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

Abstract 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.

A common cardiac manifestation in patients with COVID-19 infection is disturbances of cardiac rhythm. In a cohort study of 137 hospitalized patients with COVID-19 infection, 75 of enrolled patients complained of palpitation as a presenting symptom (Bacharova, 2019;Bertini et al., 2020) Furthermore, arrhythmias is one of the most known causes of death in critically ill patients.
A higher rate of arrhythmic events was reported in patients with COVID-19 infection particularly in those admitted to intensive care unit where the prevalence rate was double in comparison with non-intensive care unit patients (16(44.4%) vs. 7(6.9%), p < .00; Wangetal.,2020)However,thespecifictypeandpotentialunderlying mechanisms are not defined and remained a challenging issue in clinicalpractice(Vlachakisetal.,2020).
All patients were presented with features consistent with COVID-19 pneumonia based on clinical symptoms and radiological findings (CXR or computerized tomography (CT) examination of the lung).
The diagnosis of COVID-19 was confirmed by polymerase chain reaction (PCR) nasopharyngeal swab. Patients with chronic kidney disease,anti-arrhythmicmedications,pacemakerimplantation,and atrialfibrillationanduninterpretableECGpaperwerenotincluded in the present study.
The control group consisted of 46 age-and sex-matched persons who proved to have normal coronary arteries according to CT coronaryangiographyexamination,havingnolungdisease,valvularor myocardial diseases. Controls were selected from our previous work collected before the COVID-19 pandemic Nafakhi et al., 2018). Approval of this study was provided by our medicine college board.
Clinical data of the patients and ECG markers were expressed as mean ± standard deviation for continuous variables or as numbers withpercentagesforcategoricaldata.Student'st-test was used to assess the distribution of clinical patients' characteristics and ECG markers between the COVID-19 pneumonia group and controls.

| Assessment of ECG markers among COVID-19 pneumonia groups
According to the severity of COVID-19 pneumonia, patients were assigned into 3 groups as mild-moderate COVID-19 pneumonia group consisted of 48 (76%) patients not requiring hospital admission and treated at home with lung injury <50%onCTexamination,
A multi-center analysis of 431 hospitalized COVID-19 patients reportedthatQTcprolongationwasthemostfrequentfinding(38%) which can be attributed to critical illness and hypoxemia. Also, a significant prolongation in the QRS interval was found in 19% of enrolled patients, particularly among elderly patients, which can be attributed to right ventricular dysfunction in the context of respiratory failure even before starting drug therapy for COVID-19 infection (Bertini et al., 2020). Other researchers also found that  (Çınar et al., 1992; Yenerçağetal.,2020)However,lackofenrollmentofpatientswith COVID-19 pneumonia or lung involvement and controls before COVID-19infectionwerethemainlimitationsoftheabove2studies.
It has been suggested that ECG markers may have a different predictive impact among different diseases (Mandala & Di, 2017).
The prolongation of QTc interval may not increase the TDR and  group should be taken with caution because of a very small number of enrolledpatientswithcriticalstatus(5(8%))andhigherprevalenceof male and elderly patients in the critical group than in other pneumonia groups,whichmayhaveledtoaselectionbias.
Alargesamplewithafollow-upstudyisrequiredtoconfirmthe results of the present study.

CO N FLI C T O F I NTE R E S T
The authors declare that they have no conflict of interest.

DATA AVA I L A B I L I T Y S TAT E M E N T
The data that support the findings of this study are available from thecorrespondingauthoruponreasonablerequest.