a b s t r a c t

Objectives: Acute COVID-19 infection may be associated with Electrocardiogram abnormalities in pediatric patients. We have anecdotally observed EKG abnormalities in patients without MIS-C or significant cardiac disease requiring intervention or further follow-up. Our aim was to determine the incidence of abnormal EKG findings and correlate with evidence of significant cardiac pathology in pediatric patients who present to the emergency department during an acute COVID-19 infection.

Methods: We conducted a retrospective chart review of 209 pediatric patients diagnosed in the emergency de- partment with acute COVID-19 infection and had an EKG during the same encounter; patients with MIS-C were excluded. Primary objectives included determination of the incidence of EKG abnormalities in patients pre- senting to the emergency department (ED) with acute COVID-19 infection who did not require hospitalization. Secondary objectives included correlation of these findings with other concomitant testing of possible cardiac pathology (echocardiograms, biomarkers), and clinical outcomes.

Results: EKG abnormalities were identified in 84 (40%) patients. Echo was performed in 28 (13.4%) patients; only 1 was abnormal, and considered an incidental finding. The most common EKG abnormality involved nonspecific ST-T wave patterns, suggestive of but not diagnostic for underlying pericardial or myocardial disease. serum troponin and BNP values were normal in all patients tested, either with a normal or abnormal EKG. A normal EKG had a 100% sensitivity and negative predictive value in predicting a normal echocardiogram. No patients were hospitalized and there was normalization of EKG abnormalities during short-term follow up.

Conclusions: Despite a high incidence of abnormal EKG repolarization patterns in pediatric patients presenting with acute (non-MIS-C) COVID-19 infections, these patients generally do not have abnormal cardiac biomarkers or echocardiograms, and the risk for adverse cardiac events is low.

(C) 2023

1. Introduction/Background

Patients with acute COVID-19 infection may present with significant cardiac complications, not limited to myocardial dysfunction, acute cor- onary syndrome, cardiogenic shock, cardiomyopathy, heart failure, myocarditis, and arrhythmias [1,2]. Whereas ~25% adults hospitalized with COVID-19 have Cardiovascular complications [3], the incidence in

pediatric patients is comparatively quite low [4-7].

Published reports including electrocardiogram (EKG) findings in pe- diatric patients with acute COVID-19 infection are limited [8,9].

* Corresponding author at: 571 Floyd St Suite 412, Louisville, KY 40202, USA.

E-mail addresses: [email protected], [email protected] (S. Dasgupta).

Cantarutti et al. evaluated 294 pediatric patients with COVID-19 and/ or multisystem inflammatory syndrome (MIS-C) and found that 85% had cardiac involvement [10]. Of the 248 patients with Acute infection, 18% had EKG abnormalities. Other pediatric studies have demonstrated a higher incidence of EKG abnormalities and cardiac involvement in patients hospitalized with COVID-19 or MIS-C [11].

In contrast, a study of 82 children with less severe COVID-19 disease found that 9% had EKG abnormalities, and none had an abnormal echo- cardiogram (echo) [12]. We have also observed EKG abnormalities in non-hospitalized pediatric patients with acute COVID-19 infection who lacked significant structural or functional cardiac disease. We sought to determine the incidence of EKG abnormalities in a large co- hort of patients presenting to the emergency department (ED) with acute COVID-19 infection who did not require hospitalization.

https://doi.org/10.1016/j.ajem.2023.06.041

0735-6757/(C) 2023

Secondary objectives included correlation of these findings with other concomitant testing of possible cardiac pathology and clinical outcomes.

1. Methods

A retrospective chart review was performed of all pediatric patients (0-21 years) diagnosed with acute COVID-19 infection presenting to the ED from March 2020 to November 2021, and who received an EKG as ordered by ED providers during the same encounter. Only pa- tients with a positive PCR were included to eliminate potential contam- ination by false positivity in rapid antigen and home testing; in addition, patients known to have preexisting heart disease and those with MIS-C were excluded [11]. The institutional review boards at both the Univer- sity of Louisville and Norton Healthcare approved this study.

