INTRODUCTION — Coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2; previously referred to as 2019-nCoV). Patients with COVID-19 typically present with symptoms and signs of respiratory tract infection, but cardiac manifestations, including signs of myocardial injury, are common. This topic will discuss cardiac manifestations in adults with COVID-19.
Cardiac evaluation and management in adults with COVID-19 is discussed separately. (See "COVID-19: Evaluation and management of cardiac disease in adults".)
Some specific cardiac issues in adults with COVID-19 are discussed separately:
●(See "COVID-19: Myocardial infarction and other coronary artery disease issues".)
●(See "COVID-19: Arrhythmias and conduction system disease".)
Other clinical aspects of COVID-19 are discussed separately, including these and other topics:
●(See "COVID-19: Clinical features".)
●(See "COVID-19: Diagnosis".)
●(See "COVID-19: Epidemiology, virology, and prevention".)
●(See "COVID-19: Issues related to acute kidney injury, glomerular disease, and hypertension".)
●(See "COVID-19: Management in hospitalized adults".)
●(See "COVID-19: Management of the intubated adult".)
●(See "COVID-19: Hypercoagulability".)
●(See "COVID-19: Evaluation of adults with acute illness in the outpatient setting" and "COVID-19: Management of adults with acute illness in the outpatient setting".)
●(See "COVID-19: Clinical manifestations and diagnosis in children".)
●(See "COVID-19: Infection prevention for persons with SARS-CoV-2 infection".)
●(See "COVID-19: Questions and answers".)
●Potential association between mRNA vaccines to prevent SARS-CoV-2 infection and myocarditis. (See "COVID-19: Vaccines", section on 'Myocarditis'.)
ETIOLOGY — Patients with COVID-19 commonly have manifestations of heart disease, including signs of myocardial injury (see 'Troponin' below), but the causes of these findings have not been established.
Possible causes — Possible causes of myocardial injury in patients with COVID-19 include hypoxic injury; stress (takotsubo) cardiomyopathy [1,2]; ischemic injury caused by cardiac microvascular dysfunction, small vessel cardiac vasculitis [3], endotheliitis [4], or epicardial coronary artery disease (with plaque rupture or demand ischemia); right heart strain (acute cor pulmonale, with causes including pulmonary embolism [5-9], adult respiratory distress syndrome [10], and pneumonia); myocarditis [11,12]; and systemic inflammatory response syndrome (cytokine storm) [13-16]. However, the contribution of each of these causes to myocardial injury and adverse cardiovascular outcomes in this setting has not been determined. (See "Troponin testing: Clinical use" and "Diagnosis of acute myocardial infarction" and "Elevated cardiac troponin concentration in the absence of an acute coronary syndrome" and "Clinical manifestations and diagnosis of stress (takotsubo) cardiomyopathy" and "COVID-19: Evaluation and management of cardiac disease in adults", section on 'Troponin'.)
Impact of preexisting cardiovascular disease — Symptoms and signs of heart disease in a patient with COVID-19 may result from an acute disease process, from hemodynamic demands in the setting of chronic (preexisting) heart disease, or may be caused by an acute exacerbation of chronic disease.
As discussed separately, there is substantial evidence of association between preexisting cardiovascular disease (such as hypertension and coronary artery disease) and the risk and severity of COVID-19 infection [17]. The causes of this association have not been determined. Proposed mechanisms include impaired physiologic reserve (cardiovascular and pulmonary), impaired immune response, augmented inflammatory response, vulnerability to SARS-CoV-2-induced endothelial dysfunction, and effects mediated by the angiotensin-converting enzyme 2 receptor [18]. (See "COVID-19: Myocardial infarction and other coronary artery disease issues", section on 'Association between baseline CVD and COVID-19'.)
ACUTE CLINICAL MANIFESTATIONS — Patients with acute COVID-19 may present with a broad spectrum of clinical cardiac presentations: some patients manifest no clinical evidence of heart disease, some have no symptoms of heart disease but have cardiac test abnormalities (such as serum cardiac troponin elevation, asymptomatic cardiac arrhythmias, or abnormalities on cardiac imaging), and some have symptomatic heart disease. Cardiac complications include myocardial injury, heart failure (HF), cardiogenic shock, and cardiac arrhythmias including sudden cardiac arrest. The following sections review the spectrum of cardiac manifestations in patients with COVID-19.
Most patients with COVID-19 with abnormalities on cardiac testing have typical symptoms of COVID-19, including cough, fever, myalgia, headache, and dyspnea, as described separately. A minority of patients with COVID-19 present with symptoms that may suggest heart disease (such as palpitations [19] or chest pain [20]). These symptoms may or may not be accompanied by prior or concurrent symptoms typical of COVID-19 infection [13,21]. Symptoms such as dyspnea and chest pain may be caused by noncardiac and/or cardiac causes. (See "COVID-19: Clinical features", section on 'Clinical manifestations'.)
Asymptomatic heart disease — Most patients with COVID-19 with cardiac test abnormalities (such as cardiac troponin elevation, electrocardiographic [ECG] abnormalities, or cardiac imaging findings) lack symptoms of heart disease.
