Incremental prognostic value of extracellular volume fraction in hypertrophic cardiomyopathy in a large contemporary cohort

Left ventricular (LV) myocardial extracellular volume (ECV), derived from cardiac magnetic resonance (CMR) T1 mapping, reflects diffuse interstitial fibrosis and has emerged as a quantitative marker of adverse myocardial remodeling in hypertrophic cardiomyopathy (HCM). We aimed to determine the independent prognostic value of ECV beyond established clinical and imaging variables in a large contemporary HCM cohort. We evaluated 831 consecutive patients with ejection fraction (EF) ≥ 50% and HCM who underwent contrast-enhanced multiparametric CMR, including ECV and quantification of late gadolinium enhancement (LGE) between 2012-2021. Modified look-locker Inversion recovery (MOLII) sequence was used for T1 mapping according to institutional protocol. LGE was analyzed on phase-sensitive inversion recovery short-axis left ventricular images and quantified using a signal intensity threshold of ≥6 standard deviations above the mean of reference myocardium. The primary endpoint was a composite of all-cause mortality, appropriate implantable cardioverter-defibrillator (ICD) therapy, or heart transplantation. Baseline characteristics are summarized in Figure 1A. Median follow-up was 5.9 (2.7–8.3) years. The composite endpoint occurred in 106 patients (12.7%), including 94 deaths (11.3%), 11 appropriate ICD discharges (1.3%), and 1 heart transplantation (0.1%). In multivariable Cox proportional hazards analysis (calculating Hazard ratio or HR with 95% confidence interval or CI], higher age (1.07 [1.04–1.09]), New York Heart Association class ≥II (2.60 [1.35–4.99]), and higher ECV (1.07 [1.03-1.11]) were associated with higher risk of primary outcome, while septal reduction therapy was associated with lower risk (HR 0.51, 95% CI 0.28–0.94, p=0.031). Due to significant collinearity between ECV and % LGE (r=0.33, p<0.001), only ECV was entered in multivariable survival analysis. Restricted cubic spline modeling (Figure 1B) demonstrated that the risk of primary endpoint increased more steeply beyond 32% ECV. Patients with ECV ≥32% had significantly lower event-free survival compared with those with ECV <32% (adjusted HR 2.03, 95% CI 1.21-3.39, p=0.0017; Figure 1C). In a large contemporary HCM cohort, myocardial ECV was independently associated with long-term adverse outcomes. Multiparametric CMR may provide incremental prognostic information and enhance risk stratification in patients with HCM.