Original Research Article
One-Year Clinical Outcomes With SAPIEN 3
Transcatheter Aortic Valve Replacement in
High-Risk and Inoperable Patients With Severe
Aortic Stenosis
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Background: In the initial PARTNER trial (Placement of Aortic
Transcatheter Valves) of transcatheter aortic valve replacement for high-risk
(HR) and inoperable patients, mortality at 1 year was 24% in HR and 31% in
inoperable patients. A recent report of the 30-day outcomes with the lowprofile SAPIEN 3 transcatheter aortic valve replacement system demonstrated
very low rates of adverse events, but little is known about the longer-term
outcomes with this device.
Methods: Between October 2013 and September 2014, 583 HR (65%)
or inoperable (35%) patients were treated via the transfemoral (84%) or
transapical/transaortic (16%) access route at 29 US sites. Major clinical events
at 1 year were adjudicated by an independent clinical events committee, and
echocardiographic results were analyzed by a core laboratory.
Results: Baseline characteristics included age of 83 years, 42% female, and
median Society of Thoracic Surgeons score of 8.4%. At the 1-year follow-up,
survival (all-cause) was 85.6% for all patients, 87.3% in the HR subgroup, and
82.3% in the inoperable subgroup. Survival free of all-cause and cardiovascular
mortality in the transfemoral patients from the HR cohort was 87.7% and
93.3%, respectively. There was no severe paravalvular leak. Moderate
paravalvular leak (2.7%) was associated with an increase in mortality at 1 year,
whereas mild paravalvular leak had no significant association with mortality.
Symptomatic improvement as assessed by the percentage of patients in New
York Heart Association class III and IV (90.1% to 7.7% at 1 year; P<0.0001)
and by Kansas City Cardiomyopathy Questionnaire overall summary score
(improved from 46.9 to 72.4; P<0.0001) was marked. Multivariable predictors
of 1-year mortality included alternative access, Society of Thoracic Surgeons
score, and disabling stroke.
Conclusions: In this large, adjudicated registry of SAPIEN 3 HR and
inoperable patients, the very low rates of important complications resulted in a
strikingly low mortality rate at 1 year. Between 30 and 365 days, the incidence
of moderate paravalvular aortic regurgitation did not increase, and no
association between mild paravalvular leak and 1-year mortality was observed,
although a small increase in disabling stroke occurred. These results, which
likely reflect device iteration and procedural evolution, support the use of
transcatheter aortic valve replacement as the preferred therapy in HR and
inoperable patients with aortic stenosis.
Clinical Trial Registration: URL: http://www.clinicaltrials.gov. Unique
identifier: NCT01314313.
130
July 12, 2016
Howard C. Herrmann, MD
Vinod H. Thourani, MD
Susheel K. Kodali, MD
Raj R. Makkar, MD
Wilson Y. Szeto, MD
Saif Anwaruddin, MD
Nimesh Desai, MD
Scott Lim, MD
S. Chris Malaisrie, MD
Dean J. Kereiakes, MD
Steven Ramee, MD
Kevin L. Greason, MD
Samir Kapadia, MD
Vasilis Babaliaros, MD
Rebecca T. Hahn, MD
Philippe Pibarot, DVM,
PhD
Neil J. Weissman, MD
Jonathon Leipsic, MD
Brian K. Whisenant, MD
John G. Webb, MD
Michael J. Mack, MD
Martin B. Leon, MD
For the PARTNER
Investigators
Correspondence to: Howard C.
Herrmann, MD, 9038 W Gates
Pavilion, Hospital of the University
of Pennsylvania, 3400 Spruce St,
Philadelphia, PA 19104. E-mail
[email protected]
Sources of Funding, see page 138
Key Words: aortic valve
◼ aortic valve stenosis ◼
transcatheter aortic valve
replacement
© 2016 American Heart
Association, Inc.
Circulation. 2016;134:130–140. DOI: 10.1161/CIRCULATIONAHA.116.022797
One-Year Outcomes With SAPIEN 3
Clinical Perspective
What Is New?
What Are the Clinical Implications?
• The combination of new design features of
SAPIEN 3, procedural improvements, operator
experience, and improved patient selection has
contributed to a low rate of important adverse
events (including stroke) and a high rate of 1-year
survival in high-risk and inoperable patients with
severe aortic stenosis.
