Cardiac Corrected QT Interval Changes Among Patients Treated for COVID-19 Infection During the Early Phase of the Pandemic
Authors: Geoffrey A. Rubin, Amar D. Desai, Zilan Chai, Aijin Wang, Qixuan Chen, Amy S. Wang, Cameron Kemal, Haajra Baksh, Angelo Biviano, Jose M. Dizon, Hirad Yarmohammadi, Frederick Ehlert, Deepak Saluja, David A. Rubin, John P. Morrow, Uma Mahesh R. Avula, Jeremy P. Berman, Alexander Kushnir, Mark P. Abrams, Jessica A. Hennessey, Pierre Elias, Timothy J. Poterucha, Nir Uriel, Christine J. Kubin, Elijah LaSota, Jason Zucker, Magdalena E. Sobieszczyk, Allan Schwartz, Hasan Garan, Marc P. Waase, Elaine Y. Wan
Journal: JAMA Network Open (2021)

<h3>Importance</h3> Critical illness, a marked inflammatory response, and viruses such as SARS-CoV-2 may prolong corrected QT interval (QTc). <h3>Objective</h3> To evaluate baseline QTc interval on 12-lead electrocardiograms (ECGs) and ensuing changes among patients with and without COVID-19. <h3>Design, Setting, and Participants</h3> This cohort study included 3050 patients aged 18 years and older who underwent SARS-CoV-2 testing and had ECGs at Columbia University Irving Medical Center from March 1 through May 1, 2020. Patients were analyzed by treatment group over 5 days, as follows: hydroxychloroquine with azithromycin, hydroxychloroquine alone, azithromycin alone, and neither hydroxychloroquine nor azithromycin. ECGs were manually analyzed by electrophysiologists masked to COVID-19 status. Multivariable modeling evaluated clinical associations with QTc prolongation from baseline. <h3>Exposures</h3> COVID-19, hydroxychloroquine, azithromycin. <h3>Main Outcomes and Measures</h3> Mean QTc prolongation, percentage of patients with QTc of 500 milliseconds or greater. <h3>Results</h3> A total of 965 patients had more than 2 ECGs and were included in the study, with 561 (58.1%) men, 198 (26.2%) Black patients, and 191 (19.8%) aged 80 years and older. There were 733 patients (76.0%) with COVID-19 and 232 patients (24.0%) without COVID-19. COVID-19 infection was associated with significant mean QTc prolongation from baseline by both 5-day and 2-day multivariable models (5-day, patients with COVID-19: 20.81 [95% CI, 15.29 to 26.33] milliseconds;<i>P</i> &lt; .001; patients without COVID-19: −2.01 [95% CI, −17.31 to 21.32] milliseconds;<i>P</i> = .93; 2-day, patients with COVID-19: 17.40 [95% CI, 12.65 to 22.16] milliseconds;<i>P</i> &lt; .001; patients without COVID-19: 0.11 [95% CI, −12.60 to 12.81] milliseconds;<i>P</i> = .99). COVID-19 infection was independently associated with a modeled mean 27.32 (95% CI, 4.63-43.21) millisecond increase in QTc at 5 days compared with COVID-19–negative status (mean QTc, with COVID-19: 450.45 [95% CI, 441.6 to 459.3] milliseconds; without COVID-19: 423.13 [95% CI, 403.25 to 443.01] milliseconds;<i>P</i> = .01). More patients with COVID-19 not receiving hydroxychloroquine and azithromycin had QTc of 500 milliseconds or greater compared with patients without COVID-19 (34 of 136 [25.0%] vs 17 of 158 [10.8%],<i>P</i> = .002). Multivariable analysis revealed that age 80 years and older compared with those younger than 50 years (mean difference in QTc, 11.91 [SE, 4.69; 95% CI, 2.73 to 21.09];<i>P</i> = .01), severe chronic kidney disease compared with no chronic kidney disease (mean difference in QTc, 12.20 [SE, 5.26; 95% CI, 1.89 to 22.51;<i>P</i> = .02]), elevated high-sensitivity troponin levels (mean difference in QTc, 5.05 [SE, 1.19; 95% CI, 2.72 to 7.38];<i>P</i> &lt; .001), and elevated lactate dehydrogenase levels (mean difference in QTc, 5.31 [SE, 2.68; 95% CI, 0.06 to 10.57];<i>P</i> = .04) were associated with QTc prolongation. Torsades de pointes occurred in 1 patient (0.1%) with COVID-19. <h3>Conclusions and Relevance</h3> In this cohort study, COVID-19 infection was independently associated with significant mean QTc prolongation at days 5 and 2 of hospitalization compared with day 0. More patients with COVID-19 had QTc of 500 milliseconds or greater compared with patients without COVID-19.