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

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

doi:10.1016/j.hrthm.2020.05.030

Cited by 27 publications

(27 citation statements)

References 26 publications

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“…Chloroquine interacts with multiple cardiac ion channels including the human ether-a-go-go-related gene (hERG) potassium channel; a reduction in hERG channel potassium current is the main cause of acquired drug-induced long QT syndrome. Recent experimental data indicated that HCQ markedly increases the action potential dispersion and results in the development of repolarization alternans and initiates polymorphic VT [32] .…”

Section: Chloroquine / Hydroxychloroquinementioning

confidence: 99%

COVID-19 infection and cardiac arrhythmias

Manolis¹,

Manolis

et al. 2020

Trends in Cardiovascular Medicine

109

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Highlights Serious cardiac arrhythmias may be the consequence of direct effects of COVID-19 infection, but also the outcome of the deleterious effects of systemic illness and the adverse proarrhythmic reactions to drugs employed in the treatment of this pandemic Drug combinations, especially of QT-prolonging agents, can lead to higher arrhythmogenicity, compared with single drug therapies Furthermore, critically ill COVID-19 patients often have comorbidities that can trigger life-threatening ventricular arrhythmias, while acute myocardial injury increases the prevalence of arrhythmias ECG and QTc monitoring and taking appropriate measures are of critical importance to prevent, detect and manage cardiac arrhythmias in COVID-19 patients Contactless monitoring and telemetry for inpatients, especially those admitted to the ICU, as well as for outpatients needing continued management, has recently been facilitated by implementing digital health monitoring tools

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Section: Chloroquine / Hydroxychloroquinementioning

confidence: 99%

COVID-19 infection and cardiac arrhythmias

Manolis¹,

Manolis

et al. 2020

Trends in Cardiovascular Medicine

109

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“…The intracellular face of the hERG channel is large and is lined with a number of aromatic residues allowing drugs like CQ and HCQ and others to bind this part of the channel and block the outward potassium current [36] , [37] . In a recent study using ex-vivo guinea pig and rabbit heart models, it was shown that HCQ resulted in the generation of repolarization alternans and precipitated polymorphic ventricular tachycardia [38] .…”

Section: Significant Cardiac Toxicity Concernsmentioning

confidence: 99%

It is time to drop hydroxychloroquine from our COVID-19 armamentarium

Kashour

Tleyjeh

2020

Medical Hypotheses

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Chloroquine (CQ) and hydroxychloroquine (HCQ) were among the first drugs repurposed for the treatment of SARS-CoV-2 infection. A few in vitro studies confirmed that both drugs exhibited dose dependent anti-SARS-CoV-2 activities. These observations and the encouraging results from early poorly conducted observational studies created a major hype about the therapeutic potential of these drugs in the treatment of COVID-19 disease. This was further catalyzed by media and political influences leading to a widespread use of these agents. Subsequent randomized trials revealed lack of efficacy of these agents in improving the outcomes of COVID-19 or in preventing infection in post-exposure prophylaxis studies. Nevertheless, many ongoing trials continue to actively recruit tens of thousands of patients to receive HCQ worldwide. In this perspective, we address the possible mechanisms behind the lack of efficacy and the increased risk of cardiac toxicity of HCQ in COVID-19 disease. For the lack of efficacy, we discuss the fundamental differences of treatment initiation between in vitro and in vivo studies, the pitfalls of the pharmacological calculations of effective blood drug concentrations and related dosing regimens, and the possible negative effect of HCQ on the antiviral type-I interferon response. Although it has been repeatedly claimed that HCQ has a longstanding safety track record for many decades in use, we present counterarguments for this contention due to disease-drug and drug-drug interactions. We discuss the molecular mechanisms and the cumulative epidemiological evidence of HCQ cardiac toxicity.

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“…In view of the inflammatory cytokine storm highly present in patients with severe COVID-19 causing acute lung injury, anti-inflammatory medications are proposed. Although several governments and international health authorities have promoted and encouraged the treatment with chloroquine/hydroxychloroquine ( 71 , 76 , 128 , 157 ), it must nonetheless be noted that these compounds present critical risk and benefit balance issues ( 44 , 185 , 216 ). In this context, recent clinical investigations have assessed promising alternatives, including chloroquine and its hydroxyl analog hydroxychloroquine, to evaluate whether they could prevent the virus from entering host cells, preclude viral replication, and dampen exacerbation of the immune response ( 44 , 182 , 185 , 216 ).…”

Section: Introductionmentioning

confidence: 99%

Can phytotherapy with polyphenols serve as a powerful approach for the prevention and therapy tool of novel coronavirus disease 2019 (COVID-19)?

Lévy

Delvin

Marcil

et al. 2020

American Journal of Physiology-Endocrinology and Metabolism

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Much more serious than the previous severe acute respiratory syndrome (SARS) coronavirus (CoV) outbreaks, the novel SARS-CoV-2 infection has spread speedily, affecting 213 countries and causing ~17,300,000 million cases and ~672,000 (~+1500/day) deaths globally (as of July 31th, 2020). The potentially fatal COVID-19, caused by air droplets and airborne as the main transmission modes, clearly induces a spectrum of respiratory clinical manifestations, but it also affects the immune, gastrointestinal, hematological, nervous and renal systems. The dramatic scale of disorders and complications arise from the inadequacy of current treatments, absence of a vaccine and specific anti-COVID-19 drugs to suppress viral replication, inflammation and additional pathogenic conditions. This highlights the importance of understanding the SARS-CoV-2 mechanisms of actions, and the urgent need of prospecting for new or alternative treatment options. The main objective of the present review is to discuss the challenging issue relative to the clinical utility of plants-derived polyphenols in fighting viral infections. Not only is the strong capacity of polyphenols highlighted in magnifying health benefits, but also the underlying mechanisms are stressed. Finally, emphasis is placed on the potential ability of polyphenols to combat SARS-CoV-2 infection via the regulation of its molecular targets of human cellular binding and replication, as well as through the resulting host inflammation, oxidative stress and signalling pathways.

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

Cited by 27 publications

References 26 publications

COVID-19 infection and cardiac arrhythmias

COVID-19 infection and cardiac arrhythmias

It is time to drop hydroxychloroquine from our COVID-19 armamentarium

Can phytotherapy with polyphenols serve as a powerful approach for the prevention and therapy tool of novel coronavirus disease 2019 (COVID-19)?

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