Circulation: Cardiovascular Interventions

ORIGINAL ARTICLE
High-Speed Rotational Atherectomy Versus
Modified Balloons Prior to Drug-Eluting Stent
Implantation in Severely Calcified Coronary Lesions
The Randomized PREPARE-CALC Trial

BACKGROUND: Balloon dilatation or debulking seems to be essential to Mohamed Abdel-Wahab,

allow successful stent implantation in calcified coronary lesions. Compared MD
with standard balloon predilatation, debulking using high-speed rotational Ralph Toelg, MD
atherectomy (RA) is associated with higher initial procedural success albeit Robert A. Byrne, MB BCh,
with higher in-stent late lumen loss at intermediate-term follow-up. Whether PhD
modified (scoring or cutting) balloons (MB) could achieve similar procedural Volker Geist, MD
success compared with RA is not known. In addition, whether new-generation Mohamed El-Mawardy,
drug-eluting stents could counterbalance the excessive neointimal proliferation MD
triggered by RA remains to be determined. Abdelhakim Allali, MD
Tobias Rheude, MD
METHODS AND RESULTS: We randomly assigned patients with documented
Derek R. Robinson, D.Phil
myocardial ischemia and severely calcified native coronary lesions undergoing
Mohammad Abdelghani,
percutaneous coronary intervention to a strategy of lesion preparation using
MD
MB or RA followed by drug-eluting stent implantation. Stenting was performed
Downloaded from http://ahajournals.org by on June 19, 2023

Dmitriy S. Sulimov, MD
using a third-generation sirolimus-eluting stent with a bioabsorbable polymer.
Adnan Kastrati, MD
The trial had 2 primary end points: strategy success (defined as successful stent
Gert Richardt, MD
delivery and expansion with attainment of <20% in-stent residual stenosis in
the presence of TIMI [Thrombolysis in Myocardial Infarction] 3 flow without
crossover or stent failure; powered for superiority) and in-stent late lumen loss
at 9 months (powered for noninferiority). Two hundred patients were enrolled
at 2 centers in Germany (n=100 in each treatment group). The mean age of the
study population was 74.9±7.0 years; 76% were men, and 33.5% had diabetes
mellitus. Strategy success was significantly more common in the RA group (81%
versus 98%; relative risk of failure with an MB- versus RA-based strategy, 9.5;
95% CI, 2.3–39.7; P=0.0001), but mean fluoroscopy time was longer (19.6±13.4
versus 23.9±12.2 minutes; P=0.03). At 9 months, mean in-stent late lumen
loss was 0.16±0.39 mm in the MB group and 0.22±0.40 mm in the RA group
(P=0.21, P=0.02 for noninferiority). Target lesion revascularization (7% versus
2%; P=0.17), definite or probable stent thrombosis (0% versus 0%; P=1.00),
and target vessel failure (8% versus 6%; P=0.78) were low and not significantly
different between the MB and RA groups.

CONCLUSIONS: Lesion preparation with upfront RA before drug-eluting stent

implantation is feasible in nearly all patients with severely calcified coronary lesions,
is more commonly successful as a primary strategy compared with MB, and is not
associated with excessive late lumen loss. A strategy of provisional MB remains
Key Words: angioplasty, balloon
feasible, safe, and effective as long as bailout RA is readily available and may offer ◼ atherectomy ◼ drug-eluting stents
the advantages of compatibility with smaller sized catheters and less irradiation. ◼ humans ◼ risk
Both strategies are associated with excellent clinical outcome at 9 months. © 2018 American Heart Association, Inc.

CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov. Unique https://www.ahajournals.org/journal/

identifier: NCT02502851. circinterventions

Circ Cardiovasc Interv. 2018;11:e007415. DOI: 10.1161/CIRCINTERVENTIONS.118.007415 October 2018 1

