#128: Hearts on Fire – Myocarditis

December 18, 2024 | By Sam Masur

Audio

Summary:

Does thinking about myocarditis make your chest hurt? In this episode, we have a fantastic heart-to-heart with Dr. Jessica Laks (Heart Failure and Transplant at Johns Hopkins All Children’s Hospital). Together, we dive into the complexities of myocarditis – how to recognize the signs, how to triage patients, and what tests to order. Sit back, relax, and keep an open heart as she drops the heart facts about myocarditis.

Myocarditis Pearls

1. Consider myocarditis in a patient with a viral prodrome with nonspecific symptoms (fatigue, poor PO, abdominal pain), and tachycardia. 
2. Mild myocarditis can rapidly progress to fulminant disease with signs of cardiogenic shock.  
3. Children with myocarditis may develop arrhythmias and require treatment with antiarrhythmics. 
4. ECG typically demonstrates sinus tachycardia for age and non-specific changes such as ST-segment changes (flattening or depression), T-wave abnormalities, and/or T-wave inversions. An ECG with a low voltage QRS interval should raise suspicion for myocarditis, due to either overall inflammation or an associated pericardial effusion.
5. Troponin is a sign of myocardial injury, but is not specific to myocarditis and does not correlate with disease severity.

Myocarditis Notes

What is myocarditis?

“Myo” – muscle, “card” – heart, “itis” – inflammation

Together, myocarditis means inflammation of the heart muscle.

Myocarditis ranges in severity, from a subacute presentation with mild viral-type symptoms to fulminant heart failure with severe systolic and diastolic dysfunction. Children can present with non-specific symptoms of fatigue and poor intake. 

• Mild disease: May have normal to mildly abnormal labs, and echo may be normal. Depending on parental comfort level, they may be observed at home or on the floor without telemetry. 
• Severe disease: evidence of decreased function and/or an abnormal electrocardiogram (ECG). Admit to the intensive care unit (ICU) on telemetry. Given the uncertainty of where the patient is in the disease process, they may either be clinically stable or deteriorate further.

The observed incidence of myocarditis in children is roughly 1-2 per 100,000 person-years (Arola et al. 2017). That said, the incidence may be greater given the number of children who may not present to care. 

What is the pathophysiology of myocarditis?

The pathogenesis of myocarditis depends on the specific etiology. 

Editor’s Note: In viral myocarditis, death of cardiomyocytes, endothelial cells, and stromal cells activates the innate immune response through several mechanisms, leading to further activation of an inflammatory response and infiltration of cardiomyocytes by immune cells. This infiltration can lead to the development of fibrosis and cardiomyopathy. (Law et al. 2021) 

When should I suspect myocarditis?

Myocarditis should be suspected in a child with new-onset signs and symptoms of heart failure with left ventricular systolic dysfunction, particularly if there is no evidence for other etiologies, such as congenital heart disease, coronary abnormality, or familial cardiomyopathy. 

Careful triage and clinical stabilization takes precedence over creating a differential diagnosis, particularly in the acute stage. It is important to focus on ABCs (airway, breathing, and circulation) of resuscitation. 

Initial presentation:

• Vitals may show tachycardia, tachypnea, decreased blood pressure, bounding pulses 
• Arrhythmias – the most common are ventricular tachycardia, ventricular fibrillation, and atrioventricular (AV) block (Miyake et al. 2014).
• May have an associated pericarditis, so they may be more comfortable sitting up rather than laying down.

Signs of heart failure:

• Left ventricular systolic dysfunction, with the heart not squeezing properly. PAtients are unable to augment their cardiac output with increased contractility, so they become tachycardic. 
• Diastolic dysfunction may be present due to the heart not relaxing properly. 
• Deterioration following fluid bolus is concerning for myocarditis or cardiomyopathy
  • Pearl: This is a sign that the patient’s cardiac LV systolic function is decreased, end-diastolic pressure in the LV is high, and they cannot handle extra volume. As a result, blood will flow backwards into the lower pressure left atrium, into the lungs, and create pulmonary edema causing worsening tachypnea and increased work of breathing
• Right-sided heart failure secondary to left-sided heart failure may be present. Exam findings suggestive of right-sided heart failure include hepatomegaly and peripheral edema.

How is myocarditis diagnosed?

Myocarditis is primarily a clinical diagnosis. The diagnosis of myocarditis is suspected/probable, confirmed, or proven, based on clinical suspicion, cardiac magnetic resonance imaging (MRI), or biopsy, respectively. 

