Prolonged QT Interval in a Patient With Coronavirus Disease-2019: Beyond Hydroxychloroquine and Azithromycin

Anupama, B; Adhikari, Soumya; Chaudhuri, Debanik

doi:10.1177/2324709620948407

Cited by 14 publications

(17 citation statements)

References 8 publications

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“…Additionally, our data show that Hydroxychloroquine, when combined with Azithromycin at therapeutic concentration, has a high proarrhythmia risk at all concentrations tested, including clinically relevant concentrations. Similarly, proarrhythmia has recently been reported in COVID-19 patients treated with Hydroxychloroquine plus Azithromycin therapy ( Anupama et al , 2020 ; Chorin et al , 2020 ; Mercuro et al , 2020 ). Likewise, polytherapy of Hydroxychloroquine and Moxifloxacin has been reported in patients with COVID-19 ( Afsin et al , 2020 ).…”

Section: Discussionmentioning

confidence: 61%

Cardiotoxic Potential of Hydroxychloroquine, Chloroquine and Azithromycin in Adult Human Primary Cardiomyocytes

Jordaan

Dumotier

Traebert

et al. 2021

Toxicological Sciences

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Substantial efforts have been recently committed to develop COVID-19 medications, and Hydroxychloroquine alone or in combination with Azithromycin has been promoted as a repurposed treatment. While these drugs may increase cardiac toxicity risk, cardiomyocyte mechanisms underlying this risk remain poorly understood in humans. Therefore, we evaluated the pro-arrhythmia risk and inotropic effects of these drugs in the cardiomyocyte contractility-based model of the human heart. We found Hydroxychloroquine to have a low pro-arrhythmia risk, while Chloroquine and Azithromycin were associated with high risk. Hydroxychloroquine pro-arrhythmia risk changed to high with low level of K+, while high level of Mg2+ protected against pro-arrhythmic effect of high Hydroxychloroquine concentrations. Moreover, therapeutic concentration of Hydroxychloroquine caused no enhancement of elevated temperature-induced pro-arrhythmia. Polytherapy of Hydroxychloroquine plus Azithromycin and sequential application of these drugs were also found to influence pro-arrhythmia risk categorization. Hydroxychloroquine pro-arrhythmia risk changed to high when combined with Azithromycin at therapeutic concentration. However, Hydroxychloroquine at therapeutic concentration impacted the cardiac safety profile of Azithromycin and its pro-arrhythmia risk only at concentrations above therapeutic level. We also report that Hydroxychloroquine and Chloroquine, but not Azithromycin, decreased contractility while exhibiting multi-ion channel block features, and Hydroxychloroquine’s contractility effect was abolished by Azithromycin. Thus, this study has the potential to inform clinical studies evaluating repurposed therapies, including those in the COVID-19 context. Additionally, it demonstrates the translational value of the human cardiomyocyte contractility-based model as a key early discovery path to inform decisions on novel therapies for COVID-19, malaria, and inflammatory diseases.

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Section: Discussionmentioning

confidence: 61%

Cardiotoxic Potential of Hydroxychloroquine, Chloroquine and Azithromycin in Adult Human Primary Cardiomyocytes

Jordaan

Dumotier

Traebert

et al. 2021

Toxicological Sciences

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“… 32 Furthermore, there have been reports of arrhythmic storm in patients with COVID-19 in the setting of massive inflammation. 33 , 34 , 35 …”

Section: Discussionmentioning

confidence: 99%

Cardiac Corrected QT Interval Changes Among Patients Treated for COVID-19 Infection During the Early Phase of the Pandemic

