2/15/2018 DISCLOSURES OBJECTIVES. Consultant for BioSense Webster, a J&J Co. Aortic stenosis background. Short history of TAVR

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1 TRANSCATHETER AORTIC VALVE REPLACEMENT IN 2018: IS IT NOW THE STANDARD OF CARE? 22 ND ANNUAL COASTAL CARDIAC & VASCULAR CONFERENCE FEBRUARY 17, 2018 R. David Anderson, MD, MS, FACC, FSCAI Professor of Medicine Director of Interventional Cardiology Director of the UF Health Cardiac Cath Lab Program Director: Interventional Cardiology Fellowship University of Florida Health Gainesville, Florida DISCLOSURES Consultant for BioSense Webster, a J&J Co. OBJECTIVES Aortic stenosis background Short history of TAVR Review of TAVR clinical trials Some recent transcatheter cases 1

2 NATURAL HISTORY OF UNTREATED AS Ross J, et al. Circ 1968: 38 (Suppl V): AORTIC STENOSIS: SURVIVAL WITHOUT INTERVENTION Actuarial survival - % AS years Control O Keefe et el Carabello, B. A. N Engl J Med 2002;346:

3 HISTORY OF TRANSCATHETER AORTIC VALVE (TAVR) THERAPY IN US first balloon-expandable bovine pericardial percutaneous valve in animal balloon-expandable stent-mounted valve in human aortic position FDA approved the Edwards-Sapien Valve inoperable patients FDA approved Edwards-Sapien for high surgical risk 2013 CoreValve FDA approved for extreme and high surgical risk patients June 2014 second generation Sapien XT balloon expandable valve FDA approved June 2015 third generation Sapien 3 balloon expandable receives FDA green light June second generation self-expanding Evolut R FDA approved 2016 FDA approval for intermediate patients March 2017 FDA approves Evolut Pro for high or extreme risk patients WHO IS A TAVR CANDIDATE IN 2018? WHO ISN T? High or prohibitive surgical risk patients (STS risk > 8%) Porcelain aorta Hostile chest Pulmonary disease Bypass grafts at risk Pulmonary hypertension Dementia, frailty Liver disease Intermediate risk patients (STS risk > 4 - < 8%) Low risk patients in the PARTNER 3 and CoreValve Evolut R clinical trial (STS risk < 4%) 3

4 SURGICAL RISK ASSESSMENT Society of Thoracic Surgeons Risk Score (STS) STS model calculates operative risk of morbidity and mortality based upon demographic and clinical variables (riskcalc.sts.org) <4% low risk, >4 - <8% intermediate risk, >8% high risk European System for Cardiac Operative Risk Assessment EuroSCORE - basic Logistic EuroSCORE more complex EuroSCORE II adds frailty criteria (2011) 85 YO FEMALE WITH SEVERE SYMPTOMATIC AORTIC STENOSIS Class I - AVR 85 YO FEMALE WITH SEVERE SYMPTOMATIC AORTIC STENOSIS 4

5 BEYOND STS AND EUROSCORE? HOW ABOUT THE EYEBALL TEST? Grip Strength kg (Frail < 18 kg) 5 Meter Walk sec (Frail > 7 sec) Albumin (Frail < 3.5 mg/dl 5

6 Partner A n = 699 Symptomatic Severe Aortic Stenosis ASSESSMENT: High-Risk AVR Candidate 3,105 Total Patients Screened High- Risk ASSESSMENT: Transfemoal Access Total = 1,057 patients 2 Parallel Trials: Individually Powered Inoperable ASSESSMENT: Transfemoral Access Partner B n = 358 High-Risk TF High-Risk TA 1:1 Randomization 1:1 Randomization 1:1 Randomization TF TAVR VS AVR TA TAVR V S AVR TF TAVR n = 179 VS Standard Therapy n = 179 Primary Endpoint: All-Cause Mortality (1 yr) (Non-inferiority) Primary Endpoint: All-Cause Mortality Over Length of Trial (Superiority) Standard Rx (n = 179) TAVR (n = 179) 80.9% 87.5% 93.6% All-Cause Mortality (%) 50.8% 30.7% 68.0% 43.0% 53.9% 64.1% HR [95% CI] = 0.50 [0.39, 0.65] p (log rank) < % Months * In an age and gender matched US population without comorbidities, the mortality at 5 years is 40.5%. Cardiovascular Mortality (%) Standard Rx (n = 179) TAVR (n = 179) 62.4% 44.6% 30.7% 20.5% 74.5% 41.2% 80.6% 47.6% HR [95% CI] = 0.41 [0.31, 0.55] p (log rank) < % 57.3% Months 6