Charts were reviewed to collect demographic information (age, gen- der, weight, and race/ethnicity), presenting complaint, relevant past medical history, current medications, and mortality.

For the purposes of this analysis, EKG findings for each patient were classified as normal or abnormal, and abnormal findings were sub-classified into specific categories. As nonspecific but likely benign repolarization changes are relatively common in children, only repolar- ization abnormalities considered significant (e.g., T wave inversions that were diffuse or present in lateral precordial leads, ST segment elevation suggestive of pericarditis, etc.) were classified as “abnormal” (Fig. 1). Other repolarization findings such as isolated mild T wave flattening were classified as “normal.” Per institutional workflow, all EKGs were formally interpreted by pediatric electrophysiologists (SD and CLJ) subsequent to the initial patient encounter, unless an ED provider spe- cifically requested a stat EKG interpretation. The pediatric electrophysi- ologists (SD and CLJ) made the final determination of a normal vs an abnormal EKG.

We also collected levels of serum troponin and brain natriuretic pep- tide (BNP) as requested by the ED provider. Results from echocardio- grams were classified as normal or abnormal based on the reports of the interpreting cardiologist. Available follow-up data for patients with abnormal EKGs was obtained, including findings on a repeat EKG and outcomes at any subsequent pediatric cardiology consultation.

• 1. Statistical analysis

Statistical analysis was performed using SAS software version 9.4 (SAS Institute, Cary, NC). Descriptive analyses were utilized to

summarize the derivative cohort characteristics. A measure of fre- quency with corresponding percentages were used for categorical data, and median and the interquartile range (IQR) was utilized for continuous variables, all of which were non-normally distributed. The Chi-Square test or Fisher’s Exact test was used to examine the associa- tion between the categorical variables. Wilcoxon Rank Sums test was conducted to compare the medians and Shapiro-Wilk test was used to assess the normality of data. A two-sided p value <0.05 was statistically significant.

1. Results

A total of 300 patients were found to have a diagnosis of acute COVID-19 infection when an EKG was obtained during the same en- counter. Ultimately, 209 patients met inclusion criteria. The median age (IQR) of study patients was 17.0 [7] years with 67% of the patients being female. Of note, all cardiac-related testing was ordered by the re- sponsible ED provider per individual preference, sometimes simulta- neously or stepwise. The most common indication for obtaining an EKG was chest symptoms (Table 1). In this cohort, none of the patients required acute hospitalization. There was a single death in a 15-year-old female who had been diagnosed with acute COVID-19 infection eight days earlier. She subsequently developed respiratory distress and acute respiratory failure at home, and was in cardiopulmonary arrest upon arrival of EMS. Her EKG at the time of previous COVID-19 presen- tation demonstrated LVH by voltage criteria and non-specific ST-T wave changes, but an echo, troponin, or BNP were not obtained; autopsy was not performed.

EKG abnormalities were identified in 84 (40%) patients. The most common abnormality included significant ST-T wave changes (diffuse T wave inversion, T wave inversion in lateral precordial leads, ST eleva- tion suggestive of pericarditis), found in 36 (42%) patients. The EKG ab- normalities are described in detail in Table 2. A single patient had first degree AV block (echo, troponin or BNP were not obtained), and none had higher grade AV block. There were no patients with documented acute bradyarrhythmias, but 2 were later found to have tachyarrhyth- mias (see below). Thirteen patients (15.5%) had evidence of Conduction abnormalities (Table 2) with the most common being non-specific in- traventricular conduction delay. An echo was normal in all patients when performed for a conduction abnormality on EKG.

Echo was performed in 28 (13.4%) patients, and only 1 was abnor- mal. This patient’s echo demonstrated incidental mitral valve prolapse

Fig. 1. An example of an abnormal EKG in a pediatric patient with acute COVID-19 infection showing diffuse T wave flattening and T wave inversion in the lateral precordial leads.

Table 1

Demographic characteristics of pediatric patients presenting to the ED with acute COVID-19 infection.

