Understanding COVID-19-Related Heart Muscle Inflammation: What Patients Need to Know

Table of Contents

• Key Points
• Background: Why This Research Matters
• How COVID-19 May Cause Heart Muscle Inflammation
• How Common Is Myocarditis in COVID-19 Patients?
• Heart Rhythm Problems in COVID-19-Related Myocarditis
• Diagnosing COVID-19-Related Myocarditis
• Other Conditions That Can Look Like Myocarditis
• Diagnostic Tests and Imaging
• Long-Term Complications and Unknowns
• Treatment and Management
• Limitations of Current Knowledge
• Recommendations for Patients and Clinicians
• Frequently Asked Questions
• Source Information

Key Points

• COVID-19 can cause myocarditis, an inflammation of the heart muscle, through direct viral damage and an overactive immune response.
• The prevalence of myocarditis among COVID-19 patients is unclear; early reports often lacked specific diagnostic tools.
• Arrhythmias are possible; in one study, 78.7% of myocarditis patients had some form of ventricular arrhythmia.
• Diagnosis may involve blood tests, electrocardiogram, echocardiogram, cardiovascular magnetic resonance, or endomyocardial biopsy.
• Long-term effects of healed myocarditis are completely unknown, especially for patients with mild cases.

Background: Why This Research Matters

In December 2019, doctors in Wuhan, China, first described a new illness called coronavirus disease 2019 (COVID-19). Patients complained of flu-like symptoms. Scientists isolated the virus and identified it as a new strain of coronavirus, now named SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2).

The mortality rate of COVID-19 is estimated to be about 1%, meaning approximately 1 in 100 patients die from the infection. Death is mainly due to severe acute respiratory syndrome and multiorgan dysfunction, where multiple organ systems fail.

Cardiovascular complications of COVID-19 initially received less medical attention than lung problems. However, the first cases of myocarditis (inflammation of the heart muscle) in COVID-19 patients have now been reported. Myocarditis has been recognized as the cause of death in some COVID-19 patients.

The inflammation usually is focal, meaning it affects specific areas within the heart muscle rather than the whole heart. However, there is a risk of arrhythmia (abnormal heart rhythm). There is also a risk of progression to fulminant heart failure (sudden, severe heart failure) and cardiogenic shock (when the heart cannot pump enough blood to meet the body's needs).

This article outlines the possible pathophysiology (how the disease develops and affects the body) of COVID-19-related myocarditis, its clinical presentation (how it appears in patients), and the associated arrhythmias. The authors also propose criteria for screening and management of myocarditis relating to COVID-19.

How COVID-19 May Cause Heart Muscle Inflammation

Myocarditis is an inflammatory disease of the heart. It is characterized by inflammatory infiltrates (immune cells entering the heart tissue) and myocardial injury (damage to heart muscle cells) without an ischemic cause (not due to blocked blood vessels). The most commonly identifiable cause of myocarditis in the United States and other developed countries is viral infection.

Researchers Esfandiarei and McManus proposed that the pathophysiology of viral myocarditis is a combination of direct cell injury and T-lymphocyte-mediated cytotoxicity (damage caused by immune cells called T lymphocytes). This damage can be increased by cytokine storm syndrome, a severe immune reaction where the body releases too many inflammatory signals.

Interleukin-6 (IL-6) appears to be the central mediator of cytokine storm. Interleukin-6 is a protein that coordinates the proinflammatory responses from immune cells, including T lymphocytes. This process causes T-lymphocyte activation and a further release of inflammatory cytokines, which stimulate more T lymphocytes. This creates a positive feedback loop of immune activation and myocardial damage.

Cardiotropism of T lymphocytes (the tendency of these immune cells to move toward the heart) is thought to arise from interaction between heart-produced hepatocyte growth factor (HGF) and c-Met. c-Met is an HGF receptor on naïve T lymphocytes (immune cells that have not yet encountered a specific threat).

Known Human Coronaviruses as Causes of Myocarditis

Despite being a minor cause of all viral myocarditis cases, human coronaviruses have been linked to myocarditis in patients of all age groups. The viral RNAs (genetic material) of Middle East respiratory syndrome coronavirus (MERS-CoV) and SARS-CoV, which are close relatives of SARS-CoV-2, were found in the heart tissues of infected animals. This finding suggests that these coronaviruses possess cardiotropism (the ability to infect heart tissue).

