): 1249–55.
9. Smith PC. Management of reticular veins and telangiectases. Phlebology 2015; 30 (2 Suppl): 46–52.
10. O’Donnell TF, Eaddy M. Assessment of thrombotic adverse events and treatment patterns associated
with varicose vein treatment. J Vasc Surg Venous and Lymphat Disord 2015; 3: 27.
11. Cavezzi A, Parsi K. Complications of foam sclerotherapy. Phlebology 2012; 27 (Suppl 1): 46–51.
12. Yiannakopoulou E. Safety concerns for sclerotherapy of telangiectases, reticular and varicose veins.
Pharmacology 2016; 98 (1–2): 62–69.
13. Kern P, Ramelet AA, Wütschert R, Hayoz D. Compression after sclerotherapy for telangiectasias and
reticular leg veins: A randomized controlled study. J Vasc Surg 2007; 45: 1212–6.
14. Alòs J, Carreño P, López JA, et al. Efficacy and safety of sclerotherapy using polidocanol foam: A
controlled clinical trial. Eur J Vasc Endovasc Surg 2006; 31 (1): 101–07.
15. Goldman MP, Sadick NS, Weiss RA. Cutaneous necrosis, telangiectatic matting, and hyperpigmentation
following sclerotherapy etiology, prevention, and treatment. Dermatol Surg 1995; 21 (1): 19–29.
16. Goldman MP. Complications and adverse sequelae of sclerotherapy. In: Bergan J (ed). The Vein Book
2007.
17. Guex JJ. Complications of sclerotherapy: An update. Dermatol Surg 2010; 36 (Suppl 2):1056–63.
18. Weiss RA, Sadick NS, Goldman MP, Weiss MA. Post-sclerotherapy compression: Controlled comparative
study of duration of compression and its effects on clinical outcome. Dermatol Surg 1999; 25 (2): 105–
08.
19. Walenga J, Fareed J. Sulodexide for the extended treatment of venous thromboembolism. Int Angiol
2016; 35 (6): 531–33.
20. Andreozzi GM. Sulodexide in the treatment of chronic venous disease. Am J Cardiovasc Drugs 2012;
12 (2): 73–81.
21. Errichi BM, Cesarone MR, Belcaro G, et al. Prevention of recurrent deep venous thrombosis with
sulodexide: The SanVal registry. Angiology 2004; 55 (3): 243–49.
22. Flota LF, Fratti A. Chronic venous disease treated with sulodexide. Int Angiol 2017; 36: 558–64.
23. Andreozzi GM, Bignamini AA, Davi G, et al. Sulodexide for the prevention of recurrent venous
thromboembolism: The SURVET Study: A Multicenter, randomized, double-blind, placebo controlled
trial. Circulation 2015; 132 (20): 1891–97.
24. Wu B, Lu J, Yang M, Xu T. Sulodexide for venous leg ulcers. Cochrane review 2 jun 2016
25. Scultetus AH, Villavicencio JL. Microthrombectomy reduces postsclerotherapy pigmentation:
Multicenter randomized trial. J Vasc Surg 2003; 38: 896–903.
26. Bogachev VY, Boldin BV, Lobanov VN. Benefits of micronized purified flavonoid fraction as adjuvant
therapy on the inflammatory response after sclerotherapy. Int Angiol 2018; 37 (1): 71–78.
27. Bogachev VY, Boldin BV, Lobanov VN, et al. Adjuvant phlebotrophic therapy and its effect on anti-
inflammatory response after sclerotherapy. Angiol Sosud Khir 2016; 22 (4): 90–95.
28. Mlosek RK, Woźniak W, Malinowska S, et al. The removal of post-sclerotherapy pigmentation following
sclerotherapy alone or in combination with crossectomy. Eur J Vasc Endovasc Surg 2012; 43 (1): 100–05.
496
Photodocumentation in
aesthetic phlebology
Introduction
Venous pathologies in the lower limbs are closely related to the skin and subcutaneous
tissue. Ectoscopy is a fundamental part of the physical examination and is the basis
of the comprehensive classification system for chronic venous disorders (CEAP)
clinical classification.1 From early presentations, such as telangiectasias in patients
classified as CEAP 1, through varicose tributaries (CEAP 2), oedema (CEAP 3) and
ochre dermatitis (CEAP 4), to venous stasis ulcers (CEAP 5 and 6), all have skin
manifestations.
When we reduce the spectrum to venous insufficiency at its earliest stage, with
the involvement of only small varicose veins and telangiectasias, dermatological
alterations may be the only manifestation of the disease. Photography is the tool
the vascular surgeon has to document and quantify the course of treatment. Proof
of this is that the work involving the treatment of this subgroup, whether with
sclerotherapy, laser, or the combination of both, uses pre and post photos as the
main parameter to measure the success of the therapy employed.2–6
Although in some academic services photography is taught for use in the control
of the venous lesions in the lower limbs, in clinical practice it is rare to find services
that photograph patients. We believe that some of the reasons for the low number
of adopters of this practice are the cost of the equipment, the time required for the
photography and the matching of the photos before and after, the lack of technical
knowledge in photography and the difficulty of organising the image files.
Our group has gone through four stages in the maturation of the photographic
technique: the first one is represented by Hiroshi Miyake, vascular surgeon who
dedicated his life to the treatment of aesthetic venous lesions. He founded our
clinic in the early 60s and used classic 35mm film cameras and a lot of technical
rigor for documentation. The photograph was made of photographic film for slides
and one to two photos were taken in patients with more complex cases. The second
phase came with the advent of digital photography in the late 90s, allowing cost
reduction, immediate viewing, and increased photo frequency. With this increase
came the problem of storing and organising photographs. The third phase was from
2005 to 2011, approximately, when we used specific software with semiprofessional
digital cameras. We made an adaptation of a dermatology system by hanging it on
the ceiling of the room. Such an arrangement allowed comparing before then with
a “ghosting” system to align the post-treatment images with pre-treatment ones
(Intellistudio, Mirror Canfield). The system was discarded because its cost was very
high and because it often presented technical problems. The forth and current
phase is characterised by the use of digital single-lens reflex (DSLR) cameras
cropped frame and the tethering technique (use of cable for immediate storage)
and its description is the core of this text.
497
Photodocumentation in aesthetic phlebology • K Miyake, MH Grill and RB Fukushima
Figure 1: Photodocumentation with external flash pointed to a white ceiling and the camera is connected by a
tethering cable to a two-screen computer.
The objective of this chapter is to briefly discuss the main aspects of photography
to assist the physician in photographically documenting his/her treatment, to
improve his/her photographic technique and to organise the image files. We aim
to deliver a simple and effective protocol for the vascular surgeon to obtain high
resolution and reproducibility in their photos.
Photographic technique
A professional photographer uses, in his/her studio, the manual mode to establish
all the parameters for the photographs, to obtain the best image and, mainly, to
transmit the established message effectively. For this, he/her has full control of the
ambient light, flash and equipment. This, in spite of being the ideal scenario, is not
necessary seen on the day to day of doctors.
We use photography as one of our working tools. However, our environment is
not dedicated to photography and we have little time to establish all the parameters
mentioned above. Our goal is to produce similar images at various stages of
treatment without using any trick to infer improvement.7 We are adept of DSLR
machines, in automatic mode with use of external flash in TTL mode reflected to
the white ceiling (Figure 1).
Our objective is that only clinical changes are noticeable from photo to photo.
We must establish a routine, always photographing in the same environment, with
the same camera and with equivalent photographic parameters. We photographed
100% of patients undergoing procedures for more than a decade. Since 2011, we
have photographed with DSLR cameras and it is based on this experience that we
can state that, by photographing in the same space and using the same equipment,
one can use the automatic mode and the parameters will be equivalent, generally
having only ISO variation (sensor sensitivity) between the pre and post photos.
498
Photodocumentation in aesthetic phlebology
Figure 2: Example of post-treatment control with transdermal laser associated with dextrose 75% (CLaCS). The use of
augmented reality image facilitates diagnosis and treatment guidance, and also helps visualise the result.
Positioning
• K Miyake, MH Grill and RB Fukushima

