Viral Myocarditis

Earn CME/CE in your profession:

Continuing Education Activity

Myocarditis is an inflammatory process of the heart muscle (myocardium). Myocarditis can present in the acute, subacute, or chronic phase with either focal or diffuse involvement of the myocardium. Viral infections are the most frequent cause of myocarditis in the United States and other developed countries. In developing countries, rheumatic carditis, Chagas disease, and complications related to advanced HIV/AIDS are important causes of myocarditis. Myocarditis is diagnosed based on clinical presentation, and diagnosis is classically confirmed by endomyocardial biopsy. This activity reviews the evaluation and management of myocarditis and highlights the role of the interprofessional team in managing patients with this condition.


  • Apply knowledge of viral myocarditis etiology and pathophysiology to individualize treatment strategies and address potential complications, such as arrhythmias and cardiogenic shock.

  • Implement evidence-based diagnostic approaches, incorporating non-invasive tools like cardiac MRI and biomarkers, to complement the established endomyocardial biopsy for confirming diagnosis.

  • Identify the diverse clinical presentations of viral myocarditis, including acute, subacute, and chronic phases, and recognize potential complications such as congestive heart failure, arrhythmias, and cardiogenic shock.

  • Assess the severity and prognosis of viral myocarditis, utilizing risk stratification tools to identify patients who may benefit from more intensive monitoring or targeted therapies.


Myocarditis is an inflammatory heart muscle (myocardium) process with focal and diffuse involvement. Clinically, myocarditis can present as an acute, subacute, or chronic disease process.[1] The presentation can be highly variable in symptomatic patients, from generalized fatigue, malaise, chest pain, congestive heart failure (CHF), cardiogenic shock, arrhythmias, and cardiac arrest.

In the United States and other developed countries, viral infections are most frequently the cause of myocarditis. In developing countries, rheumatic carditis, Chagas disease, and complications related to advanced HIV/AIDS are significant causes of myocarditis. Other causes include toxic myocarditis, related to drugs that may cause an insidious form of the disease.[2] The exact incidence of myocarditis is unclear because of the above heterogenicity.[3]

Myocarditis is diagnosed based on clinical presentation. Diagnosis is classically confirmed by endomyocardial biopsy via established histologic, immunologic, and immunohistochemical criteria.

Myocarditis can occur in an otherwise healthy person and quickly result in progressive heart failure. Myocarditis may be acute, lasting less than 2 weeks, or chronic, lasting more than 2 weeks.


Myocarditis is thought to be caused by various infectious and noninfectious causes. Among the infectious causes, viruses are presumed to be the most common pathogen. In North America and Europe, the most frequently implicated viruses are parvovirus B-19 and human herpesvirus 6 (HHV 6), followed by Epstein-Barr virus, enterovirus, human cytomegalovirus, and adenovirus. Other pathogens that have been implicated include various bacteria, fungi, protozoa, and helminths. Multiple case reports of COVID-19 and influenza-associated myocarditis have recently been reported in the medical literature. Other common noninfectious causes of myocarditis include autoimmune disorders such as systemic lupus erythematosus, Wegener granulomatosis, and giant cell arteritis. In some patients, viral particles may be found in biopsy specimens. In almost 50% to 80% of cases, no cause is ever found.

Damage to the myocardium occurs in the following ways:

  • Direct damage by the offending agent
  • Secondary immune response triggered by the offending agent
  • Expression of cytokines in the myocardium, which leads to an inflammatory process 
  • Premature or aberrant induction of apoptosis


The incidence of myocarditis is approximately 1.5 million cases worldwide annually, and the overall incidence is unknown and probably underdiagnosed. In the United States, the frequency of myocarditis is difficult to ascertain as many cases are subclinical. In community-based populations, the prevalence and outcomes of myocarditis are unknown as epidemiologic studies suggest that most Coxsackie B virus infections, a significant cause of myocarditis, are subclinical, thus following a benign course.

According to some estimates, 1% to 5% of all patients with acute viral infections may involve the myocardium. Most patients are young and healthy. Susceptible individuals include children, pregnant women, and those who are immunocompromised.

COVID-19 and Myocarditis

The true epidemiology of COVID-19–associated cardiac diseases is difficult to establish. In a study by Shi S et al, cardiac injury was reported in 19% to 28% of COVID-19 patients in Wuhan, China, and was found to be associated with worse patient outcomes.[4]  In a Global health research network retrospective cohort study, 5% of COVID-19 patients had new onset myocarditis, and 6 months of all-cause mortality was 3.9%.[5] Patients with COVID-19 have a 16 times increased risk of myocarditis compared without COVID-19. The diagnosis of COVID-19 myocarditis is proportional to increased hospitalizations from COVID-19 infection in 2020 to 2021.[6] The incidence of myocarditis after COVID-19 mRNA vaccinations is extremely low at 0.3 to 5 cases per 100,000 in the USA and Israel, mostly in young men within a week after the second dose, with a self-limiting course.[7][8] The incidence of myocarditis associated with COVID-19 infection is 100 times higher than the mRNA vaccination.[9]


Myocarditis begins with the direct invasion of an infectious agent and its subsequent replication within or around the myocardium, causing myonecrosis leading to the destruction of the cardiac tissue from the infiltration and replication of the infectious agent.[10][11]

Later, the host cellular immune response and the offending agent activate the cytotoxic effects of host immunity. Persistence of the virus in the myocardium is associated with progressive deterioration of heart muscle function, ie, left ventricle. Marked improvement in heart function is seen once the viral genome is eliminated.[12] Exogenous or endogenous chemicals produced by the systemic pathogen might induce a toxic effect directly on the myocyte.

