Abstract 4370201: Heart of the Matter: Quantifying Fibrosis by LGE-CMR to Predict Sudden Death in Hypertrophic Cardiomyopathy

Background: Hypertrophic cardiomyopathy (HCM) is a common genetic heart condition with a variable risk of sudden cardiac death (SCD) and heart failure. Late gadolinium enhancement (LGE) by cardiac magnetic resonance (CMR) reflects myocardial fibrosis and has been linked to adverse outcomes. However, individual studies use different LGE thresholds and patient groups. Methods: We performed a systematic review and meta-analysis of peer-reviewed studies published from January 2010 to June 2025. We searched PubMed, EMBASE, and Cochrane Library for observational cohort and registry studies reporting quantitative LGE measurements (percentage of left ventricular mass) and clinical endpoints in adult HCM patients. Eligible studies had at least 12 months of follow-up, reported hazard ratios (HRs) with 95% confidence intervals (CIs) comparing high versus low LGE burden, and enrolled patients ≥18 years old. We identified five studies (Bruder et al. 2010; O’Hanlon et al. 2010; Patel et al. 2012; Chan et al. 2014; Weng et al. 2016). Two reviewers independently extracted data on study design, LGE protocol, LGE threshold, sample size, and endpoints (SCD, ventricular arrhythmias, or heart failure events). Log-transformed HRs and standard errors were calculated from reported CIs. A DerSimonian–Laird random-effects model pooled logHRs. Inter-study heterogeneity was assessed by the I 2 statistic. Results: The combined dataset included 1,323 HCM patients with LGE measurements. Individual study HRs for high LGE burden ranged from 2.75 to 4.80. The pooled HR for SCD or malignant arrhythmias in patients with higher LGE burden was 3.49 (95% CI: 2.57–4.74; p < 0.001), indicating a 3.5-fold increased risk compared with low LGE. Heterogeneity was moderate (I <span style="font-size:10.8333px">2</span> = 40%). Sensitivity analysis, excluding any single study, did not materially change the pooled estimate. Conclusions: In adult HCM patients, higher LGE extent is strongly associated with increased risk of SCD or ventricular arrhythmias. These findings support integrating quantitative LGE assessment into clinical risk stratification to guide implantable cardioverter-defibrillator decisions and patient counselling. Future studies should standardise LGE measurement protocols and investigate how LGE interacts with other risk factors.