The MitrAl Valve rEpaiR Clinical (MAVERIC) trial Fir First world - PowerPoint PPT Presentation

The MitrAl Valve rEpaiR Clinical (MAVERIC) trial Fir First world ldwid ide presentation of of th the tw two year fol ollow-up in in 45 45 patie tients with ith fu functional mitr itral l regurgitation Simon Redwood St Thomas’Hospital

Speaker's name: Simon Redwood I have the following potential conflicts of interest to report: • Study Proctor: MVRx, Inc.

Background • Patients with systolic heart failure and functional mitral regurgitation (FMR) have limited therapeutic options • Medical therapy and resynchronization therapy have limited efficacy • Surgery rarely offered • Patients have comorbidities and often are high surgical risk • Lack of evidence leading to Class IIb, Level of Evidence C – in patients who have other indications for surgery (eg requiring CABG) • Other transcatheter repair devices have shown mixed results • eg COAPT vs MITRA-FR • Transcatheter repair of FMR with annular reshaping is desirable if shown to be safe and effective

ARTO™ System description Immediate and direct A-P diameter shortening to • Septal Device treat functional mitral regurgitation No compression of left circumflex artery • Venous based delivery under fluoroscopic imaging • Acutely reversible or removable • 12 Fr Delivery System • No residual ASD , no trauma to native mitral valve • leaflets or chords GCV Device Ample room for future septal access • GCV=great cardiac vein

MAVERIC EU/AU STUDY DESIGN Multi-Centre, Single Arm 45 Patient Major Inclusion Criteria: Safety and Efficacy Study • MR Grade > 2+ 30 day , 6 month, 1 year, 2 year and 3 • NYHA Class II-IV year clinic/echo visit follow-up • Optimized medical therapy Primary Outcome Measures: Major Exclusion Criteria: • Safety: MACE at 30 days • Significant structural abnormality of the • Efficacy: MR Grade at 30 days mitral valve Secondary Outcome Measures • Known need for any cardiac surgery • NYHA Class • Life expectancy <1 year • HF Hospitalization Echo Core Lab: Bertrand Cormier, All Events • Device success CEC Adjudicated, Study Mgmt: CERC

MAVERIC EU/AU Trial Patient Flow Enrolled/Implanted Patients 3 Pts did not meet echo N=45 criteria by core lab (clinical follow-up only) Per Protocol N=42 Death n=5 Mitral reoperation n=1 100% clin FU of surviving One year follow up pts 100% echo FU of per Clinical/safety: n=39 protocol surviving/no re- Echo: n=36 op pts Death n=3 No clinic visit n=2 (survival data available) Two year follow up 100% survival data Survival data: n=45 92% clinical follow-up NYHA data: n=34 92% echo FU of per protocol surviving/no Echo: n=31 re-op pts

MAVERIC Baseline Characteristics Characteristic All Patients (N=45) Age (mean, std) 69.6 ± 12.4 Male Gender (%) 60.0 STS Score (mortality) 3.8± 3.4 Ischemic Aetiology (%) 41.8 HF Hospitalizations Prior 2 Years (mean ±sd) 0.7 ± 0.8 LVEF % 40.4 ± 9.0 Hypertension (%) 46.7 Prior MI (%) 37.8 Previous PCI (%) 33.3 Previous CABG (%) 13.3 Atrial Fibrillation (%) 44.4 Mod/Severe Renal Insuff(%) 55.8 COPD (%) 21.4 Mod/Severe Pulm HTN (%) 47.7

MAVERIC EU/AU: AP diameter immediately reduced and maintained at 2 years p=<0.0001 for all timepoints vs baseline 14% N=30

MAVERIC EU/AU: Immediate/Sustained MR Grade Reduction to 2 years 92% echo follow-up and core lab analysis P=<0.0001 all time points vs baseline MR Grade (paired) P=NS between timepoints <2+:84% <2+:91% <2+:90% Pre-pr: 65% < 3/4+ 100% 3+ 3+ 90% 3+ 1 year: 65% < 1+ 2+ 2+ 80% 4+ 2+ 91% < 2+ 70% 60% 1+ 2 year: 68% < 1+ 1+ 50% 3+ 90% < 2+ 1+ 40% 30% 20% 2+ 10% 0/TR 0/TR 0/TR 0% Pre-proced (n=31) 30 days (n=31) 1 year (n=31) 2 year (n=31) 0/TR 1+ 2+ 3+ 4+

