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Review of Hydroxychloroquine Cardiotoxicity: Lessons From the COVID-19 Pandemic
Luke R Gagnon1,2, Chandu Sadasivan1,2, Haran Yogasundaram1,2
1Department of Medicine, University of Alberta, Edmonton, Alberta, Canada.
Insights
Hydroxychloroquine and chloroquine (HCQ/CQ) showed no COVID-19 benefit and carry risks of heart problems like arrhythmias and heart failure. Cardiac monitoring is advised for patients using HCQ/CQ.
Area of Science:
- Cardiology
- Infectious Diseases
- Pharmacology
Background:
- Hydroxychloroquine and chloroquine (HCQ/CQ) were explored for COVID-19 treatment due to in vitro antiviral properties.
- While known for anti-malarial and rheumatologic uses, HCQ/CQ's cardiotoxicity is a significant concern.
- Retinopathy and neuromyopathy are established side effects, but cardiac complications are under-recognized.
Purpose of the Study:
- To review the cardiotoxicity of HCQ/CQ in COVID-19 patients.
- To discuss the mechanisms of HCQ/CQ cardiotoxicity.
- To evaluate the utility of HCQ/CQ for treating COVID-19.
Main Methods:
- Review of early clinical trials and large multi-center randomized controlled trials on HCQ/CQ for COVID-19.
- Analysis of reported cardiac complications associated with HCQ/CQ usage.
- Discussion of mechanisms leading to cardiac adverse events.
Main Results:
- Early trials suggested modest benefit, but larger studies showed no benefit and potential harm in COVID-19.
- Predominant cardiac issues in COVID-19 were arrhythmias and QT interval prolongation.
- Chronic HCQ/CQ use can lead to heart failure and cardiomyopathy (CM).
Conclusions:
- HCQ/CQ is not routinely recommended for COVID-19 due to insufficient evidence and emerging therapies.
- Cardiac evaluation with ECG is recommended before and during HCQ/CQ treatment.
- Prompt cessation of HCQ/CQ can lead to reversible cardiac changes, especially for HCQ/CQ-induced cardiomyopathy.
Purpose Of Review:
The coronavirus disease 2019 (COVID-19) pandemic has popularized the usage of hydroxychloroquine and chloroquine (HCQ/CQ) as treatments for COVID-19. Previously used as anti-malarial and now commonly used in rheumatologic conditions, preliminary in vitro studies have demonstrated these medications also have anti-viral properties. Retinopathy and neuromyopathy are well recognized complications of using these treatments; however, cardiotoxicity is under-recognized. This review will discuss the implications and cardiotoxicity of HCQ/CQ, their mechanisms of action, and their utility in COVID-19.
Recent Findings:
Early clinical trials demonstrated a modest benefit of HCQ in COVID-19, causing a push for the usage of it. However, further large multi-center randomized control centers, demonstrated no benefit, and even a trend towards worse outcomes. The predominant cardiac complication observed with HCQ in COVID-19 was cardiac arrhythmias and prolonging of the QT interval. However, with chronic usage of HCQ/CQ, the development of heart failure (HF) and cardiomyopathy (CM) can occur. Although, most adverse cardiac events related to HCQ/CQ usage in COVID-19 were secondary to conduction disorders given the short duration of treatment, HCQ/CQ can cause CM and HF, with chronic usage. Given the insufficient evidence, HCQ/CQ usage in COVID-19 is not routinely recommended, especially with novel therapies now being developed and used. Additionally, usage of HCQ/CQ should prompt initial cardiac evaluation with ECG, and yearly monitoring, with consideration for advanced imaging if clinically warranted. The diagnosis of HCQ/CQ cardiomyopathy is important, as prompt cessation can allow for recovery when these changes are still reversible.
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