key: cord-298094-ctikhqvr
authors: Elias, Pierre; Poterucha, Timothy J.; Jain, Sneha S.; Sayer, Gabriel; Raikhelkar, Jayant; Fried, Justin; Clerkin, Kevin; Griffin, Jan; DeFilippis, Ersilia M.; Gupta, Aakriti; Lawlor, Matthew; Madhavan, Mahesh; Rosenblum, Hannah; Roth, Zachary B.; Natarajan, Karthik; Hripcsak, George; Perotte, Adler; Wan, Elaine Y.; Saluja, Deepak; Dizon, Jose; Ehlert, Frederick; Morrow, John P.; Yarmohammadi, Hirad; Kumaraiah, Deepa; Redfors, Bjorn; Gavin, Nicholas; Kirtane, Ajay; Rabbani, Leroy; Burkhoff, Dan; Moses, Jeffrey; Schwartz, Allan; Leon, Martin; Uriel, Nir
title: The Prognostic Value of Electrocardiogram at Presentation to Emergency Department in Patients With COVID-19
date: 2020-08-15
journal: Mayo Clin Proc
DOI: 10.1016/j.mayocp.2020.07.028
sha: 
doc_id: 298094
cord_uid: ctikhqvr

ABSTRACT Background Rapid risk stratification is essential during the COVID-19 pandemic. We aimed to study whether combining vital signs and electrocardiogram (ECG) analysis can improve early prognostication. Methods 1,258 adults with COVID-19 seen at three hospitals in New York in March and April 2020 were analyzed. ECGs 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 patients (6%) had died and 174 (14%) were alive but receiving mechanical ventilation with 277 (22%) 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 (OR 2.5, 95% CI [1.1-6.2]), right ventricular strain (OR 2.7, 95% CI [1.3-6.1]), and ST segment abnormalities (OR 2.4, 95% CI [1.5-3.8]) were associated with death or mechanical ventilation at 48 hours. In 108 patients without these ECG abnormalities and with normal respiratory vitals (rate <20 and saturation >95%), only 5 (5%) died or required mechanical ventilation by 48 hours versus 68 of 216 patients (31%) having both ECG and respiratory vital sign abnormalities. Conclusions 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 COVID-19 and may assist with patient triage.

with Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2). 1 In the United States, COVID-19 has infected more than 3.4 million people, leading to over 138,000 deaths. 1, 2 Severe cases can result in respiratory failure with acute respiratory distress syndrome (ARDS), shock, and death. 3 Some patients remain stable with mild symptoms, and others develop rapid deterioration after a period of stability lasting up to a week or more. 1, 4, 5 Known markers of poor prognosis include age, comorbidities, and high sequential organ failure assessment (SOFA) score. 5 In patients with severe infection, numerous laboratory findings have been associated with adverse outcomes including hematological disturbances and inflammatory biomarkers. 5 However, there is a limited understanding of how presenting vital signs relate to final outcome from COVID-19, hampering the development of effective approaches for triaging patients early in their clinical course. Additionally, there is increasing evidence of the prognostic capacity of cardiac involvement in COVID-19. 6 Electrocardiographic (ECG) abnormalities have been described but there have been no large studies of ECG abnormalities in COVID-19 patients nor their correlation with clinical outcomes. 8, 9 Early triage of patient that will required higher level of care is crucial due to the high volume of patients admitted with the disease. In this study, we sought to determine if data available early in a patient's emergency department presentation (demographics, comorbidities, vital signs, and ECG) could prognosticate the composite outcome of mechanical ventilation or death by 48 hours after COVID-19 diagnosis. We hypothesized that abnormalities on ECG done at presentation would add additional prognostic capacity after adjusting for the above data in a

From March 1 st to April 3 rd , 5,587 individuals were tested for COVID-19 with 2,421 (43%) having positive results. A total of 1,258 patients who were admitted to the hospital were included in the study. Demographics, comorbidities, presentation vital signs, and outcomes are displayed in Table 1 . The mean age was 61.6 years (SD 18.4) and 563 (46%) patients were female. The most common comorbidities were hypertension (57%), diabetes (37%), obesity (34%), primary lung disease (17%), and chronic kidney disease (16%). Prior known cardiovascular disease included coronary artery disease (11%), HFrEF (7%), and HFpEF (4%).

