About 12% of nearly 100 patients hospitalized with COVID-19 (coronavirus) developed a cardiac abnormality after receiving hydroxychloroquine and azithromycin—two drugs currently being administered to some coronavirus patients worldwide—according to an uncontrolled study reported May 28 by Cedars-Sinai in the Journal of the American Heart Association.

The investigators did not collect data on the frequency of the abnormality in COVID-19 patients who were not administered hydroxychloroquine or azithromycin. "The lack of a comparison group is a limitation," said Sumeet Chugh, MD, associate director of the Smidt Heart Institute at Cedars-Sinai, medical director of the Heart Rhythm Center and senior author of the study. "Our team looks forward to future data from clinical trials that could overcome this limitation."

Hydroxychloroquine is used to treat malaria and rheumatoid conditions such as arthritis. A limited number of studies have shown the drug may have antiviral activity, leading to the hypothesis that it might be a treatment for COVID-19. Azithromycin is an antibiotic often prescribed for respiratory infections. There is emerging, observational data to suggest that these medicines may not be helpful, but several clinical trials are still in progress, so a definitive answer is not available yet.

The cardiac abnormality detected in the COVID-19 case series at Cedars-Sinai was a critical lengthening of the QT interval—a measurement recorded on an electrocardiogram (ECG) that shows the time from when the cardiac ventricles start to contract to when they finish relaxing.

"A critical lengthening means the risk of lethal arrhythmia, or abnormal heart rhythms, is high," said Chugh.

None of the coronavirus patients in the study died from arrhythmia during the study period. But the observations made in this case series suggest that physicians should closely monitor the QT interval throughout administration of hydroxychloroquine, azithromycin or the combination, according to Chugh.

"In addition, because there is very limited published data regarding the potential benefit of administering either medication alone or in combination to COVID-19 patients, the use of these two drugs must be carefully weighed against the potential risks," said Eduardo Marbán, MD, PhD, executive director of the Smidt Heart Institute and a co-author of the study.

To conduct this study, the investigators reviewed the medical charts of 98 patients admitted to Cedars-Sinai between Feb. 1 and April 4, 2020, who had a suspected or confirmed COVID-19 diagnosis and were treated with azithromycin, hydroxychloroquine or both. The patients ranged in age from 45 to 79, with 61% male and 39% female.

Out of 98 patients studied, 12 had critical prolongation of the QT interval. Overall, patients treated with the combination of drugs had a greater likelihood of lengthening the QT interval than those treated with either drug alone.

Significant prolongation was seen only in males. The cause for this gender disparity was not clear. The investigators noted that 42% of the men in the study were considered to be clinically obese, compared with 26% of the women.

The data for the study was collated and processed using a data intelligence dashboard developed at Cedars-Sinai that uses machine-learning technology.

The study was funded internally by Cedars-Sinai.

The IRB number for human subjects referenced in this article is 00620.