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Cardiac Manifestations

Last Updated: September 25, 2020

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The following is a curated review of key information and literature about this topic. It is not comprehensive of all data related to this subject. 

Overview

While SARS-CoV-2 most commonly affects the respiratory system, some patients experience cardiovascular symptoms. This often occurs in conjunction with a respiratory syndrome; cardiac manifestations as the primary symptom of disease occur rarely (Liu, May 2020).   

Cardiac manifestations reported in the literature include, but are not limited to:  

Some of these complications may be due to direct viral injury, while others may be due to indirect pressure on the cardiovascular system from SARS-CoV-2 infection. It is likely that both mechanisms are concurrent in some patients.   

To date, the mechanisms underlying COVID-19-related myocardial injury are not fully understood. Microvascular dysfunction due to coagulation derangements, systemic inflammation from cytokine release and stress on the cardiac system from hypoxemia and hemodynamic instability are all likely (Hanley, August 2020Rudski, September 2020Zheng, March 2020). SARS-CoV-2 may also infect the myocardium directly (Nishiga, July 2020Dhakal, July 2020).

Myocardial injury, as suggested by elevated troponin levels or electrocardiogram abnormalities, has been observed in 7% to 28% of hospitalized patients with COVID-19 (Guo, March 2020Guan, February 2020Wu, February 2020) and associated with poor outcomes (Lala, August 2020). The frequency of troponin elevation in patients who do not require admission or are asymptomatic is not known. While evidence of direct viral injury of cardiac myocytes has not been noted on autopsy studies, recent studies using cardiac MRI suggest myocarditis related to SARS-CoV-2 may occur (Deshmuckh, July 2020Lindner, July 2020Wang, July 2020Knight, July 2020Rajpal, September 2020).  

Here we review select key epidemiologic literature evaluating the cardiac manifestations in patients with COVID-19. Multiple studies on this topic have been published; here we focus on the largest studies and the studies with the highest level of evidence and most generalizable results. A discussion of cardiovascular risk factors that signal an increased risk of adverse outcomes in patients with COVID-19 is forthcoming.  

Key Literature   

Cardiovascular Magnetic Resonance Findings in Competitive Athletes Recovering From COVID-19 Infection (Rajpal, September 2020). 

Study population: 

  • 26 competitive U.S. college athletes (mean [SD] age, 19.5 [1.5] years with COVID-19.  
  • 15 were male [57.7%]).  
  • Twelve athletes (26.9%; including 7 female) reported mild symptoms (sore throat, shortness of breath, myalgias, fever), while others were asymptomatic. 

Primary endpoint: 

  • To use cardiac magnetic resonance (CMR) imaging to detect myocardial inflammation in competitive athletes after they completed a recommended quarantine.  

Key findings: 

  • There were no diagnostic ST/T wave changes on electrocardiogram. 
  • On transthoracic echocardiography, all athletes had normal ventricular function. 
  • No athlete had elevated serum levels of troponin I. 
  • Four athletes (15%; all male) had CMR findings consistent with myocarditis based on the presence of 2 main features of the updated Lake Louise Criteria. 
  • Pericardial effusion was present in 2 athletes with CMR evidence of myocarditis.  
  • Two of these 4 athletes with evidence of myocardial inflammation had mild symptoms (shortness of breath), while the other 2 were asymptomatic.

Limitations: 

  • None of the athletes previously had a CMR; whether the findings were new or old cannot be definitely concluded. 
  • The time between diagnosis and CMR was heterogeneous, which may have affected the results.  

Overall, in this small prospective study of athletes with COVID-19, CMR findings indicative of myocarditis were seen in several athletes, some of whom were asymptomatic.  

Prevalence and Impact of Myocardial Injury in Patients Hospitalized With COVID-19 Infection (Lala, August 2020). 

Study population: 

  • 2,736 patients admitted to Mount Sinai Health System hospitals in New York City with confirmed COVID-19 and a troponin measurement <=24 hours of admission. 
  • The median age was 66.4 years, and 59.6% were male.

Primary endpoint: 

  • To describe the degree of myocardial injury and associated outcomes in a hospitalized cohort with laboratory-confirmed COVID-19.  

Key findings: 

  • 985 (36%) patients had elevated troponin concentrations. 
  • Higher troponin concentrations (> 0.09 ng/ml) were seen in patients > 70 years. 
  • In those patients with more significant myocardial injury (troponin I > 0.09 ng/ml), cardiovascular disease (CVD), including coronary artery disease (CAD), atrial fibrillation (AF) and heart failure (HF), was more prevalent (34.9%, 13.0% and 25.3%, respectively) compared with patients with mildly elevated troponins (21.3%, 10.1% and 14.7%, respectively) and those with normal troponins (9.8%, 5.2% and 4.3%, respectively). 
  • After adjusting for disease severity and relevant clinical factors, small amounts of myocardial injury (e.g., troponin I > 0.03 to 0.09 ng/ml; n = 455; 16.6%) were significantly associated with death (adjusted hazard ratio: 1.75; 95% CI: 1.37 to 2.24; p < 0.001) while greater amounts (e.g., troponin I > 0.09 ng/dl; n = 530; 19.4%) were significantly associated with higher risk (adjusted HR: 3.03; 95% CI: 2.42 to 3.80; p < 0.001). 

