outcomes of transcatheter aortic valve replacement with ... · mack, gilbert h. l. tang, tsuyoshi...
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Outcomes of Transcatheter Aortic Valve Replacement with Balloon-Expandable Sapien3 Valve in Bicuspid Aortic Stenosis:An analysis of the STS/ACC TVT Registry
Raj R. Makkar*, Sung-Han Yoon, Martin B. Leon, Tarun Chakravarty, Sreekanth
Vemulapalli, Michael Rinaldi, Pinak B. Shah, Eric R. Skipper, Vinod H. Thourani, Vasilis
Babaliaros, Wen Cheng, Alfredo Trento, Samir R. Kapadia, Susheel Kodali, Michael J.
Mack, Gilbert H. L. Tang, Tsuyoshi Kaneko
* Smidt Heart Institute, Cedars-Sinai Medical Center, Los Angeles
2
• Grant/Research Support
• Consulting Fees/Honoraria
• Major Stock Shareholder/Equity
• Edwards Lifesciences, Abbott Inc., Medtronic, Boston Scientific
• Edwards Lifesciences, Abbott Inc., Medtronic, Boston Scientific
• Entourage Medical
Within the past 12 months, I or my spouse/partner have had a financial interest/arrangement
or affiliation with the organization(s) listed below.
Affiliation/Financial Relationship Company
Raj Makkar, MD
Disclosure Statement
Statistical analyses were performed by Edwards Lifesciences. The views or opinions presented here do not represent
those of the American College of Cardiology, The Society of Thoracic Surgeons, or the STS/ACC TVT Registry.
3
Background & Objective
1 Roberts WC, Ko JM. Frequency by decades of unicuspid, bicuspid, and tricuspid aortic valves in adults having isolated aortic valve replacement for aortic stenosis, with or without associated aortic regurgitation. Circulation. 2005;111(7):920-925
• Bicuspid aortic valve accounts for up to 50% of patients requiring surgical aortic
valve replacement in the younger population1
• As TAVR becomes a therapeutic option for younger and healthier patients, bicuspid
aortic valves will be seen more often.
• Pivotal clinical trials, including the low risk trials enrolling younger patients, have
excluded patients with bicuspid aortic valves.
• We sought to compare the outcomes of TAVR with balloon-expandable SAPIEN 3
valve in native bicuspid versus tricuspid aortic valve stenosis in the real-world
STS/ACC TVT Registry.
4
Study Population
92236 SAPIEN 3 TAVRs in STS/ACC TVT
Registry(June 2015 − Nov 2018)
552 Sites
79096 Tricuspid ASSAPIEN 3 Patients
7082 N/A, Uncertain, Unicuspid, Quadricuspid
3196 Valve-in-Valve136 Prior TAVR
2726 Bicuspid ASSAPIEN 3 Patients
5
Characteristic% or mean ± SD
Bicuspid AS(n=2726)
Tricuspid AS(n=79096)
p-value
Age (years) 73 ± 11 81 ± 8 <0.0001
STS Risk Score (%) 4.9 ± 4.0 6.5 ± 4.6 <0.0001
Male 60.4 55.1 <0.0001
NYHA III/IV 74.3 75.4 0.20
BMI (kg/m2) 29.2 ± 7.6 29.0 ± 7.3 0.13
Hypertension 84.1 91.2 <0.0001
Diabetes 35.7 38.8 0.001
Peripheral Arterial Disease 24.1 27.6 <0.0001
Carotid Stenosis 14.8 25.2 <0.0001
Atrial Fibrillation 28.8 38.7 <0.0001
Prior Stroke 10.2 11.5 0.04
Chronic Lung Disease 41.5 40.1 0.13
Prior PCI 25.2 34.0 <0.0001
Prior CABG 15.7 20.8 <0.0001
Porcelain Aorta 2.7 3.4 0.05
GFR (mL/min/1.73 m2) 65.3 ± 28.7 59.3 ± 24.5 <0.0001
5MWT (seconds) 7.5 ± 4.2 8.4 ± 5.4 <0.0001
Baseline Characteristics – Unadjusted
6
Study population
25 Covariates used for propensity matching
Age Chronic Lung Disease
Gender (male) Prior PCI
NYHA III/IV Prior CABG
BMI Porcelain Aorta
Hypertension Mean Gradient
Diabetes LVEF
Creatinine ≥ 2 Mitral Regurgitation
Peripheral Arterial
DiseaseTricuspid Regurgitation
Carotid Stenosis 5 Meter Walk Test
Atrial Fibrillation Access Site
Prior Stroke KCCQ
Immunocompromised Hemoglobin
GFR2691 Tricuspid AS
SAPIEN 3 Patients
2691 Bicuspid AS
SAPIEN 3 Patients
79096 Tricuspid AS
SAPIEN 3 Patients
3196 Valve-in-Valve
136 Prior TAVR
7082 N/A, Uncertain,
Unicuspid, Quadricuspid
2726 Bicuspid AS
SAPIEN 3 Patients
1:1 Propensity Matching
92236 SAPIEN 3 Cases in TVT Registry(June 2015 − Nov 2018)
552 Sites
7
Baseline Characteristics – Matched
Characteristic% or mean ± SD
Bicuspid AS(n=2691)
Tricuspid AS(n=2691)
p-value
Age (years) 73 ± 10 73 ± 11 0.47
STS Risk Score (%) 4.9 ± 4.0 5.1 ± 4.2 0.09
Male 60.3 61.5 0.35
NYHA III/IV 74.4 74.1 0.83
BMI (kg/m2) 29.2 ± 7.6 29.4 ± 7.4 0.30
Hypertension 84.5 84.2 0.80
Diabetes 35.8 36.8 0.43
Peripheral Arterial Disease 24.3 24.5 0.90
Carotid Stenosis 15.0 15.6 0.63
Atrial Fibrillation 29.0 29.4 0.73
Prior Stroke 10.2 10.2 0.96
Chronic Lung Disease 41.7 42.0 0.79
Prior PCI 25.5 26.6 0.34
Prior CABG 15.9 17.2 0.18
Porcelain Aorta 2.7 3.1 0.37
GFR (mL/min/1.73 m2) 65.0 ± 28.4 64.4 ± 27.2 0.39
5MWT (seconds) 7.6 ± 4.2 7.6 ± 4.0 0.79
8
Methods
• Primary end-point: Mortality and Stroke at 30-days and 1-year.
