Guidance on Minimizing Risk of Drug-Induced Ventricular Arrhythmia During Treatment of COVID-19: A Statement from the Canadian Heart Rhythm Society

Abstract

The COVID-19 pandemic has led to efforts at rapid investigation and application of drugs which may improve prognosis but for which safety and efficacy are not yet established. This document attempts to provide reasonable guidance for the use of antimicrobials which have uncertain benefit but may increase risk of QT interval prolongation and ventricular proarrhythmia, notably, chloroquine, hydroxychloroquine, azithromycin, and lopinavir/ritonavir. During the pandemic, efforts to reduce spread and minimize effects on health care resources mandate minimization of unnecessary medical procedures and testing. We recommend that the risk of drug proarrhythmia be minimized by 1) discontinuing unnecessary medications that may also increase the QT interval, 2) identifying outpatients who are likely to be at low risk and do not need further testing (no history of prolonged QT interval, unexplained syncope, or family history of premature sudden cardiac death, no medications that may prolong the QT interval, and/or a previous known normal corrected QT interval [QTc]), and 3) performing baseline testing in hospitalized patients or those who may be at higher risk. If baseline electrocardiographic testing reveals a moderately prolonged QTc, optimization of medications and electrolytes may permit therapy. If the QTc is markedly prolonged, drugs that further prolong it should be avoided, or expert consultation may permit administration with mitigating precautions. These recommendations are made while there are no known effective treatments for COVID-19 and should be revisited when further data on efficacy and safety become available.

Figure 2

How to measure the corrected QT interval (QTc). The QT interval is measured from the onset of the QRS (where it first deviates from baseline) to the intersection of the tangent of the downslope (dotted green line) with the baseline (TP segment, dotted blue line). This is corrected for heart rate by dividing by the square root of the RR interval, measured in seconds. In the presence of QRS widening (eg, bundle branch block or paced ventricular rhythm), QTc can be adjusted by subtracting the QRS duration (QRSd) that is in excess of 100 ms as in the following formula: $\text{QTc}\left(\text{adjusted}\right)=\text{ QTc}\left(\text{measured}\right)-\left(\text{QRSd }-100\right)$. If the patient is in atrial fibrillation, the QTc interval can be determined from 10 averaged atrial fibrillation beats.

Figure 1

Treatment algorithm for COVID-19 therapies that may prolong QT interval. We recommend that the use of these drugs for treating COVID-19 be within evaluative clinical trials. Note that this approach applies during a pandemic and may differ when the population risk of routine testing changes. ∗See Figure 2 for a review of how to measure the QT interval and calculate QTc. ^§Consider rechecking the QTc interval at 48 hours for inpatients with high risk features (see text) or those with borderline QTc prolongation at baseline. ECG, electrocardiography; QTc, corrected QT interval.