Updates From SURTAVI in Intermediate Risk Patients Jeffrey J. Popma, MD Professor of Medicine Harvard Medical School Director, Interventional Cardiology Beth Israel Deaconess Medical Center Boston, MA

Conflict of Interest Statement Over the past year, I have received the following: Institutional Grants: Medtronic, Boston Scientific, Abbott Vascular, Direct Flow, Cook Medical Advisory Board: Boston Scientific, Abbott Vascular, GE Healthcare, Covidien Non Vested Equity: Intelemage, Healthworks, Direct Flow Medical

It has been a long road . . .

The SURTAVI Braintrust Serruys 2012

The SURTAVI Initial Selection Criteria Serruys 2012

Serruys 2012

Serruys 2012

Revision of Protocol and the Expansion to US

Current SURTAVI Trial Design Primary Objective Evaluate in a prospective randomized fashion whether TAVI is non-inferior to SAVR with respect to composite endpoint of all-cause mortality and disabling stroke at 24 months in patients with symptomatic severe aortic stenosis and at intermediate surgical risk Primary Endpoint All-cause mortality or disabling stroke at 24-months

CoreValve SURTAVI Trial Clinical Sites Up to 115 worldwide centers in Europe, Canada, and United States

Patient Selection Frailty assessments identifies: Severe, symptomatic AS Intermediate surgical risk: Heart Team predicted risk of 30- day operative mortality is ≥3% to <15% at 30 days) Subjects with CAD and a Syntax score ≤22 will be eligible Concomitant PCI and TAVI can be performed; staging is left at discretion of operator CABG should be conducted during the index SAVR procedure Frailty assessments identifies: Subject is < 80 years of age and three or more Subject is ≥ 80 years of age and two or more Wheelchair bound, resides in an institutional care facility, BMI < 20 kg/m2, Grip strength < 16kg, Katz Index Score ≤ 4, Albumin < 3.5 g/dl

SURTAVI Trial Timeline 2012 2013 2014 2015 2016 Entry STS 4-10% Risk Based Entry Heart Team >3% to < 15% June 2012 First EU Pt Evolut R Nov 2012 First US Pt Randomized Enrollment Concluded May 2016 Activation of 40 Sites from US High and Extreme Risk Trials Activation of ~30 Additional Sites

CoreValve SURTAVI Trial Update Randomization concluded on 19-May-2016 with ~1600 subjects enrolled into primary analysis cohort Study is designed with an interim analysis which permits analysis of the primary endpoint prior to complete 24 month follow-up Data release is anticipated at ACC 2017