JACC: Advances (Aug 2025)

Sex Differences in Children and Adolescents With Hypertrophic Cardiomyopathy

  • Gabrielle Norrish, PhD,
  • Kimberley Hall, BSc,
  • Ella Field, MSc,
  • Elena Cervi, MD,
  • Olga Boleti, MD,
  • Lidia Ziółkowska, MD,
  • Iacopo Olivotto, MD,
  • Sylvia Passantino, MD,
  • Diala Khraiche, MD,
  • Giuseppe Limongelli, MD,
  • Robert G. Weintraub, MD,
  • Aris Anastasakis, MD,
  • Elena Biagini, MD,
  • Luca Ragni, MD,
  • Georgia Sarquella-Brugada, MD,
  • Sergi Cesar, MD,
  • Terrence Prendiville, MD,
  • Karen McLeod, MD,
  • Maria Ilina, MD,
  • Anwar Baban, MD,
  • Tiina H. Ojala, MD,
  • Georgia Spentzou, MD,
  • Vinay Bhole, MD,
  • Feran Gran, MD,
  • Elspeth Brown, MD,
  • Grazia Delle Donne, MD,
  • Bernadette Khodaghalian, MD,
  • Adrian Fernandez, MD,
  • Piers E.F. Daubeney, MD,
  • Katie Linter, MD,
  • Peter Kubus, MD,
  • Orhan Uzun, MD,
  • Regina Bökenkamp, MD,
  • Francesca Raimondi, MD,
  • Chiara Marrone, MD,
  • Constantio Medrano, MD,
  • Esther Gonzalez-Lopez, MD,
  • Ana Siles, MD,
  • Katarzyna Luczak-Wozniak, MD,
  • Tara Bharucha, MD,
  • Satish Adwani, MD,
  • Sabine Klaassen, MD,
  • Fernando J. Castro, MD,
  • Luis Guereta, MD,
  • Hirokuni Yamazawa, MD,
  • Gianfranco Sinagra, MD,
  • Anca Popoiu, MD,
  • Francesca Perin, MD,
  • B. Chana, MD,
  • Hans De Wilde, MD,
  • Torsten.B. Rasmussen, MD,
  • Jens Mogensen, MD,
  • Sujeev Mathur, MD,
  • Fernando Centeno, MD,
  • Zdenka Reinhardt, MD,
  • Roberto Barriales-Villa, MD,
  • Toru Kubo, MD,
  • Tiziana Felice, MD,
  • Cristina Radulescu, MD,
  • Sylvie Schouvey, MD,
  • Melissa Chaker, MD,
  • Juan Pablo Kaski, MD

DOI
https://doi.org/10.1016/j.jacadv.2025.101907
Journal volume & issue
Vol. 4, no. 8
p. 101907

Abstract

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Background: Sex differences have been described in adults with hypertrophic cardiomyopathy (HCM), but it is unknown if similar differences exist in childhood-onset disease. Objectives: This study aimed to investigate the influence of biological sex on the clinical characteristics and outcomes of children with HCM. Methods: An international retrospective cohort of patients diagnosed with nonsyndromic HCM ≤16 years was formed. Sex differences in baseline characteristics and clinical outcomes were investigated. Primary outcome was all-cause mortality or cardiac transplantation. Secondary outcomes include major arrhythmic cardiac event and heart failure event. Results: Of 1,433 patients diagnosed at a median age of 11 years (IQR: 6-14), 471 (33.0%) were female. Although there were no sex differences in phenotype in preadolescent patients (<12 years), adolescent female patients were more likely to have heart failure symptoms (n = 53 [31.9%] vs n = 86 [22.5%]; P = 0.019). Adolescent female patients had larger left atrial size (1.4 z-score [±2.3] vs 2.1 z-score [±2.5]; P = 0.0056) but there was no difference in degree of hypertrophy or proportion with obstructive disease. Over a median follow-up of 5.3 years (IQR: 2.9, 8.0) annual incidence of all-cause mortality or cardiac transplantation, major arrhythmic cardiac event or heart failure events did not vary by sex. Conclusions: Young female patients with HCM are more likely to experience heart failure symptoms and have echocardiographic features of diastolic impairment. Despite differences in phenotype, outcomes during childhood and young adulthood are not different. Further studies are required to explore the underlying mechanisms for these observed differences.

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