1. CoreValve Continued Access Study Shows Continued Improvement in 1-Year Outcomes With Self-Expanding Transcatheter Aortic Valve Replacement
Steven J. Yakubov, MD1; Daniel Watson, MD1; Michael J. Reardon, MD2; G. Michael Deeb, MD3; James B. Hermiller Jr, MD4; Jeffrey J. Popma, MD5; David A. Adams MD6
1Riverside Methodist Hospital, Columbus, OH; 2Houston-Methodist-Debakey Heart and Vascular Center, Houston, TX; 3University of Michigan Hospitals, Ann Arbor, MI; 4St. Vincent Medical Center, Indianapolis, IN; 5Beth Israel Deaconess Medical Center, Boston, MA; 6Mount Sinai Health System, New York, NY

2. Background
The CoreValve US Pivotal Extreme Risk (ER) Trial evaluated patients with aortic stenosis treated with the CoreValve self-expanding transcatheter aortic valve (TAV).
The ER Pivotal Trial reported all-cause mortality or major stroke of 26.0% at 1 year (primary endpoint) in patients with iliofemoral TAVR.
After completion of the CoreValve US Pivotal Extreme Risk (ER) Trial, patients could be enrolled in a Continued Access Study (CAS) until commercialization.
Improvement in procedural and longer-term outcomes have been reported with the evolution from randomized trials to continued access registries with the same balloon-expandable TAV.1
We evaluated 1-year outcomes from the CoreValve ER CAS to determine if continued experience led to improvements in procedural and clinical outcomes with the CoreValve TAV.
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1Fearon WF, et al. JACC Cardiovasc Interv 2014;7: 2

3. Methods
The ER Pivotal Extreme Trial recruited patients with severe AS considered at extreme risk of surgery or inoperable (STS ≥ 50%).
Patients underwent attempted implant in the ER CAS under the same inclusion and exclusion criteria and trial procedures as the Pivotal Trial.
Baseline characteristics and outcomes were compared for patients treated via iliofemoral access.
Event rates are reported as Kaplan-Meier estimates
Site-reported echocardiographic data
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4. Baseline Characteristics
Characteristic, mean ± SD or %
ER CAS N=1257
ER Pivotal
N=489
P Value
Age, years
83.5 ± 8.1
83.7 ± 8.7
0.595
Male
54.8
47.9
0.385
STS Predicted Risk of Mortality
9.1 ± 5.1
10.3 ± 5.5
<0.001
New York Heart Association class III/IV
87.4
91.8
0.008
Prior balloon aortic valvuloplasty
14.5
20.4
0.002
Prior stroke
13.8
13.7
0.971
Prior coronary artery bypass grafting
36.1
39.5
0.193
Prior percutaneous coronary intervention
40.6
37.0
0.172
Pre-existing pacemaker
23.2
26.0
0.215
Atrial fibrillation/flutter
45.3
46.8
0.569
Chronic lung disease/ COPD
56.4
58.9
0.338
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5. Comorbidities/Frailties/Disabilities
Characteristic, %
ER CAS N=1257
ER Pivotal
N=489
P Value
Severe aortic calcification
10.0
17.2
< 0.001
Porcelain aorta
4.3
4.9
0.577
Severe STS lung disease
20.2
23.5
0.130
Home oxygen
23.0
29.9
0.003
Anemia requiring transfusion
18.9
22.8
0.070
Albumin < 3.3 g/dL
18.7
18.2
0.808
5-Meter gait speed > 6 seconds
82.3
84.2
0.408
Grip strength below threshold
71.1
67.7
0.168
Falls in past 6 months
20.6
18.0
0.220
Assisted living
11.2
27.6
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6. Study Enrollment and Valve Sizes
2011
2012
2013
2014
Feb
May
Aug
Dec
ER Pivotal Enrollment
ER CAS Enrollment
26 mm 29 mm
31 mm
23, 26, 29, 31 mm
Add some thing about the change in the sizing from the initiation of the CoreValve ER Trial –
Only 2 sizes – 26 (20-23 mm diameter) and 29 mm (23-27 mm diameter)
Then added the 31 and the 23 …
Demonstrate % oversizing in 29 mm patients in pivotal
Demonstrate % oversizing in 31 mm patients in CAS
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7. Annular Sizing by Valve Size and Study Cohorts
The 23 mm valves were excluded from these analyses due to the small number implanted (Pivotal = 12; CAS = 22).

8. Procedural Outcomes Total procedure time, min 57.5 ± 34.0 65.6 ± 37.8
Characteristic, mean ± SD or %
ER CAS N=1252*
ER Pivotal
N=486*
P Value
Total procedure time, min
57.5 ± 34.0
65.6 ± 37.8
< 0.001
General anesthesia
91.7
94.4
0.050
Pre-TAVR balloon valvuloplasty performed
84.2
98.4
Post-TAVR balloon valvuloplasty performed
27.2
20.8
0.006
Valve-in-valve
4.6
2.5
0.040
1 valve implanted
94.3
95.9
0.394
Valve Size Implanted
23 mm
1.8
26 mm
34.6
29 mm
40.8
58.8
31 mm
36.5†
4.1
Device success
85.0
84.6
0.835
Site-reported implant depth, mm
4.4 ± 2.9
5.3 ± 2.7
*The number of index procedures.†23 and 31 mm valves added late during the pivotal trial.
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9. All-Cause Mortality 9

10. Cardiovascular Mortality

11. Other Safety Outcomes at 1 Year
Events, KM Rates as %
ER CAS N=1257
ER Pivotal
N=489
P Value
All-cause mortality or major stroke
22.5
26.0
0.098
Cardiovascular mortality
16.6
18.3
0.279
Any stroke
7.3
7.0
0.718
Reintervention
1.0
1.8
0.210
Major vascular complications
8.2
8.4
0.890
Life-threatening or disabling bleeding
12.6
18.0
0.004
Permanent pacemaker implant
24.6
26.9
0.397
Per ACC guidelines
23.8
19.5
0.063
AV hospitalizations
17.2
21.6
0.045
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12. Echocardiographic Findings*
*Site-reported
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13. Paravalvular Leak
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14. Conclusions
We have learned how to improve patient selection for optimal outcomes through post-hoc sub-group analyses from this trial program and the literature.
Clinical outcomes from the CAS are consistent with that reported in Pivotal ER.
Despite the use of a greater proportion of large valves, and less valve oversizing (which correlates with a higher likelihood of PVL), outcomes continue to improve.
The use of the CoreValve TAV in the STS/ACC/ TVT Registry™ 2 also showed that from initial rigorous controlled trials, to the CAS, and on to post-market surveillance registries, the results are consistent and continue to improve with experience and knowledge.
1Popma JJ, et al. Transcather Aortic Valve Replacement Using the Self-Expanding Bioprosthesis: First Report Using STS/ACC Transcatheter Valve Therapy Registry CoreValve Data. Presented at TCT 2015, San Francisco, CA. October 12, 2015
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