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REVIEWS

Transcatheter aortic valve implantation:


current and future approaches
Josep Rods-Cabau
Abstract | The first human transcatheter aortic valve implantation (TAVI) in 2002, and several subsequent
single-center series, showed the feasibility of this new approach for the treatment of patients with severe aortic
stenosis who were considered to be at very high or prohibitive surgical risk. More-recent multicenter registries
have confirmed the safety and efficacy of this procedure, despite a very-high-risk patient profile. Moreover,
the randomized, controlled PARTNER trial has confirmed both the superiority of TAVI over medical treatment in
patients not considered to be candidates for standard surgical aortic valve replacement and the noninferiority of
TAVI compared with surgical aortic valve replacement in high-risk patients. The hemodynamics of transcatheter
valves are usually excellent, although residual paravalvular aortic regurgitation (usually trivial or mild) is
frequent. Stroke, major vascular complications, and conduction disturbances leading to permanent pacemaker
implantation remain among the most-concerning periprocedural complications of TAVI. Nevertheless, promising
preliminary data exist for long-term outcomes following TAVI, valve-in-valve TAVI for surgical prosthesis
dysfunction, and for the treatment of lower-risk patients. Improvements in transcatheter valve technology,
optimization of procedural and midterm results, and confirmation of long-term durability of transcatheter valve
prostheses will determine the expansion of TAVI towards the treatment of a broader spectrum of patients.
Rods-Cabau, J. Nat. Rev. Cardiol. 9, 1529 (2012); published online 15 November 2011; doi:10.1038/nrcardio.2011.164

Introduction

Following experimental work in the transcatheter valve


field in the 1990s,1,2 the first-in-human transcatheter
aortic valve implantation (TAVI) was performed by
Cribier and colleagues in 2002.3 This case was followed
by several single-center and small multicenter registries
and series that included nonoperable or very-high-risk
patients, which were associated with promising results
that confirmed the feasibility of TAVI.418 In more-recent
years, the technology has developed very rapidly and, to
date, more than 40,000 transcatheter valves have been
implanted worldwide. The results of several large multi
center registries,1926 and the prospective, randomized
Placement of Aortic Transcatheter Valves (PARTNER)
trial,27,28 have provided definitive data confirming this
treatment as an alternative to standard surgical aortic
valve replacement (SAVR) in nonoperable and high-risk
surgical candidates. The objectives of this article are to
review the main characteristics of transcatheter valves
and TAVI procedures, and to evaluate the acute and late
outcomes associated with TAVI.

Transcatheter prosthetic valves

To date, two types of transcatheter aortic valves have


been widely used in the clinical setting: the balloonexpandable Edwards valvethe first-generation
Competing interests
The author declares associations with the following companies:
Edwards Lifesciences and St Jude Medical. See the article
online for full details of the relationships.

Cribier-Edwards, second-generation Edwards SAPIEN,


and third-generation Edwards SAPIEN XT (Edwards
Lifesciences Corporation, Irvine, CA, USA) versions
and the self-expandable CoreValve (Medtronic CV
Luxembourg S.a.r.l., Luxembourg) system.

Balloon-expandable Edwards valve


The first two generations of the Edwards valve (CribierEdwards and Edwards SAPIEN) comprised three leaflets of bovine pericardium mounted in a stainless steel
frame. The valves were implanted using 22French and
24French delivery catheters. The Edwards SAPIENXT
(Figure1a,b) is the third generation of the balloonexpandable Edwards valve, which consists of a trileaflet
pericardial bovine valve mounted in a cobalt chromium
frame. The frame design of the Edwards SAPIEN XT also
has fewer rows, columns, and vertical struts between commissure posts than the SAPIEN design. These changes
have led to a reduction in the valve size, with no loss of
radial strength. In addition, the scallop shape of the
SAPIEN XT leaflets reduces leaflet volume and improves
valve profile. The SAPIEN XT valve is available in 20mm,
23mm, 26mm, and 29mm sizes, and is implanted using
18French (for the 20mm and 23mm valves), 19French
(for the 26mm valve), or 22French (for the 29mm valve)
delivery catheter and sheath systems. Smaller 16French
(for the 20mm and 23mm valves), 18French (for the
26mm valve), and 20French (for the 29mm valve)
expandable sheaths (eSHEATH, Edwards Lifesciences
Corporation) are also available in Europe and Canada.

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Quebec Heart and


Lung Institute,
Laval University,
2725 Chemin Ste-Foy,
G1V4G5 Quebec City,
QC, Canada
josep.rodes@
criucpq.ulaval.ca

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Key points
Transcatheter aortic valve implantation (TAVI) represents a less-invasive strategy
than surgical aortic valve replacement (SAVR) for the treatment of severe
symptomatic aortic stenosis
The transfemoral approach is usually the first option for TAVI; transapical,
subclavian, axillary, and transaortic routes are alternative approaches
TAVI is currently the treatment of choice for patients not considered to be
candidates for SAVR, and a proven alternative for those considered to be at high
surgical risk
Transcatheter valves are associated with excellent hemodynamic results, usually
with concomitant improvements in the patients functional status and quality of
life; however, minor residual aortic regurgitation occurs in many patients
Periprocedural stroke, vascular and conduction disturbance complications,
occurrence of moderate or severe paravalvular aortic regurgitation, relatively high
midterm mortality, and valve durability beyond 3year follow-up are unresolved
issues in TAVI
The valve-in-valve treatment of surgical prosthesis dysfunction and the
treatment of intermediate-risk patients are two of the most-important fields for
the development of TAVI in the near future

Figure 1 | Photographs of the transcatheter prosthetic valves currently used for


transcatheter aortic valve implantation. a,b | The Edwards SAPIEN XT(Edwards
Lifesciences Corporation, Irvine, CA, USA) valve. c,d | The third generation of the
CoreValve(Medtronic CV Luxembourg S.a.r.l., Luxembourg) system (courtesy of
Marc Ruel, Ottawa Heart Institute, Ottawa, ON, Canada).

Self-expandable CoreValve system


The first generation of the CoreValve system consisted of
a self-expanding nitinol frame with a bovine pericardial
heart valve, and was implanted using a 25French delivery
catheter. The second generation of the CoreValve system
consisted of three leaflets of porcine pericardium seated
higher in the nitinol frame to provide true supra-annular
placement. The nitinol frame had been redesigned to
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increase radial force in the inflow portion and expand the


outflow diameter for a better anatomical fit. The valve was
implanted using a 21French delivery catheter. Finally, the
current, third generation of the CoreValve aortic system
(Figure1c,d) differs slightly from the previous version in
the sealing skirt (fabricated from three separate pieces
instead of one), to facilitate uniform tissue thickness and
improve the valve profile. The valve is available in 26mm,
29mm, and 31mm sizes, and is implanted using an
18French delivery catheter and sheath system.

