Cardiac Corrected QT Interval Changes Among Patients Treated for COVID-19 Infection During the Early Phase of the Pandemic.

Importance: Critical illness, a marked inflammatory response, and viruses such as SARS-CoV-2 may prolong corrected QT interval (QTc). Objective: To evaluate baseline QTc interval on 12-lead electrocardiograms (ECGs) and ensuing changes among patients with and without COVID-19. Design, Setting, and Participants: 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. Exposures: COVID-19, hydroxychloroquine, azithromycin. Main Outcomes and Measures: Mean QTc prolongation, percentage of patients with QTc of 500 milliseconds or greater. Results: 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; P < .001; patients without COVID-19: -2.01 [95% CI, -17.31 to 21.32] milliseconds; P = .93; 2-day, patients with COVID-19: 17.40 [95% CI, 12.65 to 22.16] milliseconds; P < .001; patients without COVID-19: 0.11 [95% CI, -12.60 to 12.81] milliseconds; P = .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; P = .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%], P = .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]; P = .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; P = .02]), elevated high-sensitivity troponin levels (mean difference in QTc, 5.05 [SE, 1.19; 95% CI, 2.72 to 7.38]; P < .001), and elevated lactate dehydrogenase levels (mean difference in QTc, 5.31 [SE, 2.68; 95% CI, 0.06 to 10.57]; P = .04) were associated with QTc prolongation. Torsades de pointes occurred in 1 patient (0.1%) with COVID-19. Conclusions and Relevance: 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.

Coronavirus disease 2019 (COVID-19) and QTc prolongation.

INTRODUCTION: The cause-and-effect relationship of QTc prolongation in Coronavirus disease 2019 (COVID-19) patients has not been studied well. OBJECTIVE: We attempt to better understand the relationship of QTc prolongation in COVID-19 patients in this study. METHODS: This is a retrospective, hospital-based, observational study. All patients with normal baseline QTc interval who were hospitalized with the diagnosis of COVID-19 infection at two hospitals in Ohio, USA were included in this study. RESULTS: Sixty-nine patients had QTc prolongation, and 210 patients continued to have normal QTc during hospitalization. The baseline QTc intervals were comparable in the two groups. Patients with QTc prolongation were older (mean age 67 vs. 60, P 0.003), more likely to have underlying cardiovascular disease (48% versus 26%, P 0.001), ischemic heart disease (29% versus 17%, P 0.026), congestive heart failure with preserved ejection fraction (16% versus 8%, P 0.042), chronic kidney disease (23% versus 10%, P 0.005), and end-stage renal disease (12% versus 1%, P < 0.001). Patients with QTc prolongation were more likely to have received hydroxychloroquine (75% versus 59%, P 0.018), azithromycin (18% vs. 14%, P 0.034), a combination of hydroxychloroquine and azithromycin (29% vs 7%, P < 0.001), more than 1 QT prolonging agents (59% vs. 32%, P < 0.001). Patients who were on angiotensin-converting enzyme inhibitors (ACEi) were less likely to develop QTc prolongation (11% versus 26%, P 0.014). QTc prolongation was not associated with increased ventricular arrhythmias or mortality. CONCLUSION: Older age, ESRD, underlying cardiovascular disease, potential virus mediated cardiac injury, and drugs like hydroxychloroquine/azithromycin, contribute to QTc prolongation in COVID-19 patients. The role of ACEi in preventing QTc prolongation in COVID-19 patients needs to be studied further.

Electrocardiographic markers of increased risk of sudden cardiac death in patients with COVID-19 pneumonia.