et al. 2021

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IMPORTANCECritical illness, a marked inflammatory response, and viruses such as SARS-CoV-2 may prolong corrected QT interval (QTc). OBJECTIVE To evaluate baseline QTc interval on 12-lead electrocardiograms (ECGs) and ensuing changes among patients with and without COVID-19. DESIGN, SETTING, AND PARTICIPANTS This cohort study included 3050 patients aged 18 years and older who underwent SARS-CoV-2 testing and had ECGs at Columbia University Irving Medical Center from March 1 through May 1, 2020. Patients were analyzed by treatment group over 5 days, as follows: hydroxychloroquine with azithromycin, hydroxychloroquine alone, azithromycin alone, and neither hydroxychloroquine nor azithromycin. ECGs were manually analyzed by electrophysiologists masked to COVID-19 status. Multivariable modeling evaluated clinical associations with QTc prolongation from baseline. EXPOSURES COVID-19, hydroxychloroquine, azithromycin. MAIN OUTCOMES AND MEASURES Mean QTc prolongation, percentage of patients with QTc of 500 milliseconds or greater.RESULTS A total of 965 patients had more than 2 ECGs and were included in the study, with 561 (58.1%) men, 198 (26.2%) Black patients, and 191 (19.8%) aged 80 years and older. There were 733 patients (76.0%) with COVID-19 and 232 patients (24.0%) without COVID-19. COVID-19 infection was associated with significant mean QTc prolongation from baseline by both 5-day and 2-day multivariable models 15.29 to 26.33] milliseconds;

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“…The effects on repolarization remain unclear. A risk of QT prolongation was highlighted in cases of COVID‐19 treated with hydroxychloroquine and Azithromycin, but the QT abnormality observed may have been more than just a pharmacological effect 4 …”

Section: Introductionmentioning

confidence: 99%

Prolonged QT predicts prognosis in COVID‐19

Akhtar

Gallagher

Yap

et al. 2021

Pacing Clinical Electrophis

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Background Coronavirus disease‐2019 (COVID‐19) causes severe illness and multi‐organ dysfunction. An abnormal electrocardiogram is associated with poor outcome, and QT prolongation during the illness has been linked to pharmacological effects. This study sought to investigate the effects of the COVID‐19 illness on the corrected QT interval (QTc). Method For 293 consecutive patients admitted to our hospital via the emergency department for COVID‐19 between 01/03/20 ‐18/05/20, demographic data, laboratory findings, admission electrocardiograph and clinical observations were compared in those who survived and those who died within 6 weeks. Hospital records were reviewed for prior electrocardiograms for comparison with those recorded on presentation with COVID‐19. Results Patients who died were older than survivors (82 vs 69.8 years, p < 0.001), more likely to have cancer (22.3% vs 13.1%, p = 0.034), dementia (25.6% vs 10.7%, p = 0.034) and ischemic heart disease (27.8% vs 10.7%, p < 0.001). Deceased patients exhibited higher levels of C‐reactive protein (244.6 mg/L vs 146.5 mg/L, p < 0.01), troponin (1982.4 ng/L vs 413.4 ng/L, p = 0.017), with a significantly longer QTc interval (461.1 ms vs 449.3 ms, p = 0.007). Pre‐COVID electrocardiograms were located for 172 patients; the QTc recorded on presentation with COVID‐19 was longer than the prior measurement in both groups, but was more prolonged in the deceased group (448.4 ms vs 472.9 ms, pre‐COVID vs COVID, p < 0.01). Multivariate Cox‐regression analysis revealed age, C‐reactive protein and prolonged QTc of >455 ms (males) and >465 ms (females) (p = 0.028, HR 1.49 [1.04‐2.13]), as predictors of mortality. QTc prolongation beyond these dichotomy limits was associated with increased mortality risk (p = 0.0027, HR 1.78 [1.2‐2.6]). Conclusion QTc prolongation occurs in COVID‐19 illness and is associated with poor outcome.

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Prolonged QT Interval in a Patient With Coronavirus Disease-2019: Beyond Hydroxychloroquine and Azithromycin

Cited by 14 publications

References 8 publications

Cardiotoxic Potential of Hydroxychloroquine, Chloroquine and Azithromycin in Adult Human Primary Cardiomyocytes

Cardiotoxic Potential of Hydroxychloroquine, Chloroquine and Azithromycin in Adult Human Primary Cardiomyocytes

Cardiac Corrected QT Interval Changes Among Patients Treated for COVID-19 Infection During the Early Phase of the Pandemic

Prolonged QT predicts prognosis in COVID‐19

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