key: cord-0928765-5bb1g4ri
authors: Long, Brit; Brady, William J.; Bridwell, Rachel E.; Ramzy, Mark; Montrief, Tim; Singh, Manpreet; Gottlieb, Michael
title: Electrocardiographic manifestations of COVID-19
date: 2020-12-29
journal: Am J Emerg Med
DOI: 10.1016/j.ajem.2020.12.060
sha: 206d0c3d56c51c351d061958ff3ad5bb77bc6fe8
doc_id: 928765
cord_uid: 5bb1g4ri

INTRODUCTION: Coronavirus disease of 2019 (COVID-19) is a lower respiratory tract infection caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). This disease can impact the cardiovascular system and lead to abnormal electrocardiographic (ECG) findings. Emergency clinicians must be aware of the ECG manifestations of COVID-19. OBJECTIVE: This narrative review outlines the pathophysiology and electrocardiographic findings associated with COVID-19. DISCUSSION: COVID-19 is a potentially critical illness associated with a variety of ECG abnormalities, with up to 90% of critically ill patients demonstrating at least one abnormality. The ECG abnormalities in COVID-19 may be due to cytokine storm, hypoxic injury, electrolyte abnormalities, plaque rupture, coronary spasm, microthrombi, or direct endothelial or myocardial injury. While sinus tachycardia is the most common abnormality, others include supraventricular tachycardias such as atrial fibrillation or flutter, ventricular arrhythmias such as ventricular tachycardia or fibrillation, various bradycardias, interval and axis changes, and ST segment and T waves changes. Several ECG presentations are associated with poor outcome, including atrial fibrillation, QT interval prolongation, ST segment and T wave changes, and ventricular tachycardia/fibrillation. CONCLUSIONS: This review summarizes the relevant ECG findings associated with COVID-19. Knowledge of these findings in COVID-19-related electrocardiographic presentations may assist emergency clinicians in the evaluation and management of potentially infected and infected patients.

In December 2019, an outbreak of a lower respiratory tract disease caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was first reported in Wuhan, China (1). This was subsequently termed coronavirus disease of 2019 (COVID-19) by the World Health Organization and has been declared a global pandemic, infecting over 5.1 million people and causing 330,000 deaths (2). While much of the focus has been on the respiratory system, COVID-19 can also cause a variety of cardiac complications (3) (4) (5) (6) (7) (8) and a range of electrocardiographic abnormalities. Studies have described COVID-19 related myocarditis (9- including the lungs, heart, kidneys, gastrointestinal tract, vasculature, and skin (3, 23) .

Respiratory symptoms associated with COVID-19 primarily come from ACE2 expression in the type 2 lung alveolar cells; however, over 7.5% of myocardial cells also express the ACE2 receptor (24) (25) (26) (27) (28) . While the presence of the ACE2 receptor can account for cardiac injury, the etiology of the cardiovascular effects that may occur in COVID-19 is likely multifactorial. The virus can cause a hyperinflammatory state, leading to vascular inflammation, cardiac injury, plaque instability, hypercoagulability, and myocardial depression (25) (26) (27) (28) . Pathologic data reveal cardiac interstitial inflammatory infiltration and necrosis, with blood vessels demonstrating microthrombi and inflammation (26,29-31). COVID-19 may also result in cytokine storm, sepsis, disseminated intravascular coagulation, and ultimately multiorgan dysfunction and death.

Myocardial abnormalities with ECG changes in COVID-19 may be due to this cytokine storm, hypoxic injury, electrolyte abnormalities, plaque rupture, coronary spasm, and microthrombi, as well as direct endothelial or myocardial injury (3) (4) (5) (6) (7) (8) 11, 32 ).

There are a variety of arrhythmias and ECG abnormalities that may occur in COVID-19 (3, 4, 19, 20) . Interestingly, the interpretation of the ECG, with either dysrhythmia recognition or identification of a concerning morphologic issue, is unchanged from the non-COVID-19 patient; in contrast, the context of the patient presentation and thus the clinical impact of the ECG findings has significantly changed. ECG abnormalities are common, present in 93% of hospitalized critically ill patients in one study (32). Palpitations, likely reflective of dysrhythmia, may be the initial presenting symptom in approximately 7% of patients, and one study suggests 17% of patients in the general cohort and 44% of patients in the intensive care unit (ICU) setting experience dysrhythmias (3, 4, 19, 20, 33) . Another study reported a 9.6% rate of dysrhythmias J o u r n a l P r e -p r o o f Journal Pre-proof (34) . Arrhythmias and ECG abnormalities are more common in critically ill patients (33,35), which may occur in 33-93% of these cases (36,37), and they are also associated with increased risk of in-hospital mortality (odds ratio [OR]1.95) and need for mechanical ventilation (38) . A study of 1,258 patients found atrial fibrillation/flutter (OR 2.5), right ventricular (RV) strain (OR 2.7), and ST segment abnormalities (OR 2.4) to be associated with increased risk of mechanical ventilation and death (19) . Emergency clinicians should note that RV strain electrocardiographically presents with ST segment depression and T wave inversion in the right to mid-precordial (leads V1-V4) and the inferior leads (leads II, III, and aVF). Of the inferior leads, lead III frequently demonstrates the most obvious findings due to it direct imaging of the right ventricular muscle mass. Over 8% of deaths may be due to dysrhythmias in the setting of COVID-19 (39) .

