Association of left ventricular global longitudinal strain with outcomes of severe mitral regurgitation due to severe mitral annular calcification: a retrospective cohort study

Background: Mitral annular calcification (MAC) is associated with increased mortality and a heightened risk of complications such as stroke, myocardial infarction, and arrhythmias. In advanced stages, MAC can cause severe mitral regurgitation (MR), further worsening outcomes. Prognostic markers to guide therapy in this population remain unclear. Left ventricular global longitudinal strain (LVGLS) has been linked to outcomes in MR, but its role in severe MR due to severe MAC is not well established. This study evaluated the prognostic value of LVGLS in this setting.

Methods: We conducted a single-center, retrospective study of patients with severe MAC identified from the Cleveland Clinic echocardiographic database between January 2010 and August 2023. From these, patients with mild or moderate MR and those with concomitant significant mitral stenosis (MS) were excluded. Subsequently, patients with isolated severe MR due to severe MAC were identified. Clinical and echocardiographic parameters, including LVGLS, were recorded at baseline. The primary outcome was all-cause mortality. Patients were stratified by the median LVGLS value for analysis. Survival was assessed using Kaplan-Meier analysis and Cox proportional hazards models. Restricted cubic spline was used to evaluate potential non-linear associations between LVGLS and mortality.

Results: During the study period, 10,061 patients were diagnosed with severe MAC on echocardiography at our institution. Of these, 8,912 with mild or moderate MR and 1,021 with concomitant significant MS were excluded, and 128 patients with isolated severe MR due to severe MAC were included in our study. The median follow-up was 134 days [interquartile range (IQR), 33–1,812 days]. The median age was 81 years (IQR, 71–88 years), and 35 (27.3%) were male. The median left ventricular ejection fraction (LVEF) was 63% (IQR, 56–69%), mean MR regurgitant volume was 60±20.8 mL, and median right ventricular systolic pressure was 54 mmHg (IQR, 42–71 mmHg). The median LVGLS was −14.8%±4.5%. Of the 128 patients, 45 (35.2%) underwent mitral valve intervention, 42 (93.3%) surgery and 3 (6.7%) mitral clip implantation, while 83 (64.8%) received conservative management. Among surgical cases, 37 underwent valve replacements (34 bioprosthetic) and 5 valve repairs. During follow-up, 63 patients (49.2%) died. LVGLS worse than −14.8% was associated with higher 12-month mortality (log-rank P=0.043) but not over the entire follow-up period (P=0.11). On multivariable cox regression, LVGLS was not a predictor of mortality after adjusting for other covariates [hazard ratio (HR) 1.046, 95% confidence interval (CI): 0.983–1.112].

Conclusions: In severe MR due to MAC, impaired LVGLS was associated with increased short-term but not long-term mortality. The limited long-term prognostic value may reflect the low myocardial reserve in patients with severe valvular dysfunction due to MAC, the progressive and systemic nature of the disease, and the influence of non-cardiac comorbidities.