Abstract
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.
Highlights
Hypertrophic cardiomyopathy (HCM) is the most prevalent genetic cardiac disease occurring in 2–5 per 1000 individuals, and is caused by mutations in genes encoding sarcomeric proteins.[1–3] The defining feature of HCM is unexplained left ventricular (LV) hypertrophy that mainly affects the interventricular septum (IVS)
left atrial diameter (LAD) and LV end-diastolic diameter (LVEDD) were significantly higher in stage IV compared to stage II HCM.[23]
We investigated if cardiac tissue properties were more severely affected at stage IV than stage II of HCM, and whether these properties change in a sex-specific manner
Summary
Hypertrophic cardiomyopathy (HCM) is the most prevalent genetic cardiac disease occurring in 2–5 per 1000 individuals, and is caused by mutations in genes encoding sarcomeric proteins.[1–3] The defining feature of HCM is unexplained left ventricular (LV) hypertrophy that mainly affects the interventricular septum (IVS). Hypertrophic cardiomyopathy (HCM) is the most prevalent genetic cardiac disease occurring in 2–5 per 1000 individuals, and is caused by mutations in genes encoding sarcomeric proteins.[1–3]. The defining feature of HCM is unexplained left ventricular (LV) hypertrophy that mainly affects the interventricular septum (IVS). The diseased myocardium is characterized by increased interstitial fibrosis, myofibrillar and cardiomyocyte disarray and vascular abnormalities.[4,5]. Clinical symptoms generally appear between 20–50 years of age and can range from shortness of breath to atrial fibrillation. In the majority of patients, these symptoms can be managed with therapy, and individuals have a normal life expectancy.[6]. A subset of patients suffers from life-threatening complications such as sudden cardiac arrest at a young age or progresses to end-stage heart failure.[6]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