Three stages of the disease process are listed below.

  • Acute stage (1-7 days): Defined by direct viral cytotoxicity and focal or diffuse necrosis of the myocardium with subsequent exposure to host proteins and activation of the innate immune response. Adenovirus and enterovirus cause direct cell toxicity, whereas parvovirus infests endothelium and releases pro-inflammatory cytokines. Influenza causes T-cell–regulated inflammatory response. 
  • Subacute stage (1-4 weeks): An increase in autoimmune-mediated injury with activated T cells and B cells and subsequent antibody production, creating cardiac autoantibodies and inflammatory proteins. There are higher concentrations of anti-b-myosin antibodies in patients with myocarditis with dilated cardiomyopathy than in control groups.
  • Recovery or chronic: Depends on the presence or elimination of the viral genome in the myocyte. Chronic T-cell–mediated inflammation results in remodeling and diffuse myocardial fibrosis, affecting cardiac dysfunction and leading to dilated cardiomyopathy and its sequelae, such as CHF, ventricular dysrhythmias, and abnormal ECG findings. Th17 cells are believed to play a significant role in this chronic phase of myocarditis.[13]

The chronicity of viral myocarditis depends on the favorable host genetic background based on a study by Artico et al, where 31% of patients are carriers of pathogenic genes like titin, filamin C, and desmoplakin.[14] Further knowledge of micro RNAs (miRNA) as immune response regulators in the subacute and chronic phases might shed more light on patients with persistent and progressive cardiac dysfunction.[15]

COVID-19 and Myocarditis

The exact pathophysiology mechanism of COVID-19 infection and myocarditis needs to be better established. The direct role of angiotensin-converting enzyme-2 receptors and hyperimmune response are plausible theories causing myocarditis with COVID-19.[16] COVID-19 mRNA vaccines are also associated with acute myocarditis, and the etiology is unknown. The role of mRNA immune reactivity, antibodies to SARS-CoV-2 spike proteins, and hormonal differences (ie, immune response) might be the most likely explanation.[17]


Endomyocardial biopsy is typically recommended after other causes of heart failure, such as ischemic heart disease, valvular lesions, and other causes of cardiomyopathy, have been excluded. Endomyocardial biopsy is recommended should the likelihood of the results change management or impact prognosis.

Classic histologic examination of an endomyocardial biopsy will reveal cellular infiltrates, usually histiocytic and mononuclear, with or without associated myocyte damage. Specific findings include eosinophilic, granulomatous, and giant-cell myocarditis. The infiltrates are highly variable and often associated with varying degrees of myonecrosis. With subacute and chronic myocarditis, interstitial fibrosis may result from the previous insult of the myocardial cytoskeleton.


Toxic drug-induced myocarditis is a term used to describe myocarditis caused by illicit drugs or drugs used as part of chronic medical management. Many drugs, including but not limited to cocaine, phenothiazines, alcohol, tricyclic antidepressants, and lithium, are known to cause myocarditis over time. Frequently, toxic myocarditis will run an insidious course, resulting in CHF and dilated cardiomyopathy, often irreversible.Post-mortem examinations have revealed that cocaine abusers often display myocarditis. The cause of this condition is not entirely clear, but it is thought to be linked to the drug's strong sympathomimetic effect, high levels of oxidative stress, and how metabolites interact with ion channels. Myocarditis may be responsible for structural alterations predisposing the patient to ventricular dysrhythmias associated with sudden deaths.

History and Physical

Viral myocarditis is typically seen in young males with varied clinical presentations. Patients typically present with a 7- to 14-day history of mild flulike illness, including fever, malaise, myalgia, vomiting, and diarrhea. Rarely do they have debilitating symptoms like dyspnea at rest, palpitations, and sudden cardiac death.

  • Adults typically present with chest pain (95%), dyspnea (45%), fatigue, syncope, palpitations, fever (18-35%), tachycardia, and tachypnea. Hypotension may be seen. The presence of chest pain or CHF symptoms often indicates a poor prognosis.
  • Children often present with grunting respirations and intercostal retractions. Infants often present with fulminant syndrome, including fever, hypoxia with cyanosis, respiratory distress or failure, and occasionally cardiac arrest. Much like adults, long-term prognosis correlates with the severity of their initial presentation.

The 2013 European Society of Cardiology classified acute myocarditis into 3 profiles.[3]

  1. Acute coronary syndrome-like presentation, including chest pain, ST/T wave changes on electrocardiogram (ECG), troponin elevation, and wall motion abnormalities
  2. New onset progressive heart failure, which includes impaired left and right ventricular dysfunction, nonspecific ECG changes, heart blocks, or arrhythmias
  3. Severe life-threatening fulminant conditions, such as cardiogenic shock requiring vasopressors, mechanical life support, and ventricular arrhythmias requiring defibrillation 

Patients with fulminant myocarditis have a higher rate of cardiac death and often require heart transplants within 5 years.

