Urgent Guidance for Navigating and Circumventing the QTc-Prolonging and Torsadogenic Potential of Possible Pharmacotherapies for Coronavirus Disease 19 (COVID-19)

Abstract

As the coronavirus disease 19 (COVID-19) global pandemic rages across the globe, the race to prevent and treat this deadly disease has led to the "off-label" repurposing of drugs such as hydroxychloroquine and lopinavir/ritonavir, which have the potential for unwanted QT-interval prolongation and a risk of drug-induced sudden cardiac death. With the possibility that a considerable proportion of the world's population soon could receive COVID-19 pharmacotherapies with torsadogenic potential for therapy or postexposure prophylaxis, this document serves to help health care professionals mitigate the risk of drug-induced ventricular arrhythmias while minimizing risk of COVID-19 exposure to personnel and conserving the limited supply of personal protective equipment.

Figure 1

Approach to mitigating the risk of drug-induced torsades de pointes (TdP)/drug-induced sudden cardiac death in patients with coronavirus disease 19 (COVID-19) treated following a hypothetical treatment algorithm with “off-label” hydroxychloroquine alone or in combination with azithromycin. Both medications are known HERG blockers with both QTc- prolonging and torsadogenic potential. The estimated 99th percentile QTc values (derived from otherwise healthy individuals), which places a patient in the “green light” category, are less than 460 ms before puberty, less than 470 ms in men, and less than 480 ms in women. We estimate that the baseline QTc assessment will place 90% of patients in green light, 9% in yellow light, and 1% in red light status. ∗Severe COVID-19 cases are defined as a respiratory rate of greater than 30 breaths/min (adults) or 40 breaths/min (children), oxygen saturation of 93% or less, PaO₂ to fraction of inspired oxygen ratio less than 300, or lung infiltrates involving more than 50% of the lung field after 24 to 48 hours. ^¥Repurposed antiviral alternatives such as lopinavir/ritonavir also have QTc-prolonging effects. CHF = congestive heart failure; CKD = chronic kidney disease; COPD = chronic obstructive pulmonary disease; CV = cardiovascular; ECG = electrocardiography; ICU = intensive care unit; NIAID = National Institute of Allergy and Infectious Diseases.

Figure 2

Protocols for the possible inpatient and outpatient use of a smartphone-enabled mobile electrocardiogram (ECG) to assess and monitor QTc values in patients with coronavirus disease 19. A, Inpatient protocol using dedicated institutional smartphone/tablet and mobile ECG device. Whenever possible, we strongly recommend the use of a dedicated institutional Bluetooth-enabled smartphone or tablet device that is not used for personal use (ie, phone calls or other activities) to limit the spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). B, Inpatient or outpatient protocol using personal (or institutionally loaned) smartphone/tablet and mobile ECG device. ∗Currently, the only smartphone-enabled mobile ECG with US Food and Drug Administration approval for QTc monitoring is the AliveCor KardiaMobile 6L device. PPE = personal protective equipment.