Comorbidities and excess mortality of patients with moderate mitral regurgitation

Background Patients with moderate mitral regurgitation (MR) represent a considerable subgroup of individuals with mitral valve disease. Recent studies suggest that edge-to-edge repair of MR may be appropriate for patients with less severe MR. Purpose This study aims to explore the survival of patients with moderate MR and identify outcome modifiers. Methods A retrospective analysis of 121,360 patients evaluated between 2007 and 2024 in a single tertiary center. Patients with moderate-to-severe or severe MR were excluded. The population was categorized into three mutually exclusive groups: moderate, mild-to-moderate, and ≤mild MR, with comparisons made between the three groups. Patients were censored when MR progressed or when mitral valve repair/replacement was documented. The primary outcome was all-cause mortality, employing Kaplan-Meier survival analysis and Cox proportional hazards regression models applied. Interaction analysis was performed to identify outcome modifiers. Results Final cohort included 118,149 patients [median age of 65 years (IQR,52-76), 43% women] of whom 6,024 (5%) had moderate MR. Patients with moderate MR had a higher burden of comorbidities. Over a median follow-up duration of 5.5 years (IQR 2-10), 39,000 (33%) patients died. There were 31,832 (30%) deaths in the ≤mild MR group, 3,553 (53%) in the mild-to-moderate MR group, and 3,615 (60%) in the moderate MR group. Cox regression analysis, adjusted for known mortality predictors, showed that, compared with ≤mild MR, patients with moderate MR were 19% more likely to die during follow-up (95% CI: 1.131-1.243, p < .001). Interaction analyses revealed that the excess mortality associated with moderate MR was modified by several important comorbidities. Excess mortality was particularly pronounced among frail patients (HR 1.236 vs. 1.178), non-obese patients (HR 1.202 vs. 1.179), patients with diastolic dysfunction (HR 1.218 vs. 1.160), and among individuals free of lung disease (HR 1.204 vs. 1.055), or those free of pulmonary hypertension (HR 1.301 vs. 1.190). Interaction analysis was significant for all comparisons (p for interaction < .002). Conclusions Moderate MR is strongly associated with an increased burden of comorbidities and serves as a significant, independent predictor of excess mortality. We identified several important comorbidities that modify the association between moderate MR and mortality. Our findings suggest that clinical trials for less than severe MR should target these important subgroups.