Incremental prognostic value of left ventricular global function index, a novel marker of adaptive cardiac remodelling, in hypertrophic cardiomyopathy in a large contemporary cohort

Background In hypertrophic cardiomyopathy (HCM), adaptive remodelling may affect passive left ventricular (LV) elasticity, myocardial mass and LV dimensions. Left ventricular global function index (LVGFI) on cardiac magnetic resonance (CMR), which integrates LV stroke volume, volumes, and mass, may provide incremental value beyond LV ejection fraction (LVEF), in terms of LV remodelling. We sought to measure its incremental prognostic value in a large contemporary HCM cohort. Methods We studied 2,874 consecutive patients with HCM and LVEF ≥50% undergoing contrast-enhanced CMR (between 2006-2021). %LVGFI (LV stroke volume/LV global volume) *100). LV global volume was defined as the sum of LV mean cavity volume [(LV end diastolic volume + LV end systolic volume)/2] and myocardial volume (LV mass/myocardial density of 1.05 g/ml). In addition, LGE was analyzed both as a continuous and categorical variable 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 mortality, appropriate internal cardioverter defibrillator (ICD) discharge, or heart transplantation. Results Baseline characteristics are shown in Figure 1A. Median follow-up was 8.6 (5.2-11.9) years. The composite endpoint occurred in 455 (16%) patients (of which 415 (14%) was mortality, 34 (1.2%) was appropriate ICD discharge, and 6 (0.2%) was transplantation). On multivariable Cox proportional hazards analysis (adjusted for obstructive status [nonobstructive, obstructive with and without septal reduction therapy] and relevant clinical and CMR variables), the following variables remained statistically significant (Hazard ratio or HR and [95% confidence interval or CI], all p<0.001): higher age (1.06 [1.05–1.07], male sex (HR 0.73 [0.59–0.90]), NYHA Class II or more vs I (1.67 [1.26–2.19]), obstructive HCM with septal reduction therapy (0.61 [0.46–0.81]), % LGE (1.04 [1.02-1.06], LVGFI (0.97 [0.96–0.99]). Restricted cubic spline modelling (Figure 1B) demonstrated that the risk of primary endpoint increased more steeply below LVGFI of 40%. Patients with LVGFI <40% had significantly lower event-free survival compared with those with LVGFI≥40% (adjusted HR 1.37, 95% CI 1.07–1.75; p=0.002, Figure 1C). Conclusions In this contemporary HCM cohort, LVGFI, a potentially more comprehensive marker of adaptive LV remodelling, was independently associated with long-term adverse outcomes and provided incremental prognostic information beyond established clinical/phenotypic variables, including LGE. A threshold of 40 for %LVGFI may help refine risk stratification in HCM.