Lessons from PARTNER I (A & B) CRT, Washington DC, Feb 5, 2012 Peter C. Block M.D. Andreas Gruentzig Cardiovascular Center Emory University, Atlanta, GA. Lessons from PARTNER I (A & B) What have we not yet learned CRT, Washington DC, Feb 5, 2012 What have we learned

COI Medtronic: consultant DirectFlow Medical: consultant; equity Edwards Lifesciences; PARTNER site

PARTNER I (B): TAVR = BIG WIN Lesson 1 PARTNER I (B): TAVR = BIG WIN TAVR Med Rx Death - All Cause Death - Cardiovascular NYHA Functional Class I or II Repeat Hospitalization

So far.. So good Pooled Transfemoral AVR All Cause Mortality (n=216) Are European Data Throwaways? (“Registries are NOT Truth”) Is PARTNER “Just One Trial” ? Is PARTNER I (B) a Fluke? Edwards Device So far.. So good Pooled Transfemoral AVR All Cause Mortality (n=216) Lesson 2 1992 BAV Registry Survival Canada Reg Revive Reg Revival Reg PARTNER EU France Reg BAV Registry PARTNER contr France PARTNER EU Months Post Procedure Answer: NO, NO, NO 4

The PARTNER I (A) Trial (ACC New Orleans April 2011) How about operable patients? The PARTNER I (A) Trial (ACC New Orleans April 2011) Comparing TAVR (either transfemoral or transapical) to surgical AVR in high-risk, operable patients with AS.

All-Cause Mortality Transfemoral (N=492) PARTNER I (A) = Equivalence All-Cause Mortality Transapical (N=207) All-Cause Mortality Transfemoral (N=492) Higher AVR risk brings out co-morbidities early Transcatheter Surgical AVR Co-morbidities cause greater mortality in TF’s later

Lesson 3 PARTNER 1A Conclusions Both TAVR and AVR were associated with important but different peri-procedural hazards: Strokes and major vascular complications were more frequent with TAVR Major bleeding and new onset AF were more frequent with surgical AVR TAVR and AVR are both acceptable therapies in high-risk patients; differing peri-procedural hazards should influence case-based decision-making This is the Bulleted List slide. To create this particular slide, click the NEW SLIDE button on your toolbar and choose the BULLETED LIST format. (Top row, second from left) The Sub-Heading and footnote will not appear when you insert a new slide. If you need either one, copy and paste it from the sample slide. If you choose not to use a Sub-Heading, let us know when you hand in your presentation for clean-up and we’ll adjust where the bullets begin on your master page. Also, be sure to insert the presentation title onto the BULLETED LIST MASTER as follows: Choose View / Master / Slide Master from your menu. Select the text at the bottom of the slide and type in a short version of your presentation title. Click the SLIDE VIEW button in the lower left hand part of your screen to return to the slide show. (Small white rectangle) 7

PARTNER IA: Excellent Surgical Outcomes Lesson 4 Success Better (8% mortality) than predicted (12% mortality) surgical outcomes in the “control” AVR patients. 8

The TA approach is not dead We are teachable Lesson 5 The TA approach is not dead Dewey: STS Jan 30, 2012 Results of on-going data from continued access show: Improvement in outcomes and CVA incidence for TA: THERE IS A REAL LEARNING CURVE This is the Bulleted List slide. To create this particular slide, click the NEW SLIDE button on your toolbar and choose the BULLETED LIST format. (Top row, second from left) The Sub-Heading and footnote will not appear when you insert a new slide. If you need either one, copy and paste it from the sample slide. If you choose not to use a Sub-Heading, let us know when you hand in your presentation for clean-up and we’ll adjust where the bullets begin on your master page. Also, be sure to insert the presentation title onto the BULLETED LIST MASTER as follows: Choose View / Master / Slide Master from your menu. Select the text at the bottom of the slide and type in a short version of your presentation title. Click the SLIDE VIEW button in the lower left hand part of your screen to return to the slide show. (Small white rectangle) 9

All-Cause Mortality Dewey, STS Jan 30, 2012 PARTNER IA: randomized to AVR PARTNER IA: randomized to TA vs AVR 29.1% Continued access TA 25.3% 23.6% No. at Risk AVR 92 76 71 70 67 PMA-TA 104 87 82 73 NRCA-TA 822 571 370 297 126

Stroke Dewey STS Jan 30, 2012 PARTNER IA: randomized to AVR PARTNER IA: randomized to TA vs AVR Continued access TA 10.8.% 7.0% 3.7.% No. at Risk AVR 92 72 67 66 63 PMA-TA 104 81 77 70 NRCA-TA 822 563 365 291 123

All-Cause Mortality or Stroke Dewey STS Jan 30, 2012 Continued access TA 34.8% 29.7% 25.7% No. at Risk AVR 92 72 67 66 63 PMA-TA 104 81 77 70 NRCA-TA 822 563 365 291 123

What are the TAVR lessons we still need to learn? Need to work on the negative issues: 1: BLEEDING(17%) & VASCULAR COMP (16%) 2. HEART BLOCK & the BIG HITTERS 3: CVA ~5% @ 30 days to ~8% @ 1 yr 4: PARAVALVAR LEAK ?

The next challenge: stroke prevention Umbrella/deflector devices: 3 currently available Aortic Embolic Embrella Claret dual filter Protection Device (AEPD)

But…~15% have >2+ AR… what about the LV? The PVL Issue PVL is relatively common following TAVI Most pts (~85%) have 0, 1+ or 2+ PVL PVL remains stable to 12 months But…~15% have >2+ AR… what about the LV?

My Take on PVL (for now) No PVL would be better Many TAVR pts have PVL: > 85% is mild or trivial PVL does not worsen over 1 yr PARTNER says 2+ or less PVL is tolerated by the hypertrophic LV acutely and in short term F/U Should we Rx PVL ? Who knows …….. But Senning mortality data are troubling -- ? Rx 2+ or more PVL For elderly pts long term issues may be moot No, mild Mod, severe

PARTNER 1(B) 2 yr. All Cause Mortality “Who are those guys?” Butch Cassidy 100 Standard Rx TAVR 80 Perhaps the most imp’t thing we don’t know 68.0% 43.3% 60 50.7% All-cause mortality (%) 40 30.7% 20 Months Patient selection; Patient selection; Patient selection