As noted above, some symptoms, such as dyspnea, are nonspecific and are evaluated in the context of concurrent symptoms, signs, and test findings to determine if they are more likely caused by a noncardiac condition (eg, pneumonia) or cardiac disease. (See "COVID-19: Evaluation and management of cardiac disease in adults", section on 'Targeted cardiac evaluation'.)
Myocardial injury — Myocardial injury as detected by troponin elevation is commonly identified in patients hospitalized with COVID-19, but the causes of myocardial injury have not been fully elucidated [22]. Cardiac troponin elevation does not distinguish among the causes of injury (table 1). As discussed above, there are many putative causes of myocardial injury in patients with COVID-19, but the cause in individual patients is frequently not identified. Clinical conditions associated with myocardial injury include myocarditis, stress cardiomyopathy, and myocardial infarction (MI). (See 'Possible causes' above.)
The term "myocardial injury" encompasses all conditions causing cardiomyocyte death. Cardiac troponin elevation is the generally accepted marker for identifying myocardial injury [23]. Myocardial injury is commonly clinically identified by the presence of at least one cardiac troponin value above the 99th percentile upper reference limit (URL), in accordance with the definition of myocardial injury in the Fourth Universal Definition of Myocardial Infarction [23]. While high-sensitivity cardiac troponin levels are sensitive markers of myocardial injury, some patients with disease processes causing cardiomyocyte death may have troponin levels below the 99th percentile URL [24]. (See "Troponin testing: Clinical use" and "Troponin testing: Analytical considerations" and "Elevated cardiac troponin concentration in the absence of an acute coronary syndrome" and "Biomarkers of myocardial injury other than troponin" and 'Troponin' below.)
Myocarditis — Numerous COVID-19 case reports have described findings consistent with a diagnosis of "clinically suspected myocarditis" [25-31], but there have been few cases of histologically confirmed myocarditis [32-34], and viral myocarditis caused directly by SARS-CoV-2 has not been definitively confirmed [32,35,36]. (See 'Myocardial histology and viral genome analysis' below.)
A potential association between mRNA vaccines to prevent SARS-CoV-2 infection and myocarditis is discussed separately. (See "COVID-19: Vaccines", section on 'Myocarditis'.)
Stress cardiomyopathy — Stress (takotsubo) cardiomyopathy has been reported in patients with COVID-19 [1,2,37-46]. In addition, some case reports of clinically suspected myocarditis complicating COVID-19 have described marked recovery of left ventricular (LV) systolic function within days, suggestive of stress cardiomyopathy or fulminant myocarditis.
In a review of 12 cases of stress cardiomyopathy associated with COVID-19, the mean age was 70.8 and the majority of patients were female [46]. An elevated troponin level was identified in 11 of the cases. There was no significant coronary artery disease on invasive coronary angiography in two patients, coronary artery disease in arteries supplying a different territory in one case, negative computed tomography coronary angiography in five cases, and no coronary artery disease on autopsy in one case; the coronary arteries were not examined in three cases. Complications included HF, cardiogenic shock, cardiac tamponade, and hypertensive crisis. (See "Clinical manifestations and diagnosis of stress (takotsubo) cardiomyopathy".)
Of note, a study identified increased incidence of stress cardiomyopathy in patients without COVID-19 during the COVID-19 pandemic compared with prepandemic periods [47]. (See "Clinical manifestations and diagnosis of stress (takotsubo) cardiomyopathy", section on 'Epidemiology'.)
Myocardial infarction — MI in patients with COVID-19 is discussed separately. (See "COVID-19: Myocardial infarction and other coronary artery disease issues".)
Heart failure
General prevalence — HF in patients with COVID-19 may be precipitated by acute illness in patients with preexisting known or undiagnosed heart disease (eg, coronary artery disease or hypertensive heart disease), acute hemodynamic stress (eg, acute cor pulmonale), or acute myocardial injury (eg, acute MI, stress cardiomyopathy, cytokine storm, and other possible etiologies described above) [48-50]. Cardiovascular risk factors and cardiovascular disease are highly prevalent in hospitalized patients with COVID-19. Patients with a known history of HF may suffer an acute decompensation due to the development of COVID-19 disease [21,28]. (See 'Impact of preexisting cardiovascular disease' above and "COVID-19: Myocardial infarction and other coronary artery disease issues", section on 'Association between baseline CVD and COVID-19'.)
A study of 6439 patients hospitalized with COVID-19 at a hospital in New York found that a history of HF was associated with adverse outcomes, including longer length of stay (eight versus six days), increased risk of mechanical ventilation (22.8 versus 11.9 percent; adjusted odds ratio [OR] 3.64, 95% CI 2.56-5.16), and mortality (40.0 versus 24.9 percent; adjusted OR 1.88, 95% CI 1.27-2.78) [51]. Outcomes among patients with different types of HF were similar, regardless of LV ejection fraction (LVEF).
Limited data are available on the incidence of HF in patients with COVID-19.
●In a retrospective study of 6439 patients with COVID-19 admitted to hospitals in New York City between February 2020 and June 2020, 0.6 percent of patients were diagnosed with new HF [52]. Among the patients with a new diagnosis of HF, twenty-two percent had no risk factors for cardiovascular disease.
