Inflammation across the spectrum of hypertrophic cardiac phenotypes

The hypertrophic cardiomyopathy phenotype encompasses a heterogeneous spectrum of genetic and acquired diseases characterized by the presence of left ventricular hypertrophy in the absence of abnormal cardiac loading conditions. This umbrella diagnosis includes the classic hypertrophic cardiomyopathy (HCM), due to sarcomere protein gene mutations, and its phenocopies caused by intra- or extracellular deposits, such as Fabry disease (FD) and cardiac amyloidosis (CA). All these conditions share a wide phenotypic variability which results from the combination of genetic and environmental factors and whose pathogenic mediators are poorly understood so far. Accumulating evidence suggests that inflammation plays a critical role in a broad spectrum of cardiovascular conditions, including cardiomyopathies. Indeed, inflammation can trigger molecular pathways which contribute to cardiomyocyte hypertrophy and dysfunction, extracellular matrix accumulation, and microvascular dysfunction. Growing evidence suggests that systemic inflammation is a possible key pathophysiologic process potentially involved in the pathogenesis of cardiac disease progression, influencing the severity of the phenotype and clinical outcome, including heart failure. In this review, we summarize current knowledge regarding the prevalence, clinical significance, and potential therapeutic implications of inflammation in HCM and two of its most important phenocopies, FD and CA.

Automated summary

The hypertrophic cardiomyopathy phenotype is a group of genetic and acquired diseases characterized by left ventricular hypertrophy without abnormal cardiac loading conditions. Inflammation plays a critical role in cardiovascular conditions, including cardiomyopathies, and can contribute to cardiomyocyte hypertrophy and dysfunction. Systemic inflammation may be involved in the pathogenesis of cardiac disease progression and affect the severity and outcome of the phenotype. This review summarizes the current knowledge on the prevalence, clinical significance, and therapeutic implications of inflammation in hypertrophic cardiomyopathy and its phenocopies.