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. 2020 May 11;S1547-5271(20)30435-5.
doi: 10.1016/j.hrthm.2020.05.014. Online ahead of print.

QT Interval Prolongation and Torsade De Pointes in Patients With COVID-19 Treated With Hydroxychloroquine/Azithromycin

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Free PMC article

QT Interval Prolongation and Torsade De Pointes in Patients With COVID-19 Treated With Hydroxychloroquine/Azithromycin

Ehud Chorin et al. Heart Rhythm. .
Free PMC article

Abstract

Background: There is no known effective therapy for patients with 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 regarding the potential risk of QT prolongation and induction of torsade de pointes (TdP).

Objective: to assess the change in QTc interval and arrhythmic events in patients with COVID-19 treated with HY/AZ METHODS: This is a retrospective study of 251 patients from two centers, diagnosed with COVID-19 and treated with HY/AZ. We reviewed ECG tracings from baseline and until 3 days after completion of therapy to determine the progression of QTc and incidence of arrhythmia and mortality.

Results: QTc prolonged in parallel with increasing drug exposure and incompletely shortened after its completion. Extreme new QTc prolongation to > 500 ms, a known marker of high risk for TdP had developed in 23% of patients. One patient developed polymorphic ventricular tachycardia (VT) suspected as TdP, requiring emergent cardioversion. Seven patients required premature termination of therapy. The baseline QTc of patients exhibiting extreme QTc prolongation was normal.

Conclusion: The combination of HY/AZ significantly prolongs the QTc in patients with COVID-19. This prolongation may be responsible for life threating arrhythmia in the form of TdP. This risk mandates careful consideration of HY/AZ therapy in lights of its unproven efficacy. Strict QTc monitoring should be performed if the regimen is given.

Keywords: Azithromycin; COVID-19; Hydroxychloroquine; QT interval; Torsade de pointes.

Figures

Figure 1
Figure 1
QTc prolongation and Torsdaes de point. This 68-year-old male patient, without any past medical history was found to be positive for SARS-COV 2 and HY/AZ was initiated. The patient did not receive any other QT prolonging medications. Baseline ECG is presented in panel A. ECG before the initiation of HY/AZ. QTc = 447 ms. QTc prolonged gradually to 477 ms on day 1, 480 ms on day 2 and 505 ms on day 3. In panel B, ECG at day 4 of HY/AZ revealed QTc prolongation to 546 ms. C. The same night, multiple short runs of TdP were noted on telemetry. HY/AZ was stopped, the patient developed TdP requiring cardioversion which was given in <10s due to incidental presence of a physician by the patient. Laboratory from day 4 revealed Creatinine 1.1 (mg/dL), K – 3.5 (mEq/L) and mildly elevated liver function tests.
Figure 2
Figure 2
A. Daily absolute QTc in patients treated with HY/AZ and B. change in QTc by day. Number of patients, mean QTc +/- SD are presented at each day. * represents p<0.01 for the comparison with baseline QTc. Blue lines indicate end of HY/AZ therapy.
Figure 3
Figure 3
Individual QTc changes from baseline to the individual maximal QTc. In A, patient with maximal QTc>500 ms are marked in red. In B, patients with ΔQTc>60 ms are marked in red.
Figure 4
Figure 4
Distribution of QTc ranges by day of therapy. Note that therapy was given on days 1-5 (dashed line).

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References

    1. Wang M, Cao R, Zhang L, Yang X, Liu J, Xu M, Shi Z, Hu Z, Zhong W, Xiao G. Remdesivir and chloroquine effectively inhibit the recently emerged novel coronavirus (2019-nCoV) in vitro. Cell Res Mar 2020;30:269-271. doi.org/10.1038/s41422-020-0282-0CrossRef exact
    1. Yao X., Ye F., Zhang M. In Vitro Antiviral Activity and Projection of Optimized Dosing Design of Hydroxychloroquine for the Treatment of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Clin Infect Dis Mar. 2020;9 doi: 10.1093/cid/ciaa237. - DOI
    1. Gautret P, Lagier JC, Parola P, et al. Hydroxychloroquine and azithromycin as a treatment of COVID-19: results of an open-label non-randomized clinical trial. Int J Antimicrob Agents Mar 20 2020105949. doi:10.1016/j.ijantimicag.2020.105949
    1. Ferner R.E., Aronson J.K. Chloroquine and hydroxychloroquine in covid-19. BMJ. Apr 8 2020;369:m1432. doi: 10.1136/bmj.m1432. - DOI - PubMed
    1. Chen C.Y., Wang F.L., Lin C.C. Chronic hydroxychloroquine use associated with QT prolongation and refractory ventricular arrhythmia. Clin Toxicol (Phila) 2006;44:173–175. - PubMed
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