Mitral Regurgitation Treatment in Advanced Heart Failure

Inclusion Criteria: * Age between 18 and 90 years * Significant secondary mitral regurgitation (effective regurgitant orifice area ≥ 5 30mm2) confirmed at the end of the screening period * Optimal medical therapy (OMT) according to recent guidelines. * Advanced heart failure defined as the presence of all the following criteria, despite OMT: * Severe and persistent symptoms of HF (NYHA class III or IV) * Severe cardiac dysfunction defined by a reduced left ventricular ejection fraction (LVEF) ≤35% and/or high BNP or NTproBNP levels (BNP\>125 pg/ml or NTproBNP\>400 pg/ml if sinus rhythm; BNP\>375 pg/ml or NTproBNP\>1200 pg/ml if atrial fibrillation) * Impairment of quality of life (KCCQ \< 75 points) AND severe impairment of exercise capacity with inability to exercise or low 6MWT distance (\<450 meters) or pVO2 (\<14 mL/kg/min or \<50% of predicted) OR at least 1 unplanned visit or hospitalization in the last 12 months, due to HF, and requiring intravenous diuretics and/or inotropes. Exclusion Criteria: * Unfavorable mitral valve anatomy, which implanting investigator judges as not successfully treatable by the MitraClip (i.e. mitral valve area \<3 mm2, leaflet length \<7 mm) * Echocardiographic evidence of intracardiac mass, thrombus or vegetation * Active endocarditis or active rheumatic heart disease or leaflets degenerated from rheumatic disease (i.e., noncompliant, perforated) * Active infections requiring current antibiotic therapy * Transesophageal echocardiography (TEE) contraindicated or at high risk * Untreated significant coronary artery disease requiring revascularization * Iron deficiency defined as serum ferritin \<100 μg/L, or ferritin between 100-299 μg/L and transferrin saturation \<20% and/or intravenous ferric carboxymaltose administration during the 30 days before randomization * Coronary artery bypass graft, percutaneous coronary intervention, transcatheter aortic valve replacement or cardiac resynchronization therapy within the prior 30 days * Pulmonary vein ablation or cardioversion leading to restore of sinus rhythm or AV node ablation in the last 30 days * Myocardial infarction or cerebrovascular accident within prior 30 days * Hemodynamic instability defined as systolic blood pressure \< 90mmHg and cardiogenic shock or need for inotropic support or intra-aortic balloon pump or other hemodynamic support device. * Chronic obstructive pulmonary disease, malignancy, or other comorbidities as the main cause of severe symptoms and impaired quality of life. * Life expectancy \<12 months due to non-cardiac conditions