Heart Valve Thrombosis & Neuro-Outcomes George D. Dangas, MD, FACC Professor of Medicine & Director, Cardiovascular Innovation Mount Sinai Medical Center, New York, NY George.Dangas@MountSinai.org

Independent predictors of stroke after TAVR (day 0 to 10) Iliofemoral access (HR: 0.67) Prior TIA (HR: 1.85) Prior CABG (HR: 0.61) Angina (HR: 1.68) BMI < 21 (HR: 2.14) Falls in the past 6 months (HR: 1.56) Time in OR (per min; HR: 1.003) Time of delivery catheter in body (per min; HR: 1.01) Rapid pacing during valvuloplasty (HR: 9.86) Circ Cardiovasc Interv. 2016;9:e003551.

Independent predictors of stroke after TF-TAVR Higher pre-TAVR aortic valve peak gradient Dementia 23-mm vs. 26-mm valve size Independent predictors of stroke after TA-TAVR Pure aortic stenosis withotu regurgitation More postdilations Race other than white Lower LVEF History of AF Circ Cardiovasc Interv. 2016;9:e002981

Circulation Cardiovascular Intervention 2016; 9 e004307 Art and Science of Cerebrovascular Event Prevention After Transcatheter Aortic Valve Replacement The evolving concepts of timing, risk factor contributions, and preventive strategies for cerebrovascular events (CVE) in patients undergoing transcatheter aortic valve replacement. Dangas G and Giustino G Circulation Cardiovascular Intervention 2016; 9 e004307

Strategies to prevent thrombo-embolic complications during TAVR Giustino G. & Dangas G. – Eurointervention 2015

Strategies to prevent thrombo-embolic complications after TAVR Giustino G. & Dangas G. – Eurointervention 2015

Neurological Outcomes With Embolic Protection Devices in TAVR A Systematic Review and Meta-Analysis of RCTs Giustino G, Mehran R, Verklamp R, Faggioni M, Baber U, Dangas G JACC Cardiovascular Interventions 2016; 9 (20): 2124-33

Neuroimaging Endpoints Giustino G, Mehran R, Verklamp R, Faggioni M, Baber U, Dangas G JACC Cardiovascular Interventions 2016; 9 (20): 2124-33

TLV between EP versus no EP by balloon-expandable versus self-expandable valves Giustino G, Mehran R, Verklamp R, Faggioni M, Baber U, Dangas G JACC Cardiovascular Interventions 2016; 9 (20): 2124-33

Neurologic Clinical Endpoints Giustino G, Mehran R, Verklamp R, Faggioni M, Baber U, Dangas G JACC Cardiovascular Intervention 2016; 9 (20): 2124-33

All-cause Mortality Giustino G, Mehran R, Verklamp R, Faggioni M, Baber U, Dangas G JACC Cardiovascular Intervention 9 (20): 2124-33

Perspectives WHAT IS KNOWN? Intraprocedural EP emerged as an attractive strategy to prevent intraprocedural stroke and mitigate the burden of subclinical cerebral embolization during TAVR. Previous RCTs evaluating EP devices were of small size and relatively underpowered to detect differences in neurological imaging and clinical endpoints. WHAT IS NEW? In this meta-analysis of the available RCTs, use of EP seems to be associated with a significant reduction in imaging markers of cerebral infarction and improved early clinical neurological status. WHAT IS NEXT? The safety and efficacy of routine EP during TAVR need to be established in prospective RCTs powered to detect differences in hard clinical endpoints. Giustino G, Mehran R, Verklamp R, Faggioni M, Baber U, Dangas G JACC Cardiovascular Interventions 2016; 9 (20): 2124-33

Primary Efficacy Endpoint The GALILEO Trial Primary Efficacy Endpoint Composite of Death, Stroke, MI, Symptomatic Valve Thrombosis, Systemic Thromboembolism, DVT and PE

- The ENVISAGE Trial - Successful TAVR Design Flow Chart Patients with indication to chronic oral anticoagulation RANDOMIZE 1:1 2-5 Days after the procedure Background of single Antiplatelet Therapy EDOXABAN 60 mg QD (30 mg QD in patients > 80 years of age, CrCl 30-50 ml/min or weight < 60 kg). N = 750 Warfarin (target INR 2-3) N = 750 Minimum duration of randomized therapy 12 months CLINIC FOLLOW-UP: 1, 6, 12 Months Secondary Endpoints All-cause Death, MI, Stroke or TIA, VARC-2 Life-threatening (LT) bleeding and Major bleeding Primary Endpoint - NACE [Composite of Death, MI, Stroke, TIA, systemic thromboembolism or VARC-2 Life-threatening (LT) or Major bleeding] Substudies MRI substudy 4D CT substudy Cost-Effectiveness analysis Neurocognitive function & QoL substudy