Disclosures 4/16/2018. What s New in Valvularand Structural Heart Disease. None relevant to the presentation

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1 What s New in Valvularand Structural Heart Disease Ryan C. Shelstad, MD Surgical Enthusiast, Valvular and Structural Heart Disease Bryan Heart Cardiothoracic Surgery Disclosures None relevant to the presentation No intention to discuss off label use of medical devices 1

2 Overview Background of Valvular Heart Disease Aortic Valve Stenosis, SAVR and TAVR Where we are now What s new in TAVR Latest in FDA indications A look to the Future of TAVR technology Patient Selection and Outcome Monitoring Summary Background Open Surgical Valve Replacement remains the gold standard for treatment of severe valve stenosis. Over 65,000AVRs performed annually Median mortality rates 2-3% for surgical However, as our population ages, the surgical risk is increasing Stassano P, JACC, 2009 US Population Projection by Age Group: US Census Bureau Million Figures for projections from 2010 through 2050 are from: Table 12. Projections of the Population by Age and Sex for the United States: 2010 to 2050 (NP2008-T12), Population Division, U.S. Census Bureau; Release Date: August 14,

3 Valvular Heart Disease Increases with Age Pooled Echo Data from ARIC/CARDIA/CHS Prevalence of moderate or severe disease (%) Nkomo VT et al. Lancet 2006, 368; Natural History of Aortic Stenosis Survival (percent) Latent Period Increasing obstruction, myocardial overload Symptoms Average Age Death Age (years) Adapted from Ross and Braunwald, Circulation 1968 Diagnostic Criteria for Severe Aortic Stenosis in the TAVR Era Echo based (transthoracic) Mean aortic gradient > 40 mmhg or Peak velocity > 4.0 m/sec andvalve area of <0.8 cm2 (Indexed EOA of <0.5 cm2/m2) In setting of low gradient AS, dobutamineup to 20 mcg/kg/min can be given 3

4 Surgical AVR Risk Categories (risk is a continuum) Operable AS patients Low-Intermediate Risk High Risk Too Sick Inoperable 90% 10% Factors Associated with Increased Risk for Surgical Aortic Valve Replacement Clinical Prior Sternotomy Female gender Renal dysfunction Diabetes Moderate to severe COPD Low EF NYHA Class IV Cerebrovascular disease Immunosuppression Anatomic Porcelain aorta Prior radiation Bypass graft course under sternum Prior sternectomy Non-Traditional Frailty High operative risk cirrhosis Individualized Risk Calculation 4

5 Lee DH et al Circulation. 2010; 121: Impact of Frailty on 1 Year Mortality Serum Albumin < 3.5 g/dl Grip strength <30 kg in men <20 kg in women 5 meter walk time >6 sec KATZ ADL s <6/6 Bathing Dressing Toileting Transferring Continence Feeding Green P et al Am J Cardiol 2015;116: PARTNER Study Design 2007 Symptomatic Severe Aortic Stenosis ASSESSMENT: High-Risk AVR Candidate 3,105 Total Patients Screened N = 699 High Risk Total = 1,057 patients 2 Parallel Trials: Individually Powered Inoperable N = 358 Yes ASSESSMENT: Transfemoral Access No ASSESSMENT: Transfemoral Access Transfemoral(TF) Transapical(TA) Yes No 1:1 Randomization 1:1 Randomization 1:1 Randomization Not In Study N = 244 N = 248 N = 104 N = 103 N = 179 N = 179 TF TAVR VS AVR TA TAVR VS AVR TF TAVR VS Standard Therapy Primary Endpoint: All-Cause Mortality at 1 yr (Non-inferiority) Cohort A Primary Endpoint: All-Cause Mortality Over Length of Trial (Superiority) Co-Primary Endpoint: Composite of All-Cause Mortality and Repeat Hospitalization (Superiority) Cohort B 5