●In a retrospective study of 799 patients hospitalized with COVID-19 in Wuhan, HF was identified as a complication in 49 percent of patients who died and in 3 percent of patients who recovered, despite a less than 1 percent baseline prevalence of chronic HF in the combined groups [53].
●In a study of 191 patients hospitalized in two other medical centers in Wuhan, HF was identified in 52 percent of patients who died and in 12 percent of patients who recovered [54]. These studies do not provide sufficient information to determine the incidence of new-onset HF with COVID-19, as there was not enough information provided regarding prior history of HF and risk factors for HF.
Although acute HF incidence was not documented in some series of hospitalized patients with COVID-19, elevated natriuretic peptides (such as B-type natriuretic peptide [BNP] and N-terminal pro-BNP [NT-proBNP]) are common, particularly in patients with evidence of cardiac injury, as described below. (See 'Biomarkers' below and 'Natriuretic peptides' below.)
Right heart failure — Acute cor pulmonale (right HF due to acute pulmonary hypertension) precipitated by acute pulmonary embolism or adult respiratory distress syndrome (ARDS) has been described in patients with COVID-19 [5-10,55]. Patients with COVID-19 are at risk for development of ARDS. Venous thromboembolism (including extensive deep vein thrombosis and pulmonary embolism) is common in acutely ill patients with COVID-19. (See "COVID-19: Management of the intubated adult" and "COVID-19: Hypercoagulability".)
Cardiogenic shock — Case reports have described patients with COVID-19 and acute onset of cardiogenic shock treated with inotrope and mechanical circulatory support and, in some cases, venoarterial extracorporeal membrane oxygenation (VA-ECMO) [27,56]. Rapid recovery within several days has been described in several reported cases with a time course suggestive of possible stress cardiomyopathy [28,29,57-60]. Although fulminant myocarditis was suspected in some cases of cardiogenic shock with recovery of ventricular function over days or weeks, this diagnosis has generally not been established, as endomyocardial biopsy was either not performed [26,28,57,59,60] or, when performed, did not show findings of myocarditis [29,58].
Multisystem inflammatory syndrome in adults (MIS-A) — Multisystem inflammatory syndrome (MIS) was initially described in children (MIS-C) with recent COVID-19 infection as a Kawasaki-like illness associated with fever, gastrointestinal symptoms, shock, LV systolic dysfunction, and elevated inflammatory markers. (See "COVID-19: Multisystem inflammatory syndrome in children (MIS-C) clinical features, evaluation, and diagnosis".)
Similar cases of MIS have been described in young to middle-aged adults (MIS-A) also presenting with fever, gastrointestinal symptoms, and shock with vasoplegia, LV systolic dysfunction, and elevated inflammatory markers [61,62]. Many of these patients had history of recent COVID-19 and had positive SARS-CoV-2 antibody tests, with fewer having positive SARS-CoV-2 reverse transcription polymerase chain reaction tests. This diagnosis should be considered in young adults presenting with shock and elevated inflammatory markers. This syndrome appears to be highly responsive to parenteral steroids. (See "COVID-19: Care of adult patients with systemic rheumatic disease", section on 'COVID-19 as a risk factor for rheumatologic disease'.)
Cardiac arrhythmias — The risk of cardiac arrhythmias and sudden cardiac arrest in patients with COVID-19 is discussed separately. (See "COVID-19: Arrhythmias and conduction system disease".)
CARDIAC TEST FINDINGS — A variety of cardiac test abnormalities have been described in patients with COVID-19, as described in the following sections.
Biomarkers — Cardiac troponin and natriuretic peptide (B-type natriuretic peptide [BNP] and N-terminal pro-BNP [NT-proBNP]) biomarkers are commonly elevated among hospitalized patients with COVID-19 and are associated with increased risk of mortality. In a study from Wuhan of 3219 patients (mean age 57 years) with COVID-19 hospitalized with biomarker data, elevated high-sensitivity cardiac troponin I (hs-cTnI) was detected in 6.5 percent, and an elevated NT-proBNP level was detected in 12.9 percent [24]. In a model including adjustment for age, sex, and comorbidities, the adjusted hazard ratio for 28-day mortality for hs-cTnI was 7.12 (95% CI 4.60-11.03) and for NT-proBNP was 5.11 (95% CI 3.50-7.47). These biomarkers had prognostic value at approximately half of the commonly used upper limit of normal thresholds.
A similar association between biomarker elevation and mortality risk was observed in a study from Milan of 397 hospitalized patients with COVID-19 [63]. At the time of hospital admission, 22.7 percent had elevated hs-cTnI and BNP levels, 14.9 percent had only an elevated BNP level, and 10.1 percent had only an elevated hs-cTnI. Overall mortality rate was 23.2 percent. The mortality rate was higher in patients with elevation of both biomarkers (55.6 percent), elevated BNP (33.9 percent), or hs-cTnI elevation (22.5 percent) compared with patients with no biomarker elevation (6.25 percent). In multivariate analysis, elevation of both hs-cTnI and BNP was an independent predictor of mortality (odds ratio [OR] 3.24, 95% CI 1.06-9.93).