The most common symptoms reported at the time of triage were fever (39%), cough (32%), shortness of breath (29%), gastrointestinal complaints (10%), weakness (7%), and chest pain (3%).

At 48 hours, 1,011 (80%) patients were alive without receiving mechanical ventilation, 174 (14%) received mechanical ventilation but had not died, and 73 (6%) had died ( Figure 1 ).

During the 14-day period a total of 287 patients (23%) were intubated, of which 16 (6%) were extubated and discharged, 36 (13%) were extubated but remained hospitalized, 121 (42%) remained intubated, and 115 (40%) died. The rate of early clinical decompensation was high, with a median time from hospital arrival to mechanical ventilation of 1 day (IQR 0-4) and a median time of hospital arrival to death of 6 days (IQR 3-10). Mortality increased from 231 (18%) patients at 14 days to 277 (22%) patients at 30 days.

Patients who met the primary outcome tended to be older (mean age 66.3 versus 60.4), male (62% vs 52%), have hypertension (67% vs 55%), diabetes (47% vs 34%), and CKD (20% J o u r n a l P r e -p r o o f Elias 10 vs 15%). On presentation they were more likely to have a respiratory rate >20 (50% vs 22%) and oxygen saturation <=95% (67% vs 55%). There were differences noted in earliest creatinine (median 1.3 vs 1.0 mg/dL) and CRP (184.7 vs 89.6 mg/L) but differences in ESR (73 vs 63 mm/hr) and absolute lymphocyte count (0.88 vs 1.06x10 3 cells/µL) were less pronounced.

Laboratory results are further detailed in the Supplement.

Vital sign abnormalities on presentation are shown in Table 1 . The median temperature was 37.4° C (IQR 36.8-38.2) and 361 patients (29%) had a temperature ≥ 38.0. The median heart rate was 98 (IQR 86-110) and median systolic blood pressure was 124 mmHg (IQR 111-142).

The median respiratory rate was 20/min (IQR 18-22) and the median oxygen saturation was 94% (IQR 90-97%). A total of 682 (54%) patients met criteria for abnormal respiratory vitals (respiratory rate >20, saturation <=95%, or oxygen therapy via NRB or FFM).

A total of 850 initial ECGs were available for analysis. The most common rhythm was sinus rhythm (66%) followed by sinus tachycardia (25%), and atrial fibrillation or flutter (5%). We then combined the two vital sign abnormalities and three ECG abnormalities into two binary variables (abnormal respiratory vitals and abnormal ECG findings). At 48 hours after diagnosis, 4.6% of patients with none of the three ECG abnormalities and normal respiratory vital signs received mechanical ventilation or died, compared to 31.5% of patients with any ECG abnormality and any abnormal respiratory vital sign. The presence of any of the three ECG abnormalities increased the rate of mechanical ventilation or death from 4.6% to 12.3% in patients with normal respiratory vital signs, and from 16.8% to 31.5% in patients with abnormal respiratory vital signs ( Figure 2 ). Looking at 14-day and 30-day outcome, these five variables (two respiratory vitals and three ECG abnormalities) continued to all be significant in multivariable regression. The pathway to outcome at 14 days for all patients is detailed in Figure   3 .

J o u r n a l P r e -p r o o f Elias 12

We analyzed 1,258 patients with COVID-19 seen at three hospitals in New York City during the peak of the COVID-19 pandemic. The principal findings of this study include: (1) rapid clinical deterioration is common in admitted patients, with 53% of intubations occurring within 48 hours, (2) 33% of admitted patients either died or required mechanical ventilation within fourteen days of COVID-19 diagnosis, and (3) combining abnormal ECG and abnormal respiratory vital signs quickly identifies a group of patients at high risk for mechanical ventilation or death.

