1. 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

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

3. INTRODUCTION

4. 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.

6. Natural history of imr
Lamas et al. Circulation 1997: 96:

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

8. 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

9. 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.

10. Methodology

11. 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

12. 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)

13. 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)

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

15. 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

16. 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

17. Results

20. 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%

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

23. 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.

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

25. Cumulative Failure of Mitral-Valve Repair or Replacement

26. Quality of Life Scores

27. 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

28. Discussion

29. 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%).

30. 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

32. Impact of the study

33. 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