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 Study Stroke (%) REVIVAL (55) a 3.6 VANCOUVER (114) b 5.0 PARTNER EU (61) c 3.3 SOURCE (920) d 2.9 FRENCH (853) e 3.5 UK (172) f 4.0 BELGIAN (99) g 2.0 CANADIAN (168) h 3.0 Core Valve Stroke (%) Study 1.2 ITALIAN (663) 1 NR GERMAN (588) 2 1.9 AUSTRAL.-NZ (118) 3 SPANISH (108) 4 4.5 FRENCH (66) 5 4.3 UK (460) 6 5.0 BELGIAN (141) 7 2.8 AVERAGE aKodali et al AJC 2011;107:1058-1064 bWebb TCT 2008 cLefevre et al EurHeartJ 2011;32:148-57 dThomas et al Euro PCR 2011 eGilard M EuroPCR 2011 fLudman EuroPCR 2010 gBosmans ICVTS 2011;12:762-7 hRodes-Cabau et al. JACC 2010;55:In Press 1Tamburino Circulation 2011;123;299-308 2Zahn EuroPCR 2010 3Meredith TCT2010 4Avanzas Rev Esp Cardiol 2010;63(2):141-8 5Eltchaninoff Eur Heart J 2010; Sept 15, 2010 epub 6Moat EuroPCR 2010 7Bosmans EuroPCR 2010

N Engl J Med 2011;364:2187-98

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Neurological Events at 30 Days and 1 Year All Patients (N=699)   30 Days 1 Year Outcome TAVR (N = 348) AVR (N = 351) All Stroke or TIA – no. (%) 19 (5.5) 8 (2.4) 0.04 27 (8.3) 13 (4.3) TIA – no. (%) 3 (0.9) 1 (0.3) 0.33 7 (2.3) 4 (1.5) 0.47 All Stroke – no. (%) 16 (4.6) 0.12 20 (6.0) 10 (3.2) 0.08 Major Stroke – no. (%) 13 (3.8) 7 (2.1) 0.20 17 (5.1) 0.07 Minor Stroke – no. (%) 0.34 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 p-value p-value

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

Early hazard of neurologic event TAVR %/mo AVR Figure 1a 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 AVR-TA 11 TAVR-TA 9.1 6.9 TAVR-TF 5.8 AVR-TF 2.2 2.6 67 59 114 32 106 18 179 64 160 62 223 76 170 242 102 221 92 TAVR-TF TAVR-TA AVR-TF AVR-TA

30 Day Neurological Events: PARTNER A (ITT) TA TF per cent Smith et al, NEJM, June 2011

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) 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%) Death or Stroke – pts. (%) 16 (15.4%) 11 (12.0%) 80 (9.9%) 36 (34.8%) 27 (29.7%) 163 (25.7%) 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% 31.1% 8.9% 8.9%

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 AVR TAVR AVR TAVR AVR TAVR AVR TAVR AVR TAVR AVR TAVR AVR TAVR ICU stay (d) 0-2 3-5 6-10 11-30 31-364 365-730 >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 51% procedural (<10 d) n AVR TAVR AVR TAVR AVR TAVR AVR TAVR AVR TAVR AVR TAVR AVR TAVR ICU stay (d) 0-2 3-5 6-10 11-30 31-364 365-730 >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 This is a representative example of a patient’s BRAIN MRI pre-TAVI and post TAVI . . .where we appreciate the multiple insults to both the cerebrum cerebellum. This presentation tells us there is an embolic phenomenon occuring.

Silent Cerebral Embolism after TAVR Diffusion Weighted MRI – TAVR vs Surgical AVR New Lesions Lesion Volume mm3 % Age (yrs) 78 84 67 Kahlert PK et al. Circulation 2010;121:870-878

Brain DWMRI after TAVR Valve New MRI lesions Stroke Ghanem CoreValve 73% 10% Knipp SAPIEN 58% 4% Kahlert Both 84% 0% Astarci 91% Rodes, Webb 68% 3.3%

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 2X 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