Contributor: Nick Hawkes

Hypertrophic Cardiomyopathy (HCM) is a genetic condition characterized by unexplained left ventricular hypertrophy often with a wall thickness of greater than or equal to 15mm. it often disproportionately affects the septum and can lead to development of left ventricular outflow obstruction (LVOTO). Myectomy is a targeted surgical reduction in LV mass — thereby reducing LVOTO. Nijenkamp et al analyzed samples obtained during myectomy as well as pre-myectomy echocardiographic markers of diastolic dysfunction in 71 HCM patients. The authors also compared control myocardium to HCM. In this study, female HCM patients presented later, had a higher degree of diastolic dysfunction, a higher amount of fibrosis, more compliant titin, and greater septal thickness when indexed to body surface area (IVSi) compared to males.

Data were obtained from 27 female and 44 male patients undergoing myectomy, with average ages of 50 +/- 13 and 43 +/- 13 years of age respectively (p<0.05). The E/e’ ratio, E/A ratio, and TR velocity were measurements of diastolic dysfunction. The E/e’ ratio was 23.8 +/- 7.8 for females vs 14.8 +/- 3.4 for males (p<0.0001), E/A ratio was 1.8 +/- 1.0 vs 1.3 +/- 0.5 (p<0.05), and TR velocity was 2.61 +/- 0.54 for women vs 2.15 +/- 0.54 for men (p<0.05). All values were corrected for age in the statistical model.

The mean IVS thickness in the study population was 23 +/- 7mm with no difference observed between women and men. However, when body surface area was factored in, female patients had increased IVSi (13.5+/- 5.3 vs 10.5 +/- 1.8 mm/m2), p<0.001.

Sex has an effect on titin isoforms with women showing an increased N2BA/N2B ratio compared to men (p<0.05). N2BA is the more compliant titin isoform. Staining for fibrosis showed a 6.42 +/- 0.95% collagen volume fraction (CVF) for women compared to 4.18 +/- 0.66% for men (p<0.05). Of note, passive tension of sarcomeres was elevated in HCM compared to controls, but there was no significant difference among male and female HCM patients.

No study is perfect. Data were from patients undergoing myectomy, and did not include those who underwent an alcohol septal ablation (ASA), or who didn’t have obstructive physiology. Also, the percentage of the cohort with MYBPC3 mutations was high, which may limit generalizability.

In a heartbeat… Women with HCM are more likely to undergo myectomy at an older age, with more advanced diastolic dysfunction, increased titin compliance, and more interstitial fibrosis, suggesting sex-based differences in disease process. Disease severity may also be underestimated in women with a similar IVS, but higher IVSi.

Study Link: Sex Differences at the Time of Myectomy in Hypertrophic Cardiomyopathy