Adiposity as risk factor in inherited cardiomyopathies
Adiposity as risk factor in inherited cardiomyopathies
Inherited cardiomyopathies are a heterogeneous group of myocardial diseases characterized by structural and functional abnormalities of the myocardium and are associated with an increased risk of morbidity and mortality. Although genetic variants play a central role in the development of these disorders, carriers often exhibit considerable variability in disease expression and clinical course. This suggests that additional factors modify disease expression. This thesis of Belend Mahmoud investigates whether adiposity can influences disease progression in inherited cardiomyopathies.
The first part of this thesis examined the role of obesity. A review of the literature suggests that obesity is associated with the development of dilated cardiomyopathy, although its impact on disease progression remains insufficiently understood. In a preclinical phospholamban (PLN) cardiomyopathy mouse model, obesity induced mitochondrial metabolic alterations but did not accelerate the development of the disease phenotype. In addition, a nationwide cohort study demonstrated that obesity and other lifestyle factors were not associated with clinical outcomes in patients with the PLN p.(Arg14del) variant. The second part of this thesis focuses on epicardial adipose tissue (EAT), a visceral fat depot located in direct contact with the myocardium. A larger EAT volume was associated with a more severe disease phenotype and an increased risk of life-threatening ventricular arrhythmias in both PLN cardiomyopathy and hypertrophic cardiomyopathy (HCM). In HCM, greater EAT volume was also associated with an increased risk of heart failure outcomes.
In conclusion, this thesis demonstrates that obesity plays a limited role in PLN cardiomyopathy, whereas EAT is associated with a more severe clinical course in both PLN cardiomyopathy and HCM. These findings support a potential role for the quantification of EAT in the risk stratification of inherited cardiomyopathies and provide new directions for future research and the development of therapeutic strategies.