Variable Median (Interquartile Range) or N (%)

Age (years) 17.0 (7.0)

Weight (kg) 67.4 (35.3)

Male Female

Gender

69 (33%) 140 (67%)

BMI (kg/m2) 26.0 (9.8)

Caucasian African American Hispanic/Latino Other

Race/ethnicity

Chief complaint

Past medical history

Indication for EKG

Hospital admission

103 (49%) 94 (45%) 10 (5%) 2 (1%)

SOB Chest pain Fever Syncope Abdominal pain Sore throat Other 69 (33%) 70 (34%) 45 (21%) 13 (6%) 7 (3%) 3 (1%) 2 (0.1%)

Asthma HTN Diabetes Immunocompromised Other

54 (26%) 0 (0%) 4 (2%) 5 (2%) 13 (6%)

Chest pain SOB Syncope Palpitations Other

111 (53%) 45 (21%) 16 (8%) 14 (7%) 23 (11%)

Yes No

0 (0%) 209 (100%)

Troponin (ng/ml) 0.01 (0.002)

BNP (pg/ml) 16.1 (24.7)

SOB: Shortness of breath; HTN: Hypertension; ICU: Intensive Care Unit; BNP: B-type Natriuretic Peptide.

Table 2 Description and incidence of EKG abnormalities in pediatric patients presenting to the ED with acute COVID-19 infection.

EKG findings

Yes No

Abnormality

84 (40%) 125 (60%)

Significant ST-T abnormalities 34 (40%)

Ventricular hypertrophy by voltage 18 (21%)

LVH 11 (13%)

RVH 4 (5%)

BVH 3 (3%)

Atrial enlargement 9 (11%)

LAE 8 (9%)

RAE 1 (1%)

Intraventricular conduction delay 6 (7%)

Incomplete Right bundle branch block 4 (5%)

Right bundle branch block 2 (2%)

First degree AV block 1 (1%)

Abnormal frontal plane axis 6 (7%)

with mild Mitral regurgitation; the patient’s EKG showed an abnormal frontal plane axis. Therefore, the sensitivity and specificity of an abnor- mal EKG in predicting an abnormal echo was 100% and 55.6%, respec- tively. The positive and negative predictive values were 7.7% and 100%.

Serum troponins were normal in all 143 (68.4%) patients tested; 59 of these patients had abnormal EKGs (Fig. 2). Similarly, serum BNP values were normal in all 78 (37.3%) patients tested; 38 of these patients had abnormal EKGs (Fig. 2).

Of the 84 patients with an abnormal EKGs, 34 (40.4%) had a follow- up EKG after discharge from the ED with an average total follow up du- ration of 14 months. All repeat EKGs showed normalization of the ab- normal ST-T waves. Of the 13 (15.5%) patients with evidence of a conduction abnormality on initial EKG, 11 had a repeat EKG. EKG find- ings normalized in 4 of these patients (3 with intraventricular conduc- tion delay and one with first degree AV block). Eight patients had a Pediatric Cardiology follow-up for palpitations, dizziness, or fatigue post COVID-19 infection. Six of the eight patients had a normal Pediatric

Cardiology evaluation, and were formally discharged. One patient with

Prolonged corrected QTc

(>450 ms males; >460 ms females)

4 (5%)

intermittent palpitations for a year prior to Covid infection was found to have focal atrial tachycardia on Holter. Another patient subsequently

LVH: Left ventricular hypertrophy; RVH: Right ventricular hypertrophy; BVH: Bi-ventric-

ular hypertrophy; LAE: left atrial enlargement; RAE: Right atrial enlargement; QTc: Corrected QT interval, Bazett.

presented with a common form of reentrant AV nodal-dependent sup- raventricular tachycardia, and started on anti-arrhythmic medication.

Fig. 2. Comparison of findings on EKG, echocardiogram, and serum troponin and BNP values in patients with acute COVID-19 infection.

1. Discussion

Our study found an unexpectedly high incidence (40%) of abnormal repolarization patterns on EKG in pediatric patients presenting to the ED with acute COVID-19 infection but not having MIS-C or requiring acute hospitalization. Importantly, concomitant serum troponin and BNP values and echocardiograms, when obtained by the ED provider, showed no evidence of significant related cardiac pathology. Limited follow-up data demonstrated normalization of EKG repolarization ab- normalities that were evident during acute COVID-19 infection.