Pre-TAVI work-up

The work-up before TAVI using the Edwards or CoreValve


prostheses is summarized in Figure2. Evaluation of the size
(by CT angiography or iliofemoral angiography), tortu
osity, and degree of calcification (assessed by CT) of iliofe
moral arteries is mandatory to determine the suitability of
the transfemoral approach.
The size of the aortic annulus is usually measured
by transthoracic echocardiography, transesophageal
echocardiography, CT angiography, or a combination
of these imaging techniques. Accurate measurementof
the aortic annulus is critical to determine the transcatheter valve size, which is systematically oversized
(by 25mm) with respect to the diameter of the aortic
annulus. Although sizing the aortic annulus with transesophageal echocardiography has been associated with
good clinical results in most cases, some studies have
suggested a tendency towards an underestimation of the
aortic annulus by echocardiography as compared with
CT angiography.2933 CT studies have clearly shown the
oval shape of the aortic annulus in most patients, further
highlighting the complexity of aortic annulus measurement. Indeed, CT angiography studies with 3D-imaging
reconstruction also provide very accurate spatial and temporal resolution for the evaluation of the aortic annulus.33
Importantly, annulus measurements and valve oversizing
have been mostly based on industry recommendations
rather than on scientific evidence. Future studies will have
to further evaluate the most-appropriate imaging modality to measure the aortic annulus and determine the gold
standard for aortic-annulus measurements before TAVI
as well as the most-appropriate degree of valve oversizing.
Coronary angiography is performed before the proce
dure to evaluate the presence and severity of coronary
artery disease. In cases of severe stenoses in the main coro
nary vessels, complete or partial coronary revasculariza
tion is often performed before TAVI, although no data
showing the superiority of this strategy compared with
no revascularization exist.

Approaches used for TAVI


Transfemoral approach
The transfemoral route (Figure3a) is the first choice
of approach in the vast majority of centers performing
TAVI procedures. As stated above, an accurate evaluation of the iliofemoral anatomy is of major importance
in determining the appropriateness of this approach for
each individual patient. The procedure is performed in
a catheterization laboratory or a hybrid operating room.
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Although surgical cut-down was the technique used for
the transfemoral approach at the beginning of the TAVI
experience, most centers are now using a fully percutaneous technique for this approach. This strategy makes it
possible to avoid the use of general anesthesia, especially
if the procedure is performed without transesophageal
echocardiographic guidance.

Transapical approach
The transapical approach (Figure3b) was first reported
as an alternative to the transfemoral approach in 2006by
Litchenstein and colleagues, 7 who used the CribierEdwards valve system. The approach requires a small
left lateral thoracotomy and a direct puncture of the left
ventricular apex. A 24French (for the 23mm and 26mm
valves) or 26French (for the 29mm valve) sheath is used
to advance the Edwards SAPIEN XT valve, and implanta
tion is performed in a similar way to that used with the
transfemoral approach (see the next section on valve
placement). In the era when larger catheters (22French)
were used for the transfemoral approach, about half of the
TAVI procedures with the Cribier-Edwards and Edwards
SAPIEN valves were performed using the transapical
approach;19,20 this percentage is expected to decrease with
the use of smaller (18French) catheters. First-in-human
CoreValve implantation by the transapical approach has
been reported,34 but this approach has not been further
developed for this valve system.
Potential advantages of the transapical approach
include the avoidance of using large catheters though
the iliofemoral system, aortic arch, ascending aorta,
and aortic valve; improved coaxility of the valve prosthesis within the aortic annulus, which can be especially
helpful in cases of horizontal aorta;35 and the possibility
of obtaining very accurate transesophageal echocardiographic images for valve positioning, which might lead
to a reduction in the amount of contrast used during the
procedures.35 The main disadvantages are the need for
a thoracotomy; a greater degree of myocardial injury,
owing to the apical perforation of the left ventricle;36 and
the potentially life-threatening bleeding complications
associated with the surgical repair of the apex.
Transaortic approach
In 2009 and 2010, the use of the transaortic approach
through a small right or mid sternotomy (Figure3c) was
proposed as an alternative approach with the Corevalve
and Edwards systems.3739 Although requiring sternotomy,
this approach avoids the use of large catheters through the
iliofemoral system and aortic arch, and avoids puncture
of the ventricular apex.
Subclavian approach
The left subclavian approach (Figure3d) has emerged
as an alternative to the transfemoral approach with the
CoreValve system.40,41 A surgical cut-down is needed
to isolate the subclavian artery (usually the left vessel).
The very short distance between the vascular access and
the native aortic valve might be associated with better
control of the CoreValve prosthesis during positioning

Patients considered at very high risk or nonsurgical candidates

Evaluation by a TAVI multidisciplinary team


(interventional cardiologists and cardiac surgeons)

Medical treatment

Patients eligble for TAVI

Surgical aortic
valve replacement

Coronary angiography
Transthoracic/transesophageal echocardiogram
CT
CT angiography and/or iliofemoral angiography

Iliofemoral axis >6 mm (Edwards SAPIEN XT20 mm, 23 mm or CoreValve26 mm, 29 mm, 31 mm)
Iliofemoral axis >6.5 mm (Edwards SAPIEN XT 26 mm)
Iliofemoral axis >7 mm (Edwards SAPIEN XT 29 mm)
Absence of significant peripheral vascular disease
Absense of severe iliofemoral calcification
Yes
Transfemoral approach using the
Edwards SAPIEN XT or CoreValve systems

No
Transapical approach using the
Edwards SAPIEN XT system
or
Subclavian-axillary approach using the
CoreValve system with
axilo-subclavian axis >6 mm
and/or >7 mm with patent LIMA graft
or
Transaortic approach using the
Edwards SAPIEN XT or CoreValve systems

Figure 2 | Pre-procedural work-up in patients with severe aortic stenosis who are
candidates for a TAVI procedure with the Edwards SAPIEN XT(Edwards Lifesciences
Corporation, Irvine, CA, USA) valve or CoreValve(Medtronic CV Luxembourg S.a.r.l.,
Luxembourg) systems. Abbreviations: CT, computed tomography; LIMA, left internal
mammary artery; TAVI, transcatheter aortic valve implantation.

and deployment. However, any injury of the subclavian


artery would translate into a major intrathoracic bleeding that might be difficult to control. Tamburino etal.22
reported the use of the subclavian approach in up to 20%
of the patients included in the Italian registry.

Transaxillary approach
First-in-human CoreValve implantation by the trans
axillary approach (Figure3e) has been reported.42 Like
the subclavian approach, a surgical cut-down is performed to isolate the left axillary artery, and the sheath
and delivery catheters are advanced through the axillary
artery. The potential advantage of this approach versus
the subclavian approach is that any injury to the axillary
artery could be easily repaired with no major clinical
consequences, as compared with the potentially lifethreatening consequences of a subclavian-artery injury.
Indeed, and unlike in iliofemoral vessels, occlusion of
the axillary artery would be compensated by the col
lateral circulation between the thyrocervical trunk of the
subclavian artery and the subscapular artery.