The physical examination findings are similar to CHF and may include an S3 gallop, rales, tachycardia, and dependent edema. 

Special cases of myocarditis include the following:

  • Sarcoid myocarditis presents with heart block and associated lymphadenopathy.
  • Giant cell myocarditis presents with ventricular tachycardia and heart failure.
  • Acute rheumatic fever presents with chorea, erythema marginatum, polyarthritis, and subcutaneous nodules.


Most patients will present with nonspecific ECG findings like sinus tachycardia, wide QRS patterns, low voltage, prolonged QT, variable atrioventricular (AV) blocks, and acute myocardial infarction patterns.[18]

The stage of the disease process in which cardiac markers like troponin may be elevated is unclear. Elevated troponin levels may suggest more damage to the heart muscle, indicating myonecrosis. However, negative levels do not necessarily rule out the possibility of this diagnosis. Tests to determine complete blood count (CBC), erythrocyte sedimentation rate (ESR), and c-reactive protein (CRP) levels are recommended. Elevated white blood cell and CRP levels or faster ESR might occur but are inconclusive for diagnosing the condition.[19]

Viral antibody titers should also be ordered, including coxsackievirus group B, HIV, CMV, Epstein-Barr virus, hepatitis, and influenza viruses. IgM titers typically increase 4-fold during the acute phase, with a gradual fall as the disease progresses; therefore, serial titers may be helpful.[20]

Transthoracic echocardiogram (TTE) is usually the first imaging modality of choice in suspected myocarditis, specifically in unstable patients where cardiac MRI cannot be performed. However, TTE has limited diagnostic accuracy because myocarditis does not have specific echocardiographic findings. The most common finding includes preserved left ventricular ejection fraction (LVEF) without regional wall motion abnormalities. It may show nonspecific findings such as reduced left ventricular function, global hypokinesis, and regional wall motion abnormalities. When the left ventricle appears globally hypokinetic but not dilated and demonstrates increased wall thickness and echogenicity (edema), and right ventricular dysfunction is observed, it may indicate the presence of fulminant myocarditis.

Two-dimensional speckle-tracking echocardiography is a diagnostic and prognostic tool for patients with suspected viral myocarditis.[21] Additionally, real-time myocardial contrast echocardiography can offer further insight into the ventricles' inflammatory process, although its sensitivity and specificity have yet to be determined.[22][21] Scintigraphy with Indium-111 labeled antimyosin antibodies can localize and visualize dead myocardial tissue areas by highlighting the intracellular proteins because of loss of cell membrane integrity.[23] 

Cardiac MRI is the best noninvasive imaging modality for both diagnosis and follow-up. The diagnosis of myocarditis through cardiac MRI relies on the Lake Louise Criteria, initially released in 2009 and later revised in 2018. The original Lake Louise Criteria (2009) proposed a clinical cardiac MRI protocol for evaluating the principal tissue targets in myocarditis, including:

  • Myocardial edema - increased Tweighted signal intensity 
  • Hyperemia and capillary leak - early gadolinium enhancement (EGE)
  • Myocyte necrosis and fibrosis - late gadolinium enhancement (LGE)

Supportive criteria include associated impairment of global or regional systolic left ventricular function and pericardial effusion. The presence of 2 of the 3 criteria supports the diagnosis of myocarditis with 74% sensitivity and 86% specificity.[24]

In the subsequent decade, significant advancements in cardiac MRI technology enabled high-resolution and clinically applicable quantitative T1-and T2-mapping techniques. These are particularly sensitive in detecting significant increases in myocardial free water content, hence their utility in detecting myocarditis. Accordingly, the Lake Louise Criteria were updated in 2018 to include parametric mapping.

According to the revised Lake Louise Criteria 2018, in the setting of clinically suspected acute myocarditis, cardiac MRI findings are consistent with myocardial inflammation if both T1- and T2-based criteria are present, as follows:

  • T2-based imaging: regional or global increase in myocardial T2 signal, either on T2-weighted imaging or T2-mapping
  • T1-based imaging: regional or global increase in myocardial T1-signal, either on native myocardial T1-mapping, extracellular volume (ECV) quantification, or LGE imaging in a predominantly non-ischemic pattern

Supportive criteria include:

  • The presence of pericardial effusion in cine cardiac MRI images or high signal intensity of the pericardium in LGE images, T1 mapping or T2 mapping
  • The presence of systolic left ventricular wall motion abnormality in cine cardiac MRI images

Most cases of acute myocarditis have normal LVEF with no wall motion abnormalities. Myocardial tissue characterization is crucial for diagnosis; therefore, MRI is of immense value. In patients with contraindications to cardiac MRI, a PET scan using 18F-fluoro-2-deoxyglucose can be used, although it may be nonspecific.[25]

Endomyocardial biopsy, considered the gold standard for diagnosis, is rarely utilized. Endomyocardial biopsy has limited sensitivity and specificity, as inflammation across the myocardium may be diffuse or focal in myocarditis. More importantly, histologic diagnosis rarely has an impact on therapeutic approaches. However, according to 2020 expert consensus, biopsy should be performed if a patient's condition is deteriorating. Other indications for endomyocardial biopsy are severe heart failure, high-degree AV block, cardiogenic shock, suspected inflammatory cardiomyopathy, and idiopathic causes. The Heart Failure Society of America does recommend a myocardial biopsy.[26] An endomyocardial biopsy within 2 weeks of symptom onset with the collection of 4 to 6 specimens for the best yield is recommended. Cardiac catheterization may be required in some patients to rule out coronary artery disease.

