The Mitral Revolution: Transcatheter Repair (and Replacement?) Going Mainstream

Transcription

1 The Mitral Revolution: Transcatheter Repair (and Replacement?) Going Mainstream Matthew J. Price MD Director, Cardiac Catheterization Laboratory Scripps Clinic La Jolla, CA, USA

2 92 yr-old male, Significant DOE, No Longer Can Participate in His Barbershop Quartet Due to Dyspnea on Singing (Baritone) TEE: Severe primary (degenerative) MR due to flail anterior leaflet

3 92 yr-old male, Significant DOE, No Longer Can Participate in His Barbershop Quartet Due to Dyspnea on Singing (Baritone) Heart team: high/prohibitive risk for open repair/replacement 2 MitraClips implanted: trace residual MR Discharged home POD#1 Follow-up: At 1 month, trace MR, back to singing in quartet

4 U.S. MitraClip Indication For Use: "Prohibitive Risk" Primary MR (Degenerative MR) Significant symptomatic degenerative (primary) MR ( 3+) Determined to be at prohibitive* risk for mitral valve surgery by a heart team, which includes a cardiac surgeon experienced in mitral valve surgery DMR - Prolapse DMR - Flail *STS 6; frailty; porcelain aortal; phtn; liver disease; extenuating circumstances, etc

5 MitraClip represented 33% of ALL mitral valve procedures (open or transcatheter) performed within the Scripps Health system in MitraClip Open MV Repair Open MVR All surgeries involving MV

6 Improving Acute and Long-term Outcomes of the MitraClip for Degenerative MR: The Next-Generation XTR NTR XTR Improved Leaflet Coaptation 15 mm 18 mm Clip Length MitraClip XTR Clip: 3mm longer Clip Arms & Grippers Increased leaflet coaptation length 9 mm 12 mm Coaptation Length Clip Arms at 120 degrees 17 mm Grippers with 6 rows of frictional elements (compared to 4 rows in MitraClip NT) Leaflet insertion to engage 6 rows of frictional elements is approximately 9mm (compared to 6mm for MitraClip NT) Longer clip and Gripper covers to support longer Clip Arms 22 mm See Important Safety Information referenced within. Not to be reproduced, distributed or excerpted Abbott. All rights

7 55 yr-old F with Non-Ischemic Dilated CM, EF 36%, Narrow QRS, NYHA Class III Symptoms Despite Optimal Medical Therapy (Entresto/BetaBlocker/Aldactone) Echocardiography: normal leaflets and apparatus apical displacement (tenting) of mitral valve leaflets LVESD 5.2 cm EROA 0.41cm2, RV 64ml/beat, RF 65%, consistent with severe functional MR according to ASE criteria

8 55 yr-old F with Non-Ischemic Dilated CM, EF 35%, Narrow QRS, NYHA Class III Symptoms Despite Optimal Medical Therapy Medical optimization confirmed by heart failure team Enrolled in COAPT Continued Access Registry (FMR off-label, not covered commercially by CMS) 2 MitraClips implanted: trace residual MR Discharged home POD#2

9 How Are Patients with Isolated FMR Treated?

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11 Key Inclusion Criteria 1. Ischemic or non-ischemic cardiomyopathy with LVEF 20%-50% and LVESD 7 0mm 2. Moderate-to-severe (3+) or severe (4+) secondary MR confirmed by an independent echo core laboratory prior to enrollment (US ASE criteria) 3. NYHA functional class II-IVa (ambulatory) despite a stable maximallytolerated GDMT regimen and CRT (if appropriate) per societal guidelines 4. Pt has had at least one HF hospitalization within 12 months and/or a BNP 30 0pg/ml* or a NT-proBNP pg/ml* 5. Not appropriate for mitral valve surgery by local heart team assessment 6. IC believes secondary MR can be successfully treated by the MitraClip SCRIPPS 2 Adjusted by a 4% reduction in the BNP or NT-proBNP cutoff for every increase of 1 kg/m 2 in BMI >20 kg/m CLINIC

