Myocarditis – 10 Interesting Facts, Causes, Symptoms, Diagnosis and Treatment

What is Myocarditis

Myocarditis is inflammation of the heart muscle (myocardium). When heart muscle is inflamed, the heart cannot pump blood in an efficient way.

As a result heart muscle may get damaged and swollen, and you may experience fast heart rhythms. Severe cases of myocarditis can cause heart failure.

Myocarditis is an underdiagnosed cause of acute heart failure, sudden death, and chronic dilated cardiomyopathy.

In developed countries, viral infections commonly cause myocarditis; however, in the developing world, rheumatic carditis, Trypanosoma cruzi, and bacterial infections such as diphtheria still contribute to the global burden of the disease.

10 Interesting Facts of Myocarditis

1. Myocarditis is inflammation of the myocardium, which typically manifests as chest pain, heart failure and/or arrhythmias; may be mild and self-limited or fulminant, with severe left ventricular dysfunction and need for hemodynamic support
2. Most commonly related to viral infection but can result from bacterial, fungal, or parasitic infection; cardiotoxins; hypersensitivity reactions to drugs; and systemic autoimmune disorders
3. Classic presentation of acute, nonfulminant myocarditis occurs within 1 to 4 weeks after onset of a viral syndrome; symptoms are nonspecific (eg, fatigue, decreased exercise tolerance, palpitations, pseudo-ischemic chest pain at rest) 
4. Occurs across the age spectrum, but young adults are most commonly affected. Older patients may present with de novo heart failure. Infants and children may have a less specific presentation, with fever, lethargy, and poor feeding
5. In contrast to acute myocarditis, fulminant myocarditis presents with rapid onset of heart failure, progressing to cardiogenic shock within 1 or 2 days. Sudden cardiac death may occur 
6. Initial diagnostic evaluation includes ECG (typically abnormal findings with a variety of ST-T wave changes and sometimes evidence of conduction abnormalities); chest radiograph; echocardiogram; and results of basic laboratory testing, including levels of cardiac troponin (typically elevated), brain natriuretic peptide (elevated if heart failure is present), and inflammatory biomarkers (nonspecific, but often elevated) 
7. Cardiac MRI can support the diagnosis and may obviate need for endomyocardial biopsy, especially if a combination of T-1 and T-2 based myocarditis markers are present on imaging 
8. Treatment is primarily supportive, with appropriate management of heart failure, cardiogenic shock, and arrhythmias according to established clinical practice guidelines. Patients with fulminant myocarditis and cardiogenic shock usually require mechanical circulatory support with ECMO (extracorporeal membrane oxygenation) or a ventricular assist device. Cardiac transplant may be required
9. Specific, evidence-supported treatments directed against myocardial inflammation are lacking; however, high-dose IV immunoglobulin is commonly administered to children with myocarditis and may be considered for adults with myocarditis and refractory heart failure. Giant cell myocarditis and myocarditis associated with systemic autoimmune disease may respond to combination immunosuppressive therapies 
10. Prognosis varies by disease presentation, histologic subtype, and age. Acute, nonfulminant myocarditis often resolves spontaneously without significant sequelae, but may relapse or become chronic and progress to dilated cardiomyopathy. Fulminant myocarditis often has a good prognosis with full recovery if aggressively managed at onset, especially in children

What are the causes?

Common causes of this condition include:

• Viral infections.
• Bacterial infections.
• Parasitic infections.
• Fungal infections.
• Radiation.
• Reactions to medicines.
• Exposure to certain chemicals or toxins.
• Autoimmune diseases.
• Inflammatory conditions.
• Connective tissue diseases.

What are the symptoms?

Symptoms of this condition include:

• Chest pain.
• Shortness of breath.
• Fast or abnormal heart rhythms.
• Fatigue.
• Swelling in the feet or legs.
• Fever.
• Body aches.
• Fainting.

Mild cases of this condition may not cause symptoms.

How is this diagnosed?

This condition may be hard to diagnose because it can look like other conditions. It may be diagnosed based on:

• Your symptoms. The condition may be suspected if your symptoms appear after a recent infection.
• A physical exam.
• Tests, such as:
  • Blood tests to check for signs of infection or heart damage.
  • An electrocardiogram to show your heart’s electrical patterns and rhythms.
  • A chest X-ray to look at your heart and lungs.
  • An echocardiogram or other imaging tests to look at how well your heart is working.
  • A test called cardiac catheterization to check for inflammation or infection.

How is this treated?

Treatment for this condition depends on the cause. It may include taking medicines, such as:

• Heart medicines like beta blockers or angiotensin-converting enzyme (ACE) inhibitors. These medicines help strengthen the heart and help it beat more regularly.
• Diuretic medicine. This medicine can help get rid of extra fluid in the body. Extra fluid can make the heart work harder.
• Steroid medicine. This medicine reduces swelling.
• Medicine for pain.
• Anti-inflammatory medicine. This medicine reduces inflammation in the heart.
• Antibiotic medicines. These may be prescribed if a bacterial infection caused the condition.

Follow these instructions at home:

Medicines

• Take over-the-counter and prescription medicines only as told by your health care provider.
• If you were prescribed an antibiotic medicine, take it as told by your health care provider. Do not stop taking the antibiotic even if you start to feel better.

General instructions

• Do not use any products that contain nicotine or tobacco, such as cigarettes and e-cigarettes. If you need help quitting, ask your health care provider.
• Avoid or limit alcohol.
• Avoid people who are sick.
• Wash your hands with soap and water regularly to avoid getting an infection. If soap and water are not available, use hand sanitizer.
• Return to your normal activities as told by your health care provider. Ask your health care provider what activities are safe for you.
• Keep all follow-up visits as told by your health care provider. This is important.

