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Ethics statement The animal study was reviewed and approved by Institutional Animal Care Committee, Ferdowsi University of Mashhad

Intervention once MR is already in the decompensated phase is accompanied with high morbidity and mortality due to recurrence of HF ( MV repair is the preferred mode of therapy considering the lower operative mortality, superior long-term survival, and fewer valve related complications from bleeding and endocarditis compared to valve replacement ( Secondary MR Pharmacologic therapy comprising of a combination of angiotensin receptor neprilysin inhibitors, angiotensin converting enzyme inhibitors, angiotensin receptor blockers, beta blockers, mineralocorticoid receptor antagonists, and diuretics is recommended in the management of HF with reduced ejection fraction and severe MR ( secondary MR

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