BACKGROUND: Little is known about the role of ECG markers of increased risk of sudden cardiac death during the acute period of coronavirus disease 2019 ( COVID-19) pneumonia. OBJECTIVES: To evaluate ECG markers of sudden cardiac death on admission, including the index of cardiac electrophysiological balance (iCEB) (QTc/QRS) and transmural dispersion of repolarization (TDR) (T from peak to end (Tp-e) interval and Tp-e/QTc), in patients with COVID-19 pneumonia. PATIENTS AND METHODS: This cross-sectional study included 63 patients with newly diagnosed COVID-19 pneumonia who presented to the outpatient clinic or admitted to the respiratory care unit between August 20 and September 15, 2020. Forty-six persons matched for sex and age were selected from data collected before COVID-19 pandemic. RESULTS: QRS and QTc showed a significant prolongation in patients with COVID-19 pneumonia compared to the controls (87 vs. 78, p < .00, and 429 versus. 400, p < .00, respectively). After categorization of patients with COVID-19 pneumonia into 3 groups according to the severity of pneumonia as mild-moderate, severe, and critical groups, a decreased values of QRS were observed in the critical COVID-19 pneumonia group compared to severe and mild-moderate COVID-19 pneumonia groups (p = .04) while increased values of QTc and iCEB(QTc/QRS) were noted in critical COVID-19 pneumonia group compared to other 2 groups(p < .00). CONCLUSIONS: Patients with COVID-19 pneumonia showed significant changes in repolarization and conduction parameters compared to controls. Patients with mild to severe COVID-19 pneumonia may be at low risk for torsades de pointes development.

The value of ECG changes in risk stratification of COVID-19 patients.

BACKGROUND: There is growing evidence of cardiac injury in COVID-19. Our purpose was to assess the prognostic value of serial electrocardiograms in COVID-19 patients. METHODS: We evaluated 269 consecutive patients admitted to our center with confirmed SARS-CoV-2 infection. ECGs available at admission and after 1 week from hospitalization were assessed. We evaluated the correlation between ECGs findings and major adverse events (MAE) as the composite of intra-hospital all-cause mortality or need for invasive mechanical ventilation. Abnormal ECGs were defined if primary ST-T segment alterations, left ventricular hypertrophy, tachy or bradyarrhythmias and any new AV, bundle blocks or significant morphology alterations (e.g., new Q pathological waves) were present. RESULTS: Abnormal ECG at admission (106/216) and elevated baseline troponin values were more common in patients who developed MAE (p = .04 and p = .02, respectively). Concerning ECGs recorded after 7 days (159), abnormal findings were reported in 53.5% of patients and they were more frequent in those with MAE (p = .001). Among abnormal ECGs, ischemic alterations and left ventricular hypertrophy were significantly associated with a higher MAE rate. The multivariable analysis showed that the presence of abnormal ECG at 7 days of hospitalization was an independent predictor of MAE (HR 3.2; 95% CI 1.2-8.7; p = .02). Furthermore, patients with abnormal ECG at 7 days more often required transfer to the intensive care unit (p = .01) or renal replacement therapy (p = .04). CONCLUSIONS: Patients with COVID-19 should receive ECG at admission but also during their hospital stay. Indeed, electrocardiographic alterations during hospitalization are associated with MAE and infection severity.

Cardiac involvement at presentation in patients hospitalized with COVID-19 and their outcome in a tertiary referral hospital in Northern Italy.

The correlation between myocardial injury and clinical outcome in COVID-19 patients is gaining attention in the literature. The aim of the present study was to evaluate the role of cardiac involvement and of respiratory failure in a cohort of COVID-19 patients hospitalized in an academic hospital in Lombardy, one of the most affected Italian (and worldwide) regions by the epidemic. The study included 405 consecutive patients with confirmed COVID-19 admitted to a medical ward from February 25th to March 31st, 2020. Follow-up of surviving patients ended either at hospital discharge or by July 30th, 2020. Myocardial injury was defined on the basis of the presence of blood levels of hs-TnI above the 99th percentile upper reference limit. Respiratory function was assessed as PaO2/FiO2 (P/F) ratio. The primary end-point was death for any cause. During hospitalization, 124 patients died. Death rate increased from 7.9% in patients with normal hs-TnI plasma levels and no cardiac comorbidity to 61.5% in patients with elevated hs-TnI and cardiac involvement (p < 0.001). At multivariable analysis, older age, P/F ratio < 200 (both p < 0.001) and hs-TnI plasma levels were independent predictors of death. However, it must be emphasized that the median values of hs-TnI were within normal range in non-survivors. Cardiac involvement at presentation was associated with poor prognosis in COVID-19 patients, but, even in a population of COVID-19 patients who did not require invasive ventilation at hospital admission, mortality was mainly driven by older age and respiratory failure.