Furthermore, some coronavirus proteins were shown to make the viruses highly infectious to human cells. Nakagawa and colleagues demonstrated that MERS-CoV-D4a, a mutant MERS-CoV strain that lacks the 4a accessory protein, had less efficient replication in laboratory cells compared to the wild-type MERS-CoV. The 4a accessory protein is thought to inhibit protein kinase R-mediated phosphorylation of eukaryotic initiation factor 2.

Failure to phosphorylate the eukaryotic initiation factor 2 impairs stress granule formation. The stress granule helps sequester host proteins important for translation and reduces viral protein synthesis. Therefore, suppression of stress granules promotes viral replication. Similarly, SARS-CoV enhances its RNA translation via the Nsp1 protein.

Possible Pathophysiology of SARS-CoV-2-Related Myocarditis

SARS-CoV-2 gains entry into human cells by binding its spike protein to the membrane protein angiotensin-converting enzyme 2 (ACE2). However, the spike protein must first be cleaved at the S1/S2 and subsequently at the S2' sites to enable binding to ACE2. Cleavage at the S1/S2 site seems to be mediated by TMPRSS2, a serine protein.

ACE2 can be found on ciliated columnar epithelial cells of the respiratory tract, type II pneumocytes (lung cells), and cardiomyocytes (heart muscle cells). Therefore, it is plausible that SARS-CoV-2 infects the human heart, especially in cases of heart failure where ACE2 is upregulated (increased in number). However, the presence of viral receptors does not always predict tropism (whether the virus will actually infect that tissue).

At least 6 known accessory proteins can be transcribed by the SARS-CoV-2 genome. Whether any of the accessory proteins provide an infectivity advantage, as in MERS-CoV and SARS-CoV, remains to be determined.

How Common Is Myocarditis in COVID-19 Patients?

The prevalence of myocarditis among COVID-19 patients is unclear. This uncertainty exists partly because the early reports often lacked the specific diagnostic modalities to assess myocarditis.

Some researchers argued that up to 7% of COVID-19-related deaths were attributable to myocarditis. However, this figure was assumed and not based on confirmatory diagnoses of myocarditis. Therefore, it may be an overestimate.

In contrast, many laboratories are rationing tests and are first screening for known pathogens that cause flu-like symptoms. If a positive pathogen is identified, then testing for SARS-CoV-2 is not performed. This approach is erroneous and likely to miss the true frequency of SARS-CoV-2 infection. This approach assumes mutual exclusivity of SARS-CoV-2 (meaning it assumes patients cannot have both infections at the same time).

One report identified 24.5% of COVID-19 patients as having coinfection with other viruses. Approximately 1 in 4 COVID-19 patients also had another viral infection. Hence, it is possible that many cases of COVID-19-related myocarditis were missed due to a lack of SARS-CoV-2 diagnosis.

Certain ethnic groups may be disproportionately affected by SARS-CoV-2. COVID-19 death rates were shown to be higher among the African American population than other ethnicities in many American states. Although this may be partially explained by the greater number of cardiovascular risk factors or genetic predisposition to poorer cardiac outcomes, healthcare disparities cannot be dismissed. Bias in health and care provisions may be the driving force behind disproportionate suffering in minorities.

Heart Rhythm Problems in COVID-19-Related Myocarditis

Arrhythmia is recognized as one of the possible clinical manifestations of COVID-19 patients. One observational study of the clinical characteristics of COVID-19 patients in Hubei, China, reported a 7.3% incidence of heart palpitations among its 137 patients. This means approximately 7 in 100 patients experienced palpitations.

Moreover, Wang and colleagues reported that arrhythmia was a cause of intensive care unit transfer in 44.4% of COVID-19 patients. This means nearly 1 in 2 patients were transferred to intensive care because of heart rhythm problems. Caution is encouraged when interpreting these data, as the sample size tends to be small and hence prone to overestimation.

The exact nature of the arrhythmias was not usually reported. Therefore, assessing whether the arrhythmias are secondary to other conditions such as electrolyte imbalance or pre-existing arrhythmias is difficult. The actual prevalence of arrhythmias in COVID-19 patients remains unknown.

