Abstract Body (Do not enter title and authors here): Background: Left ventricular global longitudinal strain (LV-GLS) assessed by cardiac magnetic resonance feature tracking (CMR-FT) is an emerging marker for predicting adverse outcomes in hypertrophic cardiomyopathy (HCM), but its incremental prognostic value and potential mechanistic role in sudden cardiac death (SCD) risk stratification remain unclear.
Objectives: To evaluate the incremental prognostic utility of LV-GLS beyond current European Society of Cardiology (ESC) and American College of Cardiology/American Heart Association (ACC/AHA) SCD risk models, and to explore whether LV-GLS mediates the relationship between myocardial hypertrophy, fibrosis, and SCD risk in patients with HCM.
Methods: We retrospectively analyzed 2,009 HCM patients (mean age 50±14 years; 70% men) who underwent CMR imaging between 2010 and 2017. LV-GLS was quantified using cine-CMR feature tracking. The primary endpoint included SCD and aborted SCD. Prognostic performance was assessed using time-dependent receiver operating characteristic (ROC) analysis, Kaplan-Meier survival analysis, and competing risk regression. Mediation analysis was used to investigated how LV-GLS mediated the association between myocardial abnormalities and SCD.
Results: Over a median follow-up of 88.2 months, 85 patients (4.2%) experienced SCD events. These patients had significantly lower absolute LV-GLS values (9.0±3.6% vs. 11.1±3.6%, P < .001). In competing risk regression, LV-GLS independently predicted SCD after adjustment for ESC (sHR: 1.12 per 1% decrease, 95% CI: 1.06–1.22, P < .001) and AHA risk factors (sHR: 1.09, 95% CI: 1.02–1.18, P = .016). Adding LV-GLS improved the 5-year predictive accuracy of both ESC and AHA models (area under the curve [AUC]: from 0.71 to 0.76 and 0.71 to 0.75, respectively). Absolute LV-GLS with a cutoff of 9.23% also stratified risk in patient subgroups with either Class II or Class III recommendations for implantable cardioverter-defibrillator (ICD) implantation (all log-rank P < .001). Mediation analysis showed LV-GLS partially mediated the relationship between maximum wall thickness and SCD (proportion-mediated: 23.1%, P < .001), and between extent of fibrosis and SCD (proportion-mediated: 17.5%, P < .001).
Conclusions: In HCM patients, CMR-derived LV-GLS is an incremental predictor of SCD beyond current guideline-based risk models and partially mediates the association between myocardial abnormalities and SCD.