• These excellent 1-year follow-up data with SAPIEN
3 support the use of transcatheter aortic valve
replacement as the preferred therapy in high-risk
and inoperable patients with aortic stenosis and further evaluation of this device in lower-risk patients.
T
he initial PARTNER trial (Placement of Aortic Transcatheter Valves) of transcatheter aortic valve replacement
(TAVR) for high-risk (HR) and inoperable patients with
severe symptomatic aortic stenosis (AS) demonstrated a
marked survival advantage compared with medical management but a high 1-year mortality of 24% in HR patients
(despite no difference compared with surgery) and 31% in
inoperable patients after TAVR.1,2 Mortality was attributable
to a combination of cardiovascular and noncardiovascular
causes.3 Similar results have been reported in other studies. In the extreme risk for surgery trial of a self-expanding
prosthesis, the 1-year mortality was 26%.4 An initial report
on the commercial use of TAVR in the United States from
the Society of Thoracic Surgeons (STS)/American College
of Cardiology transcatheter valve therapies registry reported 1-year mortality of 24%.5
Recently, the SAPIEN 3 prosthesis system (Edwards
Lifesciences Inc) has become available. This lower-profile
device has a balloon-expandable cobalt-chromium frame
with bovine pericardial leaflets and an external fabric
Circulation. 2016;134:130–140. DOI: 10.1161/CIRCULATIONAHA.116.022797
Methods
Patients
The PARTNER II trial is a multicenter evaluation of TAVR with
multiple arms and comparators. Between October 2013
and September 2014, 583 HR and inoperable patients were
enrolled at 29 US sites in a single-arm, nonrandomized registry (PARTNER II SAPIEN 3 High Risk Cohort) for comparison
in a noninferiority analysis with historical control subjects
(Clinicaltrials.gov NCT01314313). A nested registry (nested
registry 7) included 11 patients who received the 20-mm-diameter device. All patients had severe symptomatic native trileaflet severe degenerative AS with a mean echocardiographic
gradient ≥40 mm Hg or jet velocity >4.0 m/s and an aortic
valve area ≤0.8 cm2. Patients were deemed at high risk on
the basis of an STS-predicted risk of 30-day mortality >8%
or at a ≥15% risk of mortality after evaluation by the local
heart team. Patients were considered inoperable if the risk of
death or serious morbidity as assessed by a cardiologist and 2
cardiac surgeons exceeded 50%. Important exclusion criteria
included congenital bicuspid disease, ejection fraction <20%,
renal failure, severe mitral or aortic regurgitation, or recent
neurological event. Other inclusion and exclusion criteria for
the PARTNER trial have previously been published.2
Study Device and Procedure
The SAPIEN 3 transcatheter heart valve (THV) system (Edwards
Lifesciences Inc) is a balloon-expandable device. It includes a
cobalt-chromium alloy frame to allow a low crimped profile with
high radial strength, bovine pericardial leaflets, and an adaptive
external polyethylene terephthalate fabric seal. The device is supplied in 4 diameters: 20, 23, 26, and 29 mm. The 20-mm valve
size was introduced into the trial, with identical inclusion and
exclusion criteria, in a separate nested registry (nested registry
7) after enrollment was completed with the 3 larger sizes. The
device is inserted with a dedicated delivery catheter (Commander
transfemoral) that is compatible with 14F (≤26-mm-diameter
THV) and 16F (29-mm THV) expandable introducer sheaths. The
transapical and direct aortic delivery system (Certitude) uses an
18F (≤26-mm THV) or 21F (29-mm THV) sheath.
Valve replacement was done under general anesthesia,
monitored anesthesia care, or conscious sedation, with transesophageal or transthoracic echocardiographic and fluoroscopic guidance according to the usual practice and at the
discretion of the local site. Computed tomography–guided
annular sizing was used routinely, and all patients were presented to a clinical committee to confirm eligibility, sizing, and
access before implantation.
Study Design and Analysis
The PARTNER study was approved by the institutional review
board at each participating site, and all patients provided written
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• In this large, adjudicated registry of high-risk and
inoperable patients undergoing transcatheter aortic
valve replacement with the SAPIEN 3 system, a low
rate of early complications contributed to a very low
rate of 1-year mortality, a high rate of transfemoral
access (84%), and a strikingly high all-cause and cardiovascular 1-year survival in the high-risk transfemoral subgroup (89.3% and 93.3%, respectively).
