Abstract 4348778: Natural History and Outcomes of Massive Left Ventricular Hypertrophy in Childhood Hypertrophic Cardiomyopathy

Background: Massive left ventricular hypertrophy (mLVH) is a risk factor for sudden cardiac death (SCD) in children with hypertrophic cardiomyopathy (HCM). However, little else is understood about pediatric mLVH. Here we compare pediatric HCM patients with and without mLVH. Methods: This was a retrospective cohort study using two HCM databases, the Sarcomeric Human Cardiomyopathy Registry and the International Paediatric Hypertrophic Cardiomyopathy Consortium. Pediatric onset mLVH was defined as maximal LV wall thickness (MLVWT) ≥30 mm or MLVWT z-score ≥ +20 at <18 years of age. A comparison group with HCM and no documented mLVH at <18 years was identified. HCM phenocopies were excluded. Demographic and clinical data were collected. Composite outcomes included: major ventricular arrhythmia (MVA) - SCD, aborted SCD, appropriate ICD therapy; heart failure (HF) - NYHA class III/IV, transplant, heart failure death, LVEF <50%; and major adverse cardiac events (MACE) - any MVA or HF outcomes excepting LVEF <50%, or stroke. Time-to-event analyses were performed using Cox proportional hazards models. Serial MLVWT data were collected for the mLVH group (censored after myectomy or transplant). Results: We included 587 patients: 186 with mLVH and 401 without. Age at HCM diagnosis was younger (9.2 v. 13.6 years; p <0.001) and sarcomeric genetic variants more prevalent in children with mLVH (table 1). They were also more likely to experience MACE [unadjusted HR 2.6 (95%CI 1.7-3.9)], MVA [HR 3.1 (1.8-5.2)], and HF [HR 1.9 (1.1-3.1)]. These associations remained significant when adjusted for sex and age at HCM diagnosis (figure 2). In 115 patients with serial MLVWT data, comparison of first and last (median ages 11.6 and 16.9 years) measurements showed increased absolute MLVWT (median 26 v. 31 mm, p <0.001) but no change in z-score (median +22 v. +23, p = 0.25). The last MLVWT recorded was less than the largest MLVWT recorded in 47 (41%) patients including 25 (22%) in whom the reduction was >5 mm. At last evaluation, 25 (22%) patients no longer met z-score criteria for mLVH (18 with prior MLVWT ≥30 mm). Conclusions: mLVH is an important phenotypic finding in children with HCM which disproportionately affects those diagnosed in early childhood with sarcomeric disease, who are more likely to experience adverse HCM-related events. Apparent regression of mLVH is seen in a significant minority of patients, the mechanisms and implications of which require further evaluation.