Nevertheless, arrhythmias could occur in the context of myocarditis. Peretto and colleagues reported in a recent study that 78.7% of myocarditis patients exhibited some form of ventricular arrhythmia (abnormal heart rhythms originating in the lower chambers of the heart). This means approximately 8 in 10 myocarditis patients experienced ventricular arrhythmias. The characteristics of arrhythmias differ between active and healed myocarditis, suggesting that the pathophysiology depends on the stage of myocardial injury.

How Arrhythmias May Develop in COVID-19-Related Myocarditis

Concerning SARS-CoV-2, the possible pathophysiology of arrhythmias includes five mechanisms:

1. Direct injury to cardiomyocytes disrupting the plasma membrane and electrical conduction
2. Infection of the pericardium (the sac around the heart) causing massive edema (swelling)
3. Ischemia (reduced blood flow) from microvascular disease due to possible infection of the pericytes (cells that support blood vessels)
4. Re-entrant arrhythmias due to myocardial fibrosis or scars
5. Proinflammatory cytokines predisposing to arrhythmogenicity (the tendency to develop abnormal heart rhythms)

Mechanisms 1, 2, and 3 could occur in the acute setting (during the initial infection). Mechanisms 4 and 5 occur in chronic or healed myocarditis (after the initial infection has resolved).

In mechanism 5, proinflammatory cytokines (such as IL-6) might cause displacement of plakoglobin, a desmosomal protein, from the cardiomyocyte membrane. This could be arrhythmogenic, as inadequate cell-to-cell adherence is postulated to damage the cell membrane. This damage leads to cardiac cell death and fibrofatty replacement (scar tissue formation). Moreover, reduced surface expression of desmosomal proteins is a known etiology (cause) of arrhythmogenic cardiomyopathies.

Substantial evidence now suggests an increase in serum IL-6 in COVID-19 patients, especially in those with severe presentations. Therefore, it is plausible that SARS-CoV-2 infection precipitates arrhythmias in patients with a genetic predisposition. Clinicians should be vigilant for arrhythmias, especially in areas where both the COVID-19 burden and the arrhythmogenic cardiomyopathy prevalence are high, such as the North-Eastern (Veneto) region of Italy.

Diagnosing COVID-19-Related Myocarditis

Clinical Presentation

The clinical presentation of SARS-CoV-2 myocarditis varies among cases. Some patients may present with relatively mild symptoms, such as fatigue and dyspnea (shortness of breath). Others report chest pain or chest tightness on exertion.

Many patients do deteriorate, showing symptoms of tachycardia (rapid heart rate) and acute-onset heart failure with cardiogenic shock. In these severe cases, patients may also present with signs of right-sided heart failure. These signs include raised jugular venous pressure (visible bulging of neck veins). These signs also include peripheral edema (swelling in the legs and ankles). These signs also include right upper quadrant pain (pain in the upper right abdomen).

The most emergent presentation is fulminant myocarditis, defined as ventricular dysfunction and heart failure within 2 to 3 weeks of contracting the virus. The early signs of fulminant myocarditis usually resemble those of sepsis (a severe whole-body response to infection). The patient often presents febrile (with fever) with low pulse pressure, cold or mottled extremities, and sinus tachycardia (a fast but regular heart rhythm).

Laboratory Investigations

Results of blood tests from myocarditis patients often show elevated levels of lactate and other inflammatory markers. These markers include C-reactive protein, erythrocyte sedimentation rate, and procalcitonin. These markers usually are raised in keeping with the clinical presentation of infection.

It is critical to distinguish fulminant myocarditis from sepsis. This distinction matters because fluid resuscitation, a common sepsis protocol, exacerbates fulminant myocarditis with fluid overload. The authors encourage testing patients for baseline cardiac enzymes, such as troponin and N-terminal pro-B-type natriuretic peptide (NT-proBNP), on hospital admission.

Cardiac troponin I (cTnI), cardiac troponin T (cTnT), NT-proBNP, and BNP levels usually are elevated in myocarditis. This elevation occurs due to acute myocardial injury and possible ventricular dilation. Elevations of both troponin and NT-proBNP levels were observed in the COVID-19-related myocarditis cases.

