The Future of Medicine Who to TAVR? Azeem Latib MD EMO-GVM Centro Cuore Columbus and San Raffaele Scientific Institute, Milan, Italy
FIRST PATIENT TO UNDERGO PTCA FIRST PATIENT TO UNDERGO TAVI Grüntzig A. The Lancet 1978;1:263 Cribier A. et al. Circulation. 2002 Dec 10;106(24):3006-8 2017 2002 Progressive worsening of acute limb ischemia : - Leg amputation 4 months after TAVI - No post-operative recovery Slide courtesy of Dr Stephan Windecker
What physicians said about TAVR It will never work Don t touch the pericardial tissue, it s fragile and cannot withstand crimping to a smaller profile The native calcified aortic valve cannot be stented open If you tried to stent open the calcified native valve, you will cause strokes by embolizing the calcium and debris The THV cannot/will not be retained and will embolize itself THVs will have smaller valve areas and therefore be inferior to surgical valves in performance The THV cannot be made durable The THV will have perivalvular leaks which will cause endocarditis Cardiologists know nothing about Aortic Stenosis and should not treat these patients! Slide courtesy of Yuval Binur
TAVR is Available in More Than 65 Countries Around the World >400,000 total implants to date
DEVICES FOR TRANSCATHETER AORTIC VALVE IMPLANTATION 2007 2017
Impact of Experience and New TAVR Systems on Vascular Complications Fearon, ACC 2013; Hayashida, JACC Card Int 2011; 4(8): 851-8; Nuis, AJC 2011; 107: 1824-29; Toggweiler, JACC 2012; 59(2): 113-8
All-Cause Mortality at 30 Days Edwards SAPIEN Valves (As Treated) 20% 15% PARTNER 1 and 2 Trials (Overall and TF Patients) 10% 5% 6.3% 5.2% 3.7% 4.5% 3.5% 2.2% 1.6% 1.1% 1.1% 0% P1B (TF) P1A (All) P1A (TF) P2B (TF) P2B XT (TF) S3HR (All) S3HR (TF) S3i (All) S3i (TF) 175 344 240 271 282 583 491 1072 947 SAPIEN SXT SAPIEN 3
Published 2010 2011 2012 2013 2014 2015 AS with no symptoms Symptomatic AS: SAVR Risk Low Intermediate High Extreme PARTNER 1B PARTNER 1A Corevalve US HR Corevalve US ER CHOICE NOTION PARTNER 2B PARTNER 2A Pipeline of TAVR Trials across the spectrum of aortic stenosis Investigational devices Edwards Sapien/Sapien XT/S3 2016 2017 PARTNER 2 S3i SURTAVI PARTNER 2 S3 Medtronic CoreValve/Evolut R Boston Lotus Upcoming Direct Flow Medical Direct Flow UK TAVI Abbott Vascular Portico 2017 REBOOT REPRISE 3 SALUS (stopped) Symetis Acurate Neo Any available TAVR system PARTNER 3 PORTICO IDE 2018 2019 2020 2021 EARLY TAVR US Evolut R LR NOTION 2 SOLVE-TAV SCOPE 1 TAVR UNLOAD SCOPE 2 24 TAVR RCTs Capodanno D, Leon MB. EuroIntervention 2016
THE EVOLUTION OF CLINICAL EVIDENCE TAVI superior to medical Rx > TAVI noninferior or superior to SAVR TAVI noninferior or superior (TF access) to SAVR =/> =/>
30-Day Safety and Procedure-related Complications SAVR TAVR Stroke Shock Acute renal failure (stg 2-3) > 2 U blood transfusions Major vascular complications PM implantation 5.6 % 3.4% 3.8% 1.1% 4.4% 1.7% 29.8% 9.2% 1.1% 6.0% 6.6% 25.9% Reardon MJ et al, NEJM 2017
Total Aortic Regurgitation* Intermediate Risk 100% 90% 80% 70% 60% 50% 40% 30% 20% 10% 0% 3% 36% 1% 7% 5% 34% 61% 93% 61% 90% 60% 90% TAVR (N=832) SAVR (N=707) TAVR (N=599) 1% 9% SAVR (N=506) 5% 35% TAVR (N=299) Discharge 12 Months 24 Months 1% 9% SAVR (N=244) Severe Moderate Mild None/trace * Implanted population, core lab adjudicated 11
Paravalvular Regurgitation (VI) 3-Class Grading Scheme P < 0.001 P < 0.001 Moderate 8.0% Moderate 0.6% Mild 3.5% Mild 26.8% No. of echos 30 Days 2 Years TAVR 872 600 Surgery 757 514
Meta-analysis of TAVR vs. SAVR Death or disabling stroke at 1-year 4 randomized trials (N =5,002) Pagnesi M, Chiarito M, Stefanini GG, Testa L, Reimers B, Colombo A, Latib A JACC Cardiovasc Interv 2017
STS Score SURGICAL RISK AND AGE Mean Age across studies: 83 84 83 83 84 82 83 82 11.6 11.7 10.3 10.3 8.4 7.3 5.8 5.2 PARTNER 1B PARTNER 1A CoreValve ER PARTNER 2B SAPIEN 3 HR CoreValve HR PARTNER 2A SAPIEN 3 IR
STS >15% 2017 ESC/EACTS GUIDELINES FOR THE MANAGEMENT OF AORTIC STENOSIS: UPDATE IN RISK CATEGORISATION Extreme STS >10% High SURGERY Low TAVI STS 4-10% Intermediate Increased Risk Low STS <4% The favourable results of TAVI have been reproduced in multiple large-scale, nationwide registries supporting the generalizability of outcomes observed in randomized controlled trials. This favours the use of TAVI over surgery in elderly patients at increased surgical risk. However, the final decision between SAVR and TAVI (including the choice of access route) should be made by the Heart Team.