Contact a health care provider if:

• You have a fever.
• Your symptoms continue to get worse, and medicine does not help
• You have swelling in your legs, feet, or face.
• Your breathing is faster than normal.
• You have constipation or diarrhea.

Get help right away if:

• You have severe chest pain.
• You have shortness of breath.
• You have problems breathing.
• You become more pale than normal.
• Your hands or legs are cold and blue.
• You pass out or faint.
• You have fast or abnormal heart rhythms.
• You have nausea, vomiting, and abdominal pain.

These symptoms may represent a serious problem that is an emergency. Do not wait to see if the symptoms will go away. Get medical help right away. Call your local emergency services (911 in the U.S.). Do not drive yourself to the hospital.

Additional Info on Myocarditis

Pitfalls

• Athletes with myocarditis may still be at risk for arrhythmia and sudden death despite resolution of acute myocardial inflammation and must be carefully evaluated before return to athletic activities 

Myocarditis is inflammation of the myocardium, which typically manifests as chest pain, heart failure, and/or arrhythmias; may be mild and self limited or fulminant with severe left ventricular dysfunction and need for hemodynamic support

Most commonly related to viral infection but may be a result of bacterial, fungal, or parasitic infection; or cardiotoxins, drugs, and systemic autoimmune disorders

Clinical diagnosis of myocarditis may be established by noninvasive clinical criteria; definitive diagnostic confirmation has classically been established by endomyocardial biopsy

Classification

• By symptom onset and disease phase 
  • Acute (nonfulminant) myocarditis
    • Onset is less distinct than fulminant myocarditis 
    • Symptoms are less severe and treatment with inotropes and vasopressors is typically not necessary
  • Fulminant myocarditis (about 10% of cases) 
    • Abrupt new-onset unexplained class IV heart failure symptoms (identified as developing acutely over 1-2 days) with normal-sized or dilated left ventricle and hemodynamic compromise 
    • Refractory sustained arrhythmias are common
    • Symptoms require treatment with inotropes or vasopressors or mechanical circulatory support
    • More common in children than adults 
  • Chronic myocarditis
    • Characterized by cardiac repair and remodeling
    • Chronic inflammation and fibrosis may occur, leading to dilated cardiomyopathy and irreversible systolic and diastolic dysfunction (Related: Dilated cardiomyopathy)
• By type of myocardial inflammatory cell infiltrate (may also have distinct clinical presentations) 
  • Common
    • Lymphocytic myocarditis 
      • Typically presents as acute or fulminant myocarditis
      • Resolves spontaneously or may progress to chronic myocarditis and ultimately to dilated cardiomyopathy (Related: Dilated cardiomyopathy)
  • Rare
    • Giant cell myocarditis 
      • Most cases are in young, healthy people; a few cases are associated with systemic autoimmune disease
      • Presentation is aggressive but more subtle than fulminant myocarditis
      • Can deteriorate very quickly into cardiogenic shock and multiorgan failure; short survival time with standard therapy
      • However, relatively favorable outcome at 12 months, when patients are treated with high-dose multiagent immunosuppressive therapy 
    • Eosinophilic myocarditis 
      • Several distinct associations, with presentations ranging from minimally symptomatic to fulminant
        • Idiopathic (large proportion of cases)
        • Allergic eosinophilic: caused by hypersensitivity reaction to a foreign antigen, typically a drug
        • Associated with immune-related disorders: eosinophilic granulomatosis with polyangiitis (formerly Churg-Strauss syndrome), hypereosinophilic syndrome
        • Associated with infections
        • Associated with pregnancy or cancer (very rare)

Clinical Presentation

History

• Antecedent infection is common but may have been unrecognized by the patient
  • Nearly any virus (and less commonly, a wide variety of other pathogens) may cause myocarditis; symptoms vary widely and may include fever, headache, respiratory symptoms, and/or rash
• Recent use of new drug associated with myocarditis or recent vaccine administration (especially tetanus) may suggest hypersensitivity as the mechanism of myocardial inflammation
• The patient may have a known autoimmune or inflammatory disease associated with myocarditis, or suggestive symptoms may be present (eg, rash, joint pain or swelling, preexisting respiratory symptoms, ocular symptoms suggesting uveitis)
• Presentation varies greatly and ranges from mild chest pain and palpitations to cardiogenic shock and ventricular arrhythmia with sudden death
  • Classic presentation is as acute, nonfulminant syndrome occurring within 1 to 4 weeks after onset of a viral syndrome 
    • Symptoms may be nonspecific
      • Fatigue; decreased exercise tolerance
      • Dyspnea with exertion
      • Palpitations
      • Chest pain at rest
      • Unexplained syncope
    • May present with de novo congestive heart failure, especially in middle-aged or older adults
  • Fulminant myocarditis presents with rapid onset of heart failure, progressing to cardiogenic shock
    • When associated with prodromal viral infection, usually occurs within 2 weeks of infection 
    • Severe heart failure symptoms develop abruptly over 1 to 2 days 
    • May present with sustained arrhythmias
• Presentation in children varies with age
  • Newborns and infants are typically more severely affected than older children and adults and are more likely to present with circulatory shock and acute dilated cardiomyopathy (Related: Dilated cardiomyopathy)
  • Less severe, nonspecific presentations include fussiness, lethargy, fever, poor feeding and feeding difficulties, vomiting, and difficulty breathing
  • Children older than 2 years may have chest pain, abdominal pain, myalgias, cough, and lethargy 