Valve placement

Balloon aortic valvuloplasty is systematically performed


before valve implantation for both types of prosthetic
valves currently used in TAVI, although Grube etal. have

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a

Figure 3 | Approaches used for transcatheter aortic valve implantation. a | The transfemoral approach. The delivery
catheter for implantation of the valve prosthesis is advanced through the right or left femoral arteries. b | The transapical
approach. After left lateral minithoracotomy (usually between the fifth and sixth intercostal spaces), the delivery catheter
for implantation of the valve prosthesis is advanced through the left ventricular apex. c | The transaortic approach. After
right or mid ministernotomy, the delivery catheter for implantation of the valve prosthesis is advanced directly through the
ascending aorta. d | The subclavian approach. The delivery catheter for implantation of the valve prosthesis is advanced
through the subclavian artery (usually the left vessel). e | The transaxillary approach. The delivery catheter for implantation
of the valve prosthesis is advanced through the axillary artery (usually the left vessel).

suggested direct implantation of the CoreValve system


with no prior balloon valvuloplasty.43 The Edwards valve
is positioned using fluoroscopy, angiography, and transesophageal echocardiography, and valve expansion is
achieved by balloon inflation under rapid pacing (180
220bpm) to minimize cardiac output and avoid valve
embolization during valve implantation (Figure4a,b).
CoreValve positioning is usually performed by fluoro
scopy and angiography, and the valve is deployed without
rapid pacing, by retracting the outer sheath of the delivery
catheter (Figure4ce).

Outcomes of the procedure

Findings from the eight largest multicenter registries and


series of TAVI published in the past few years are summarized in Table1. The patients included in the multicenter registries were considered nonoperable or at very
high surgical risk, with mean logistic EuroSCORE >20%
and Society of Thoracic Surgeons (STS) score >8%.1926
Most patients were octogenarians, about half of them
had prior coronary artery disease, about one-third had
chronic kidney disease, and about a quarter had chronic
obstructive pulmonary disease or peripheral vascular
disease. Overall, the procedural success rate was >90%
in all studies. Valve embolization or conversion to open
heart surgery occurred in ~1% of the patients (0.33.0%
for valve embolization; 0.52.3% for conversion to open
heart surgery).
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The PARTNER trial is, to date, the only prospective,


randomized trial on TAVI. The findings are summarized
in Table1. PARTNER included two differentiated cohorts
of patientsthose considered to be nonoperable (that is,
comorbidities leading to a predicted risk of 50% of death
by 30days after surgery or a serious irreversible condition; patients with comorbidities leading to a life expectancy <1year were excluded)27 and those considered to
be at high surgical risk (that is, predicted risk of operative mortality 15% as determined by site surgeon and
cardiologist; guideline of STS score 10).28 The Edwards
SAPIEN valve was used in all cases. The primary end
point was all-cause mortality at 1year follow-up, and the
trial was powered to demonstrate the superiority of TAVI
versus medical treatment (including balloon valvuloplasty) for the nonoperable cohort and the noninferiority
of TAVI versus SAVR for the high-surgical-risk cohort.

Mortality
In the aforementioned multicenter registries and series,
mortality was systematically <10% in patients treated
using the transfemoral approach and ranged from
11.3% to 16.9% in patients treated using the transapical approach, probably owing to the higher risk profile
of the patients treated via the latter route.1926 At 1year
follow-up, the survival rates were ~80% (7585%) for
the transfemoral approach and ~70% (6378%) for the
transapical approach.
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In the nonoperable cohort of the PARTNER trial,27
the 30-day mortality was 5.0% in the TAVI group (trans
femoral approach in all patients) and 2.8% in the medical
treatment group (P=0.41). Importantly, up to 84% of
the patients in the medical treatment group had at least
one procedure of balloon aortic valvuloplasty during the
study period. At 1year follow-up, mortality was 30.7%
in the TAVI group, compared with 50.7% in the medical
treatment group (P<0.0001).
In the high-risk PARTNER trial cohort,28 30-day mortal
ity was 3.4% in the TAVI group, compared with 6.5% in
the SAVR group (P=0.07). Mortality at the 1year followup was 24.2% and 26.8% in the TAVI and SAVR groups,
respectively (P=0.44). In patients eligible for the trans
femoral approach, mortality at the 30-day and 1year
follow-ups in the TAVI group were 3.3% and 22.2%, respectively, and 6.2% and 26.4% in the SAVR group (P=0.13 for
30-day mortality, P=0.29 for 1year mortality). In patients
ineligible for the transfemoral approach, mortality at the
30-day and 1year follow-ups was 3.8% and 29%, respectively, in the TAVI group (using the transapical approach)
and 7.0% and 27.9% in the SAVR group (P=0.32 for 30-day
mortality, P=0.85 for 1year mortality).
Very few data on the long-term results associated
with TAVI procedures exist. Gurvitch etal. reported a
survival rate of 51% at 3year follow-up in 88 patients
who had undergone TAVI with the balloon-expandable
Cribier-Edwards or Edwards SAPIEN valves.44 Among
the patients who survived the TAVI procedure, the survival rates were 74% and 61% at the 2year and 3year
follow-ups, respectively. Buellesfeld etal. reported a
survival rate of 72% at 2year follow-up after TAVI with
the CoreValve system.45 The patients included in these
studies represent the initial TAVI experience and the use of
very early versions of the transcatheter valve and delivery
catheter systems, which, together with the learning-curve
phenomenon, has probably had a negative influence on the
results. Indeed, in the past few years, 1year survival rates
from some registries have been reported to be 80%,1926
and we can expect better survival rates at the 2year and
3year follow-ups in the coming years. Importantly, no
structural failures of the transcatheter valves have been
seen in studies with a follow-up of more than 1year.44,45
The baseline and procedural factors associated with
poorer outcomes after TAVI are shown in Table2.
In summary, baseline cardiovascular factors (low
left ventricular ejection fraction [LVEF], pulmonary
hypertension, and severe mitral regurgitation) and periprocedural complications (low cardiac output, major
vascular complications, cardiac tamponade, conversion
to open heart surgery, acute kidney injury, stroke, and
moderate-to-severe residual aortic regurgitation) seem
to have a major role in acute mortality and in mortality
occurring during the 1year follow-up period.19,22,26,4651
Generally, noncardiac comorbidities, such as chronic
obstructive pulmonary disease, chronic kidney disease,
and liver disease, are important predictors of mortality
during the follow-up period, rather than of acute mortality.19,22,26,4651 Indeed, studies have shown that most deaths
occurring late after TAVI are of noncardiac origin,19,48,52

Figure 4 | Valve implantation of balloon-expandable and self-expandable


transcatheter valves. a | Deployment of a balloon-expandable Edwards SAPIEN XT
(Edwards Lifesciences Corporation, Irvine, CA, USA) valve. The white arrow indicates
the balloon during maximal expansion. b | Fluoroscopic image of an Edwards
SAPIEN XTvalve (white arrow) after valve implantation. c,d|Deployment of a selfexpandable CoreValve(Medtronic CV Luxembourg S.a.r.l., Luxembourg) system
(courtesy of Marc Ruel, Ottawa Heart Institute, Ottawa, ON, Canada). The white
arrows indicate the outer sheath that is being retracted to allow the expansion of
the valve. e|Fluoroscopic image of a third-generation CoreValvesystem (white
arrow) after valve implantation (courtesy of Marc Ruel, Ottawa Heart Institute,
Ottawa, ON, Canada).

highlighting the importance of patient selection in the


results of TAVI at midterm follow-up.
Surgical risk scores, such as logistic EuroSCORE and
STS score, have been used to estimate the mortality risk
of the patients undergoing SAVR and TAVI. Although
the logistic EuroSCORE has been shown to be a predictor of 30-day and 1year mortality in some studies of
TAVI,48,53 this risk score seems to overestimate the risk
of mortality in most cases.5456 By contrast, the mortality
risk as determined by the STS score seems to be close to
the observed mortality in patients undergoing SAVR and
TAVI,19,27,28,55 although no studies to date have found this
score to be an accurate predictor of acute and midterm
mortality after TAVI. In addition to baseline and procedural factors, the learning-curve phenomenon and the
improvements in valve prosthesis and delivery catheters
have also been associated with a substantial improvement
in the results obtained with TAVI.5759

