Valvular Heart Disease Transcatheter Valve Therapies. October 2016 Brian Whisenant MD

Transcription

1 Valvular Heart Disease Transcatheter Valve Therapies October 2016 Brian Whisenant MD

2 Disclosure Statement of Financial Interest Within the past 12 months, I or my spouse/partner have had a financial interest/arrangement or affiliation with the organization(s) listed below. Affiliation/Financial Relationship Consultant, Honoraria: Equity, Honoraria: Consultant, Honoraria: Company Edwards Medical JNJ/Coherex Boston Scientific

3 Population at Risk for Aortic Stenosis Is Increasing Over 40 Million People in the United States Over the Age of 65 1 AS is estimated to be prevalent in up to 7% of the population over the age of 65 2 Source: US Census Bureau 1 1. United States 2010 Census. Washington, DC: US Census Bureau Otto CM. Heart. 2000;84:

4 Symptoms of Aortic Stenosis Shortness of breath Fatigue Angina Syncope/presyncope Other Atrial fibrillation Symptoms of AS are frequently attributed to normal signs of aging. Many patients appear asymptomatic, but have curtailed their activity to accommodate their abilities.

5 Operative Rates for Severe Aortic Stenosis Approximately half of patients with severe symptomatic AS do not undergo surgery No AVR AVR Bach DS et al. Circ Cardiovasc Qual Outcomes. 2009; 2: ; Bouma BJ et al. Heart. 1999;82: ; Charlson E et al. J Heart Valve Dis. 2006;15: ; Iung B et al. Eur Heart J. 2003;24: ; Pellikka PA et al, Circulation. 2005;111:

6 Mitral Regurgitation An Undertreated Population 1,700,000 MR Grade 3+ 1,2 1,670, ,000 Annual MV Surgery 3 30,000 1.Patel et al. Mitral Regurgitation in Patients with Advanced Systolic Heart Failure, J of Cardiac Failure, ACC/AHA 2008 Guidelines for the Management of Patients with Valvular Heart Disease, Circulation: Gammie, J et al, Trends in Mitral Valve Surgery in the United States: Results from the STS Adult Cardiac Database, Annals of Thoracic Surgery 2010.

7 Valvular Heart Disease Who does and does not receive valve surgery? High Risk Percent Medium Risk Low Risk Extreme Risk High Risk Medium Risk Palliation Candidate Technically Inop Healthy but elderly 0 AVR Low Risk Nada

8 Monday: Cardiogenic Shock 58 YO Man transferred from New Mexico Sunday night on.08 Epi with EF ~10%, Lactate 10, SBP ~85, critical aortic stenosis Venous Cannula for cardiopulmonary bypass

9 Wednesday: Failed Bioprosthetic Mitral Valve 77 YO woman from St. George with porcine MVR 2007, now with severe MR and class 3 HF Transseptal Delivery and Balloon Inflation of S3 Valve S3 THV within Mosaic valve

10 Friday: randomized to PCI/TAVR in P3 Trial 75 YO man SOB carrying luggage up stairs at Heathrow S3 THV Baseline Angio LCX & RCA Stents

11 Risk Evolution PARTNER 1 demonstrated TAVR to be: superior to standard therapy in patients who were not candidates for surgery equivalent to surgery in high-risk patients PARTNER 2 compares TAVR to SAVR in Intermediate risk patients

12 Transcatheter Heart Valve Device Evolution Partner 1 Partner 2 Partner 3 Valve Technology Sheath Compatibility 22-24F 16-20F 14-16F Available Valve Sizes 23mm 26mm 29mm* 23 mm 26 mm 20 mm 23 mm 26 mm 29 mm

