COVID-19 Prolongs QT Interval Independent of Other Factors

Megan Brooks

April 26, 2021

Editor's note: Find the latest COVID-19 news and guidance in Medscape's Coronavirus Resource Center.

COVID-19 infection is associated with a significant increase in the corrected QT interval (QTc) in hospitalized patients, independent of common clinical factors associated with QTc prolongation, including hydroxychloroquine and azithromycin treatment, new research indicates.

"Clinicians should be aware that COVID-19 infection can prolong corrected QTc in patients," Elaine Y. Wan, MD, director of electrophysiology research, Columbia University Medical Center, New York City, told | Medscape Cardiology.

The results were published online April 23 in JAMA Network Open.  

"We performed a detailed and comprehensive study in which expert electrophysiologists read all the 12-lead electrocardiograms of hospitalized patients with and without COVID-19 infection," Wan explained.

The cohort involved 965 patients (58% men, 26% Black, 20% 80 years and older) hospitalized at Columbia University Irving Medical Center from March 1 through May 1, 2020; 733 patients (76%) had COVID-19 and 232 (24%) did not.

The major finding, said Wan, is that patients with COVID-19 infection had prolonged QTc at day 2 (mean increase, 24.7 ms) and at day 5 (mean increase, 27.3 ms) of hospitalization, compared with patients without COVID-19 infection, "even after adjusting for age, gender, and comorbidities, including use of possible QT prolonging drugs."

In multivariate analysis, factors significantly associated with prolonged QTc in COVID-19 patients were age of at least 80 years, severe kidney disease, elevated high sensitivity troponin, and elevated lactate dehydrogenase.

Although not the primary focus of the study, the use of any combination of hydroxychloroquine with azithromycin, hydroxychloroquine alone, or azithromycin alone was associated with significant QTc prolongation, the researchers report.

What's "more intriguing," they say, is that 25% of patients with COVID-19 who had not received either drug still had a QTc interval of 500 ms or greater, compared with 11% of their COVID-negative peers.

"In patients with COVID-19, especially those receiving hydroxychloroquine with azithromycin, simply checking a baseline pretreatment ECG assessment of QTc may not be sufficient," Wan and colleagues suggest.

"Obtaining 12-lead ECGs to follow the QTc during hospitalization for COVID-19 infection, especially in those older than 80 years, with severe chronic kidney disease, and those with elevated troponin levels is prudent practice," they say.

The authors also note that one patient with COVID-19 had Torsades de pointes. This patient had a QTc of 528 ms and a magnesium level of 1.4 mg/dL and received intravenous azithromycin. The incidence of Torsades de pointes in the setting of COVID-19 infection in recent studies is "similarly low and limited to rare events," they note.

Collateral Damage

"This is a large and important study," write Susan P. Etheridge, MD, and S. Yukiko Asaki, MD, University of Utah, Salt Lake City, in a linked editorial.

Emerging data suggest that SARS-CoV-2 leads to a decrease in cardiac contractility and an increase in susceptibility to arrhythmias by affecting ion channels. Excessive inflammation can further alter the function of several ion channels, specifically K+ and Ca2+ channels, leading to inflammatory cardiac channelopathies, QT prolongation, and arrhythmias, they point out.

"This collateral damage from COVID-19 infections highlights the importance of monitoring the QT interval during acute illness, correcting all possible contributing factors, such as fever and electrolyte disturbances, and avoiding medications known to lengthen repolarization. Changes in the QT may be an early predictor of myocyte viral damage, a viral channelopathy, and may herald the development of arrhythmias," Etheridge and Asaki write.

The finding of prolonged QTc in the setting of a COVID-19 infection, they add, "like so much to do with this disease, leaves us frustrated about what to do next. The arrhythmias that occur as a consequence of disordered ventricular repolarization — Torsade de pointes, polymorphic ventricular tachycardia, and ventricular fibrillation — are treatable, yet a mechanism for avoiding them would be ideal."

"There are data indicating that increasing the serum K+ level and certainly avoiding a low K+ might shorten the QTc. Sodium channel-blocking agents, such as mexiletine, can shorten the QT interval even in patients without a sodium channelopathy. How these strategies can be used in a patient with COVID-remains uncharted territory," Etheridge and Asaki conclude.

The study had no commercial funding. Wan has no relevant disclosures. A complete list of author disclosures is available with the original article.

JAMA Netw Open. Published online April 23, 2021. Full text, Editorial


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