Sinus tachycardia is the most common supraventricular tachycardia encountered in the ill COVID-19 patient, resulting from the usual causes, including hypovolemia, hypoperfusion, hypoxia, elevated body temperature, pain, and anxiety. After sinus tachycardia, atrial fibrillation ( Figure 1 ) is the next most commonly seen SVT (40) (41) (42) ; atrial fibrillation can present in a number of different fashions, including new-onset, recurrence of a pre-existing dysrhythmia, and persistence of permanent atrial fibrillation with new rapid ventricular response. In the majority of found atrial fibrillation/flutter was present in 14.3% of patients at admission and occurred in 10.1% of patients during hospitalization (39) . Another study found atrial fibrillation/flutter to be present in 22% of critically ill patients requiring mechanical ventilation (32). Atrial fibrillation is more common in patients following an inflammatory insult such as cardiomyopathy from COVID-19 and occurs in up to half of the patients admitted to an ICU (41) (42) (43) (44) (45) (46) . Two case reports demonstrated the highly variable impact that COVID-19 has on the heart (47,48); in one case (47), the patient presented in atrial flutter and then converted the atrial fibrillation, eventually reverting to sinus rhythm 48 hours later.

There is a paucity of literature evaluating the presence of other types of SVT, such as atrioventricular nodal reentry tachycardia (AVNRT), in COVID-19 patients. In most instances of AVNRT from the pre-COVID-19 era, patients with AVNRT are frequently younger and lack significant acute and chronic cardiorespiratory ailments; this typical AVNRT presentation likely explains the relative paucity of literature on this dysrhythmia in the COVID-19 patient. Refer to Figure 2 for the ECG of a 19 year-old patient with palpitations and dyspnea who presented with AVNRT. The patient was appropriately treated with adenosine but experienced persistent dyspnea after uncomplicated conversion to sinus tachycardia; further evaluation revealed that she was positive for COVID-19 and was admitted to the hospital with persistently lower oxygen saturations. She ultimately did well and was discharged from the hospital 5 days later, without AVNRT recurrence.

J o u r n a l P r e -p r o o f Journal Pre-proof Malignant ventricular arrhythmias are a known complication of viral myocarditis and cardiomyopathy, with ventricular tachycardia (VT) and/or ventricular fibrillation (VF) occurring in 1-6% of patients (19, 35, 36, (49) (50) (51) (52) . In patients with COVID-19, these arrhythmias may be due to a combination of QT interval prolonging medications, metabolic abnormalities, and myocardial inflammation (19, 20, 46, (49) (50) (51) (52) (53) . COVID-19 patients with elevated troponin have been shown to have a higher incidence of VT than those with normal troponins (5, 44) .

VT with a pulse is seen with both monomorphic and polymorphic presentations. Monomorphic ventricular tachycardia (MVT) is the most frequent form of VT seen in the COVID-19 patient, frequently resulting from structural heart disease such as acute coronary syndrome with STEMI, myocardial injury, or myocarditis; patients with pre-existing structural heart disease of many types can provide the substrate for MVT during periods of extreme physiologic stress due to the range of issues encountered in the COVID-19-infected patient. Polymorphic VT (PVT), including the PVT subtype torsade de pointes, results from functional (i.e., non-structural) heart disease and is likely less common; it most often occurs in situations involving medication toxicities, electrolyte abnormality, and various pro-arrhythmic states (e.g. Brugada syndrome, long QT syndrome).

Cardiac arrest dysrhythmias include the traditional 4 rhythm scenarios: the "shockable" (54) (55) (56) (57) (58) . A study conducted in Italy found close to a 60% increase in OHCA in 2020 compared to 2019 (54) . A second study in France found a 52% increase in OHCA between February and April 2020, compared to 2019 (55) . This unfortunate increased rate of OHCA has also been seen in the United States. For example, in New York City there was a three-fold higher rate of patients undergoing resuscitation in the out-of-hospital setting when compared to a similar 2019 pre-pandemic period; the odds ratio (OR) of encountering "nonshockable" dysrhythmias increased significantly with an OR for PEA of 3.50 and an OR for asystole of 1.99 (56) . The mortality rate of patients in cardiac arrest increased in all three studies (54) (55) (56) . There are several factors that may contribute to this increased occurrence with more frequent poor outcome, including the COVID-19 infection itself as well as the delays in seeking care related to the pandemic, and lower rates of important bystander care in the pre-arrival period of cardiac arrest management (59) .