CRITERIA TO GUIDE THE HEART TEAM FAVOURS TAVI FAVOURS SAVR CLINICAL CHARACTERISTICS ANATOMICAL AND TECHNICAL ASPECTS ASSOCIATED CONDITIONS REQURING INTERVENTION Baumgartner et al, European Heart Journal (2017)
Low Risk
STS database 2002-2010 (141,905 pts) 6.2% 13.9% High risk (STS > 8%) Intermediate risk (STS 4-8%) 79.9% Low risk (STS <4%) Courtesy of N. Piazza
The PARTNER 3 Trial Study Design Symptomatic Severe Calcific Aortic Stenosis Low Risk ASSESSMENT by Heart Team (STS < 4%, TF only) TF - TAVR (SAPIEN 3) 1:1 Randomization (n=1228) Surgery (Bioprosthetic Valve) PARTNER 3 Registries Alternative Access (n=100) (TA/TAo/Subclavian) CT Imaging Sub-Study (n=200) Actigraphy/QoL Sub-Study (n=200) CT Imaging Sub-Study (n=200) Actigraphy/QoL Sub-Study (n=200) Bicuspid Valves (n=100) PRIMARY ENDPOINT: Composite of all-cause mortality, all strokes, or re-hospitalization at 1 year post-procedure ViV (AV and MV) (n=100) Follow-up: 30 days, 6 mos, 1 year and annually through 10 years
MEDTRONIC TAVR IN LOW RISK PATIENTS TRIAL DESIGN & LEAFLET SUB-STUDY Patient Population: Low Risk Cohort Determined by Heart Team to be low surgical risk Primary Endpoint: Safety: Death, all stroke, life-threatening bleeding, major vascular complications, or AKI at 30 days Efficacy: Death or major stroke at 2 years Sample Size: ~1200 Subjects Follow-up Evaluations: 30-days, 6-month, 18-month, and 1 Through 5 years Number of Sites: Up to 80 sites
New Indications
My Thoughts
TAVI Clinical Use in 2018: (evidence & common sense) >75-years old and increased surgical risk >80-years old, irrespective of surgical risk Special populations where TAVI is preferred Previous sternotomy, Valve-in-Valve Small annulus Low EF & Low flow-low gradient (irrespective of contractile reserve) CKD with low GFR Patient preference The younger, the lower the risk, the more important it becomes to have: Transfemoral access Excellent result must be predictable Coronary access guaranteed esp. after TAVI-in-TAVI Ability to re-valve (i.e. TAVI-in-TAVI)
TAVI for all Intermediate & Low Risk? Yes Transfemoral Predictable outcomes with low risk of PVL Low PPM rate Future coronary access maintained Expert valve center with known outcomes No Associated valvular pathology that cannot be treated percutaneously High risk aortic anatomy (bicuspid, severe LVOT calcification, high risk of coronary occlusion) Loss of coronary access with TAVI-in-TAVI
Coronary access after TAVI can be challenging
What about coronaries after performing a TAVI on a degenerated TAVI?
Coronary access after TAVI-in-TAVI: a glimpse into the future A post-tavi CT study of 263 patients after implantation of different valves 35.4% (93/263) patients found to have high-risk for impaired coronary access of at least one coronary LM 26.6% (70) RCA 22.8% (60) Both coronaries 14.1% (37)
Performance Benchmarks for Expert Valve Centers All-cause mortality Major (disabling) strokes Major vascular complications New permanent pacemakers Mod-severe para-valvular regurgitation Current <3% <2% <5% <10% < 5% Future <1% <1% <2% <8% 0%
Estimated Global TAVR Growth SOURCE: Credit Suisse TAVI Comment January 8, 2015. ASP assumption for 2024 and 2025 based on analyst model. Revenue split assumption in 2025 is 45% U.S., 35% EU, 10% Japan, 10% ROW In the next 10 years, TAVR growth will increase X4!
Slide courtesy of Francesco Maisano