儿童肥厚型心肌病中重度左心室肥厚的自然史：多注册研究分析

原文

BACKGROUND: Massive left ventricular hypertrophy (LVH) is a risk factor for sudden cardiac death in children with hypertrophic cardiomyopathy (HCM), but little is understood about its natural history. METHODS: Patients with pediatric-onset HCM identified from 2 registries (SHaRe [Sarcomeric Human Cardiomyopathy Registry] and IPHCC [International Paediatric Hypertrophic Cardiomyopathy Consortium]) with or without massive LVH were compared. Massive LVH was defined as absolute maximal left ventricular wall thickness (MLVWT) ≥30 mm or MLVWT z score ≥+20 at <18 years of age. Data from SHaRe and IPHCC include encounters from January 1960 through March 2024 and January 1970 through March 2024, respectively. Demographic, clinical, and serial MLVWT data were collected. Composite outcomes included major ventricular arrhythmia event (sudden cardiac death, aborted sudden cardiac death, or appropriate implantable cardioverter defibrillator therapy); heart failure (HF) event (left ventricular ejection fraction <50%, New York Heart Association class III or IV, transplant, or HF-related death); major adverse cardiac event (stroke or any major ventricular arrhythmia or HF outcome aside from left ventricular ejection fraction <50%); and HCM-related mortality (sudden cardiac death or HF-related death). Time-to-event analyses were performed using Cox proportional hazards models. RESULTS: We identified 587 patients (54 female [30%]). In 186 children with massive LVH, age at diagnosis was younger (median, 9.2 years [interquartile range, 2.1-13.1 years]) versus 13.6 years (9.7-15.5 years; P<0.001) and sarcomeric genetic variants more prevalent (72% versus 61%; P=0.034), as was HCM-related mortality (unadjusted hazard ratio, 3.3 [95% CI,1.2-9.7]; P=0.026), major adverse cardiac events (hazard ratio, 2.6 [1.7-3.9]; P<0.001), major ventricular arrhythmia (hazard ratio, 3.1 [1.8-5.2]; P<0.001), and HF (hazard ratio, 1.9 [1.1-3.1]; P=0.013). These associations remained significant when adjusted for sex and age at HCM diagnosis. In 115 patients with massive LVH with serial MLVWT data (62%), MLVWT increased significantly from first to last measurements (median, 26 mm [interquartile range, 18-32 mm] versus 31 mm [26-35 mm]; P<0.001), but there was no difference between z scores (median, +22 [interquartile range, +18 to +26] versus +23 [+20 to +28]; P=0.25). The last absolute MLVWT recorded was >5 mm less than the largest recorded MLVWT in 25 patients (22%). CONCLUSIONS: In pediatric HCM, massive LVH disproportionately affects those diagnosed in early childhood with sarcomeric disease, with increased risk for adverse events. Significant MLVWT regression is seen in nearly a quarter of patients.