A negative troponin result cannot exclude myocarditis. This is particularly true for atypical forms such as giant cell myocarditis. This is also true for those patients in the chronic phase. Negative serial high-sensitivity cardiac troponin still is helpful in the acute phase. A negative result makes diagnosis of acute myocarditis significantly less likely. In COVID-19 patients, the (NT-pro)BNP level also could increase secondary to myocardial stress, a possible knock-on effect from severe respiratory illness.

Electrocardiogram Findings

Electrocardiogram (ECG) abnormalities commonly seen with pericarditis, such as ST elevation and PR depression, may be observed in myocarditis. However, these findings are not sensitive in detecting the disease, and their absence is not exclusionary. For example, one COVID-19-related myocarditis case showed neither ST elevation nor PR depression.

Other ECG abnormalities can be observed in myocarditis. These include new-onset bundle branch block, QT prolongation, pseudoinfarct pattern, premature ventricular complexes, and bradyarrhythmia (slow heart rhythm) with advanced atrioventricular nodal block.

Other Conditions That Can Look Like Myocarditis

Several other conditions can mimic COVID-19-related myocarditis. Doctors must consider these possibilities when evaluating patients.

Acute Coronary Syndrome

In the context of raised cardiac troponin levels, acute coronary syndrome (heart attack or unstable angina) is highly suspicious. However, epicardial disease (blockage of the large coronary arteries on the heart's surface) can be ruled out by coronary angiography. Coronary angiography is an X-ray test that shows blood flow in the heart's arteries.

Many COVID-19 patients were reported to have a detectable level of cTnI, even when they had no overt cardiac symptoms. This finding does not generally represent type 1 myocardial infarction (heart attack caused by a blocked artery). It is possible that the raised troponin level is a result of an exacerbation of the patient's subclinical coronary artery disease by sepsis, which increases cardiac oxygen demand.

This increased demand worsens oxygen supply-demand mismatch, which could precipitate ischemia that results in type 2 myocardial infarction (heart damage due to reduced oxygen supply rather than a blocked artery). Serial cardiac biomarkers can help detect myocardial injury, especially in the event of rising biomarker trend.

Sepsis-Related Cardiomyopathy

A case series study showed that 67% of critically ill COVID-19 patients required vasopressors (medications to raise blood pressure) and that 33% developed cardiomyopathy. This means approximately 2 in 3 critically ill patients needed blood pressure support, and 1 in 3 developed heart muscle dysfunction.

This raises suspicion of sepsis-related cardiomyopathy, a disease characterized by reversible myocardial dysfunction. The myocardial injury is thought to arise from increased nitric oxide production, which suppresses the cardiomyocyte's response to calcium and downregulates the heart's b1-adrenergic receptors.

The 3 cardinal signs of sepsis-related cardiomyopathy are:

1. Left ventricular dilation (enlargement of the heart's main pumping chamber)
2. Impaired ejection fraction (reduced pumping ability)
3. Recovery in 7 to 10 days

Stress-Induced Cardiomyopathy (Takotsubo Cardiomyopathy)

Takotsubo cardiomyopathy is a nonischemic cardiomyopathy characterized by transient weakening of the cardiomyocytes and subsequent ballooning of the apex (the tip of the heart). Its clinical manifestations mimic those of acute coronary syndrome, including chest pain, ECG abnormalities, and elevations of cardiac biomarkers.

However, Takotsubo cardiomyopathy usually is preceded by an emotional or physical stressor. Of note, a case report described a COVID-19 patient who initially presented as having reverse Takotsubo cardiomyopathy, a variant form of Takotsubo cardiomyopathy.

Diagnostic Tests and Imaging

The American Heart Association (AHA) recommends further testing for patients having signs consistent with myocarditis with 1 or more cardiac imaging methods. These methods include echocardiogram (ultrasound of the heart) or cardiovascular magnetic resonance (CMR, a detailed imaging test using magnets and radio waves).

The echocardiogram usually is more readily deployed because it is portable. Especially under time and resource constraints, devices such as the hand-held, point-of-care ultrasound machine can be advantageous. These devices offer accessibility and relative ease of disinfecting for infection control.

The cardinal signs of myocarditis on echocardiogram are increased wall thickness, chamber dilation, and pericardial effusion (fluid around the heart) in the background of ventricular systolic dysfunction (reduced pumping function).

