Can an energy-deficient heart grow bigger and stronger?

Since its initial description by two French pathologists more than a century ago (1), hypertrophic cardiomyopathy (HCM), a genetic model of cardiac hypertrophic response (2), has remained an intriguing disease that has fascinated clinicians and scientists alike. While it is easy to fathom a hypertrophic cardiac response to an external stressor, a myocyte loss, or gross cardiac dysfunction, there is no increase in external load, no discernible myocyte loss, or no gross cardiac dysfunction in HCM. Thus, how would one explain the development of cardiac hypertrophy in HCM? As early as in 1975, Grossman et al. (3) proposed enhanced myocardial contractility alone, evidenced by an increased left ventricular ejection fraction, could be responsible for the development of cardiac hypertrophy. Accordingly, increased