Myocardial injury is an important marker for severe COVID-19. 8 ECG remains the simplest assessment for myocardial involvement. To our knowledge, no study on COVID-19 has had a majority of patients with ECGs done at presentation and assessed its prognostic capacity.

While triage and management during a patient's admission evolves when additional information such as laboratory values and imaging become available, it is important to be able to quickly screen patients upon arrival to the ED to plan for the level of care they may need. Abnormalities in initial vitals and presentation ECG can be detected rapidly in a range of clinical settings. More studies are needed to determine how initial presentation affects outcome beyond the most acute phase of COVID-19.

Understanding risk factors for COVID-19 severity remains critical due to a need for rapid triage as well as potentially guiding resource allocation. Studies have reported age, hypertension, diabetes, SOFA score, neutrophilia, elevated LDH, and D-Dimer as prognostic factors for patients with COVID-19. 5, 9 A study from New York described male gender, obesity, elevated J o u r n a l P r e -p r o o f Elias 13 liver function tests, ferritin and C-reactive protein as predictors of mechanical ventilation. 9 In addition, cardiac injury, as measured by elevated troponin levels, carries a particularly poor prognosis. [10] [11] [12] The Brescia-COVID respiratory severity scale is the most easily applied decision tool developed to date, basing risk on presenting vital signs and chest radiograph, but lacks input variables that point to extra-pulmonary involvement which we believe is critical for effective triage. 13 Unfortunately, the majority of risk factors identified so far are laboratory values that will not be immediately available upon presentation. Utilizing data immediately available such as vital signs and ECG provides a quick, simple and effective assessment of the patient's prognosis.

Herein, we reported a significant increase in event rate when abnormal ECG was incorporated into multivariable regression, with higher prognostic value than every other variable in the model except for abnormal respiratory vitals. We propose that in the setting of triaging COVID-19 patients in the ED, ECG be treated as a sixth vital sign.

During this study period the New York Department of Health found 962 deaths at home were from confirmed or suspected COVID-19 accounting for 9.3% of total COVID-19 deaths in New York City. 14 Given these sobering statistics, our analysis of hospitalized patients may underestimate illness severity on presentation and raising concern that some patients may be seeking or receiving medical attention too late in their disease course. In the Wuhan experience, the median time of symptom onset to dyspnea was 5 days, symptom onset to hospital admission 7 days, and symptom onset to ARDS 8 days. 15 A study including 655 of our patients found a median of 5 days of symptoms before presentation to the ED. 16 J o u r n a l P r e -p r o o f

Once respiratory symptoms develop in COVID-19, rapid clinical decline appears to be quite common. In addition to disease specific factors, there are patient and medical system features that likely contribute to critical illness of presentation. The news media has highlighted hospital overcrowding and the importance of social distancing which may make patients more likely to wait before contacting the medical system. When patients call their physicians with possible COVID-19 related symptoms, they are often encouraged to avoid medical attention due to concerns about either disseminating the virus or receiving a nosocomial infection. Considering more intubations occurred within the first 24 hours than any other day, patients who had respiratory symptoms for many days may have benefited from earlier assessment. It remains unclear if earlier presentation would have changed clinical outcome.

The American College of Emergency Physicians among others has noted lack of evidence as the key hurdle to devising criteria for safe triage from the ED. 17 Amongst those patients planned for admission, it remains a challenge to determine who is likely to decompensate requiring intensive care in the following days. Our study found that amongst a cohort of COVID-19 patients slated for admission, normal respiratory vitals and no evidence of atrial fibrillation/flutter, right ventricular overload, or ST segment deviation meant there was <5% chance of poor outcome in the next 48 hours. Considering this population only included patients sick enough for admission, we feel these criteria can quickly and effectively determine who is safe for lower acuity settings.