Troponin — Cardiac troponin elevation is a marker of myocardial injury and is commonly identified in patients hospitalized with COVID-19, but the causes of troponin elevation have not been fully elucidated [22]. The frequency of myocardial injury (as reflected by elevation in cardiac troponin levels) is variable among hospitalized patients with COVID-19, with reported frequencies of 7 to 36 percent [11,64-69]. The frequency of troponin elevation appears to be lower among patients with mildly symptomatic COVID-19 [70]. Frequencies of troponin elevation in various COVID-19 series are difficult to compare due to use of differing troponin assays, 99th percentile upper reference limit (URL) thresholds, and sampling times [71]. Limited data are available on the frequency of troponin elevations in asymptomatic or only mildly symptomatic patients with SARS-CoV-2 infection. (See 'Possible causes' above and 'Myocardial injury' above.)
Studies have identified greater frequency and magnitude of troponin elevations in hospitalized patients with more severe disease and worse outcomes [11,17,54,64,67,68,72,73]. A systematic review and meta-analysis found that an elevated troponin level was among the clinical factors most strongly associated with an adverse composite outcome (including death, severe presentation, hospitalization in the intensive care unit, and/or mechanical ventilation; OR 10.58, 95% CI 5.00-22.40) [17]. Other clinical features associated with high risk of the composite outcomes were history of cardiovascular disease, acute kidney injury, increased procalcitonin, increased D-dimer, and thrombocytopenia. An elevated troponin level was also one of the clinical features associated with in-hospital death.
In a study from New York of 2736 hospitalized patients (mean age 66.4 years) with COVID-19, 36 percent of patients had elevated hs-cTnI levels [69]. Troponin elevation was more prevalent among patients with known cardiovascular disease or cardiovascular risk factors. The mortality rate during hospitalization was 18.5 percent. In adjusted analysis, even mildly elevated hs-cTnI (0.03 to 0.09 ng/mL) was associated with risk of death (adjusted hazard ratio [HR] 1.75, 95% CI 1.37-2.24), while greater elevations were associated with higher risk (troponin >0.09 ng/mL; adjusted HR 3.03, 95% CI 2.42-3.80).
In a series of 416 patients with COVID-19 who were hospitalized at Renmin Hospital in Wuhan, 19.7 percent had hs-cTnI above the 99th percentile URL on admission [11]. Patients with this marker of myocardial injury were older and had more comorbidities (including chronic HF in 14.6 versus 1.5 percent), greater laboratory abnormalities (including higher levels of C-reactive protein, procalcitonin, and aspartate aminotransferase), more lung radiographic abnormalities, and more complications compared with those without myocardial injury. The mortality rate was also higher in those with myocardial injury (51.2 versus 4.5 percent). The risk of death starting from the time of symptom onset was more than four times higher in patients with evidence of myocardial injury on admission (HR 4.26, 95% CI 1.92-9.49).
In a study from Wuhan of 311 hospitalized patients with COVID-19 and available hs-cTnI levels, independent risk factors for death included hs-cTnI concentration (OR 1.92, 95% CI 1.41-2.59), comorbidity (OR 9.07, 95% CI 2.52-32.66), C-reactive protein concentration (OR 1.98, 95% CI 1.34-2.92), D-dimer concentration (OR 1.55, 95% CI 1.13-2.13), lymphocyte count (OR 0.52, 95% CI 0.29-0.95), and blood oxygen saturation (OR 0.85, 95% CI 0.77-0.94) [73].
In another study from Wuhan, elevation in hs-cTnI above the 99th percentile URL was identified on admission in 46 percent of nonsurvivors versus 1 percent of survivors [54]. In contrast, a study of 24 critically ill COVID-19 patients in Seattle with a 50 percent mortality rate found elevated troponin levels early after intensive care unit admission in only 2 of 13 (15 percent) tested patients, but troponin assays may have differed [66]. A study found considerably greater prevalence of preexisting cardiovascular disease and cardiac risk factors in patients with evidence of myocardial injury compared with those without elevated biomarkers [11]. Thus, it is not yet possible to determine whether myocardial injury is an independent risk marker in COVID-19 or if the risk associated with it is related to the burden of preexisting cardiovascular disease.
In patients with COVID-19, troponin elevation may be initially detected prior to, at the time of, or following hospital admission [25-28,54,65,67,74]. A variety of time courses for troponin elevation have been observed:
●Mild – Patients hospitalized with COVID-19 commonly have mild troponin elevation (typically <99th percentile URL), with modest rise or fall on subsequent days, typically remaining well below the 99th percentile URL [65]. This appears to be the most common pattern of troponin elevation in patients with COVID-19 and is often associated with no cardiac symptoms. This pattern has been described in patients with COVID-19 who survived after hospitalization [54].
●Moderate time-limited – Some patients have an early moderately elevated troponin level (which may approach or exceed the 99th percentile URL), which may fall on subsequent days. This pattern was seen in anecdotal reports of patients with clinically suspected myocarditis or stress cardiomyopathy [25-28].
●Progressive – Some patients with moderate troponin elevation at hospital admission suffer clinical deterioration with respiratory failure accompanied by progressive troponin elevation, along with elevations in other biomarkers (eg, D-dimer, interleukin 6, ferritin, and lactate dehydrogenase) with accelerated rise after the second week of hospitalization [54,67]. This progression to cytokine storm has been described in nonsurvivors, with death occurring at a median of 18.5 days after symptom onset [54].
