Hypertrophic cardiomyopathy: an updated review on diagnosis, prognosis, and treatment

Modeling Hypertrophic Cardiomyopathy: Mechanistic Insights and Pharmacological Intervention

“…Elevated intracellular Ca 2+ and dysfunctional Ca 2+ cycling are commonly reported to be central to the pathogenesis of HCM, and inhibition of Ca 2+ entry by L-type Ca 2+ channel blockers has been investigated for the treatment of HCM [97]. In a hPSC-CM model of R663H-β-MHC mutation, diltiazem abolished calcium-handling abnormalities and arrhythmias, whereas verapamil also prevented myocyte hypertrophy, fully alleviating the HCM phenotype [60].…”

“…The allosteric modulator of cardiac myosin, mavacamten, reduces contractility by decreasing the ATPase activity of cardiac MHC in a mouse model of HCM [101], also showing effectiveness in reversing the hypercontactility seen in truncated MYBPC hPSC-CM mutants [108]. Phase III clinical trials are now ongoing to test mavacamten efficacy in adults with symptomatic obstructive HCM (ClinicalTrials.gov NCT03470545), with completion expected in June 2020 [97]. Conversely, omecamtiv mecarbil (OM) is being tested to treat hypocontractility in patients by augmenting the speed of ATP hydrolysis, thus increasing myosin head binding to actin, which results in an enhanced force-producing state [109].…”

“…HCM is defined by thickening of the left ventricle (LV) that is associated with preserved to increased ejection fraction [1]. Diagnosis of HCM relies on detection of increased LV wall thickness by several imaging technologies as well as by genetic screening [1,97].…”

“…There is no current effective treatment for HCM, and heart transplantation is the only long-term solution [97].…”

A new stone for a new path, from “physiology to the bedside”

“…Left ventricular hypertrophy (LVH) is prevalent in clinical practice; it is associated with increased risk of heart failure, diastolic dysfunction, arrhythmias, and sudden cardiac death. Typical LVH is defined as the thickening of interventricular wall and/or septum in non-invasive imaging [3,5]. Microscopically, the sizes of cardiomyocytes of LVH region are enlarged, accompanied by the augmentation of protein synthesis, sarcomeric structural disarray, and apoptosis [3].…”