6 PARTNER Cohort B-Inoperable Primary Endpoint: All-Cause Mortality All-cause mortality (%) Standard Rx TAVI at 1 yr = 20.0% NNT = 5.0 pts HR [95% CI] = 0.54 [0.38, 0.78] P (log rank) < % 30.7% Leon et al, NEJM 2010; 363: Months Numbers at Risk TAVI Standard Rx Repeat Hospitalizations Repeat Hospitalization (%) Standard Rx TAVR at 1 yr = 26.9% NNT = 3.7 pts HR [95% CI] = 0.41 [0.30, 0.58] p (log rank) < % 27.0% at 2 yr = 37.5% NNT = 2.7 pts 72.5% 35.0% Months Numbers at Risk TAVR Standard Rx Quality of Life Assessment for TAVR: Kansas City Cardiomyopathy Questionnaire Change in KCCQ-Overall Summary Score Large Medium Small Deterioration No Change 546 outpts with HF KCCQ assessed at baseline and 5 weeks Extent of deterioration or improvement assessed by physician based on sx and exam and correlated with KCCQ-Overall Clinically Summary Important Change Small = 5 points Small Medium Large Moderate = 10 points Large = 20 points Improvement Spertus J et al Am Heart J 2005; 150:

7 Primary Endpoint: KCCQ Overall Summary TAVR Control MCID = 5 points = 13.9 = 20.7 = MCID = minimum clinically important difference KCCQ Subscales Symptom Score 100 MCID = 5 points 80 Physical Limitations 100 MCID = 5 points 80 TAVR Control =10.2 =17.5 = =9.8 P=0.008 =13.7 P=0.002 = Quality of Life 100 MCID = 5 points Social Limitations 100 MCID = 5 points =16.2 =24.8 = =15.2 =25.3 = MCID = minimum clinically important difference Five Year Mortality: Inoperable Arm of PARTNER Kapadia SR et al Lancet 2015; 385:

8 TAVR Procedure Baseline Aortography TAVR Procedure 8

9 Valve Positioning Valve Implantation--Sapien Post-Valve Evaluation 9

10 TEE Imaging Post TAVR TA Access Site Transapical Insertion 10

11 Transapical Implantation PARTNER Study Design 2007 Symptomatic Severe Aortic Stenosis ASSESSMENT: High-Risk AVR Candidate 3,105 Total Patients Screened N = 699 High Risk Total = 1,057 patients 2 Parallel Trials: Individually Powered Inoperable N = 358 Yes ASSESSMENT: Transfemoral Access No ASSESSMENT: Transfemoral Access Transfemoral(TF) Transapical(TA) Yes No 1:1 Randomization 1:1 Randomization 1:1 Randomization Not In Study N = 244 N = 248 N = 104 N = 103 N = 179 N = 179 TF TAVR VS AVR TA TAVR VS AVR TF TAVR VS Standard Therapy Primary Endpoint: All-Cause Mortality at 1 yr (Non-inferiority) Cohort A Primary Endpoint: All-Cause Mortality Over Length of Trial (Superiority) Co-Primary Endpoint: Composite of All-Cause Mortality and Repeat Hospitalization (Superiority) Cohort B Five Year Mortality: PARTNER Study High Risk Cohort Mack MJ et al Lancet 2015; 385:

12 Complications of TAVR vs SAVR Stroke Paravalvular Leak (Aortic Insufficiency) Need for New Permanent Pacemaker Neurological Events at 30 Days and 1 Year All Patients (N=699) 30 Days 1 Year Outcome TAVR (N = 348) AVR (N = 351) p-value TAVR (N = 348) AVR (N = 351) p-value All Stroke or TIA no. (%) 19 (5.5) 8 (2.4) (8.3) 13 (4.3) 0.04 TIA no. (%) 3 (0.9) 1 (0.3) (2.3) 4 (1.5) 0.47 All Stroke no. (%) 16 (4.6) 8 (2.4) (6.0) 10 (3.2) 0.08 Major Stroke no. (%) 13 (3.8) 7 (2.1) (5.1) 8 (2.4) 0.07 Minor Stroke no. (%) 3 (0.9) 1 (0.3) (0.9) 2 (0.7) 0.84 Death/maj stroke no. (%) 24 (6.9) 28 (8.2) (26.5) 93 (28.0) 0.68 Five Year Risk of TIA/Stroke: PARTNER Study High Risk Cohort TAVR SAVR Mack MJ et al Lancet 2015; 385:

