It is well-established that severe secondary mitral regurgitation (MR) is associated with more rapid clinical decline in patients with heart failure with reduced ejection fraction (HFrEF). Secondary MR simultaneously is the most widely prevalent, and a clinically important form of, mitral valve disease. Multiple trials have demonstrated that optimizing guideline-directed medical therapy (GDMT) in patients with HFrEF not only improves systolic function and clinical outcomes, but also improves MR severity. For some patients, however, optimal medical therapy does not result in adequate MR severity reduction or symptom improvement, or both, and thus, therapy for severe secondary MR remains a current unmet clinical need as our understanding of the disease continues to evolve. Previously, conventional surgery was pursued as a treatment of secondary MR; however, the results have been less impressive than for primary MR, where surgical repair is lifesaving. Additionally, most patients with severe secondary MR are sub-optimal or prohibitive-risk surgical candidates, and therefore, surgery is offered only to a minority of patients.