Cardiac mechanopathies: regional stress maldistribution as a primary determinant of myocardial disease

The heart relies on finely tuned spatial heterogeneity in wall structure, fibre orientation, blood distribution and excitation–contraction coupling to maintain mechanical homeostasis. Even minor deviations may interact with anisotropy to promote maladaptation and disease. While cardiomyopathies have classically been attributed to primary cellular defects, emerging evidence suggests that abnormal regional stress may act as a primary driver of pathology even in the absence of intrinsic sarcomeric dysfunction. This review proposes the concept of ‘cardiac mechanopathies’, conditions in which misdirected or disproportionate mechanical forces are hypothesised to act as primary determinants of maladaptive remodelling, culminating in a cardiomyopathic phenotype. Clinical paradigms include arrhythmogenic mitral valve prolapse and apical hypertrophic cardiomyopathy with papillary muscle displacement. While a direct causality link still needs to be established, this concept is conceived as a working hypothesis for future studies. Advanced imaging may help identify subtle structural abnormalities early, while insights into the molecular basis of maladaptation may reveal new therapeutic targets. Clinically, studies are needed to understand whether reducing mechanical stress through interventions and lifestyle modifications can mitigate disease expression and progression.