Treatment / Management

For the most part, treatment of myocarditis is supportive and aimed at preserving left ventricular function. Treatments range from activity limitation to rhythm control and CHF management. Due to the lack of large multicenter randomized control trials, treatment recommendations for myocarditis are primarily based on expert consensus. Any patient suspected of having myocarditis, whether they are symptomatic or not, should be admitted to the hospital. The patient should be monitored for arrhythmias and signs of decompensation. A transthoracic echocardiogram should be obtained. Patients experiencing chest pain upon admission should be considered for a coronary CT angiogram or cardiac catheterization.

Along with providing supportive care, patients who present with heart failure and ventricular dysfunction should be treated according to current heart failure guidelines. Patients with heart failure often require diuretics and inotropic support. Long-term treatment with ACE inhibitors is recommended. Avoid cardiotoxic drugs and NSAIDs, as they can hinder the healing of the myocardium and exacerbate the inflammatory process. Some patients may require anticoagulation. The use of antiarrhythmics requires good clinical judgment, as many of these agents also have negative inotropic effects that may worsen heart failure. The use of aspirin is uncertain when it comes to acute myocarditis. Beta-blockers should be avoided in patients with heart blocks. Patients with a heart block may need a temporary pacemaker, while a permanent pacemaker is recommended if symptoms persist and the patient is ready to be discharged home.[27] 

Physical activity should be limited during the acute phase of the disease. Exercise or nuclear stress testing should be avoided with acute symptoms. Intra-aortic balloon pump counterpulsation, Impella system, and veno-arterial extracorporeal oxygenation should be considered in patients with cardiogenic shock refractory to medical therapy.

Multicenter trials evaluating antivirals and immunosuppressive therapies, such as IVIG, have shown no benefit. Management of chronic viral myocarditis is similar to current heart failure guidelines. Viral myocarditis was initially thought to be fully reversible, but recent literature proves this may not be true. The prognosis of patients with myocarditis depends on the severity of the inflammatory process and the presentation of symptoms. Patients with severe disease and life-threatening arrhythmias have a poor prognosis and will likely require a mechanical assist device.[28] In this case, they will need to be considered for cardiac transplantation, but this is only an option if a suitable donor is found.

European guidelines suggest waiting for the resolution of the acute phase before implantation of an automatic implantable cardioverter defibrillator (AICD). Still, more recent data from the Lombardy registry and a study by Rosier et al. showed that the patients presenting with ventricular tachyarrhythmia in the acute phase of myocarditis who have received AICD implantation early for secondary prophylaxis had a high risk of recurrence for major arrhythmic events over a follow-up of 3 years.[29][30] On the other hand, patients presenting with sustained ventricular tachycardia or ventricular fibrillation will benefit from AICD implantation during the acute phase at discharge from the hospital for secondary prophylaxis. Patients with LVEF of less than or equal to 35% with acute myocarditis should be discharged with a wearable cardiac defibrillator for primary prophylaxis and optimal medical therapy and then reevaluated at 3 months for AICD implantation.[31] Professional athletes with an AICD should have it programmed for higher rate cutoffs and duration detection to help reduce inappropriate shocks during physical activity.[32] 

Patients with mild symptoms do improve spontaneously, but recovery can take months. Repeat assessment with echocardiograms is necessary. Patients who continue to do poorly should be referred to a tertiary care center where assist devices and transplant services are available.

Differential Diagnosis

The following conditions must be ruled out when diagnosing of myocarditis.

  • Carnitine deficiency
  • Coarctation of the aorta
  • Coronary artery anomalies
  • Cardiac tumor
  • Dilated cardiomyopathy
  • Endocardial fibroelastosis
  • Enteroviral infections
  • Genetics of von Gierke disease
  • Genetics of glycogen-storage disease type II
  • Medial necrosis of coronary arteries
  • Nonviral myocarditis
  • Shock
  • Valvar aortic stenosis
  • Viral pericarditis


Patients with mild myocarditis usually have a good prognosis. Poor prognostic factors include low ejection fraction, left bundle branch block, and syncope. The patients may also develop varying degrees of heart block and require permanent pacing. Cardiogenic shock is the most common cause of death, with the highest mortality rates in postpartum cardiomyopathy.

Cardiac MRI is an effective tool for predicting adverse events and diagnosing viral myocarditis. LGE on cardiac MRI within 5 days of the patient's presentation was strongly associated with poor outcomes, including sudden cardiac death, sustained ventricular tachycardia, hospitalization, and transplantation, even in those with a normal LVEF.[33] On cardiac MRI at 6-month follow-up, the finding of LGE without edema favors definitive fibrosis, indicating a poorer prognosis.[34] Evaluating left ventricular global longitudinal strain through speckle tracking echocardiography and cardiac MRI has a prognostic value. In cases of myocarditis, a decrease in this strain predicts a higher risk of experiencing nonsustained ventricular tachycardia in the future. The presence of LGE with decreased global longitudinal strain portends a poor prognosis, whereas the absence of LGE with increased global longitudinal strain suggests a favorable prognosis.[35]

Patients with acute fulminant myocarditis have an excellent long-term prognosis if the disease is recognized quickly and appropriate supportive care is initiated early. In one study, a survival rate of 93% at 11 years was demonstrated. The long-term prognosis of those with less severe disease was generally good, with a 3- to 5-year survival rate of 56% to 83%.