Although CMR offers major imaging advantages over echocardiography, it is limited by several factors. These limitations include out-of-hours availability, the requirement for some breath holding, slower throughput, and, given the high contagiousness of COVID-19, the requirement for deep cleaning after use.

If CMR is performed, the results should be interpreted according to the revised Lake Louise consensus criteria:

1. Edema (swelling)
2. Irreversible cell injury
3. Hyperemia (increased blood flow) or capillary leak

CMR myocardial edema and/or scarring were observed in all of the SARS-CoV-2-related myocarditis cases for which CMR results were reported.

If CMR proves prohibitive, cardiac computed tomography (CT) scan with contrast enhancement and ECG gating is an effective alternative. This is especially useful when the patient is to undergo high-resolution CT scan of the chest for assessment of acute respiratory distress syndrome. Contrast-enhanced cardiac CT will add very little scanning time and in this situation is particularly useful to perform a test rapidly with minimal requirement for breath holding.

Without CMR or contrast-enhanced CT results, distinguishing myocarditis from other differential diagnoses is difficult.

Endomyocardial Biopsy

Both the AHA and European Society of Cardiology (ESC) recommend endomyocardial biopsy (EMB) as the definitive diagnostic tool for myocarditis. Endomyocardial biopsy involves taking a small sample of heart tissue for laboratory examination. However, both societies recognize the limitations of EMB in terms of expertise required, contagious spread risk, and false-negative rate.

If obtained, EMB samples should be immunohistochemically tested for inflammatory infiltrates. RNA/DNA extraction should be performed to test for the presence of viral genomes.

Regarding the contagious spread risk, should coronary angiography be deemed necessary, it is reasonable to perform the right heart procedures and/or EMB concomitantly. These will add minimal risk while adding 15 minutes to the procedure time. EMB also serves as an opportunity for accurate diagnosis and provides tissues for the development of specific biomarkers, which could be useful for developing a diagnostic test for SARS-CoV-2 myocarditis.

In the event of patient death, the authors suggest that an autopsy, including the heart, be performed. This will allow observation of the gross and microscopic pathology of the heart, including multiple left and right ventricular segments. This may illuminate new biological pathways for COVID-19 treatments, knowledge that is critically needed and will bring immense societal benefit in this trying time.

Long-Term Complications and Unknowns

While the acute inflammation and injury to the heart are the current focus receiving attention, the long-term effects of healed myocarditis are completely unknown. Most infected patients experience mild, self-limiting symptoms; are managed in the community; and are not undergoing clinical testing such as ECG or cardiac imaging.

Because the emphasis is evaluating and admitting patients with severe lower respiratory tract symptoms, many patients with possible myocarditis will never be evaluated. Some of these patients may survive the acute event but may be at risk for subsequent arrhythmias.

In a study of patients with active and healed myocarditis, monomorphic ventricular tachycardia was more frequent in those with healed than acute myocarditis. Monomorphic ventricular tachycardia is a fast, regular heart rhythm originating in the lower chambers. Regular ventricular arrhythmias were also more frequent in those with healed than acute myocarditis. However, the presence of viral genomes on EMB was not associated with the occurrence of malignant arrhythmias.

Treatment and Management

Managing Myocarditis

The AHA recently published a scientific statement on the recognition and initial management of fulminant myocarditis. The AHA recommends implementing the initial management protocol for cardiogenic shock in patients with fulminant myocarditis.

This protocol includes administration of inotropes (medications that strengthen heart contractions) and/or vasopressors (medications that raise blood pressure) and mechanical ventilation. Longer-term management involves mechanical circulatory support. This support includes extracorporeal membrane oxygenation (ECMO, a machine that oxygenates blood outside the body). This support also includes ventricular assist device (a mechanical pump implanted in the heart). This support also includes intra-aortic balloon pump (a device that helps the heart pump blood).

The ESC did not endorse the use of intravenous immunoglobulin (IVIG, a treatment made from donated antibodies) due to a lack of supporting evidence. The ESC also discouraged the use of corticosteroids in active-infection myocarditis, citing the ineffectiveness of corticosteroids in a randomized controlled trial.

Evidence from Case Reports

Case reports of coronavirus-related myocarditis provide a glimpse into the efficacy of some of the aforementioned treatments. The authors summarize 9 case reports of patients with coronavirus-related myocarditis.