 Abdel-Wahab et al; PREPARE-CALC
WHAT IS KNOWN
• Balloon dilatation or debulking is commonly per-
formed to allow successful stent implantation in
calcified coronary lesions.
• Compared with standard balloon predilatation,
debulking using high-speed rotational atherec-
tomy is associated with higher initial procedural
success albeit with higher in-stent late lumen loss
at intermediate-term follow-up.
WHAT THE STUDY ADDS
• This is the first randomized trial to compare lesion
preparation of severely calcified coronary lesions
using a modified (scoring or cutting) balloon-based
strategy compared with rotational atherectomy.
• Strategy success is higher with rotational atherec-
tomy. It does not result in higher late lumen loss at
9 months when combined with a modern drug-
eluting stent.
• A strategy of provisional modified balloon angio-
plasty remains feasible, safe, and effective as long
as bailout rotational atherectomy is readily avail-
able, and clinical outcome is excellent with both
strategies.
P
ercutaneous coronary intervention (PCI) is a
widely used treatment for patients with complex
obstructive coronary artery disease. In elderly
Downloaded from http://ahajournals.org by on June 19, 2023
patients, patients with diabetes mellitus, and in those
with advanced renal disease, coronary calcification is
common.1,2 PCI of calcified coronary lesions remains
challenging, despite significant improvements in the
available tools and techniques.
Because of resistant plaque burden and irregular
lesion surface, heavily calcified stenoses are difficult to
dilate adequately and may contribute to failure of stent
delivery or incomplete stent expansion.3–6 PCI of calci-
fied lesions is associated with significantly increased
periprocedural complications, long-term adverse clini-
cal events, and high rates of revascularization.1,2,7 To
address these challenges, lesion preparation of calcified
lesions before stent implantation has been established
as a prerequisite to achieve adequate results.
Rotational atherectomy (RA) can effectively modify
calcified plaques. Its mechanism of action relies on
removing part of the obstructive atheroma by differ-
ential cutting, facilitating balloon dilatation, plaque
fracture, stent delivery, and expansion.8,9 In the ran-
domized ROTAXUS trial (Rotational Atherectomy Prior
to Taxus Stent Treatment for Complex Native Coronary
Artery Disease),6 a strategy of routine lesion prepara-
tion of calcified lesions with RA before first-generation
drug-eluting stent (DES) implantation was more com-
monly successful than standard balloon predilatation.
However, in-stent late lumen loss (LLL) at 9 months was
Circ Cardiovasc Interv. 2018;11:e007415. DOI: 10.1161/CIRCINTERVENTIONS.118.007415
higher with RA, and restenosis rates after both tech-
niques were still significant.
Recently, modified balloons (MB) have been used
increasingly in complex coronary lesions, including
ostial, diffuse, and fibrocalcific ones. These specially
designed balloons have either small cutting blades
(eg, Flextome Cutting Balloon; Boston Scientific Corp,
Natick, MA) or nitinol spiral wires (eg, AngioSculpt
Scoring Balloon; Spectranetics, Colorado Springs, CO),
which apply focal concentrations of dilating force and
thereby assist in luminal expansion of rigid coronary
lesions. The feasibility and safety of these balloons for
the treatment of complex coronary lesions have been
reported with good immediate results,10–12 but no com-
parative studies to other techniques exist.
To date, no randomized data are available compar-
ing the preparation of calcified lesions with an ather-
ectomy-based strategy versus an MB-based strategy.
The aim of our study was to assess the comparative
performance of both strategies in a randomized trial
conducted in patients with severely calcified coronary
lesions receiving current-generation DES.
METHODS
Patients and Study Design
PREPARE-CALC (Comparison of Strategies to Prepare Severely
Calcified Coronary Lesions) is a randomized controlled trial in
patients with myocardial ischemia and severely calcified native
coronary artery lesions. The trial was performed at 2 high-
volume, experienced interventional study sites in Germany,
and fully trained operators with several years of interventional
experience performed the procedures. The data that support
the findings of this study are available from the correspond-
ing author upon reasonable request.
Between September 2014 and October 2017, 200 eligible
patients who gave written informed consent were random-
ized 1:1 to a strategy of coronary lesion preparation using
MB (cutting or scoring) or RA followed by DES implantation.
Patients were considered for inclusion in the trial if they met
all inclusion and none of the exclusion criteria. The main
inclusion criteria were angiographically proven coronary
artery disease; presence of anginal symptoms or reproducible
ischemia in the target area by electrocardiography, functional
stress testing, or fractional flow reserve; target reference
vessel diameter between 2.25 and 4.0 mm; luminal diam-
eter reduction of 50% to 100%; and severe calcification of
the target lesion as defined by cineangiography (radiopaci-
ties noted without cardiac motion before contrast injection
generally compromising both sides of the arterial lumen).13
Principal exclusion criteria were myocardial infarction (MI)
within 1 week, decompensated heart failure, target lesions in
coronary artery bypass grafts, in-stent restenosis, and target
vessel thrombus. Details of all inclusion and exclusion criteria
are shown in Table I in the Data Supplement.
The study was conducted in accordance with the provi-
sions of the Declaration of Helsinki and with the International
Conference on Harmonization Good Clinical Practices. The
October 2018 2
 Abdel-Wahab et al; PREPARE-CALC
institutional ethics committee of the 2 participating centers
approved the trial protocol.
Randomization and Procedures
Randomization was performed through computer-generated
block randomization forms for each participating center.
Allocation sequence was concealed using sealed, opaque
envelopes. After the patient provided a written informed
consent, a numbered envelope was opened in sequence,
assigning the patient to either MB predilatation or RA in a 1:1
randomization fashion. The date of randomization marked
the patient’s entry into the study, and the assigned interven-
tional technique had to be performed as soon as possible.
Coronary angiography was performed according to the
conventional and local standards. Percutaneous intervention
was either performed in the same setting, if the patient had
been consented to the study before the procedure and angio-
graphic eligibility had been determined, or in a separate set-
ting. In case of multivessel disease, all other vessels should
have been successfully treated before the assigned treatment
was applied to the target vessel(s), preferably in a separate
setting.
After the decision to perform intervention, patients
received 325 to 500 mg aspirin intravenously or orally (if they
did not receive it within the prior 12 hours) and an oral load-
ing dose of 600 mg clopidogrel. Alternative antiplatelet drugs,
such as prasugrel or ticagrelor, were allowed but were left to
the operator’s discretion. Immediately before intervention,
intraarterial or intravenous heparin was given to maintain an
activated clotting time ≥250 seconds or 200 to 250 seconds if
Downloaded from http://ahajournals.org by on June 19, 2023
a GP (glycoprotein) IIb/IIIa receptor blocker had been adminis-
tered. The use of GP IIb/IIIa antagonists, other antithrombotics
(eg, bivalirudin), and further cardiac medications was left to
the discretion of the treating physician.
Optical coherence tomography (OCT) was recommended
before lesion preparation and at the end of the procedure.
Preprocedural OCT results were not used for clinical deci-
sion-making. Results of the OCT analysis will be reported
separately.
If the patient was randomized to lesion preparation with
an MB-based strategy, predilatation with conventional bal-
loons (compliant or noncompliant) was allowed before and
after MB angioplasty to facilitate device crossing and stent
placement. MB angioplasty was performed by the Flextome
Cutting Balloon (Boston Scientific), the AngioSculpt Scoring
Balloon (AngioScore, Inc), or the Scoreflex Scoring Balloon
(OrbusNeich Medical, Inc, Hong Kong). The use of more than
1 balloon was allowed. The size of the final balloon used was
chosen in a 1:1 ratio according to the vessel size. Crossover
to RA was only allowed if the lesion was not crossable by any
balloon, not crossable by any MB even after standard bal-
loon predilatation, not adequately dilatable (ie, complete bal-
loon expansion without a visible residual waist could not be
achieved), or the stent could not be delivered to the lesion
despite complete balloon expansion.
RA was performed by the Rotablator (Boston Scientific
Scimed, Natick, MA). The burr size was selected to reach a
burr/vessel ratio of 0.5 (maximum 0.7 if needed). Rotational
speed ranged between 140 000–180 000 rotations per minute.
The burr was parked immediately proximal to the lesion to
Circ Cardiovasc Interv. 2018;11:e007415. DOI: 10.1161/CIRCINTERVENTIONS.118.007415
avoid injury to the healthy vessel segment. Heparin, vera-
pamil, and nitroglycerin were administered during RA as an
intracoronary infusion, and a temporary pacemaker wire was
inserted during RA of the right coronary artery and the left
circumflex artery in patients with a dominant left system.
Balloon dilatation after RA and before stent implantation was
recommended.
Stenting was performed using a new-generation sirolimus-
eluting stent with a bioabsorbable polymer (Orsiro; Biotronik
AG, Bülach, Switzerland). More than 1 study stent was per-
mitted for treatment of the target lesion(s). The appropriate
stent length for the target lesion should have been ≥4 mm
longer than the lesion length to allow for coverage between
healthy vessel segments, with adequate stent overlapping.
Postdilatation was performed at the operator’s discretion.
On procedure completion, intracoronary nitroglycerin was
administered, and final angiography of the vessel was per-
formed in at least 2 orthogonal views that showed the target
site free of foreshortening or vessel overlap.
Follow-Up and End Points
After PCI, patients were prescribed 100 mg of aspirin daily
indefinitely and 75 mg of clopidogrel (or an alternative anti-
platelet drug) for at least 6 months. Patients on oral antico-
agulation were prescribed dual therapy with clopidogrel for
at least 6 months. An electrocardiography was performed
24 hours postprocedure or before discharge, whichever
occurred first. Additional 12-lead ECGs were required to doc-
ument any suspicious cardiac ischemic episodes. In addition,
CK (creatine kinase), CK-MB, and troponin T were measured
between 6 and 24 hours postprocedure. If any biomarker ele-
vation was noted postprocedure, additional measurements
were performed, as needed. During hospital stay, patients
were clinically monitored for the occurrence of any adverse
events and any additional coronary interventional treatment.
At 9 months, a clinic visit and a repeat coronary angiography
were performed. Further clinical follow-up is planned at 1
and 2 years.
The primary end point of the trial was strategy success,
defined as successful stent delivery and expansion with attain-
ment of <20% in-stent residual stenosis of the target lesion in
the presence of TIMI (Thrombolysis in Myocardial Infarction)
3 flow without crossover or stent failure.6 The coprimary
end point of the trial was in-stent LLL, defined as the dif-
ference between the postprocedure and 9-month in-stent
angiographic minimal lumen diameter. Secondary end points
included procedural duration, contrast dye amount, peripro-
cedural MI, in-segment LLL (inside the stent or within 5 mm
proximal or distal to the stent), binary restenosis (in-stent and
in-segment), stent thrombosis, and target vessel failure at 9
months, 1 year, and 2 years. Stent thrombosis was defined
as proposed by the Academic Research Consortium.14 Target
vessel failure was defined as a composite of cardiac death,
target vessel-related MI, and clinically driven target vessel
revascularization. Detailed end point definitions are provided
in the Data Supplement. Clinical follow-up at 1 and 2 years is
ongoing and will be reported when complete.
All major cardiac events (including the primary and sec-
ondary end points) were adjudicated by an independent clini-
cal event comittee. All cases of crossover were assessed by
October 2018 3
 Abdel-Wahab et al; PREPARE-CALC
the clinical event comittee for their conformity with the trial
protocol, and only cases with a protocol-defined indication
for crossover were adjudicated as such.
Quantitative Angiographic Analysis
Baseline, postprocedural, and follow-up coronary angio-
grams were digitally recorded and assessed off-line by the
quantitative angiographic core laboratory (ISAR Research
Center, Munich, Germany) with an automated edge-detec-
tion system (Qangio, version 7.3; Medis Medical Imaging
Systems, the Netherlands) by independent personnel blinded
to treatment allocation. Measurements were performed on
cineangiograms recorded after the intracoronary administra-
tion of nitroglycerine using the same single worst-view pro-
jection at all times. The contrast-filled nontapered catheter
tip was used for calibration. Quantitative analysis was per-
formed on both the in-stent and in-segment areas (including
the stented segment, as well as both 5 mm margins proximal
and distal to the stent). Intraobserver variability was calcu-
lated at 0.09±0.07 mm for the measurement of vessel size.
Qualitative morphological lesion characteristics were charac-
terized by standard criteria. Coronary calcification was cat-
egorized based on the angiographic classification scheme of
Mintz et al.13
Statistical Analysis
Our group has shown in the ROTAXUS study6 that the end
point strategy success was significantly higher in lesions pre-
treated with RA compared with standard balloon predilata-
Downloaded from http://ahajournals.org by on June 19, 2023
tion, particularly in severely calcified lesions (92.3% versus
71.3%; P=0.001). Assuming a strategy success rate of 90%
versus 75% for lesions pretreated with RA versus lesions pre-
treated with MB in this study, a sample size of 200 patients
(100 in each arm) was calculated to provide a power of 80%
at an α level of 0.05. For the coprimary end point of LLL,
assuming an LLL of 0.2 mm in both groups, an SD of 0.5
mm, a noninferiority margin of ≤0.2 mm, and an average of
1.3 lesions per patient,6 a noninferiority sample size of 148
patients (74 in each arm) was calculated given a power of
80% at an α level of 0.05.15 With an expected attrition rate
of 20% for an angiographic end point, a total of 186 patients
(93 in each arm) would be needed, who have already been
accounted for in the calculation of the superiority end point.
On this basis, we designed the trial to include 200 patients,
with 100 patients in each group.
All statistical analyses were performed by an indepen-
dent statistician. Primary and secondary end points were
analyzed on an intention-to-treat basis. The coprimary end
point of in-stent LLL at 9 months was also analyzed on an
as-treated basis. Categorical measures were compared using
a χ2 test or Fisher exact test as required. Continuous variables
were compared using a 2-sided unpaired t test or a Mann-
Whitney U test, as appropriate. For lesion-level data, differ-
ences between groups were checked for significance with
generalized estimating equations to address intrapatient
correlation in patients who underwent multilesion interven-
tion. The estimated relative risk is the ratio of the risk prob-
abilities, and a CI was constructed based on a logarithmic
transformation. Missing data were assumed to be missing
Circ Cardiovasc Interv. 2018;11:e007415. DOI: 10.1161/CIRCINTERVENTIONS.118.007415
at random. Prespecified subgroup analyses (stratified by age,
sex, diabetes mellitus, chronic kidney disease, left ventricular
function, previous bypass surgery, and lesion location) and
post hoc subgroup analyses were performed, with relative
risks and 95% CIs calculated together with formal tests for
interaction. Event-free survival was assessed using Kaplan-
Meier method.
All tests were 2 sided, and a P value of 0.05 was consid-
ered statistically significant. No adjustment was made for the
primary and secondary end point comparisons. The steering
committee had full access to all the data in the study and took
responsibility for its integrity and the data analysis.
RESULTS
Baseline Clinical and Angiographic
Characteristics
Of 200 patients enrolled in the study, 100 patients
(75 men; 75.0±6.9 years of age) were randomized to
lesion preparation with MB angioplasty (MB group) and
100 patients (77 men; 74.8±7.1 years of age) to lesion
preparation with RA (RA group). The study flowchart
is summarized in Figure 1. There were no significant
differences between both groups with respect to clini-
cal presentation (mostly stable angina), cardiovascular
risk factors, prevalence of chronic renal failure, or his-
tory of coronary interventions (Table 1). Multivessel dis-
ease was common and was present in the majority of
patients in both groups.
Overall, 278 lesions were treated (1.39 lesions
per patient): 137 in the MB group and 141 in the
RA group. Patients were well balanced with respect
to lesion location and morphology (Table 2), with
the majority of lesions located in the left anterior
descending coronary artery. The target lesions were
of high-grade stenosis (mean diameter stenosis by
visual estimate 83.54±8.76% in the MB group and
83.02±10.35% in the RA group) and had several cri-
teria signifying lesion complexity in addition to severe
calcification (33.4% with moderate or severe tortuos-
ity, 41.7% located at bifurcations, and 26.9% ostial
lesions), resulting in 95.6% of lesions categorized
as type B2/C according to the American College of
Cardiology/American Heart Association classification.
Lesion characteristics were well balanced between
both study groups.
Procedural Details
Procedural details are shown in Table 2. Almost all pro-
cedures (n=199) were performed through the femoral
access route. Most procedures (86.6%) were performed
through a 7F guiding catheter, although more proce-
dures in the MB group were performed with smaller
sized catheters. Unfractionated heparin was used in the
majority of procedures, and the median dose was 7500
October 2018 4
 Abdel-Wahab et al; PREPARE-CALC