Physical examination

• Patients with acute, nonfulminant myocarditis present with a range of manifestations; patients may appear well with normal findings on physical examination or may have physical signs of myocarditis
  • Rapid or irregular pulse, or both
  • In infants, tachypnea and diaphoresis during feeding with poor weight gain
  • In children, tachycardia, tachypnea, and abnormal respiratory examination results are most common when myocarditis is the ultimate diagnosis; fever may be present
  • If congestive heart failure develops, expected findings may include:
    • Elevated jugular venous pressure
    • Rales and wheezes
    • S₃ gallop
    • Hepatomegaly
    • Peripheral edema
• Expected findings with development of fulminant myocarditis:
  • Cardiopulmonary examination reflects heart failure and pulmonary edema
  • New cardiac murmur (mitral or tricuspid regurgitation) may appear
  • Altered mental status, tachycardia, hypotension, and evidence of poor distal perfusion with cardiogenic shock

Causes

• Myocardial inflammation resulting from a wide range of inciting events
  • Viral infection is the most common antecedent event; cases without other identified cause are usually considered to be secondary to undocumented viral infection
    • Mechanism is an immune response leading to organ dysfunction
    • Common viral causes include adenoviruses, enteroviruses (especially coxsackievirus), parvoviruses (especially B19V), influenza viruses, measles virus, and human herpesvirus 6
    • Less common viral infections include cytomegalovirus, HSV, HCV, HIV, and Epstein-Barr virus
  • Other infectious agents
    • Bacterial infection as a cause is less common than viral infection
      • Staphylococcus, Streptococcus, Pneumococcus, Meningococcus, Gonococcus, Salmonella, Brucella and Nocardia species; Corynebacterium diphtheriae, Haemophilus influenzae, Mycobacterium tuberculosis, andMycoplasma pneumoniae
      • Spirochetal infections, especially Borrelia burgdorferi (Lyme carditis) and Leptospira species
      • Rickettsial infections, including Rickettsia rickettsii, Rickettsia tsutsugamushi, andCoxiella burnetii
    • Fungal infection
      • Aspergillus, Actinomyces, Blastomyces, Candida, Coccidioides, Cryptococcus, Histoplasma, Mucormycoses, and Sporothrix
    • Parasitic infection (associated with eosinophilic myocarditis)
      • Trypanosoma cruzi, Toxoplasma gondii, Trichinella spiralis, Echinococcus granulosus, and Taenia solium
      • Entamoeba and Leishmania species
  • Exposure to myocardial toxins
    • Chemotherapeutic agents (eg, anthracyclines, cyclophosphamide)
    • Stimulants such as amphetamines (excluding amphetamine salts used to treat attention-deficit/hyperactivity disorder) and cocaine
    • Catecholamine excess related to pheochromocytoma
    • Heavy metals
    • Physical agents such as radiation and electric shock
  • Hypersensitivity states
    • Drug-induced
      • Associated with use of antiseizure agents (primarily carbamazepine) and antipsychotics (primarily clozapine) as well as a number of antibiotics
        • Most cases of myocarditis develop early in the course of drug use; when related to clozapine use, manifestations may occur up to 2 years after initiation of drug therapy 
        • Amongst antibiotics, minocycline and β-lactam antibiotics are most frequently associated
      • Associated with the use of immune checkpoint inhibitors (treatment with anti-PD1, anti-CTLA4, or both) for cancer therapy
        • Most cases occur early in therapy, after 1 or 2 doses 
    • Vaccine-induced; noted after tetanus and smallpox vaccines in case reports
  • Myocardial inflammation may occur as a component of many systemic autoimmune, inflammatory, and other systemic disease states
    • Eosinophilic granulomatosis with polyangiitis (Churg-Strauss syndrome)
    • Granulomatosis with polyangiitis (Wegener granulomatosis)
    • Hypereosinophilic syndrome
    • Systemic lupus erythematosus
    • Scleroderma
    • Polymyositis (Related: Polymyositis and dermatomyositis)
    • Sarcoidosis
    • Behçet disease (Related: Behçet syndrome)
    • Rheumatoid arthritis
    • Kawasaki disease (Related: Kawasaki disease)
    • Inflammatory bowel disease (Related: Kawasaki disease)
    • Myasthenia gravis
    • Type 1 diabetes mellitus (Related: Diabetes mellitus type 1 in adults)
    • Thyrotoxicosis (Related: Hyperthyroidism)
    • Malignancy

Risk factors and/or associations

Age

• Most frequent in young adults; however, may affect people of all ages
• In children, there is a bimodal distribution by age: infancy and mid-teenage years
• Fulminant myocarditis of unknown origin is more common in children and neonates

Sex

• Men are more frequently diagnosed with myocarditis and have a worse prognosis than women

Other risk factors/associations

• Genetic (familial) association with dilated cardiomyopathy or myocarditis (based on current diagnostic criteria)