Limitations: 

  • Study used electronic health records rather than manual chart review for patient-level data extraction; therefore, electrocardiogram findings were not used to correlate troponin elevations. 
  • Outcomes analyses were focused upon troponin measurements made at hospital admission, rather than upon serial troponin measurements obtained over the course of each patient’s hospital stay. 
  • Use of anticoagulation and antiviral therapy was not included in the study; these therapeutic agents could have had an effect on cardiovascular morbidity. 
  • Mechanisms of death were not determined (i.e., from cardiovascular vs. non-cardiovascular causes). 

Overall, in this large retrospective cohort study, patients with elevation of troponin had a higher risk of death, and the effect increased with the degree of increase in troponin.  

Outcomes of Cardiovascular Magnetic Resonance Imaging in Patients Recently Recovered From COVID-19 (Puntmann, July 2020).

Study population: 

  • Prospective observational cohort study of 100 recently recovered patients in Germany.

Primary endpoint: 

  • To evaluate the presence of myocardial injury in patients recently recovered from COVID-19 illness.

Key findings: 

  • 53 (53%) were male, and the mean age was 49 years (standard deviation, 14 years). 
  • The median (IQR) time interval between COVID-19 diagnosis and cardiovascular magnetic resonance (CMR) imaging was 71 (64-92) days. 
  • Of the 100 patients recently recovered from COVID-19, 67 (67%) recovered at home, while 33 (33%) required hospitalization.  
  • At the time of CMR, high-sensitivity troponin T was detectable (> 3 pg/mL) in 71 patients recently recovered from COVID-19 (71%) and significantly elevated (> 13.9 pg/mL) in 5 of those patients (5%). 
  • Infected patients were more likely to have cardiac manifestations compared to individuals in the control group. 
  • CMR revealed 78 patients had structural changes to their hearts, 76 had evidence of a biomarker signaling cardiac injury typically found after a heart attack and 60 had ongoing myocardial inflammation — independent of preexisting conditions, severity and overall course of the acute illness and time from the original diagnosis. 

Limitations: 

  • Small sample size. 
  • Single-center study. 
  • Did not include patients during acute COVID-19 infection or those who were asymptomatic.  

Overall, in this small prospective study, CMR revealed cardiac involvement and myocardial inflammation in a majority of patients, independent of other conditions and disease severity.  

Association of Cardiac Infection With SARS-CoV-2 in Confirmed COVID-19 Autopsy Cases (Lindner, July 2020). 

Study population: 

  • Cohort study of 39 autopsy cases with cardiac tissue collected from patients in Germany with confirmed COVID-19 via RT-PCR. 

Primary endpoint: 

  • To evaluate the presence of SARS-CoV-2 in the myocardial tissue from autopsy cases and to document a possible cardiac response to that infection.  

Key findings: 

  • The median age of patients was 85 years (IQR 78-89); 23 were women (59%).  
  • Pneumonia was evaluated as cause of death in 35 individuals (89.7%). 
  • SARS-CoV-2 was documented in the cardiac tissue of 24 of 39 patients (61.5%).  
  • Viral load > 1,000 copies/μg RNA was documented in 16 of 39 patients (41%); a cytokine response panel was increased in these 16 patients compared with 15 patients without SARS-CoV-2 in the heart.  
  • Comparison of 15 patients without cardiac infection with 16 patients with > 1,000 copies per μg RNA revealed no inflammatory cell infiltrates or differences in leukocyte numbers. 

Limitations: 

  • Small sample size. 
  • Autopsy study design with an older population. 
  • Limited clinical information on the patients included in the study was available. 

In this small autopsy study of patients with confirmed COVID-19, SARS-CoV-2 could be detected in cardiac tissue of the majority of patients, but inflammatory cell infiltrates were not seen.  

Cardiovascular Implications of Fatal Outcomes of Patients With COVID-19 (Guo, March 2020). 

Study population: 

  • A retrospective single-center case series of 187 patients with COVID-19 in Wuhan, China. 

Primary endpoint: 

  • To evaluate the association of underlying cardiovascular disease (CVD) and myocardial injury with fatal outcomes in patients with COVID-19.  