Other cardiac test abnormalities (such as ECG alterations and cardiac imaging findings) have been observed in patients with and without elevated troponin levels. The finding of a cardiac test abnormality without concurrent troponin elevation suggests a condition not associated with myocardial injury (including preexisting cardiac disease or a process not causing cardiomyocyte death) or a missed troponin level elevation due to limited troponin sampling or troponin elevation below 99th percentile URL thresholds [22]. (See "COVID-19: Evaluation and management of cardiac disease in adults", section on 'ECG'.)
Natriuretic peptides — Natriuretic peptides (BNP and NT-proBNP) are commonly elevated in hospitalized patients with COVID-19, and natriuretic peptide elevation is associated with mortality risk, as described above. (See 'Biomarkers' above.).
Natriuretic peptide elevation is commonly associated with cardiac troponin elevation. In the above described series of 416 hospitalized patients with COVID-19, NT-proBNP levels were significantly higher in patients with elevated troponin levels than in patients without troponin elevation (1689 versus 139 pg/mL) [11].
Electrocardiogram — The various ECG findings observed in patients with COVID-19 likely reflect the combined effects of acute illness and chronic heart disease (since cardiovascular risk factors are highly prevalent in this population). The range of ECG findings was illustrated in a study of 756 patients (mean age 63 years) hospitalized with COVID-19 in New York [75]. The mortality rate was 11.9 percent during the follow-up period of two to seven weeks. Cardiovascular risk factors and conditions were common, including obesity (37 percent), diabetes mellitus (29 percent), hypertension (57 percent), coronary artery disease (CAD, 14 percent) and HF (7 percent). This study did not include data on troponin levels or comparison with prior ECGs.
●Atrial fibrillation or flutter was observed in 5.6 percent. Atrial premature beats (APBs) were observed in 7.7 percent and premature ventricular contractions in 3.4 percent.
●Right bundle branch block (RBBB) was identified in 7.8 percent, left bundle branch block in 1.5 percent, and nonspecific intraventricular conduction delay (IVCD) in 2.5 percent.
●Repolarization abnormalities included localized ST elevation in 0.7 percent, localized T-wave inversion in 10.5 percent, and nonspecific repolarization abnormalities in 29 percent.
●In a multivariable model including age, clinical characteristics, and ECG findings, the variables associated with risk of death were presence of CAD, an immunosuppressed state, hypoxemia, and the following ECG findings: APBs (OR 2.57, 95% CI 1.23-5.36), RBBB or IVCD (OR 2.61, 95% CI 1.32-5.18), localized T-wave inversion (OR 3.49, 95% CI 1.56-7.80), and nonspecific repolarization abnormality (OR 2.31, 95% CI 1.27-4.21).
Cardiac imaging
Echocardiogram — A variety of echocardiographic findings have been identified in patients with COVID-19 [76-79], as illustrated by a study of an unselected population of 100 patients hospitalized with COVID-19 [79].
●Transthoracic echocardiography (TTE) findings included right ventricular (RV) dilation and dysfunction (39 percent), LV diastolic dysfunction (16 percent), and LV systolic dysfunction (10 percent). Patients with an elevated troponin level or worse clinical condition had worse RV function.
●Among the 20 percent of patients with subsequent clinical deterioration, the most common echocardiographic findings were worsened RV function (12 patients) and worsened LV systolic and diastolic function (5 patients). Femoral deep vein thrombosis was identified in 5 of 12 patients with RV failure.
The spectrum of findings in patients with COVID-19 with a clinical indication for TTE was illustrated by an international survey including data on 1216 patients (mean age 62) from 69 countries [76]:
●The most common indications for TTE were suspected left-sided HF (40 percent), elevated cardiac biomarkers (26 percent), and right-sided HF (20 percent). Preexisting heart disease was noted in 26 percent of patients.
●Fifty-five percent of patients had an abnormal TTE, including LV abnormalities in 39 percent and RV abnormalities is 33 percent. A slightly lower prevalence of echocardiographic abnormalities (46 percent) was detected in the subgroup of patients with no known preexisting heart disease.
●TTE LV findings were considered suggestive of diagnoses including acute MI (3 percent), myocarditis (3 percent), and stress cardiomyopathy (3 percent). Severe ventricular (left, right, or biventricular) dysfunction was observed in 14 percent. Cardiac tamponade was identified in 1 percent.
●TTE findings changed management in 33 percent of patients.
The prognostic importance of major TTE abnormalities was demonstrated by a study of 305 patients (mean age 63 years) who had undergone TTE during hospitalization for COVID-19 [80]. Troponin elevation was observed in 62.3 percent of these patients. Patients with troponin elevation had more ECG abnormalities and higher prevalence of major TTE abnormalities (including LV wall motion abnormalities, global LV dysfunction, LV diastolic dysfunction grade II or III, RV dysfunction, and pericardial effusions) than patients without troponin elevation. Rates of in-hospital mortality were 5.2 percent in patients without myocardial injury, 18.6 in those with myocardial injury without TTE abnormalities, and 31.7 percent in patients with myocardial injury and TTE abnormalities. Following multivariable adjustment, myocardial injury with TTE abnormalities was associated with higher risk of death, but myocardial injury without TTE abnormalities was not.
