Stroke After TAVR Surgeon View Michael Mack M

Stroke After TAVR: Surgeon View Michael Mack, M. D. Baylor Healthcare System Dallas, TX

Michael J. Mack, MD I have no real or apparent conflicts of interest to report. My presentation will include off label discussions: Edwards Sapien Valve

Stroke VARC Definition

Stroke After TAVR • • • Stroke After Surgical AVR Stroke After TAVR Cause of Stroke with TAVR Possible Solutions Will Stroke Limit TAVR?

Stroke After TAVR • • • Stroke After Surgical AVR Stroke After TAVR Cause of Stroke with TAVR Possible Solutions Will Stroke Limit TAVR?

Observed Stroke

2 -2. 5%

Stroke After TAVR • • • Stroke After Surgical AVR Stroke After TAVR Cause of Stroke with TAVR Possible Solutions Will Stroke Limit TAVR?

TAVR – Stroke Edwards (TF) Core Valve Stroke (%) REVIVAL (55) a VANCOUVER (114) b 3. 6 1. 2 ITALIAN (663) 1 5. 0 NR GERMAN (588) 2 PARTNER EU (61) c 3. 3 1. 9 AUSTRAL. -NZ (118) 3 SOURCE (920) d 2. 9 0 FRENCH (853) e 3. 5 4. 5 FRENCH (66) 5 UK (172) f 4. 0 4. 3 UK (460) 6 BELGIAN (99) g 2. 0 5. 0 BELGIAN (141) 7 h CANADIAN (168) 3. 0 2. 8 AVERAGE Study SPANISH (108) 4 a. Kodali et al AJC 2011; 107: 1058 -1064 1 Tamburino Circulation 2011; 123; 299 -308 c. Lefevre et al Eur. Heart. J 2011; 32: 148 -57 3 Meredith TCT 2010 b. Webb TCT 2008 2 Zahn Euro. PCR 2010 d. Thomas et al Euro PCR 2011 4 Avanzas Rev Esp Cardiol 2010; 63(2): 141 -8 e. Gilard M Euro. PCR 2011 f. Ludman Euro. PCR 2010 g. Bosmans ICVTS 2011; 12: 762 -7 h. Rodes-Cabau et al. JACC 2010; 55: In Press 5 Eltchaninoff Eur Heart J 2010; Sept 15, 2010 epub 6 Moat Euro. PCR 2010 7 Bosmans Euro. PCR 2010

N Engl J Med 2011; 364: 2187 -98

Editorial Response N Engl J Med 2011; 364: 2256 -58

Neurological Events at 30 Days and 1 Year All Patients (N=699) 30 Days Outcome TAVR (N = 348) 1 Year AVR p-value TAVR (N = 351) (N = 348) AVR p-value (N = 351) All Stroke or TIA – no. (%) 19 (5. 5) 8 (2. 4) 0. 04 27 (8. 3) 13 (4. 3) 0. 04 TIA – no. (%) 3 (0. 9) 1 (0. 3) 0. 33 7 (2. 3) 4 (1. 5) 0. 47 All Stroke – no. (%) 16 (4. 6) 8 (2. 4) 0. 12 20 (6. 0) 10 (3. 2) 0. 08 Major Stroke – no. (%) 13 (3. 8) 7 (2. 1) 0. 20 17 (5. 1) 8 (2. 4) 0. 07 Minor Stroke – no. (%) 3 (0. 9) 1 (0. 3) 0. 34 3 (0. 9) 2 (0. 7) 0. 84 Death/maj stroke – no. (%) 24 (6. 9) 28 (8. 2) 0. 52 92 (26. 5) 93 (28. 0) 0. 68

Neurologic Events in PARTNER-A As treated (AT) analysis of types of neurological events (Sept 2010 datalock) Major 58% TIA 26% Minor 16% Major 69% 31/344 TIA 25% Minor 6% 16/315 47 patients, 49 events § Ischemic- 72%, hemorrhagic- 0%, Isch → hem- 4%, unknown- 24%

Early hazard of neurologic event TAVR %/mo AVR Months after Procedure

Neurological events at 30 days and 1 year (AT, n= 657) TF stratum (n= 461) TF TAVR vs. AVR