Mechanical circulatory support was deployed in 2 of 7 cases for which treatment modalities were reported. Presumably, in a more hemodynamically stable case (where blood circulation is stable), medical treatment consisting of inotropes or vasopressors was sufficient to mitigate the ventricular systolic dysfunction.

In some cases, immunomodulatory treatments were given. Zeng and colleagues and Hu and colleagues reported the use of corticosteroid and intravenous immunoglobulin. A recent meta-analysis on corticosteroid and intravenous immunoglobulin use in pediatric myocarditis concluded that intravenous immunoglobulin may improve ventricular systolic function but failed to find support for corticosteroid use.

However, immunosuppression might pose a risk for more severe clinical disease, especially in the presence of active viral replication. Therefore, it is reasonable to withhold or minimize the use of immunosuppression in SARS-CoV-2 patients, especially in the setting of a positive viral genome on EMB.

Tocilizumab, an anti-IL-6 receptor monoclonal antibody (a laboratory-made antibody that blocks the IL-6 receptor), is now being tested in a multicenter randomized controlled trial. This trial recruits COVID-19 patients with raised IL-6 levels. This antibody might be beneficial in the setting of cytokine storm syndrome and help reduce myocardial inflammation.

Limitations of Current Knowledge

The authors acknowledge several important limitations in the current understanding of COVID-19-related myocarditis.

• The prevalence of myocarditis among COVID-19 patients remains unclear because early reports often lacked specific diagnostic modalities.
• The exact nature of arrhythmias in COVID-19 patients was not usually reported, making it difficult to assess whether arrhythmias are secondary to other conditions.
• The actual prevalence of arrhythmias in COVID-19 patients remains unknown.
• Many patients with possible myocarditis are never evaluated because the emphasis is on admitting patients with severe respiratory symptoms.
• The long-term effects of healed myocarditis are completely unknown.
• Endomyocardial biopsy has limitations including the expertise required, contagious spread risk, and false-negative rate.
• Immunosuppression might pose a risk for more severe clinical disease, especially in the presence of active viral replication.

Recommendations for Patients and Clinicians

Based on this review, the authors offer several recommendations for healthcare providers and patients.

For Clinicians

1. Be vigilant for arrhythmias, especially in areas where both COVID-19 burden and arrhythmogenic cardiomyopathy prevalence are high.
2. Test patients for baseline cardiac enzymes, including troponin and NT-proBNP, on hospital admission.
3. Distinguish fulminant myocarditis from sepsis because fluid resuscitation, a common sepsis protocol, exacerbates fulminant myocarditis with fluid overload.
4. Use echocardiogram or cardiovascular magnetic resonance for patients with signs consistent with myocarditis.
5. Consider cardiac CT with contrast enhancement when CMR is not feasible.
6. Consider endomyocardial biopsy as the definitive diagnostic tool when appropriate.
7. Withhold or minimize immunosuppression in SARS-CoV-2 patients, especially with positive viral genome on EMB.
8. Perform autopsy including the heart in the event of patient death to advance knowledge.

For Patients

• Seek medical attention if you experience chest pain, chest tightness on exertion, fatigue, or shortness of breath during or after COVID-19 infection.
• Be aware that some patients develop severe symptoms including rapid heart rate, heart failure, and cardiogenic shock.
• Understand that the long-term effects of COVID-19-related myocarditis remain unknown, especially for mild cases.
• Follow up with your healthcare provider about heart health after recovering from COVID-19.

Frequently Asked Questions

What is COVID-19-related myocarditis?

Myocarditis is inflammation of the heart muscle. In COVID-19, the virus may directly damage heart cells and trigger an overactive immune response. The inflammation is usually focal, affecting specific areas rather than the whole heart. It can cause abnormal heart rhythms and, in severe cases, sudden severe heart failure or cardiogenic shock, where the heart cannot pump enough blood.

How common is myocarditis in COVID-19 patients?

The prevalence is unclear. Early reports often lacked specific diagnostic tools, and one suggestion that up to 7% of COVID-19 deaths were due to myocarditis was assumed, not confirmed, so it may be an overestimate. Testing practices that stop after finding another virus may also miss cases. About 24.5% of COVID-19 patients in one report had another viral infection at the same time.

