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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.
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).
A broad spectrum of cardiac manifestations related to COVID-19 has been reported in the literature, including, but not limited to:
- Asymptomatic cardiac abnormalities: Some patients manifest no symptoms of heart disease but show cardiac test abnormalities (abnormal troponins or magnetic resonance imaging).
- Myocardial injury: Elevated cardiac troponin levels suggesting myocardial injury are common among patients hospitalized with COVID-19. Clinical conditions associated with myocardial injury include the following:
- Myocarditis: Myocarditis is commonly suspected in patients with COVID-19, but not always seen histologically (Rajpal, September 2020, Daniels, May 2021).
- Myocardial infarction: STEMI patients with concurrent COVID-19 infection have worse outcomes (Choudry, September 2020).
- Stress cardiomyopathy: Stress (takotsubo) cardiomyopathy is also a complication of COVID-19 infection (Fried, June 2020).
- Cardiogenic shock: Myocarditis or infarction can be further complicated by cardiogenic shock (Fried, June 2020).
- Arrhythmias: Patients with myocardial injury, infarction, shock, and or electrolyte disturbances are prone to arrythmias and conduction abnormalities (Wang, February 2020).
- Multisystem inflammatory syndrome in adults (MIS-A): Multisystem inflammatory syndrome (MIS) is a rare but severe complication of COVID-19 initially characterized in children (MIS-C) but later reported in adults (MIS-A).
- Heart failure: Heart failure may be precipitated by acute on chronic heart disease, acute hemodynamic stress or from myocardial injury in patients with COVID-19 (Chen, March 2020; Zhou, March 2020).
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 2020; Rudski, September 2020; Zheng, March 2020). SARS-CoV-2 may also infect the myocardium directly (Nishiga, July 2020; Dhakal, 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 2020; Guan, February 2020; Wu, February 2020) and has been 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 (Deshmukh, July 2020; Lindner, July 2020; Wang, August 2020; Knight, July 2020; Rajpal, 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.
Long-Term Cardiovascular Outcomes of COVID-19 (Xie, February 2022).
This study of U.S. Department of Veteran Affairs data highlights that the risk and one-year burden of cardiovascular disease in survivors of acute COVID-19 infection are substantial.
- VA cohort of 153,760 U.S. veterans who survived the first 30 days of COVID-19.
- Two control groups:
- A contemporary cohort consisting of 5,637,647 users of the U.S. VA system with no evidence of SARS-CoV-2 infection.
- A historical cohort (predating the COVID-19 pandemic) consisting of 5,859,411 non-COVID-19-infected VA users during 2017.
- Risks and 12-month burdens of prespecified incident cardiovascular outcomes in the overall cohort and based on care setting — nonhospitalized, hospitalized and admitted to ICU.
- Individuals with COVID-19 are at increased risk of incident cardiovascular disease spanning several categories, including cerebrovascular disorders, dysrhythmias, ischemic and nonischemic heart disease, pericarditis, myocarditis, heart failure and thromboembolic disease.
- These risks were evident even among individuals who were not hospitalized during the acute phase of the infection and increased in a graded fashion according to the care setting during the acute phase.
- The demographic composition of this cohort (majority White and male) might limit generalizability.
- Database may have classified patients with COVID-19 as controls if not tested.
- Misclassification bias and residual confounding given use of electronic database.
Association Between COVID-19 and Myocarditis Using Hospital-Based Administrative Data — United States, March 2020–January 2021 (Boehmer, August 2021).
In this cohort study, patients with COVID-19 had nearly 16 times the risk for myocarditis compared with patients who did not have COVID-19, and risk varied by sex and age.
- The cohort included all patients from the Premier Healthcare Database Special COVID-19 Release (PHD-SR) with at least one inpatient or hospital-based outpatient encounter with discharge during March 2020-January 2021.
- The percentage of patients with myocarditis was calculated among patients with and without COVID-19, overall and by sex (male or female) and age group (<16, 16-24, 25-39, 40-49, 50-64, 65-74, and ≥75 years).