Diagnostic Procedures

Primary diagnostic tools

• Suspect myocarditis based on clinical presentation after exclusion of alternate causes for presenting manifestations
  • Most common presentation patterns include chest pain, arrhythmia, heart failure, or all 3
  • Other conditions with similar patterns of presentation include angiographically significant coronary artery disease, valvular heart disease, congenital heart disease, and hypertensive cardiomyopathy
• First line evaluation for patients who present with clinically suspected myocarditis
  • The following initial evaluation is recommended for all patients: 
    • 12-lead ECG; consider Holter monitor 
    • Chest radiograph
    • Transthoracic echocardiogram 
    • Inflammatory biomarkers (ie, erythrocyte sedimentation rate and C-reactive protein; WBC count) 
    • Cardiac troponin level 
  • The following tests may be recommended in consultation with cardiologist based on individual clinical presentation:
    • Cardiac MRI 
    • Focused laboratory evaluation 
      • Brain natriuretic peptide or NT-proBNP (N-terminal-proBNP) when heart failure is suspected but uncertain 
      • Routine viral serologies are not recommended; however, serologies to identify suspected HCV infection, suspected rickettsial infection, Lyme disease in endemic areas, and HIV in high-risk patients are recommended 
      • Testing for associated systemic disease if suggested by presentation (eg, autoimmune disorder such as systemic lupus erythematosus)
• Clinical diagnosis of myocarditis can be made with the following clinical criteria: 
  • 1 or more compatible clinical presentations, and
  • 1 or more additional diagnostic criteria (ie, a newly abnormal compatible ECG or Holter monitor result, elevated cardiac troponin level, functional or structural abnormality on cardiac imaging, or specific pattern on cardiac MRI)
  • If asymptomatic (ie, compatible clinical presentation is absent), must meet 2 diagnostic criteria from different categories (ECG; laboratory; imaging)
• Guidelines differ regarding some aspects of second tier evaluation for patients with clinical myocarditis, particularly indications for confirmatory endomyocardial biopsy
  • European guidelines recommend that all patients fulfilling the criteria for clinically suspected myocarditis should also undergo the following evaluations: 
    • Coronary angiography (to exclude ischemic heart disease)
      • Important when clinical presentation is compatible with acute coronary syndrome
    • Endomyocardial biopsy for definitive diagnosis
      • Considered the gold standard for diagnosis and, in some cases, can identify underlying cause
  • American College of Cardiology/American Heart Association guidelines accept more selective use of endomyocardial biopsy than European guidelines 
    • Noninvasive diagnostic criteria can be used to diagnose suspected or probable acute myocarditis when diagnosis is suspected and endomyocardial biopsy is infeasible or not clearly indicated 
    • Biopsy is strongly recommended (Class I recommendation) only for patients with severe presentation in the following scenarios: 
      • Patients with new-onset heart failure of less than 2 weeks’ duration associated with a normal-sized or dilated left ventricle and hemodynamic compromise
      • New-onset heart failure of 2 weeks’ to 3 months’ duration associated with a dilated left ventricle and new ventricular arrhythmias, second- or third-degree heart block, or failure to respond to usual care within 1 to 2 weeks
  • American College of Cardiology Foundation/American Heart Association heart failure guidelines recommend endomyocardial biopsy when seeking a specific diagnosis will likely influence therapy 
    • Biopsy is suggested for most patients with presentation consistent with giant cell myocarditis, eosinophilic myocarditis, and myocarditis associated with a systemic autoimmune/inflammatory condition (eg, systemic lupus erythematosus, cardiac sarcoid) because immunosuppressive therapy may be beneficial 

Laboratory

• Laboratory studies are indicated for all patients with suspected myocarditis to support diagnosis 
  • Markers of inflammation and infection
    • Erythrocyte sedimentation rate, C-reactive protein levels, or both 
      • May be elevated with myocarditis
      • Nonspecific, often elevated with acute pericarditis as well
    • WBC count 
      • Eosinophilia suggests possibility of underlying hypersensitivity reaction (eg, to a drug) or another type of eosinophilic myocarditis; however, peripheral eosinophilia is absent in 25% of patients with eosinophilic myocarditis 
  • Troponin levels 
    • Troponin I and troponin T may be elevated in adults and children with acute myocarditis 
  • Brain natriuretic peptide or NT-proBNP (N-terminal-proBNP) levels 
    • Often elevated
    • Can help to distinguish respiratory symptoms of cardiac (versus pulmonary) origin, if elevated

Imaging

• Chest radiograph
  • Appearance may be normal or show cardiomegaly and pulmonary vascular congestion if heart failure is present
• Cardiovascular MRI
  • Indicated for clinically stable patients to support diagnosis of myocarditis 
  • Requires breath-holding sequences; infants and young children (and those who are severely ill) require intubation and mechanical ventilation
  • Can support but not definitively exclude diagnosis; may not detect less severe forms of disease 
  • Best for identifying acute, active inflammation and less well established for identifying chronic myocarditis 
    • Highest sensitivity exists for diagnosis of acute inflammation if performed within 2 weeks of symptom onset 
  • Utility is limited in patients with frequent ventricular and atrial arrhythmias 
  • Use Lake Louise criteria; consensus-based recommendation for modification of original criteria is available 
    • Strong evidence with increased specificity for myocardial inflammation exists when study shows both myocardial edema and other markers of inflammatory myocardial injury
    • Findings consistent with myocardial inflammation include: 
      • Myocardial edema
      • Markers of inflammatory myocardial injury
        • T1-based criteria include:
          • Increased myocardial T1 relaxation time
          • Increased extracellular volume
          • Late gadolinium enhancement
            • Late gadolinium enhancement correlates with a greater risk of assist device implantation, transplant, or death in both children and adults 
        • T2-based criteria include:
          • Global or regional increase of myocardial T2 relaxation time
          • Increased signal intensity in T2-weighted images
        • Note that presence of positive T1- and T2-based markers increases specificity for diagnosing acute myocardial inflammation; however, having only 1 marker may still support a diagnosis of acute myocardial inflammation but with less specificity 
    • Supportive evidence includes presence of left ventricle dysfunction or pericardial effusion 
  • Indications for repeating cardiovascular MRI in 1 to 2 weeks include: 
    • Failure to meet full criteria
    • No criteria met in patient presenting with very recent onset of symptoms with strong clinical suspicion for myocarditis

