Experience With Hydroxychloroquine and Azithromycin in the Coronavirus Disease 2019 Pandemic: Implications for QT Interval Monitoring.

Background Despite a lack of clinical evidence, hydroxychloroquine and azithromycin are being administered widely to patients with verified or suspected coronavirus disease 2019 (COVID-19). Both drugs may increase risk of lethal arrhythmias associated with QT interval prolongation. Methods and Results We analyzed a case series of COVID-19-positive/suspected patients admitted between February 1, 2020, and April 4, 2020, who were treated with azithromycin, hydroxychloroquine, or a combination of both drugs. We evaluated baseline and postmedication QT interval (corrected QT interval [QTc]; Bazett) using 12-lead ECGs. Critical QTc prolongation was defined as follows: (1) maximum QTc ≥500 ms (if QRS <120 ms) or QTc ≥550 ms (if QRS ≥120 ms) and (2) QTc increase of ≥60 ms. Tisdale score and Elixhauser comorbidity index were calculated. Of 490 COVID-19-positive/suspected patients, 314 (64%) received either/both drugs and 98 (73 COVID-19 positive and 25 suspected) met study criteria (age, 62±17 years; 61% men). Azithromycin was prescribed in 28%, hydroxychloroquine in 10%, and both in 62%. Baseline mean QTc was 448±29 ms and increased to 459±36 ms (P=0.005) with medications. Significant prolongation was observed only in men (18±43 ms versus -0.2±28 ms in women; P=0.02). A total of 12% of patients reached critical QTc prolongation. Changes in QTc were highest with the combination compared with either drug, with much greater prolongation with combination versus azithromycin (17±39 ms versus 0.5±40 ms; P=0.07). No patients manifested torsades de pointes. Conclusions Overall, 12% of patients manifested critical QTc prolongation, and the combination caused greater prolongation than either drug alone. The balance between uncertain benefit and potential risk when treating COVID-19 patients should be carefully assessed.

Cardiac arrhythmias in hospitalized patients with COVID-19: A prospective observational study in the western United States.

Arrhythmias have been reported frequently in COVID-19 patients, but the incidence and nature have not been well characterized. Patients admitted with COVID-19 and monitored by telemetry were prospectively enrolled in the study. Baseline characteristics, hospital course, treatment and complications were collected from the patients' medical records. Telemetry was monitored to detect the incidence of cardiac arrhythmias. The incidence and types of cardiac arrhythmias were analyzed and compared between survivors and non-survivors. Among 143 patients admitted with telemetry monitoring, overall in-hospital mortality was 25.2% (36/143 patients) during the period of observation (mean follow-up 23.7 days). Survivors were less tachycardic on initial presentation (heart rate 90.6 ± 19.6 vs. 99.3 ± 23.1 bpm, p = 0.030) and had lower troponin (peak troponin 0.03 vs. 0.18 ng/ml. p = 0.004), C-reactive protein (peak C-reactive protein 97 vs. 181 mg/dl, p = 0.029), and interleukin-6 levels (peak interleukin-6 30 vs. 246 pg/ml, p = 0.003). Sinus tachycardia, the most common arrhythmia (detected in 39.9% [57/143] of patients), occurred more frequently in non-survivors (58.3% vs. 33.6% in survivors, p = 0.009). Premature ventricular complexes occurred in 28.7% (41/143), and non-sustained ventricular tachycardia in 15.4% (22/143) of patients, with no difference between survivors and non-survivors. Sustained ventricular tachycardia and ventricular fibrillation were not frequent (seen only in 1.4% and 0.7% of patients, respectively). Contrary to reports from other regions, overall mortality was higher and ventricular arrhythmias were infrequent in this hospitalized and monitored COVID-19 population. Either disease or management-related factors could explain this divergence of clinical outcomes, and should be urgently investigated.