- Within the cohort of 36,005,294 patients, 1,452,773 (4.0%) received a diagnosis of COVID-19, and 5,069 (0.01%) received a diagnosis of myocarditis.
- Among patients with myocarditis, 2,116 (41.7%) had a history of COVID-19.
- The risk for myocarditis was 0.146% among patients with COVID-19 and 0.009% among patients without COVID-19.
- Among patients with COVID-19, the risk for myocarditis was higher among males (0.187%) than among females (0.109%) and was highest among adults aged ≥75 years (0.238%), 65-74 years (0.186%), and 50-64 years (0.155%) and among children aged <16 years (0.133%).
- Possible misclassification of cases due to use of administrative codes, not confirmed by clinical data.
- Underlying medical conditions and alternative etiologies for myocarditis (e.g., autoimmune disease) were not ascertained or excluded.
- Dataset does not include encounters for COVID-19, myocarditis and COVID-19 vaccination occurring outside of PHD-SR hospital systems. Generalizability many be limited.
Prevalence of Clinical and Subclinical Myocarditis in Competitive Athletes with Recent SARS-CoV-2 Infection (Daniels, May 2021).
Cardiac magnetic resonance imaging may provide important information on the prevalence of clinical and subclinical myocarditis in college athletes recovering from symptomatic and asymptomatic COVID-19 infections.
- The Big Ten COVID-19 Cardiac Registry, an observational study of athletes confirmed positive for SARS-CoV-2 by polymerase chain reaction testing.
- Myocarditis via cardiac magnetic resonance imaging.
- In a large sample of 2,461 athletes, 1,597 (64.9%) underwent complete comprehensive screening testing, including CMR imaging without prior selection.
- 37 (2.3%) of these athletes demonstrated diagnostic criteria for myocarditis by CMR imaging: nine had clinical myocarditis, and 28 had subclinical myocarditis.
- If cardiac testing was based on cardiac symptoms alone, only five athletes would have been detected (detected prevalence, 0.31%).
- Not all athletes who tested positive for SARS-CoV-2 infection underwent baseline CMR imaging evaluation prior to September 2020.
- CMR variability may have influenced prevalence estimates.
- Lack of standardization.
- CMR imaging may not be easily accessible, may be expensive and local expert interpretation capacity may be insufficient.
Cardiovascular diseases burden in COVID-19: Systematic review and meta-analysis (Hessami, October 2020).
Overall, in this systematic review and meta-analysis of 159,698 patients, there was an association of a high burden of cardiovascular disease among COVID-19 patients, which was significantly associated with mortality and ICU admission.
- A systematic review and meta-analysis of 56 studies related to COVID-19 ICU admission and mortality outcomes as well as 198 papers with descriptive outcomes, including a total of 159,698 COVID-19 patients.
- To study cardiovascular disease burden among COVID-19 patients.
- Acute cardiac injury (OR 13.29, 95% CI, 7.35-24.03), hypertension (OR 2.60, 95% CI, 2.11-3.19), heart failure (OR 6.72, 95% CI, 3.34-13.52), arrhythmia (OR 2.75, 95% CI, 1.43-5.25), coronary artery disease (OR 3.78, 95% CI, 2.42-5.90) and cardiovascular disease (OR 2.61, 95% CI, 1.89-3.62) were significantly associated with mortality.
- Arrhythmia (OR 7.03, 95% CI, 2.79-17.69), acute cardiac injury (OR 15.58, 95% CI, 5.15-47.12), coronary heart disease (OR 2.61, 95% CI, 1.09-6.26), cardiovascular disease (OR 3.11, 95% CI, 1.59-6.09) and hypertension (OR 1.95, 95% CI, 1.41-2.68) were also significantly associated with ICU admission in COVID-19 patients.
- High heterogeneity of studies in population.
- Compounding effects of comorbidities in ICU admission and mortality were not considered.
