Disopyramide is effective and safe in patients with obstructive hypertrophic cardiomyopathy. However, its cellular and molecular mechanisms of action are unknown. We tested disopyramide in cardiomyocytes from the septum of surgical myectomy patients: disopyramide inhibits multiple ion channels, leading to lower Ca transients and force, and shortens action potentials, thus reducing cellular arrhythmias. The electrophysiological profile of disopyramide explains the efficient reduction of outflow gradients but also the limited prolongation of the QT interval and the absence of arrhythmic side effects observed in 39 disopyramide-treated patients. In conclusion, our results support the idea that disopyramide is safe for outpatient use in obstructive patients.
Keywords: AP, action potential; DAD, delayed afterdepolarization; EAD, early afterdepolarization; ECG, electrocardiography; HCM, hypertrophic cardiomyopathy; ICa-L, L-type Ca current; IK, delayed-rectifier K current; INaL, late Na current; LVOT, left ventricular outflow tract; NCX, Na+/Ca2+ exchanger; QT interval; RyR, ryanodine receptor; SR, sarcoplasmic reticulum; action potentials; arrhythmias; diastolic dysfunction; hERG, human ether-à-go-go-related gene; hypertrophic cardiomyopathy; pCa, Ca activation level; safety.
© 2019 The Authors.