Longevity of transcatheter and surgical bioprosthetic aortic valves in patients with severe aortic stenosis and lower surgical risk Lars Sondergaard, MD, DMSc Professor of Cardiology Rigshospitalet Copenhagen, Denmark - On behalf of the NOTION trial investigators

Lars Sondergaard conflicts of interest I do not have any potential conflict of interest I have the following potential conflicts of interest to report: Honorarium: Medtronic Institutional grant/research support: Medtronic Consultant: Medtronic Employment in industry: Owner of a healthcare company: Stockholder of a healthcare company: Other(s):

Nordic Aortic Valve Intervention Trial the NOTION trial TAVI has become a standard treatment for patients with severe aortic stenosis and higher surgical risk Ongoing controlled trials will help to define the role of TAVI in patients at lower surgical risk The Nordic Aortic Valve Intervention (NOTION) trial was the first to randomise lower risk patients to either SAVR or TAVI (CoreValve)

The Notion Trial summary Objective: To compare TAVI vs. SAVR in lower risk patients >70 years eligible for surgery (all-comers population) Primary outcome: Composite rate of all-cause mortality, stroke or myocardial infarction at 1 year (VARC II-defined) Secondary outcomes: Safety and efficacy (NYHA), echocardiographic outcomes(VARC II-defined) Design: Prospective, multi-centre, non-blinded, randomised trial (N=280) Enrollment period: December 2009 - April 2013

The NOTION Trial all-cause mortality 31.1% 29.4% Number at risk: 142 139 138 135 130 119 100 52 134 128 125 123 118 110 92 58

The NOTION Trial aortic valve performance * * * * * *p < 0.001 TAVI vs. SAVR TAVI SAVR * * * *

The NOTION Trial valve durability analysis Analysis of the durability of TAVI is important as the therapy looks to expand to patients with longer life expectancy A post-hoc analysis of prosthetic valve durability using expanded definitions for valve dysfunction and failure was undertaken The implanted cohort of patients was analysed

The NOTION Trial durability analysis methods (I) Bioprosthetic valve dysfunction (BVD) was defined as: Structural valve deterioration (SVD) or Non-structural valve deterioration (NSVD) or Bioprosthetic valve thrombosis or Endocarditis – 2 major criteria according to modified Duke criteria Capodanno et al. Eur Heart J, in press

The NOTION Trial durability analysis methods (II) Structural valve deterioration (SVD) Moderate or severe haemodynamic SVD Mean gradient ≥20 mmHg or Mean gradient ≥10 mmHg change from baseline or Moderate/severe intra-prosthetic aortic regurgitation (AR) (new or worsening from baseline) Non-structural valve deterioration (NSVD) Moderate/severe patient-prosthesis mismatch at 3 months or Moderate/severe paravalvular regurgitation (PVL) Capodanno et al. Eur Heart J, in press

The NOTION Trial structural valve deterioration TAVI SAVR n=139 n=135 SVD Moderate haemodynamic SVD 2.9% (4/139) 20.7% (28/135) Severe haemodynamic SVD 0.7% (1/139) 3.0% (4/135) 26.1% 3.9% Number at risk: 139 134 130 124 112 94 50 135 118 101 92 74 41

The NOTION Trial structural valve dysfunction through 5 years components TAVI SAVR n=139* n=135* P-value SVD 3.6% (5/139) 21.5% (29/135) <0.0001 Moderate haemodynamic SVD 2.9% 20.7% Mean gradient ≥20 mmHg 2.2% 19.3% Mean gradient ≥10 and <20 mmHg change from 3mo 1.4% 8.1% Moderate Central AR 0% Severe haemodynamic SVD 0.7% 3.0% Mean gradient ≥40 mmHg 1.5% Mean gradient ≥20 mmHg change from 3mo Severe Central AR *Not all subjects have completed 5 year follow-up

The NOTION Trial non-structural valve dysfunction through 5 years components TAVI SAVR n=139* n=135* P-value NSVD 54.0% (75/139) 57.8% (78/135) 0.52 Moderate/severe PPM at 3 months 43.2% Moderate PPM at 3 Months 30.9% 29.6% Severe PPM at 3 Months 12.3% 28.2% Moderate/severe PVL 21.6% 1.5% Moderate PVL 20.9% Severe PVL 0.7% 0% *Not all subjects have completed 5 year follow-up

The NOTION Trial bioprosthetic valve dysfunction through 5 years components TAVI SAVR n=139* n=135* P-value BVD 55.4% (77/139) 65.2% (88/135) 0.10 SVD 3.6% 21.5% <0.0001 NSVD 54.0% 57.8% 0.52 Thrombosis 0% NA Endocarditis 4.3% 5.9% 0.55 *Not all subjects have completed 5 year follow-up Subjects could have more than 1 component of BVD

The NOTION Trial durability analysis methods (III) Bioprosthetic valve failure defined as: Valve-related death Death caused by BVD or sudden unexplained death following diagnosis of BVD Aortic valve re-intervention TAVI or SAVR following diagnosis of BVD Severe hemodynamic SVD Mean gradient ≥40 mmHg or Mean gradient ≥20 mmHg change from baseline or Severe AR (new or worsening from baseline) Capodanno et al. Eur Heart J, in press

The NOTION Trial bioprosthetic valve failure TAVI SAVR P-value n=139 n=135 BVF Valve-related deaths 4.3% (6/139) 3.7% (5/135) 0.80 Re-intervention 2.2% (3/139) 0.0% (0/135) 0.25 Severe haemodynamic SVD 0.7% (1/139) 3.0% (4/135) 0.21 9.5% 8.5% Number at risk: 139 135 132 126 115 96 51 124 117 109 91 54

The NOTION Trial limitations NOTION enrolled patients from 2009-2013 when echo- based sizing was standard of care instead of CT sizing No core lab was used for evaluation of echocardiographic examinations

The NOTION Trial conclusions Through 5 years follow-up of the NOTION trial: Excellent haemodynamic valve performance was maintained Bioprosthetic failure was low and similar for the self- expanding transcatheter (CoreValve) and the surgical valves implanted Structural valve deterioration was significantly greater for SAVR compared with TAVI There was no valve thrombosis and similar rates of endocarditis for both groups