Abstract
Background/Objectives: Chronic aortic regurgitation (AR) can remain asymptomatic despite progressive myocardial damage. While current surgical guidelines rely heavily on left ventricular ejection fraction (LVEF) and symptoms, these measures may fail to detect subclinical myocardial dysfunction. Global longitudinal strain (GLS), a sensitive echocardiographic marker, has emerged as a potential early biomarker in valvular disease. Therefore, this systematic review aims to assess whether impaired GLS is significantly associated with adverse clinical outcomes including symptom onset, reduced LVEF, and the need for aortic valve intervention among patients with asymptomatic moderate to severe AR and preserved LVEF. Methods: This systematic review and meta-analysis followed PRISMA guidelines and was registered with PROSPERO (CRD42024579540). Comprehensive searches of PubMed, Embase, and the Cochrane Library were completed on November 28, 2024. Screening, deduplication, and blinding were conducted using Rayyan. Eligible studies included adults with chronic, asymptomatic moderate to severe AR and preserved LVEF who underwent GLS measurement. Risk of bias was assessed using the National Heart, Lung, and Blood Institute (NHLBI) tool. A random-effects meta-analysis was performed on studies reporting multivariate hazard ratios (HRs) and 95% confidence intervals. Results: Twelve studies (N = 3278) were included in the systematic review, and four studies (n = 1125) were eligible for meta-analysis. Impaired GLS was significantly associated with adverse outcomes, yielding a pooled HR of 1.359 (95% CI: 1.106-1.668; p = 0.003). Heterogeneity was substantial (I(2) = 77%), and the 95% prediction interval ranged from 0.553 to 3.340, indicating potential variability in future settings. Conclusions: GLS is a promising prognostic biomarker for identifying subclinical cardiac dysfunction in asymptomatic moderate to severe AR with preserved LVEF. Its use may enhance early risk stratification and optimize timing for surgical intervention. Larger prospective studies are needed to validate specific GLS thresholds for clinical decision-making.