• Between 30 days and 1 year, no increase in the
low rate of moderate paravalvular aortic regurgitation (2.7%) was observed, and there was no association between mild paravalvular regurgitation
and 1-year mortality. Patients experienced marked
improvement in symptoms and quality of life.
seal. Early 30-day outcomes with this system have demonstrated very low rates of adverse events.6,7 However,
little is known about the longer-term results with the SAPIEN 3 device. Here, we report the 1-year outcomes with
the SAPIEN 3 TAVR system in a large US multicenter
registry of HR and inoperable patients with severe AS.
Herrmann et al
informed consent. The study was designed and monitored by
the sponsor, Edwards Lifesciences Inc, and by an executive
committee of interventional cardiologists and cardiac surgeons.
The sponsor funded the study and participated in site selection,
collection of the data, and data monitoring. The executive committee had unrestricted access to the data, and the authors
analyzed the data and prepared all drafts of the manuscript.
The prespecified primary end point was the nonhierarchical
composite event rate of death, all stroke, and aortic insufficiency
(time frame of safety at 30 days and effectiveness at 1 year).
All outcomes were adjudicated by a clinical events committee
according to the second VARC 2 (Valve Academic Research
Consortium) definitions8,9 except stroke (which used a modified
VARC 2 definition), and echocardiograms were analyzed by an
independent core laboratory. Other events are site reported.
Statistical Methods
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All analyses were performed with data from the valve implant
population. Categorical variables were compared with the use
of the Fisher exact test or χ2 test, as appropriate. Continuous
variables are presented with summary statistics and compared
by use of the t test. Variables were compared between time
points with the paired t test or the McNemar test for continuous
and categorical variables, respectively. Kaplan–Meier survival
curves summarize time to event outcomes, and comparisons
were made with the log-rank test. Multivariable analyses were
performed with Cox regression models. Stroke was included
as a time-dependent variable along with relevant baseline variables, which were identified from stepwise regression with an
entry/stay criterion of 0.10. Candidate variables included age,
STS score, sex, left ventricular ejection fraction, stroke volume
index, chronic obstructive pulmonary disease, diabetes mellitus, risk category, and access. Additional models are presented
including each early outcome variable (vascular complications,
paravalvular leak [PVL], acute kidney injury, and existing or new
permanent pacemaker, all defined by day 30) with the relevant
baseline variables; these models measure time from day 30
and exclude subjects who died by day 30. Statistical significance was defined at an α level of ≤0.05. All analyses were
performed with SAS version 9.4 (SAS Institute Inc.).
Results
Baseline Characteristics
The study population comprised 583 patients; 384 were
considered HR (65.9%) and 199 were considered inoperable (34.1%; Table 1). The mean±SD age was 82.7±8.1
years; 42% were women; and 90% had New York Heart
Association class III or IV symptoms. The median STS
Table 1. Baseline Characteristics
Combined
HR
Inoperable
583
384 (65.9)
199 (34.1)
82.7 (46–100)
83.4 (46–98)
80.3 (55–100)
<0.001
1.88±0.27
1.86±0.27
1.92±0.27
0.02
245 (42)
153 (40)
92 (46)
0.14
8.4 (6.50–10.0)
8.6 (7.50–9.95)
7.40 (4.60–10.40)
0.002
6.10 (3.80–10.85)
6.64 (4.07–11.00)
5.57 (3.15–10.59)
0.04
525 (90.1)
345 (89.8)
180 (90.5)
0.82
Cirrhosis, n (%)
11 (1.9)
6 (1.6)
5 (2.5)
0.52
Hostile chest, n (%)*
58 (10.0)
12 (3)
48 (24)
0.0001
n (%)
Age, mean (range), y
BSA, m2
Female sex, n (%)
STS score, median (IQR), %
EuroScore, median (IQR)
NYHA class III/IV, n (%)
P Value
Frailty, n (%)†
180 (30.9)
99 (25.8)
81 (40.7)
0.0002
COPD, n (%)
259 (44.6)
162 (42.3)
97 (49.0)
0.12
Severe COPD, n (%)
78 (13.4)
47 (12.2)
31 (15.6)
0.26
If COPD, O2 dependent, n (%)
68 (26.5)
28 (17.4)
40 (41.7)
0.0001
Diabetes mellitus, n (%)‡
204 (35)
127 (33)
74 (37)
0.42
CKD (creatinine ≥2.0), n (%)
70 (12.0)
47 (12.2)
23 (11.6)
0.81
Prior CABG, n (%)
193 (33.1)
126 (32.8)
67 (33.7)
0.84
Atrial fibrillation, n (%)
255 (43.7)
160 (41.7)
95 (47.7)
0.16
Prior PPM, n (%)
95 (16.3)
66 (17.2)
29 (14.6)
0.42
BSA indicates body surface area; CABG, coronary artery bypass graft; CKD, chronic kidney disease; COPD, chronic obstructive pulmonary disease; HR,
high risk; IQR, interquartile range; NYHA, New York Heart Association; PPM, permanent pacemaker; and STS, Society of Thoracic Surgeons.
