Role of Embolic Protection during TAVR

Transcription

1 Role of Embolic Protection during TAVR Samir Kapadia, MD Professor of Medicine Section head, Interventional Cardiology Director, Cardiac Catheterization Laboratories

2 Disclosure Co PI for Sentinel Trial

3 Questions Is Stroke a Problem with TAVR in 2017? How Common is Stroke in Comparison With SAVR? Does Cerebral Protection Work?

4 Questions Is Stroke a Problem with TAVR in 2017? How Common is Stroke in Comparison With SAVR? Does Cerebral Protection Work?

5 Stroke Rates in Randomized Trials 1 Leon, et al., N Engl J Med 2010;363: ; 2 Webb, et al., J Am Coll Cardiol Intv 2015;8: ; 3 Smith, et al., N Engl J Med 2011;364: ; 4 Leon, et al., N Engl J Med 2016;374: ; 5 Popma, et al., J Am Coll Cardiol 2014;63: ; 6 Adams, et al., N Engl J Med 2014;370:1790-8;;

6 Stroke Rates with Contemporary Devices Weighted average (n=5,952) ~3.1% 71% BE (S3+XT) 29% SE (EvolutR+CV) 1 Manoharan, et al., J Am Coll Cardiol Intv 2015; 8: ; 2 Moellman, et al., presented at PCR London Valves 2015; 3 Linke, et al., presented at PCR London Valves 2015; 4 Kodali, et al., Eur Heart J 2016; doi: /eurheartj/ehw112; 5 Vahanian, et al., presented at EuroPCR 2015; 6 Webb, et. al. J Am Coll Cardiol Intv 2015; 8: ; 7 DeMarco, et al, presented at TCT 2015; 8 Meredith, et al., presented at PCR London Valves 2015; 10 Falk, et al., presented at EuroPCR 2016; 11 Kodali, presented at TCT 2016; Reardon, M Published in NEJM March % of SENTINEL patients were evaluated prospectively by neurologists. Clinical Events Committee included 2 stroke neurologists.

7 Stroke Risk With Second Generation TAVR valves Meta-analysis of ~20 non-randomized, mostly FIM, valve-company sponsored studies 2.4% major stroke at 30-days Athappan, et al. A systematic review on the safety of second-generation transcatheter aortic valves. EuroIntervention 2016; 11:

8 TVT Stroke Rate 3 2,5 2 1,5 1 0,5 0 % 30 Day Stroke 2,6 2,6 2,6 2,4 0.15% PCI

9 Mortality After Stroke TF TAVR PARTNER Trial Kapadia et al, Circ Int 2016

10 Mortality after Stroke CoreValve High Risk Trial No. at Risk Major Stroke No Major Stroke

11 Rodes- Cabau 2011 Ghanem 2010 Arnold 2010 Kahlert 2010 Astarci 2011 DEFLECT III control arm 2015 Bijuklic 2015 CLEAN- TAVI control arm PROTAVI-C NeuroTAVR MRI Lesions After TAVR 100% 90% 80% 70% 60% 50% 40% 30% 20% 10% 0% % of TAVI patients with new cerebral lesions on DW-MRI 1. Rodes-Cabau, et al., JACC 2011; 57(1): Ghanem, et al., JACC 2010; 55(14): Astarci, et al., EJCTS 2011; 40: Arnold, et al., JACC:CVI 2010; 3(11): Lansky, et al., EHJ 2015; May Kahlert, et al., Circulation. 2010;121: Bijuklic, et al., JACC: CVI Linke, et al., TCT Vahanian, TCT Lansky, et al. London Valves Sacco et al., Stroke Vermeer et al., Stroke Vermeer et al., New Engl J Med 2009

12 Overt Stroke Size, Number, LOCATION Size Number Location

13 Neurocognitive Changes and Lesions Lesion Volume, All Territories, P= Fit Plot for chgzoverall Change in Overall z-score (follow-up - baseline) log10totvolpp_allt Fit 95% Confidence Limits 95% Prediction Limits

14 Stroke Risk Summary Stroke risk is decreased compared to early feasibility trials (but not much) and is still a significant clinical problem

15 Questions Is Stroke a Problem with TAVR in 2017? How Common is Stroke in Comparison With SAVR? Does Cerebral Protection Work?