The photographer should always be positioned perpendicularly to the point of
interest and we suggest the use of lenses of standard focal lengths. We usually use
three focal lengths on our DSLR cropped frame: 17mm for panoramic photos
(wide angle), 35mm for general lesions (normal view) and 55mm for smaller details
(zoomed view).
To maintain the frame, our experience has also shown that it is enough for the
photographer to have access to the previous image and to know the focal length
used to photograph the control in an equivalent way. Keeping a pre-established
order of each part of the lower limb also helps in this process. In our service, we
use some parameters to facilitate reframing in the re-photographing:
• The bed, when electric, must be at the minimum height
• We always start with a panoramic photo, with the patient lying down and the
photo showing from the feet to the beginning of the thighs
• We start the photos on the left side of the patient
• An imaginary line between the camera and the patient’s bone should form a
90-degree angle
• The patient’s waist should be parallel to the table, lying in the decubitus
ventral or dorsal position
• When flexing the knee or ankle, the angle of 90 degrees should be maintained.
• After finishing the photos on the left side, we move to the right side and
restart with the panoramic photo
• After finishing the front, the patient changes to ventral position and we restart
the photographs. At the end, we will have four panoramic photos and in
our service an average of 40–50 photos with and without augmented reality
(VeinViewer, Christie Medical).
Usually two or more photos are taken of each incidence. Combined telangiectasias
are documented with and without augmented reality to highlight the presence of the
feeding vein.8 This strategy is interesting for the control of the short-term evolution
(one to three weeks) where the inflammation triggered by the procedure can
mask the final result, but the occlusion of the feeding vein shows good prognosis
of the treatment.
499
Figure 3: Evolution of surgical treatment: endovenous laser ablation of the right great saphenous vein, ligation of
perforant veins and removal of tributaries in orthostatic position. Left to right: before, three days and two months after
the procedure.
As a general rule, the decubitus position works very well for the recording of
ulcers, telangiectasias and, in particular, reticular veins with use of augmented
reality. Tributary veins are better recorded with patients in the standing position.
Flash and TTL function

