Incremental prognostic value of extracellular volume fraction in hypertrophic cardiomyopathy in a large contemporary cohort
TL;DR
In a large contemporary HCM cohort, myocardial ECV was independently associated with long-term adverse outcomes and Multiparametric CMR may provide incremental prognostic information and enhance risk stratification in patients with HCM.
Abstract
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.Figure