Immature and mature myocardium in the pathophysiology of hypertrophic cardiomyopathy

Hypertrophic cardiomyopathy (HCM) is the most common inherited cardiomyopathy. The pathognomonic finding is the thickening of the myocardial layer, usually of the left ventricular wall. This hypertrophy is often caused by variants in genes encoding sarcomeric proteins. Additionally, non-genetic factors contribute to the complex pathophysiology. Interestingly, these genetic and non-genetic factors result in quite uniform pathological changes, e.g., diastolic dysfunction and hypercontractility can be regarded as pathophysiological hallmarks of the disease. A potential explanation for this might be that embryological factors along with a first adaptive and later maladaptive myocardial remodeling prime myocardial hypertrophy. The present review compares the immature and mature myocardium to further assess the impact of embryological factors on the pathophysiology of HCM. According to the literature, there are differences between the immature and mature myocardium affected by sarcomeric variants at the molecular level. At the same time, the early postnatal period seems to be fundamental to sarcomeric alterations that later drive hypertrophy. Given the shared down-stream pathological changes, fetal-like reprogramming might be the pathophysiological molecular merging point of immature and mature myocardium finally driving the maladaptive hypertrophic remodeling in HCM. More research on such embryonic factors might allow for further HCM-specific targeted therapy.