The lighting in the doctor’s office is, as a rule, unsuitable for photography. Especially
when we use the camera in hand (limiting the maximum opening time of the
diaphragm) and we want a photo with minimum granulation (low ISO).
When we find ourselves in a situation like this, where the parameters have already
been optimised and yet we do not have the proper exposure, using the flash is an
option to improve the light.9,10
A practical example of increasing the light source using the flash is to reflect it
to the ceiling. Thus, the flash illuminates the entire area above the scene and makes
it a soft source of light for the object. This technique is only possible with external
flash cameras and it should be remembered that the ceiling and walls of the room
must be white (Figure1).
Another feature that facilitates the use of modern flashes is TTL (Through The
Lens). This system consists of a pre-shot light that precedes the photograph and
penetrates through the lens, allowing the camera in automatic mode and flash in
the TTL module to calculate the parameters of the photograph taking into account
the extra luminosity in the exposure.11
Cameras
Smartphones have evolved immensely and, in situations of adequate lighting, are
able to produce photographs comparable to those of semi-professional equipment.
For those who are starting to photograph the evolution of their cases, this can
offer a simple solution. Negative aspects of using cell phones are, among others,
the impossibility of using an external flash in scenes of low light, the limitation of
adjustments and, even, the better acceptance of the patient in accepting a photo
when using a camera dedicated to this purpose.12,13
500
Cameras are classified into three main categories: point-and-shoot or compact

cameras, DSLR and mirrorless cameras.14–16
We recommend DSLR cameras because of cost, professional appearance and the
possibility of using external flash. It is worth remembering that the possibility of
photography in tethering can be an important factor in the decision to purchase
the equipment.
Storage and organisation

Digital sensors are formed by a large set of pixels. These, in turn, are formed by
the overlap of the three basic colours, red, green and blue (RGB). The amount
of each of these colours in the pixels will define the colour of that point and
the set of points in the final image. The higher the amount of pixels, the higher is
the resolution.17
The initial file generated has a separate representation of each of the basic colours

