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Research Article: Prognostic factors for cardiovascular-related mortality in pediatric hypertrophic cardiomyopathy: a retrospective cohort study with survival analysis and X-tile stratification

Date Published: 2026-04-21

Abstract:
To identify prognostic factors associated with cardiovascular-related mortality in children with hypertrophic cardiomyopathy (HCM) and to explore outcome-oriented risk stratification using optimal cut-off values for continuous variables. This retrospective cohort study included 41 children diagnosed with HCM at The First Affiliated Hospital of Guangxi Medical University between January 1, 2013, and October 1, 2024. Baseline demographic characteristics, clinical manifestations, chest radiographic findings, electrocardiographic features, echocardiographic parameters, and serum biochemical indices were collected. Cardiovascular-related mortality was defined as the primary endpoint, with follow-up censored at the last clinical contact for patients lost to follow-up. Univariate Cox proportional hazards regression was performed to screen variables associated with mortality. Optimal cut-off values for continuous variables were determined using X-tile software, followed by Kaplan–Meier survival analysis and log-rank testing to compare survival differences between risk strata. Univariate Cox analysis showed no significant associations between baseline categorical clinical variables and cardiovascular-related mortality, with only a borderline sex-related difference observed. In contrast, several echocardiographic parameters were significantly associated with mortality. Increased left ventricular end-diastolic diameter (LVEDd) (HR?=?1.084, p =?0.049), left ventricular end-systolic diameter (LVESd) (HR?=?1.136, p =?0.018), interventricular septal thickness (IVSd) (HR?=?1.145, p =?0.037), and left ventricular posterior wall thickness (LVPWd) (HR?=?1.718, p =?0.001) were associated with higher risk, whereas higher left ventricular ejection fraction (LVEF) (HR?=?0.953, p =?0.020) and left ventricular fractional shortening (LVFS) (HR?=?0.924, p =?0.016) were associated with reduced risk. Elevated creatine kinase (CK), lactate dehydrogenase (LDH), cardiac troponin I (cTnI), aspartate aminotransferase (AST), and alanine aminotransferase (ALT) were also significantly associated with increased mortality (all p <?0.05). X-tile–derived cut-off values further stratified survival, with significantly worse outcomes observed in patients above threshold values for LVEDd (38?mm), LVESd (23?mm), IVSd (12?mm), LVPWd (9?mm), CK (179 U/L), LDH (416 U/L), cTnI (0.06?ng/mL), AST (44 U/L), and ALT (38 U/L), and below threshold values for LVEF (60%) and LVFS (32%) (multiple p <?0.05, several p <?0.001). This single-center real-world cohort suggests that cardiovascular-related mortality in pediatric HCM is more consistently associated with echocardiographic indicators reflecting left ventricular remodeling, hypertrophic burden, and systolic function, as well as biochemical markers of myocardial injury and metabolic stress. X-tile–based stratification of continuous variables provides intuitive and potentially actionable risk thresholds for intra-cohort follow-up and early risk warning. However, the generalizability of these thresholds requires validation in larger, multicenter cohorts.

Introduction:
Pediatric hypertrophic cardiomyopathy (HCM) is one of the most common inherited cardiomyopathies in childhood and is characterized by myocardial hypertrophy, reduced left ventricular compliance, impaired cardiac function, and a wide spectrum of arrhythmic manifestations ( 1–3 ). Among children and adolescents, HCM represents a major cause of sudden cardiac death of cardiac origin ( 4 ). Compared with adult HCM, pediatric HCM exhibits greater heterogeneity in age at onset, etiological composition, clinical…

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