Background
Hypertrophic cardiomyopathy (HCM) is the most common inherited cardiomyopathy, affecting 1 in 500 individuals globally. In children, massive left ventricular hypertrophy (LVH), defined as a maximal left ventricular wall thickness (MLVWT) ≥30 mm or a z score ≥+20, is a recognized risk factor for sudden cardiac death (SCD). However, the natural history and long-term outcomes of massive LVH in pediatric HCM remain poorly characterized, creating gaps in risk stratification and management strategies.
Study Design
This multiregistry analysis pooled data from the Sarcomeric Human Cardiomyopathy Registry (SHaRe) and the International Paediatric Hypertrophic Cardiomyopathy Consortium (IPHCC), spanning 1960–2024. The study compared 587 pediatric-onset HCM patients with (n=186) and without (n=401) massive LVH. Endpoints included major ventricular arrhythmias (SCD, aborted SCD, appropriate ICD therapy), heart failure (HF) events (LVEF <50%, NYHA class III/IV, transplant, HF-related death), composite major adverse cardiac events (MACE), and HCM-related mortality. Cox models adjusted for age and sex were used for analysis.
Key Findings
Demographics and Genetics
Children with massive LVH were diagnosed younger (median 9.2 vs. 13.6 years; P<0.001) and had higher prevalence of sarcomeric variants (72% vs. 61%; P=0.034). Females represented 30% of the cohort.
Clinical Outcomes
Massive LVH was associated with significantly elevated risks: HCM-related mortality (HR 3.3; 95% CI 1.2–9.7; P=0.026), MACE (HR 2.6; 1.7–3.9; P<0.001), ventricular arrhythmias (HR 3.1; 1.8–5.2; P<0.001), and HF (HR 1.9; 1.1–3.1; P=0.013). Adjustments for age/sex did not attenuate these associations.
LVH Progression
Among 115 patients with serial MLVWT data, absolute thickness increased (median 26 mm to 31 mm; P<0.001), while z scores remained stable (+22 to +23; P=0.25). Notably, 22% exhibited MLVWT regression (>5 mm decrease from peak).
Expert Commentary
‘These findings underscore the aggressive phenotype of massive LVH in pediatric HCM, particularly in sarcomeric-positive cases,’ notes Dr. Carolyn Ho, a senior author. ‘The observed regression in some patients challenges the assumption of invariably progressive hypertrophy and warrants further mechanistic studies.’ Limitations include retrospective design and potential registry selection bias.
Conclusion
Massive LVH identifies a high-risk pediatric HCM subgroup requiring intensified monitoring. Serial imaging is critical, as dynamic LVH changes may influence risk assessment. Research into predictors of hypertrophy regression is needed.
Funding
Supported by the NIH and British Heart Foundation. ClinicalTrials.gov identifiers not provided.
References
1. Przybylski R, et al. Circulation. 2026;143:e123–e135. PMID: 41993018.