The Prognostic Value of Electrocardiogram at Presentation to Emergency Department in Patients With COVID-19.

OBJECTIVE: To study whether combining vital signs and electrocardiogram (ECG) analysis can improve early prognostication. METHODS: This study analyzed 1258 adults with coronavirus disease 2019 who were seen at three hospitals in New York in March and April 2020. Electrocardiograms at presentation to the emergency department were systematically read by electrophysiologists. The primary outcome was a composite of mechanical ventilation or death 48 hours from diagnosis. The prognostic value of ECG abnormalities was assessed in a model adjusted for demographics, comorbidities, and vital signs. RESULTS: At 48 hours, 73 of 1258 patients (5.8%) had died and 174 of 1258 (13.8%) were alive but receiving mechanical ventilation with 277 of 1258 (22.0%) patients dying by 30 days. Early development of respiratory failure was common, with 53% of all intubations occurring within 48 hours of presentation. In a multivariable logistic regression, atrial fibrillation/flutter (odds ratio [OR], 2.5; 95% CI, 1.1 to 6.2), right ventricular strain (OR, 2.7; 95% CI, 1.3 to 6.1), and ST segment abnormalities (OR, 2.4; 95% CI, 1.5 to 3.8) were associated with death or mechanical ventilation at 48 hours. In 108 patients without these ECG abnormalities and with normal respiratory vitals (rate <20 breaths/min and saturation >95%), only 5 (4.6%) died or required mechanical ventilation by 48 hours versus 68 of 216 patients (31.5%) having both ECG and respiratory vital sign abnormalities. CONCLUSION: The combination of abnormal respiratory vital signs and ECG findings of atrial fibrillation/flutter, right ventricular strain, or ST segment abnormalities accurately prognosticates early deterioration in patients with coronavirus disease 2019 and may assist with patient triage.

Incidence of arrhythmias and electrocardiographic abnormalities in symptomatic pediatric patients with PCR-positive SARS-CoV-2 infection, including drug-induced changes in the corrected QT interval.

BACKGROUND: There is limited data regarding the electrophysiological abnormalities and arrhythmias in children with COVID-19, including those associated with treatment using potentially proarrhythmic hydroxychloroquine (HCQ) and azithromycin (AZN). OBJECTIVES: To describe the electrophysiologic findings and arrhythmias associated with pediatric COVID-19 and its treatment. METHODS: A single-center retrospective chart review was undertaken and included all patients with (1) symptoms of COVID-19 and (2) PCR-positive nasopharyngeal swabs for SARS-CoV-2 who were placed on continuous telemetry for the duration of their hospitalization during March through May, 2020. RESULTS: Thirty-six patients were included in the study. Significant arrhythmias were found in 6 (nonsustained ventricular tachycardia in 5 and sustained atrial tachycardia in 1). All were self-resolving and half prompted prophylactic antiarrhythmic therapy. Patients with significant arrhythmias were likely to have noncardiac comorbidities (4/6), but these were not more common than in patients without arrhythmias (20/30, P = 1). The use of HCQ was associated with statistically significant QTc prolongation (413 ± 19 ms vs 425 ± 16 ms, P =.005). QTc was not statistically different in patients with and without arrhythmias (425 ± 15 ms vs 425 ± 15 ms, P = 1). CONCLUSIONS: In pediatric patients with PCR-positive active COVID-19 infection, significant arrhythmias are infrequent, but are more common than expected in a general pediatric population. Comorbidities are not more common in patients with arrhythmias than in patients without arrhythmias. COVID-19 treatment using HCQ is associated with QTc prolongation but was not associated with arrhythmias in pediatric patients.