Major periprocedural complications


The most-important complications associated with
TAVI are summarized in Table1. Notably, the definition of major complications associated with TAVI has
not been standardized, which might explain at least

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Table 1 | Findings from the large multicenter TAVI registries, series, and randomized controlled trial
Study, n

Approach

Valve type

Canadian,19
n=339

TF in 162;
TA in 177

SOURCE,20
n=1,038

MeanSD, or
median (IQR),
Logistic Euro
SCORE (%)

Procedural
success
(%)

30-day
mortality
(%)

Major
vascular
complica
tions (%)

Stroke (%)

Hemodialysis
(%)

Permanent
pacemaker
(%)

1-year
survival
(%)

CribierAll: 27.716.3;
Edwards
TF: 25.814.9;
in 57;
TA: 29.417.2
SAPIEN
in 275;
SAPIENXT
in 7

All: 93.3;
TF: 90.5;
TA: 96.1

All: 10.4;
TF: 9.5;
TA: 11.3

All: 13;
TF: 13.1;
TA: 13.0

All: 2.3;
TF: 3.0;
TA: 1.7

All: 2.6;
TF: 1.8;
TA: 3.4

All: 4.9;
TF: 3.6;
TA: 6.2

All: 76;
TF: 75;
TA: 78

TF in 463;
TA in 575

SAPIEN

TF: 25.714.5;
TA: 29.116.3

All: 93.8;
TF: 95.2;
TA: 92.7

All: 8.5;
TF: 6.3;
TA: 10.3

All: 7.0;
TF: 10.6;
TA: 2.4

All: 2.5;
TF: 2.4;
TA: 2.6

All: 4.3;
TF: 1.3;
TA: 7.1

All: 7.0;
TF: 6.7;
TA: 7.3

All: 76.1;
TF: 81.1;
TA: 72.1

European,21
n=646

TF in 646

CoreValve

TF: 23.113.8

TF: 97.2

TF: 8.0

TF: 1.9

TF: 1.9

N/A

TF: 9.3

N/A

Italian,22
n=663

TF in 599;
SC in 64

CoreValve

All: 23.013.7

All: 98.0

All: 5.4

All: 2.0

All: 1.2

N/A

All: 16.6

All: 85

France,23
n=244

TF with
SAPIEN
in 95;
TA with
SAPIEN
in 71;
TF with
CoreValve
in 66;
SC with
CoreValve
in 12

SAPIEN
in 166;
CoreValve
in 78

All: 25.611.4;
TF with
SAPIEN:
25.611.3;
TA with
SAPIEN:
26.811.6;
TF with
CoreValve:
24.711.2;
SC with
CoreValve:
24.614.5

All: 98.3

All: 12.7;
TF with
SAPIEN:
8.4;
TA with
SAPIEN:
16.9;
TF with
CoreValve:
15.1;
SC with
CoreValve:
8.3

All: 7.3;
TF with
SAPIEN:
6.3;
TA with
SAPIEN:
5.6;
TF with
CoreValve:
7.5;
SC with
CoreValve:
8.3

All: 3.6;
TF with
SAPIEN:
4.2;
TA with
SAPIEN:
2.8;
TF with
CoreValve:
4.5;
SC with
CoreValve:
0

All: 1.6;
TF with
SAPIEN:
1.0;
TA with
SAPIEN:
2.8;
TF with
CoreValve:
1.5;
SC with
CoreValve:
0

All: 11.8;
TF with
SAPIEN:
5.3;
TA with
SAPIEN:
5.6;
TF with
CoreValve:
25.7;
SC with
CoreValve:
25.0

N/A

German,24
n=697

TF in 644;
SC in 22;
TA in 26;
TAo in 5

SAPIEN
in 109;
CoreValve
in 588

All: 20.513.2

All: 98.4

All: 12.4

All: 19.5

All: 2.8

N/A

All: 39.3;
SAPIEN:
22.0;
CoreValve:
42.5

N/A

Belgian,25
n=328

TF or TA
with
SAPIENin
187;
TF with
CoreValve
in 141

SAPIEN
in 187;
CoreValve
in 141

All: 2816;
SAPIEN:
3016;
CoreValve:
2515

All: 97.0;
SAPIEN:
97.0;
CoreValve:
98.0

All: 11.0;
SAPIEN:
12.0;
CoreValve:
11.0

N/A

All: 5.0;
SAPIEN:
5.0;
CoreValve:
4.0

All: 6;
SAPIEN:
6;
CoreValve:
7

All: 13;
SAPIEN: 5;
CoreValve:
22

TF with
SAPIEN:
82;
TA with
SAPIEN:
63;
TF with
CoreValve:
79

UK,26 n=870

TF in 599;
Other
approaches
in 271

SAPIEN
in 410;
CoreValve
in 452

All: 18.5
(11.7, 27.9);
TF: 17.1
(11, 25.5);
Other routes:
21.4
(14.4, 33.6);
CoreValve:
18.1
(11.1, 27.9);
SAPIEN: 18.5
(12.4, 27.7)

All: 97.2;
TF: 97.3;
Other
routes:
97.1;
CoreValve:
98.2;
SAPIEN:
98.1

All: 7.1;
TF: 5.5;
Other
routes:
10.7;
CoreValve:
5.8;
SAPIEN:
8.5

All: 6.3;
TF: 8.4;
Other
routes:
1.9;
CoreValve:
6.2;
SAPIEN:
6.3

All: 4.1;
TF: 4.0;
Other
routes:
4.1;
CoreValve:
4.0;
SAPIEN:
4.2

N/A

All: 16.3;
CoreValve:
24.4;
SAPIEN:
7.4

All: 78.6;
TF: 81.5;
Other
routes:
72.3;
CoreValve:
78.3;
SAPIEN:
79.4

PARTNER
non-operable
cohort,27
n=179

TF in 179

SAPIEN

TF: 26.417.2

TF: 98.8

TF: 5.0

TF: 16.2

TF: 6.7

TF: 1.1

TF: 3.4

TF: 69.3

PARTNER
high-risk
cohort,28
n=348

TF in 244;
TA in 104

SAPIEN

All: 29.316.5

N/A

All: 3.4;
TF: 3.3;
TA: 3.8

All: 11.0

All: 4.6

All: 2.9

All: 3.8

All: 75.8;
TF: 77.8;
TA: 71

Edwards Lifesciences Corporation (Irvine, CA, USA) is the manufacturer and registered trademark owner of the Cribier-Edwards, SAPIEN, and SAPIEN XTvalves. Medtronic Inc. (Minnesota, MN, USA)
manufactures the CoreValve, which is a registered trademark of Medtronic CV Luxembourg S.a.r.l., Luxembourg. Abbreviations: IQR, interquartile range; N/A, data not available; SC, subclavian; TA,
transapical; TAo, transaortic; TAVI, transcatheter aortic valve implantation; TF, transfemoral.