What heart rhythm problems can occur?

Arrhythmias are possible. In one study of 137 patients in Hubei, China, 7.3% reported heart palpitations. Another report found arrhythmia caused intensive care transfer in 44.4% of COVID-19 patients. In a separate study, 78.7% of myocarditis patients had some form of ventricular arrhythmia. The exact nature of these arrhythmias was not usually reported, so the true prevalence remains unknown.

How is COVID-19-related myocarditis diagnosed?

Doctors may use blood tests for troponin and NT-proBNP, which are often elevated, and an electrocardiogram, though its findings are not sensitive. The American Heart Association recommends echocardiogram or cardiovascular magnetic resonance for patients with signs of myocarditis. Endomyocardial biopsy, taking a small heart tissue sample, is the definitive diagnostic tool, but it has limitations including expertise required and false-negative rate.

What symptoms should make me seek medical attention?

Seek medical attention if you experience chest pain, chest tightness on exertion, fatigue, or shortness of breath during or after COVID-19 infection. Some patients develop severe symptoms including rapid heart rate, heart failure, and cardiogenic shock. The most emergent presentation is fulminant myocarditis, defined as ventricular dysfunction and heart failure within 2 to 3 weeks of contracting the virus.

What are the long-term effects?

The long-term effects of healed myocarditis are completely unknown. Many patients with mild, self-limiting symptoms are managed in the community and never undergo testing such as ECG or cardiac imaging, so possible myocarditis may never be evaluated. Some may survive the acute event but be at risk for subsequent arrhythmias. In one study, monomorphic ventricular tachycardia was more frequent in healed than acute myocarditis.

How is COVID-19-related myocarditis treated?

For fulminant myocarditis, the American Heart Association recommends initial management for cardiogenic shock, including inotropes, vasopressors, and mechanical ventilation. Longer-term management may involve mechanical circulatory support such as ECMO, ventricular assist device, or intra-aortic balloon pump. The European Society of Cardiology did not endorse intravenous immunoglobulin and discouraged corticosteroids in active-infection myocarditis. Immunosuppression may pose a risk with active viral replication.

When should a patient with suspected COVID-19-related myocarditis seek a second opinion?

Seek a second opinion when the diagnosis is uncertain. Myocarditis can look like acute coronary syndrome, sepsis-related cardiomyopathy, or stress-induced cardiomyopathy, and distinguishing them is difficult without cardiac magnetic resonance or contrast-enhanced CT. Endomyocardial biopsy is the definitive diagnostic tool but has a false-negative rate and requires expertise. A second opinion can review imaging, troponin and NT-proBNP trends, and ECG findings, and help confirm whether immunosuppression should be withheld, especially with active viral replication. Diagnostic Detectives Network provides independent expert second opinions.

Source Information

Original Article Title: Recognizing COVID-19–related myocarditis

Authors: Bhurint Siripanthong, BA(Cantab); Saman Nazarian, MD, PhD, FHRS; Daniele Muser, MD; Rajat Deo, MD, MTR; Pasquale Santangeli, MD, PhD; Mohammed Y. Khanji, MBBCh, MRCP, PhD; Leslie T. Cooper Jr., MD; C. Anwar A. Chahal, MBChB, MRCP, PhD

Author Affiliations: School of Clinical Medicine, University of Cambridge, Cambridge, United Kingdom; Division of Cardiovascular Medicine, Hospital of the University of Pennsylvania, Philadelphia, Pennsylvania; Department of Cardiology, Newham University Hospital and Barts Heart Centre, Barts Health NHS Trust, London, United Kingdom; NIHR Barts Biomedical Research Centre, William Harvey Research Institute, Queen Mary University of London, London, UK; Mayo Clinic, Jacksonville, Florida; Mayo Clinic, Rochester, Minnesota; and Royal Papworth Hospital, Cambridge, United Kingdom

Publication: HeartRhythm 2020;17:1463-1471. Published by Elsevier Inc. on behalf of Heart Rhythm Society.

DOI: https://doi.org/10.1016/j.hrthm.2020.05.001

Note: This patient-friendly article is based on peer-reviewed research. The original article was published as an open-access article through the Elsevier COVID-19 resource centre, which provides free information on the novel coronavirus COVID-19.