Female patients with stage II hypertrophic cardiomyopathy exhibited more severe cellular remodeling, including lower capillary density and more fibrosis, compared to men, while progression to stage IV was marked by a significant reduction in capillary density.
Observational (n=94)
Yes
Female patients with stage II hypertrophic cardiomyopathy exhibit more advanced cellular remodeling than males at the time of myectomy, and reduced capillary density may drive progression to end-stage heart failure.
p-value: p=<0.05
Hypertrophic cardiomyopathy (HCM) is the most frequent genetic cardiac disease with a prevalence of 1:500 to 1:200. While most patients show obstructive HCM and a relatively stable clinical phenotype (stage II), a small group of patients progresses to end-stage HCM (stage IV) within a relatively brief period. Previous research has shown sex-differences in stage II HCM with more diastolic dysfunction in female than in male patients. Moreover, female patients more often show progression to heart failure. Here we investigated if differences in functional and structural properties of the heart may underlie sex-differences in disease progression from stage II to stage IV HCM. Cardiac tissue from stage II and IV patients was obtained during myectomy (n = 54) and heart transplantation (n = 10), respectively. Isometric force was measured in membrane-permeabilized cardiomyocytes to define active and passive myofilament force development. Titin isoform composition was assessed using gel electrophoresis, and the amount of fibrosis and capillary density were determined with histology. In accordance with disease stage-dependent adverse cardiac remodeling end-stage patients showed a thinner interventricular septal wall and larger left ventricular and atrial diameters compared to stage II patients. Cardiomyocyte contractile properties and fibrosis were comparable between stage II and IV, while capillary density was significantly lower in stage IV compared to stage II. Women showed more adverse cellular remodeling compared to men at stage II, evident from more compliant titin, more fibrosis and lower capillary density. However, the disease stage-dependent reduction in capillary density was largest in men. In conclusion, the more severe cellular remodeling in female compared to male stage II patients suggests a more advanced disease stage at the time of myectomy in women. Changes in cardiomyocyte contractile properties do not explain the progression of stage II to stage IV, while reduced capillary density may underlie disease progression to end-stage heart failure.
Nijenkamp et al. (Tue,) conducted a observational in Hypertrophic cardiomyopathy (n=94). Stage IV (end-stage) hypertrophic cardiomyopathy vs. Stage II hypertrophic cardiomyopathy and non-failing controls was evaluated on Capillary density and cellular remodeling (p=<0.05). Female patients with stage II hypertrophic cardiomyopathy exhibited more severe cellular remodeling, including lower capillary density and more fibrosis, compared to men, while progression to stage IV was marked by a significant reduction in capillary density.
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