Excessive physical activity during acute myocarditis may increase the risk of sudden cardiac death. Professional athletes should refrain from competitive events for at least 3 to 6 months from the onset of myocarditis, regardless of the severity of symptoms, age, and sex. Before resuming participation in competitive sports, a complete evaluation and functional testing should be performed.

Life-threatening arrhythmias should be treated appropriately with AICD. The most likely mechanism for arrhythmias in acute myocarditis includes pathogen-mediated cell lysis, inflammatory changes, increased edema, cytokine release, gap junction dysfunction, and abnormal calcium handling secondary to iron channel impairment. Chronic myocarditis can also pose a risk for arrhythmias secondary to ongoing chronic inflammation, scar formation, and ventricular dysfunction.

Postoperative and Rehabilitation Care

Long-term follow-up every 3 months is needed as recovery can take months or years. Patients with cardiac transplantation should be followed appropriately by their transplant team.


Consults in these departments should be considered when diagnosing myocarditis. 

  • Electrophysiology to evaluate the need for AICD and pacemakers in patients with sustained ventricular arrhythmias or heart blocks 
  • Cardiology for evaluation and medical optimization in myocarditis with heart failure
  • Interventional cardiology to evaluate for cardiac catheterization
  • Physical medicine and rehabilitation for cardiac rehabilitation

Deterrence and Patient Education

Patients should be educated about vaccination against measles, rubella, polio, influenza, and mumps. Patients with heart failure should be told to eat a low-salt diet and avoid strenuous activities.

Pearls and Other Issues

All individuals who are suspected of having or have been diagnosed with acute myocarditis should be admitted to the hospital for monitoring of hemodynamic instability. Immediate complications of myocarditis include ventricular arrhythmias, left ventricular aneurysms, CHF, and dilated cardiomyopathy.

Enhancing Healthcare Team Outcomes

In the collaborative approach to treating and managing viral myocarditis, physicians, nurses, pharmacists, and other health professionals play crucial roles, each contributing their unique skills and expertise. Physicians must identify and diagnose the diverse clinical presentations of viral myocarditis, differentiating it from other causes of myocardial inflammation. On the other hand, nurses excel in patient care, applying their knowledge to screen high-risk individuals promptly and assess the severity of the condition. Pharmacists are vital in implementing evidence-based treatment strategies, selecting appropriate medications, and ensuring medication safety and interactions.

All health professionals must adhere to high ethical standards, prioritizing patient well-being and autonomy throughout the treatment journey. Effective interprofessional communication is essential for sharing critical information, discussing treatment plans, and providing holistic patient-centered care. Care coordination among team members enhances patient outcomes by facilitating seamless transitions between different phases of care and promoting a cohesive approach to management. By synergizing their skills, strategies, ethics, responsibilities, interprofessional communication, and care coordination, healthcare professionals can improve patient safety, enhance team performance, and ultimately achieve better patient-centered care when treating and managing viral myocarditis.



Michael Kang


Venu Chippa


Jason An


11/20/2023 3:57:47 PM



Bejiqi R, Retkoceri R, Maloku A, Mustafa A, Bejiqi H, Bejiqi R. The Diagnostic and Clinical Approach to Pediatric Myocarditis: A Review of the Current Literature. Open access Macedonian journal of medical sciences. 2019 Jan 15:7(1):162-173. doi: 10.3889/oamjms.2019.010. Epub 2019 Jan 4     [PubMed PMID: 30740183]

Level 2 (mid-level) evidence


Price JF. Congestive Heart Failure in Children. Pediatrics in review. 2019 Feb:40(2):60-70. doi: 10.1542/pir.2016-0168. Epub     [PubMed PMID: 30709972]


Caforio AL, Pankuweit S, Arbustini E, Basso C, Gimeno-Blanes J, Felix SB, Fu M, Heliö T, Heymans S, Jahns R, Klingel K, Linhart A, Maisch B, McKenna W, Mogensen J, Pinto YM, Ristic A, Schultheiss HP, Seggewiss H, Tavazzi L, Thiene G, Yilmaz A, Charron P, Elliott PM, European Society of Cardiology Working Group on Myocardial and Pericardial Diseases. Current state of knowledge on aetiology, diagnosis, management, and therapy of myocarditis: a position statement of the European Society of Cardiology Working Group on Myocardial and Pericardial Diseases. European heart journal. 2013 Sep:34(33):2636-48, 2648a-2648d. doi: 10.1093/eurheartj/eht210. Epub 2013 Jul 3     [PubMed PMID: 23824828]