Figure 1. Study flowchart.

MB indicates modified balloon; PCI, percutane-
ous coronary intervention; RA, rotational ather-
ectomy; and SES, sirolimus-eluting stent.

IU (range, 4000–20 000), with no significant differences 6.0%), but the difference was not statistically signifi-
between groups. The use of a GP IIb/IIIa inhibitor was cant (P=0.09). Fluoroscopy time was significantly longer
rare (2 patients in the RA group). in the RA group, with no significant differences in total
Balloon predilatation (before or after MB and after
RA) was performed in the majority of lesions using Table 1. Baseline Characteristics (n=200 Patients)
mostly (87.0%) noncompliant balloons, with a similar
MB (n=100) RA (n=100) P Value
mean balloon size and mean inflation pressure in both
Age, y 75.0±6.9 74.8±7.1 0.79
Downloaded from http://ahajournals.org by on June 19, 2023

groups (Table 2). The use of more than 1 predilatation

balloon was numerically more common in the MB group Men 75 (75%) 77 (77%) 0.74

(46.6% versus 35.3%; P=0.08). In the MB group, the Height, cm 172.3±9.5 172.0±8.7 0.82
Angiosculpt scoring balloon was the most frequently Weight, kg 84.2±15.8 83.2±17.1 0.65
used device (83.8%), followed by the Scoreflex scor- Diabetes mellitus 34 (34%) 33 (33%) 0.88
ing balloon (12.9%) and the Flextome cutting bal- Hypertension 93 (93%) 93 (93%) 1.00
loon (3.3%). The MB balloon had a mean diameter of
Dyslipidemia 69 (69%) 68 (68%) 0.88
2.94±0.34 mm, a mean length of 10.59±2.33 mm, and
Current smokers 9 (9%) 15 (15%) 0.19
was inflated at a mean pressure of 15.6±3.0 atm. For
RA, a single burr was used in most lesions (95.1%) with Chronic renal failure* 21 (21%) 26 (26%) 0.40

a mean burr size of 1.52±0.16 mm. The mean stent Previous MI 22 (22%) 21 (21%) 0.86
length/lesion was well beyond the mean lesion length. Previous PCI 55 (55%) 47 (47%) 0.25
All but 4 lesions (98.5%) were treated with the protocol- Previous CABG 13 (13%) 6 (6%) 0.09
assigned stent. After stenting, balloon postdilatation
Unstable angina 9 (9%) 8 (8%) 0.80
was performed for the vast majority (82.0%) of treated
Atrial fibrillation 11 (11%) 18 (18%) 0.23
lesions in both groups, with the mean maximum post-
dilatation pressure slightly but not significantly higher Left main disease 37 (37%) 23 (23%) 0.03

in the MB group (21.85±4.64 versus 20.94±4.88 atm; Multivessel disease 70 (70%) 74 (74%) 0.52
P=0.12). LV ejection fraction, % 56.9±10.6 55.7±11.7 0.45
Multilesion PCI 42 (42%) 35 (35%) 0.31

