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QT interval prolongation and torsade de pointes in patients with COVID-19 treated with
Ehud Chorin1, Lalit Wadhwani1, Silvia Magnani2
1Leon H. Charney Division of Cardiology, Cardiac Electrophysiology, NYU Langone Health, New York University Grossman School of Medicine, New York, New York.
Insights
Hydroxychloroquine/azithromycin (HY/AZ) significantly prolongs the corrected QT (QTc) interval in COVID-19 patients, increasing the risk of dangerous arrhythmias like torsade de pointes (TdP). Careful monitoring is essential if this unproven treatment is used.
Area of Science:
- Cardiology
- Infectious Diseases
- Pharmacology
Background:
- Coronavirus disease 2019 (COVID-19) lacks effective therapies.
- Hydroxychloroquine/azithromycin (HY/AZ) gained widespread use for COVID-19 despite unproven efficacy.
- Concerns exist regarding HY/AZ's potential for QT interval prolongation and torsade de pointes (TdP).
Purpose of the Study:
- To assess the impact of HY/AZ on corrected QT (QTc) interval in COVID-19 patients.
- To evaluate the incidence of arrhythmic events associated with HY/AZ treatment in COVID-19.
Main Methods:
- Retrospective study of 251 COVID-19 patients treated with HY/AZ.
- Electrocardiographic tracings analyzed from baseline to 3 days post-therapy.
- Evaluation of QTc interval progression, arrhythmia incidence, and mortality.
Main Results:
- QTc interval prolonged with increasing HY/AZ exposure, with incomplete shortening post-therapy.
- 23% of patients developed extreme QTc prolongation (>500 ms), a TdP risk marker.
- One patient experienced polymorphic ventricular tachycardia (suspected TdP); 7 required therapy termination.
Conclusions:
- The HY/AZ combination significantly prolongs the QTc interval in COVID-19 patients.
- This prolongation poses a risk for life-threatening arrhythmias, including TdP.
- Given unproven efficacy, HY/AZ therapy requires careful consideration and strict QTc monitoring.
Background:
There is no known effective therapy for patients with coronavirus disease 2019 (COVID-19). Initial reports suggesting the potential benefit of hydroxychloroquine/azithromycin (HY/AZ) have resulted in massive adoption of this combination worldwide. However, while the true efficacy of this regimen is unknown, initial reports have raised concerns about the potential risk of QT interval prolongation and induction of torsade de pointes (TdP).
Objective:
The purpose of this study was to assess the change in corrected QT (QTc) interval and arrhythmic events in patients with COVID-19 treated with HY/AZ.
Methods:
This is a retrospective study of 251 patients from 2 centers who were diagnosed with COVID-19 and treated with HY/AZ. We reviewed electrocardiographic tracings from baseline and until 3 days after the completion of therapy to determine the progression of QTc interval and the incidence of arrhythmia and mortality.
Results:
The QTc interval prolonged in parallel with increasing drug exposure and incompletely shortened after its completion. Extreme new QTc interval prolongation to >500 ms, a known marker of high risk of TdP, had developed in 23% of patients. One patient developed polymorphic ventricular tachycardia suspected as TdP, requiring emergent cardioversion. Seven patients required premature termination of therapy. The baseline QTc interval of patients exhibiting extreme QTc interval prolongation was normal.
Conclusion:
The combination of HY/AZ significantly prolongs the QTc interval in patients with COVID-19. This prolongation may be responsible for life-threatening arrhythmia in the form of TdP. This risk mandates careful consideration of HY/AZ therapy in light of its unproven efficacy. Strict QTc interval monitoring should be performed if the regimen is given.
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