MIDA

Published

Suri RM, et al. "Association between early surgical intervention vs watchful waiting and outcomes for mitral regurgitation due to flail mitral valve leaflets". JAMA. 2013. 310(6):609-616.
PubMed • PDF

Clinical Question

Among patients with flail mitral regurgitation but without a class I indication for surgical correction, is early surgery associated with improved survival compared to medical management?

Bottom Line

In this retrospective study of patients with chronic flail mitral regurgitation (MR), early surgery was associated with improved survival compared to medical management.

Major Points

The 2006 ACC/AHA guidelines provide a class I recommendation for MV surgery in two groups of chronic severe MR patients: 1) those with symptoms of heart failure and 2) those without symptoms but with mild-moderate LV dysfunction. The role of surgery for patients without these indications has been debated.

The 2013 Mitral Regurgitation International Database (MIDA) study retrospectively studied the cardiovascular outcomes of patients with chronic severe flail MR but without class I indications for surgical intervention. 1,021 patients at six US and European centers were followed for a mean of 10.3 years. Patients were categorized into two groups: early surgery (received surgery within 3 months of diagnosis) and watchful waiting (medical management alone for the first 3 months followed by medical or surgical treatment as determined by the patient's treating physician). Of note, 22.6% of patients had class IIa indications for mitral valve surgery, and 59% of the watchful waiting group eventually underwent mitral valve surgery. Early surgery was associated with a reduction in the primary outcome of all-cause mortality; early surgery was also associated with less heart failure than the medical management cohort, but there was no difference in the rate of new atrial fibrillation between groups.

While the study provides some insight into the difference between early surgery and watchful waiting in chronic severe flail MR, this study is limited by its retrospective design. The investigators attempted to correct for confounding between-group variables through the use of propensity score matching and inverse probability weighting. These statistical methods are common among retrospective cohort studies, and allow adjustment for investigator-determined variables such as age, sex, etc. However, the authors' analysis is still likely to overestimate the differences between the early surgery and watchful waiting groups due to unmeasured confounders.

Guidelines

ACC/AHA Valvular Heart Disease (2014, adapted)

• MV surgery recommended for symptomatic patients with chronic severe stage D primary MR and LVEF >30% (class I, level B)
• MV surgery is recommended for asymptomatic patients with chronic severe stage C2 primary MR and LVEF 30-60% and/or LVESD ≥40 mm (class I, level B)
• MV repair is recommended over MV replacement when surgery is indicated for patients with chronic severe primary MR that is:
  • Limited to the posterior leaflet (class I, level B)
  • Involving the anterior leaflet or both leaflets when a "successful and durable repair" can occur (class I, level B)
• MV repair is reasonable in asymptomatic patients with chronic severe stage C1 primary MR with LVEF >60% and LVESD <40 mm if successful and durable repair without redisdual MR is >95% and expected mortality <1% while being performed at a Heart Valve Center of Excellence (class IIa, level B)
• MV repair is reasonable for asymptomatic patients with chronic severe stage C1 primary, nonrheumatic MR with LVEF >60% and LVESD <40 mm if high likelihood of repair if new AF or PA systolic arterial pressure >50 mmHg (class IIa, level B)

Design

• Multicenter, retrospective cohort study
• N=1,021
  • Early surgery (n=446)
  • Medical management (n=575)
• Setting: 6 centers in the US and Europe
• Enrollment: 1980-2004
• Mean follow-up: 10.3 years
• Analysis: Propensity score matching, inverse probability weighting
• Primary outcome: All-cause mortality

Population

Inclusion Criteria

• MR with a flail leaflet found on TTE between 1980-2004

Exclusion Criteria

• Class I indication for surgical correction:
  • Current heart failure symptoms
  • LVEF <60%
  • LVESD ≥40 mm
• Ischemic mitral regurgitation
• Aortic valve disease
• Congenital heart disease
• Mitral stenosis
• Prior valve surgery
• HF symptoms due to MR
• Comorbid contraindication to surgery
• Echocardiographic features suggestive of MR due to ischemic, functional, or non-flail pathology

Baseline Characteristics

Comparisons are medical management vs. early surgery.

• Demographics:
  • Age: 67 vs. 62 years (P<0.001)
  • Male sex: 72.1% vs. 73.0% (P=0.56)
• Minimal symptoms: 32.5% vs. 52.5% (P<0.001)
• PMH:
  • HTN: 37.4% vs. 36.5% (P=0.78)
  • Class IIa surgical indication: 19.1% vs. 27.1% (P=0.002)
    • AF: 10.0% vs. 12.4% (P=0.21)
    • pHTN: 11.8% vs. 16.8% (P=0.02)
• Cardiac data:
  • LVEF: 68.6% vs. 68.7% (P=0.65)
  • HR: 75 vs. 74 BPM (P=0.28)
  • LVEDD: 56.0 vs. 57.7 mm (P<0.001)
  • LVESD: 32.2 vs. 33.5 mm (P<0.001)
  • LVESD/BSA: 17.6 vs. 17.9 mm/m² (P=0.04)
  • LA diameter: 48.0 vs. 49.2 mm (P=0.03)
  • Posterior valve flailing: 86.0% vs. 87.4% (P=0.52)

Interventions

• Inclusion in a group as defined by clinical management:
  • Early surgery - Surgery performed in first 3 months following diagnosis
  • Medical management - Medical management in first 3 months with either surgical or medical management thereafter

Outcomes

Comparisons are medical management vs. surgery. Abbreviations: P-Y, person-years; RR, rate ratio.

Primary Outcome

All-cause mortality

Overall: Surgery better

Unadjusted: HR 0.55; 95% CI 0.41-0.72; P<0.001

Propensity score-matched: HR 0.52; 95% CI 0.35-0.79; P<0.002

Inverse probability-weighted: HR 0.66; 95% CI 0.52-0.83; P<0.001

3-12 months: 2.8 vs. 0.6/100 P-Y (RR 0.3; 95% CI 0.03-0.08; P=0.03)

1-5 years: 3.6 vs. 1.0/100 P-Y (RR 0.3; 95% CI 0.02-0.05; P<0.001)

>5 years: 4.4 vs. 2.1/100 P-Y (RR 0.5; 95% CI 0.4-0.7; P<0.001)

Secondary Outcomes

Heart failure

Surgery better

Unadjusted: HR 0.29; 95% CI 0.19-0.43; P<0.001

Propensity score-matched: HR 0.44; 95% CI 0.26-0.76; P=0.003

Inverse probability-weighted: HR 0.51; 95% CI 0.36-0.72; P<0.001

New atrial fibrillation

No difference

Unadjusted: HR 0.85; 95% CI 0.64-1.13; P=0.26

Propensity score-matched: HR 1.28; 95% CI 0.84-1.95; P=0.25

Inverse probability-weighted: HR 1.05; 95% CI 0.81-1.37; P=0.72

Criticisms

• Not randomized
• No strict definition of medical therapy
• Asymptomatic severe MR due to flail leaflet is uncommon (only occurred in about 7 patients per enrolling center in this study) and therefore, difficult to generalize study results
• Group assignment were not based on level IIa infdications
• About a third of patients had mild symptoms though were not referred for surgery despite the level I indication to do so
• The high rate of development of heart failure in the medical therapy group implies inadequate follow-up
• Unclear success of surgeries
• In regards to choice of replacement vs. repair, those included in this analysis underwent replacement at a lower rate (7%) than is the usual in the US population (44%)
• Uneven baseline characteristics

Funding

Not disclosed.