Procedural Outcome Unfractionated heparin 98 (98%) 99 (99%) 1.00

Bivalirudin 2 (1%) 1 (1%) 1.00
Procedural complications and outcome are shown in
Table 3. Large coronary dissections, perforations, and GP IIb/IIIa antagonists 0 (0%) 2 (2%) 0.50

no/slow-flow phenomena were rare and were not sig-
nificantly different in both groups. Periprocedural side
branch compromise was twofold higher in the MB
group compared with the RA group (13.0% versus
Values are n (%) or mean±SD. CABG indicates coronary artery bypass
graft; GP, glycoprotein; LV, left ventricle; MB, modified balloon; MI, myocardial
infarction; PCI, percutaneous coronary intervention; and RA, rotational
atherectomy.
*Defined as glomerular filtration rate <60 mL/min.

Circ Cardiovasc Interv. 2018;11:e007415. DOI: 10.1161/CIRCINTERVENTIONS.118.007415 October 2018 5

 Abdel-Wahab et al; PREPARE-CALC

Table 2. Angiographic and Procedural Characteristics (n=278 Lesions) Table 3. Procedural and In-Hospital Outcome (n=200 Patients)

P MB (n=100) RA (n=100) P Value

MB (n=137) RA (n=141) Value
Procedural duration, min 78.5±40.6 88.2±34.9 0.07
Location 0.30
Fluoroscopy time, min 19.6±13.4 23.9±12.2 0.03
 Left main 20 (14.6%) 15 (10.6%)
Contrast amount, mL 230.0±93.8 233.0±109.1 0.83
 Left anterior descending 61 (44.5%) 78 (55.3%)
Large dissection, >5 mm 7 (7%) 3 (3%) 0.33
 Left circumflex 16 (11.7%) 16 (11.3%)
Perforation 2 (2%) 4 (4%) 0.68
 Right coronary artery 40 (29.2%) 32 (22.7%)
Pericardial effusion 0 (0%) 3 (3%) 0.24
Reference vessel diameter, mm 3.31±0.44 3.25±0.47 0.25
No/slow flow 0 (0%) 2 (2%) 0.49
Lesion length, mm 30.07±18.30 29.81±15.23 0.55
Final TIMI flow <III 0 (0%) 1 (1%) 0.99
Diameter stenosis, % 83.54±8.76 83.02±10.35 0.80
Residual stenosis >20% 2 (2%) 0 (0%) 0.49
Ostial location 35 (25.5%) 40 (28.4%) 0.52
Stent failure 4 (4%) 1 (1%) 0.36
Bifurcation 61 (44.5%) 55 (39.0%) 0.37
Crossover 16 (16%) 0 (0%) <0.0001
Moderate/severe tortuosity 44 (32.1%) 49 (34.7%) 0.89
Strategy success* 81 (81%) 98 (98%) 0.0001
Chronic total occlusion 4 (2.9%) 4 (2.8%) 1.00
Death 0 (0%) 0 (0%) 1.00
B2/C lesion 129 (94.2%) 137 (97.2%) 0.62
MI 1 (1%) 2 (2%) 1.00
7F guiding catheter 111 (81.0%) 130 (92.2%) 0.002
Target vessel re-PCI 0 (0%) 0 (0%) 1.00
MB diameter, mm 2.94±0.34 … …
CABG 0 (0%) 0 (0%) 1.00
MB pressure, atm 15.6±3.0 … …
Stent thrombosis 0 (0%) 0 (0%) 1.00
Use of >1 MB 12 (8.7%) … …
Access site complications 5 (5%) 3 (3%) 0.72
MB-to-artery ratio 0.90±0.11 … …
Values are n (%) or mean±SD. CABG indicates coronary artery bypass graft;
Starting burr size, mm … 1.52±0.17 … MB, modified balloon; MI, myocardial infarction; PCI, percutaneous coronary
Maximum burr size, mm … 1.53±0.18 … intervention; RA, rotational atherectomy; and TIMI, Thrombolysis in Myocardial
Infarction.
Use of >1 burr … 7 (4.9%) … *See text for definition.
Rotational speed (RPM) … 164 224±23 827 …
Downloaded from http://ahajournals.org by on June 19, 2023

Balloon predilatation 103 (75.2%) 119 (84.4%) 0.04 9.5; 95% CI, 2.3–39.7; P=0.0001). The main driving
No. of predilatation balloons 1.70±0.93 1.54±0.87 0.13 factor for strategy failure was the need to crossover to
Maximum predilatation balloon 2.88±0.43 2.97±0.42 0.21 RA in the MB group (16% versus 0%; P<0.0001). The
diameter, mm reasons for crossing over in the MB group are detailed
Maximum predilatation balloon 19.48±4.83 18.83±3.73 0.77 in Table II in the Data Supplement. Crossing over to RA
pressure, atm
was most commonly because of uncrossable (n=8) or
No. of stents per lesion 1.71±0.85 1.52±0.63 0.03 undilatable (n=6) lesions.
Total stent length per lesion, 35.41±18.00 35.63±15.69 0.94 Results with respect to the primary end point were
mm
consistent in the majority of prespecified and post hoc
Minimum stent diameter, mm 3.14±0.44 3.13±0.48 0.90 subgroups (Figure 2). The difference between both
Maximum stent diameter, mm 3.37±0.45 3.31±0.41 0.23 strategies was attenuated in the following subgroups:
Maximum stent implantation 17.47±3.54 16.47±2.87 0.02 female patients, left anterior descending coronary artery
pressure, atm as target vessel, stenosis severity <80%, and non–type
Balloon postdilatation 117 (83.0%) 111 (81.0%) 0.70 C lesions. Allowing for centers as a random effect made
Maximum postdilatation 3.70±0.54 3.68±0.49 0.76 little difference to the results of the primary end point (P
balloon diameter, mm for superiority remained at 0.0001).
Maximum postdilatation 21.86±4.65 20.95±4.88 0.12
balloon pressure, atm

Values are n (%) or mean±SD. MB indicates modified balloon; RA, rotational
atherectomy; and RPM, rotations per minute.
procedural time or the amount of contrast dye between
both groups.
Strategy success, the primary end point of the trial,
was significantly more common in the RA group (81%
in the MB group versus 98% in the RA group; relative
risk of failure with an MB- versus RA-based strategy,
In-Hospital Events
There were no deaths or reinterventions during hospi-
talization. The incidence of protocol-defined peripro-
cedural MI was low and not significantly different in
both groups (1% in the MB group versus 2% in the
RA group). Postprocedural CK, CK-MB, and troponin T
levels (24 hours post-PCI) were analyzed in 198, 154,
and 161 patients, respectively. The median values of
all 3 markers were not significantly different between

Circ Cardiovasc Interv. 2018;11:e007415. DOI: 10.1161/CIRCINTERVENTIONS.118.007415 October 2018 6

 Abdel-Wahab et al; PREPARE-CALC
Downloaded from http://ahajournals.org by on June 19, 2023

Figure 2. Subgroup analyses for strategy success.

