Electrophysiological and Contractile Effects of Disopyramide in Patients With Obstructive Hypertrophic Cardiomyopathy: a Translational Study
Raffaele Coppini, Cecilia Ferrantini, Josè Manuel Pioner, Lorenzo Santini, Zhinuo J. Wang, Chiara Palandri, Marina Scardigli, Giulia Vitale, Leonardo Sacconi, Pierluigi Stefàno, Laura Flink, Katherine Riedy, Francesco Saverio Pavone, Elisabetta Cerbai, Corrado Poggesi, Alessandro Mugelli, Alfonso Bueno-Orovio, Iacopo Olivotto and Mark V. Sherrid
Modeling Results on the Action of Disopyramide on the Dispersion of Repolarization
(A) Representative superimposed action potentials at baseline (black traces) and in the presence of disopyramide 5 μmol/l (blue traces) in endocardial (Endo) and epicardial (Epi) models of human ventricular cardiomyocytes at 1 Hz pacing. (B) APD90% at baseline (black) and in the presence of disopyramide 5 μmol/l (blue), for the different cell types. *p < 0.05, paired Student’s t test. (C) Endocardial APD shortening in HCM endocardial cardiomyocytes under disopyramide 5 μmol/l action as a function of baseline APD90%. (D) Cellular mechanisms underlying endocardial APD shortening in responders (dark blue) versus nonresponders (light blue) to disopyramide. *p < 0.05, unpaired Student’s t test. (E) RT90% in a ventricular model of obstructive HCM. Disopyramide reduces maximum dispersion of repolarization in the septal hypertrophic region while only slightly prolonging repolarization in nonhypertrophic epicardium, leading to QT shortening in septal compared with modest QT prolongation in lateral precordial electrocardiogram leads (V1 and V5 shown). CTRL = control model; IKr = rapid delayed-rectifier K+ current; RyR = ryanodine receptor; other abbreviations as in Figures 1 to 4.