Functional testing

• 12-lead ECG 
  • Indicated for all patients with clinically suspected myocarditis 
  • Neither specific nor sensitive for myocarditis 
  • Findings typically abnormal 
  • Most common findings in acute phase of clinical myocarditis are nonspecific and include: 
    • Sinus tachycardia with low-voltage QRS complexes
    • T-wave changes (T-wave inversion)
  • Other findings may include:
    • ST-T segment elevation is typically concave and diffuse without reciprocal changes 
    • ST segment depression may occur 
    • New Q waves 
    • Reduced R wave height 
    • PR depression may resemble findings associated with acute myocardial infarction or pericarditis
  • Conduction delays and arrhythmias are common, occurring in more than half of patients 
    • Conduction delays may include first- to third-degree atrioventricular block, bundle branch block, intraventricular conduction delay (wide QRS) 
    • Arrhythmias may include frequent premature ventricular contractions, supraventricular tachycardia, sinus arrest, atrial fibrillation, ventricular tachycardia or fibrillation, and asystole 
    • Atrioventricular conduction delay in the context of mild left ventricular dilation suggests Lyme carditis (often associated with complete heart block), cardiac sarcoidosis, or giant cell myocarditis 
    • Myocarditis due to Trypanosoma cruzi may be associated with complete heart block
  • Negative predictors for survival include QRS prolongation, northwest axis deviation, and new left bundle branch block 
• Holter monitor
  • Consider if there are symptoms or ECG signs of arrhythmia
    • Tachyarrhythmias are often nonsustained and typically do not cause hemodynamic compromise except in fulminant disease 
    • Reported ventricular arrhythmia occurrence is more frequent in myocarditis due to HIV, Borrelia burgdorferi in Lyme disease, Corynebacterium diphtheriae, Trypanosoma cruzi, giant cell myocarditis, and cardiac sarcoid 
    • Conversely, ventricular arrhythmias are rare in myocarditis associated with systemic lupus erythematosus and other systemic autoimmune diseases 
• Transthoracic echocardiogram 
  • Indicated for all patients with clinically suspected myocarditis as a useful measurement tool of cardiac chamber sizes, wall thickness, and systolic and diastolic function 
    • Although it is not diagnostic of myocarditis, it can assess for other causes of heart failure
  • Findings vary and may include:
    • Regional wall motion abnormalities
    • Diastolic dysfunction with preserved ejection fraction
    • Global ventricular dysfunction
    • Ventricular thrombi (up to 25% of patients) 
    • Pericardial effusion
  • Marked left ventricular dilation and normal wall thickness is often noted in patients with acute myocarditis
  • Nondilated, thickened, and hypocontractile left ventricle is often noted in patients with fulminant myocarditis
    • Right ventricular dysfunction is uncommon; however, when present, it is a strong predictor of the need for heart transplant 

Procedures

Endomyocardial biopsy

General explanation

• Tissue samples are taken from right or left ventricle for light microscopy, viral polymerase chain reaction, and immunohistochemistry 
• Performed via cardiac catheterization
• At least 3 samples are obtained to decrease sampling error 
• Peripheral blood sample is obtained at time of biopsy to exclude systemic viral infection 

Indication

• Gold standard for diagnostic confirmation; however, procedure is no longer routine in most patients when clinical diagnosis is clear and results are not anticipated to alter management 

Complications

• Low complication rate (less than 1%) if performed by experienced team 
  • Major complications are rare and include cardiac rupture, cardiac tamponade, and complete atrioventricular block 
  • Minor complications include pericardial effusion, conduction abnormalities, and arrhythmias 
  • Complications are more frequent in pediatric patients, with an increased risk of ventricular perforation 

Interpretation of results

• May characterize underlying cause and type of inflammation (eg, giant cell, eosinophilic, sarcoidosis), which will then help guide specific therapy (eg, immunosuppression, antimicrobials) 
• Techniques to determine underlying cause include histology, immunohistochemistry, and viral genome analysis 
• Definitive diagnosis is established by histologic and immunohistochemical criteria (WHO/International Society and Federation of Cardiology Task Force) 
  • Histologic criteria
    • Inflammatory infiltrates in the myocardium
    • Nonischemic necrosis
    • Myocyte degeneration
  • Immunohistochemical criteria
    • 14 leukocytes/mm² or higher, including up to 4 monocytes/mm²
    • 7 CD3-positive T-lymphocytes/mm² or higher
• Sampling error may lead to false-negative results 

Other Diagnostic Tools

• Clinical diagnostic criteria
  • Classically, diagnosis has been considered definitive only with histologic and immunohistochemical evidence from endomyocardial biopsy
  • The European Society of Cardiology Working Group on Myocardial and Pericardial Diseases noninvasive diagnostic criteria for clinically suspected myocarditis include: 
    • At least 1 clinical presentation with at least 1 of the specific diagnostic criteria, or at least 2 specific diagnostic criteria from different categories if patient is asymptomatic
      • Clinical presentations
        • Acute chest pain, either pericarditic or pseudo-ischemic
        • New onset of or worsening dyspnea at rest or during exercise and/or fatigue, with or without other signs of heart failure
        • Palpitation or unexplained arrhythmia symptoms
        • Syncope
        • Aborted sudden cardiac death
        • Unexplained cardiogenic shock
      • Specific diagnostic criteria
        • Category 1: newly abnormal ECG finding or Holter/stress test features or both, with any of the following:
          • Atrioventricular block (first-, second-, or third-degree) or bundle branch block
          • ST-T wave changes (ST elevation or non-ST elevation, T-wave inversion)
          • Reduced R wave height
          • Abnormal Q waves
          • Intraventricular conduction delay
          • Sinus arrest
          • Low voltage, frequent premature beats
          • Ventricular tachycardia, ventricular fibrillation, or asystole
          • Supraventricular tachycardia
          • Atrial fibrillation
        • Category 2: elevated troponin T or troponin I levels (indicating myocardial cytolysis)
        • Category 3: functional and structural abnormalities on cardiac imaging
          • Regional wall motion or global systolic or diastolic function abnormality; may be accompanied by:
            • Ventricular dilation
            • Increased wall thickness
            • Pericardial effusion
            • Endocavitary thrombi
        • Category 4: edema or classical myocarditis pattern on late gadolinium enhancement on cardiac MRI