12 Baseline Characteristics (i)

13 Baseline Characteristics (ii) HF parameters MitraClip + GDMT (N=302) GDMT alone (N=312) Etiology of HF Echo core lab MitraClip + GDMT (N=302) GDMT alone (N=312) MR severity - Ischemic 60.9% 60.6% - Mod-to-sev (3+) 49.0% 55.3% - Non-ischemic 39.1% 39.4% - Severe (4+) 51.0% 44.7% EROA, cm ± ± 0.15 NYHA class -I 0.3% 0% LVESD, cm 5.3 ± ± II 42.7% 35.4% LVEDD, cm 6.2 ± ± III 51.0% 54.0% LVESV, ml ± ± IV 6.0% 10.6% LVEDV, ml ± ± 72.9 HF hosp w/i 1 year 58.3% 56.1% LVEF, % 31.3 ± ± 9.6 Prior CRT 38.1% 34.9% - 40% 82.2% 82.0% Prior defibrillator 30.1% 32.4% RVSP, mmhg 44.0 ± ± 14.0

14 Medication Use at Baseline Maximally-tolerated doses MitraClip + GDMT GDMT alone (n=302) (n=312) Beta-blocker 91.1% 89.7% ACEI, ARB or ARNI 71.5% 62.8% Mineralocorticoid receptor antagonist 50.7% 49.7% Nitrates 6.3% 8.0% Hydralazine 16.6% 17.6% Diuretic 89.4% 88.8% Chronic oral anticoagulant 46.4% 40.1% Aspirin 57.6% 64.7% P2Y12 receptor inhibitor 25.2% 22.8% Statin 62.6% 60.6%CLINIC SCRIPPS

15 Primary Effectiveness Endpoint Hospitalizations for HF within 24 months Annualized rates of HF hospitalization* NNT (24 mo) = 3.1 [95% CI 1.9, 8.2] GDMT alone MitraClip + GDMT 67.9% 283/416.8 pt-yrs 35.8% 160/446.5 pt-yrs 0% 10% 20% 30% 40% *Joint frailty model HR (95% UCL] = 0.53 [0.66] P< % 60% 70% 80%

16 Primary Effectiveness Endpoint All Hospitalizations for HF within 24 months Cumu ulative HF Hospita alizations (n) MitraClip + GDMT GDMT alone 250 in 151 pts in 92 pts 100 HR (95% CI] = 0.53 [ ] P< Time After Randomization (Months) No. at Risk: Median [25%, 75%] FU = 19.1 [11.9, 24.0] mos MitraClip GDMT SCRIPPS CLINIC

17 All-cause Mortality All-cause Mortality (%) 100% MitraClip + GDMT GDMT alone 80% 60% NNT (24 mo) = 5.9 [95% CI 3.9, 11.7] 40% HR [95% CI] = 0.62 [ ] P< % 29.1% 20% 0% 0 No. at Risk: MitraClip + GDMT GDMT alone Time After Randomization (Months)

18 Powered Secondary Endpoints - Tested in hierarchical order1 P-value 1. MR grade 2+ at 12 months < All-cause mortality at 12 months2 < Death and all HF hospitalization through 24 months (Finkelstein-Schoenfeld) < Change in QOL (KCCQ) from baseline to 12 months < Change in 6MWD from baseline to 12 months < All-cause hospitalizations through 24 months NYHA class I or II at 12 months < Change in LVEDV from baseline to 12 months All-cause mortality at 24 months < Death, stroke, MI, or non-elective CV surgery for device-related compls at 30 days3 < All powered for superiority unless otherwise noted; 2Powered for noninferiority of the device vs. the control group; 3Powered for noninferiority against an objective performance goal

19 Primary Safety Endpoint Freedom from Device-related Complications within 12 months 100% MitraClip procedure attempted 96.6%* 94.8% [95% LCL] 90% 88% OPC 80% 70% 60% P<0.001 Device-related complications N=293 9 (3.4%) - Single leaflet device attachment 2 (0.7%) - Device embolization 1 (0.3%) - Endocarditis requiring surgery 0 (0.0%) - Mitral stenosis requiring surgery 0 (0.0%) - Left ventricular assist device implant 3 (1.2%) - Heart transplant 2 (0.8%) - Any device-related complication requiring non-elective CV surgery 1 (0.3%) 50% *KM estimate; **Calculated from Z test with Greenwood s method of estimated variance against a pre-specified objective performance goal of 88%