Abstract

Graphical Abstract

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Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a highly infectious virus that causes coronavirus disease (COVID-19), a respiratory syndrome associated with high rates of critical illness and mortality.^{1 , 2} As a consequence, there is a need to identify prognostic markers that can aid clinicians in the rapid triage of patients, guide clinical decision making, and inform patients and their families about the anticipated disease trajectory . Electrocardiography (ECG) is a broadly available diagnostic test that can be quickly performed without exposing a large number of personnel to SARS-CoV2 . ECG has demonstrated incremental prognostic value in population-based studies and in patients with a variety of underlying cardiovascular conditions, including hypertension,^{3, 4, 5, 6, 7} and thus offers a particularly appealing modality during the current pandemic . We thus sought to determine whether findings on the first presenting ECG provide prognostic information, specifically related to death, and subsequently provide insights on myocardial processes underlying a poor prognosis.

Methods

Results

Patient Characteristics

From March 3, 2020, through April 9, 2020, 945 patients presented to our hospital and were confirmed by PCR to have SARS-CoV-2. Of these patients, 768 underwent an ECG at or near the time of their admission; 12 patients were excluded from analysis for complete ventricular pacing (Fig. 1 ). Among the remaining 756 patients, the median time between presentation to the ED and initial ECG was less than 1 day and 94.3% had their ECG within 1 day of presentation. Clinical characteristics of the population are shown in Table 1 . The mean age was 63.3 ± 16 years, 37% were women, 61% of patients were nonwhite, 37% had obesity, and 29% had diabetes mellitus. Cardiovascular conditions were common: 57% had hypertension, 14% had CAD, 7% had heart failure, and 7% had a prior stroke. More than one-half (55%) required supplemental oxygen within the first 3 hours of presentation.

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Figure 1

Patients presenting with coronavirus disease-19 from March 3, 2020, to April 9, 2020.

Table 1

Baseline Clinical Characteristics of 756 Patients Hospitalized With Coronavirus Disease-19 With 12-Lead Electrocardiograms, Overall and by Survival Status

Variable	All (N = 756)	Survived (n = 666)	Died (n = 90)	P Value
Age (years)				<.001
Mean ± SD	63.3 ± 16.0	61.1 ± 15.3	79.3 ± 11.8
Median	64.0	62.0	79.6
Interquartile range	51.9–74.6	50.6–72.2	72.2–88.4
Female sex	278 (36.8%)	248 (37.2%)	30 (33.3%)	.546
Race				<.001
White	296 (39.2%)	243 (36.5%)	53 (58.9%)
Black	89 (11.8%)	83 (12.5%)	6 (6.7%)
Asian	56 (7.4%)	47 (7.1%)	9 (10.0%)
Other	162 (21.4%)	154 (23.1%)	8 (8.9%)
Not specified	153 (20.2%)	139 (20.9%)	14 (15.6%)
Smoker				.001
Never smoker	554 (73.3%)	499 (74.9%)	55 (61.1%)
Active smoker	29 (3.8%)	28 (4.2%)	1 (1.1%)
Former smoker	173 (22.9%)	139 (20.9%)	34 (37.7%)
Obesity (n = 716)	267 (37.3%)	241 (38.3%)	26 (30.2%)	.185
Coronary artery disease	109 (14.4%)	80 (12.0%)	29 (32.2%)	<.001
Heart failure	55 (7.3%)	39 (5.9%)	16 (17.8%)	<.001
Stroke	55 (7.3%)	38 (5.7%)	17 (18.9%)	<.001
Diabetes	222 (29.4%)	194 (29.1%)	28 (31.1%)	.792
Hypertension	427 (56.5%)	360 (54.1%)	67 (74.4%)	<.001
Pulmonary disease	142 (18.8%)	116 (17.4%)	26 (28.9%)	.013
Home oxygen use	155 (20.5%)	135 (20.3%)	20 (22.2%)	.771
Renal disease	72 (9.5%)	58 (8.7%)	14 (15.6%)	.059
Rheumatic disease	46 (6.1%)	41 (6.2%)	5 (5.6%)	1.000
Active cancer	42 (5.6%)	29 (4.4%)	13 (14.4%)	<.001
Immunosuppressed	25 (3.3%)	15 (2.3%)	10 (11.1%)	<.001
Hypoxemia within 3 hours	414 (54.8%)	343 (51.5%)	71 (78.9%)	<.001
Home medication number > median (4)	323 (42.7%)	264 (39.6%)	59 (66.3%)	<.001

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SD, standard deviation.

Hypoxemia within 3 hours defined by need for supplemental oxygen. Obesity if body mass index >30 kg/m² or ≥27.5 kg/m² in Asians.