16 Stroke : TAVR versus SAVR 8 P1A P2A S3i SURTAVI ,4 2,6 5,5 6,1 2,7 6,1 3,4 5, Days TAVR SAVR TAVR SAVR TAVR SAVR TAVR SAVR

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18 Stroke Detection and Reporting Strokes = 34 patients (17%; 95% CI, 12-23%) TIA = 4 patients (2%; 95% CI, 0-4%) 25 strokes were not included in STS database STS database reported 13 patients (6.6%) with stroke but 4 did not have stroke by DeNOVO (alcohol withdrawal, no deficit by day 7) Masse, circulation, 2014

19 Diagnosis Stroke diagnosis requires careful neurologist evaluation for being accurate Brain infarction ( covert stroke ) is more common Neurocognitive changes may correlate with covert strokes

20 TAVR and SAVR Stroke Risk of stroke with TAVR is not higher than risk of stroke with SAVR

21 Questions Is Stroke a Problem with TAVR in 2017? How Common is Stroke in Comparison With SAVR? Does Cerebral Protection Work?

22 Cerebral Protection

23 Claret Medical Sentinel Cerebral Protection System CAUTION: Investigational Device. Limited to investigational use by United States law.

24 Sentinel Filters Protection Fully Protected 74% brain volume Partially Protected 24% brain volume Unprotected 2% brain volume Zhao M, et al. Regional Cerebral Blood Flow Using Quantitative MR Angiography. AJNR 2007;28:

25 30-Day MACCE Sentinel vs. Control (ITT) 20% 15% % of Patients with an Event 10% 7.3% 9.9% 5% 0% N=17 N=11 Sentinel (Safety + Test) (N=234) Control (N=111) Error bars represent upper bound of the 95% Upper CI

26 SENTINEL Study: Procedural Stroke 63% Reduction *Fisher Exact Test 95% of SENTINEL patients were evaluated by neurologists Clinical Events Committee included 2 stroke neurologists SENTINEL trial. Data presented at Sentinel FDA Advisory Panel, February 23, 2017

27 Type of Tissue Identified Acute + organizing thrombus Arterial wall + thrombus Valve tissue Calcium nodules Foreign material + thrombus Myocardium + thrombus Organizing

28 Morphometric Analysis: Embolic Material by Particle Size >=150 um 0.15 mm 99% 0.5 mm >= 500 um 91% 1 mm >= 1000 u 55% 2 mm >=2000 um 14% 0% 20% 40% 60% 80% 100% Percent of Patients with at Least One Particle of Given Size

29 Patient Level Meta-analysis: CLARET Lesion Volume in Protected Territories Data presented at Sentinel FDA Advisory Panel, February 23, 2017

30 Ulm Sentinel study 802 all-comer consecutive TAVR patients at University of Ulm were prospectively enrolled A propensity-score analysis was done matching the 280 patients protected with Sentinel to 280 control patients In multivariable analysis, TAVR without cerebral emboli protection (p=0.044) was the only independent predictor for stroke at 7-days TAVR without cerebral emboli protection (p=0.028) and STS score (<8 vs. >8) (p=0.021) were the only independent predictors for mortality and stroke at 7-days Wörhle J, Seeger J, et al. DGK Mannheim 2017; CSI-Ulm-TAVR Study clinicaltrials.gov NCT

31 TriGuard Device: REFLECT trial Single-wire nitinol frame and mesh filter with pore size of 130μm designed to deflect cerebral emboli during TAVI while allowing maximal blood flow Positioned across all 3 cerebral vessels and maintained by a stabilizer in the innominate Delivered via 9 Fr sheath from the femoral artery

32 Efficacy Measures, % TriGuard TM Pooled Analysis: In Hospital Results Primary Safety Endpoint Of 30 Day MACCE: 18.2% TG vs 24.1% Control, p=0.44 Patient level pooled analysis from the TriGuard TM Trials (N=142) P= ,2 0 0 VARC 2 Disabling stroke P=0.05 VARC 2 Stroke P= ,0 ASA Stroke MOCA NIHSS or MoCA TG P=0.38 Control P= P= DW-MRI Lesion Lansky et al PCR 2016

33 Predictors of Stroke, Neuro events or MRI findings Author N Event rate Approach Clinical predictors Anatomical predictors Tay et al % TA/TF H/O stroke/tia Carotid stenosis* Nuis et al % TF New onset AF Baseline AR >3+ Amat Santos et al % TA/TF New onset AF None Franco et al % TA/TF None Post-dilation Miller et al % TA/TF History of stroke Non TF-TAVR candidate Smaller AVA Cabau et al % (MRI) TA/TF Male, History of CAD Higher AVG Fairbairn et al % (MRI) TF Age Aortic atheroma Nombela-Franco et al % TA/TF Balloon postdilatation, valve dislodgement, New onset AF, PVD, Prior CVA

34 Summary There is benefit of emboli prevention Clinical benefit Covert stroke benefit We can t reliably identify patients at risk and 99% patients have embolic material in filter Device is safe Emboli prevention devices should be considered in all patients undergoing TAVR