20 | JANUARY 2012 | VOLUME 9

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Table 2 | Factors predictive of 30-day and 1year mortality after trancatheter aortic valve implantation
Predictive factor

Study, n

Mortality period

OR or HR
for mortality

95% CI

Chronic obstructive pulmonary disease

Rods-Cabau etal.,19 n=339


Sinning etal.,47 n=77
Moat etal.,26 n=870

1year
1year
1year

1.75
2.9
1.41

1.092.83
1.27.1
1.001.98

Chronic kidney disease

Rods-Cabau etal.,19 n=339


Thomas etal.,48 n=463 for TF
Thomas etal.,48 n=575 for TA
Sinning etal.,47 n=77

1year
1year
1year
30days
1year
30days to 1year

2.30
2.09
1.44
5.9
3.9
2.53

1.383.84
1.343.26
1.051.98
1.424.8
1.69.5
1.016.35

Baseline noncardiac variables

Tamburino etal.,22 n=663


Diabetes mellitus

Tamburino etal.,22 n=663

30days
1year

2.66
2.45

1.265.65
1.195.07

BMI <20kg/m2

Wenaweser etal.,49 n=200

30days

6.60

1.4829.5

Prior stroke

Wenaweser etal., n=200


Tamburino etal.,22 n=663

30days
30days to 1year

4.41
5.47

1.1616.8
1.4720.39

Carotid artery stenosis >50%

Thomas etal.,48 n=463 for TF


Thomas etal.,48 n=575 for TA

1year
1year

0.07
0.48

0.010.43
0.300.76

Liver disease

Thomas etal.,48 n=463 for TF


Thomas etal.,48 n=575 for TA

1year
1year

2.47
2.89

1.045.85
1.515.53

Dyslipidemia

Thomas etal.,48 n=463 for TF

1year

0.61

0.390.95

Systemic hypertension

Thomas etal.,48 n=463 for TF

1year

0.53

0.350.82

Smoking

Thomas etal.,

n=463 for TF

1year

2.42

1.513.90

Coagulopathy

Thomas etal.,48 n=463 for TF

1year

5.09

1.4917.39

Low left ventricular ejection fraction (<40%)

Tamburino etal.,22 n=663

30days

3.51

1.627.62

Low left ventricular ejection fraction (<50%)

Moat etal.,26 n=870

1year

1.49

1.032.16

Pulmonary hypertension

Rods-Cabau etal.,19 n=339


Sinning etal.,47 n=77
Tamburino etal.,22 n=663

30day
1year
1year
1year

2.09
1.88
3.1
3.21

1.024.43
1.173.0
1.37.6
1.198.71

Coronary artery disease

Sinning etal.,47 n=77


Dewey etal.,50 n=171

1year
30days

4.6
10.1

1.119.9
2.1174.8

Prior balloon aortic valvuloplasty

Tamburino etal.,22 n=663

30days

2.87

1.246.65

Moderate or severe mitral regurgitation

Rods-Cabau etal., n=339


Tamburino etal.,22 n=663

30days
1year

3.01
4.62

1.098.24
1.6612.87

Prior acute pulmonary edema

Tamburino etal.,22 n=663

1year
30days to 1year

2.75
2.70

1.325.72
1.096.68

Bagur etal.,53 n=213


Sinning etal.,47 n=77

30days
30days
1year
30days
1year

4.14
4.9
5.9
5.47
2.79

1.4212.13
1.220.4
2.414.5
1.2324.21
1.365.71

49

48

Baseline cardiac variables

19

Periprocedural complications
Acute kidney injury

Nuis etal.,46 n=126


Need for hemodynamic support

Rods-Cabau etal.,19 n=339

30days
1year

6.84
2.58

2.0422.93
1.116.0

Conversion to open heart surgery

Tamburino etal.,22 n=663

30days

38.68

2.86522.59

Cardiac tamponade

Tamburino etal.,

n=663

30days

10.97

1.5975.61

Major vascular complications

Tamburino etal.,22 n=663

30days

8.47

1.6742.82

Procedural stroke

Tamburino etal.,22 n=663

1year

15.76

3.2775.90

Moderate or severe aortic regurgitation


(2+)

Tamburino etal., n=663


Abdel Wahab etal.,51 n=690
Moat etal.,26 n=870

30days to 1year
30days
1year

3.79
2.43
1.66

1.579.10
1.224.85
1.102.51

22

22

some of the variation in the complication rates observed


among TAVI studies and preclude any meaningful comparison between them. In early 2011, the Valve Academic

Research Consortium (VARC) proposed standardized


consensus definitions for important clinical end points,
including major complications in TAVI.60 This consensus

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document represents an important step forward in
providing consistency across studies and in contributing
to a more-appropriate evaluation of TAVI technology.
Another important consideration when reviewing the
findings of TAVI studies is that, in all published multi
center TAVI registries and series, except SOURCE, 20
data was captured without source verification, and
nodata-monitoring or event-adjudication committee
was established for the validation of clinical events.
Major vascular complications
The use of large sheaths (1824French) in a very old
(usually octogenarian) population has led to a high rate
(>5% to 10% in most series) of major vascular complica
tions during TAVI procedures.428 Accurate evaluation
of the iliofemoral arteries before the procedure (see
Figure2), and the use of alternatives to the transfemoral
approach in borderline cases, seem to have a major role
in avoiding such complications.61,62 The use of smaller
catheters might also have a substantial impact on therate
of vascular complications (complication rate for the
CoreValve system: <5% with 18French sheaths versus
>20% with 24French sheaths).1618,21,22 Finally, appropriate
vascular access with true anterior entry in a disease-free
segment of the common femoral artery is also important.
This access can be achieved using echocardiographically
guided Seldinger puncture, although this puncture technique is used in only a few centers. Alternatively, puncture
can be guided by advancing a catheter into the femoral
artery via the contralateral sitea widespread practice,
but one that does not appropriately depict a disease-free
area of the femoral artery or guarantee a true anterior
entry during the puncture of the artery.
Importantly, the occurrence of major vascular complica
tions has been shown to be an independent predictor of
30-day mortality.22,61 The TAVI team should be able to treat
these complications rapidly and appropriately or have some
back-up with experienced peripheral interventionalists
or vascular surgeons.
In the past, surgical cut-down and vascular repair were
used in most transfemoral TAVI cases performed with
22French catheters, but most centers are now using
percutaneous closure devices such as Prostar or Perclose
(both Abbott Vascular Inc, Red City, CA, USA) in transfemoral cases performed with 18French catheters.6366
Despite the promising preliminary results obtained with
the use of these percutaneous closure devices, more data
are needed to determine the safety and efficacy of these
devices in patients undergoing TAVIprocedures.
Stroke
The occurrence of cerebrovascular events is one of the
most-worrisome complications of TAVI. The 30-day
stroke rate was ~3.5% (ranging from 1.2% to 6.7%) in
the multicenter registries and series and the PARTNER
trial.1928 In the high-risk cohort of the PARTNER trial,
the stroke rate tended to be higher in the TAVI group than
in the SAVR group at 30days (4.6% versus 2.4%, P=0.12)
and at the 1year follow-up (6.0% versus 3.2%, P=0.08).28
The nonoperable cohort of the PARTNER trial also
22 | JANUARY 2012 | VOLUME 9