Discussion

This analysis of more than 750 patients with ECGs is the largest study of noninvasive diagnostic testing in patients with confirmed COVID-19 to date. Our findings revealed that APCs, RBBB/IVB, localized T-wave inversion, and nonspecific repolarization abnormalities were associated with an increased odds of death after accounting for age and other important clinical characteristics. ST segment elevation, previously described as an important complication of this disease,⁹ was rare on presentation. Our findings underscore the potential for ECGs to serve as a valuable tool to inform prognosis, even before many patients develop respiratory failure requiring invasive mechanical ventilation; and provide insights on myocardial processes at play.

APCs occurred in 7.7% of patients, and were associated with a 2.57-fold increased odds of death. Historically, the presence of APCs have correlated with increased left ventricular filling pressures, especially after acute myocardial infarction. Whether the presence of APCs in this clinical scenario is indicative of elevated filling pressures and/or increased myocardial stiffness is not known.^{10, 11, 12} However, cytokine hypersecretion, a common finding in COVID-19, has also been linked to transient cardiac systolic and diastolic dysfunction.¹³ Additionally, our observation of T-wave inversions on ECG and the presence of CAD as risk factors for death, coupled with recent data showing that troponin elevations are common,^{14 , 15} suggest a potential role for subendocardial ischemia as well. Future studies examining the complex interplay between SARS-CoV-2 infection and cardiovascular perturbations like elevated filling pressures, left ventricular stiffness, and myocardial ischemia represent an important and fruitful area for future investigation.

Nonspecific repolarization abnormalities were also associated with death, an observation that has been made in the general population.⁵ However, the striking aspect of our observation is that it predicted death in a very short time period—during hospitalization. Meanwhile, myocardial injury as defined by localized ST segment elevation was rare, occurring in just 5 patients, only 1 of whom died. ST elevation has been described in the setting of COVID-19^{9 , 16}; however, our data suggest that this is not a common finding on hospital presentation and suggest that other findings, which may otherwise be overlooked, merit greater attention up front by clinicians caring for patients with COVID-19.

RBBB/IVB was additionally associated with death, and may reflect a higher incidence of early right ventricular (RV) dysfunction in this population. Given the high rate of respiratory failure in a significant proportion of infected individuals, cardiac dysfunction secondary to increased afterload on the right ventricle (referred to as acute cor pulmonale) is not unexpected. Although ECG findings are insensitive for the detection of acute cor pulmonale,¹⁷ RBBB has been attributed to acute RV overload and distention in multiple studies of acute pulmonary embolism, with a higher frequency noted in cases with larger clot burdens.¹⁸ In a recent study, RV dysfunction was associated with a higher risk of mortality in patients with COVID-19, independent of all other echocardiographic parameters.¹⁹ To our knowledge, the present study is the first to show that RBBB at the time of presentation, often before the development of acute respiratory failure, is associated with worse survival. Importantly, the mechanisms of pulmonary vascular disease in COVID-19 are incompletely understood and may include early vascular endothelial injury, microcirculatory thrombi, and pulmonary venous thromboembolism.²⁰ Therefore, the ECG may provide early evidence for an “RV at risk,” even before the onset of severe hypoxemia, pulmonary vasoconstriction, and overt clinical deterioration.

Our study has several strengths. First, clinical data and outcomes were manually abstracted from the electronic health record using a process that has previously shown high reliability.¹ Comorbid conditions manually abstracted from different sections of a medical chart (and often include data from free-text sections of the chart) may be more comprehensive than automated data abstractions from the electronic health record which rely on structured fields and/or billing codes. Second, all ECGs were interpreted by experienced electrocardiographers, which has several advantages, including improved accuracy over automated interpretation.²¹ Our study also has several limitations. First, because the course of this disease is ongoing in our institution, data on death for all patients are inherently incomplete, which may bias the results. Of note, all patients had at least 2 weeks of outcome data. Additionally, we had incomplete laboratory data for the majority of patients included in our study. Markers of myocardial injury (namely, troponin and B-type natriuretic peptide) were obtained clinically at the discretion of the clinician caring for the patient, and often well after the initial presentation to the hospital, which is when these ECGs were obtained. Owing to concerns about confounding by indication, we did not include laboratory data in this analysis. Additionally, given that we did not have prior ECGs in all patients, we did not compare the presentation ECG with prior ECGs for the presence of new findings, and this factor should be studied further. We did not formally assess the reliability of the 2 ECG readers. However, these readers review more than 100,000 ECGs per year at this institution and have historically been concordant in their interpretation. Finally, given the large number of variables analyzed, it is possible that some of the associations reported occurred by chance. However, our findings are consistent with emerging data that myocardial processes are an important prognostic indicator in COVID-19.^{14 , 15 , 19}

In conclusion, our data show that the ECG may be a useful prognostic tool in COVID-19, even among patients who are yet to require invasive mechanical ventilation. Our findings highlight that patients with ECG findings of both left sided heart disease (APCs, IVB, repolarization abnormalities) and right-sided disease (RBBB) have a higher odds of death. Localized ST segment elevation at presentation was rare.

Disclosures

Footnotes

References