1. Latest Data from Balloon Expendable Trials
E. Murat Tuzcu, MD

2. Disclosures: No conflict of interest
E. Murat Tuzcu, MD

3. First Randomized Trial in Intermediate Risk Patients
SAPIEN XT was randomized to surgery
S3i enrolled using the same exact protocol
Pre-specified S3i comparison to surgery utilizing propensity score analysis
PII A was a randomized trial of SAVR v Sapien XT in Intermediate Risk patients.
The S3 valve became available after enrollment was complete but before the 2 year Primary Endpoint of PII A (as dictated by the FDA).
PII S3i is a single arm study within P2A using the S3 valve in intermediate risk patients.
Entry criteria for patients in the randomized trial and the registry were virtually identical.
Outcomes of S3i were compared to the SAVR patients in PII A at 1 year using Propensity Scoring Methodology as agreed with the FDA

4. All-Cause Mortality or Disabling Stroke (%)
PARTNER 2 Trial – 10 EP (ITT) All-Cause Mortality or Disabling Stroke 1 10 20 30 40 50
TAVR
Surgery
p (log rank) = 0.253
HR [95% CI] = 0.89 [0.73, 1.09]
All-Cause Mortality or Disabling Stroke (%)
21.1%
16.4%
19.3%
8.0%
14.5%
6.1% 3 6 9 12 15 18 21 24
Months from Procedure
Number at risk:
Surgery
1021
838
812
783
770
747
735
717
695
TAVR
1011
918
901
870
842
825
811
801
774

5. All-Cause Mortality or Disabling Stroke (%)
TF Primary Endpoint (AT) All-Cause Mortality or Disabling Stroke 1
p (log rank) = 0.04
HR: 0.78 [95% CI: 0.61, 0.99]
16.3%
20.0% 3 6 9 12 15 18 21 24 10 20 30 40 50
15.8%
7.5%
11.7%
4.5%
TF TAVR
TF Surgery
All-Cause Mortality or Disabling Stroke (%)
Months from Procedure
Number at risk:
TF Surgery
722
636
624
600
591
573
565
555
537
TF TAVR
762
717
708
685
663
652
644
634
612

6. Sapien T3 – P2A Propensity Matched
Unadjusted Time-to-Event Analysis All-Cause Mortality (AT) 10 20 30 40
P2A Surgery
SAPIEN 3 TAVR
All-Cause Mortality (%)
13.0%
4.0%
7.4%
1.1% 3 6 9 12
Months from Procedure
Number at risk:
P2A Surgery
944
859
836
808
795
S3 TAVR
1077
1043
1017
991
963

7. Mortality, Stroke or AR ≥ Moderate
Confirmed: SAPIEN 3 is Better Than Surgery for Intermediate-Risk Patients
Propensity Sore Analysis merely confirmed that the large raw differences seen in KM Curves are indeed statistically significant
Mortality, Stroke or AR ≥ Moderate
The Propensity Scoring analysis merely confirmed the differences seen in the unadjusted data and showed that the S3 patients had improved outcomes compared to surgery in the Primary Outcome of mortality, stroke or AR> Mod

8. Health Status after TAVR P2A TAVR vs. SAVR
MCID = 5 points
2 year D = 19 points
KCCQ
D = 11.4 P < 0.001
D = -0.4 P = NS
D = 0.5 P = NS
Significant interaction (P<0.001) between treatment effect and access site for the primary endpoint and multiple secondary endpoints
ANCOVA analysis; adjusted for baseline
MCID = minimum clinically important difference
Cohen TCT 2016 8

9. Overall Clinical Status TF Cohort
Cohen TCT 2016 9
*P-values from ordinal logistic regression

10. Alive, KCCQ-OS > 60, No KCCQ-OS decline
Health Status after TAVR S3 –P2A TAVR vs. SAVR
Alive, KCCQ-OS > 60, No KCCQ-OS decline
Health status was evaluated in terms of categorical analyses as well so as to allow for a more global evaluation of a patient’s overall status after their valve replacement. Patients were defined as having a favorable outcome at 1 year if they were alive, had a KCCQ-overall summary score of greater than 60 (which generally correlates with New York Heart association class II symptoms) and if they did not have a significant decline (defined as greater than 10 points) in their KCCQ-overall summary score from baseline. Here again, S3-TAVR was found to be consistently superior to both surgical aVR as shown in the left panel as well as XT-TAVR as shown in the right panel.
Baron TCT 2016