7 HR [95% CI] = 1.04 [0.86, 1.24] p (log rank) = % 62.4% Error Bars Represent 95% Confidence Limits No. at Risk TAVR SAVR HR [95% CI] = 1.05 [0.83, 1.33] p (log rank) = % 47.6% Error Bars Represent 95% Confidence Limits No. at Risk TAVR SAVR p = 0.64 p = 0.91 p = 0.35 p = % 14% 15% 20% 15% 19% 94% 94% 7

8 p < Error Bars = ± 1 Std Dev No structural valve deterioration that required re-intervention. TAVR SAVR p < Error Bars = ± 1 Std Dev TAVR SAVR SAPIEN Platforms in PARTNER Device Evolution SAPIEN SAPIEN XT SAPIEN 3 Valve Technology Sheath Compatibility 22-24F 16-20F 14-16F Available Valve Sizes 23 mm 26 mm 29 mm 23 mm 26 mm 20 mm 23 mm 26 mm 29 mm 8

9 ADVANCES IN CATHETER DESIGN First, second, third generation Second and third generation Expandable sheath, second and third generation WHAT NATIVE AS LOOKS LIKE TO SURGEONS The PARTNER 2A and S3i Trials Study Design Intermediate Risk Symptomatic Severe Aortic Stenosis Intermediate Risk ASSESSMENT by Heart Valve Team P2 S3i n = 1078 P2A n = 2032 ASSESSMENT: Optimal Valve Delivery Access Yes ASSESSMENT: Transfemoral Access No Transfemoral (TF) Transapical / Transaortic (TA/TAo) Transfemoral (TF) Transapical / TransAortic (TA/TAo) 1:1 Randomization 1:1 Randomization TF TAVR SAPIEN 3 TA/TAo TAVR SAPIEN 3 TF TAVR SAPIEN XT VS Surgical AVR TA/Tao TAVR SAPIEN 3 VS Surgical AVR Primary Endpoint: All-Cause Mortality, All Stroke, or Mod/Sev AR at One Year (Non-inferiority Propensity Score Analysis) 9

10 Primary Endpoint (ITT) - P2A All-Cause Mortality or Disabling Stroke 1 All-Cause Mortality or Disabling Stroke (%) % Surgery TAVR 16.4% 14.5% HR [95% CI] = 0.89 [0.73, 1.09] p (log rank) = % 19.3% 6.1% Months from Procedure Number at risk: Surgery TAVR TF Primary Endpoint (ITT) P2A All-cause Mortality or Disabling Stroke All-Cause Mortality or Disabling Stroke (%) % 4.9% TF Surgery TF TAVR 15.9% 12.3% HR: 0.79 [95% CI: 0.62, 1.00] p (log rank) = Months from Procedure Number at risk: TF Surgery TF TAVR % 16.8% A WORD OF CAUTION ABOUT TRANSAPICAL ACCESS 10

11 TA VS TF TAVR J Am Coll Cardiol Intv 2017;10: Unadjusted Time-to-Event Analysis All-Cause Mortality (AT) P2 S3i 40 P2A Surgery SAPIEN 3 TAVR All-Cause Mortality (%) % 4.0% 7.4% 0 1.1% Months from Procedure Number at risk: P2A Surgery S3 TAVR Unadjusted Time-to-Event Analysis All Stroke (AT) P2 S3i 40 P2A Surgery SAPIEN 3 TAVR 30 All Stroke (%) % 8.2% 0 2.7% 4.6% Months from Procedure Number at risk: P2A Surgery S3 TAVR

12 Unadjusted Time-to-Event Analysis All-Cause Mortality and All Stroke (AT) 40 P2A Surgery All-Cause Mortality / Stroke Rate (%) SAPIEN 3 TAVR 9.7% 3.7% 18.8% 10.8% Months from Procedure Number at risk: P2A Surgery S3 TAVR Echocardiography Findings (VI) Aortic Valve Area 2.50 Surgery TAVR 2.00 Valve Area (cm²) p < p < p < p = NS 0.00 Baseline 30 Day 1 Year 2 Year No. of Echos Surgery TAVR Error bars represent ± Standard Deviation Severity of PVR at 30 Days and All-cause Mortality at 2 Years (VI) Moderate/Severe Mild None/Trace Overall Log-Rank p = Mod/Sev (reference = None/Trace) p (Log-Rank) < All-Cause Mortality (%) % Mild (reference = None/Trace) p (Log-Rank) = % 13.5% Months from Procedure Number at risk: Moderate/Sev Mild None/Trace

13 F A J E H G E also C B I D A LITTLE ABOUT THE LAST PATIENT 96 yo female Class 3 NYHA symptoms COPD HTN Osteoporosis Mild-moderate mitral stenosis Severe aortic stenosis mean gradient = 42 mm Hg STS risk = 9% Frailty criteria 6/6 Katz Frail by 5 meter walk (9.11 sec, > 7 sec) 23 mm Sapien 3 MAC Discharged home pod #1 CAN WE STREAMLINE THE TAVR PROCEDURE? 13

