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 ECG s. Critical QT c prolongation was defined as follows: (1) maximum QT c ≥500 ms (if QRS <120 ms) or QT c ≥550 ms (if QRS ≥120 ms) and (2) QT c 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 QT c 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 QT c prolongation. Changes in QT c 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 QT c 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.

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.

1 Background: Despite a paucity of clinical evidence, hydroxychloroquine and 2 azithromycin are being administered widely to patients with verified or suspected 3 COVID-19. Both drugs may increase risk of lethal arrhythmias associated with QT 4 interval prolongation.5Methods: We performed a case series of COVID-19 positive/suspected patients admitted 6 between 2/1/2020 and 4/4/2020 who were treated with azithromycin, hydroxychloroquine 7 or a combination. We evaluated baseline and post-medication QT interval (QTc, Bazett's) 8 using 12-lead ECGs. Critical QTc prolongation was defined as: a) maximum QTc ≥500 ms 9 (if QRS <120 ms) or QTc ≥550 (if QRS ≥120 ms) and b) increased QTc of ≥60 ms. Tisdale 10 score and Elixhauser comorbidity index were calculated. 11 Results: Of 490 COVID-19 positive/suspected patients, 314 (64%) received either/both 12 drugs, and 98 (73 COVID-19 positive, 25 suspected) met study criteria (age 62±17 yrs, 13 61% male). Azithromycin was prescribed in 28%, hydroxychloroquine in 10%, and both in 14 62%. Baseline mean QTc was 448±29 ms and increased to 459±36ms (p=0.005) with 15 medications. Significant prolongation was observed only in men (18±43 ms vs -0.2±28 ms 16 in women, p=0.02). 12% of patients reached critical QTc prolongation. In a multivariable 17 logistic regression, age, sex, Tisdale score, Elixhauser score, and baseline QTc were not 18 associated with critical QTc prolongation (p>0.14). Changes in QTc were highest with the 19 combination compared to either drug, with many-fold greater prolongation with the 20 combination vs. azithromycin alone (17±39 vs. 0.5±40 ms, p=0.07). No patients 21 manifested torsades de pointes. 22. CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review)Conclusions: Overall, 12% of patients manifested critical QTc interval prolongation, 1 and traditional risk indices failed to flag these patients. With the drug combination, QTc 2 prolongation was several-fold higher compared to azithromycin alone. The balance 3 between uncertain benefit and potential risk when treating COVID-19 patients with 4 these drugs should be carefully assessed prior to use. 7 2/1/2020 and 4/4/2020 who received either AZ and/or HCQ as part of their medical 8 treatment. A detailed, retrospective chart review was then performed via the electronic 9 health record (Epic, Verona, WI) at our institution. Of the PUI and confirmed COVID-19 10 cases, we only included patients who had at least two 12-lead electrocardiograms 11 (ECGs) performed in our MUSE system between 1/1/2020 and 4/5/2020. Patients with 12 paced ventricular rhythms, atrial fibrillation, atrial flutter, supraventricular tachycardia, or 13 ECGs otherwise unsuitable for accurate QT interval measurement were excluded. 14 Additionally, patients without ECGs performed on day 2 of medication administration or 15 later were excluded (Figure 1). Our hospital policy states that daily ECGs sh...

Increased concentrations of inflammatory markers (IL-2 and anti-HSP60) are associated with an increased CAC at baseline and follow-up in healthy asymptomatic adults. Future studies should be carried out to assess its association with early development of atherosclerosis.

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Transendocardial stem cell injection in patients with ischemic cardiomyopathy (ICM) improves left ventricular function and structure but has ill‐defined effects on ventricular arrhythmias. We hypothesized that mesenchymal stem cell (MSC) implantation is not proarrhythmic. Post hoc analyses were performed on ambulatory ECGs collected from the POSEIDON and TAC‐HFT trials. Eighty‐eight subjects (mean age 61 ± 10 years) with ICM (mean EF 32.2% ± 9.8%) received treatment with MSC (n = 48), Placebo (n = 21), or bone marrow mononuclear cells (BMC) (n = 19). Heart rate variability (HRV) and ventricular ectopy (VE) were evaluated over 12 months. VE did not change in any group following MSC implantation. However, in patients with ≥ 1 VE run (defined as ≥ 3 consecutive premature ventricular complexes in 24 hours) at baseline, there was a decrease in VE runs at 12 months in the MSC group (p = .01), but not in the placebo group (p = .07; intergroup comparison: p = .18). In a subset of the MSC group, HRV measures of standard deviation of normal intervals was 75 ± 30 msec at baseline and increased to 87 ± 32 msec (p =.02) at 12 months, and root mean square of intervals between successive complexes was 36 ± 30 msec and increased to 58.2 ± 50 msec (p = .01) at 12 months. In patients receiving MSCs, there was no evidence for ventricular proarrhythmia, manifested by sustained or nonsustained ventricular ectopy or worsened HRV. Signals of improvement in ventricular arrhythmias and HRV in the MSC group suggest a need for further studies of the antiarrhythmic potential of MSCs. Stem Cells Translational Medicine 2017;6:1366–1372

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