*Hostile chest includes porcelain aorta, prior irradiation, left internal mammary artery across the midline, multiple prior sternotomies, and severe chest
deformity.
†Site reported by surgeon principal investigator.
‡Combined type 1 and II (insulin and non–insulin dependent).
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One-Year Outcomes With SAPIEN 3
Table 2. Procedural Details
HR, n (%)
Inoperable,
n (%)
P Value
TF
491 (84.2)
324 (84.4)
167 (83.9)
0.89
TA
57 (9.8)
40 (10.4)
17 (8.5)
0.47
TAo
35 (6.0)
20 (5.2)
15 (7.5)
0.26
TA/TAo
92 (15.8)
60 (15.6)
32 (16.1)
0.89
Mortality
Valve size implanted, mm diameter
20
11 (1.9)
7 (1.8)
4 (2.0)
1.0
23
200 (34.3)
138 (35.9)
62 (31.2)
0.25
26
227 (38.9)
140 (36.5)
87 (43.7)
0.09
29
145 (24.9)
99 (25.8)
46 (23.1)
0.48
HR indicates high risk; TA, transapical; TAo, transaortic; and TF,
transfemoral.
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score and EuroSCORE II were 8.4 (interquartile range,
6.50–10.0) and 6.10 (interquartile range, 3.80–10.85),
respectively. There was a high rate of comorbid conditions, including cirrhosis (2%), hostile chest (10%), frailty
(31%), severe chronic obstructive pulmonary disease
(13%), diabetes mellitus (35%), chronic kidney disease
(12%), and prior coronary artery bypass graft (33%). Patients who were considered inoperable had more comorbidities than HR patients, including a greater incidence of
frailty, oxygen-dependent chronic obstructive pulmonary
disease, and hostile chest (Table 1).
Procedural Details
A transfemoral approach was used in 491 patients
(84.2%). Alternative access sites included transapical in
57 patients (9.8%) and transaortic in 35 patients (6.0%;
Table 2). Only 2% of patients received the smallest (20mm diameter) prosthesis, whereas 25% required the
largest (29-mm diameter) device (Table 2). Compared
There were 15 deaths by 30 days and an additional 71
deaths by 1 year. Five patients withdrew consent, and
7 patients were lost to follow-up, which was obtained in
485 patients (98.6%) at 1 year. At the 1-year follow-up,
survival was 85.6% for all patients (Figure 1), 87.7% for
transfemoral patients, and 74.7% for transapical/transaortic patients (P=0.0006, log rank for transfemoral
versus transapical/transaortic; Table 3 and Figure 2A).
Survival was higher, but not statistically significantly different, in HR (87.3%) compared with inoperable (82.3%)
patients (Figure 1). All-cause and cardiovascular survival
was highest in HR and transfemoral patients, with allcause survival of 89.3% in transfemoral HR patients (Table 3 and Figure 2B). Cardiovascular survival was 91.9%
overall, 92.6% in the HR subgroup, and 90.4% in the
inoperable subgroup.
Clinical Outcomes
The rates of all and major (disabling) stroke occurring
within 30 days were 1.4% and 0.9%, respectively, and
increased to 4.3% and to 2.4%, respectively, between
30 days and 1 year (Table 3). There was no difference
in the rates of disabling strokes between the HR and
inoperable or between the transfemoral and transapical/
transaortic groups. Marked symptomatic improvement
was demonstrated by several measures. The percentage
Figure 1. Kaplan–Meier survival curves
for all-cause mortality.
Kaplan–Meier survival curves for all-cause
mortality is shown for all, high-risk (HR), and
inoperable (INOP) patients.