Differential Diagnosis

Most common

• Critical coarctation of the aorta
• Anomalous origin of the left coronary artery from pulmonary artery
• Sepsis in neonates
• Hypoglycemia 
• Pericarditis
• Cardiomyopathy
• Acute Coronary Syndrome
• Endocarditis

Treatment Goals

• Stabilize and support adequate hemodynamics 
• Manage causative infection or condition when possible 

Admission criteria

Admit hemodynamically stable, asymptomatic, or mildly symptomatic patients suspected of having myocarditis and initiate clinical monitoring until a definitive diagnosis is established 

• Condition may progress quickly to cardiopulmonary emergency even if systolic function is initially preserved

Criteria for ICU admission

• Admit hemodynamically unstable patients and patients with other severe presentation (eg, chest pain that suggests acute coronary syndrome, arrhythmia, heart failure) to an ICU with hemodynamic monitoring, cardiac catheterization, and endomyocardial biopsy capability 

Recommendations for specialist referral

• Consult cardiologist for all patients with myocarditis for further diagnostic and treatment recommendations
• Patients with fulminant myocarditis should be managed by a cardiologist and team of other physicians with expertise in critical care in a facility with ventricular assist device and ECMO (extracorporeal membrane oxygenation) capability 
• Consider consultation with an infectious disease specialist in patients with suspected underlying infectious cause for diagnostic and treatment recommendations
• Consult a rheumatologist to direct appropriate immunosuppressive therapy for patients with underlying systemic autoimmune and inflammatory disease processes

Treatment Options

Treat patients symptomatically based on standard therapeutic approaches for the primary presentation (ie, heart failure, arrhythmia) 

• Treatment of heart failure is guided by the patient’s hemodynamic stability
  • Hemodynamically unstable patients
    • Admit patients to an ICU capable of respiratory and mechanical cardiopulmonary support for management of heart failure 
    • Manage according to current clinical practice guidelines for heart failure and cardiogenic shock
    • Consider ECMO (extracorporeal membrane oxygenation) or ventricular assist devices for acute or fulminant cases with cardiogenic shock and severe ventricular dysfunction 
    • Consider cardiac transplant if pharmacologic support and mechanical assistance are unsuccessful in stabilizing the patient 
      • Cardiac transplant is generally not recommended for patients in the acute phase of the disease, as recovery is possible; however, transplant may be considered if the patient cannot otherwise be stabilized
  • Hemodynamically stable patients 
    • Treat patients with standard therapy for heart failure, including diuretics, ACE inhibitor, or angiotensin-receptor blockade, and β-adrenergic blockade 
    • Consider aldosterone antagonists for patients with persistent heart failure unresponsive to other treatments 
• Manage arrhythmias (which range from conduction delays to life-threatening ventricular tachycardia or ventricular fibrillation) according to current clinical practice guidelines; therapies may include antiarrhythmic drugs and device therapies 
  • No evidence to support cause-based strategy for arrhythmia treatment 
  • Temporary pacing may be needed for complete atrioventricular block 
  • Indications for cardiac defibrillator device
    • For patients with ventricular tachycardia or ventricular fibrillation, consider bridging the period to recovery using a wearable cardiac defibrillator 
    • For patients who have experienced cardiac arrest caused by ventricular fibrillation or after symptomatic ventricular tachycardia, an implantable cardiac defibrillator device may be necessary 
    • Consider placement of an implantable device in patients who have giant cell myocarditis with ventricular fibrillation or hemodynamically unstable ventricular tachycardia if meaningful survival longer than 1 year is expected 

Specific therapies may be indicated in certain situations

• Viral myocarditis
  • IV immunoglobulin
    • Use is controversial because data are limited and inconclusive 
    • Some experts administer IV immunoglobulin to children with acute myocarditis; consult a pediatric cardiologist for guidance
  • Antiviral therapies
    • Use of such therapies is not routine in either children or adults
    • Data are limited and additional research is needed
    • When the viral pathogen is known or strongly suspected, antiviral drugs with known efficacy against that pathogen are appropriate
      • Ganciclovir has been used successfully to treat severe cytomegalovirus myocarditis 
      • Oseltamivir is typically given for presumed or confirmed concurrent  influenza infection 
  • Glucocorticoids
    • Data are limited and additional research is needed
    • May improve left ventricular ejection fraction in patients with viral myocarditis based on small trials of poor methodologic quality; mortality reduction has not been consistently proved 
• Other infectious causes of myocarditis 
  • Appropriate pathogen-directed therapies to eradicate underlying infection are indicated although there may be little direct effect on the myocardium
• Giant cell myocarditis
  • Immunosuppression
    • Data suggest that patients with biopsy-confirmed giant cell myocarditis benefit from therapy with immunosuppressive agents, alone and in combination 
    • Combined immunosuppression (regimen of 2-4 drugs, which included cyclosporine) resulted in 69% transplant-free survival at 1 year, 58% at 2 years, and 52% at 5 years, although malignant ventricular rhythms recurred or persisted in most of these patients 
    • Rule out active infection using polymerase chain reaction on endomyocardial biopsy samples before beginning immunosuppression therapy 
• Myocarditis with known eosinophilic histology and myocarditis associated with known systemic autoimmune or inflammatory condition
  • Identification of an underlying condition is relevant to treatment selection
    • Myocarditis associated with extracardiac autoimmune disease (eg, systemic lupus erythematosus, eosinophilic granulomatosis, polyangiitis) or inflammatory disease (eg, cardiac sarcoid) with no evidence of viral infection
      • Glucocorticoids with or without an immunosuppressive agent are the cornerstone of treatment
      • Must have a negative viral polymerase chain reaction result on biopsy specimen before treatment
    • Parasitic infection: appropriate antiparasitic agent