13 Key Questions about TAVR after the PARTNER Trial Stroke (? higher with TAVR that SAVR) Major Bleeding Vascular Complications (large delivery device) Paravalvular Leak Need for permanent pacemaker? Valve durability The PARTNER II Trial: Study Design Symptomatic Severe Aortic Stenosis n=2000 Randomized Patients Yes Operable (STS 4) ASSESSMENT: Transfemoral Access ASSESSMENT by Heart Valve Team No Two Parallel Randomized Trials +3 Nested Registries Inoperable ASSESSMENT: Transfemoral Access n=500 Randomized Patients Transfemoral (TF) Transapical (TA) Yes >7mm Yes 6-7mm No 1:1 Randomization 1:1 Randomization 1:1 Randomization 6-7mm Registry TF TAVR SAPIEN XT VS Surgical AVR TAVR: TA / TAO VS Surgical AVR TF TAVR SAPIEN XT VS TF TAVR SAPIEN TA Registry TAO Registry Primary Endpoint: All-Cause Mortality + Major Stroke at Two Years (Non-inferiority) Primary Endpoint: All-Cause Mortality + Major Stroke + Repeat Hospitalization at One Year (Non-inferiority) Additional Registry:Transcatheter Valve-in-Surgical Valve Registry 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) SAPIEN SXT SAPIEN 3 13

14 Strokes (All) at 30 Days Edwards SAPIEN Valves 20% 15% PARTNER 1 and 2 Trials (Overall and TF Patients) 10% 5% 6.7% 5.6% Neurologist evaluations (pre- and post) 4.1% 4.3% 1.5% 2.6% 0% P1B (TF) P1A (All) P2B (TF) P2B XT (TF) S3HR (All) S3i (All) SAPIEN SAPIEN XT SAPIEN 3 Valve Durability at 5 Years PARTNER High Risk Group Aortic Valve Mean Gradient p < Error Bars = ± 1 Std Dev No structural valve deterioration that required re-intervention. TAVR SAVR

15 New Technology: Medtronic CoreValve Loading/Release Handle 18F Capsule 12F Shaft Over-the-wire compatible Self-Expanding, Nitinol Scaffold, Porcine Pericardium CoreValveUS PivitolTrial: Surgical AVR versus TAVR in High Risk Patients with Aortic Stenosis 15

16 CoreValve High Risk US Trial Surgical AVR vs TAVR Reardon MJ et al. J Am Coll Cardiol. 2015; 66(2): Medtronic Evolut R Valve Valve-in-Valve Deployment 16

17 Putting the Structure back in Structural Heart Mitral Valve Disease 17

18 Mitral Repair vs Replacement Circulation. 2003;108:

19 Transseptal Interventions Valve-in-Valve Mitral Replacement Mitral Clip (Regurgitation, Non Surgical candidates only) Coming soon: Native TranscatheterMitral valve Replacement (TMVR) TMVR at Bryan Heart Pre and Post TEE 19

20 Implications of Valve-in-Valve Indication Shift away from mechanical valves at earlier age Reduction in need for reoperativevalve replacement Reinforces recommendation for mitral valve repair when possible and favors bioprosthetic valve when replacement is necessary Current FDA Approval TAVR is approved for patients with severe aortic stenosis: Inoperable or High risk (STS>8% or other high risk clinical features) OR Intermediate (STS 4-8%) for surgical AVR Symptomatic with NYHA Class II CHF Life expectancy >1 year Bicuspid Aortic Valve is NOT a contraindication Prior Aortic or Mitral Surgical valve prosthetic degeneration Stenosis OR Regurgitation Evaluated by Heart Team (IC and two CT surgeons) Patient Selection: The Valve Clinic Lindman BR et al. J Am Coll Cardiol Intv. 2014;7(7):

