Enhanced risk stratification in hypertrophic cardiomyopathy through the integration of extracellular volume fraction on cardiovascular magnetic resonance

Abstract Background Myocardial scar and diffuse interstitial fibrosis can be assessed non-invasively using late gadolinium enhancement (LGE) and extracellular volume fraction (ECV) on contrast-enhanced cardiovascular magnetic resonance (CMR). While extensive LGE is an established marker for sudden cardiac death (SCD) and heart failure (HF) in hypertrophic cardiomyopathy (HCM), the prognostic value of ECV remains unclear. Purpose This study investigated the incremental prognostic value of ECV beyond LGE in patients with HCM. Methods Consecutive HCM patients undergoing CMR in 2012–2024 were analyzed. LGE and global ECV were quantified, and their associations with the primary endpoint of HCM-related events–a composite of SCD events, HF events, and HCM-related death–were examined. Results Among 990 patients (median age 58 IQR 49–67 years; male 68.3%), 64 (6.5%) experienced the primary endpoint over a median follow-up of 3.2 (IQR 1.3–5.8) years. LGE (median 7.1%, IQR 2.3–16.9%) and ECV (median 29.0%, IQR 26.6–32.0%) were moderately correlated (R=0.604, p0.001). Risk of the primary endpoint, as well as individual outcomes of SCD and HF events, increased with both higher LGE (unadjusted HR 1.04, 95% CI 1.03–1.06, per 1%) and ECV (unadjusted HR 1.16, 95% CI 1.12–1.20, per 1%), with optimal cutoffs of LGE≥27% and ECV≥35% determined by maximally selected rank statistics. Patients with ECV≥35% had more symptoms, a more severe phenotype with greater systolic and diastolic dysfunction, and more pathogenic gene variants. Patients with elevated ECV had significantly higher HCM-related event rates, even those without extensive LGE (using the cutoff of either ≥27% or ≥15%). ECV remained significantly associated with the primary endpoint (adjusted HR 1.08, 95% CI 1.02–1.15, per 1%) after adjustment for key disease variables, including left ventricular ejection fraction and LGE, and demonstrated significant incremental prognostic value over LGE. Notably, the association of ECV with HCM-related events was stronger than that of LGE in multivariable models. The prognostic value of ECV was consistent across various subgroups, including low-risk patients. Conclusion Increased ECV is an independent predictor of HCM-related outcomes. Even among patients with low LGE burden, elevated ECV identifies a high-risk subgroup. Incorporating global ECV assessment into routine CMR evaluations of HCM patients can enhance patient risk stratification and guide management.Incremental value of ECV in HCM Predictors of HCM-related events