11. Cut Points for frailty components
PARTNER 2 Trial – Frailty
Cut Points for frailty components
Variable
Cutoff
AUC
p-value
Katz 6
0.53
0.003
Gait Speed (m/sec)
0.63
0.52
0.04
Albumin
3.8
0.56
0.0006
Grip Strength (Female) 13
0.3
Grip Strength (Male) 26
0.54
0.01
Number of criteria met to be considered frail 2
0.0001
Green TCT 2016

12. 2-Year Outcomes Stratified by Frailty Status – Death
13.9%
19.6%
15.9%
20.6% 10 20 30 40 50
TAVR (vs. SAVR)
HR [95% CI: 0.69, 1.23] p=0.3 Among Frail
HR [95% CI: 0.63, 1.2] p=0.4 Among Non-Frail 3 6 9 12 15 18 21 24
TAVR: Non-Frail
TAVR: Frail
SAVR: Non-Frail
SAVR: Frail
Overall Log-Rank p-value = 0.01
Months
Death (%)
Numbers at Risk
TAVR: Non-Frail
526
496
488
470
461
452
447
444
433
TAVR: Frail
476
441
430
419
403
397
388
382
365
SAVR: Non-Frail
515
462
449
434
428
417
407
396
387
SAVR: Frail
482
392
377
371
357
353
345
331
Green TCT 2016

13. Valve Safety: Case Reviews of Hemodynamic ‘Outliers’
PARTNER 1 Trial
Hemodynamic Trends over 5 Years
Valve Safety: Case Reviews of Hemodynamic ‘Outliers’
VARC-2 ID’d ‘mild AS’ in 3-48%
Similar rates in SAVR and TAVR
Impractical for case review
↑ AV mean gradient ≥ 20 mmHg
N=10 (0.45%)
6 deaths (3 CV), no reintervention
Any mean gradient ≥ 40 mmHg
N=11 (0.46%)
8 deaths (2 CV), 1 reintervention
Any DVI ≤ 0.25
N=44 (1.8%)
22 deaths (5 CV), no reintervention
Douglas TCT 2016

14. Does PVR Regress Paired comparison of PVR grade at 30 days and 1 year (1,213 patients)
- 73% (24/33) of the patients with ≥ moderate PVR at 30 days showed a reduction in PVR severity at 1 year
- 0.9% (11/1180) of the patients with < moderate PVR at 30 days had a worsening of PVR at 1 year
Pibarot TCT 2016

15. Mitral Regurgitation: Baseline and Discharge
As baseline, 3 percent of patients had severe, 18 percent had moderate and 51 percent had mild mitral regurgitation prior to TAVR implantation.
In contrast, at discharge, 2 percent of patients had severe mitral regurgitation, representing a 33% relative reduction but an overall 1% absolute reduction in prevalence following TAVR implantation.
In addition 14 percent of patents had moderate regurgitation, representing a 22% and 13.7% relative reduction these classifications.
40 percent had no mitral regurgitation, representing a 42 increase in this category.
Petersen TCT 2016

16. Impact of Residual MR on Acute Heart Failure Readmission
Severe
Moderate 1 2 3 4 5 20 40 60 80
100
Mild
None
Years
#/100 patients
p-value < .0001 23 26 52 65
Plotted here is the association of severity of mitral valve regurgitation at discharge following TAVR and incidence of readmission for heart failure, adjusted by nested cohort methodology for the competing risk of death.
Note that while the prevalence of severe mitral regurgitation is less and the prevalence of moderate mitral regurgitation is increased compared with baseline, the risk of readmission with severe mitral regurgitation is unchanged but the risk of moderate regurgitation is increased compared to regurgitation grade at baseline.
Petersen TCT 2016

17. Edwards Transcatheter Valve Evolution
Untreated
Equine Tissue
Untreated
Equine Tissue
Treated
Bovine Tissue
TFX Treated
Bovine /CC
Bovine/CC Skirt lower 1/3
Andersen
Pig implant, 5/89
Cribier-Edwards™
FIM, 4/15/02
Edwards SAPIEN™
8/07
Sapien XT™
1/10
Sapien 3™
2013 17 17 17