Diagnostic Tools

• ECG typically demonstrates sinus tachycardia for age and non-specific changes such as ST-segment changes (flattening or depression), T-wave abnormalities, and/or T-wave inversions. Dr. Laks emphasizes the importance of evaluating other causes of tachycardia, such as SVT. Patients with ectopy on ECG warrants observation on telemetry. Further, she states a low voltage QRS interval should raise suspicion for myocarditis.

• Echocardiogram is critical for assessing cardiac function. The degree of dysfunction may be mild in a subacute case or severe in a fulminant presentation. Increased wall thickness may be seen secondary to interstitial edema in the acute phase. Pericardial effusion can be associated with myocarditis (Law et al. 2021). Bedside point-of-care ultrasound (POCUS) can be useful for those who have experience with accurately evaluating normal cardiac function. It should not replace a formal echocardiogram and cardiologist’s interpretation. 

• Chest x-ray is useful for assessing the cardiac silhouette and the lung fields. A large cardiac silhouette may raise suspicion for a longer term problem, such as a dilated cardiomyopathy, which could have been tipped over into poor function in the setting of an infection. Many patients with acute myocarditis have not had the time for the heart to dilate. Chest x-ray can also give an idea of if there is concomitant pulmonary edema that may require diuresis.

• A CBC and CRP can help assess the presence of infectious causes. Anemia is also an important etiology of tachycardia.

• A CMP is useful in the assessment of end-organ damage in the setting of decreased cardiac output. Watch out for decreased urine output as an early indication of decreased renal perfusion!

• Viral testing can be useful in the assessment of infectious etiology, though a viral pathogen is not always readily identified. Viral load may correlate with outcome. 

• BNP can be useful as part of the assessment of fluid status and need for diuresis, particularly if the patient does not have a line to assess central venous pressure. BNP is not specific to myocarditis, but is a good marker of heart failure and can provide a clue of how sick the patient is. It can be useful to follow BNP over time to see how they’re improving over time.

• Troponin is a sign of myocardial injury, though the utility is controversial in pediatrics. It is not sensitive or specific to myocarditis and has not been shown to correlate with cardiac dysfunction, though it can be reassuring to see it normalize over time.

• • Cardiac MRI is a useful tool for diagnosis of myocarditis. The 2018 Lake Louise Criteria provide diagnostic criteria based on myocardial edema, hyperemia and capillary leak, irreversible injury, systolic or diastolic dysfunction, increased wall thickness, pericardial effusion, and intracavitary thrombi (Ferreira et al. 2018).

• Endomyocardial biopsy was historically the gold standard for diagnosis of myocarditis. The Dallas Criteria provide criteria for active myocarditis as mononuclear infiltrates and myocyte necrosis or degeneration without histologic evidence of ischemic injury (Aretz et al. 1987). Endomyocardial biopsy has fallen out of favor given the invasiveness and high false-negative rate due to the often focal nature of myocarditis (Chow et al. 1989). Therefore, endomyocardial biopsy is typically reserved for patients with an uncertain diagnosis based on non-invasive testing. 

What are the etiologies of myocarditis?

• The etiology of myocarditis is most commonly idiopathic. 
• Viral infections are the most commonly identified cause, notably parvovirus B19 and human herpesvirus. Bacterial, fungal, spirochetal, rickettsial, and protozoal infections can be associated with development of myocarditis. Autoimmune conditions, drug hypersensitivity reactions, drugs of abuse, toxins, and allo-antigens have also been implicated in myocarditis in children (Law et al. 2021).

What else is on the differential diagnosis for myocarditis?

When evaluating a patient with a presentation suspicious for myocarditis, one should also consider other diagnoses that can lead to systolic or diastolic dysfunction:

• • Dilated cardiomyopathy is difficult to differentiate from myocarditis. It may present with a more subacute course without fever, greater left ventricular dimension, relatively lower cardiac enzyme elevation, and lack of arrhythmia (Suthar et. al 2018).

• Restrictive cardiomyopathy is characterized by diastolic dysfunction due to decreased myocardial compliance. It is often caused by diseases that cause interstitial fibrosis, infiltrative diseases (i.e. amyloidosis or sarcoidosis), or storage diseases such as Fabry disease. Echocardiographic findings include non-dilated ventricles and restrictive filling patterns (Rapezzi et a. 2022).

• Constrictive pericarditis is characterized by diastolic dysfunction due to external factors, such as a stiff, fibrotic pericardium. It is difficult to distinguish from restrictive cardiomyopathy (Hirshfeld & Johnston-Cox 2021).