As a retrospective analysis during an ongoing pandemic, this study has multiple limitations. First, at the time of data abstraction many patients remained hospitalized with their final outcomes unclear. To ensure equal exposure time, outcome was assessed at 48 hours and J o u r n a l P r e -p r o o f Elias 15 again at 14 days. It is likely that additional adverse outcomes will accumulate in these patients as their course progresses. To mitigate for this, we reassessed mortality two weeks past censoring at 30 days. Second, data were abstracted from the medical record, and it is probable that comorbidities were incompletely characterized. Third, this analysis begins at the time of presentation to the hospital. The timing of symptom onset was only captured in about half of these patients. Lastly, our institution only tested patients who were planned to be admitted so this cohort does not reflect all patients presenting to the hospital with symptoms concerning for COVID-19. J o u r n a l P r e -p r o o f

No funding sources were utilized for conducting this research.

Authors have no conflicts of interest to disclose. (8) 43 (6) 12 (9) 9 (21) Abbreviations: SD indicates standard deviation, COPD indicates chronic obstructive pulmonary disease, CKD indicates stage 3 or greater chronic kidney disease, HFrEF indicates heart failure with reduced ejection fraction which was defined as a clinical diagnosis of systolic heart failure or a baseline echocardiogram with left ventricular ejection fraction < 50%, HFpEF indicates heart failure with preserved ejection fraction, CAD indicates obstructive coronary artery disease. ECG indicates electrocardiogram. mm indicates millimeters, ms indicates milliseconds. Right ventricular overload was defined as the presence of right ventricular hypertrophy or S1Q3T3. Any ST segment elevation/depression includes sub-millimeter changes from baseline, but ST elevations and depressions must have occurred in two contiguous leads to be considered positive. Early triage of patient that will required higher level of care is crucial due to the high volume of patients admitted with the disease. In this study, we sought to determine if data available early in a patient's emergency department presentation (demographics, comorbidities, vital signs, and ECG) could prognosticate the composite outcome of mechanical ventilation or death by 48 hours after COVID-19 diagnosis. We hypothesized that abnormalities on ECG done at presentation would add additional prognostic capacity after adjusting for the above data in a 

Abstracted laboratory data included white blood cell count, absolute lymphocyte count, hemoglobin, creatinine, c-reactive protein (CRP), and erythrocyte sedimentation rate (ESR). For each lab assay, the first laboratory test that was performed during the encounter was defined as "initial" test. In addition, the most abnormal result (peak or nadir depending on clinical relevance) of each lab any point during the 14-day period was recorded. 

Analysis of clinical outcomes was assessed by chart review. Patients were grouped into one of 3 mutually exclusive groups: (1) alive, never required mechanical ventilation, (2) Patients who met the primary outcome tended to be older (mean age 66.3 versus 60.4), male (62% vs 52%), have hypertension (67% vs 55%), diabetes (47% vs 34%), and CKD (20% J o u r n a l P r e -p r o o f vs 15%). On presentation they were more likely to have a respiratory rate >20 (50% vs 22%) and

oxygen saturation <=95% (67% vs 55%). There were differences noted in earliest creatinine (median 1.3 vs 1.0 mg/dL) and CRP (184.7 vs 89.6 mg/L) but differences in ESR (73 vs 63 mm/hr) and absolute lymphocyte count (0.88 vs 1.06x10 3 cells/µL) were less pronounced.

Laboratory results are further detailed in the Supplement.

Vital sign abnormalities on presentation are shown in Table 1 . The median temperature was 37.4° C (IQR 36.8-38.2) and 361 patients (29%) had a temperature ≥ 38.0. The median heart rate was 98 (IQR 86-110) and median systolic blood pressure was 124 mmHg (IQR 111-142).