Cardiovascular magnetic resonance — Cardiovascular magnetic resonance (CMR) abnormalities have been identified in patients with COVID-19 as well as in patients who have recently recovered from COVID-19, though most reported abnormalities have been nonspecific. CMR findings identified in some of these patients include elevations in native T1 (a nonspecific finding seen with acute myocardial injury, fibrosis, or infiltration), T2 (a marker of edema), and, less commonly, late gadolinium enhancement (a marker of acute myocardial injury, fibrosis, or infarction). Since limited endomyocardial biopsy data and no follow-up data have been reported, the clinical significance of these findings is uncertain. Moreover, since no patients had a CMR examination before COVID-19, it remains undetermined whether the abnormal findings might have already been present and therefore be unrelated to COVID-19. (See "Clinical utility of cardiovascular magnetic resonance imaging", section on 'Myocardial disease'.)
●In an unselected cohort – A CMR study included 100 patients (mean age 49 years) who had recovered from COVID-19, including 18 with asymptomatic SARS-CoV-2 infection, 49 with mild to moderate symptoms, and 33 with severe symptoms requiring hospitalization [81]. Preexisting cardiovascular conditions such as hypertension, diabetes mellitus, and known coronary artery disease were equally common among patients who remained at home and those who were hospitalized. Patients referred for CMR for cardiac symptoms were excluded. Comparisons were made with healthy controls as well as with risk factor-matched controls.
•Among the 33 hospitalized patients, 15 patients had a significantly elevated hs-cTnI during hospitalization. Among all the patients, 5 percent has significant hs-cTnI elevation at the time of CMR. CMR was performed two to three months after the initial positive COVID-19 test.
•Abnormal CMR findings were frequent among those who had recovered from COVID-19, including elevated myocardial native T1 (73 percent), elevated myocardial native T2 (60 percent), myocardial late gadolinium enhancement (LGE; 32 percent), and pericardial LGE (22 percent). Baseline CMR data were not available.
-In healthy controls, T1 and T2 elevations were rare and LGE was not seen.
-In risk-factor matched controls, CMR abnormalities were identified, although at lower frequencies than in the COVID-19 group: elevated native T1 (40 percent), elevated native T2 (9 percent), myocardial LGE (17 percent), and pericardial LGE (15 percent).
•Endomyocardial biopsy in three patients with elevated hs-cTnI, elevated native T1 and T2, LGE, and LVEF <50 percent revealed lymphocytic infiltration; necrosis was not described and no viral genome was detected.
•The LV was mildly dilated and LVEF and RVEF were mildly depressed in patients recovered from COVID-19 compared with healthy controls and risk-factor matched controls (for LVEF 56 versus 60 and 61 percent, respectively; for RVEF 56 versus 60 and 59 percent).
●In athletes – CMR findings have also been reported among athletes who have recovered from COVID-19 [82-85]. The clinical significance of these findings is uncertain since CMR findings are nonspecific and endomyocardial biopsy data were not reported. Studies have identified CMR findings including LGE in a minority of healthy adult athletes with no prior COVID-19 infection [86-89]:
•Collegiate athletes – After small studies identified CMR abnormalities in collegiate athletes recovering from COVID-19 [82,89], a larger study found that CMR findings consistent with clinically suspected myocarditis were rare [84]. In a study of 145 university student athletes (mean age 20 years; 74 percent male), CMR examination was performed at a median of 15 days after the positive COVID-19 tests [84]. Most patients experienced mild, moderate, or no symptoms during the acute COVID-19 infection. Two patients (1.4 percent) had findings consistent with updated Lake Louise criteria for clinically suspected myocarditis (see "Clinical manifestations and diagnosis of myocarditis in adults", section on 'Updated Lake Louise criteria'). One of these patients had patchy midmyocardial and subepicardial LGE with associated elevated T2-weighted signal, transient troponin I elevation, and pericardial enhancement. CMR examination of the second patient revealed a 1 cm focus of mild epicardial LGE at the inferior basal LV wall with corresponding elevated T2-weighted signal; an additional small nonspecific LGE focus was identified at the inferior RV insertion. No endomyocardial biopsy data were available. 40 patients (27.6 percent) had small nonspecific foci of LGE.
In an earlier study of 26 competitive collegiate athletes (mean age 19.5 years), CMR examination was performed 11 to 53 days after diagnosis of COVID-19 [82]. Twelve athletes had experienced mild COVID-19 symptoms and 14 were asymptomatic. None of the athletes had elevated serum troponin I levels or diagnostic ST/T-wave changes on ECG. Ventricular volumes and function were normal on echocardiogram and CMR imaging. Four athletes (15 percent) had CMR findings consistent with updated Lake Louise criteria for clinically suspected myocarditis. Eight athletes (30 percent) had nonspecific LGE.
