Dutch-AMR: Early Mitral Valve Repair Versus Watchful Waiting in Asymptomatic Patients With Severe Mitral Regurgitation
Dutch-AMR: Early Mitral Valve Repair Versus Watchful Waiting in Asymptomatic Patients With Severe Mitral Regurgitation
Rationale:

 Severe asymptomatic organic Mitral Valve (MV) regurgitation with preserved left ventricular
 (LV) function is a challenging clinical entity as data on the recommended treatment strategy
 for these patients are scarce and conflicting, which is reflected in current guidelines.
 European guidelines advocate a more conservative strategy i.e. watchful waiting, with yearly
 echocardiography, whilst American guidelines are more in favour of early surgery to
 reconstruct the MV, i.e. MV repair (in contrast to MV replacement) in order to prevent future
 LV dysfunction and complaints.

 A number of non-randomised trials show a favourable outcome of early surgery: in the study of
 Enriquez-Sarano et al. for instance, the early surgery strategy has shown to be associated
 with improved long-term survival, decreased cardiac mortality, and decreased morbidity
 compared with the conservative management [1]. On the other hand, non-randomised trials
 describe also that a conservative strategy (i.e. watchful waiting) can be safely
 accomplished. If facilitated surgery is performed in this population (50% at 10 years
 follow-up according to Rosenhek et al [2]), it has proven to be eventually associated with
 good perioperative and postoperative outcome when careful follow-up is being carried out [2].

 Objective:

 To compare early MV repair versus watchful waiting in asymptomatic patients with severe
 organic mitral valve regurgitation and preserved left ventricular function.

 Study design:

 Multicenter, registry trial.

 Study population:

 250 Asymptomatic patients (18-75 years old) with severe organic MV regurgitation and
 preserved left ventricular function. The current European Society of Cardiology (ESC)
 guidelines on Valvular Heart Disease will be applied [3]. These guidelines are also used in
 the Netherlands. Accordingly, patients with an indication for MV surgery will not be
 included.

 Intervention:

 Intervention will be early MV repair compared to a watchful waiting strategy.
Inclusion Criteria:

 -  18-75 years.

 -  Asymptomatic patients. "Asymptomatic" is defined as absence of subjective limitations
 of exercise capacity or complaints expressed by the patient and confirmed by the
 treating cardiologist.

 -  Severe organic mitral valve regurgitation. "Severe organic mitral valve regurgitation"
 is defined as non-ischemic mitral valve regurgitation with an organic cause (intrinsic
 valve lesion) as determined by echocardiographic core-lab reading based on the
 criteria for definition of severe MR as issued by the ESC guidelines [4]. For
 practical reasons, referring cardiologists can use an ESC guidelines based index that
 was validated in the investigator's core-lab (Jansen et al, Practical
 echocardiographic semi-quantitative scoring system to determine severity of mitral
 regurgitation. Abstract presentation at ESC EUROECHO Congress 2011 and annual spring
 congress 2012 Netherlands Society of Cardiology).

 -  Preserved left ventricular function, "Preserved left ventricular function" is defined
 as left ventricular ejection fraction >60% and left ventricular end-systolic dimension
 <45 mm (no indexed value, measured by echocardiography).

 -  The likelihood of MV repair should be more than 90% determined by the local heart team
 with a cardiologist and cardiothoracic surgeon.

 Exclusion Criteria:

 -  Pulmonary hypertension (>50 mmHg at rest).

 -  Atrial fibrillation, either on 12-lead ECG or holter-monitoring.

 -  Physical inability as determined by the heart team to undergo surgery.

 -  Other life-threatening morbidity.

 -  Higher expected surgical risks in advance, according to the dedicated heart team.

 -  Patients with moderate to severe kidney disease (estimated glomerular filtration rate
 (eGFR) less than 30 mL/min).

 -  Flail leaflet together with a left ventricular end systolic diameter (LVESD) ≥40 mm
 (no indexed value)