Fatal arrhythmias: Another reason why doctors remain cautious about chloroquine/hydroxychloroquine for treating COVID-19

Ilija Uzelac; Shahriar Iravanian; Hiroshi Ashikaga; Neal K. Bhatia; Conner Herndon; Abouzar Kaboudian; James C. Gumbart; Elizabeth M. Cherry; Flavio H. Fenton

doi:10.1016/j.hrthm.2020.05.030

Fatal arrhythmias: Another reason why doctors remain cautious about chloroquine/hydroxychloroquine for treating COVID-19

Ilija Uzelac, Shahriar Iravanian, Hiroshi Ashikaga, Neal K. Bhatia, Conner Herndon, Abouzar Kaboudian, James C. Gumbart, Elizabeth M. Cherry, Flavio H. Fenton

School of Medicine

Research output: Contribution to journal › Article › peer-review

8 Scopus citations

Abstract

Background: Early during the current coronavirus disease 19 (COVID-19) pandemic, hydroxychloroquine (HCQ) received a significant amount of attention as a potential antiviral treatment, such that it became one of the most commonly prescribed medications for COVID-19 patients. However, not only has the effectiveness of HCQ remained questionable, but mainly based on preclinical and a few small clinical studies, HCQ is known to be potentially arrhythmogenic, especially as a result of QT prolongation. Objective: The purpose of this study was to investigate the arrhythmic effects of HCQ, as the heightened risk is especially relevant to COVID-19 patients, who are at higher risk for cardiac complications and arrhythmias at baseline. Methods: An optical mapping technique utilizing voltage-sensitive fluorescent dyes was used to determine the arrhythmic effects of HCQ in ex vivo guinea pig and rabbit hearts perfused with the upper therapeutic serum dose of HCQ (1000 ng/mL). Results: HCQ markedly increased action potential dispersion, resulted in development of repolarization alternans, and initiated polymorphic ventricular tachycardia. Conclusion: The study results further highlight the proarrhythmic effects of HCQ.

Original language	English (US)
Pages (from-to)	1445-1451
Number of pages	7
Journal	Heart Rhythm
Volume	17
Issue number	9
DOIs	https://doi.org/10.1016/j.hrthm.2020.05.030
State	Published - Sep 2020

Keywords

Action potential duration dispersion
Arrhythmias
Experimental optical mapping
Hydroxychloroquine
Long QT syndrome
T-wave alternans

ASJC Scopus subject areas

Cardiology and Cardiovascular Medicine
Physiology (medical)

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10.1016/j.hrthm.2020.05.030

Cite this

@article{2a63f01f9cea42c6b28d9836f75a236f,

title = "Fatal arrhythmias: Another reason why doctors remain cautious about chloroquine/hydroxychloroquine for treating COVID-19",

abstract = "Background: Early during the current coronavirus disease 19 (COVID-19) pandemic, hydroxychloroquine (HCQ) received a significant amount of attention as a potential antiviral treatment, such that it became one of the most commonly prescribed medications for COVID-19 patients. However, not only has the effectiveness of HCQ remained questionable, but mainly based on preclinical and a few small clinical studies, HCQ is known to be potentially arrhythmogenic, especially as a result of QT prolongation. Objective: The purpose of this study was to investigate the arrhythmic effects of HCQ, as the heightened risk is especially relevant to COVID-19 patients, who are at higher risk for cardiac complications and arrhythmias at baseline. Methods: An optical mapping technique utilizing voltage-sensitive fluorescent dyes was used to determine the arrhythmic effects of HCQ in ex vivo guinea pig and rabbit hearts perfused with the upper therapeutic serum dose of HCQ (1000 ng/mL). Results: HCQ markedly increased action potential dispersion, resulted in development of repolarization alternans, and initiated polymorphic ventricular tachycardia. Conclusion: The study results further highlight the proarrhythmic effects of HCQ.",

keywords = "Action potential duration dispersion, Arrhythmias, Experimental optical mapping, Hydroxychloroquine, Long QT syndrome, T-wave alternans",

author = "Ilija Uzelac and Shahriar Iravanian and Hiroshi Ashikaga and Bhatia, {Neal K.} and Conner Herndon and Abouzar Kaboudian and Gumbart, {James C.} and Cherry, {Elizabeth M.} and Fenton, {Flavio H.}",

note = "Publisher Copyright: {\textcopyright} 2020 Heart Rhythm Society",

year = "2020",

month = sep,

doi = "10.1016/j.hrthm.2020.05.030",

language = "English (US)",

volume = "17",

pages = "1445--1451",

journal = "Heart Rhythm",

issn = "1547-5271",

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TY - JOUR

T1 - Fatal arrhythmias

T2 - Another reason why doctors remain cautious about chloroquine/hydroxychloroquine for treating COVID-19

AU - Uzelac, Ilija

AU - Iravanian, Shahriar

AU - Ashikaga, Hiroshi

AU - Bhatia, Neal K.

AU - Herndon, Conner

AU - Kaboudian, Abouzar

AU - Gumbart, James C.

AU - Cherry, Elizabeth M.

AU - Fenton, Flavio H.

PY - 2020/9

Y1 - 2020/9

N2 - Background: Early during the current coronavirus disease 19 (COVID-19) pandemic, hydroxychloroquine (HCQ) received a significant amount of attention as a potential antiviral treatment, such that it became one of the most commonly prescribed medications for COVID-19 patients. However, not only has the effectiveness of HCQ remained questionable, but mainly based on preclinical and a few small clinical studies, HCQ is known to be potentially arrhythmogenic, especially as a result of QT prolongation. Objective: The purpose of this study was to investigate the arrhythmic effects of HCQ, as the heightened risk is especially relevant to COVID-19 patients, who are at higher risk for cardiac complications and arrhythmias at baseline. Methods: An optical mapping technique utilizing voltage-sensitive fluorescent dyes was used to determine the arrhythmic effects of HCQ in ex vivo guinea pig and rabbit hearts perfused with the upper therapeutic serum dose of HCQ (1000 ng/mL). Results: HCQ markedly increased action potential dispersion, resulted in development of repolarization alternans, and initiated polymorphic ventricular tachycardia. Conclusion: The study results further highlight the proarrhythmic effects of HCQ.

AB - Background: Early during the current coronavirus disease 19 (COVID-19) pandemic, hydroxychloroquine (HCQ) received a significant amount of attention as a potential antiviral treatment, such that it became one of the most commonly prescribed medications for COVID-19 patients. However, not only has the effectiveness of HCQ remained questionable, but mainly based on preclinical and a few small clinical studies, HCQ is known to be potentially arrhythmogenic, especially as a result of QT prolongation. Objective: The purpose of this study was to investigate the arrhythmic effects of HCQ, as the heightened risk is especially relevant to COVID-19 patients, who are at higher risk for cardiac complications and arrhythmias at baseline. Methods: An optical mapping technique utilizing voltage-sensitive fluorescent dyes was used to determine the arrhythmic effects of HCQ in ex vivo guinea pig and rabbit hearts perfused with the upper therapeutic serum dose of HCQ (1000 ng/mL). Results: HCQ markedly increased action potential dispersion, resulted in development of repolarization alternans, and initiated polymorphic ventricular tachycardia. Conclusion: The study results further highlight the proarrhythmic effects of HCQ.

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KW - Arrhythmias

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KW - Long QT syndrome

KW - T-wave alternans

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Fatal arrhythmias: Another reason why doctors remain cautious about chloroquine/hydroxychloroquine for treating COVID-19

Abstract

Keywords

ASJC Scopus subject areas

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