MAVERIC EU/AU: LV and LA Volumes Reduced at 30 days and Improved at 2 years LVEDVi LVESVi 11% 15% p= 0.004 vs baseline p= 0.14 vs baseline LAVi 17% p= 0.004 vs baseline

MAVERIC EU/AU: 50% reduction in Regurgitant Volume, 44% reduction in EROA and 39% reduction in Vena Contracta EROA Regurgitant Volume p = <0.0001 vs baseline p= <0.0001 vs baseline 44% 50% P=<0.0001 P=<0.0001 P=<0.0001 P=0.009 P=<0.0001 P=<0.0001 Vena Contracta p= 0.001 vs baseline 39% P=<0.0001 P=0.002 P=0.001

MAVERIC EU/AU: Sustained NYHA Improvement to 2 years 92% clinical follow-up of all surviving(n=37)/no-reop (n=36) patients p= <0.0001 at all timepoints vs baseline NYHA Class (paired data) 100% IV Baseline: 36% Class II IV III 90% 30 days: 80% Class I/II III III 80% 2 years: 80% Class I/II 70% 60% III II 50% II II 40% 30% 20% II I 10% I I 0% Pre proced (n=34) 30 days (n=34) 1 year (n=34) 2 years (n=34) I II III IV

MAVERIC EU/AU: Low Rate of Heart Failure Hospitalisation To 2 Years CEC Adjudicated 30 days 1 year 2 year N=45 N=44 N=44 Event N (KM%) cumulative Cumulative N (KM %) N (KM%) HF Hospitalisation 0 (0) 4 (9.3%) 8 (19.8%) Death 0 (0) 5 (11.3%) 8 (18.1%) HF Hospitalisation 0 (0) 8 (18.0%) 14(31.9%) or Death

MAVERIC EU/AU: Heart Failure Hospitalisation 2 years prior to/after ARTO 60.0% 62% 50.0% p=0.001 52.3% 40.0% 30.0% 20.0% 19.8% 10.0% 0.0% 2 yrs prior to ARTO 2 yrs after ARTO

MAVERIC EU/AU: Major Adverse Events to Two Year Follow-Up Safety at 6 months 30 days 1 year 2 Year CEC Adjudicated Event N=45 N=44 N=44 N(KM %) N (KM%) N(KM%) Safety Composite Endpoint at 1 2(4.4%) 8 (17.8%) 11(24.4%) year* Death 0 5 (11.3%) 8(18.1%) Cardiovascular 0 5 (11.3%) 8(18.1%) Non-cardiovascular 0 0 0 Stroke 0 1 (2.3%) 1(2.3%) Myocardial Infarction 0 1 (2.3%) 1(2.3%) Device Related Cardiac Surgery 0 1 (2.3%) 1(2.3%) Cardiac Tamponade 1 (2.2%) 1 (2.2%) 1(2.2%) Renal Failure 1 (2.2%) 3 (7.0%) 3(7.0%) *Death, Stroke, MI, cardiac tamponade, device related cardiac surgery, renal failure

Why is this important? • At 2 year follow-up, significant reduction in MR grade by all measures. • The ARTO System is the only transcatheter mitral repair technology to report a significant long term (2 year) reduction in LVEDV in patients with FMR. • NYHA class after the ARTO procedure demonstrates improved and stable outcomes from the procedure to two years. Importantly, a 62% reduction in heart failure hospitalisation at 2 years. • The primary safety composite endpoint is low at 24.4%, as is mortality at 18.1% with no deaths attributed to the device or procedure • This study demonstrates the 2 year efficacy and safety of the ARTO System for the treatment of functional mitral regurgitation.

MAVERIC patients vs COAPT And MITRA-FR patients

Mortality Cause and Timing CV vs Related to Days post Cause of death MR Grade at Patient Number non-CV Device/Procedure? procedure (CEC adjudicated) baseline/latest visit (CEC adjudicated) (CEC adjudicated) 826-03-1005 32 Cardiovasc No/No Ischemic heart disease 2+/2+ 826-04-1003 73 Cardiovasc No/No Ischemic heart disease 4+++/4+ 61-03-1004 176 Cardiovasc No/No Heart failure 4+/2+ 61-01-1006 258 Cardiovasc No/No Heart Failure 3+/2+ 61-03-1003 279 Cardiovasc No/No Heart failure 4+/1+ 371-01-1010 567 Cardiovasc No/No Heart failure 3+/1+ 371-01-1005 568 Cardiovasc No/No Heart failure 3+/1+ 826-03-1003 592 Cardiovasc No/No Heart failure 4+/2+