showed a higher rate of stroke or transient ischemic attack


at 30days (6.7% versus 1.7%, P=0.03) and at the 1year
follow-up (10.6% versus 4.5%, P=0.04) among patients
who underwent TAVI compared with those managed
conservatively (including balloon aortic valvuloplasty
in 84% of the patients).27 Also, MRI studies have shown
an incidence of silent cerebral ischemic defects as high
as 6684% following TAVI, irrespective of the valve type
andapproach.6769
Although transcranial Doppler studies have shown
that cerebral emboli can occur at any time during the
TAVI procedure, most occur during positioning and
implantation of the valve prosthesis,70,71 indicating that
the embolization of valve particles from the native
calcified aortic valve leaflets might be an important
mechanism for cerebral emboli associated with TAVI.
This hypothesis could partially explain why clinical
and MRI studies have failed to demonstrate any difference in stroke rate between transfemoral and transapical procedures, despite the use of large catheters in
the aortic arch and ascending aorta, and the retrograde
crossing of the native aortic valve, being avoided in the
transapicalapproach.
Nietlispach etal. showed the feasibility of using an
embolic protection device (Embrella embolic deflector system , Edwards Lifesciences, Irvine, CA, USA)
during TAVI,72 and future studies will have to evaluate
the usefulness of this and other such devices, including
those from SMT Medical Technologies (Herzliya, Israel)
and Claret Medical (Santa-Rosa, CA, USA), in reducing
cerebral embolic events during TAVI procedures.
However, data from the PARTNER trial27 showed that
as much as half of the postprocedural (30-day) cerebrovascular events occurred more than 24h after the procedure, indicating that embolic mechanisms other than the
use of catheters and native valve stretching might have a
role in a substantial proportion of cases. A substudy of the
PARTNER trial73 indicated that periprocedural cerebrovascular events early after TAVI were associated with a
smaller native aortic valve area, whereas those occurring
late after the procedure were mostly related to a higher
atherosclerotic burden. This finding supports the lack of
correlation between TAVI and late neurologic events. The
combination of clopidogrel and aspirin has been empirically recommended as treatment after TAVI,1928 but future
studies will have to determine the optimal antithrombotic
regimen after these procedures.
Coronary obstruction
Coronary ostia obstruction (especially of the left
maincoronary artery) can occur following TAVI,7479 but
the global incidence of this life-threatening complica
tion is very low (<1%).528 This complication is related
to the displacement of the native aortic leaflet towards
the coronary ostia during valve prosthesis implantation,
and the risk seems to be higher in patients with heavily
calcified leaflets, especially in those with some degree of
aortic sinus effacement, low aortic implantation of the
coronary ostia, and long aortic valve leaflets. However,
the low number of cases reported to date has precluded a
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Acute kidney injury


The incidence of acute kidney injury, and the need for
hemodialysis, after TAVI has ranged from 11.7% to 28%,
and from 1.4% to 15.7%, respectively.46,47,53,8082 In the
high-risk cohort of the PARTNER trial,28 the need for
renal replacement therapy was similar in the TAVI and
SAVR groups at 30days (2.9% and 3.0%, respectively)
and at the 1year follow-up (5.4% and 6.5%, respectively).
Chronic kidney disease is a common comorbidity (preva
lence 3050%) in patients undergoing TAVI,1827 and
increasing degrees of preprocedural renal dysfunction are
associated with an increasing rate of postprocedural acute
kidney injury.81,82 In addition, periprocedural blood transfusion has been recognized as a major predictive factor

2.4

* P <0.05 versus baseline


NS

Mean gradient (mmHg)

60
50

2.0

47 17

1.61 0.40*

1.6
1.50 0.36*

40

1.2
30
20

0.8
0.60 0.14

10

10 4*

0.4

10 4*

0.0
Baseline

Discharge

1-year follow-up

P = 0.007
(TAVI vs SAVR-ST and SAVR-SL)

P = NS

60
50

50
Patients with severe PPM (%)

Myocardial infarction
TAVI has been associated with a variable rate of myo
cardial infarction, ranging from 0% to 16.3%.428 This variability is probably related to the lack of uniformity in the
definition of periprocedural myocardial infarction among
the various TAVI studies. The VARC definition for periprocedural myocardial infarction is the occurrence of new
symptoms or signs of ischemia associated with an elevation of cardiac biomarkers (preferably creatine kinaseMB)
at least 10 times the upper normal limit or at least 5 times
the upper normal limit with new pathological Q waves.60
However, one study has shown that some degree of myocardial injury occurs in most TAVI procedures, and a
higher degree of myocardial injury was associated with
a reduced LVEF recovery and increased cardiac mortality
at midterm follow-up.36

a 70

40

TAVI
33

32

30

SAVR-ST

31

SAVR-SL

27

20
13
9

10
0

1618
(n = 18)

1920
(n = 66)

2122
(n = 48)

2325
(n = 18)

Annulus size (mm)

c 100

Moderate
Patients with aortic regurgitation (%)

specific recommendation on the cut-off for the distance


between the aortic annulus and the coronary ostia, size of
the sinus of Valsalva, or amount of leaflet calcification that
should contraindicate TAVI because of a prohibitive risk
of coronary occlusion. In patients considered at risk for
this complication (as evaluated by CT angiography during
the work-up before TAVI), the use of aortic angiography
during balloon valvuloplasty before valve implantation
might be helpful in determining whether valve leaflet
displacement would compromise the coronary flow
after valve prosthesis implantation. Notably, several case
reports have already shown the feasibility of performing a coronary angioplasty through the struts of the
transcatheter valve.7479

Aortic valve area (cm2)

Figure 5 | Valve hemodynamics following TAVI with the


balloon-expandable CribierEdwards and Edwards SAPIEN
(Edwards Lifesciences Corporation, Irvine, CA, USA) valve
(on the basis of the work of Clavel etal.95). a|Mean gradient
and aortic valve area after TAVI (at hospital discharge and at
1year follow-up). b|Incidence of severe PPM according to
aortic annulus size following TAVI, SAVR-ST, and SAVR-SL.
c | Residual aortic regurgitation following TAVI (at hospital
discharge and at 1year follow-up). Abbreviations:
NS, not significant; PPM,prosthesispatient mismatch;
SAVR-SL,surgical aortic valve replacement with stentless
surgical valves; SAVR-ST, surgical aortic valve replacement
with stented surgical valves; TAVI, transcatheter aortic
valveimplantation.

Mild

80
46

42

Trivial
None

60

40

26

38
20

22
12
0
At discharge

At 1-year follow-up

of post-TAVI acute kidney injury,46,53,80,82 highlighting


the need to avoid unnecessary transfusions in such cases.
Importantly, the occurrence of acute kidney injury has
been associated with worse acute and midterm outcomes
after TAVI.46,47,53,8082

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50

TAVI (n = 41)
SAVR (n = 120)

LVEF (%)

45

= 14 15%

= 7 11%

40
35
30
0
Baseline

Discharge

At 1-year follow-up

Figure 6 | Changes in LVEF after TAVI and SAVR in patients


with severe aortic stenosis and low LVEF (on the basis of
the work of Clavel etal.101). *Different from SAVR
(P<0.05). Different from baseline (P<0.05). Different
from discharge (P<0.05). Abbreviations: LVEF, left
ventricular ejection fraction; SAVR, surgical aortic valve
replacement; TAVI, transcatheter aortic valve implantation.