•Professional athletes – A protocol for return-to-play cardiac testing in professional athletes also identified a low rate of CMR findings consistent with clinically suspected myocarditis [85]. Return-to-play testing was performed between May and October 2020 in 789 professional athletes (mean age 35, 98.5 percent male) [85]. Return-to-play testing was performed in patients with prior symptomatic COVID-19 (58 percent) as well as in patients with asymptomatic or mildly symptomatic infection (42 percent) and included a troponin level, a 12-lead ECG, and a resting transthoracic echocardiogram. Among the 30 athletes (3.8 percent) with one or more abnormal screening test results, 27 underwent CMR. CMR findings consistent with clinically suspected myocarditis were identified in 3 athletes (0.4 percent of the cohort) and with pericarditis in 2 athletes (0.3 percent).
Myocardial histology and viral genome analysis — Myocarditis is commonly suspected in patients with COVID-19 and elevated cardiac troponin levels. However, there have been few reported cases of histologically confirmed myocarditis [32-34], and viral myocarditis directly caused by SARS-CoV-2 has not been definitively confirmed by histologic and viral genome analysis [32]. Immune-mediated myocarditis has been hypothesized but not confirmed.
●Viral myocarditis – Proof that SARS-CoV-2 is a cause of viral myocarditis requires identification of histologic findings of active myocarditis (ie, inflammatory infiltrate [lymphocytic, eosinophilic, neutrophilic, giant cell, granulomatous, or mixed] plus myocyte necrosis not typical of ischemic injury [90]), identification of the SARS-CoV-2 genome or viral particles in cardiomyocytes, and exclusion of known cardiotropic viruses [12]. Cardiotropic viruses that are known to be associated with myocarditis (eg, enterovirus, which is associated with diarrhea, and parvovirus B19, which is associated with a pseudoinfarct presentation) were not searched for in most of the reported cases and might be involved.
Case series and reports that have included endomyocardial biopsy results illustrate that identification of SARS-CoV-2 in specimens from the upper or lower respiratory tract is not sufficient to prove that concomitant myocardial injury was caused by SARS-CoV-2 myocarditis [3,25-27,81].
•In a few patients with COVID-19, myocarditis has been histologically confirmed but viral genome was not identified in the myocardium [34,91,92].
•In a series of 104 patients undergoing endomyocardial biopsy for suspected myocarditis or unexplained HF during the COVID-19 pandemic, low loads of SARS-CoV-2 genome were detected in biopsy tissue in five cases [32]. Among these five cases, Dallas criteria for myocarditis were met in one patient and another patient had evidence of borderline myocarditis. However, blood samples were not examined to determine whether the detected SARS-CoV-2 genome might have resulted from circulating blood.
•A case report described a patient with COVID-19 who developed cardiogenic shock; light and electron microscopy of endomyocardial biopsy specimens revealed low-grade interstitial and endocardial inflammation, with viral particles identified in cytopathic macrophages but not in cardiomyocytes, which showed nonspecific features (eg, focal myofibrillar lysis and lipid droplets) [29].
In autopsy series, the above described requirements for identification of SARS-CoV-2 viral myocarditis have not been met [36,93-100], as illustrated by the following examples:
•An international multicenter study of cardiac tissue from the autopsies of 21 patients with COVID-19 found increased interstitial macrophage infiltration in 18 cases (86 percent) and lymphocytic infiltration in 3 cases (14 percent) [101]. Acute myocyte injury in the RV was identified in four cases. Troponin levels were nominally but not significantly higher among patients with lymphocytic infiltration. Electron microscopy was performed on only three cases without myocarditis and was negative for virions.
•In a report from Hamburg of autopsies performed in 12 patients with COVID-19, lymphocytic infiltrates without myocyte necrosis were identified in the RV myocardium in one patient who died of pulmonary embolism and pneumonia [6]. The SARS-CoV-2 genome was found in the myocardium in this case and in other patients in this series without lymphocytic infiltrates in the myocardium [93].
•Another study from Hamburg described cardiac tissue findings in 39 autopsy cases with confirmed COVID-19 [100]. Viral load above 1000 copies per mcg RNA was identified in 16 of 39 patients (41 percent). A cytokine response panel of six proinflammatory genes was increased in those 16 patients compared with 15 patients without SARS-CoV-2 in cardiac tissue. However, there were no significant inflammatory cell infiltrates associated with SARS-CoV-2 in the heart.
•In a report from Brussels of postmortem findings in 17 patients with COVID-19, all except two patients had one or more comorbidity (such as hypertension, diabetes mellitus, cerebrovascular disease, coronary artery disease, and cancer) [94]. There was no evidence of myocarditis in any of the patients. Two patients had evidence of acute MI and 15 patients had signs of chronic ischemic heart disease.
Further investigation, including histologic examination of cardiac tissue in COVID-19 patients, is required to characterize the relationship between COVID-19 and myocardial injury. Since biopsy-proven myocarditis may occur in the absence of troponin release, autopsy studies of COVID-19 victims, regardless of troponin levels, are helpful in clarifying whether SARS-CoV-2 is a new cause of viral myocarditis [35].