The median respiratory rate was 20/min (IQR 18-22) and the median oxygen saturation was 94%

(IQR 90-97%). A total of 682 (54%) patients met criteria for abnormal respiratory vitals (respiratory rate >20, saturation <=95%, or oxygen therapy via NRB or FFM).

A total of 850 initial ECGs were available for analysis. The most common rhythm was sinus rhythm (66%) followed by sinus tachycardia (25%), and atrial fibrillation or flutter (5%). 

All variables in Table 1 Figure 2 ). Looking at 14-day and 30-day outcome, these five variables (two respiratory vitals and three ECG abnormalities) continued to all be significant in multivariable regression. The pathway to outcome at 14 days for all patients is detailed in Figure   3 . Myocardial injury is an important marker for severe COVID-19. 8 ECG remains the simplest assessment for myocardial involvement. To our knowledge, no study on COVID-19 has had a majority of patients with ECGs done at presentation and assessed its prognostic capacity.

While triage and management during a patient's admission evolves when additional information such as laboratory values and imaging become available, it is important to be able to quickly screen patients upon arrival to the ED to plan for the level of care they may need. Abnormalities in initial vitals and presentation ECG can be detected rapidly in a range of clinical settings. More studies are needed to determine how initial presentation affects outcome beyond the most acute phase of COVID-19.

Understanding risk factors for COVID-19 severity remains critical due to a need for rapid triage as well as potentially guiding resource allocation. Studies have reported age, hypertension, diabetes, SOFA score, neutrophilia, elevated LDH, and D-Dimer as prognostic factors for patients with COVID-19. 5, 9 A study from New York described male gender, obesity, elevated J o u r n a l P r e -p r o o f liver function tests, ferritin and C-reactive protein as predictors of mechanical ventilation. 9 In addition, cardiac injury, as measured by elevated troponin levels, carries a particularly poor prognosis. [10] [11] [12] The Brescia-COVID respiratory severity scale is the most easily applied decision tool developed to date, basing risk on presenting vital signs and chest radiograph, but lacks input variables that point to extra-pulmonary involvement which we believe is critical for effective triage. 13 Unfortunately, the majority of risk factors identified so far are laboratory values that will not be immediately available upon presentation. Utilizing data immediately available such as vital signs and ECG provides a quick, simple and effective assessment of the patient's prognosis.

Herein, we reported a significant increase in event rate when abnormal ECG was incorporated into multivariable regression, with higher prognostic value than every other variable in the model except for abnormal respiratory vitals. We propose that in the setting of triaging COVID-19 patients in the ED, ECG be treated as a sixth vital sign.

During this study period the New York Department of Health found 962 deaths at home were from confirmed or suspected COVID-19 accounting for 9.3% of total COVID-19 deaths in New York City. 14 Given these sobering statistics, our analysis of hospitalized patients may underestimate illness severity on presentation and raising concern that some patients may be seeking or receiving medical attention too late in their disease course. In the Wuhan experience, the median time of symptom onset to dyspnea was 5 days, symptom onset to hospital admission 7 days, and symptom onset to ARDS 8 days. 15 A study including 655 of our patients found a median of 5 days of symptoms before presentation to the ED. 16 J o u r n a l P r e -p r o o f J o u r n a l P r e -p r o o f (6) 12 (9) 9 (21) Abbreviations: SD indicates standard deviation, COPD indicates chronic obstructive pulmonary disease, CKD indicates stage 3 or greater chronic kidney disease, HFrEF indicates heart failure with reduced ejection fraction which was defined as a clinical diagnosis of systolic heart failure or a baseline echocardiogram with left ventricular ejection fraction < 50%, HFpEF indicates heart failure with preserved ejection fraction, CAD indicates obstructive coronary artery disease. ECG indicates electrocardiogram. mm indicates millimeters, ms indicates milliseconds. Right ventricular overload was defined as the presence of right ventricular hypertrophy or S1Q3T3. Any ST segment elevation/depression includes sub-millimeter changes from baseline, but ST elevations and depressions must have occurred in two contiguous leads to be considered positive. Variables from Table 1 with p-values under .05 in univariable logistic regression were included in multivariable logistic regression and reported above.

Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China

An interactive web-based dashboard to track COVID-19 in real time

First Case of 2019 Novel Coronavirus in the United States

Covid-19 in Critically Ill Patients in the Seattle Region -Case Series

Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study

Coronavirus Disease 2019 (COVID-19) and Cardiovascular Disease

The Variety of Cardiovascular Presentations of COVID-19

Association of Cardiac Injury With Mortality in Hospitalized Patients With COVID-19 in

Risk Factors Associated With Acute Respiratory Distress Syndrome and Death in Patients With Coronavirus Disease

Cardiovascular Implications of Fatal Outcomes of Patients With Coronavirus Disease 2019 (COVID-19)

Risk factors of fatal outcome in hospitalized subjects with coronavirus disease 2019 from a nationwide analysis in China. Chest 2020. 12

Presenting Characteristics, Comorbidities, and Outcomes Among 5700 Patients Hospitalized With COVID-19 in the New York City Area. JAMA 2020. 14. Confirmed and Probable COVID-19 Deaths Weekly Report. NYC Health

Clinical Characteristics of 138 Hospitalized Patients With 2019 Novel Coronavirus-Infected Pneumonia in Wuhan, China

Characterization and Clinical Course of 1000 Patients with COVID-19 in New York: retrospective case series

ACEP COVID-19 Field Guide

Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China

An interactive web-based dashboard to track COVID-19 in real time

First Case of 2019 Novel Coronavirus in the United States

Covid-19 in Critically Ill Patients in the Seattle Region -Case Series

Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study

Coronavirus Disease 2019 (COVID-19) and Cardiovascular Disease

The Variety of Cardiovascular Presentations of COVID-19

Association of Cardiac Injury With Mortality in Hospitalized Patients With COVID-19 in

Risk Factors Associated With Acute Respiratory Distress Syndrome and Death in Patients With Coronavirus Disease

Cardiovascular Implications of Fatal Outcomes of Patients With Coronavirus Disease 2019 (COVID-19)

Risk factors of fatal outcome in hospitalized subjects with coronavirus disease 2019 from a nationwide analysis in China. Chest 2020. 12

Presenting Characteristics, Comorbidities, and Outcomes Among 5700 Patients Hospitalized With COVID-19 in the New York City Area. JAMA 2020. 14. Confirmed and Probable COVID-19 Deaths Weekly Report. NYC Health

Clinical Characteristics of 138 Hospitalized Patients With 2019 Novel Coronavirus-Infected Pneumonia in Wuhan, China

Characterization and Clinical Course of 1000 Patients with COVID-19 in New York: retrospective case series

ACEP COVID-19 Field Guide

We would like to thank Vijay Rajaram, who provided invaluable assistance with the development and debugging of data visualization in the manuscript. We would also like to thank Andrea Kim who was essential in data abstraction. 

We would like to thank Vijay Rajaram, who provided invaluable assistance with the development and debugging of data visualization in the manuscript. We would also like to thank Andrea Kim who was essential in data abstraction.J o u r n a l P r e -p r o o f

No funding sources were utilized for conducting this research.

Authors have no conflicts of interest to disclose. 1011 We assessed the ability to prognosticate 48 hour outcome utilizing the first electrocardiogram and vital signs recorded in the emergency department. ECG abnormality was defined as the presence of atrial fibrillation or flutter, right ventricular hypertrophy or S1Q3T3, or any ST elevation or depression in two contiguous leads. Respiratory vital sign abnormality was defined as a respiratory rate >20, saturation <= 95%, or requiring oxygen therapy by non-rebreather or full face mask. The absence of any of these ECG abnormalities and any respiratory abnormality made the likelihood of intubation or death at 48 hours < 5%.