14 COREVALVE SELF-EXPANDING PIVOTAL TRIAL DESIGN CoreValve US Pivotal Trials Extreme Risk High Risk Iliofemoral Access > 18 Fr Sheath Randomization 1:1 Yes No Versus CoreValve Iliofemoral CoreValve Non- Iliofemoral N=487 N=147 TCT 2013 LBCT CoreValve SAVR EVOLUTION OF FDA APPROVED SELF-EXPANDING TRANSCATHETER VALVES Evolut Pro 14

15 Mortality TCT TCT Gradient EOA TCT

16 COREVALVE HIGH RISK TRIAL HOW DO PATIENTS FEEL? J Am Coll Cardiol 2016;67(22): HOW DID THE VALVES PERFORM? J Am Coll Cardiol 2016;67(22):

17 SURTAVI Trial of Intermediate Risk Patients REARDON MJ ET AL. N ENGL J MED 2017;376: SURTAVI CLINICAL TRIAL REARDON MJ ET AL. N ENGL J MED 2017;376: The PARTNER 3 Trial Study Design Symptomatic Severe Calcific Aortic Stenosis Low Risk ASSESSMENT by Heart Team (STS < 4%, TF only) 1:1 Randomization (n=1228) TF - TAVR Surgery (SAPIEN 3) (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 17

18 The PARTNER 3 Trial Key Inclusion Criteria Severe, calcific aortic stenosis AVA 1.0 cm 2 or AVA index 0.6 cm 2 /m 2 Mean gradient 40 mmhg or jet velocity 4.0 m/sec Symptom status NYHA Functional Class 2, or Exercise test with reduced exercise capacity, abnormal BP response, or arrhythmias, or Asymptomatic with LVEF < 50% Heart Team agrees patient is low operative risk and STS < 4% Informed consent in all patients EARLY TAVR-Study Flowchart 53 18

19 FUTURE DIRECTIONS OF SELF-EXPANDING VALVE THERAPY Low risk trial underway Asymptomatic trial under design Other possible trials Bicuspid aortic valve Aortic regurgitation Moderate aortic stenosis with LV dysfunction HISTORY OF PERCUTANEOUS VALVE THERAPY IN US CONT. March 2015 FDA approves CoreValve for treatment of bioprosthetic valve-in-valve patients October 2015 second generation Sapien XT FDA approved for valve-in-valve June 2017 Sapien 3 approved for valve in valve in aortic or mitral position CASE PRESENTATION 83 yo female with history of aortic stenosis 19mm Mitroflow for AS in 2008 TIA HTN HLD GI Bleed Now CHF with mean gradient of 63 mm Hg, AVA 0.6 cm2 19

20 VALVE IN VALVE APP VALVE IN VALVE APP VALVE IN VALVE APP 20

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22 CASE PRESENTATION 76 yo female HTN, HLD, DM Prior PCI and CABG Sleep apnea on CPAP Atrial fib and prior CVA Prior severe MR with repair and 25 mm Duran Ancore ring in 2009 Now severe mitral stenosis ViV Mitral app suggests a 29 mm Sapien PARTNER I and II Trials Neurologist evaluations (pre- and post) SAPIEN SAPIEN XT SAPIEN 3 22

23 INCIDENCE OF SYMPTOMATIC STROKE AFTER INVASIVE PROCEDURES 100% 80% 60% 40% 20% 0% **Astarci 2011, Ghanem 2010, Kahlert 2010, Rodés-Cabau 2011*Knipp 2005, Stolz % Incidence of New DW MRI Brain Lesions 80% 60% 40% 20% 0% Most studies with complete neurocognitive battery show a consistent association between brain infarcts, neurocognitive decline, and dementia **Astarci 2011, Ghanem 2010, Kahlert 2010, Rodés-Cabau 2011*Knipp 2005, Stolz Silent cerebral embolic events are common New DW-MRI lesions post TAVR DW-MRI: sensitivity 94%; specificity 97% for detecting stroke considered procedure of choice to detect acute neurologic deficits 23

24 EMBOLIC PROTECTION DEVICES 24

25 PROTECTION AGAINST CEREBRAL EMBOLISM DURING TRANSCATHETER AORTIC VALVE REPLACEMENT 25

26 THE FUTURE Many more devices in development Lower and lower risk patients being treated. SUMMARY Third generation TAVR now available only 15 years from first patient. Transcatheter aortic valve replacement is rapidly becoming standard of care. CT surgeons have added TAVR training to their ACGME requirements Catheter-based therapies for structural heart disease continues to expand. 26

27 Valve Model Notes Perimount Magna Ease 3300 Yes crack Perimount Magna 3000 Yes crack Perimount RSR 2800 No crack Perimount 2700 Yes crack 27