Nishith Patel Waikato Cardiothoracic Unit Everest 2 5 year outcomes Nishith Patel Waikato Cardiothoracic Unit

INTRODUCTION

Background (no more than 7 slides) MITRACLIP (ABBOT VASCULAR) DEVLOPED AS A PERCUTANEOUS ALTERNATIVE TO REDUCE MR. IT APPROXIMATES THE MITRAL VALVE LEAFLETS MODELLED ON THE ALFIERI DOUBLE ORIFICE TECHNIQUE FOR SURGICAL MV REPAIR; 1-year outcomes of everest II Surgery more effective for reducing mr Percutaneous approach safer than surgery https://youtu.be/GDxXTZ1I12s

objective Given the increased prevalence of mr and lack of annuloplasty with perc repair, What is the durability of perc repair compared to surgery What is the impact of either technique on long-term survival, symptoms, and lv remodelling

Methodology

Methods – study design Multicentre, randomised, non-blinded trial of mitraclip vs convential surgery for the treatment of mr Pre-specified 5-year follow-up Randomised in a 2:1 ratio (mitraclip to surgery) 37 study centres in north america between 2005 and 2008. Inclusion criteria: Moderate to severe (3+) or severe (4+) chronic mr Symptomatic with LVEF >25% and LV ESD <55mm or Asymptomatic with 1 or more of the following: LVEF 25-60% LV ESD >40mm New-onset AF PASP >50mmhg at rest or 60mmhg during exercise Primary regurgitant jet originated from malcoaptation of a2 and p2 scallops Both functional and degenerative mr were eligible.

Methods – Surgical Details Baseline and follow-up echos assessed by independent echo core lab – University of san francisco Trial designed by abbott Harvard clinical research institute contracted by abbott to perform data management, analysis and clinical event adjudication.

methods Mitraclip Surgery Under ga Using toe and fluoroscopy in cardiac cath lab 2nd mitraclip deployed if first did not result in adequate reduction in mr Patients given aspirin 325mg OD for 6 months and clopidogrel 75mg od for 30 days. Surgery Discretion of the surgeon

Methods – Endpoints at 5 years Freedom from death, surgery for mv dysfunction, and 3+ or 4+ MR Freedom from death Freedom from surgery for mv dysfunction Freedom from death and surgery for my dysfunction Additional pre-specified endpoints: Change in lv dimensions and volumes NYHA class Quality of life

Methods – Statistical Analysis Analysed as the all-treated cohort for 5-year analysis Excludes patients randomised but not treated Time-to event analyses using kaplein meier curves, log-rank test and cox- proportional hazards regression analysis Sub-group analysis: age, mr aetiology, lv function

Results

Results (STUDY FLOW) Study Flow: All-Treated Group Data are shown for patients in the all-treated cohort evaluated for the 5-year efficacy endpoint. Because the primary endpoint required echocardiographic assessment of mitral regurgitation (MR), patients with missing MR grade at 5-year follow-up were excluded from the analysis.

Results (Baseline Characteristics)

Results: EFFICACY ENDPOINTS AT 5-YEARS

ResultS: 5-YEAR CLINICAL OUTCOMES 5-Year Clinical Outcomes: Percutaneous Repair and Surgery for Mitral Regurgitation Kaplan-Meier curves depict (A) freedom from the composite of death, mitral valve (MV) surgery, or reoperation, (B) freedom from death, (C) freedom from MV surgery or reoperation, and (D) landmark analysis of freedom from MV surgery or reoperation beyond 6 months after percutaneous repair or surgery. Although patients undergoing percutaneous repair more commonly required surgery for residual mitral regurgitation during the first year after treatment, comparably low rates of surgery for MV dysfunction with either percutaneous or surgical therapy were seen between 1- and 5-year follow-up. RCT = randomized clinical trial.

Results: SEVERITY OF MR AND SYMPTOMS Severity of MR and Heart Failure Symptoms Post-Treatment For patients who survived to 5 years and had pertinent data reported at each time point, comparisons are seen for (A) echocardiographic severity of MR in 101 and 40 patients in the device and surgery arms, respectively, and (B) New York Heart Association functional class in 105 and 40 patients in the device and surgery arms, respectively. MR = mitral regurgitation.

Results: SUBGROUP ANALYSES

Results: PREDICTORS OF 5-YEAR MORTALITY

Author’s Conclusion 5-YEAR RESULTS OF EVEREST II SUPPORT THE SUPERIORITY OF SURGERY IN REDUCING MR BUT IT ALSO SUPPORTS THE LONG-TERM SAFETY OF MITRACLIP AND THE DURABILITY OF MR REDUCTION AFTER PERCUTANEOUS REPAIR BEYOND 1 YEAR, WORSENING MR AND SURGERY FOR MV DYSFUNCTION OCCURRED RARELY AFTER EITHER SURGERY OR PERC REPAIR. SIMILARLY IMPROVEMENTS IN SYMPTOMS AND LV DIMENSIONS REMAINED STABLE THROUGH 5-YEAR FOLLOW-UP, MITIGATING CONCERNS THAT RESIDUAL MR AFTER DEVICE PLACEMENT AND THE ABSENCE OF AN ANNULOPLASTY RING WOULD RESULT IN WORSENING MR AND LV DYSFUNCTION. DESPITE REDUCTION IN MR, FUNCTIONAL MR INCREASED RISK OF LONG-TERM MORTALITY.

Discussion

Strengths of the study First rct of perc repair versus surgery Independent echo core lab Independent adjudication committee

Limitations of the study Heterogeneous study populations: functional and degenerative mr Inclusion criteria: 3+ regurgitation Only 24% had 4+ (Severe) regurgitation Needs to mirror clinical practice 5% of patients had mild-moderate mr Use of core lab before recruitment Quality of centres: Breakdown of centres not provided Mean number mitraclip/centre was 5 and surgery/centre 2.5 High proportion of surgeons in trial performed <15 mv repairs per year 14% of patients in surgical arm had mv replacement

LIMITATIONS PATIENT COMPLIANCE HIGH PERCENTAGE OF WITHDRAWAL ITT VS TREATED COHORT ANAESTHETISE AFTER INDUCTION ? INCLUSION OF LOW-RISK ASYMPTOMATIC PATIENTS HIGH RATE OF VALVE REPLACEMENT Test on high risk patients

Impact of the study

How has the study impacted on practice Role for percutaenous mitral valve repair Inoperable or high risk patients Functional mr patients