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July 12, 2016
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Combined,
n (%)
with transfemoral patients, those treated with an alternative access approach had higher median STS scores
(9.1 versus 8.4; P=0.002) and were significantly more
likely to have diabetes mellitus, chronic kidney disease,
a history of myocardial infarction or coronary artery bypass graft, and peripheral vascular disease. There were
no significant differences in access site or valve prosthesis between the HR and inoperable cohorts.
Herrmann et al
Table 3. Outcomes at 1 Year (Kaplan–Meier Estimates, as Treated)
Combined, % (n)
HR, % (n)
Inoperable, % (n)
P Value
All-cause mortality
14.4 (82)
12.7 (48)
17.7 (34)
0.14
TF
12.3 (59)
10.7 (34)
15.7 (25)
0.17
TA/TAo
25.3 (23)
23.7 (14)
28.4 (9)
0.54
8.1 (45)
7.4 (27)
Cardiovascular mortality
TF
6.7 (31)
TA/TAo
16.2 (14)
All stroke
4.3 (23)
Major (disabling) stroke
Repeat hospitalization
6.1 (19)
14.4 (8)
9.6 (18)
0.38
7.8 (12)
0.57
19.4 (6)
0.44
5.6 (20)
1.8 (3)
0.03
2.4 (13)
3.0 (11)
1.3 (2)
0.16
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17.1 (96)
15.6 (57)
19.9 (39)
0.13
Total AR moderate or greater
2.6 (10)
1.2 (3)
5.5 (7)
0.02
All-cause mortality and stroke
17.2 (98)
16.4 (62)
18.8 (36)
0.60
All-cause mortality, stroke, AR
moderate or greater
20.6 (108)
19.0 (65)
23.7 (43)
0.19
New PPM
16.8 (96)
14.5 (54)
21.3 (42)
0.02
AR indicates aortic regurgitation; HR, high risk; PPM, permanent pacemaker; TA, transapical; TAo, transaortic; and TF, transfemoral.
of patients in New York Heart Association class III and
IV decreased from 90% at baseline to 13% at 30 days
(P<0.0001) and further to 8% (P=NS for comparison
with 30 days) at 1 year (Figure 3). Similar improvements
were observed in the 6-minute walk test (134±116 m at
baseline to 179±132 m at 1 year; P<0.0001) and the
overall summary score of the Kansas City Cardiomyopathy Questionnaire (46.9±22.6 at baseline to 72.4±22.4
at 1 year; P<0.0001). A new permanent pacemaker was
required in 13.3% and 16.8% of patients at 30 days and
1 year, respectively. With the exclusion of patients with
a baseline pacemaker, the Kaplan–Meier estimated rate
for a new permanent pacemaker at 1 year was 20.1%. At
1 year, rehospitalization occurred in 17.1% of patients,
and a total of 3 patients required surgical aortic valve
replacement (1 periprocedurally for valve embolization
and 2 between 30 and 365 days for prosthetic valve
endocarditis). No patients had structural valve deterioration or clinical valve thrombosis.
Echocardiographic Outcomes
Baseline echocardiographic data in this study population confirmed severe AS with a peak gradient of 76±23
mm Hg, mean gradient of 45±14 mm Hg, and calculated
aortic valve area of 0.67±0.17 cm2. Left ventricular ejection fraction was 56±15%. At 1 year after TAVR, the peak
and mean gradients decreased to 21±9 and 11±5 mm Hg
and the aortic valve area increased to 1.67±0.38 cm2,
with no significant change between 30 days and 1 year.
Hemodynamic values by valve size are shown in Figure 4.
Aortic regurgitation was evaluated in 374 patients
at 1 year by the echocardiographic core laboratory.
Transvalvular aortic regurgitation was mild in 1.3% of
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patients, and no patient had more than mild aortic regurgitation. Moderate PVL was present in 2.9% of patients
at 30 days and 2.7% of patients at 1 year (P=0.86). In a
paired analysis of 364 patients with evaluable echocardiograms at 30 days and 1 year, there was no difference
in PVL over time. At 1 year, no or trace PVL was present in 68.1% of patients, mild PVL was seen in 29.1%,
moderate PVL was present in 2.7%, and no patient had
severe PVL. Values are shown in Figure 5. Survival at 1
year based on the severity of 30-day PVL demonstrated
no difference between those patients with no/trace and
those with mild PVL, with a reduced survival in the 16
patients with moderate PVL (Figure 6).