Patients hospitalized with COVID-19 are at increased risk of cardiac arrest, but the rhythms associated with cardiac arrest vary in the inpatient population. A study focusing on hospitalized patients in New York City noted that asystole occurred most often, followed by PEA and then pulseless VT/VF (39). Another study found 9 patients out of 700 experienced cardiac arrest, with only one having a shockable rhythm (57) . A study of 136 Chinese inpatients with COVID-19 complicated by cardiac arrest during hospitalization found most arrests were respiratory in origin with non-shockable rhythms (90% asystole and 4% PEA); only 3% survived to 30 days, with just 1% having intact neurologic function (58) .

Bradycardias and AVB are less commonly encountered as compared to tachydysrhythmias, though they may account for up to 11.8% of cardiac dysrhythmias (60, 61) . A case report details a patient with COVID-19 presenting with first-degree atrioventricular block (AVB); during hospitalization, the rhythm transitioned to Mobitz type 1 second-degree AVB with further evolution ultimately to third-degree AVB (60) . Other cases describe older patients with multiple cardiac risk factors experiencing progression to high-grade AVB (second-degree type II and third-degree AVB) and/or intra-ventricular conduction block; many of these patients developing these more concerning conduction abnormalities progressed rapidly to cardiac arrest (56, (60) (61) (62) (63) (64) .

Three of these dysrhythmias (sinus bradycardia, junctional rhythm, idioventricular rhythm) occurred immediately prior to cardiac arrest onsetthus, in these cases, the development of significant bradycardia in the critically ill COVID-19 patient is a major marker of risk of impending cardiovascular collapse (65) .

QT interval prolongation may occur in over 13% of patients with COVID-19 infection, and several medications previously used for COVID-19 may prolong the QT interval, including chloroquine, hydroxychloroquine, and azithromycin (66) (67) (68) . QT interval prolongation is associated with more critical illness requiring ICU admission, as well as cardiac injury and mortality (61, 69) . Left and right bundle branch blocks may occur in up to 12% of patients at the time of admission or during hospitalization (32,39). Significant QT interval prolongation may lead to torsade des pointes. Figure 3 is the ECG of a patient with COVID-19-related myocarditis; the ECG reveals atrial fibrillation with a mean rate of approximately 100 bpm, J o u r n a l P r e -p r o o f Journal Pre-proof significant QRS complex widening, right axis deviation, poor R wave progression, and ST segment elevation in the anterolateral leads.

QRS complex axis deviation has been reported, usually involving situations presenting with RV strain; such patients are frequently experiencing acute respiratory failure from multi-lobar pneumonia and/or pulmonary embolus with large clot burden. Electrocardiographically, these patients present with right axis deviation along with prominent R waves in leads V1 and V2 and ST segment depression/T wave inversion in leads II, III, aVF, and V1 to V4 (19) . Figure 4 shows the inferior and right to mid precordial leads with T wave inversion, indicative of RV strain, in a patient with significant pulmonary embolus.

The interpretation of the ECG in the patient with chest pain or a similar presentation is more challenging now in the COVID-19 pandemic. Emergency clinicians must consider STEMI, myocardial injury, and myocarditis, as all three clinical entities present with ST segment and T wave abnormalities. COVID-19 infection associated with myocardial injury may demonstrate ST segment deviations (elevation or depression), T wave inversion, and pathologic Q waves (3) (4) (5) 19, 20, 69) . One study found ST segment and T wave changes to be the most common abnormality in patients requiring ICU admission, occurring in 40% of patients (70) . Another investigation noted that nonspecific repolarization changes including ST segment and T wave abnormalities were encountered in 41% of patients; reportedly, these findings resulted from myocardial injury and are associated with poor outcomes, including increased need for ICU admission, more frequent mechanical ventilatory support, and increased mortality (32,40). A can demonstrate ECG findings resembling occlusive AMI, such as focal ST segment elevation with reciprocal change (11, 72, 73) .

In the patient with ST segment elevation, the distinction between STEMI, myocardial injury, and myocarditis may not be possible strictly based upon ECG interpretation, which can make this particularly challenging. In the aforementioned case series of ST segment elevation in COVID- (71) 

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