Abstract 2159: Relationship Between Sex, Shape, and Substrate in Hypertrophic Cardiomyopathy
Background: Hypertrophic cardiomyopathy (HCM) is a disease(s) of extraordinary genetic and clinical heterogeneity. Recently, significant sex-related differences in HCM were reported with females being older at diagnosis and exhibiting greater left ventricular outflow tract obstruction (LVOTO) than males. However, this effect of sex on HCM phenotype did not consider the effect of either septal morphology or underlying pathogenic substrate. Here, we sought to evaluate the influence of sex on the HCM phenotype in a large cohort of unrelated patients with genetically and morphologically classified HCM.
Methods: Comprehensive genotyping of 15 HCM-susceptibility genes encoding myofilament and Z-disc proteins of the cardiac sarcomere has been completed for 382 unrelated patients with HCM (210 male, mean left ventricular wall thickness (MLVWT) 21.5 ± 6 mm). Blinded to the genotype, the septal morphology as visualized by echocardiography was graded as reverse curvature-, sigmoidal-, apical-, or neutral contour-HCM.
Results: Consistent with previous observations derived from other patient cohorts, overall females were
significantly older at diagnosis (45.1 ± 20 vs. 35.8 ± 17 years; p<0.001),
had greater LVOTO (53.5 ± 45 vs. 41.7 ± 42 mmHg; p = 0.001),
were more likely to have concomitant hypertension (19% vs 11%, p = 0.02), and
had a higher rate of surgical myectomy (49% vs 36%, p = 0.01) than males.
However, these gender-based differences were seen only among patients with either mutation-negative HCM or sigmoidal shaped HCM (p < 0.0001). There was no discernible effect of sex on age at diagnosis or degree of obstruction among either the 145 patients (66 female) with myofilament HCM, the 131 patients with reverse septal curvature or the 37 patients with apical-HCM.
Conclusions: In this largest published cohort of comprehensively genotyped and morphologically classified patients with clinically diagnosed HCM, we observed that the striking sex-related differences in the clinical phenotype are confined largely to mutation negative/sigmoidal shaped HCM. Sex is not a significant genetic modifier in sarcomeric HCM.