Intraventricular conduction abnormalities


New-onset intraventricular conduction disturbances,
particularly new left bundle branch block, occur frequently
after TAVI (718% with the balloon-expandable Edwards
valves, 3083% with the self-expandableCoreValve).8391
Direct mechanical injury of the left bundle branch and
inflammation created by the stent containing the valve
prosthesis are potential mechanisms for these conduction disturbances. Interestingly, Nuis etal. have reported
that about half of these conduction disturbances occur
during balloon valvuloplasty before valve implantation. 89 Unsurprisingly, the presence of a prior right
bundle branch block seems to be an important predictor
of complete atrioventricular block and need for pacemaker implantation after TAVI.88,9194 Among procedural variables, the use of the CoreValve system and a
deeper (ventricular) implantation of the valve prosthesis are the two most-important factors determining the
occurrence of conduction disturbances and the need
for pacemaker implantation.23,25,26,84,86,88,90,91 CoreValve
implantation is associated with a need for permanent
pacemaker in ~20% of patients (systematically >9% to
10%, but up to ~40% in some series) compared with
in ~5% of patients implanted with the Edwards valves
(almost systematically <7%).1928,8494 The nitinol frame of
the CoreValve might produce a higher pressure on the
ventricular septum as compared to the stainless steel or
cobalt chromium frame of the Edwards valves, leading to
an increased riskof damaging the left bundle branch. Also,
a higher rate ofdeeper implantation of the CoreValve
system (>5mm from aortic annulus) might partially
explain the differences between the two devices. In the
PARTNER trial,27,28 the rate of permanent pacemaker
implantation after TAVI with the balloon-expandable
Edwards SAPIEN valve was 3.4% and 3.8% in the nonoperable and high-risk cohorts, respectively, with no differences compared with the medical treatment (5.0%)
and SAVR (3.6%) groups. Further studies are needed
to better determine the predictive factors of complete
24 | JANUARY 2012 | VOLUME 9

atrioventricular block and pacemaker implantation


following TAVI. These studies should lead to the
implementation of preventive measures of this frequent
and important post-TAVIcomplication.

Hemodynamics of transcatheter valves


Despite transcatheter valves being expanded within
severely calcified native aortic valves that are left in
place, the hemodynamic results after TAVI are excellent, with mean residual gradients <15mmHg and aortic
valve areas >1.5cm2.328 Importantly, these hemodynamic
results seem to be maintained at midterm follow-up.
Also, Claveletal. demonstrated that the hemodynamic
results associated with TAVI (using the Cribier-Edwards
and Edwards SAPIEN valves) were superior to those
obtained with stented and stentless surgical biopros
theses, especially in patients with small (<20mm) aortic
annulus95 (Figure5). In accordance with these results,
Smith etal. showed the superior hemodynamics of transcatheter valves compared with surgical valves in the highrisk cohort of the prospective, randomized PARTNER
trial.28 These good hemodynamic results might parti
ally be explained by the systematic oversizing of the
transcatheter valves with respect to the aortic annulus,
although some experimental and CT studies have suggested that the frame of the transcatheter valve adapts
to the dimension of the aortic annulus,96,97 and the final
aortic valve area after TAVI has been shown to be mainly
determined by the size of the aortic annulus as evaluated
by echocardiography.98 Alsoand possibly most relevant
for patients with small aortic annulusthe stent of transcatheter valves is much thinner than that of the stented
valves used for SAVR, which results in minimal obstruction to blood flow. In 2011, Kalavrouziotis etal. confirmed the outstanding results of TAVI with the 23mm
balloon-expandable Edwards SAPIEN valve in a series
of 34 consecutive patients with small (<20mm, mean
18.5mm) aortic annulus, with a mean residual gradient
of <12mmHg and an incidence of severe prosthesis
patient mismatch as low as 5.9%.99 The improvement in
valve hemodynamics associated with TAVI translates into
a significant improvement in LVEF, especially in patients
with low LVEF.6,95,100,101 Indeed, Clavel etal. showed that
the ventricular function of most patients with low (<50%)
LVEF undergoing TAVI had normalized at 1year followup;101 this finding compared favorably with those patients
with low LVEF undergoing SAVR (Figure6).
However, although trivial or mild in most cases and
moderate or moderate-to-severe in ~10% (517%) of
patients, the incidence of TAVI-associated prosthetic
regurgitation (mostly paravalvular) is very high (65
89%).328,51,95 In the high-risk cohort of the PARTNER
trial,28 some degree of paravalvular aortic regurgitation
occurred in 77% (12% moderate or severe) of patients
in the TAVI group compared with 26% (0.9% moderate or severe) in the SAVR group (P<0.001). Several
studies have shown that the degree of paravalvular
and transvalvular residual aortic regurgitation remains
stable at midterm (1-year) follow-up,14,27,28,95 but studies
with a longer follow-up are needed to further evaluate
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Table 3 | Main characteristics of emerging transcatheter valves
Valve type

Valve
material

Stent
material

Valve
size
(mm)

Delivery catheter
size (French)

Approach

Mechanism
of expansion

Repositionable?

Year of
first-inhuman
study

Direct Flow Medical(Direct Flow


Medical, Santa Rosa, CA, USA)126,127

Bovine
pericardium

No stent
(polyester
fabric cuff)

23, 25

18

Transfemoral
or subclavian

Inflation of
ring balloons
by a polymer

Yes

2006

Heart Leaflet Technologies (Heart Leaflet


Technologies, Maple Grove, MN, USA)

Porcine
pericardium

Nitinol

21, 23

18

Transfemoral

Selfexpandable

Yes

2009

Innovare (Braile Biomedical, So Jos do


Rio Preto, Brazil)128,129

Bovine
pericardium

Stainless
steel

20, 22,
24, 26,
28

20 (for 20, 22,


& 24mm valves);
22 (for 26
& 28mm valves)

Transapical

Balloon
expandable

No

2008

JenaValve(JenaValve Technology,
Munich, Germany)130

Porcine
native aortic
valve leaflets

Nitinol

23, 25,
27

32

Transapical

Selfexpandable

Yes

2009

Portico(St. Jude Medical, StPaul,


MN, USA)

Porcine
pericardium

Nitinol

23,25

18

Transfemoral

Selfexpandable

Yes

2011

SadraLotus Medical (Boston Scienfic


SciMed Inc, Maple Grove, MN, USA)131

Bovine
pericardium

Nitinol

23, 27

18

Transfemoral

Selfexpandable

Yes

2007

Symetis Accurate (Symetis, Ecublens,


Switzerland)132

Porcine
native aortic
valve leaflets

Nitinol

23, 25,
27

28

Transapical

Selfexpandable

Yes

2009

Engager(Medtronic Inc, Minneapolis,


MN, USA)133,134

Bovine
pericardium

Nitinol

23, 26

28

Transapical

Selfexpandable

Yes

2008

the progression and potential clinical impact of these


residual leaks. Notably, the presence of moderate or
severe residual aortic regurgitation has been identified
as an independent predictor of acute and late mortality
following TAVI.22,26,51
Several factors have been associated with the occurrence of moderate or severe aortic regurgitation. Valve
malpositioning (too aortic or too ventricular) might be the
reason for moderate-to-severe residual paravalvular aortic
regurgitation, and this can be treated with the implantation of a second valve (valve-in-valve procedure). 102,103
Also, CoreValve malpositioning (low implantation) can
sometimes be corrected by snaring and repositioning
thevalve.104 A high degree of calcification of the native
aortic valve, a large aortic annulus, a small valve area, and a
high angle between the ascending aorta and the left ventri
cular outflow tract, have also been associated with an
increased rate of moderate-to-severe paravalvular aortic
regurgitation.51,105107 Some studies have also suggested
that echocardiography might undersize aortic-annulus
measurements, as compared with CT, and this undersizing could be associated with an increased degree of para
valvular leak because of the selection of an undersized
valve prosthesis.2932,51 In addition to providing more information about the predictive factors of significant residual
aortic regurgitation, further research is needed to improve
transcatheter valve technology to further reduce the
incidence and severity of paravalvular leaks.