Shi S,Qin M,Shen B,Cai Y,Liu T,Yang F,Gong W,Liu X,Liang J,Zhao Q,Huang H,Yang B,Huang C, Association of Cardiac Injury With Mortality in Hospitalized Patients With COVID-19 in Wuhan, China. JAMA cardiology. 2020 Mar 25;     [PubMed PMID: 32211816]

Level 2 (mid-level) evidence


Buckley BJR, Harrison SL, Fazio-Eynullayeva E, Underhill P, Lane DA, Lip GYH. Prevalence and clinical outcomes of myocarditis and pericarditis in 718,365 COVID-19 patients. European journal of clinical investigation. 2021 Nov:51(11):e13679. doi: 10.1111/eci.13679. Epub 2021 Sep 18     [PubMed PMID: 34516657]

Level 2 (mid-level) evidence


Boehmer TK, Kompaniyets L, Lavery AM, Hsu J, Ko JY, Yusuf H, Romano SD, Gundlapalli AV, Oster ME, Harris AM. Association Between COVID-19 and Myocarditis Using Hospital-Based Administrative Data - United States, March 2020-January 2021. MMWR. Morbidity and mortality weekly report. 2021 Sep 3:70(35):1228-1232. doi: 10.15585/mmwr.mm7035e5. Epub 2021 Sep 3     [PubMed PMID: 34473684]


Witberg G, Barda N, Hoss S, Richter I, Wiessman M, Aviv Y, Grinberg T, Auster O, Dagan N, Balicer RD, Kornowski R. Myocarditis after Covid-19 Vaccination in a Large Health Care Organization. The New England journal of medicine. 2021 Dec 2:385(23):2132-2139. doi: 10.1056/NEJMoa2110737. Epub 2021 Oct 6     [PubMed PMID: 34614329]


Mevorach D, Anis E, Cedar N, Bromberg M, Haas EJ, Nadir E, Olsha-Castell S, Arad D, Hasin T, Levi N, Asleh R, Amir O, Meir K, Cohen D, Dichtiar R, Novick D, Hershkovitz Y, Dagan R, Leitersdorf I, Ben-Ami R, Miskin I, Saliba W, Muhsen K, Levi Y, Green MS, Keinan-Boker L, Alroy-Preis S. Myocarditis after BNT162b2 mRNA Vaccine against Covid-19 in Israel. The New England journal of medicine. 2021 Dec 2:385(23):2140-2149. doi: 10.1056/NEJMoa2109730. Epub 2021 Oct 6     [PubMed PMID: 34614328]


Maiese A, Frati P, Del Duca F, Santoro P, Manetti AC, La Russa R, Di Paolo M, Turillazzi E, Fineschi V. Myocardial Pathology in COVID-19-Associated Cardiac Injury: A Systematic Review. Diagnostics (Basel, Switzerland). 2021 Sep 8:11(9):. doi: 10.3390/diagnostics11091647. Epub 2021 Sep 8     [PubMed PMID: 34573988]

Level 1 (high-level) evidence


Gannon MP, Schaub E, Grines CL, Saba SG. State of the art: Evaluation and prognostication of myocarditis using cardiac MRI. Journal of magnetic resonance imaging : JMRI. 2019 Jun:49(7):e122-e131. doi: 10.1002/jmri.26611. Epub 2019 Jan 13     [PubMed PMID: 30637834]


Kurdi M, Zgheib C, Booz GW. Recent Developments on the Crosstalk Between STAT3 and Inflammation in Heart Function and Disease. Frontiers in immunology. 2018:9():3029. doi: 10.3389/fimmu.2018.03029. Epub 2018 Dec 19     [PubMed PMID: 30619368]


Pietsch H, Escher F, Aleshcheva G, Lassner D, Bock CT, Schultheiss HP. Detection of parvovirus mRNAs as markers for viral activity in endomyocardial biopsy-based diagnosis of patients with unexplained heart failure. Scientific reports. 2020 Dec 18:10(1):22354. doi: 10.1038/s41598-020-78597-4. Epub 2020 Dec 18     [PubMed PMID: 33339949]


Sozzi FB, Gherbesi E, Faggiano A, Gnan E, Maruccio A, Schiavone M, Iacuzio L, Carugo S. Viral Myocarditis: Classification, Diagnosis, and Clinical Implications. Frontiers in cardiovascular medicine. 2022:9():908663. doi: 10.3389/fcvm.2022.908663. Epub 2022 Jun 20     [PubMed PMID: 35795363]


Artico J, Merlo M, Delcaro G, Cannatà A, Gentile P, De Angelis G, Paldino A, Bussani R, Ferro MD, Sinagra G. Lymphocytic Myocarditis: A Genetically Predisposed Disease? Journal of the American College of Cardiology. 2020 Jun 23:75(24):3098-3100. doi: 10.1016/j.jacc.2020.04.048. Epub     [PubMed PMID: 32553263]


Kuehl U, Lassner D, Gast M, Stroux A, Rohde M, Siegismund C, Wang X, Escher F, Gross M, Skurk C, Tschoepe C, Loebel M, Scheibenbogen C, Schultheiss HP, Poller W. Differential Cardiac MicroRNA Expression Predicts the Clinical Course in Human Enterovirus Cardiomyopathy. Circulation. Heart failure. 2015 May:8(3):605-18. doi: 10.1161/CIRCHEARTFAILURE.114.001475. Epub 2015 Mar 11     [PubMed PMID: 25761932]