in each pixel. The name of this file is “RAW”, as it is an unprocessed file. Thus, to
visualise the image, this information has to be interpreted by software. That is why
almost all compact cameras and smartphones immediately compress this file to a
simpler format. The most used formats are TIFF, PNG and JPEG.
Storage in RAW format has numerous advantages. It contains all the information
generated by the sensor. Thus, it is possible to reformat several of the parameters
like white balance, exposure and even the type of colour style. Additionally, any
programme that modifies the colours of the pixels (for example, Photoshop) has
to create a compact version of that file. The original file is inviolable, therefore,
this is the only format accepted as proof by the judicial system of several countries
(including Brazil).18 Its main disadvantages are the size and the necessity of using
specific programmes for its handling.
For beginners, we suggest using JPEG. It is the most compact and user-friendly
format. Virtually every photo editing or storage programme supports this format.
For colleagues who have already incorporated photography on a daily basis I
suggest using RAW or the mixed RAW + JPEG solution. For this, you need fast
digital cards and computers with good processors. The heaviest file is a valuable
backup if legal documentation of our treatment is required or for the specific
processing of photos for classes, congresses and research. On a daily basis, we only
work with JPEG versions under compression of up to 5 megapixels, good enough
for full HD or even 4K screens.
For the organisation of these files we suggest the creation of a system of folders
and subfolders contemplating the following prerogatives:
• The patient’s main folder contains the identification number and then
(optional) the name (e.g. 12345 example)
• The subfolders with the photos contain, already in its identification, the year,
month and day of the photograph followed or not by another identifier (2018-
01-15 example); so, regardless of the operating system or photo management,
the images will be arranged in chronological order.
With this system of folders already created, we can use two different strategies to
organise the photos on a daily basis:
1. iIt is the simplest and most reliable way. It does not require extra
software or features, only that you respect a basic rule: you must start the
session by registering an image that contains the patient’s identification
501
data. Thus, all the photos contained in the interval between two
identification screens are of the patient identified between the two. This
targeting can be done at any time interval (once a day, weekly, etc.)
and does not have to be done by the same person that did the photos.
Features such as wireless transfer, direct camera photography or through
memory cards with this specification can streamline the workflow but
maintains the need to respect the photo ID rule and often require a more
advanced knowledge of information technology for its proper functioning.
2. Pre-identification with the tethering technique: Since 2016, we have adopted
this technique, which uses a special cable (tethering) to immediately send
the images to the computer. With this, we can identify the destination folder
before the session starts. In addition to having access to the result in almost
real time, we have the peace of mind that the files are already organised.
A number of software is compatible with this technique. We use Adobe Lightroom
because of its reliability, as one of the most widely used file management tools
for photographers worldwide, as well as its feature of keeping files in the original
operating system folders, allowing access to files by other programmes and
facilitating a possible migration to another system.
Lightroom also allows for side-by-side photo comparison, a feature we use at
the time of post procedure photography. Our “phlebosuite” (a complete aesthetic
phlebology procedure room) is mounted with two full HD screens side by side
and we keep the pre reference photo on the left screen and the newly captured
image is automatically directed to the right screen. As a rule, the result of the
treatment of microvarices tends to be underestimated before access to pre and post
photography.19 With this real-time visualisation routine, both the medical staff
and patients have a more real idea of the evolution of the pathology, facilitating
decision making and adherence to treatment.
502
Summary
• At the early stage of venous insufficiency, dermatological alterations may be

the only manifestation of the disease, and photography is the tool the vascular
surgeon has to document and quantify the course of treatment.
• We have developed a simple and effective protocol for the vascular surgeon to
obtain high resolution and reproducibility in their photos. The objective is to
produce similar images at various stages of treatment.
• A routine must be established, with the photographs always being done
in the same environment, with the same camera and with equivalent
photographic parameters.
• The decubitus position works well for the recording of ulcers, telangiectasias
and reticular veins with the use of augmented reality. Tributary veins are

