Nishith Patel Waikato Cardiothoracic Unit Journal Club Two Year Outcomes of Surgical Treatment of Severe Ischaemic Mitral Regurgitation Nishith Patel Waikato Cardiothoracic Unit Journal Club

Nishith Patel Waikato Cardiothoracic Unit Journal Club N ENGL J MED 374;4. January 28, 2016 Nishith Patel Waikato Cardiothoracic Unit Journal Club

INTRODUCTION

DEFINITION OF imr Ischemic mr usually follows a posterior wall mi involving the right and/or cx artery, with limited revasc reversibility. The infarct can influence valve performance: posterior annular dilatation, leaflet tethering due to infarct expansion, papillary muscle elongation.

Natural history of imr Lamas et al. Circulation 1997: 96:827-33.

Repair vs replacement for imr in observational studies Milano et al. Ann Thor Surg 2008.

TO REPAIR OR repLACE? REPAIR: REPAIR: Higher rate of recurrent MR Mitral Stenosis REPLACEMENT: Higher risk of periop death Long-term thromboembolism Endocarditis SVD REPAIR: Lower periop mortality and morbidity Preservation of subvalvular apparatus REPLACEMENT: Durable correction

objective To determine the short and mid-term mortality, morbidity and lv remodelling in patients with severe imr treated with mitral valve replacement versus repair. Null hypothesis: There would be no between-group difference in the lvesvi at 1 year.

Methodology

Methods – study design Multicentre, RCT Eligibility CARDIOTHORACIC SURGICAL TRIALS NETWORK Funded by the NIH and the CIHR 22 centres Eligibility Chronic severe IMR (ERO ≥ 0.4cm2 on TTE with tethering as a major mechanism) CAD (with or without the need for revasc) Eligible for repair or replacement Imr assessed using resting tte and integrative criteria Verified by independent core lab

METHODS – EXCLUSION CRITERIA Any evidence of structural (chordal or leaflet) mitral valve disease or ruptured papillary muscle Lack of mitral valve tethering Prior mitral valve repair Severe pulmonary hypertension, assessed by right heart catheterization, and defined by PVR ≥ 4 WU unless responsive to vasodilator therapy with resultanT PVR < 4 WU Contraindications to CPB Inability to derive ERO and ESVI by transthoracic echocardiography Planned concomitant intra-operative procedures (with the exception of tricuspid valve repair, closure of patent foramen ovale [PFO] or atrial septal defect [ASD]) Clinical signs of cardiogenic shock at the time of randomization ST segment elevation MI requiring intervention within 7 days prior to randomization Chronic renal insufficiency defined by Cr ≥ 2.5 or chronic renal replacementtherapy (chronic hemo- or peritoneal dialysis)

Methods – randomisation RANDOMIZATION Mvrepair or Mvrepalcement (chordal sparing) Performed intraoperatively following sternotomy but before cannulation Stratified according to centre Block randomisation to ensure equivalence of group size Mv repair Approved complete rigid or semi-rigid annuloplasty ring Downsized to correct annular dilatation Mv replacement Preservation of subvalvular apparatus Technique of preservation, choice of valve and suture technique were at the discretion of the surgeon All patients – maximal medical therapy (aspirin, statins, b-blockers, ace-I, CRT)

METHODS - TRAINING CARDIOTHORACIC SURGEONS 15 mitral valve procedures per year (averaged over 2 years)

Methods – study endpoints Primary outcome: Degree of LV reverse remodelling at 1 year Lv end-systolic volume index (LVESVI)(ml/m2) Assessed by tte Secondary outcomes: Death Macce (death, cva, redo mv surgery, hospital admission for hf, increase in nyha class) Recurrent mr Rehospitalisation Quality of life Lv size and function Followed for 2 years All study investigators unaware of overall outcome data

Methods – Statistical Analysis Power calculation 90% power to detect a 15ml/m2 difference in lvesvi from baseline to 1-year. Baseline lvesvi assumed to be 100ml/m2 Improvements of 20ml/m2 in the repair group and 35ml/m2 in the replacement Similar rate of death in both groups at 1 year of 10-20% 2-tailed wilcoxan rank-sum test to compare lvesvi at 2 years ITT analysis Long-rank test to compare rates of death and macce Functional status (nyha and ccs) by chi-square tests

Results

Results – primary outcome Mean lvesvi at 2-years Repair: 52.6 ± 27.7 ml/m2 (mean change from baseline: -9.0 ml/m2) Replacement: 60.6 ± 39.0 ml/m2 (mean change from baseline: -6.5 ml/m2) P=0.19 Mean LVEF: Repair: 42.5 ± 11.8% Replacement: 37.6 ± 11.8%

Clinical End Points, Serious Adverse Events, and Hospitalizations at 2 Years.

TIME-TO-EVENT CURVES FOR DEATH Figure 1. Time-to-Event Curves for Death. Shown are the proportions of patients who died in the mitral-valve (MV) repair group and the mitral-valve replacement group at 2 years. The most frequent underlying causes of death were multisystem organ failure (in 20.8% of patients), heart failure (in 17.0%), and sepsis (in 13.2%). The tick marks indicate censored data.

Time-to-Event Curves for Major Adverse Cardiac or Cerebrovascular Events (MACCE).

Cumulative Failure of Mitral-Valve Repair or Replacement

Quality of Life Scores

Author’s Conclusion In patients undergoing mitral-valve repair or replacement for severe ischaemic mitral regurgitation, there is no difference in left ventricular reverse remodeling or survival at 2 years. LVESVI improved significantly from baseline in both groups This predominantly occurred in the 1st year There was little further improvement in the 2nd year Mitral regurgitation recurred more frequently in the repair group, resulting in more heart-failure–related adverse events and cardiovascular admissions. 58.8% of patients in the repair group had mod or severe mr compared to 3.8% in the replacement group at 2 years

Discussion

Strengths of the study Multicentre, RCT Independent core lab Independent adverse events adjurdication committee In experienced hands, 30-day mortality for management of severe imr is reasonable (repair: 1.6%, replacement: 4.0%).

Limitations of the study Less than 10% of the 3000 patients screened were actually recruited. Primary end-point was an echocardiographic measurement of lv remodelling Lvesvi has been correlated with clinical outcomes, such as nyha class, hospitalisation, survival Evaluating survival would require thousands of patients Underpowered to assess survival differences TTE may underestimate presence of mr in patients with replacement valves Very little information on repair methods: Techniques for leaflet tethering and papillary elongation applied? Adequacy of repair? Selection of patients for repair using echo features

Impact of the study

How has the study impacted on practice Taken the focus away from mitral valve repair Good repair is better than a replacement; and both are better than a bad repair However what is a good repair? Focused on preserving sub-valvular apparatus Continues to highlight that replacement is still associated with higher post-op mortality