Oudit GY, Kassiri Z, Jiang C, Liu PP, Poutanen SM, Penninger JM, Butany J. SARS-coronavirus modulation of myocardial ACE2 expression and inflammation in patients with SARS. European journal of clinical investigation. 2009 Jul:39(7):618-25. doi: 10.1111/j.1365-2362.2009.02153.x. Epub 2009 May 6     [PubMed PMID: 19453650]


Bozkurt B, Kamat I, Hotez PJ. Myocarditis With COVID-19 mRNA Vaccines. Circulation. 2021 Aug 10:144(6):471-484. doi: 10.1161/CIRCULATIONAHA.121.056135. Epub 2021 Jul 20     [PubMed PMID: 34281357]


Zhang T, Miao W, Wang S, Wei M, Su G, Li Z. Acute myocarditis mimicking ST-elevation myocardial infarction: A case report and review of the literature. Experimental and therapeutic medicine. 2015 Aug:10(2):459-464     [PubMed PMID: 26622337]

Level 3 (low-level) evidence


Lazaros G, Oikonomou E, Tousoulis D. Established and novel treatment options in acute myocarditis, with or without heart failure. Expert review of cardiovascular therapy. 2017 Jan:15(1):25-34     [PubMed PMID: 27858465]


Tselios K, Urowitz MB. Cardiovascular and Pulmonary Manifestations of Systemic Lupus Erythematosus. Current rheumatology reviews. 2017:13(3):206-218. doi: 10.2174/1573397113666170704102444. Epub     [PubMed PMID: 28675998]


Hsiao JF, Koshino Y, Bonnichsen CR, Yu Y, Miller FA Jr, Pellikka PA, Cooper LT Jr, Villarraga HR. Speckle tracking echocardiography in acute myocarditis. The international journal of cardiovascular imaging. 2013 Feb:29(2):275-84. doi: 10.1007/s10554-012-0085-6. Epub 2012 Jun 27     [PubMed PMID: 22736428]


Afonso L, Hari P, Pidlaoan V, Kondur A, Jacob S, Khetarpal V. Acute myocarditis: can novel echocardiographic techniques assist with diagnosis? European journal of echocardiography : the journal of the Working Group on Echocardiography of the European Society of Cardiology. 2010 Apr:11(3):E5. doi: 10.1093/ejechocard/jep183. Epub 2009 Nov 24     [PubMed PMID: 19939815]


Alexander C, Oberhausen E. Myocardial scintigraphy. Seminars in nuclear medicine. 1995 Apr:25(2):195-201     [PubMed PMID: 7597421]


Ferreira VM, Schulz-Menger J, Holmvang G, Kramer CM, Carbone I, Sechtem U, Kindermann I, Gutberlet M, Cooper LT, Liu P, Friedrich MG. Cardiovascular Magnetic Resonance in Nonischemic Myocardial Inflammation: Expert Recommendations. Journal of the American College of Cardiology. 2018 Dec 18:72(24):3158-3176. doi: 10.1016/j.jacc.2018.09.072. Epub     [PubMed PMID: 30545455]


Ammirati E, Frigerio M, Adler ED, Basso C, Birnie DH, Brambatti M, Friedrich MG, Klingel K, Lehtonen J, Moslehi JJ, Pedrotti P, Rimoldi OE, Schultheiss HP, Tschöpe C, Cooper LT Jr, Camici PG. Management of Acute Myocarditis and Chronic Inflammatory Cardiomyopathy: An Expert Consensus Document. Circulation. Heart failure. 2020 Nov:13(11):e007405. doi: 10.1161/CIRCHEARTFAILURE.120.007405. Epub 2020 Nov 12     [PubMed PMID: 33176455]

Level 3 (low-level) evidence


Bailey JR, Loftus A RN, Allan RJC. Myopericarditis: recognition and impact in the military population. Journal of the Royal Army Medical Corps. 2019 Dec:165(6):451-453. doi: 10.1136/jramc-2018-001056. Epub 2018 Nov 14     [PubMed PMID: 30429297]


Kusumoto S, Kawano H, Takeno M, Yonekura T, Koide Y, Abe K, Doi Y, Fukae S, Komiya N, Maemura K. Cardiogenic shock due to left ventricular outflow obstruction and complete atrioventricular block in a patient with hypertrophic cardiomyopathy with acute myocarditis. Internal medicine (Tokyo, Japan). 2012:51(18):2565-71     [PubMed PMID: 22989828]


Miyake CY, Teele SA, Chen L, Motonaga KS, Dubin AM, Balasubramanian S, Balise RR, Rosenthal DN, Alexander ME, Walsh EP, Mah DY. In-hospital arrhythmia development and outcomes in pediatric patients with acute myocarditis. The American journal of cardiology. 2014 Feb 1:113(3):535-40. doi: 10.1016/j.amjcard.2013.10.021. Epub 2013 Nov 9     [PubMed PMID: 24332245]


