Early Surgery Versus Conventional Treatment for Asymptomatic Severe Mitral Regurgitation
Early Surgery Versus Conventional Treatment for Asymptomatic Severe Mitral Regurgitation
The timing of surgical intervention in asymptomatic patients with severe degenerative mitral
 regurgitation (MR) remains controversial. The benefit of early surgery has been suggested in
 prospective, observational studies, whereas a watchful waiting strategy seemed to be safe and
 effective in the other prospective study. The consensus guidelines for the performance of
 early surgery in asymptomatic patients with severe MR are different, reflecting controversy.
 Clinical outcome in asymptomatic patients with MR is poorly defined and it is important to
 identify high-risk patients in whom early surgery may be warranted. Thus, the investigators
 try to compare long-term outcomes of early surgery with those of a conventional-treatment
 strategy in a large prospective cohort of asymptomatic patients with severe degenerative MR
 using a propensity analysis, and to identify high-risk subgroups to whom early surgery is
 more beneficial.
Surgery is the only definitive therapy for severe mitral regurgitation (MR) and the
 guidelines recommend surgery for management of MR to symptomatic patients or asymptomatic
 patients with left ventricular (LV) dysfunction. However, the timing of surgical intervention
 in asymptomatic patients with severe MR remains unclear due to the lack of randomized
 clinical trials comparing early surgery versus watchful waiting. The benefit of early surgery
 has been suggested in prospective, observational studies, whereas a watchful waiting strategy
 seemed to be safe and effective in the other prospective study. The consensus guidelines for
 the performance of early surgery in asymptomatic patients with severe MR are different,
 reflecting controversy. The 2006 American College of Cardiology/American Heart Association
 (ACC/AHA) guidelines recommend early surgery for asymptomatic patients if the success rate of
 mitral valve repair is expected to exceed 90%, but the 2007 European Society of Cardiology
 (ESC) guidelines recommend watchful waiting for such patients.

 Clinical outcome in asymptomatic patients with MR is poorly defined and it is important to
 identify high-risk patients in whom early surgery may be warranted. Older patients and those
 with a larger effective regurgitant orifice (ERO) showed increased mortality under medical
 management, but it is controversial whether early surgery would improve clinical outcome of
 such patients, because the performance of surgery in high-risk patients might be associated
 with increased operative risk. Although randomized trials are required to establish
 indications for early surgery, ethical and financial constraints do not allow us to conduct a
 randomized trial and the investigators choose to perform a propensity analysis in a large
 prospective cohort of patients. The investigators try to compare long-term outcomes of early
 surgery with those of a conventional-treatment strategy that is based on current guidelines
 in a large prospective cohort of asymptomatic patients with severe degenerative MR using a
 propensity analysis, and examine the hypothesis that the reduction in cardiac mortality or
 cardiac event by early surgery is particularly evident among patients aged > 50 years or
 those with ERO ≥ 0.4 square centimeter.

 All patients suspected of MR undergo transthoracic echocardiography. Entry evaluation
 includes demographic data, clinical presentation, physical findings and echocardiographic
 data. Eligibility is determined after a patient undergoes a thorough evaluation of clinical
 and echocardiographic data. After the eligible patient has signed informed consent, entry
 into the registry will take place. The treatment groups will not be randomly assigned and the
 choice of early surgery or conventional treatment for each patient is at the discretion of
 the attending physician, who explains the potential benefits of early surgery and procedural
 risks in detail and considers the preferences of individual patients most importantly.
 Patients in the early surgery group should undergo mitral valve surgery within 6 months of
 enrollment. Patients in the conventional treatment group will be treated according to the
 2006 ACC/AHA guidelines and they will be educated to report immediately to a study
 coordinator or an investigator if they experience any symptoms, and referred for surgery if
 exertional dyspnea, LV ejection fraction <0.60, LV end-systolic dimension >40 mm, Doppler
 estimated pulmonary artery pressure > 50 mmHg, or atrial fibrillation develops. All patients
 will be followed at 3 months, 6 months, and 1 year; and at 6-month intervals thereafter until
 close-out of the study, and educated to call a study coordinator or an investigator if they
 experience any adverse events.

 The Executive Committee will approve the final trial design and protocol. This committee will
 also be responsible for reviewing the final results, determining the methods of presentation
 and publication, and selection of secondary projects and publications. Members of the
 committee will include the PI and persons who will organize this study. The Data Safety
 Monitoring Board (DSMB) will review the safety data from this study and make recommendations
 based on safety analyses of serious adverse events and protocol deviation. The Clinical
 Events Committee will meet regularly to review and adjudicate all clinical events that occur
 throughout the study period. The statistical analysis will be performed according to the
 prespecified analysis plan as described in the study protocol.
Inclusion Criteria:

 -  asymptomatic patients

 -  severe degenerative MR

 -  preserved left ventricular systolic function

 Exclusion Criteria: According to the recommendations of the 2006 American College of
 Cardiology/American Heart Association (ACC/AHA) guidelines for surgical indications of
 severe MR, the criteria for exclusion from the study are defined as follows.

 -  patients with the presence of exertional dyspnea, or angina

 -  left ventricular ejection fraction < 0.60

 -  left ventricular end-systolic dimension > 40 mm

 -  atrial fibrillation

 -  significant aortic valve disease

 -  Doppler-estimated systolic pulmonary artery pressure > 50 mmHg

 -  patients who were not candidates for early surgery based on age > 80 years and
 coexisting malignancies

 -  patients who did not consent to participate