Subgroup analyses are shown for the primary end point of strategy success among patients who were randomly assigned to undergo lesion preparation with
either a modified balloon or rotational atherectomy. The P value for interaction represents the likelihood of interaction between the variable and the relative treat-
ment effect. Risk ratios are for rotational atherectomy versus modified balloon. CABG indicates coronary artery bypass graft; GFR, glomerular filtration rate; and LV,
left ventricle.

both study groups (CK 119 versus 112 U/L, P=0.77;
CK-MB 17.5 versus 19 U/L, P=0.95; troponin T 0.09
versus 0.09 ng/mL, P=0.97; for the MB and RA group,
respectively).
Quantitative Angiographic Analysis
Details of baseline quantitative coronary angio-
graphic analysis are listed in Table 4. Baseline mini-
mal lumen diameter was slightly but not significantly
smaller in the MB group. In general, vessel size was
smaller and lesion length shorter compared with the
visual estimation provided by the operators, with no
significant differences between both study groups.
Although severe calcification was an entry criterion
for the study, the angiographic core laboratory adju-
dicated 25% of treated lesions as moderately calci-
fied, with no significant differences between both
groups. After treatment, no significant differences
were observed in residual diameter stenosis or acute
lumen gain between patients randomized to MB ver-
sus RA (Table 4).
The 9-month angiographic follow-up is based on
160 patients (80%); 84 patients (112 lesions) ran-
domized to the MB group and 76 patients (97 lesions)
randomized to the RA group. The median time to fol-
low-up angiography was not different between both
groups (275; interquartile range, 261–285 versus 277
[270–291] days, respectively; P=0.35). The only dif-
ference observed between patients with and without
angiographic follow-up is that the latter were older
(77.1±5.4 versus 74.3±7.2 years; P=0.009). Details of
the follow-up quantitative coronary angiographic anal-
ysis are shown in Table III in the Data Supplement. At
9 months, mean in-stent LLL (the coprimary end point)
was 0.16±0.39 mm in the MB group and 0.22±0.40
mm in the RA group (P=0.21; Figure 3). The estimated
mean difference in LLL between the MB and RA group
was 0.075 mm, with a 95% CI of −0.04 to 0.19 mm,
which did not exceed the predefined margin of 0.20

Circ Cardiovasc Interv. 2018;11:e007415. DOI: 10.1161/CIRCINTERVENTIONS.118.007415 October 2018 7

 Abdel-Wahab et al; PREPARE-CALC

Table 4. Baseline Quantitative Coronary Angiography Data (n=278

Lesions)
Nine-Month Clinical Outcome
Complete clinical follow-up over 9 months was avail-
MB (n=136) RA (n=137) P Value
able for all 200 patients (100%). At 9 months, overall
Before procedure
mortality was 2% in both groups (P=1.00). Between
 Lesion length, mm 20.16±11.88 20.86±12.30 0.63
discharge and 9 months, spontaneous myocardial
 Reference vessel 3.08±0.47 3.10±0.49 0.84 infarction occurred in 2 patients in the MB group and
diameter, mm
none in the RA group. Clinically indicated target vessel
 Minimal lumen 1.07±0.34 1.15±0.35 0.07 revascularization was twice as high in the MB group,
diameter, mm
but the event rates were low and statistically not signifi-
 Diameter stenosis, % 65.18±9.53 63.43±9.80 0.16
cantly different between both groups (6% versus 3%;
 Severe calcification* 100 (73.0%) 104 (76.5%) 0.46 P=0.50). Cumulative incidence curves for the secondary
Immediately after procedure end point of target vessel failure are shown in Figure I
 Minimal lumen in the Data Supplement. No cases of stent thrombosis
diameter, mm were observed in both groups (Table 5).
  In-stent 2.81±0.47 2.85±0.43 0.56
  In-segment 2.58±0.53 2.62±0.67 0.61
 Diameter stenosis, % DISCUSSION
  In-stent 12.34±5.14 12.62±5.36 0.63 To our knowledge, PREPARE-CALC is the second
  In-segment 17.12±7.39 17.58±7.31 0.59 randomized clinical trial comparing different strate-
 Acute gain, mm gies for lesion preparation in patients with calcified
  In-stent 1.74±0.45 1.70±0.42 0.45 coronary artery disease treated with DES and the
  In-segment 1.50±0.51 1.47±0.64 0.61
first randomized trial to compare an MB-based strat-
egy with a strategy of RA. In an elderly population
Values are n (%) or mean±SD. MB indicates modified balloon; and RA,
with complex calcific atherosclerotic disease treated
rotational atherectomy.
*As adjudicated by the Angiographic Core Lab. at 2 experienced PCI centers, the primary end point
of strategy success was higher with RA, which was
mm. Therefore, noninferiority for the coprimary end mainly attributed to a higher frequency of crossover
Downloaded from http://ahajournals.org by on June 19, 2023

point was met at a P value of 0.02. The results were
consistent in an as-treated analysis, although LLL in
the MB group was slightly lower (0.14±0.40 versus
0.22±0.39 mm; P=0.16). Binary restenosis (both in-
stent and in-segment) was low and not significantly dif-
ferent between both groups.
and stent failure in the MB group. Compared with
lesion preparation with an MB, RA did not result in
higher LLL at 9 months when combined with a mod-
ern DES, and clinical outcome was excellent with both
strategies with low mortality, MI, and target vessel
revascularization rates.

Figure 3. Late lumen loss at 9 mo.

Cumulative frequency curves of the coprimary
end point of in-stent late lumen loss at 9-mo
follow-up angiography in both study groups.

Circ Cardiovasc Interv. 2018;11:e007415. DOI: 10.1161/CIRCINTERVENTIONS.118.007415 October 2018 8