Functional class and quality of life


Improvements in the NYHA functional class following TAVI have systematically been reported.328 Most
patients are in NYHA classIII before the procedure and

improve to NYHA classI or II at midterm follow-up.


Exercise capacity, as evaluated by the 6min walk test,
has also been shown to increase after TAVI.108,109 Several
studies have determined the effect of TAVI on quality
of life using the Short Form (SF)12, SF36, Kansas City
Cardiomyopathy, EuroQuol5D, and Duke Activity
Status Index questionnaires, and all showed TAVIassociated improvement in quality of life at 612months
after implantation. 110116 However, some studies have
indicated a lack of improvement in quality of life, functional status, or both in a substantial proportion of
patients (2030%) after TAVI,13,112,117 in part related to
comorbidities such as severe mitral regurgitation and
chronic kidney disease.112,117 Future studies will have to
continue evaluating the benefits of TAVI for both functional status and quality of life and further identifying the
patients with aortic stenosis who might not benefit from
this treatment (survival without improvement) owing
to an excessive comorbidity burden.

Looking to the future


Lower-risk patients
The rapid and substantial improvements in TAVI
technology and the increasing treatment-center experi
ence in the past few years, the results obtained in multi
center registries and, more importantly, the results
from the high-risk cohort of the PARTNER trial have
provided the basis for evaluating whether TAVI should
be used for the treatment of a lower-risk population
with aortic stenosis. Indeed, some preliminary results
of TAVI in intermediate-risk patients with severe aortic
stenosis have been promising.118 Two TAVI studies on
intermediate-risk patients are planned in the near future.

NATURE REVIEWS | CARDIOLOGY

VOLUME 9 | JANUARY 2012 | 25


2011 Macmillan Publishers Limited. All rights reserved

REVIEWS
a

Figure 7 | Images of emerging transcatheter valve technology (valves with first-in-man data). a | Direct Flow Medical
(Direct Flow Medical, Santa Rosa, CA, USA) valve. Permission obtained from Direct Flow Medical. b | HLT (Heart Leaflet
Technologies, Maple Grove, MN, USA) valve. 2011 HLT, Inc. a Bracco Group Co. c | Innovare (Braile Biomedical, So Jos
do Rio Preto, Brazil) valve. Courtesy of Diego Gaia, Federal University of So Paulo, Brazil. d | JenaValve(JenaValve
Technology, Munich, Germany). Permission obtained from JenaValve Technology. e | Portico(St-Jude Medical, St Paul, MN,
USA) valve. f| SadraLotus Medical (Boston Scientific SciMed Inc, Maple Grove, MN, USA) valve. 2011 Boston Scientific
Corporation or its affiliates. All rights reserved. Used with permission of Boston Scientific Corporation. g | Symetis
Accurate (Symetis SA, Lausanne, Switzerland) valve. Permission obtained from Symetis. h | Engager(Medtronic Inc.,
Minneapolis, MN, USA) valve. 2010 Medtronic, Inc. Image provided by Medtronic, Inc.

For cohortA of the PARTNERII trial,119 investigators


will randomly assign patients with aortic stenosis and
STS score of 48% (that is, intermediate risk), or specific
qualifying intermediate risk criteria requiring formal
petition to the executive committee heart-valve team
(which will include cardiac surgeons and interventional
cardiologists), to TAVI or SAVR. Patients with concomitant coronary artery disease will be substratified to
percutaneous coronary intervention plus TAVI versus
CABG surgery plus SAVR. The estimated sample size is
1,5002,000 patients, and ~50 US centers are expected to
participate. The Surgical Replacement and Transcatheter
Aortic Valve Implantation (SURTAVI) trial 120 will
include elderly (70years) patients with aortic stenosis
and an STS score of 38%. Approximately 1,200 patients
will be randomly assigned to TAVI or SAVR, and ~40
European centers are expected to participate. In addition, a randomized study comparing TAVI and SAVR
in Danish patients 70years of age, irrespective of their
expected surgical risk, is presently ongoing.121 The results
of these randomized trials should determine the exact
role of TAVI for the treatment of intermediate-risk
patients with severe aortic stenosis.

Treatment of surgical prosthesis dysfunction


A high number of patients undergoing SAVR require
reintervention as a result of the limited durability of
surgical bioprosthesis. Several reports have shown the
feasibility of TAVI for the treatment of surgical bioprosthesis dysfunction, including of stented and stentless
26 | JANUARY 2012 | VOLUME 9

valves, which opens up a new avenue for the treatment of


this challenging group of patients.122125 However, larger
studies are needed to prove the safety and good clinical
outcomes associated with this valve-in-valve strategy in
all of the different types of surgical valve prostheses.

Emerging transcatheter valve technology


Various transcatheter valves are being developed. The
main characteristics of the new transcatheter valves
with first-in-human data are summarized in Table3
andFigure7.

Conclusions

TAVI represents a less-invasive strategy than SAVR for the


treatment of severe symptomatic aortic stenosis. TAVI is
currently the treatment of choice for patients considered
not to be candidates for SAVR and is a proven alternative
for those considered to be at high surgical risk. Despite
the good acute and midterm clinical results obtained in
large multicenter series and registries and the randomized, controlled PARTNER trial, efforts should be made
to improve patient selection and reduce periprocedural
complications such as stroke, major vascular complications, and the need for permanent pacemaker implantation. Importantly, TAVI should be performed in centers
with highly experienced interventional and surgical
teams. Also, a close collaboration between interventional
cardiologists and cardiac surgeons (the so-called heart
team) as well as careful training of the team seem to have
a major role in achieving a successful TAVI program.
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REVIEWS
Transcatheter valve hemodynamics are excellent, and
even superior to those achieved with surgically implanted
valves, but residual paravalvular aortic regurgitation
(moderate in 517% of cases) remains an issue that
should be addressed in the near future. Preliminary
data on long-term outcomes, valve-in-valve procedures
for the treatment of surgical valve dysfunction, and the
treatment of lower-risk patients have been promising, but
further studies are needed to confirm these results. These
studies might result in the expansion of TAVI to the treatment of a much broader spectrum of patients with severe
aorticstenosis.
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Acknowledgments
The author wishes to thank Mlanie Ct, MSc,
(Quebec Heart and Lung Institute, Quebec City, QC,
Canada) for her outstanding work in the preparation
of tables and figures.

VOLUME 9 | JANUARY 2012 | 29


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