13 The PARTNER 2A Trial Participating Sites 2032 Randomized Pts: 49 at Intermountain Medical Center

14 The PARTNER 2A Trial Study Design Symptomatic Severe Aortic Stenosis ASSESSMENT by Heart Valve Team Operable (STS 4%, <8%) Randomized Patients n = 2032 Yes ASSESSMENT: Transfemoral Access No Transfemoral (TF) Transapical (TA) / TransAortic (TAo) 1:1 Randomization (n = 1550) 1:1 Randomization (n = 482) TF TAVR (n = 775) VS. Surgical AVR (n = 775) TA/TAo TAVR (n = 236) VS. Surgical AVR (n = 246) Primary Endpoint: All-Cause Mortality or Disabling Stroke at Two Years

15 Primary Endpoint (AT) All-Cause Mortality or Disabling Stroke 1 All-Cause Mortality or Disabling Stroke (%) Surgery HR [95% CI] = 0.87 [0.71, 1.07] TAVR p (log rank) = % 16.6% 18.9% 8.0% 14.0% 5.7% Number at risk: Months from Procedure Surgery TAVR

16 TF Primary Endpoint (AT) All-Cause Mortality or Disabling Stroke 1 All-Cause Mortality or Disabling Stroke (%) % 4.5% TF Surgery TF TAVR 15.8% 11.7% HR: 0.78 [95% CI: 0.61, 0.99] p (log rank) = % 16.3% Number at risk: Months from Procedure TF Surgery TF TAVR

17 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

18 Paravalvular Regurgitation (VI) 3-Class Grading Scheme 100% 80% P < P < Moderate 8.0% Mild 26.8% Moderate 0.6% Mild 3.5% 60% 40% Severe Moderate Mild None/Trace 20% 0% TAVR Surgery TAVR Surgery No. of echos 30 Days 2 Years TAVR Surgery

19 Severity of PVR at 30 Days and All-cause Mortality at 2 Years (VI) All-Cause Mortality (%) Moderate/Severe Mild None/Trace Overall Log-Rank p = Mod/Sev (reference = None/Trace) p (Log-Rank) < % Mild (reference = None/Trace) p (Log-Rank) = % 13.5% 0 Number at risk: Months from Procedure Moderate/Sev Mild None/Trace

20 The PARTNER 2A Trial NEJM

21 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 TA/TAo TAVR Surgical TF TAVR VS TA/Tao TAVR VS AVR Surgical AVR Primary Endpoint: All-Cause Mortality, All Stroke, or Mod/Sev AR at One Year (Non-inferiority Propensity Score Analysis)

22 PARTNER Trials Device Evolution Partner 1 Partner 2 Partner 3 Valve Technology Sheath Compatibility 22-24F 16-20F 14-16F Available Valve Sizes 23 mm 26 mm 23 mm 26 mm 29 mm 20 mm 23 mm 26 mm 29 mm

23 Baseline Patient Characteristics Demographics (AT) Characteristic TAVR (n = 1077) Surgery (n = 944) p-value Age - yrs 81.9 ± ± Male - % BMI - kg/m ± ± Median STS Score - % 5.2 [4.3, 6.3] 5.4 [4.4, 6.7] NYHA Class III or IV - % mean ± SD, median [IQR]

24 Unadjusted Time-to-Event Analysis All-Cause Mortality and All Stroke (AT) 40 P2A Surgery All-Cause Mortality / Stroke Rate (%) TAVR 9.7% 3.7% 18.8% 10.8% 0 Number at risk: P2A Surgery S3 TAVR Months from Procedure

25 Unadjusted Clinical Events At 30 Days and 1 Year (AT) Events (%) 30 Days 1 Year TAVR Surgery TAVR Surgery Death All-cause Cardiovascular Neurological Events Disabling Stroke All Stroke All-cause Death and Disabling Stroke

26 Paravalvular Regurgitation P < P < % Moderate 1.5% 80% Mild 39.8% 60% 40% Severe Moderate Mild None/Trace 20% 0% TAVR Surgery TAVR Surgery No. of echos 30 Days 1 Year P2A Surgery S3i TAVR