 Abdel-Wahab et al; PREPARE-CALC
Table 5. Clinical Outcome at 9 Months (n=200 Patients)
MB (n=100) RA (n=100)
Death 2 (2%)
 Cardiac death 1 (1%)
 Noncardiac death 1 (1%)
MI 3 (3%)
 Target vessel MI 1 (1%)
 Periprocedural MI 1 (1%)
 Spontaneous MI 2 (2%)
Stent thrombosis (definite/ 0 (0%)
probable)
TLR 7 (7%)
TVR 8 (8%)
 Clinically indicated TVR 6 (6%)
Any revascularization 21 (21%)
Target vessel failure 8 (8%)
Values are n (%). MB indicates modified balloon; MI, myocardial infarction;
RA, rotational atherectomy; TLR, target lesion revascularization; and TVR, target
vessel revascularization.
Severe coronary calcification is encountered in up to
20% of patients treated with PCI,1 with an even higher
prevalence in certain patient subgroups, particularly the
elderly and those with extensive atherosclerotic disease.
Clinical practice guidelines emphasize the importance
of lesion preparation before attempting stent implan-
tation for a variety of reasons: calcium often impairs
Downloaded from http://ahajournals.org by on June 19, 2023
balloon advancement, prevents adequate balloon dila-
tation, impairs stent delivery, damages stent struts or
polymeric coatings during vigorous stent advancement,
and prevents adequate stent expansion and apposi-
tion.1–3,16,17 Therefore, PCI of calcified coronary lesions
is usually more complex and time consuming and may
be associated with higher periprocedural and long-term
complications if procedures are not adequately planned
and executed.1,2 A variety of tools and techniques are
currently available for lesion preparation, including
standard balloons (compliant and noncompliant), MB
(cutting and scoring), the recently introduced lithoplasty
balloon, as well as atheroablative techniques, such as
rotational, orbital, and laser atherectomy. The choice
between these different strategies is largely dependent
on their availability and on operator preference and
experience, with no well-defined criteria that favor one
technique over the other. In this setting, assessing the
feasibility, safety, and efficacy of these different tech-
niques in the context of a randomized controlled trial is
of clinical interest.
Strategy success is an outcome measure meant to
characterize the success of lesion preparation and ulti-
mately stent implantation with a certain PCI strategy
and is thus an appropriate end point for the compara-
tive evaluation of the feasibility of different tools and
techniques. Theoretically, including crossovers from one
Circ Cardiovasc Interv. 2018;11:e007415. DOI: 10.1161/CIRCINTERVENTIONS.118.007415
group to the other in the composite primary end point
P Value may be considered a source of bias. However, assess-
2 (2%) 1.00
ing the success of a balloon-based strategy justifies the
inclusion of crossovers as an important measure of stra-
1 (1%) 1.00
tegic failure. In addition, indications for crossovers were
1 (1%) 1.00
clearly defined in the trial protocol and independently
2 (2%) 1.00 adjudicated by the event committee. In our trial, a strat-
2 (2%) 1.00 egy of predilatation with an MB failed in almost 20%
2 (2%) 1.00 of attempted procedures. The majority of these failures
0 (0%) 0.50 were because of the inability of the balloon to reach
0 (0%) 1.00
the target lesion or to completely expand inside the
calcified rigid plaque, and the procedures could only
2 (2%) 0.17 be successfully completed with bailout atherectomy.
This can be partly explained by the difficulties associ-
3 (3%) 0.21
ated with MB delivery because of its higher crossing
3 (3%) 0.50
profile,16 although the majority of procedures were per-
8 (8%) 0.01 formed with the more flexible and deliverable scoring
6 (6%) 0.78 balloon, and predilatation with low-profile balloons to
allow subsequent passage of the MB was allowed and
commonly adopted by the treating cardiologist. On the
contrary, virtually all patients (and lesions) were treat-
able with RA. No crossover to balloon dilatation was
encountered, and the only 2 cases of strategy failure
with RA were because of extensive wire-induced dis-
section preventing further percutaneous treatment in
one case and stent failure in the other case. This find-
ing signifies the feasibility of RA in nearly every calcified
lesion, although the feasibility in chronic total occlu-
sions cannot be assessed from this trial because of the
low number of included patients.
Although RA seems to be successful in almost all
calcified lesions, the procedure requires more fluoros-
copy time and is usually longer than a balloon-based
PCI procedure—a finding that was also observed in
the ROTAXUS trial.6 In addition, the technique is some-
what different to standard PCI and requires additional
training and experience. Because 80% of patients with
severe calcification are treatable with MB, characteriz-
ing the subgroup that is only treatable with atherectomy
remains of clinical significance. Crossing-over to RA
enables procedural success but may be associated with
longer procedural time, increased procedural costs, and
higher periprocedural complications.18,19 Despite the
consistent finding of a higher strategy success with RA
in the majority of patient and lesion subsets in this trial,
subgroup analysis suggests that male patients, lesions
located in the right coronary artery or left circumflex
artery, severe (≥80%), and type C lesions more often
require RA compared with female patients, lesions
located in the left anterior descending coronary artery,
less severe (<80%), and type B2 lesions. However, fur-
ther assessment of factors associated with bailout RA is
necessary and may be enhanced by intravascular imag-
ing. Previous small studies using intravascular ultra-
sound and more recently OCT suggest optimal stent
expansion is better achieved if calcified plaques are
October 2018 9
 Abdel-Wahab et al; PREPARE-CALC
fractured before stent implantation.9,20 In this trial, OCT
was recommended before lesion preparation and at the
end of the PCI procedure and was performed in the
majority of treated lesions. Analysis of this subgroup is
planned and may give further mechanistic insights into
the criteria of success of both MB- and RA-based strate-
gies in this setting.
We observed a low rate of procedural complications,
which supports the safety of both strategies consider-
ing the complexity of treated patients and anatomies.
However, the pattern of complications goes in the
expected direction, with numerically more dissections
and side branch compromise in the MB arm and more
slow-flow and pericardial effusions in the RA arm, which
can be explained by the different mechanism of action
of both techniques (plaque laceration versus removal).
This may also explain the significantly higher number
of implanted stents per lesion in the MB group. One of
3 pericardial effusions in the RA group was induced by
a transient pacemaker lead introduced during atherec-
tomy of the right coronary artery, which is a common
practice but might not be necessary in all patients as
recently recommended.8 However, and despite proce-
dural complexity, clinical events during the in-hospital
period were rare, and periprocedural MI was uncom-
mon. Although the effect of center and operator expe-
rience cannot be determined from this study, treatment
of heavily calcified lesions requires special techniques,
and, in elective cases, should probably be performed in
Downloaded from http://ahajournals.org by on June 19, 2023
a well-equipped setting to facilitate the achievement of
similar outcomes.
One of the interesting findings in this trial is the
excellent acute luminal gain achieved with MB, which
was not significantly different from that obtained with
RA. Previous trials have consistently shown a higher
acute gain with RA compared with standard balloon
angioplasty,6,21,22 signifying more complete vessel prep-
aration and better lumen/stent expansion. The design
of cutting and scoring balloons and their focused force
expansion appears to allow more consistent dilatation
