Electrophysiological and Contractile Effects of Disopyramide in Patients With Obstructive Hypertrophic Cardiomyopathy
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 chann...
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| Language: | English |
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Elsevier
2019-11-01
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| Series: | JACC: Basic to Translational Science |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2452302X19301871 |
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doaj-383410aaa4f04130b18b186ad5f7d1d62020-11-25T01:35:07ZengElsevierJACC: Basic to Translational Science2452-302X2019-11-0147795813Electrophysiological and Contractile Effects of Disopyramide in Patients With Obstructive Hypertrophic CardiomyopathyRaffaele Coppini, MD, PhD0Cecilia Ferrantini, MD, PhD1Josè Manuel Pioner, PhD2Lorenzo Santini, MS3Zhinuo J. Wang, PhD4Chiara Palandri, MS5Marina Scardigli, PhD6Giulia Vitale, MS7Leonardo Sacconi, PhD8Pierluigi Stefàno, MD9Laura Flink, MD10Katherine Riedy, MD11Francesco Saverio Pavone, PhD12Elisabetta Cerbai, PhD13Corrado Poggesi, MD14Alessandro Mugelli, MD15Alfonso Bueno-Orovio, PhD16Iacopo Olivotto, MD17Mark V. Sherrid, MD18Department NeuroFarBa, University of Florence, Florence, Italy; Address for correspondence: Dr. Raffaele Coppini, Department NeuroFarBa, University of Florence, Viale G. Pieraccini 6, 50139 Firenze, Italy.Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy; Cardiomyopathy Unit, Careggi University Hospital, Florence, ItalyDepartment of Experimental and Clinical Medicine, University of Florence, Florence, ItalyDepartment NeuroFarBa, University of Florence, Florence, ItalyDepartment of Computer Sciences, University of Oxford, Oxford, United KingdomDepartment NeuroFarBa, University of Florence, Florence, ItalyEuropean Laboratory for Nonlinear Spectroscopy (LENS), University of Florence, Sesto Fiorentino, Italy and National Institute of Optics, National Research Council, Florence, ItalyDepartment of Experimental and Clinical Medicine, University of Florence, Florence, ItalyEuropean Laboratory for Nonlinear Spectroscopy (LENS), University of Florence, Sesto Fiorentino, Italy and National Institute of Optics, National Research Council, Florence, ItalyDepartment of Experimental and Clinical Medicine, University of Florence, Florence, Italy; Cardiomyopathy Unit, Careggi University Hospital, Florence, ItalyDivision of Cardiology, San Francisco Veterans Affairs Medical Center and University of California-San Francisco, San Francisco, CaliforniaHypertrophic Cardiomyopathy Program, New York University Langone Health, New York, New YorkEuropean Laboratory for Nonlinear Spectroscopy (LENS), University of Florence, Sesto Fiorentino, Italy and National Institute of Optics, National Research Council, Florence, ItalyDepartment NeuroFarBa, University of Florence, Florence, ItalyDepartment of Experimental and Clinical Medicine, University of Florence, Florence, ItalyDepartment NeuroFarBa, University of Florence, Florence, ItalyDepartment of Computer Sciences, University of Oxford, Oxford, United KingdomDepartment of Experimental and Clinical Medicine, University of Florence, Florence, Italy; Cardiomyopathy Unit, Careggi University Hospital, Florence, ItalyHypertrophic Cardiomyopathy Program, New York University Langone Health, New York, New YorkSummary: 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, safetyhttp://www.sciencedirect.com/science/article/pii/S2452302X19301871 |
| collection |
DOAJ |
| language |
English |
| format |
Article |
| sources |
DOAJ |
| author |
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 |
| spellingShingle |
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 Electrophysiological and Contractile Effects of Disopyramide in Patients With Obstructive Hypertrophic Cardiomyopathy JACC: Basic to Translational Science |
| author_facet |
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 |
| author_sort |
Raffaele Coppini, MD, PhD |
| title |
Electrophysiological and Contractile Effects of Disopyramide in Patients With Obstructive Hypertrophic Cardiomyopathy |
| title_short |
Electrophysiological and Contractile Effects of Disopyramide in Patients With Obstructive Hypertrophic Cardiomyopathy |
| title_full |
Electrophysiological and Contractile Effects of Disopyramide in Patients With Obstructive Hypertrophic Cardiomyopathy |
| title_fullStr |
Electrophysiological and Contractile Effects of Disopyramide in Patients With Obstructive Hypertrophic Cardiomyopathy |
| title_full_unstemmed |
Electrophysiological and Contractile Effects of Disopyramide in Patients With Obstructive Hypertrophic Cardiomyopathy |
| title_sort |
electrophysiological and contractile effects of disopyramide in patients with obstructive hypertrophic cardiomyopathy |
| publisher |
Elsevier |
| series |
JACC: Basic to Translational Science |
| issn |
2452-302X |
| publishDate |
2019-11-01 |
| description |
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 |
| url |
http://www.sciencedirect.com/science/article/pii/S2452302X19301871 |
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