The role of global longitudinal strain in predicting fatal arrhythmic events in hypertrophic cardiomyopathy: An up-to-date systematic review and Meta-analysis

Sudden cardiac death (SCD) remains a leading cause of mortality in patients with hypertrophic cardiomyopathy (HCM). Accurate identification of individuals at high risk is essential for guiding implantable cardioverter-defibrillator (ICD) therapy. Global longitudinal strain (GLS), an echocardiographic parameter derived from speckle-tracking imaging, reflects subclinical left ventricular systolic dysfunction and may serve as an adjunctive risk marker for fatal ventricular arrhythmias (VAs). A systematic review and meta-analysis were conducted following PRISMA guidelines. PubMed and the Cochrane Library were searched from inception to April 2025 for studies assessing the association between GLS and SCD and/or fatal VAs in HCM. Out of 1050 identified records, seven studies comprising 2167 patients (mean age 54.7 years) met inclusion criteria. All included studies were of moderate-to-high quality (Newcastle-Ottawa Scale ≥6). In the pooled quantitative synthesis of three studies, patients with reduced GLS (<15%) had a significantly higher risk of fatal VAs [hazard ratio/odds ratio (HR/OR): 1.10, 95% (confidence interval) CI 1.04-1.17]. On the other hand, 1% worsening of GLS was not associated with SCD and/or fatal VAs (HR/OR: 1.09, 95% CI 0.89-1.33). A combined meta-analysis using data from seven studies showed a significant association between GLS and SCD and/or fatal VAs in patients with HCM (HR/OR: 1.10, 95% CI 1.03-1.18). GLS is associated with risk of fatal arrhythmic events in HCM and may help identify higher-risk patients, but evidence from observational studies does not prove causality and may be confounded. GLS could aid shared decision-making about ICDs in borderline cases when combined with established risk factors, but should not be used alone. Prospective multicenter studies with standardized imaging are needed to validate thresholds, confirm added prognostic value, and show impact on outcomes.