Abstract
<jats:title>ABSTRACT</jats:title> <jats:sec> <jats:title>Background</jats:title> <jats:p>Neonatal-onset hypertrophic cardiomyopathy (HCM) is a rare condition with limited data regarding clinical presentation, genetic background, and long-term outcomes. We aimed to characterize the phenotype and prognosis of HCM presenting in neonates.</jats:p> </jats:sec> <jats:sec> <jats:title>Methods</jats:title> <jats:p>This is a multicenter retrospective study including patients diagnosed with HCM before 1 year of age. Neonatal-onset HCM was defined as presentation ≤28 days of life. Clinical, genetic, instrumental data, treatment, and outcomes were collected. Primary outcome included overall and cardiac survival, major arrhythmic events (MAEs), implantable cardioverter-defibrillator (ICD) implantation, and cardiac surgery.</jats:p> </jats:sec> <jats:sec> <jats:title>Results</jats:title> <jats:p>Among 321 pediatric HCM, 21% were diagnosed during infancy and 75% were neonates. Median age at diagnosis was 1 day (IQR 0–6), 82% presented within the first week of life. Prenatal suspicion was in 25%. At presentation, 41% were symptomatic. RASopathies represented the most common etiology (41%), followed by gene-elusive (31%), mitochondrial/inborn errors of metabolism (18%), and sarcomeric (8%). Left ventricular outflow tract obstruction was frequent in sarcomeric and RASopathy. Overall survival was 92% and cardiac survival was 96% at 2 years; long-term survival was 88% at 30 years. ICDs were implanted in 8%; 21% required cardiac surgery. Survival free from ICD was 40% at 15 year and 47% from myectomy. All events occurred in patients presenting within the first weeks of life.</jats:p> </jats:sec> <jats:sec> <jats:title>Conclusions</jats:title> <jats:p>Neonatal-onset HCM is characterized by etiologic heterogeneity, predominance of syndromic and non-sarcomeric etiologies, and long-term cardiovascular morbidity. Presentation within the first days of life identifies a high-risk subgroup requiring intensive surveillance and specialized multidisciplinary management.</jats:p> </jats:sec>