1. Are we ready to perform TAVI in Intermediate Risk Patients?
CRT 2013
Washinton DC, February 28, 2013
Are we ready to perform TAVI in Intermediate Risk Patients?
Eberhard Grube MD FACC, FSCAI
Heart Center University Bonn , Bonn, Germany
Stanford University, School of Medicine, Stanford, California

2. Eberhard Grube, MD
Consulting: Medtronic CoreValve, Boston Scientific Corporation, Cordis Corporation, Johnson and Johnson and Abbott Vascular
Honoraria: Boston Scientific Corporation and Biosensors International
Stocks, Stock Options, other ownership interest: Medtronic CoreValve and Biosensors International
Off-Label: Off-label use of stents and valve prosthesis

3. Better TAVR Outcomes in Lower Risk Patients
N=420 patients (105 per quartile)
Quartile 1
Quartile 4
Age, years
81.1 years
78.9 years
Logistic Euroscore, %
25.4%
17.8%
STS-PROM, %
7.13%
4.8%
Crude 30 day Mortality, %
11.4%
3.8%
Lange JACC 2012;59:280–7)

4. “Risk Creep” Favors TAVR Preferentially

5. “Risk Creep” Favors TAVR Preferentially

6. Identifying Patient Risk
Top 33% Surgical Risk
STS ≥ 4
Top 7% Surgical Risk
STS > 8
Two-thirds of patients will remain optimal surgical candidates
“Cohort C”
Extreme
Risk
Surgical Aortic Valve Replacements 70-90,000 yearly
PARTNER IIA
SURTAVI
Intermediate
≈ 26%
STS PROM < 4%
30-Day Mortality < 2-4%
Futility
CoreValve High Risk
PARTNER A
CoreValve Extreme Risk
PARTNER B
Inoperable 20-50K

7. Shift to Lower Risk Mean EuroSCORE in CoreValve ADVANCE Study
varied by Country (p-value < 0.001)
EuroPCR 2012

8. TAVI for Intermediate Patients
Munich and BERMUDA Triangle Studies
Beyond Risk Models
Intermediate Risk Trials

9. Lange, R. et al, JACC 2012 “TAVI and Lower Surgical Risk Patients.”
Intermediate Patients: Munich Study
Lange, R. et al, JACC “TAVI and Lower Surgical Risk Patients.”

10. BERMUDA Triangle Study
BERn – MUnich - rotterDAm
TVT 2011

11. BERMUDA Triangle Study
3666 patients enrolled
TAVI – 782 (21.3%)
SAVR – 2884 (87.7%)
2882 patients excluded based on propensity score TAVI – 390 (49.9%)
SAVR – 2492 (86.4%)
Propensity score matched patients n = 784
TAVI - 392
SAVR- 392
Lost to follow-up: 4 (1.0%)
Lost to follow-up: 15 (3.8%)
392 analysed
392 analysed

12. Intermediate patients from the TAVI matched cohort
4-8% STS – 152 patients
3-8% STS – 255 patients

13. 30-day cumulative all-cause mortality (STS 3-8)
BERMUDA Triangle Study
30-day cumulative all-cause mortality (STS 3-8)
TAVI
(n=255)
SAVR
(n=255)
7.9%
7.1%

14. 1-year cumulative all-cause mortality (STS 3-8)
BERMUDA Triangle Study
1-year cumulative all-cause mortality (STS 3-8)
TAVI
(n=255)
SAVR
(n=255)
18.8%
17.0%

15. BERMUDA Triangle Study
Conclusions
Patients with severe aortic stenosis and an intermediate surgical risk have a similar overall mortality at 30 days and 1 years irrespective of the treatment (TAVI or SAVR)
It appears that there is a difference in clinical outcomes between men and women
The efficacy of TAVI in intermediate risk populations and the differences in outcomes between men and women warrants further evaluation in the context of randomized control trials 15

16. TAVI for Intermediate Patients
BERMUDA Triangle Study
Beyond Risk Models
Intermediate Risk Trials

17. Interplay of Frailty-Disability-Co-Morbidity
ADL
IADLs
Difficulty or dependency in daily living
Charlson
Co-Morbidities
Two or more medical conditions
21.5%
5.7%
46.2%
Frailty
Impairment in multiple systems that leads to a decline in homeostatic reserve and resiliency

18. Variables Included in Various Risk Models
Frailty is not represented in any of the commonly used risk scores
STS has begun collecting 5-meter gait speed as a measure of frailty
EuroSCORE II has added “Poor mobility” defined as severe impairment of mobility secondary to musculoskeletal or neurological dysfunction
Dewey J Thor CV Surgery 2008; 135:180

19. Interplay of Frailty-Disability-Co-Morbidity
Improved Frailty Assessments are Needed for:
- Utility v. Futility
Current risk stratification methods are not sufficient to stratify frailty
Complete assessment includes
- Frailty
- Disability
- Co-Morbidity
Important interactions with pulmonary disease and cognitive function
We still have work to do to to find the risk index

20. TAVI for Intermediate Patients
BERMUDA Triangle Study
Beyond Risk Models
Intermediate Risk Trials

21. Patient Selection
Presented By Prof. Patrick Serruys, MD on behalf of

22. CoreValve SURTAVI Trial
Evaluate the safety and efficacy of TAVI in Subjects with severe, symptomatic AS at intermediate surgical risk by randomizing Subjects to either SAVR or TAVI with the Medtronic CoreValve® System
Enrolling approximately 2,500 Subjects randomized 1:1 to TAVI and SAVR in up to 75 European, Canadian, and US centers.
STS mortality risk ≥ 4% and ≤ 10%
Heart Team Evaluation
Randomization
need for revascularization
TAVR only
SAVR + CABG
SAVR only
TAVR +
PCI
SAVR
Medtronic CoreValve TAVR

23. PARTNER II Trial Operable Inoperable
Symptomatic Severe Aortic Stenosis
ASSESSMENT by Heart Valve Team
Operable
(STS ≥4)
Inoperable
n=2000 Randomized Patients
n=500 Randomized Patients
Two Parallel
Randomized Trials
+5 Nested Registries
ASSESSMENT: Transfemoral Access
Transapical (TA)
Transfemoral (TF)
1:1 Randomization
Yes No
TF TAVR
SAPIEN
ASSESSMENT: Transfemoral Access
TA Registry
SAPIEN XT
Primary Endpoint: All-Cause Mortality + Disabling Stroke + Repeat Hospitalization at One Year (Non-inferiority)
1:1 Randomization VS
Yes >7mm No
Yes 6-7mm
6-7mm Registry
TF TAVR SAPIEN XT
Surgical AVR
Primary Endpoint: All-Cause Mortality + Major Stroke at Two Years (Non-inferiority)
TAVR:
TA / TAO VS
TAO Registry
29 mm valve Registry
TCT 2012

24. Conclusions
Although we have reasons to believe that Intermediate Risk patients will profit from TAVI outcome, we will need randomized data (Partner II, SURTAVI) to definitely extend and recommend TAVI in Intermediate Risk patients
Future risk models/scores will need to contemplate frailty, disability and co-morbidities
Additional “issues” need to be resolved such as procedural complications, durability of valves etc…