21 Current Screening Approach An Imaging Intensive Technology TTE Gradients, annulus DSE for low gradient AS TEE Less of a role in screening Cardiac catheterization Coronaries, RHC, Ascending and Abdominal aortography and wire straightening ETT for severe AS w/o Sxs Cardiac CT Critical role in screening and procedural planning Peripheral CTA Evaluate route Cardiac CT Aortic Valve Area: measured in systole using planimetry was 0.85 cm squared Annular Area: 403 mm2 Aorta at Aortic Valve Annulus: 23 x 19 mm Aorta at Sinus: 30.4 mm dia. Aorta Sinotubular Junc. 26 mm dia. Aortic valve: Height to RCA 14 mm Height to LM 12.7 mm CT Lower Extremity Angiography RCI A 8.1mm LCIA 7.3 mm REIA 7.3 mm LEIA 7.1 mm RCFA 7.4 mm LCFA 7.4 mm Aorta 16 mm 21

22 Multi-modality imaging is important for patient selection and treatment guidance PRE-PROCEDURAL EVALUATION 21 mm 24 mm 17 mm PERI-PROCEDURAL EVALUATION Summary: Milestones in TAVR Partner I: Establishes TAVR superior to nonoperative management Partner I: TAVR and SAVR equivalent in High Risk Patients 2016: FDA approves TAVR for intermediate risk patients 2017: FDA approves TAVR for Valve-in Valve application in Aortic and Mitral positions Outcome Monitoring Mandatory National Registry Comprehensive prospective observational database (>400 data elements) Supported by CMS/FDA FU includes 30-days, 1-year (incl. QOL measures) TVT compliance linked to reimbursement 22

23 Outcome Report Metrics In hospital Mortality & Adverse events Procedure success Acute kidney injury 30-Day and 1-Year outcomes All cause mortality Stroke MI Bleeding events Valve performance Quality of Life (KCCQ) Real World Experience One Year Outcomes from TVT Registry Holmes DR et al. JAMA. 2015;313(10): TAVR Categories Operable AS patients Low-Intermediate Risk High Risk Too Sick Inoperable 90% 10% 23

24 CoreValve SURTAVI Trial Randomized 1:1, non-inferiority study Multicenter up to 75 centers in Europe Canada United States Sample size: Approx. 2,500 5-year FU Severe symptomatic aortic stenosis STS mortality risk 4% and 10% Heart Team Evaluation Confirm Inclusion/Exclusion & Intermediate Risk Classification Randomization Stratified by need for revascularization N = ~2,500 patients Medtronic CoreValve TAVI SAVR TAVI + PCI TAVI only SAVR + CABG SAVR only Conclusions SAVR remains the Gold Standard treatment for Aortic Stenosis. Surgical Repair/Replacement remains the Gold Standard for Mitral Regurgitation Valve disease is increasing as our patients are living longer and patients are becoming higher risk for open heart surgery TAVR is currently FDA approved for treatment of high or intermediate risk patients with symptomatic aortic stenosis The PARTNER trial in inoperable patients demonstrated: Marked decreased in mortality at 1 and 5 years Reduced rehospitalization for CHF Improved symptom status and quality of life compared Trials of High Risk patients (PARTNER Cohort A and CoreValve Pivotal US Study) Similar or improved survival with TAVR vs SAVR Conclusions (cont) The PARTNER II trail in intermediate risk patients demonstrated comparable outcomes to SAVR Expansion of Valve-in-Valve indications influences the initial management of valvularheart disease and further reinforces the need for a Multidisciplinary Valve Team approach Patient selection remains critically important and requires a team approach to customize intervention strategies,optimize outcomes, as well as avoid futile care The development of the TVT registry has been an important aspect in the regulatory and research agenda for the roll out of TAVR and allows for benchmarking of outcomes nationally. Lower risk patients and Native Mitral valve interventions are the expected next steps in Structural Heart interventions 24