Multivariable Analysis
Two separate multivariable analyses were performed.
In the first one using baseline patient characteristics,
including HR versus inoperable and access approach
(transfemoral versus transapical/transaortic), independent predictors of all-cause mortality were major stroke
(hazard ratio, 10.33; 95% confidence interval, 4.62–
23.09; P<0.0001) and use of alternative access (hazard ratio, 2.06; 95% confidence interval, 1.26–3.36;
P=0.0039). In a second landmark analysis from 30 days
examining the effect of early procedural complications,
moderate PVL was also an independent predictor of allcause mortality at 1 year (hazard ratio, 3.75; 95% confidence interval, 1.57–8.96; P=0.0029).
Discussion
This is the first report of adjudicated registry data in a
large cohort of HR and inoperable patients with severe
Circulation. 2016;134:130–140. DOI: 10.1161/CIRCULATIONAHA.116.022797
One-Year Outcomes With SAPIEN 3
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Kaplan–Meier survival curves for all-cause
mortality are shown for transfemoral (TF),
high-risk (HR), TF inoperable (INOP), transapical (TA)/transaortic (TAo) HR, and TA/TAo
INOP patients.
AS at 1 year after TAVR with the SAPIEN 3 THV system.
The major findings of this study are the following: (1) The
low rate of complications with this device contributed to
a very low rate of 1-year mortality; (2) the low profile of
the device allowed a high rate of transfemoral access
(84%) with a low rate of vascular complications; (3) in
this regard, strikingly high all-cause survival and cardiovascular 1-year survival were observed in the HR trans-
Figure 3. New York Heart Association
class at 30 days and 1 year in survivors.
Circulation. 2016;134:130–140. DOI: 10.1161/CIRCULATIONAHA.116.022797
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Figure 2. Kaplan–Meier survival curves
for all-cause mortality by access and
group.
Herrmann et al
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Figure 4. Valve hemodynamics (aortic valve area and gradient over time, line graph).
femoral subgroup (89.3% and 93.3%, respectively); (4)
between 30 days and 1 year, no increase in the low rate
of moderate paravalvular aortic regurgitation (2.7%) was
observed, and there was no association between mild
PVL and 1-year mortality; (5) an increase in the rate of all
stroke (1.4% to 4.3%) and major stroke (0.9% to 2.4%)
was observed between 30 days and 1 year; and (6) excellent valve prosthesis hemodynamics are sustained at
1 year and result in markedly improved patient symptoms and quality of life.
The low mortality rate reported in this study is particularly striking compared with prior studies with previous-generation balloon-expandable valves and likely
reflects multiple factors. First, this third-generation SAPIEN balloon-expandable valve has a number of technical advances that contribute to fewer procedural complications. The cobalt-chromium frame design allows
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a smaller crimped profile (18F–21F outer diameter)
that can be inserted through 14F to 16F expandable
sheaths. This increases the percentage of patients eligible for transfemoral access, which has been associated with improved survival even after adjustment for
other differences between transfemoral and transapical patient comorbidities.10 Vascular complications after TAVR have been associated with mortality in almost
all studies and were 32% at 1 year in the PARTNER
1B study of inoperable patients, 18% in the PARTNER
1A study of HR patients with the first-generation SAPIEN THV, and 17% in PARTNER IIB with the SAPIEN XT
THV1,2,11 compared with <10% in the present study with
SAPIEN 3.12
A second design factor that may have contributed
to the reduced mortality with SAPIEN 3 likely has to do
with the ease of positioning resulting from its slightly
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One-Year Outcomes With SAPIEN 3
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longer length and balloon inflation characteristics that
allow a degree of “self-centering.” Valve malpositioning
with resultant severe aortic regurgitation, the need for
a second valve-in-valve implantation, and the potential
need for cardiopulmonary support or urgent surgery
have been associated with a particularly high mortality.13
In this study, the frequency of procedural valve-in-valve
implantations and urgent aortic valve replacement was
low (1.4%).