●Immune myocarditis – The possibility of COVID-19-associated myocarditis (ie, myocarditis caused by immune activation and not direct infection) has been suggested but not established. Data to support this hypothesis are limited by the nonsystematic approaches to diagnosis of myocarditis (eg, lack of endomyocardial biopsy with virological analysis, failure to exclude other causes of myocardial inflammation or injury) [12,35]. Immune-mediated myocarditis requires biopsy proven evidence of a characteristic pattern of inflammation (eg, lymphocytic, eosinophilic, giant cells), cardiomyocyte necrosis not typical of infarction, and no evidence of infection as assessed by molecular techniques [12,35,102]. The presence of "inflammation" in the heart on noninvasive imaging and/or biochemical evidence of myocardial injury, with or without cardiac symptoms, is not sufficient to establish the diagnosis of immune-mediated myocarditis. For example, in a study of 112 cases of COVID-related "myocarditis," only 17 patients had a biopsy [92].
LONG-TERM CARDIOVASCULAR EFFECTS — Among patients who had COVID-19, the risk of cardiovascular (CV) disease may be increased due to the myocardial stress or hypercoagulable state associated with COVID-19 (see 'Myocardial injury' above). While no direct causal mechanism has been established between COVID-19 and CV disease, limited data suggest that patients who had COVID-19 may have a higher risk of CV disease when compared with patients who did not have COVID-19.
In a study that recorded the one-year incidence of CV disease among almost 5.8 million United States veterans, patients who had COVID-19 had an increased risk of death or major adverse CV events (eg, stroke, MI, arrhythmias, HF) when compared with a group of patients who did not have COVID-19 (23 excess CV events per 1000 patients with COVID-19; adjusted hazard ratio 1.55, 95% CI 1.5-1.6) [103]. In addition, patients hospitalized with more severe COVID-19 (ie, hospitalized for COVID-19) were more likely to develop CV disease when compared with patients with less severe COVID-19.
SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: COVID-19 – Index of guideline topics".)
INFORMATION FOR PATIENTS — UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." The Basics patient education pieces are written in plain language, at the 5th to 6th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10th to 12th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.
Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.)
●Basics topics (see "Patient education: COVID-19 overview (The Basics)" and "Patient education: COVID-19 vaccines (The Basics)")
SUMMARY AND RECOMMENDATIONS
●Adults with coronavirus disease 2019 (COVID-19) commonly have manifestations of heart disease including signs of myocardial injury, but the causes of these findings have not been established. Putative causes of myocardial injury in patients with COVID-19 include myocarditis, hypoxic injury, stress (takotsubo) cardiomyopathy, ischemic injury caused by cardiac microvascular damage or epicardial coronary artery disease (with plaque rupture or demand ischemia), right heart strain (cor pulmonale), and systemic inflammatory response syndrome (cytokine storm). (See 'Etiology' above.)
●Adults with COVID-19 present with a broad spectrum of clinical cardiac presentations: some patients manifest no clinical evidence of heart disease, some have no symptoms of heart disease but have cardiac test abnormalities (such as serum cardiac troponin elevation, asymptomatic cardiac arrhythmias, or abnormalities on cardiac imaging), and some have symptomatic heart disease. Cardiac complications include myocardial injury, heart failure (HF), cardiogenic shock, multisystem inflammatory syndrome in adults, and cardiac arrhythmias including sudden cardiac arrest. (See 'Acute clinical manifestations' above.)
●Myocardial injury (as reflected in elevated cardiac troponin levels) is common among patients hospitalized with COVID-19, but the cause in individual patients is frequently not identified. The presence and magnitude of troponin elevation is associated with more severe disease and worse outcomes. Clinical conditions associated with myocardial injury include myocarditis, stress cardiomyopathy, and myocardial infarction. (See 'Troponin' above and 'Myocardial injury' above.)
●HF in patients with COVID-19 may be precipitated by acute illness in patients with preexisting known or undiagnosed heart disease (eg, coronary artery disease or hypertensive heart disease), acute hemodynamic stress (eg, acute cor pulmonale), or incident acute myocardial injury. (See 'Heart failure' above.)
●Cardiac troponin and natriuretic peptide (B-type natriuretic peptide [BNP] and N-terminal pro-BNP) biomarkers are commonly elevated among hospitalized patients with COVID-19 and are associated with increased risk of mortality. (See 'Biomarkers' above and 'Troponin' above and 'Natriuretic peptides' above.)
●Echocardiography findings prevalent in patients with COVID-19 include right ventricular dilation and dysfunction and left ventricular diastolic and systolic dysfunction. (See 'Echocardiogram' above.)
●Cardiovascular magnetic resonance abnormalities have been identified in patients who have recently recovered from COVID-19. Since limited endomyocardial biopsy data and no follow-up data have been reported, the clinical significance of these findings is uncertain. Moreover, since no patients had a CMR examination before COVID-19, it remains undetermined whether the abnormal findings might have already been present and therefore be unrelated to COVID-19. (See 'Cardiovascular magnetic resonance' above.)
●Myocarditis is commonly suspected in patients with COVID-19 and elevated cardiac troponin levels. However, there have been few reported cases of histologically confirmed myocarditis, and viral myocarditis caused by SARS-CoV-2 has not been definitively confirmed by myocardial histologic and viral genome analysis. (See 'Myocardial histology and viral genome analysis' above.)
●Among patients who had COVID-19, the risk of cardiovascular (CV) disease may be increased. (See 'Long-term cardiovascular effects' above.)