• Kawasaki disease (KD) with coronary involvement should be considered in a child with history of diagnosed KD or prolonged fever, conjunctival injection, rash, mucocutaneous changes, cervical lymphadenopathy and/or lab criteria consistent with atypical KD (McCrindle et al. 2017).

• Lupus carditis is a rare (5-10% of patients) manifestation of systemic lupus erythematosus that may present with myocarditis, pericarditis, or endocarditis. It is most common in those with recent diagnosis and high disease activity. Testing for auto-antibodies (ANA, anti-dsDNA, and anti-Smith antibodies) and rheumatology consultation is helpful (du Toit et al. 2023).

• Chemotherapy-related cardiac dysfunction is a known side effect of various chemotherapeutic agents, typically anthracyclines in pediatric patients. It is characterized by irreversible, dose-related cardiotoxicity, though can also cause an acute inflammatory response. Consider this diagnosis in patients treated for malignancy (Linschoten et al. 2018).  

• Infective endocarditis (IE) is an infection of the heart valves or endocardium. Though rare, IE is associated with significant morbidity and mortality, even in children with structurally normal hearts. Consider IE in a patient with fever, new murmur, and/or heart failure symptoms. Neonates may present with poor feeding, respiratory distress, tachycardia, and/or hypotension (Baltimore et al. 2015).

Clinical Management of Myocarditis

The management of myocarditis varies widely based on the severity of the clinical presentation, whether a subacute myocarditis or fulminant heart failure with cardiogenic shock. 

• For a hemodynamically stable patient with mild disease, telemetry and close monitoring on the general pediatric floor may be sufficient. These children can have rapid clinical decline, so observation in a pediatric intensive care unit or cardiovascular intensive care unit can be reasonable. 
• Children who develop arrhythmias may require antiarrhythmic pharmacotherapy, cardioversion, and/or cardiopulmonary resuscitation (Miyake et al. 2014).
• Antivirals for identified viral triggers (if available) and antibiotics for a known bacterial cause 
• At times, inotropic support may be necessary – milrinone is typically first line as it improves ventricular contractility, lusitropy (relaxation), and afterload. Epinephrine is typically reserved for children in cardiogenic shock. 
• Children who present in cardiogenic shock often require mechanical support such as extracorporeal membrane oxygenation (ECMO) or a ventricular assist device (VAD). 
• The role of adjuncts, such as intravenous immunoglobulin (IVIG) and steroids, is not well-established in pediatrics. Some data suggest that IVIG, steroids, or a combination of both may be safe (Schauer et al. 2023). That said, no prospective studies exist to date, so there are no robust recommendations regarding these therapies.

Long-term Outcomes of Myocarditis

Most children who present with myocarditis tend to do well and recover cardiac function over time. 

• Oral heart failure medications may be useful in the post-discharge management of children with myocarditis. These therapies include diuretics to improve venous congestion and angiotensin-converting enzyme inhibitors (ACE-Is) or angiotensin II receptor blockers (ARBs) for afterload reduction. Aldosterone agonists and beta-blockers, such as carvedilol, may be useful for ventricular remodeling (Williams et al. 2023).

• Athletes require close follow-up prior to return to play given the high risk of arrhythmia with strenuous exercise. The American Heart Association and American College of Cardiology recommend: 
  • Athletes who present with myocarditis undergo resting echocardiogram, 24-hour Holter monitor, and exercise stress test no less than 3-6 months after the initial illness.
  • It is reasonable to return to play if  ventricular systolic function has normalized; serum markers of myocardial injury, inflammation, and heart failure have normalised; clinically relevant arrhythmias are absent on Holter monitor and exercise stress test.

Some portion of children (16 out of 171, 9.4%, in a multi-center cohort study) require transplantation (Butts et al. 2017).

Goal

Listeners will explain the basic pathophysiology, diagnosis, and management of myocarditis in order to recognize it propmotly to provide appropriate treatment.

Learning Objectives

After listening to this episode listeners will…  

1. Recall the basic pathophysiology of myocarditis
2. Be familiar with the ECG changes in myocarditis
3. Recognize the importance of close monitoring and disposition in myocarditis
4. Describe the utility of laboratory studies in a patient with myocarditis
5. Learn about the treatment of myocarditis

Disclosures

Dr. Laks reports no relevant financial disclosures. The Cribsiders report no relevant financial disclosures. 

Citation

Rago, AR, Laks, J, Kelly, JM, Masur, S, Chiu C. “128: Hearts on Fire – Myocarditis”. The Cribsiders Pediatric Podcast. https:/www.thecribsiders.com/ December 18, 2024