Rosier L, Zouaghi A, Barré V, Martins R, Probst V, Marijon E, Sadoul N, Chauveau S, Da Costa A, Badoz M, Peyrol M, Barraud J, Massoullie G, Eschalier R, Espinosa M, Lesaffre F, Garcia R, Degand B, Noël A, Mansourati J, Extramiana F, Algalarrondo V, Devilliers H, Cottin Y, Gandjbakhch E, Guenancia C. High Risk of Sustained Ventricular Arrhythmia Recurrence After Acute Myocarditis. Journal of clinical medicine. 2020 Mar 20:9(3):. doi: 10.3390/jcm9030848. Epub 2020 Mar 20     [PubMed PMID: 32244983]


Ammirati E, Cipriani M, Moro C, Raineri C, Pini D, Sormani P, Mantovani R, Varrenti M, Pedrotti P, Conca C, Mafrici A, Grosu A, Briguglia D, Guglielmetto S, Perego GB, Colombo S, Caico SI, Giannattasio C, Maestroni A, Carubelli V, Metra M, Lombardi C, Campodonico J, Agostoni P, Peretto G, Scelsi L, Turco A, Di Tano G, Campana C, Belloni A, Morandi F, Mortara A, Cirò A, Senni M, Gavazzi A, Frigerio M, Oliva F, Camici PG, Registro Lombardo delle Miocarditi. Clinical Presentation and Outcome in a Contemporary Cohort of Patients With Acute Myocarditis: Multicenter Lombardy Registry. Circulation. 2018 Sep 11:138(11):1088-1099. doi: 10.1161/CIRCULATIONAHA.118.035319. Epub     [PubMed PMID: 29764898]


McDonagh TA, Metra M, Adamo M, Gardner RS, Baumbach A, Böhm M, Burri H, Butler J, Čelutkienė J, Chioncel O, Cleland JGF, Coats AJS, Crespo-Leiro MG, Farmakis D, Gilard M, Heymans S, Hoes AW, Jaarsma T, Jankowska EA, Lainscak M, Lam CSP, Lyon AR, McMurray JJV, Mebazaa A, Mindham R, Muneretto C, Francesco Piepoli M, Price S, Rosano GMC, Ruschitzka F, Kathrine Skibelund A, ESC Scientific Document Group. 2021 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure. European heart journal. 2021 Sep 21:42(36):3599-3726. doi: 10.1093/eurheartj/ehab368. Epub     [PubMed PMID: 34447992]


Olshansky B, Atteya G, Cannom D, Heidbuchel H, Saarel EV, Anfinsen OG, Cheng A, Gold MR, Müssigbrodt A, Patton KK, Saxon LA, Wilkoff BL, Willems R, Dziura J, Li F, Brandt C, Simone L, Wilhelm M, Lampert R. Competitive athletes with implantable cardioverter-defibrillators-How to program? Data from the Implantable Cardioverter-Defibrillator Sports Registry. Heart rhythm. 2019 Apr:16(4):581-587. doi: 10.1016/j.hrthm.2018.10.032. Epub 2018 Oct 31     [PubMed PMID: 30389442]


Lassen MCH, Skaarup KG, Lind JN, Alhakak AS, Sengeløv M, Nielsen AB, Espersen C, Ravnkilde K, Hauser R, Schöps LB, Holt E, Johansen ND, Modin D, Djernaes K, Graff C, Bundgaard H, Hassager C, Jabbari R, Carlsen J, Lebech AM, Kirk O, Bodtger U, Lindholm MG, Joseph G, Wiese L, Schiødt FV, Kristiansen OP, Walsted ES, Nielsen OW, Madsen BL, Tønder N, Benfield T, Jeschke KN, Ulrik CS, Knop FK, Lamberts M, Sivapalan P, Gislason G, Marott JL, Møgelvang R, Jensen G, Schnohr P, Søgaard P, Solomon SD, Iversen K, Jensen JUS, Schou M, Biering-Sørensen T. Echocardiographic abnormalities and predictors of mortality in hospitalized COVID-19 patients: the ECHOVID-19 study. ESC heart failure. 2020 Dec:7(6):4189-4197. doi: 10.1002/ehf2.13044. Epub 2020 Oct 22     [PubMed PMID: 33089972]


Aquaro GD, Ghebru Habtemicael Y, Camastra G, Monti L, Dellegrottaglie S, Moro C, Lanzillo C, Scatteia A, Di Roma M, Pontone G, Perazzolo Marra M, Barison A, Di Bella G, “Cardiac Magnetic Resonance” Working Group of the Italian Society of Cardiology. Prognostic Value of Repeating Cardiac Magnetic Resonance in Patients With Acute Myocarditis. Journal of the American College of Cardiology. 2019 Nov 19:74(20):2439-2448. doi: 10.1016/j.jacc.2019.08.1061. Epub     [PubMed PMID: 31727281]


Fischer K, Obrist SJ, Erne SA, Stark AW, Marggraf M, Kaneko K, Guensch DP, Huber AT, Greulich S, Aghayev A, Steigner M, Blankstein R, Kwong RY, Gräni C. Feature Tracking Myocardial Strain Incrementally Improves Prognostication in Myocarditis Beyond Traditional CMR Imaging Features. JACC. Cardiovascular imaging. 2020 Sep:13(9):1891-1901. doi: 10.1016/j.jcmg.2020.04.025. Epub 2020 Jul 15     [PubMed PMID: 32682718]