The incidence of EKG abnormalities in our patient cohort was higher than prior reports [8-10,12], and may reflect selection bias as this retro- spective study was limited to patients with acute COVID-19 infection who received an EKG, most often for chest complaints. The most com- mon EKG abnormality involved ST-T waves, potentially a common phe- nomenon but simply non-specific in any patient with acute illness [13]. Specifically, in patients with COVID-19 infection, it is hypothesized that T wave changes on an EKG may be secondary to direct myocardial injury (sicker patients with myocarditis, elevated troponin) or indirect myo- cardial injury because of inflammation and autoimmune response to the infection (patients with mild illness) [14]. It is noteworthy that we classified EKGs with subtle or borderline Repolarization abnormalities as “normal” for the purpose of analysis.

Recent studies in adults hospitalized with Covid have also described repolarization abnormalities as the most common EKG abnormality [15,16]. In addition, De Carvalho and co-workers reported that the pres- ence of an abnormal EKG frontal plane axis and Left bundle branch block pattern indicated a higher risk of in-hospital mortality [15]. Although repolarization abnormalities were also common in our study of non- hospitalized pediatric patients, none of our patients had left bundle branch block. Additionally, an echo failed to demonstrate any cardiac pathology when performed for conduction abnormalities noted on EKG. There was only a single patient with left axis deviation on EKG, and this was associated with a congenital mitral valve anomaly by echo.

While studies have described a high incidence of echo abnormalities in adult patients with hospitalized COVID-19 [17], the incidence of echo abnormalities in non-hospitalized pediatric patients remains low [18,19], in line with our findings. In addition, all patients with an abnor- mal EKG had normal troponin and BNP levels, further support of the nonspecific nature of these EKG findings in pediatric patients with acute COVID-19 infection. Importantly, in patients with follow-up EKGs, repolarization abnormalities recorded during acute COVID-19 in- fection had normalized. We did not suspect that COVID-19 infection contributed to arrhythmias subsequently documented in 2 patients, one with chronic palpitations prior to presenting to the ED, and the other developing a relatively common form of childhood SVT likely due to a congenital predisposition.

Limitations of this study include its retrospective nature, the small sample size from a single institution, and selection bias as patients had presented to the ED. Findings from this study therefore pertain to pedi- atric patients who are not critically ill at presentation, rather than those requiring hospitalization or found to have MIS-C. The study only in- cluded those with RT-PCR positive COVID-19 tests, excluding those who may have had a truly positive non-rt-PCR test. Finally, the sensi- tivity, specificity, positive and negative predictive values should be interpreted with caution as only a small percentage of patients under- went an echocardiogram in this study.

1. Conclusion

Our study shows that the incidence of abnormal repolarization pat- terns in pediatric patients presenting to the ED with acute COVID-19 in- fection, but not MIS-C, is unexpectedly high. However, serum biomarkers (troponin, BNP), echocardiograms did not indicate

significant myocardial involvement. In addition, the incidence of Major adverse cardiac events was low in patients after discharge and EKG repolarization abnormalities normalized during short-term follow-up. Larger studies, preferably in a multicenter setting, are re- quired to validate these findings.

Funding source

This research did not receive any specific grant from funding agen- cies in the public, commercial, or not-for-profit sectors.

CRediT authorship contribution statement

Andrew Van Hersh: Writing – review & editing, Writing – original draft, Methodology, Investigation, Data curation. Kahir Jawad: Writing – review & editing, Validation, Methodology, Investigation, Formal anal- ysis. Yana Feygin: Writing – review & editing, Validation, Methodology, Investigation, Formal analysis. Christopher Johnsrude: Writing – review & editing, Validation, Supervision, Methodology, Conceptua- lization. Soham Dasgupta: Writing – review & editing, Writing – original draft, Validation, Supervision, Methodology, Investigation, Conceptualization.

Declaration of Competing Interest

The authors have no relevant conflicts of interest to disclose.

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