Relationship between sex, shape, and substrate in hypertrophic cardiomyopathy.
BACKGROUND
Hypertrophic cardiomyopathy (HCM) is a disease characterized by substantial genetic, morphologic, and prognostic heterogeneity. Recently, sex-related differences in HCM were reported, with women being older at diagnosis and exhibiting greater left ventricular outflow tract obstruction than men. 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 13 HCM-susceptibility genes encoding myofilament and Z-disc proteins of the cardiac sarcomere was performed previously on 382 unrelated patients with HCM. Blinded to the genotype, the septal morphology was graded as reverse-curvature, sigmoidal, apical, or neutral-contour HCM by echocardiography.


RESULTS
Overall, women (a) were significantly older at diagnosis (45.1 +/- 20 vs 35.8 +/- 17 years, P < .001), (b) had greater left ventricular outflow tract obstruction (53.5 +/- 45 vs 41.7 +/- 42 mm Hg, P = .009), (c) were more likely to have concomitant hypertension (19% vs 11%, P = .02), and (d) had a higher rate of surgical myectomy (49% vs 36%, P = .01) than men. Interestingly, these sex-based differences were apparent only among patients with sigmoidal HCM (P < .001).


CONCLUSIONS
In this largest 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 the subset of mutation-negative sigmoidal HCM. Whereas mutations within the sarcomere appear to dominate the disease process, in their absence, sex has a significant modifying effect, specifically noted in cases of sigmoidal HCM.
Bos
J Martijn
JM
Department of Internal Medicine, Division of Cardiovascular Diseases, Mayo Clinic, Rochester, MN 55905, USA.
Theis
Jeanne L
JL
Tajik
A Jamil
AJ
Gersh
Bernard J
BJ
Ommen
Steve R
SR
Ackerman
Michael J
MJ
D000328:Adult; D002312:Cardiomyopathy, Hypertrophic / Q000000981:diagnostic imaging* / Q000235:genetics*; D004452:Echocardiography; D005260:Female; D018740:Genetic Heterogeneity; D006801:Humans; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D012720:Severity of Illness Index; D012737:Sex Factors