of rigid atherosclerotic lesions in a way that seems to
allow similar stent expansion compared with RA. If the
MB is able to cross and expand, final luminal gain is
comparable with atherectomy.
The main drawback of RA in previous trials was its
association with an exaggerated neointimal response
probably triggered by thermal injury and resulting in
higher rates of revascularization compared with balloon
angioplasty.21,22 In ROTAXUS, and despite the higher
acute gain, LLL after RA followed by implantation of
a first-generation DES (TAXUS; Boston Scientific) was
significantly higher compared with standard balloon
predilatation.6 In PREPARE-CALC, RA was, for the first
time, not associated with excessive neointimal response,
with a low LLL that is noninferior compared with the
control arm. This observation may be explained by the
Circ Cardiovasc Interv. 2018;11:e007415. DOI: 10.1161/CIRCINTERVENTIONS.118.007415
cotreatment with a modern ultrathin strut sirolimus-
eluting stent with a biodegradable polymer (Orsiro),
which has been previously associated with favorably
low rates of target lesion revascularization and stent
thrombosis and even lower target vessel failure rates
compared with everolimus-eluting stents.23 The advan-
tages of this stent in the setting of severe coronary
calcification are probably twofold: first, the stent back-
bone provides flexibility and deliverability in severely
calcified lesions with a double-helix stent design and
ultrathin struts24; second, its superior efficacy in inhibit-
ing neointimal response appears to counterbalance the
effects of thermal injury thereby neutralizing its effect
on restenosis.
Overall, the clinical event rates in this trial at 9 months
are low, particularly when compared with previous tri-
als with similar patient and lesion complexity.6,25,26 This
may be explained by the profile of included patients
(elderly with complex lesions but with stable coronary
artery disease, preserved left ventricular function, and
low incidence of atrial fibrillation) and by the success of
performed interventions (aggressive lesion preparation,
high rate of postdilatation, high acute gain, low residual
stenosis, few periprocedural complications, and mod-
ern DES). The numerically fewer target lesion revas-
cularization and target vessel revascularization events
in the RA group are encouraging and correspond to a
lower angiographic binary restenosis rate, but the trial
remains underpowered to assess differences in these
clinical end points.
This study has some limitations. First, it includes a
cohort almost exclusively treated through the femo-
ral access route. Although complex procedures, such
as RA, often require large sized catheters and optimal
guide catheter support, advances in transradial tools
may allow the performance of these interventions via
the radial access route as well. On the contrary, an
interaction of the trial primary end points with the
access route is highly unlikely. Second, the majority of
cases in the MB group were performed using a scoring
rather than a cutting balloon, and thus, the differential
performance of the latter cannot be adequately deter-
mined from this study. MB with enhanced flexibility has
been recently developed and may potentially increase
success rates compared with those reported in this trial.
However, even if crossover cases caused by failure of
MB delivery are excluded from the trial’s primary end
point, strategy success remains significantly higher
in the RA group (87% versus 98%; P=0.005), which
undermines the superiority of RA in this setting. Finally,
the trial included patients predominantly experiencing
stable coronary artery disease, and, therefore, its find-
ings cannot be applied to patients presenting with an
acute coronary syndrome.
In conclusion, lesion preparation with upfront RA
before DES implantation is feasible in nearly all patients
October 2018 10
 Abdel-Wahab et al; PREPARE-CALC
with complex calcified coronary lesions and is more
commonly successful as a primary strategy compared
with MB. Patients treated with elective RA coupled with
a modern DES do not experience excessive LLL. On the
contrary, a strategy of provisional MB remains feasible,
safe, and effective as long as bailout RA is readily avail-
able and may offer the advantages of compatibility
with smaller sized catheters, relatively shorter proce-
dural time, and less irradiation.
ARTICLE INFORMATION
Received September 12, 2018; accepted September 14, 2018.
The Data Supplement is available at https://www.ahajournals.org/doi/
suppl/10.1161/CIRCINTERVENTIONS.118.007415.
Correspondence
Mohamed Abdel-Wahab, MD, Department of Cardiology, Heart Center Leipzig,
Leipzig University Hospital, Strümpellstraße 39, 04289 Leipzig, Germany. Email
mohamed.abdel-wahab@medizin.uni-leipzig.de
Affiliations
Department of Cardiology, Heart Center, Segeberger Kliniken, Bad Segeberg,
Germany (M.A.-W., R.T., V.G., A.A., M.A., D.S.S., G.R.). Department of
Cardiology, Heart Center Leipzig, Leipzig University Hospital, Germany
(M.A.-W., D.S.S.). Department of Cardiology, Deutsches Herzzentrum
München, Technical University of Munich, Germany (R.A.B., T.R., A.K.). German
Center for Cardiovascular Research, partner site Munich Heart Alliance,
Germany (R.A.B., A.K.). Department of Cardiology, Vivantes Wenckebach
Hospital, Berlin, Germany (M.E.-M.). Department of Mathematics, University
of Sussex, Brighton, United Kingdom (D.R.R.).
Downloaded from http://ahajournals.org by on June 19, 2023
Acknowledgments
We are grateful to the clinical research group at the Heart Center, Segeberger
Kliniken GmbH, especially Susanne Sachse, Friederike Geyer, Daniela
Schürmann-Kuchenbrandt, and Monika Bahnsen-Maass.
Sources of Funding
This study is financed by the Heart Center, Segeberger Kliniken GmbH, Bad
Segeberg, Germany.
Disclosures
Dr Abdel-Wahab reports being a proctor for Boston Scientific. Drs Toelg and
Richardt report speaker honoraria from Boston Scientific, Abbott Vascular, and
Biotronik. Dr Byrne reports lecture fees from B. Braun Melsungen AG, Boston
Scientific, Biotronik, and Micell Technologies and research funding to the insti-
tution from Boston Scientific and Celonova Biosciences. Dr Geist reports lecture
fees from Boston Scientific. The other authors report no conflicts.
REFERENCES
1. Généreux P, Madhavan MV, Mintz GS, Maehara A, Palmerini T, Lasalle
L, Xu K, McAndrew T, Kirtane A, Lansky AJ, Brener SJ, Mehran R, Stone
GW. Ischemic outcomes after coronary intervention of calcified vessels
in acute coronary syndromes. Pooled analysis from the HORIZONS-AMI
(Harmonizing Outcomes With Revascularization and Stents in Acute
Myocardial Infarction) and ACUITY (Acute Catheterization and Urgent
Intervention Triage Strategy) TRIALS. J Am Coll Cardiol. 2014;63:1845–
1854. doi: 10.1016/j.jacc.2014.01.034
2. Bourantas CV, Zhang YJ, Garg S, Iqbal J, Valgimigli M, Windecker S, Mohr
FW, Silber S, Vries Td, Onuma Y, Garcia-Garcia HM, Morel MA, Serruys
PW. Prognostic implications of coronary calcification in patients with
obstructive coronary artery disease treated by percutaneous coronary
intervention: a patient-level pooled analysis of 7 contemporary stent tri-
als. Heart. 2014;100:1158–1164. doi: 10.1136/heartjnl-2013-305180
Circ Cardiovasc Interv. 2018;11:e007415. DOI: 10.1161/CIRCINTERVENTIONS.118.007415
3. Levine GN, Bates ER, Blankenship JC, Bailey SR, Bittl JA, Cercek B,
Chambers CE, Ellis SG, Guyton RA, Hollenberg SM, Khot UN, Lange RA,
Mauri L, Mehran R, Moussa ID, Mukherjee D, Nallamothu BK, Ting HH;
American College of Cardiology Foundation; American Heart Association
Task Force on Practice Guidelines; Society for Cardiovascular Angiography
and Interventions. 2011 ACCF/AHA/SCAI guideline for percutaneous
coronary intervention. A report of the American College of Cardiology
Foundation/American Heart Association Task Force on Practice Guidelines
and the Society for Cardiovascular Angiography and Interventions. J Am