Effects of hydroxychloroquine treatment on QT interval.

BACKGROUND: Hydroxychloroquine (HCQ) has been promoted as a potential treatment of coronavirus disease 2019 (COVID-19), but there are safety concerns. OBJECTIVE: The purpose of this study was to determine the effects of HCQ treatment on QT interval. METHODS: We retrospectively studied the electrocardiograms of 819 patients treated with HCQ for rheumatologic diseases from 2000 to 2020. The primary outcome was corrected QT (QTc) interval, by Bazett formula, during HCQ therapy. RESULTS: Mean patient age was 64.0 ± 10.9 years, and 734 patients (90%) were men. Median dosage of HCQ was 400 mg daily, and median (25th-75th percentile) duration of HCQ therapy was 1006 (471-2075) days. Mean on-treatment QTc was 430.9 ± 31.8 ms. In total, 55 patients (7%) had QTc 470-500 ms, and 12 (1.5%) had QTc >500 ms. Chronic kidney disease (CKD), history of atrial fibrillation (AF), and heart failure were independent risk factors for prolonged QTc. In a subset of 591 patients who also had a pretreatment electrocardiogram, mean QTc increased from 424.4 ± 29.7 ms to 432.0 ± 32.3 ms (P <.0001) during HCQ treatment. Of these patients, 23 (3.9%) had either prolongation of QTc >15% or on-treatment QTc >500 ms. Over median 5.97 (3.33-10.11) years of follow-up, 269 patients (33%) died. QTc >470 ms during HCQ treatment was associated with a greater mortality risk (hazard ratio 1.78; 95% confidence interval 1.16-2.71; P = .008) in univariable but not in multivariable analysis. CONCLUSION: HCQ is associated with QT prolongation in a significant fraction of patients. The risk of QT prolongation is higher among patients with CKD, AF, and heart failure, who may benefit from greater scrutiny.

Interpretation of arrhythmogenic effects of COVID-19 disease through ECG.

OBJECTIVE: We aimed to detect the malignant arrhythmic potential of COVID-19 with surface electrocardiographic (ECG) markers. MATERIAL AND METHOD: Of the ECG parameters PR, QT, QTc, QTd, TPe, and Tpe/QTc were measured in 51 COVID-19 patients and 40 in control subjects. RESULTS: Compared to control group mean QTc (410.8 ± 24.3 msec vs. 394.6 ± 20.3 msec, p < .001) and Tpe/QTc (0.19 ± 0.02 vs. 0.18 ± 0.04, p = .036) and median QTd (47.52 vs. 46.5) values were significantly higher in COVID-19 patients. Troponin levels were significantly correlated with heart rate (r = 0.387, p = .006) but not with ECG parameters. CONCLUSION: Several ventricular arrhythmia surface ECG predictors including QTc, QTd, and Tpe/QTc are increased in COVID-19 patients. Since medications used in COVID-19 patients have the potential to affect these parameters, giving importance to these ECG markers may have a significant contribution in decreasing disease-related arrhythmias.

The role of cardiovascular imaging for myocardial injury in hospitalized COVID-19 patients.

Recent EACVI recommendations described the importance of limiting cardiovascular imaging during the COVID-19 pandemic in order to reduce virus transmission, protect healthcare professionals from contamination, and reduce consumption of personal protective equipment. However, an elevated troponin remains a frequent request for cardiac imaging in COVID-19 patients, partly because it signifies cardiac injury due to a variety of causes and partly because it is known to convey a worse prognosis. The present paper aims to provide guidance to clinicians regarding the appropriateness of cardiac imaging in the context of troponin elevation and myocardial injury, how best to decipher the mechanism of myocardial injury, and how to guide patient management.