Drug therapy

• IV immunoglobulin
  • Consider for viral myocarditis in children (often given routinely despite lack of convincing evidence of efficacy) 
    • Immune Globulin (Human) Solution for injection; Neonates, Infants, Children, and Adolescents: 2 g/kg IV as a single dose. Efficacy data is limited and variable. Systemic reviews and multi-institutional analyses have failed to prove efficacy or survival benefit.
    • Immune Globulin (Human) Solution for injection; Neonates, Infants, Children, and Adolescents: 2 g/kg IV as a single dose. Efficacy data is limited and variable. Systemic reviews and multi-institutional analyses have failed to prove efficacy or survival benefit.
    • Immune Globulin (Human) Solution for injection; Neonates, Infants, Children, and Adolescents: 2 g/kg IV as a single dose. Efficacy data is limited and variable. Systemic reviews and multi-institutional analyses have failed to prove efficacy or survival benefit.
    • Immune Globulin (Human) Solution for injection; Neonates, Infants, Children, and Adolescents: 2 g/kg IV as a single dose. Efficacy data is limited and variable. Systemic reviews and multi-institutional analyses have failed to prove efficacy or survival benefit.

Nondrug and supportive care

Discontinue any drug implicated as a possible cause of hypersensitivity myocarditis

Instruct all patients to restrict physical activity throughout the acute phase of illness 

• Regardless of age, sex, and left ventricular function, athletes with myocarditis (probable or confirmed) should not participate in competitive or leisure sports until: 
  • Resolution of all symptoms, and:
  • Results of retesting are normal (resting echocardiogram, 24-hour Holter monitoring, and an exercise ECG) performed no less than 3 to 6 months after the initial illness, and: 
  • European guidelines recommend that the nonparticipation period should be 6 months from onset of illness 
• Nonathletes should also restrict physical activity for at least 6 months 
• Reassess the patient after resolution of clinical presentation before releasing them to resume competitive sports 

Procedures

Mechanical circulatory support

General explanation 

• Provides cardiopulmonary support when the heart can no longer provide adequate physiologic support. Used as a bridge to recovery or a bridge to cardiac transplant
  • ECMO (extracorporeal membrane oxygenation)
    • Can be either venovenous (provides oxygenation alone) or venoarterial (for oxygenation and circulatory support); venoarterial circuit (often femoral vein to femoral artery) is used for fulminant myocarditis
    • Venoarterial circuit includes a continuous-flow centrifugal pump and a membrane oxygenator for gas exchange
    • A venous cannula drains deoxygenated blood into the membrane oxygenator for gas exchange, and oxygenated blood is subsequently infused back into the patient through an arterial cannula
  • Ventricular assist device: left (most common), right, or biventricular
    • Mechanical pump is positioned surgically or percutaneously, depending on device
    • Many device configurations are available. One such left ventricular assist device involves percutaneous placement (via the femoral artery) at apex of left ventricle with blood inflow from the left ventricle and arterial return pumped to the ascending aorta
    • For durable, portable units, a battery pack and small control unit are worn externally, connected to the pump through a lead into a skin port

Indication

• Fulminant myocarditis with cardiogenic shock

Complications

• Bleeding
• Infection
• Pump thrombosis
• Device malfunction
• Stroke

Implantable cardioverter defibrillator

General explanation 

• Insertion of single or dual chamber leads to detect and respond to ventricular arrhythmias
• Device may be either entirely subcutaneous or transvenous
• Delivers high-voltage cardioversion or defibrillation shocks to treat ventricular fibrillation and tiered therapyto treat ventricular tachycardia
• Defibrillation shocks are synchronized to the intracardiac electrogram, so cardioversion and defibrillation are essentially equivalent when delivered by these devices

Indication

• Patients with myocarditis after cardiac arrest caused by ventricular fibrillation or after symptomatic ventricular tachycardia 

Complications

• Lead-related complications, including malfunction or displacement 
• Inappropriate shocks 
• Psychological sequelae have been associated with use
• Rare complications include subclavian stenosis, thrombus, hemorrhage, and hematoma 

Cardiac pacing 

General explanation

• Transvenous endocardial pacing 
  • Insertion of small, distal tip electrode for pacing and sensing via internal or external jugular, subclavian, brachial, or femoral route. Pacemakers use a separate lead for each chamber paced

Indication

• Temporary pacemaker insertion is indicated for patients with myocarditis and third-degree atrioventricular block 

Complications

• Procedure-related complications include hematoma, thrombophlebitis/phlebitis, lead dislodgement, infection, pneumothorax or hemothorax, myocardial perforation, and air embolism
• Device malfunction (failure to sense, failure to capture)