- Cardiovascular implications could be preexisting or developed by the infection.
Cardiovascular Magnetic Resonance Findings in Competitive Athletes Recovering From COVID-19 Infection (Rajpal, September 2020).
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.
- 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 seven female) reported mild symptoms (sore throat, shortness of breath, myalgias, fever), while others were asymptomatic.
- To use CMR imaging to detect myocardial inflammation in competitive athletes after they completed a recommended quarantine.
- 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 two main features of the updated Lake Louise Criteria.
- Pericardial effusion was present in two athletes with CMR evidence of myocarditis.
- Two of these four athletes with evidence of myocardial inflammation had mild symptoms (shortness of breath), while the other two were asymptomatic.
- None of the athletes previously had a CMR; whether the findings were new or old could not be ascertained.
- The time between diagnosis and CMR was different for different athletes leading to inconsistent results.
Prevalence and Impact of Myocardial Injury in Patients Hospitalized With COVID-19 Infection (Lala, August 2020).
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.
- 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.
- To describe the degree of myocardial injury and associated outcomes in a hospitalized cohort with laboratory-confirmed COVID-19.
- 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, including coronary artery disease, atrial fibrillation and heart failure, 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, 1.37-2.24; 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, 2.42-3.80; p<0.001).
- 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 influenced cardiovascular morbidity.
- Mechanisms of death were not determined (i.e., from cardiovascular vs. noncardiovascular causes).
Outcomes of Cardiovascular Magnetic Resonance Imaging in Patients Recently Recovered From COVID-19 (Puntmann, July 2020).
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.
- Prospective observational cohort study of 100 recently recovered patients in Germany.
- To evaluate the presence of myocardial injury in patients recently recovered from COVID-19 illness.
- 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 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 five 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.
- Small sample size.
- Single-center study.
- Did not include patients during acute COVID-19 infection or those who were asymptomatic.
Association of Cardiac Infection With SARS-CoV-2 in Confirmed COVID-19 Autopsy Cases (Lindner, July 2020).
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.
- Cohort study of 39 autopsy cases with cardiac tissue collected from patients in Germany with confirmed COVID-19 via RT-PCR.
- 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.
- 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.
- Small sample size.
- Autopsy study design with an older population.
- Limited clinical information on the patients included in the study was available.
Cardiovascular Implications of Fatal Outcomes of Patients with Coronavirus Disease 2019 (COVID-19) (Guo, March 2020).
Overall, in this retrospective cohort study, patients with increased troponin T levels had a greater risk of death than those without elevated troponins.
- A retrospective single-center case series of 187 patients with COVID-19 in Wuhan, China.
- To evaluate the association of underlying cardiovascular disease and myocardial injury with fatal outcomes in patients with COVID-19.
- 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%]).
- 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.
Association of Cardiac Injury with Mortality in Hospitalized Patients With COVID-19 in Wuhan, China (Shi, March 2020).
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.
- A cohort study of 416 patients with confirmed COVID-19 at a single center in Wuhan, China.
- 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.
- 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<0.001).
- More comorbidities (e.g., hypertension in 49 of 82 [59.8%] vs. 78 of 334 [23.4%]; p<0.001).
- 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<0.001).
- In a Cox regression model, patients with versus 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]).
- 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.
Characteristics and Outcomes of 21 Critically Ill Patients With COVID-19 in Washington State (Arentz, March 2020).
Overall, in this small case series of primarily elderly patients who were critically ill with COVID-19, 33% of patients developed cardiomyopathy.
- A case series of 21 patients with confirmed COVID-19 in the ICU at Evergreen Hospital in Washington state.
- To describe the clinical presentation, characteristics, and outcomes of incident cases of COVID-19 admitted to the ICU.
- 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 observed in 15 of 15 patients (100%) requiring mechanical ventilation. Eight of 15 (53%) developed severe ARDS by 72 hours.
- Cardiomyopathy developed in seven patients (33%).
- 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.