Early Percutaneous Mitral Intervention in Asymptomatic Moderate Mitral Stenosis
Early Percutaneous Mitral Intervention in Asymptomatic Moderate Mitral Stenosis
Although percutaneous mitral commissurotomy (PMC) has been accepted as an effective treatment
 for symptomatic patients with moderate or severe mitral stenosis (MS), most asymptomatic
 patients are not candidates for PMC owing to the small but inherent procedure-related risks.
 Asymptomatic patients with MS show good survival rates up to 10 years, but there was a sudden
 deterioration precipitated by atrial fibrillation or embolism in half of the patients.
 Because the success rates of PMC were improved to more than 95% in ideal patients from highly
 selected centers and early PMC may decrease the occurrence of adverse events, such as atrial
 fibrillation or embolism, experienced centers tend to perform PMC at an early stage of
 disease. However, the potential benefits of early preemptive PMC in asymptomatic patients
 should be balanced against the real risks related to the procedure, and further studies of
 the efficacy of PMC in the prevention of embolism are necessary to extend its indications to
 asymptomatic patients. To the best of our knowledge, No randomized trials have been performed
 to ascertain the optimal timing of intervention in asymptomatic patients with significant MS.
 The early percutaneous MITral Intervention versus conventional manaGement in Asymptomatic
 moderate miTral stEnosis (MITIGATE) trial was designed to compare clinical outcomes of early
 intervention with those of a conventional management based on current guidelines in
 asymptomatic moderate mitral stenosis.
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.
Inclusion Criteria:

 -  asymptomatic patients with moderate MS who are potential candidates for early
 percutaneous mitral commissurotomy

 Exclusion Criteria:

 -  patients with exertional dyspnea

 -  total echocardiographic score > 10

 -  moderate to severe mitral regurgitation

 -  left atrial thrombi

 -  significant aortic valve disease,

 -  left ventricle (LV) ejection fraction (EF) <50%

 -  Doppler-estimated pulmonary artery systolic pressure >50 mmHg

 -  those who were not candidates for early intervention based on age > 70 years or the
 presence of coexisting malignancies