• Secondary end-point: Procedural complications, in-hospital adverse events,
post-procedural echocardiographic assessment of the valve, functional status
and health status at 30 days and 1 year.
• To compare death and stroke between bicuspid and tricuspid cohorts, the
patients in the study cohort were linked with Centers for Medicare and Medicaid
Services (CMS) claims data, in addition to the follow-up obtained from the TVT
registry.
9
Baseline Echo
Characteristic% or mean ± SD
Bicuspid AS(n=2691)
Tricuspid AS(n=2691)
p-value
AV Mean Gradient (mmHg) 45.2 ± 15.0 44.9 ± 15.2 0.51
AV Area (cm2) 0.71 ± 0.23 0.71 ± 0.21 0.15
LVEF (%) 53.5 ± 14.7 52.5 ± 15.0 0.02
Annular Size (mm) 25.1 ± 3.2 24.6 ± 3.0 <0.0001
Mitral Regurgitation (mod/sev) (%) 20.6 21.7 0.39
Tricuspid Regurgitation (mod/sev) (%) 14.0 14.1 0.86
10
Characteristic%
Bicuspid AS(n=2691)
Tricuspid AS(n=2691)
p-value
Transfemoral access 93.6 93.9 0.65
Conscious Sedation 42.8 44.1 0.33
Valve Size <0.0001
20mm 2.7 3.1 0.33
23mm 23.0 28.5 <0.0001
26mm 39.1 42.0 0.03
29mm 35.2 26.4 <0.0001
Procedural Data
11
Characteristic% or mean ± SD
Bicuspid AS(n=2691)
Tricuspid AS(n=2691)
p-value
Device success 96.5 96.6 0.87
Procedure Time, min 100.7 ± 51.8 98.2 ± 52.1 0.08
Fluoroscopy Time, min 18.5 ± 11 17.1 ± 10.2 <0.0001
Conversion to open surgery 0.9 0.4 0.03
Annulus Rupture 0.3 0.0 0.02
Cardiopulmonary bypass 1.4 1.0 0.13
Aortic dissection 0.3 0.1 0.34
Coronary Obstruction 0.4 0.3 0.34
Need for a second valve 0.4 0.2 0.16
Procedural Outcomes
12
30-Day Outcomes
KM estimate % Bicuspid Tricuspid AS p-value
All-cause mortality 2.6 2.5 0.82
All stroke 2.4 1.6 0.02
Life-threatening bleeding 0.1 0.1 0.99
Major vascular complication 0.9 1.0 0.68
New pacemaker 9.1 7.5 0.03
Aortic valve reintervention 0.2 0.3 0.79
13
1-year Mortality and All Stroke Unadjusted Cohort
Log rank P < 0.001
HR: 0.75 [95% CI: 0.65, 0.87]
All-C
au
se M
ort
ality
(%)
0
5
10
15
20
25
30
35
40
Time in Months
0 3 6 9 12
10.4%
14.4%
Bicuspid
Tricuspid
2726 1272 1235 1175 947
79096 41830 40133 37794 30309
Number at risk
2726 1247 1209 1148 923
79096 41050 39266 36851 29459
P = 0.721
HR: 1.04 [95% CI: 0.83, 1.31]
3.4%
3.7%
Str
oke (
%)
Bicuspid
Tricuspid
0
5
10
15
20
25
30
35
40
Time in Months0 3 6 9 12
Number at risk
Bicuspid
Tricuspid
Bicuspid
Tricuspid
14
Bicuspid
Tricuspid
1-Year Mortality – Matched
2691 1259 1222 1162 934
2691 1367 1326 1256 977
P= 0.31HR: 0.90 [95% CI: 0.73, 1.10]
10.5%
12.0%
All-C
au
se M
ort
ality
(%
)
0
5
10
15
20
25
30
35
40
Time in Months
0 3 6 9 12
Bicuspid
Tricuspid
Number at risk
15
Bicuspid
Tricuspid
1-Year Stroke – Matched
2691 1234 1196 1135 910
2691 1341 1296 1226 952
P= 0.16HR: 1.28 [95% CI: 0.91, 1.79]
3.1%
3.4%
Str
oke (
%)
Time in Months
0 3 6 9 12
Bicuspid
Tricuspid
Number at risk
0
5
10
15
20
25
30
35
40
16
Bicuspid
Tricuspid
1-Year Mortality or Stroke – Matched
2691 1234 1196 1135 910
2691 1341 1296 1226 952
P= 0.75HR: 0.97 [95% CI: 0.81, 1.16]
12.9%
14.1%
Mo
rtality
or
Str
oke (
%)