better recorded with patients in the standing position.
• We recommend the use of DSLR cameras because of their cost and
professional appearance, and the possibility of using external flash.
• We suggest the implementation of a process for storage and organisation
of the files, with two different strategies to organise the photos on a daily
basis: identification at the end of the routine, or pre-identification with the
tethering technique.
References
1. Eklof B, Rutherford RB, Bergan JJ, et al. Revision of the CEAP classification for chronic venous disorders:
consensus statement. J Vasc Surg 2004; 40 (6): 1248–52.
2. Rocha EF, Filho JP, Lotufo RDEA, et al. Quantitative analysis of sclerotherapy results by using digital
photography and a computer program. Dermatol Surg 2006; 32: 902–06.
3. Munia MA, Wolosker N, Munia CG, et al. Comparison of laser versus sclerotherapy in the treatment of
lower extremity telangiectases: A prospective study. Dermatol Surg 2012; 38: 635–39.
4. Kern P, Ramelet A-A, Wutschert R, et al. A double- blind, randomized study comparing pure
chromated glycerin with chromated glycerin with 1% lidocaine and epinephrine for sclerotherapy of
telangiectasias and reticular veins. Dermatol Surg 2011; 37: 1590–94.
5. Scultetus AH, Villavicencio JL, Kao T-C, et al. Microthrombectomy reduces postsclerotherapy pigmen-
tation: multicenter randomized trial. J Vasc Surg 2003; 38: 896–903.
6. Parlar B, Blazek C, Cazzaniga S, et al. Treatment of lower extremity telangiectasias in women by foam
sclerotherapy vs. Nd:YAG laser: a prospective, comparative, randomized, open-label trial. J Eur Acad
Dermatol Venereol 2015; 29: 549–54.
7. Nayler JR. Clinical photography: A guide for the clinician. Journal of Postgraduate Medicine 2003; 49
(3): 256–62.
8. Miyake RK, HD Zeman, FH Duarte, et al. Vein imaging: A new method of near infrared imaging, where
a processed image is projected onto the skin for the enhancement of vein treatment. Dermatologic
Surgery 2006; 32 (8): 1031–38.
9. Salles F. Mnemocine. Manual de fotografia e cinematografia básica. http://bit.ly/2EGT07x [Accessed
15 February 2018]
10. Nikon D3200 Instruction Manual. http://bit.ly/1y4meih [ Date accessed 15 February 2018]
11. Canon Speedlite 430EXII Instruction Manual. http://bit.ly/2GgoKgS [Date accessed 15 February 2018]
12. Leger MC, Wu T, Haimovic A, et al. Patient perspectives on medical photography in dermatology.
Dermatologic Surgery 2014; 40 (9): 1028–37.
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13. Hsieh C, Duri Y, Ashish C, et al. Patient perception on the usage of smartphones for medical
photography and for reference in dermatology. Dermatologic Surgery 2015; 41 (1): 149–54.
14. Wakabayashi D. Wall Street Journal. The point-and-shoot camera faces its existential moment. http://
on.wsj.com/2C10bqm [Date accessed 15 February 2018]
15. Barco L, Ribera M, Casanova JM. Guide to buying a camera for dermatological photography. Actas
Dermo-Sifiliográficas 2012; 103 (6): 502–10.
16. Mansurov N. Fotografia-DG. Mirrorless vs. DSLR. http://bit.ly/2Ge0HiU [Accessed 15 February 2018]
17. Miot HA, Pedreira Paixão M, Macedo Paschoal F. Basics of digital photography in dermatology.” Anais
Brasileiros de Dermatologia 2006; 81 (2): 174–80.
18. Araujo JCBA. Âmbito Jurídico. Fotografia digital como prova no processo – Aspectos tecnológicos.
http://bit.ly/2ErdwWA [Date accessed 15 February 2018]
19. Santiago FR, Piscoya M, Chi Y-W. Change in perception of sclerotherapy results after exposure to pre-
post intervention photographs. Phlebology 2017; 268355517736178.
504

