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

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

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)

“Risk Creep” Favors TAVR Preferentially

“Risk Creep” Favors TAVR Preferentially

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

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

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

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

BERMUDA Triangle Study BERn – MUnich - rotterDAm TVT 2011

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

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

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%

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%

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

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

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

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

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

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

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

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

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

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…