27 The PARTNER 2A and S3i Trial Lancet TAVR now FDA Approved and Medicare Covered for Patients with an Intermediate Risk for Surgical Aortic Valve Replacement

28 Partner 3: Low Risk 1228 Patients Primary Endpoint: 1 Year death, Stroke, Rehospitalization Key Inclusion Criteria: > 65 years of age TF Access (~5.5 mm) Predicted operative risk < 2% (STS < 4) Key Exclusion Criteria: Any Frailty CAD warranting CABG Planned surgery for: MR, AF Bicuspid valve

29 TAVR at Intermountain Medical Center May 15, 2009 October 7, 2016 Multidisciplinary commitment to each unique patient Evaluation Procedures Complication management Quarterly THV Procedures Total = Q2 Q3 Q4 Q1 Q2 Q3 Q4 Q1 Q2 Q3 Q4 Q1 Q2 Q3 Q4 Q1 Q2 Q3 Q4 Q1 Q2 Q

30

31 Intermountain TVT TAVR Report 50 th Pctl = Median

32 2015 Length of Stay Post TAVR (TVT data) Intermountain Commercial Aortic Valves All Access and Vendor* Mean LOS = 3.2 Days, Median 2.0 Days Number of Patients >8 Days: TAVR to Discharge 184 Sequential Patients (survive to discharge)

33 TAVR Today - Less invasive procedure with acute hemodynamic benefit and rapid return to activity - Preferred therapy for intermediate, high, and prohibitive risk patients - Ongoing randomization for low risk (< 4%) - The heart team should reach a consensus on the preferred therapy for each individual patient.

34 Why Does the Mitral Valve Fail? 1) Primary Valve Disease - Degenerative Mitral Regurgitation/DMR - Mitral Prolapse Flail leaflet - SOC is surgical repair 2) Secondary Valve Disease Functional Mitral Regurgitation/FMR A function of the ventricular disease - Ischemic or dilated cardiomyopathy - SOC is Medical Therapy

35 Surgery for Secondary MR 1. Sick patients & hearts Limited tolerance for insult Independent AEs 2. LV function may not tolerate removal of low resistance outlet 3. Preserve chest for LVAD & transplant Event-free Survival Time (Days) Wu AH, et al. J Am Coll Cardiol 2005;45: No Mortality Benefit

36 CABG + MV Repair vs CABG Alone Ischemic CM Michler RE et al. N Engl J Med 2016;374:

37 Degenerative Mitral Valve Repair Quadrangular Resection & Annular Ring Repair is considered preferable over replacement for DMR. Lower risk, better hemodynamics, greater durability. Replacement may be more effective than repair for FMR. Less MR, similar hemodynamics with large annulus, less concern for durability

38 Mitral Valve Repair Center Patients Repair In Hospital Mortality Freedom from severe MR Mt. Sinai % 0.8% 96% - 7 yrs U Penn % 0.2% 97% - 8 yrs Mayo 3 * % 0.2% 95% < mod 5 yrs *Robotic MV repair Where is the unmet need? 1. J Thorac Cardiovasc Surg Aug;144(2): Ann Thorac Surg 2015; 99: Circulation Nov 24;132(21):1961-8

39 Hospital volume, mitral repair rates and mortality: US hospitals treating Medicare patients Range 1,239 Hospitals; 125,079 Patients All Mitral Procedures No of Hospitals % Mitral Repairs Repair Rate % Range No of Hospitals % < % > > > 65% of hospitals perform < 5 Medicare mitral repairs per year Overall Replacement = 61.7% Overall hospital mortality = 10.7% Vassileva CM, et al. J Cardiovasc Thorac Surg 2015; 149: pp

40 Unmet Need in Mitral Regurgitation Less invasive option for elderly and high risk surgical DMR patients Is there a role for transcatheter mitral therapies in FMR patients?