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Vascular and Endovascular

Limit of Liability/Disclaimer Warranty

Acute stroke controversies

25 I s there a role for carotid endarterectomy or carotid stenting in

31 Is protamine reversal of heparin safe during carotid endarterectomy?

39  CSVI appraisal is again required

41  uantitative analysis of embolic filter debris load during carotid artery

Technique and technologies controversies

53 New thoracic descending thoracic aortic stent graft

57  EVAR using a new visceral manifold device

Controversies associated with underlying pathologies, connective tissue disor-

65  ndovascular repair in patients with connective tissue disorders—

73  izing matters when it comes to remodelling and false lumen

81  educed radiation and choice of imaging modality for endoleak

89  eficiencies in operator behaviour—premature atypical malignancies

Stroke from Thoracic Endovascular aortic Procedures (STEP) controversies

97 The use of filter protection in TEVAR patients—lessons learned from

103  ranscranial Doppler—the ultimate cerebrovascular monitoring

115 Controversies in management of short, angulated, wide and

123  se of EndoAnchors for elective EVAR

129 Use of covered stents for visceral and aortoiliac injuries

137 Predictors of long-term survival after fenestrated endovascular aortic

149  ebate: FEVAR is best for juxta-renal aneurysmal repair–against the

Abdominal aortic controversies

Screening and centralisation of services

159 Screening for abdominal aortic aneurysm is cost-effective and a policy

181 Generation of high-performance teams in emergency aortic surgery—

191 Risk of abdominal aortic aneurysm among relatives of abdominal

197  VAR does not have worse outcomes in women

Internal iliac artery preservation controversies

205 Establishing evidence for endovascular aneurysm repair of the iliac

209  arallel graft use for internal iliac artery preservation

Results and follow-up of EVAR

219  evice labelling is not always in the patient’s interests

233  einterventions after EVAR: “On”and “off” instructions for use

245  rediction of less vigorous follow-up based upon the first

251 Tomographic ultrasound measures associated with abdominal aortic

Alternative access to control endoleak controversies

267 Alternative access to control endoleaks controversies—transarterial

275 The transarterial approach for treatment of type II endoleaks

285  lternative access to control endoleaks—para endograft

Technical controversies for open abdominal aortic aneurysm repair

293 The AIDA study—a randomised multicentre three-armed clinical trial

Peripheral arterial ischaemia controversies

WHETHER to intervene, WHEN to INTERVENE, INTERVENTION METHOD AND

311  overed endovascular reconstruction of the aortic bifurcation

319 Endovascular vs. open treatment of severe aortoiliac occlusive

335  ndovascular first for critical limb ischaemia is a concept without

343 Endovascular first for critical limb ischaemia is a concept without

Emerging devices and interventional techniques: Vessel preparation devices

357 The use of directional atherectomy prior to drug-coated balloons

Drug-coated balloons, stents, drug-eluting stents and bioabsorbable scaffolds

367 I LLUMENATE: European randomised controlled trial two-year results

373  he potential value of swirling flow—the BioMimics 3D study

Access techniques and peri-interventional imaging

383 The potential value of IVUS-guided superficial femoral artery

389 Vector velocity ultrasound—a new ultrasound technique

397 Limb salvage in acute ischaemia due to occlusion of popliteal aneurysm

Critical limb ischaemia controversies

411 How to change a service and the stages of changing a service

417 Percutaneous femoropopliteal bypass—the DETOUR I trial

425 Controversies in the local management of diabetic foot ulcers

Venous and lymphatic controversies

WHETHER to intervene, WHEN to intervene, HOW to intervene:

25 I s there a role for carotid endarterectomy or carotid stenting in

31 Is protamine reversal of heparin safe during carotid endarterectomy?

39 CSVI appraisal is again required

41 uantitative analysis of embolic filter debris load during carotid artery

53 New thoracic descending thoracic aortic stent graft

57 EVAR using a new visceral manifold device

65 ndovascular repair in patients with connective tissue disorders—

73 izing matters when it comes to remodelling and false lumen

81 educed radiation and choice of imaging modality for endoleak

89 eficiencies in operator behaviour—premature atypical malignancies

97 The use of filter protection in TEVAR patients—lessons learned from

103 ranscranial Doppler—the ultimate cerebrovascular monitoring

115 Controversies in management of short, angulated, wide and

123 se of EndoAnchors for elective EVAR

129 Use of covered stents for visceral and aortoiliac injuries

137 Predictors of long-term survival after fenestrated endovascular aortic

149 ebate: FEVAR is best for juxta-renal aneurysmal repair–against the

159 Screening for abdominal aortic aneurysm is cost-effective and a policy

181 Generation of high-performance teams in emergency aortic surgery—

191 Risk of abdominal aortic aneurysm among relatives of abdominal

197 VAR does not have worse outcomes in women

205 Establishing evidence for endovascular aneurysm repair of the iliac

209 arallel graft use for internal iliac artery preservation

219 evice labelling is not always in the patient’s interests

233 einterventions after EVAR: “On”and “off” instructions for use

245 rediction of less vigorous follow-up based upon the first

251 Tomographic ultrasound measures associated with abdominal aortic

267 Alternative access to control endoleaks controversies—transarterial

275 The transarterial approach for treatment of type II endoleaks

285 lternative access to control endoleaks—para endograft

293 The AIDA study—a randomised multicentre three-armed clinical trial

311 overed endovascular reconstruction of the aortic bifurcation

319 Endovascular vs. open treatment of severe aortoiliac occlusive

335 ndovascular first for critical limb ischaemia is a concept without

343 Endovascular first for critical limb ischaemia is a concept without

357 The use of directional atherectomy prior to drug-coated balloons

367 I LLUMENATE: European randomised controlled trial two-year results

373 he potential value of swirling flow—the BioMimics 3D study

383 The potential value of IVUS-guided superficial femoral artery

389 Vector velocity ultrasound—a new ultrasound technique

397 Limb salvage in acute ischaemia due to occlusion of popliteal aneurysm

411 How to change a service and the stages of changing a service

417 Percutaneous femoropopliteal bypass—the DETOUR I trial

425 Controversies in the local management of diabetic foot ulcers

437 Haemodynamics—objective assessment of venous and lymphatic

443 Strain-gauge plethysmography

451 Surgical treatment of late-stage lymphoedema and advanced

461 Evidence for cyanoacrylatic ablation

477 The pros and cons of endovenous cyanoacrylate

485 Retrospective review of complications in 577 consecutive cases of

491 Reducing hyperpigmentation after sclerotherapy using an

497 Photodocumentation in aesthetic phlebology