Electrophysiological and Contractile Effects of Disopyramide in Patients With Obstructive Hypertrophic Cardiomyopathy A Translational Study

Year: 2019

Authors: Coppini R., Ferrantini C., Pioner JM., Santini L., Wang ZNJ., Palandri C., Scardigli M., Vitale G., Sacconi L., Stefano P., Flink L., Riedy K., Pavone FS., Cerbai E., Poggesi C., Mugelli A., Bueno-Orovio A., Olivotto I., Sherrid MV.

Autors Affiliation: Univ Florence, Dept NeuroFarBa, Viale G Pieraccini 6, I-50139 Florence, Italy; Univ Florence, Dept Expt & Clin Med, Florence, Italy; Careggi Univ Hosp, Cardiomyopathy Unit, Florence, Italy; Univ Oxford, Dept Comp Sci, Oxford, England; Univ Florence, European Lab Nonlinear Spect LENS, Sesto Fiorentino, Italy; CNR, Natl Inst Opt, Florence, Italy; San Francisco VA Med Ctr, Div Cardiol, San Francisco, CA USA; Univ Calif San Francisco, San Francisco, CA 94143 USA; New York Univ Langone Hlth, Hypertroph Cardiomyopathy Program, New York, NY USA.

Abstract: 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. (C) 2019 The Authors. Published by Elsevier on behalf of the American College of Cardiology Foundation.

Journal/Review: JACC-BASIC TO TRANSLATIONAL SCIENCE

Volume: 4 (7)      Pages from: 795  to: 813

More Information: Supported by the European Union’s Horizon 2020 Research and Innovation Programme (grant 777204, SILICO-FCM, to Drs. Ferrantini, Pioner, Poggesi, and Olivotto), the Italian Ministry of Health (grants RF-2013-02356787, NET-2011-02347173, and GR-2011-02350583 to Drs. Ferrantini and Olivotto), Regione Toscana (FAS-Salute 2014, project ToRSADE to Drs. Coppini, Santini, and Cerbai), a British Heart Foundation Intermediate Basic Science Research Fellowship (FS/17/22/32644 to Drs. Wang and Bueno-Orovio) and an ARCHER RAP Award. All authors have reported that they have no relationships relevant to the contents of this paper to disclose.
KeyWords: action potentials; arrhythmias; diastolic dysfunction; hypertrophic cardiomyopathy; QT interval; safety
DOI: 10.1016/j.jacbts.2019.06.004

Citations: 41
data from “WEB OF SCIENCE” (of Thomson Reuters) are update at: 2024-11-24
References taken from IsiWeb of Knowledge: (subscribers only)

Connecting to view paper tab on IsiWeb: Click here
Connecting to view citations from IsiWeb: Click here