Moderate Secondary Mitral Regurgitation: Evolving Evidence and Management Strategies (JACC September 2025-1)-Article: Moderate Secondary Mitral Regurgitation: Evolving Evidence and Management Strategies

Article: Moderate Secondary Mitral Regurgitation: Evolving Evidence and Management Strategies

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This 2025 JACC state-of-the-art review by Riccardi et al. focuses on moderate secondary mitral regurgitation (SMR) in patients with heart failure (HF). SMR arises due to left ventricular (LV) or atrial disease without primary valve leaflet abnormalities and is common in HF. It is classified by mechanism into ventricular SMR (associated with reduced ejection fraction, LV dilation, and papillary muscle displacement) and atrial SMR (associated with preserved EF, left atrial dilation, and often atrial fibrillation). The review emphasizes the clinical significance of moderate SMR, which, despite prior focus on severe SMR, is prevalent and prognostically important across HF phenotypes including reduced (HFrEF), mildly reduced (HFmrEF), and preserved ejection fraction (HFpEF).<br /><br />Echocardiographic grading of SMR severity uses multiparametric measures: effective regurgitant orifice area (EROA), regurgitant volume (RVol), regurgitant fraction (RFrac), and vena contracta width. Moderate SMR is defined quantitatively by EROA of 0.20-0.29 cm², RVol 30-44 mL, or RFrac 30-39%. The dynamic nature of SMR and limitations in echocardiography challenge accurate assessment; advanced imaging such as 3D transesophageal echo, cardiac MRI, and stress testing enhance diagnosis.<br /><br />Prevalence studies reveal moderate SMR ranges widely: 6-32% in HFrEF, ~10% in HFmrEF, and 7-14% in HFpEF; reaching over 40% in advanced HF cohorts. Moderate SMR is associated with increased risks of mortality, HF hospitalization, and heart transplantation, especially in those with reduced EF.<br /><br />Management begins with optimization of guideline-directed medical therapy (GDMT), including neurohormonal blockers, angiotensin receptor-neprilysin inhibitors, and sodium-glucose cotransporter 2 inhibitors, which can reduce SMR severity. Cardiac resynchronization therapy, pulmonary vein isolation for atrial fibrillation, and transcatheter aortic valve replacement may also ameliorate moderate SMR.<br /><br />Surgical correction for moderate SMR has not shown clear benefits and carries added risks. Mitral transcatheter edge-to-edge repair (M-TEER) has demonstrated symptomatic and hospitalization benefits for severe SMR and emerging data suggest possible benefits in select moderate SMR patients. The recent RESHAPE-HF2 trial, which included moderate SMR patients, showed reduced HF hospitalizations but no mortality benefit with M-TEER. Registries like EXPANDed reinforce that M-TEER reduces MR severity and improves quality of life even in moderate SMR. Nonetheless, randomized trials dedicated to moderate SMR patients are needed to confirm efficacy and inform guidelines.<br /><br />The review highlights gaps in evidence regarding optimal diagnostic criteria, the role of stress imaging, and patient selection for intervention. Artificial intelligence tools show promise in standardizing MR assessment and prognostication. Future research should incorporate multiparametric imaging, consider GDMT optimization, and evaluate M-TEER’s role in moderate SMR to improve clinical outcomes and quality of life in HF patients.

Keywords

moderate secondary mitral regurgitation

heart failure

left ventricular disease

atrial disease

echocardiographic grading

guideline-directed medical therapy

mitral transcatheter edge-to-edge repair

cardiac resynchronization therapy

RESHAPE-HF2 trial

artificial intelligence in MR assessment