A multicenter, prospective study conducted in Europe to assess ECG changes and arrhythmias in COVID-19 patients treated with hydroxychloroquine (HCQ) in different clinical settings found that short-term treatment with the drug, alone or in combination with other QT-prolonging drugs, was associated with only modest QTc prolongation and no directly attributable arrhythmic deaths. The findings were published Sept. 25 in EP Europace. Serial ECG recordings at 36-72 hours and later than 96 hours after treatment onset were able to detect QTc changes that might suggest therapy modification.

A total of 649 patients positive for COVID-19 and treated with HCQ were enrolled from seven institutions between March 10 and April 10, 2020. All enrolled patients had a baseline and at least one ECG at 48 hours. The mean age was 61.9 years and 299 (46.1%) were male. The most common presentation symptoms were fever, dry cough and dyspnea.

A Tisdale score, which assesses the risk of QT prolongation, was determined for each patient at baseline; 55.5% were at low risk and 38.5% at moderate risk. The patients selected for home treatment had mild respiratory symptoms and 88.1% had a low arrhythmic risk. A QTc prolongation >60 ms was considered abnormal, requiring reassessment of the patient's medical status and drug administration/interactions. HCQ suspension was mandatory for a QTc >550 ms, but suspension for shorter values based on clinical judgement was also performed.

HCQ therapy (200 mg twice daily) was administered at home in 126 (19.4%) patients, in the hospital medical ward in 495 (76.3%) patients, and in the intensive care unit in 28 (4.3%) patients. On the first day, 58.6% of patients took a loading dose of HCQ (400 mg twice). Overall, 53.8% of patients took HCQ alone, 30% received two QT-prolonging drugs, and 13.6% received three.

An ECG was obtained in 358 patients at 36-72 hours after starting HCQ and in 404 patients after 96 hours.

A significant QT/QTc interval prolongation was observed (p<0.001), but the magnitude of the increase was modest (+13 [9-16] ms). Baseline QT/QTc length and presence of fever (p=0.001) at admission were the most important determinants of QT/QTc prolongation.

Over a median follow-up of 16 days, no arrhythmia-related deaths were reported. The overall major ventricular arrhythmia rate was low (1.1%), and centralized event evaluation determined none were related to QT or HCQ therapy.

No differences in QT/QTc prolongation and QT-related arrhythmias were observed across different clinical settings, with non–QT-related arrhythmias being more common in the intensive care setting.

The authors, led by Alessio Gasperetti, MD, write, "[p]rovided that an adequate ECG monitoring strategy is implemented, the short-term HCQ treatment used in COVID-19 patients seems to be safe, regardless of the clinical setting in which it is started." While noting the limitations of their study, including the lack of routinely available 24-hour telemetry and loop recorders for all enrolling centers and variation in the HCQ dose across hospitals, they write this experience provides a framework to enable HCQ therapy implementation in different clinical settings for future efficacy trials.

"Previous studies have also suggested that hydroxychloroquine was relatively safe when given alone, but when combined with azithromycin, which can also lengthen the QT interval, the combination can lead to rare but life-threatening arrhythmias," noted Kim A. Eagle, MD, MACC, editor-in-chief of ACC.org.

Clinical Topics: Arrhythmias and Clinical EP, Congenital Heart Disease and Pediatric Cardiology, COVID-19 Hub, Heart Failure and Cardiomyopathies, Implantable Devices, Genetic Arrhythmic Conditions, SCD/Ventricular Arrhythmias, Atrial Fibrillation/Supraventricular Arrhythmias, Congenital Heart Disease, CHD and Pediatrics and Arrhythmias, Novel Agents, Statins

Keywords: Hydroxychloroquine, Pharmaceutical Preparations, COVID-19, severe acute respiratory syndrome coronavirus 2, Long QT Syndrome, Arrhythmias, Cardiac, Electrocardiography, Drug Interactions, Dyspnea, Intensive Care Units, Critical Care

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