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42 Mitral Leaflet Clip Patient Demographics Description US Registry Patients Pts w/leaflet Clip Procedures 2,649 Mean Age 79 yrs Median Age 81 yrs Prev Cardiac Surgery 36.2% Prior Stroke 10.1% Diabetes Mellitus 26.4% Chronic Lung Disease 40.1% STS >=8% MV Replacement 56.6%

43 Mitral Leaflet Clip Safety Metrics Adverse Hospital Events US Registry Patients (%) Mortality 2.1 Stroke (any) 0.3 Acute Kidney Injury (stage 3) 0.9 Disabling & threatening bleed 1.3 Length of Stay median post procedure 2.0 days

44 Mitral Leaflet Clip Efficacy Metrics Results US Registry Patients (%) Mitral Regurgitation None or trace/trivial 15.9 Mild (1+) 44.8 Moderate (2+) 31.4 Moderate severe, severe (3-4+) 8.0 Mitral valve mean gradient Acceptable (< 5 mmhg) 71.4 Possible Acceptable (<=8 mmhg) 93.7

45 MitraClip from TVT report vs. Isolated mitral valve surgery from the STS database Description MitraClip N=2649 Surgery N=40,093 Mean Age 79 yrs 60 yrs Median Age 81 yrs 61 yrs Prev Cardiac Surgery 29.3% 5.6% PVD 18.6% 5.5% Chronic Lung Disease % STS >=8% MV Replacement 56.6% 4% Chatterjee, et al. Ann Thorac Surg 2013; 96(5):

46 MitraClip from TVT report 2015 vs. Isolated mitral valve surgery from the STS database Description MitraClip N=2,649 Surgery N=40,093 Mean Age 79 yrs 60 yrs Median Age 81 yrs 61 yrs Prev Cardiac Surgery 29.3% 5.6% PVD 18.6% 5.5% Chronic Lung Disease % STS >=8% MV Replacement 56.6% 4% Mortality 2.1% 2.9% Chatterjee, et al. Ann Thorac Surg 2013; 96(5):

47 COAPT FMR Trial Significant FMR ( 3+ by core lab) Symptomatic heart failure subjects who are treated per standard of care Determined by the site s local heart team as not appropriate for mitral valve surgery 555 Patients Randomize 1:1 Mitral Leaflet Clip N=215 Control group Standard of care N=215 Clinical and TTE follow-up: Baseline, Treatment, 1-week (phone), 1, 6, 12, 18, 24, 36, 48, 60 months

48 Transcatheter Mitral Valve

49 Mitral Regurgitation Conclusions Mitral Valve Disease should be cared for in high volume tertiary centers with an expert multidisciplinary team. Mitral Valve Repair is the standard of care for DMR. Mitral leaflet clipping is a safe, effective alternative for patients in whom surgery poses a significant risk. Functional Mitral Regurgitation is currently being evaluated in the COAPT Trial. Additional repair and replacement strategies are being developed for functional and degenerative mitral regurgitation.

50 Risk for Endocarditis Antibiotic Prophylaxis Highest risk - antibiotic prophylaxis is generally recommended Prosthetic heart valve Valve repair with prosthetic material Prior history of IE Repaired or unrepaired cyanotic congenital heart disease, Moderate risk - antibiotic prophylaxis is NOT generally recommended Hypertrophic cardiomyopathy Mitral valve prolapse with valvular regurgitation and/or valvular thickening Unrepaired ventricular septal defect, unrepaired patent ductus arteriosus Acquired valvular dysfunction (eg, mitral or aortic regurgitation or stenosis) Low risk Antibiotics have never been recommended for people with these conditions: Physiologic, functional, or innocent heart murmurs Mitral valve prolapse without regurgitation or valvular leaflet thickening Mild tricuspid regurgitation Simple atrial septal defect Atrial septal defect, ventricular septal defect, or patent ductus arteriosus that was successfully closed (either surgically or with a catheter-based procedure) more than six months previously Circulation 2007 Oct 9;116(15):

51 Thank You Structural Heart Disease Program intermountainheartinstitute.org