Time in Months
0 3 6 9 12
Bicuspid
Tricuspid
Number at risk
0
5
10
15
20
25
30
35
40
17
Timing of All-Stroke Events
0%
10%
20%
30%
40%
50%
0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30
Bicuspid (N=63)
Tricuspid (N=41)
P-value=0.54
18
Paravalvular Leak – Matched
81.5% 83.7%74.4% 77.2% 75.7% 78.8%
17.0% 15.5%23.6% 20.5% 21.1% 18.7%
1.3% 0.7% 2.0% 2.3% 3.0% 2.5%
0.1% 0.1% 0.1% 0.1% 0.2% 0.0%
0%
20%
40%
60%
80%
100%
Bicuspid(n=2179)
Tricuspid(n=2233)
Bicuspid(n=1711)
Tricuspid(n=1782)
Biscuspid(n=593)
Tricuspid(n=673)
Severe
Moderate
Mild
None/Trace
Discharge 30-day 1-year
p=0.44p=0.17p=0.08
19
0
15
30
45
60
Baseline Discharge 30-day 1-year
Me
an
Gra
die
nt
(mm
Hg
)
Mean Gradient
Bicuspid Tricuspid
p=0.69
Hemodynamics – Matched
p=0.15 p=0.86p=0.51
0
0.5
1
1.5
2
2.5
3
Baseline Discharge
AV
A (
cm
2)
Aortic Valve AreaBicuspid Tricuspid
p=0.15 p=0.34
20
3.4% 3.5%
54.9% 54.7% 59.7% 60.8%
22.2% 22.4%
38.4% 37.7% 32.3% 32.7%
59.9% 60.3%
6.3% 6.9% 6.8% 5.3%14.4% 13.8%
0.5% 0.6% 1.2% 1.1%
0%
20%
40%
60%
80%
100%
Bicuspid(n=2667)
Tricuspid(n=2664)
Bicuspid(n=1958)
Tricuspid(n=2015)
Biscuspid(n=752)
Tricuspid(n=804)
IV
III
II
I
NYHA Class – Matched
Baseline 30-day 1-year
p=0.93 p=0.80 p=0.70
21
0
20
40
60
80
100
120
Baseline 30-day 1-year
KC
CQ
Ove
rall
Su
mm
ary
S
co
re
Bicuspid
Tricuspid
KCCQ – Matched
p=0.87 p=0.52 p=0.15
n=2460 n=2463 n=1992 n=1990 n=732 n=776
22
Limitations
• Lack of center-independent adjudication of adverse events as well as potential under-reporting of adverse events.
• Bicuspid AS represents a heterogeneous anatomic cohort, It is possible that the operators selected the most favorable anatomic subsets while excluding patients with highest risk anatomical features
• Lack of a control group of bicuspid AS patients treated surgically
• Impact of aortopathy on outcomes could not be assessed
23
Summary
• In this largest real life registry of all consecutive TAVRs in the US, TAVR with balloon expandable Sapien 3 valve for Bicuspid AS, compared to tricuspid AS, was associated with
• Similar survival at 30 days and 1 year
• Increased risk of aortic root injury and conversion to open heart surgery; although overall rate was still low (<1.0%).
• Increased peri-procedural and 30 day stroke rates
• Equivalent hemodynamics (Similar and significant reduction in transaortic gradients, improvement in aortic valve areas and frequency of paravalvular leak rates)
• Similar improvement in Quality of Life metrics (NYHA class and KCCQ scores)
24
Clinical Implications
• This analysis suggests that select bicuspid anatomy is amenable to TAVR with current generation balloon-expandable TAVR technology with acceptable clinical outcomes.
• These data provide an argument for TAVR to be a reasonable alternative for bicuspid AS in patients who are intermediate or high risk for surgical aortic valve replacement and provide a sound basis to conduct a randomized clinical trial in young patients with bicuspid AS who are low risk for surgery.