Monitoring

• Follow all patients who have had myocarditis long-term using clinical assessment, ECG, and echocardiography 
• Monitoring regarding sports participation
  • Time between initial assessment and reassessment before returning to sports depends on disease severity
    • Screen patients every 6 months during follow-up before they participate in sports 
    • Evaluate patients with a resting echocardiogram, 24-hour Holter monitoring, and exercise ECG before returning to competitive sports 
      • The following criteria should be met before athletes resume training and competitive sports: 
        • Ventricular function within normal range
        • Normal levels of serum markers of myocardial injury, inflammation, and heart failure
        • Absence of arrhythmias on Holter monitor and exercise ECG findings
      • There is no definitive recommendation regarding whether late gadolinium enhancement on cardiac MRI should be resolved before returning to sports

Complications

• Dilated cardiomyopathy
  • Clinical diagnosis characterized by dilation and impaired contraction of the left or both ventricles that is not explained by abnormal loading conditions or coronary artery disease 
  • Myocarditis progresses to dilated cardiomyopathy in about 20% of patients 
    • In children, may develop up to 12 years after initial diagnosis 
    • Many patients (25%-35%) who progress to dilated cardiomyopathy have detectable viral genome on endomyocardial biopsy 
• Arrhythmia
  • Acute-phase arrhythmias are usually self-limiting when properly managed, but can be refractory and fatal in fulminant myocarditis 
  • More commonly reported with giant cell myocarditis and with HIV myocarditis (as compared with myocarditis related to more common infections) 
  • Factors that may be associated with increased arrhythmic risk include sinus bradycardia, prolonged QRS duration, wall-motion abnormalities and systolic dysfunction, persistent or fluctuating cardiac troponin levels, late gadolinium enhancement on cardiac MRI, and frequent nonsustained ventricular arrhythmias 
  • Implantable cardioverter defibrillator placement is usually deferred to allow time for spontaneous resolution of myocarditis, but earlier placement may be warranted in giant cell myocarditis
• Sudden cardiac death 
  • May occur without antecedent symptoms or macroscopic cardiac abnormalities 
  • In the acute phase, physical exertion is associated with increased risk 
  • Registry autopsy data on trained high school and college athletes in the United States identify myocarditis as an underlying condition in a small percentage of sudden deaths 
• Valvular insufficiency related to papillary muscle rupture has been reported

Prognosis

• Patients may have full or partial recovery; relapse may occur years after the first episode 
• Prognosis is variable and determined by disease class, histology, clinical presentation, and patient age
  • Disease class
    • Acute myocarditis 
      • Approximately 50% of cases resolve within 2 to 4 weeks 
        • Prognosis is excellent in patients with acute lymphocytic myocarditis (most common histologic type of acute myocarditis), mild symptoms, and preserved left ventricular ejection fraction; most patients improve spontaneously without sequela 
        • Children with acute myocarditis are expected to have a good prognosis and high chance for recovery of left ventricular function 
      • About 25% of cases progress to persistent cardiac dysfunction 
      • 12% to 25% of cases deteriorate acutely; result is death or end-stage dilated cardiomyopathy requiring heart transplant 
        • Biventricular dysfunction at presentation is a major predictor of death or need for transplant 
        • Acute myocarditis has been shown to cause sudden death in up to 12% of cases 
    • Fulminant myocarditis 
      • Patients with hemodynamic compromise at presentation have excellent long-term prognosis if aggressive therapy is initiated early in the fulminant phase 
      • Patients with fulminant disease are more likely to recover left ventricular function than those with acute, nonfulminant myocarditis 
      • Sickest patients at presentation have best recovery odds, especially in younger patients who are treated with mechanical circulatory support 
  • Histology
    • Giant cell myocarditis has a poorer survival rate than other histopathologic types of myocarditis 
      • Patients often require heart transplant although it may be prevented by early treatment with combination immunosuppressive therapy 
        • In a review of 32 patients, transplant-free survival with immunosuppressive therapy was 69% at 1 year, 58% at 2 years, and 52% at 5 years
        • Sustained ventricular tachyarrhythmias during follow-up were common
      • Median survival of less than 6 months for both adults and children without transplant 
      • Recurs in up to 25% of patients after heart transplant 
  • Clinical presentation (in patients with acute lymphocytic myocarditis)
    • Increased likelihood of cardiac death or need for transplant is associated with the following: 
      • Syncope
      • Right ventricular systolic dysfunction at presentation
      • Elevated pulmonary artery pressure
      • Advanced New York Heart Association functional class
    • Increased risk for death is associated with the following: 
      • Prolonged QRS duration of 120 milliseconds 
      • Immunohistologic signs of inflammation (eg, CD3 or CD68)
    • Poor long-term prognosis is predicted by the presence of any of the following signs: 
      • Acute hemodynamic instability
      • Presentation with heart failure and left ventricular ejection fraction less than 45% 
      • Intraventricular conduction abnormalities
      • Extensive structural derangement of the ventricular myocardium with left ventricular remodeling and dysfunction
  • Prognosis in children
    • Histologic resolution is noted in about 73% of patients at 6 months and 96% at 1 year from presentation 

Prevention

• There is currently no prevention strategy for myocarditis with the exception of ensuring current vaccination status, as this ensures protection against some potentially causative viral infections 

Summary

• Myocarditis is inflammation of the heart muscle (myocardium).
• Mild cases of myocarditis may not cause symptoms.
• Myocarditis may be hard to diagnose because it can look like other conditions.
• Treatment for myocarditis includes treating the underlying cause of the disease.

Sources

Caforio AL et al: 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. Eur Heart J. 34(33):2636-48, 2648a-2648d, 2013 Reference