Heart failure and severe mitral regurgitation (MR) are mutually dependent. Secondary MR is a consequence of chronic heart failure in patients with severely depressed left ventricular ejection fraction (LV-EF) and LV dilatation. Severe MR in heart failure patients worsens prognosis and accelerates LV dilatation and decline in LV-EF. Interventional therapies have changed clinical practice for heart failure patients with secondary MR. In this review we summarize the available data of patients with chronic heart failure undergoing transcatheter edge-to-edge mitral valve repair (TMVR) with the MitraClip® system for severe secondary mitral regurgitation. TMVR could be a therapeutic option with a favorable long-term outcome even in patients with severely depressed LV-EF. Selection criteria predicting mortality in patients undergoing TMVR comprise clinical, laboratory and echocardiographic parameters and can help for clinical decision-making. Ongoing randomized trials will influence the use of interventional treatment of MR in these high-risk patients.