Optimal cut off point of LVEF value using cardiovascular magnetic resonance for prognostic stratification in end stage hypertrophic cardiomyopathy

Background In hypertrophic cardiomyopathy (HCM), end-stage disease is traditionally defined by a left ventricular ejection fraction (LVEF) below 50%. This threshold is widely used and supported by observational data linking it to increased mortality. However, this binary definition may oversimplify the continuum of systolic dysfunction and fail to accurately capture its prognostic significance. Purpose To determine the optimal cut-off point of LVEF for predicting long-term all-cause mortality in a large cohort of consecutive end-stage HCM patients. Methods We retrospectively analysed all patients referred for cardiovascular magnetic resonance (CMR) assessment of HCM at three French tertiary centres between 2008 and 2024. The primary endpoint was all-cause mortality, obtained from the French National Death Registry. A conditional inference tree (C-Tree) was applied to identify the optimal cut-off point of LVEF for predicting all-cause mortality. Cox proportional hazards models were used to assess the association between LVEF and mortality, adjusting for relevant clinical and imaging covariates: sex, age, BMI, hypertension, smoking status, diabetes, history of heart failure hospitalisation, history of atrial fibrillation, chronic kidney disease, right ventricular dysfunction and indexed end-diastolic volume. A restricted cubic spline model assessed the continuous relationship between LVEF and all-cause mortality, adjusted for covariates used in the Cox model. Results Among 2,875 eligible patients with HCM, we included 691 patients (mean age 53 ± 7 years, 54% male) with a LVEF <50% for the study. The optimal cut-off point of LVEF for predicting all-cause mortality was 40%. Among those, 492 patients had a LVEF of 40–50%, and 199 a LVEF <40%. After a median follow-up of 8.5 years (IQR 5.9–11.0), 226 deaths occurred. Ten-year survival was approximately 85% in the 40–50% group and 35% in the <40% group (p<0.001). These patients with LVEF < 40% had more advanced structural and functional abnormalities: larger LV end-diastolic volumes (LVEDV indexed 99 ±11 vs 83 ±7 mL/m², p<0.001), higher prevalence of right ventricular dysfunction (28% vs 5%, p<0.001), and greater presence (66% vs 26%) and extent (2.4 ± 1.9 vs 0.6 ± 1.2 segments; p<0.001) of late gadolinium enhancement (LGE). Even after adjustment, a LVEF value <40% was strongly associated with increased mortality (adjusted HR 23.6, 95% CI 14.6–38.1; p<0.001) (Figure 1). Adjusted spline modelling showed a sharp rise in mortality risk below 40%, gradually trending toward a plateau at lower LVEF values (Figure 2). Conclusion Using a large cohort of consecutive end-stage HCM patients, a LVEF threshold of 40% identifies a subgroup with markedly increased mortality, even after adjustment for all traditional prognostic factors. This cut-off is associated with more advanced structural remodelling and a higher fibrosis burden, supporting its clinical relevance in defining end-stage disease in HCM.