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

Raffaele Coppini, MD, PhD; Cecilia Ferrantini, MD, PhD; Josè Manuel Pioner, PhD; Lorenzo Santini, MS; Zhinuo J. Wang, PhD; Chiara Palandri, MS; Marina Scardigli, PhD; Giulia Vitale, MS; Leonardo Sacconi, PhD; Pierluigi Stefàno, MD; Laura Flink, MD; Katherine Riedy, MD; Francesco Saverio Pavone, PhD; Elisabetta Cerbai, PhD; Corrado Poggesi, MD; Alessandro Mugelli, MD; Alfonso Bueno-Orovio, PhD; Iacopo Olivotto, MD; Mark V. Sherrid, MD

JACC: Basic to Translational Science (Nov 2019)

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

Raffaele Coppini, MD, PhD,
Cecilia Ferrantini, MD, PhD,
Josè Manuel Pioner, PhD,
Lorenzo Santini, MS,
Zhinuo J. Wang, PhD,
Chiara Palandri, MS,
Marina Scardigli, PhD,
Giulia Vitale, MS,
Leonardo Sacconi, PhD,
Pierluigi Stefàno, MD,
Laura Flink, MD,
Katherine Riedy, MD,
Francesco Saverio Pavone, PhD,
Elisabetta Cerbai, PhD,
Corrado Poggesi, MD,
Alessandro Mugelli, MD,
Alfonso Bueno-Orovio, PhD,
Iacopo Olivotto, MD,
Mark V. Sherrid, MD

Affiliations

Raffaele Coppini, MD, PhD: Department NeuroFarBa, University of Florence, Florence, Italy; Address for correspondence: Dr. Raffaele Coppini, Department NeuroFarBa, University of Florence, Viale G. Pieraccini 6, 50139 Firenze, Italy.
Cecilia Ferrantini, MD, PhD: Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy; Cardiomyopathy Unit, Careggi University Hospital, Florence, Italy
Josè Manuel Pioner, PhD: Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy
Lorenzo Santini, MS: Department NeuroFarBa, University of Florence, Florence, Italy
Zhinuo J. Wang, PhD: Department of Computer Sciences, University of Oxford, Oxford, United Kingdom
Chiara Palandri, MS: Department NeuroFarBa, University of Florence, Florence, Italy
Marina Scardigli, PhD: European Laboratory for Nonlinear Spectroscopy (LENS), University of Florence, Sesto Fiorentino, Italy and National Institute of Optics, National Research Council, Florence, Italy
Giulia Vitale, MS: Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy
Leonardo Sacconi, PhD: European Laboratory for Nonlinear Spectroscopy (LENS), University of Florence, Sesto Fiorentino, Italy and National Institute of Optics, National Research Council, Florence, Italy
Pierluigi Stefàno, MD: Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy; Cardiomyopathy Unit, Careggi University Hospital, Florence, Italy
Laura Flink, MD: Division of Cardiology, San Francisco Veterans Affairs Medical Center and University of California-San Francisco, San Francisco, California
Katherine Riedy, MD: Hypertrophic Cardiomyopathy Program, New York University Langone Health, New York, New York
Francesco Saverio Pavone, PhD: European Laboratory for Nonlinear Spectroscopy (LENS), University of Florence, Sesto Fiorentino, Italy and National Institute of Optics, National Research Council, Florence, Italy
Elisabetta Cerbai, PhD: Department NeuroFarBa, University of Florence, Florence, Italy
Corrado Poggesi, MD: Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy
Alessandro Mugelli, MD: Department NeuroFarBa, University of Florence, Florence, Italy
Alfonso Bueno-Orovio, PhD: Department of Computer Sciences, University of Oxford, Oxford, United Kingdom
Iacopo Olivotto, MD: Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy; Cardiomyopathy Unit, Careggi University Hospital, Florence, Italy
Mark V. Sherrid, MD: Hypertrophic Cardiomyopathy Program, New York University Langone Health, New York, New York

Journal volume & issue: Vol. 4, no. 7
pp. 795 – 813

Abstract

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Summary: 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. Key Words: action potentials, arrhythmias, diastolic dysfunction, hypertrophic cardiomyopathy, QT interval, safety

Published in JACC: Basic to Translational Science

ISSN: 2452-302X (Online)
Publisher: Elsevier
Country of publisher: United States
LCC subjects: Medicine: Internal medicine: Specialties of internal medicine: Diseases of the circulatory (Cardiovascular) system
Website: https://www.journals.elsevier.com/jacc-basic-to-translational-science/

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