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 ejectionfraction (LVEF) ≤35% and/or high BNP or NTproBNP levels (BNP>125 pg/ml orNTproBNP>400 pg/ml if sinus rhythm; BNP>375 pg/ml or NTproBNP>1200 pg/ml ifatrial fibrillation)

• Impairment of quality of life (KCCQ < 75 points) AND severe impairment ofexercise 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 orhospitalization in the last 12 months, due to HF, and requiring intravenousdiuretics and/or inotropes.

Exclusion Criteria:

• Unfavorable mitral valve anatomy, which implanting investigator judges as notsuccessfully treatable by the MitraClip (i.e. mitral valve area <3 mm2, leafletlength <7 mm)

• Echocardiographic evidence of intracardiac mass, thrombus or vegetation

• Active endocarditis or active rheumatic heart disease or leaflets degenerated fromrheumatic 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 carboxymaltoseadministration during the 30 days before randomization

• Coronary artery bypass graft, percutaneous coronary intervention, transcatheteraortic valve replacement or cardiac resynchronization therapy within the prior 30days

• Pulmonary vein ablation or cardioversion leading to restore of sinus rhythm or AVnode ablation in the last 30 days

• Myocardial infarction or cerebrovascular accident within prior 30 days

• Hemodynamic instability defined as systolic blood pressure < 90mmHg and cardiogenicshock or need for inotropic support or intra-aortic balloon pump or otherhemodynamic support device.

• Chronic obstructive pulmonary disease, malignancy, or other comorbidities as themain cause of severe symptoms and impaired quality of life.

• Life expectancy <12 months due to non-cardiac conditions