Key findings: 

  • Overall, 66 (35.3%) had underlying CVD, including hypertension, coronary heart disease and cardiomyopathy. 
  • 52 (27.8%) had elevated troponin T (TnT) levels.  
  • Mortality during hospitalization was 7.62% (8 of 105) for patients without underlying CVD and normal TnT levels; 13.33% (4 of 30) for those with underlying CVD and normal TnT levels; 37.50% (6 of 16) for those without underlying CVD but elevated TnT levels; and 69.44% (25 of 36) for those with underlying CVD and elevated TnT levels.  
  • Patients with underlying CVD were more likely to have elevated TnT levels compared to patients without CVD (36 [54.5%] vs. 16 [13.2%]). 

Limitations: 

  • The sample size was relatively small.  
  • As this was a retrospective study, specific information regarding cardiovascular complications and inflammation such as echocardiography were not included. 
  • The causes of death may have involved multiple organ dysfunction in most cases, and it is difficult to differentiate if myocardial injury was the main and direct cause in an individual case. 

Overall, in this retrospective cohort study, patients with increased troponin T levels had a greater risk of death than those without elevated troponins.  

Association of Cardiac Injury With Mortality in Hospitalized Patients With COVID-19 in Wuhan, China (Shi, March 2020).  

Study population: 

  • A cohort study of 416 patients with confirmed COVID-19 at a single center in Wuhan, China. 

Primary endpoint: 

  • To explore the association between cardiac injury (defined as blood levels of cardiac biomarkers (hs-TnI) above the 99th-percentile upper reference limit) and mortality in patients with COVID-19. 

Key findings: 

  • 82 patients (19.7%) had cardiac injury. 
  • Notable findings in those with cardiac injury compared to patients without cardiac injury:  
    • Older age (median [range] age, 74 [34-95] vs. 60 [21-90] years; p<.001). 
    • More comorbidities (e.g., hypertension in 49 of 82 [59.8%] vs. 78 of 334 [23.4%]; p<.001). 
    • Higher leukocyte counts (median [interquartile range (IQR)], 9,400 [6,900-13,800] vs. 5,500 [4,200-7,400] cells/μL).  
    • Higher levels of C-reactive protein (median [IQR], 10.2 [6.4 – 17.0] vs. 3.7 [1.0 – 7.3] mg/dL). 
    • Higher procalcitonin (median [IQR], 0.27 [0.10 – 1.22] vs. 0.06 [0.03 – 0.10] ng/mL). 
    • Creatinine kinase–myocardial band (median [IQR], 3.2 [1.8 – 6.2] vs. 0.9 [0.6 – 1.3] ng/mL). 
    • Higher proportion of multiple mottling and ground-glass opacity in radiographic findings (53 of 82 patients [64.6%] vs. 15 of 334 patients [4.5%]).  
  • Patients with cardiac injury had higher mortality than those without cardiac injury (42 of 82 [51.2%] vs. 15 of 334 [4.5%]; p<.001). 
  • In a Cox regression model, patients with vs. those without cardiac injury were at a higher risk of death, both during the time from symptom onset (hazard ratio, 4.26 [95% CI, 1.92 – 9.49]) and from admission to endpoint (hazard ratio, 3.41 [95% CI, 1.62 – 7.16]). 

Limitations: 

  • Single-center study with a small cohort of patients with cardiac injury; results may not be generalizable. 
  • Because the clinical observation of patients was ongoing, many patients with and without cardiac injury had not reached clinical endpoints.

Overall, in this retrospective cohort study, patients with high-sensitive troponin T levels above the 99th-percentile upper reference limit had a greater risk of death than those without elevated troponins.  

Characteristics and Outcomes of 21 Critically Ill Patients With COVID-19 in Washington State (Arentz, March 2020). 

Study population: 

  • A case series of 21 patients with confirmed COVID-19 in the ICU at Evergreen Hospital in Washington state.  

Primary endpoint: 

  • To describe the clinical presentation, characteristics and outcomes of incident cases of COVID-19 admitted to the intensive care unit (ICU).  

Key findings: 

  • The mean age was 70 years (range, 43-92 years), with 52% male.  
  • Comorbidities were identified in 18 cases (86%), with chronic kidney disease and congestive heart failure being the most common.  
  • An abnormal chest radiograph was observed in 20 patients (95%) at admission. The most common findings on initial radiograph were bilateral reticular nodular opacities (11 patients [52%]) and ground-glass opacities (10 [48%]). By 72 hours, 18 patients (86%) had bilateral reticular nodular opacities and 14 (67%) had evidence of ground-glass opacities.  
  • Mechanical ventilation was initiated in 15 patients (71%), with acute respiratory distress syndrome (ARDS) observed in 15 of 15 patients (100%) requiring mechanical ventilation. Eight of 15 (53%) developed severe ARDS by 72 hours.  
  • Cardiomyopathy developed in 7 patients (33%). 

Limitations: 

  • Small sample size from a single center. 
  • The study population included older residents of skilled nursing facilities, and it is not likely to be broadly applicable to other patients with critical illness.  

Overall, in this small case series of primarily elderly patients who were critically ill with COVID-19, 33% of patients developed cardiomyopathy.  

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