Neurological events at 30 days and 1 year (AT, n= 657) TA stratum (n= 196) TA TAVR vs. AVR

Neurologic events Considering competing risk of death % TAVR-TF TAVR-TA 242 102 221 223 76 170 AVR-TA 11 9. 1 6. 9 TAVR-TF 5. 8 AVR-TF 2. 6 2. 2 179 64 160 114 32 106 67 59

30 Day Neurological Events: PARTNER A (ITT) per cent TA TF Smith et al, NEJM, June 20

TA- CAP Clinical Outcomes at 30 Days and 1 Year (AT) n=822 All percents are KM estimates. 30 Days 1 Year Outcome PMA-TA (n = 104) AVR (n = 92) NRCA-TA (n = 822) All-Cause Mortality – pts. (%) 9 (8. 7%) 7 (7. 6%) 66 (8. 2%) 30 (29. 1%) 23 (25. 3%) 148 (23. 6%) Stroke – pts. (%) 7 (7. 0%) 5 (5. 5%) 16 (2. 0%) 10 (10. 8%) 6 (7. 0%) 22 (3. 7%) 16 (15. 4%) 11 (12. 0%) 80 (9. 9%) 36 (34. 8%) 27 (29. 7%) 163 (25. 7%) Death or Stroke – pts. (%) Note: p-values between NRCA-TA vs PMA-TA and NRCA-TA vs AVR are all not significant.

What Does A Patient REALLY Want To Know ? • What are my chances of being alive with out a stroke ?

Partner I-A-Death /Neurologic Events 32. 5% 8. 9% 31. 1%

Stroke After TAVR • • • Stroke After Surgical AVR Stroke After TAVR Cause of Stroke with TAVR Possible Solutions Will Stroke Limit TAVR?

PARTNER-A: Timing of Neurological Events 6 -10 11 -30 31 -364 365 -730 AVR TAVR 3 -5 TAVR 0 -2 AVR TAVR ICU stay (d) AVR TAVR n >730

The Source

New Onset Atrial Fibrillation – 31. 9% Cerebrovascular event/Systemic Embolization 13. 6% vs. 3. 2% p=0. 021

Stroke After TAVR • • • Stroke After Surgical AVR Stroke After TAVR Cause of Stroke with TAVR Possible Solutions Will Stroke Limit TAVR?

Stroke after TAVR Role of Embolic Protection

PARTNER-A: Timing of Neurological Events 6 -10 11 -30 31 -364 365 -730 AVR TAVR 3 -5 AVR 0 -2 TAVR ICU stay (d) AVR TAVR n AVR 51% procedural (<10 d) >730

Brain DWMRI after TAVR

Diffusion-Weighted MRI Study Philipp Kahlert, MD West German Heart Center Essen Pre-TAVI Post-TAVI Example of an 82 -year-old patient two days after successful TAVI

Silent Cerebral Embolism after TAVR Diffusion Weighted MRI – TAVR vs Surgical AVR Lesion Volume New Lesions mm 3 % Age (yrs) 78 84 67 Kahlert PK et al. Circulation 2010; 121: 870 -878

Brain DWMRI after TAVR Valve New MRI lesions Stroke Core. Valve 73% 10% SAPIEN 58% 4% Kahlert Both 84% 0% Astarci Both 91% 0% SAPIEN 68% 3. 3% Ghanem Knipp Rodes, Webb

Stroke After TAVR • • • Stroke After Surgical AVR Stroke After TAVR Cause of Stroke with TAVR Possible Solutions Will Stroke Limit TAVR?

Stroke After TAVR • Stroke is 2 X higher with TAVR vs. surgical AVR • Stroke is related to age • Stroke is related to atherosclerotic disease burden • Stroke is caused by mainly by manipulation at the diseased aortic valve • Role of embolic protection intuitive but not proven

Stroke After TAVR • Cerebral emboli occur in most patients with only a small minority being clinically apparent • New onset post operative atrial fibrillation probably plays a role • There is probably not a significant late hazard risk of stroke with TAVR • Role of postoperative anticoagulation/antiplatelet therapy unknown