Early Percutaneous Mitral Intervention in Asymptomatic Moderate Mitral Stenosis (MITIGATE)

• Composite of cardiovascular event [ Time Frame: Participants will be followed for the duration of the trial, an expected average of 3 years ] [ Designated as safety issue: Yes ]
  Composite of cardiovascular mortality, cerebral infarction, systemic embolic events that occurred during follow-up, and PMC-related complications; procedural mortality and urgent MV surgery.
  
  

• all-cause death and each component of cardiovascular event [ Time Frame: Participants will be followed for the duration of the trial, an expected average of 3 years ] [ Designated as safety issue: Yes ]
  all-cause death and any component of composite primary end point.
  
  

We enroll consecutive asymptomatic patients with moderate mitral stenosis who are candidates for both early percutaneous mitral commissurotomy (PMC) and conventional treatment at 3 centers in Seoul, Korea.

Echocardiographic evaluation is performed before enrollment, immediately after PMC and annually during follow-up. All patients undergo two-dimensional echocardiography and/or transesophageal echocardiography to detect left atrial thrombi. Morphologic features of the mitral valve (MV) are categorized as described previously (14), and total echocardiographic score is obtained by adding the scores for leaflet mobility, thickness, calcification, and subvalvular lesions. The MVA is measured by direct planimetry of the mitral orifice, and MS severity is graded as mild, moderate, or severe when MVA was > 1.5, 1.0 to 1.5, or < 1.0 cm2, respectively. The severity of mitral and tricuspid regurgitation is assessed semiquantitatively or using quantitative methods and classified as mild, moderate, or severe. Pulmonary artery systolic pressure (PAP) is estimated by continuous wave Doppler with the simplified Bernoulli equation.

All study patients regularly visit their attending physicians at 3 monthly interval for maintenance of anticoagulation therapy or every year for annual re-evaluation. Patients in the conventional treatment group who become symptomatic during follow-up are referred for PMC or mitral valve surgery. An embolic event is defined as a systemic embolism fulfilling both prespecified criteria: acute onset of clinical symptoms or signs of embolism and occurrence of new lesions confirmed by imaging studies. A specific diagnosis of cerebral infarction is confirmed by an experienced neurologist and additional brain magnetic resonance imaging is performed if indicated.

We estimate that a sample size of 166 patients would provide 80% power to detect a significant difference with respect to the primary end point at the 2-sided significance level of 0.05, assuming 3-year event rates of 13% in the conventional treatment group and 2% in the early PMC group, and drop-out rate of 5%. These rates are based on the results of our previous study. Analyses are performed on an intention-to-treat basis. To analyze primary outcome, estimates of cumulative event rates are calculated by the Kaplan-Meier method and compared employing the log-rank test. For Kaplan-Meier analysis, we analyze all clinical events by time to first event. Hazard ratios with 95% confidence intervals are derived with the use of the Cox proportional hazards model.