Coll Cardiol. 2011;58:e44–e122. doi: 10.1016/j.jacc.2011.08.007
4. Fitzgerald PJ, Ports TA, Yock PG. Contribution of localized calcium depos-
its to dissection after angioplasty. An observational study using intravas-
cular ultrasound. Circulation. 1992;86:64–70.
5. Moussa I, Di Mario C, Moses J, Reimers B, Di Francesco L, Martini G,
Tobis J, Colombo A. Coronary stenting after rotational atherectomy in
calcified and complex lesions. Angiographic and clinical follow-up results.
Circulation. 1997;96:128–136.
6. Abdel-Wahab M, Richardt G, Joachim Büttner H, Toelg R, Geist V,
Meinertz T, Schofer J, King L, Neumann FJ, Khattab AA. High-speed
rotational atherectomy before paclitaxel-eluting stent implantation in
complex calcified coronary lesions: the randomized ROTAXUS (Rotational
Atherectomy Prior to Taxus Stent Treatment for Complex Native Coronary
Artery Disease) trial. JACC Cardiovasc Interv. 2013;6:10–19. doi:
10.1016/j.jcin.2012.07.017
7. Madhavan MV, Tarigopula M, Mintz GS, Maehara A, Stone GW, Généreux
P. Coronary artery calcification: pathogenesis and prognostic implications.
J Am Coll Cardiol. 2014;63:1703–1714. doi: 10.1016/j.jacc.2014.01.017
8. Barbato E, Carrié D, Dardas P, Fajadet J, Gaul G, Haude M, Khashaba A,
Koch K, Meyer-Gessner M, Palazuelos J, Reczuch K, Ribichini FL, Sharma
S, Sipötz J, Sjögren I, Suetsch G, Szabó G, Valdés-Chávarri M, Vaquerizo
B, Wijns W, Windecker S, de Belder A, Valgimigli M, Byrne RA, Colombo
A, Di Mario C, Latib A, Hamm C; European Association of Percutaneous
Cardiovascular Interventions. European expert consensus on rotational
atherectomy. EuroIntervention. 2015;11:30–36. doi: 10.4244/EIJV11I1A6
9. Maejima N, Hibi K, Saka K, Akiyama E, Konishi M, Endo M, Iwahashi
N, Tsukahara K, Kosuge M, Ebina T, Umemura S, Kimura K. Relationship
between thickness of calcium on optical coherence tomography and crack
formation after balloon dilatation in calcified plaque requiring rotational
atherectomy. Circ J. 2016;80:1413–1419. doi: 10.1253/circj.CJ-15-1059
10. Fonseca A, Costa Jde R Jr, Abizaid A, Feres F, Abizaid AS, Costa R, Staico R,
Mattos LA, Sousa AG, Grube E, Sousa JE. Intravascular ultrasound assess-
ment of the novel AngioSculpt scoring balloon catheter for the treatment
of complex coronary lesions. J Invasive Cardiol. 2008;20:21–27.
11. de Ribamar Costa J Jr, Mintz GS, Carlier SG, Mehran R, Teirstein P, Sano
K, Liu X, Lui J, Na Y, Castellanos C, Biro S, Dani L, Rinker J, Moussa I,
Dangas G, Lansky AJ, Kreps EM, Collins M, Stone GW, Moses JW, Leon
MB. Nonrandomized comparison of coronary stenting under intravas-
cular ultrasound guidance of direct stenting without predilation versus
conventional predilation with a semi-compliant balloon versus predila-
tion with a new scoring balloon. Am J Cardiol. 2007;100:812–817. doi:
10.1016/j.amjcard.2007.03.100
12. Redfors B, Maehara A, Witzenbichler B, Weisz G, Stuckey TD, Henry TD,
McAndrew T, Mehran R, Kirtane AJ, Stone GW, Généreux P. Outcomes
after successful percutaneous coronary intervention of calcified lesions
using rotational atherectomy, cutting-balloon angioplasty, or balloon-only
angioplasty before drug-eluting stent implantation. J Invasive Cardiol.
2017;29:378–386.
13. Mintz GS, Popma JJ, Pichard AD, Kent KM, Satler LF, Chuang YC, Ditrano
CJ, Leon MB. Patterns of calcification in coronary artery disease. A statisti-
cal analysis of intravascular ultrasound and coronary angiography in 1155
lesions. Circulation. 1995;91:1959–1965.
14. Cutlip DE, Windecker S, Mehran R, Boam A, Cohen DJ, van Es GA, Steg PG,
Morel MA, Mauri L, Vranckx P, McFadden E, Lansky A, Hamon M, Krucoff
MW, Serruys PW; Academic Research Consortium. Clinical end points
in coronary stent trials: a case for standardized definitions. Circulation.
2007;115:2344–2351. doi: 10.1161/CIRCULATIONAHA.106.685313
15. Julious SA. Sample sizes for clinical trials with normal data. Stat Med.
2004;23:1921–1986. doi: 10.1002/sim.1783
16. Barbato E, Shlofmitz E, Milkas A, Shlofmitz R, Azzalini L, Colombo A.
State of the art: evolving concepts in the treatment of heavily calcified
and undilatable coronary stenoses - from debulking to plaque modifica-
tion, a 40-year-long journey. EuroIntervention. 2017;13:696–705. doi:
10.4244/EIJ-D-17-00473
17. Windecker S, Kolh P, Alfonso F, Collet JP, Cremer J, Falk V, Filippatos G,
Hamm C, Head SJ, Jüni P, Kappetein AP, Kastrati A, Knuuti J, Landmesser
October 2018 11
 Abdel-Wahab et al; PREPARE-CALC
U, Laufer G, Neumann FJ, Richter DJ, Schauerte P, Sousa Uva M, Stefanini
GG, Taggart DP, Torracca L, Valgimigli M, Wijns W, Witkowski A; Authors/
Task Force Members. 2014 ESC/EACTS guidelines on myocardial revascu-
larization: the Task Force on Myocardial Revascularization of the European
Society of Cardiology (ESC) and the European Association for Cardio-
Thoracic Surgery (EACTS) developed with the special contribution of
the European Association of Percutaneous Cardiovascular Interventions
(EAPCI). Eur Heart J. 2014;35:2541–2619. doi: 10.1093/eurheartj/ehu278
18. Kawamoto H, Latib A, Ruparelia N, Boccuzzi GG, Pennacchi M, Sardella
G, Garbo R, Meliga E, D’Ascenzo F, Moretti C, Rossi ML, Presbitero P, Ielasi
A, Magri C, Nakamura S, Colombo A. Planned versus provisional rota-
tional atherectomy for severe calcified coronary lesions: insights from the
ROTATE multi-center registry. Catheter Cardiovasc Interv. 2016;88:881–
889. doi: 10.1002/ccd.26411
19. Allali A, Abdel-Wahab M, Sulimov DS, Jose J, Geist V, Kassner G, Richardt
G, Toelg R. Comparison of bailout and planned rotational atherectomy
for heavily calcified coronary lesions: a single-center experience. J Interv
Cardiol. 2017;30:124–133. doi: 10.1111/joic.12361
20. Lee MS, Shlofmitz E, Kong J, Lluri G, Srivastava PK, Shlofmitz R. Impact
of the use of intravascular imaging on patients who underwent orbital
atherectomy. J Invasive Cardiol. 2018;30:77–80.
21. Reifart N, Vandormael M, Krajcar M, Göhring S, Preusler W, Schwarz F,
Störger H, Hofmann M, Klöpper J, Müller S, Haase J. Randomized compar-
ison of angioplasty of complex coronary lesions at a single center. Excimer
Laser, Rotational Atherectomy, and Balloon Angioplasty Comparison
(ERBAC) study. Circulation. 1997;96:91–98.
Downloaded from http://ahajournals.org by on June 19, 2023
Circ Cardiovasc Interv. 2018;11:e007415. DOI: 10.1161/CIRCINTERVENTIONS.118.007415
22. Dill T, Dietz U, Hamm CW, Küchler R, Rupprecht HJ, Haude M, Cyran
J, Ozbek C, Kuck KH, Berger J, Erbel R. A randomized comparison of
balloon angioplasty versus rotational atherectomy in complex coronary
lesions (COBRA Study). Eur Heart J. 2000;21:1759–1766. doi: 10.1053/
euhj.2000.2242
23. Kandzari DE, Mauri L, Koolen JJ, Massaro JM, Doros G, Garcia-
Garcia HM, Bennett J, Roguin A, Gharib EG, Cutlip DE, Waksman R;
BIOFLOW V Investigators. Ultrathin, bioresorbable polymer sirolimus-
eluting stents versus thin, durable polymer everolimus-eluting stents
in patients undergoing coronary revascularisation (BIOFLOW V): a
randomised trial. Lancet. 2017;390:1843–1852. doi: 10.1016/S0140-
6736(17)32249-3
24. Tittelbach M, Diener T. Orsiro - The first hybrid drug-eluting stent, open-
ing up a new class of drug-eluting stents for superior patient outcomes.
Intervent Cardiol. 2011;6:142–144. doi: 10.15420/icr.2011.6.2.142
25. Lee MS, Martinsen BJ, Shlofmitz R, Shlofmitz E, Lee AC, Chambers J.
Orbital atherectomy treatment of severely calcified coronary lesions in
patients with impaired left ventricular ejection fraction: one-year out-
comes from the ORBIT II study. EuroIntervention. 2017;13:329–337. doi:
10.4244/EIJ-D-16-00301
26. Lipiecki J, Brunel P, Morice MC, Roguelov C, Walsh SJ, Richardt G,
Eerdmans P, Zambahari R, Berland J, Copt S, Stoll HP, Urban P. Biolimus
A9 polymer-free coated stents in high bleeding risk patients under-
going complex PCI: evidence from the LEADERS FREE randomised
clinical trial. EuroIntervention. 2018;14:e418–e425. doi: 10.4244/
EIJ-D-18-00293
October 2018 12