The low rate of moderate PVL (2.6%) and no severe
PVL may reflect the benefit of the external fabric seal. In
addition, 3-dimensional computed tomography–guided
THV sizing was used routinely in this trial and likely also
contributed to more optimal annular coverage. In this
regard, it is notable that the new permanent pacemaker
rate is slightly higher than reported in trials with earlygeneration SAPIEN devices. A recent report identified
implantation depth and oversizing as independent predictors of new permanent pacemaker implantation with
SAPIEN 3, suggesting a potential procedural opportunity
to reduce the rate.14
The small increase in stroke between 30 days and
1 year is not surprising in this elderly population with
multiple risk factors for stroke, including atrial fibrillation
in >40% of patients. Studies, including GALILEO (Global
Study Comparing a Rivaroxaban-Based Antithrombotic
Strategy to an Anti-Platelet-Based Strategy After Transcatheter Aortic Valve Replacement; Clinicaltrials.gov
NCT02556203), comparing antiplatelet and anticoagulation strategies aimed at reducing post-TAVR thromboembolic events are underway.
Finally, improved operator experience and patient selection likely contributed to the observed improvement
in patient survival. The mean STS score of this patient
population (8.2%) is lower than the >11% in the earlier
PARTNER trials but nonetheless represents an HR group
of patients with multiple comorbidities and frailty. The
low rate of noncardiovascular mortality at 1 year (6.3%)
Figure 6. Effect of 30-day paravalvular
leak on 1-year mortality.
CI indicates confidence interval; and HR,
hazard ratio.
Circulation. 2016;134:130–140. DOI: 10.1161/CIRCULATIONAHA.116.022797
July 12, 2016
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ARTICLE
Figure 5. Paired analysis of paravalvular
aortic regurgitation (bar graphs over
time).
Herrmann et al
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suggests improved selection of patients expected to
benefit from successful TAVR and fewer patients in
whom survival is limited by other comorbid conditions.
Despite the low profile of this device, high rate of
transfemoral access, and improved operator experience, the rate of conscious sedation and monitored
anesthesia care was only 16%. Several recent studies
and registries from outside the United States have demonstrated the feasibility, safety, and cost savings associated with the avoidance of general anesthesia and implementation of fast-track protocols.15,16 Increased use of
these minimalist approaches to transfemoral TAVR, particularly well suited to SAPIEN 3, may represent an opportunity to further improve outcomes with this device in
the current era. Alternatively, it is possible that the high
use of transesophageal echocardiography guidance for
sizing and postimplantation optimization contributed to
the observed high success rates.
The multivariable analysis confirms the benefit of the
transfemoral approach, as shown in other studies.10 It is
not surprising that procedural complications, including
major stroke, are associated with later mortality. However, this study demonstrates that mild PVL after SAPIEN
3 implantation is not associated with 1-year mortality, a
difference from the first-generation SAPIEN device. With
earlier-generation devices, even mild PVL was independently associated with mortality at 2 years with a clear
trend at 1 year.17,18 The present analysis demonstrates
no evidence for even a trend at 1 year, but longer-term
follow-up is necessary to confirm this observation.
This study is not a randomized comparison with other
devices or patient populations; therefore, such comparisons should be considered exploratory. Nonetheless,
the inclusion and exclusion criteria are identical to the
criteria of the prior PARTNER trials, allowing the limited
comparisons in this article.
Conclusions
The third-generation balloon-expandable SAPIEN 3 THV is
associated with a very low rate of early and 1-year complications and 1-year mortality in HR and inoperable patients
with severe AS. The combination of new design features
of SAPIEN 3, procedural improvements, operator experience, and improved patient selection has contributed to a
low rate of important adverse events (including stroke) and
a high rate of 1-year survival in HR and inoperable patients
with severe AS. These excellent 1-year follow-up data with
SAPIEN 3 support the use of TAVR as the preferred therapy in HR and inoperable patients with AS, as well as
further evaluation of this device in lower-risk patients.
Acknowledgments
Statistical analysis was conducted by Rupa Parvataneni, MS,
and Girma Minalu Ayele, PhD (Cardiovascular Research Foun138
July 12, 2016
dation). The assistance of Maria Alu, MS (Columbia University
Medical Center), in manuscript preparation is gratefully acknowledged.
Sources of Funding
The PARTNER Trial was funded by Edwards Lifesciences, and
the protocol was designed collaboratively by the sponsor and
the Trial Executive Committee. The sponsor was involved in
data collection and management but was not involved in the
design and conduct of this substudy; the analysis and interpretation of the data; or the preparation, review, and approval of
the manuscript.
