Sex Differences in Children and Adolescents With Hypertrophic Cardiomyopathy

Abstract

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.

Keywords: adolescent; hypertrophic cardiomyopathy; phenotype; sex differences.

Graphical abstract

Figure 1

Sex Distribution by Age of Baseline Evaluation

Central Illustration

Sex Differences in Children With Hypertrophic Cardiomyopathy HCM = hypertrophic cardiomyopathy.

Figure 2

Heart Failure Events by Sex (A) Graph shows cumulative incidence of heart failure events during follow-up by sex (male 0.51 per 100 patient-years [95% CI: 0.35-0.73] vs female 0.67 per 100 patient-years [95% CI: 0.43-1.03]; P = 0.342) (B) Bar chart shows age at the time of heart failure event by sex.

Figure 3

Arrhythmic Events by Sex (A) Graph shows freedom from arrhythmic events during follow-up by sex (male 1.88 per 100 patient-years [95% CI: 1.55-2.29] vs female 1.41 per 100 patient-years [95% CI: 1.04-1.91]; P = 0.112) (B) Bar chart shows age at the time of arrhythmic event by sex. MACE = major arrhythmic cardiac event.