Background: Despite advances in our understanding of the genetic causes of hypertrophic cardiomyopathy (HCM), a large portion of this patient population do not carry sarcomere gene mutations when screened. It remains largely unknown why patients without sarcomere mutations develop asymmetric myocardial hypertrophy.
Methods: We performed a retrospective analysis of probands with HCM who underwent genetic testing to determine if clinical phenotypes were different depending on sarcomere mutation status. A medical history, three generation family history and clinical phenotyping were performed on 127 probands with HCM. Genetic screening was performed using clinically available HCM genetic testing panels.
Results: We found that probands with HCM with pathogenic sarcomere mutations were over three times more likely to have a family history of HCM (66% vs 17%, p<0.0001) and were diagnosed with HCM at a much younger age (32 vs 51 years old, p<0.0001). In contrast, probands with HCM without sarcomere mutations were significantly more obese (body surface area p=0.003, body mass index p=0.04 adjusted for age) and were more likely to present with left ventricular outflow tract obstruction (p=0.0483).
Conclusion: Patients with sarcomere mutation negative HCM present at an older age and are more obese compared with patients with sarcomere mutation positive HCM. The role of ageing and obesity in asymmetric myocardial hypertrophy warrants further investigation.
Keywords: cardiomyopathies; cardiomyopathy; genetic diseases; hypertrophic; inborn.
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