Disclosures
Dr Herrmann has received research grant support from Edwards Lifesciences, St. Jude Medical, Medtronic, Boston Scientific, Abbott Vascular, Gore, Siemens, Cardiokinetix, and Mitraspan; has received consulting fees/honoraria from Edwards
Lifesciences and Siemens; and holds equity in Microinterventional Devices. Dr Thourani is a member of the PARTNER Trial
Steering Committee and a consultant for Edwards Lifesciences, Sorin Medical, St. Jude Medical, and DirectFlow. Dr Kodali
is a consultant for Edwards Lifesciences and a member of the
Scientific Advisory Board of Thubrikar Aortic Valve. Dr Szeto
has received consulting fees/honoraria from Microinterventional Devices. Dr Makkar has received grants from Edwards
Lifesciences and St. Jude Medical; is a consultant for Abbott
Vascular, Cordis, and Medtronic; and holds equity in Entourage
Medical. Dr Hahn has received research support from Philips
Healthcare and consulting fees/honoraria from Edwards Lifesciences. Dr Pibarot holds the Canada Research Chair in Valvular Heart Diseases, Canadian Institutes of Health Research,
Ottawa, ON, Canada, and has received research grant support
from Edwards Lifesciences. Dr Weissman has received grants
from Edwards Lifesciences, Abbott Vascular, Medtronic, Sorin, Direct Flow Medical, Boston Scientific, and JenaValve. Drs
Pibarot, Hahn, Weissman, and Leipsic have core laboratory
contracts with Edwards Lifesciences for which they receive no
direct compensation. Dr Webb has received consulting fees/
honoraria from Edwards Lifesciences. Drs Webb, Mack, and
Leon are members of the PARTNER Trial Executive Committee, for which they receive no direct compensation. The other
authors report no conflicts.
AFFILIATIONs
From Perelman School of Medicine at the University of Pennsylvania, Philadelphia (H.C.H., W.Y.S., S.A., N.D.); Emory University, Atlanta, GA (V.H.T., V.B.); Columbia University Medical Center, New York, NY (S.K.K., R.T.H., M.B.L.); Cedars-Sinai Medical
Center, Los Angeles, CA (R.R.M.); University of Virginia, Charlottesville (S.L.); Northwestern University, Chicago, IL (S.C.M.);
The Christ Hospital, Cincinnati, OH (D.J.K.); Ochsner Clinic, New
Orleans, LA (S.R.); Mayo Clinic, Rochester, MN (K.L.G.); Cleveland Clinic, OH (S.K.); Department of Medicine, Laval University,
Quebec, Canada (P.P.); Medstar Health Research Institute and
Georgetown University, Washington, DC (N.J.W.); St. Paul’s HosCirculation. 2016;134:130–140. DOI: 10.1161/CIRCULATIONAHA.116.022797
One-Year Outcomes With SAPIEN 3
pital, Vancouver, BC, Canada (J.L., J.G.W.); Intermountain Medical Center, Salt Lake City, UT (B.K.W.); and Baylor Scott and
White Health, Plano, TX (M.J.M.); and the PARTNER Trial Publication Office, New York, NY (H.C.H., V.H.T., S.K.K., R.R.M., D.J.K.,
S.K., V.B., R.T.H., P.P., N.J.W., J.L., J.G.W., M.J.M., M.B.L.).
FOOTNOTES
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Circulation. 2016;134:130–140. DOI: 10.1161/CIRCULATIONAHA.116.022797
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One-Year Clinical Outcomes With SAPIEN 3 Transcatheter Aortic Valve Replacement in
High-Risk and Inoperable Patients With Severe Aortic Stenosis
Howard C. Herrmann, Vinod H. Thourani, Susheel K. Kodali, Raj R. Makkar, Wilson Y. Szeto,
Saif Anwaruddin, Nimesh Desai, Scott Lim, S. Chris Malaisrie, Dean J. Kereiakes, Steven
Ramee, Kevin L. Greason, Samir Kapadia, Vasilis Babaliaros, Rebecca T. Hahn, Philippe
Pibarot, Neil J. Weissman, Jonathon Leipsic, Brian K. Whisenant, John G. Webb, Michael J.
Mack and Martin B. Leon
For the PARTNER Investigators
Circulation. 2016;134:130-140
doi: 10.1161/CIRCULATIONAHA.116.022797
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