Myocarditis in Adults: ED Presentations, Evaluation, and Management

Authors: Toni Riveros, MD, MPH (@thefeelsEM, Emergency medicine resident, Cook County Hospital) and Michael Schindlbeck (Associate Program Director, Cook County Hospital) // Edited by: Alex Koyfman, MD (@EMHighAK) and Brit Long, MD (@long_brit)

Case

A previously healthy 32-year-old female presents with 2 weeks of gradually progressive chest pain and shortness of breath. These symptoms initially presented with concurrent fevers, myalgias, nasal congestion, and a sore throat, all of which resolved within a few days of onset.  Her vital signs upon presentation to the emergency department include HR 128, RR 24, BP 107/59, Temp 99.5 F°, SpO2 94%.  Her physical exam is notable for a toxic appearing patient in moderate respiratory distress with inspiratory crackles extending halfway up the bilateral lung fields on auscultation accompanied by 1+ bilateral pretibial edema.

Etiology

Myocarditis is an inflammatory condition of the myocardial tissues of the heart which typically results in some degree of secondary cardiac dysfunction. The true incidence of myocarditis is difficult to determine, secondary to the wide variability in clinical presentations and limitations in definitive diagnostic testing (1). Still, it is recognized as an important cause of both sudden cardiac death and the development of dilated cardiomyopathy (2,3).

Myocarditis has many causes but can be grouped broadly into infectious, (bacterial, parasitic, viral), immune-mediated, and toxic etiologies. Among viral etiologies, enteroviruses are often associated with myocarditis, but influenza, hepatitis viruses, HIV, herpes viruses, and Parvo B-19 are also known causes (3).

Immune-mediated causes of myocarditis include SLE, scleroderma, and giant cell types (3). Exposure to toxic agents including doxorubicin, antiretroviral medications, clozapine, and cocaine can precipitate the disease (3).

Bacterial pathogens associated with myocarditis include Lyme disease secondary to Borrelia burgdorferi along with mycoplasmal, chlamydial, and streptococcal infections.  Parasitic organisms include toxoplasmosis and trichinosis. Chagas’ disease, transmitted by the parasite Trypanosoma cruzi, is endemic from Mexico through South America and is a substantial cause of cases worldwide (4).

Pathophysiology

Our understanding of the pathophysiology of myocarditis continues to evolve. It is currently thought that the disease occurs in a three-step process (5). In the acute setting, infectious, autoimmune, or toxic agents cause direct damage to the cardiac myocytes. Subsequent myocyte destruction exposes their intracellular components, leading to immune system activation and secondary inflammation via the activation of cytokines and the actions of B-cells and T-cells (5). Later during the disease, progressive myocardial damage continues when the now-sensitized immune system mistakenly attacks the myocytes themselves (5).

Presentation

As myocarditis can present with a wide spectrum of symptoms, timely diagnosis requires a high index of clinical suspicion.  In viral cases, patients may have an ongoing or recent respiratory or gastrointestinal infection. In adults, symptoms commonly include dyspnea, palpitations, orthopnea, and chest pain (6). In a European study of 3,000 adult patients with suspected myocarditis, the most common presenting symptom was dyspnea (72%), while only 32% reported chest pain (6). The nature of chest pain with myocarditis is widely variable, ranging from pleuritic to anginal chest pain (7).  Patients may present anywhere along the spectrum of congestive heart failure with symptoms from fatigue and peripheral edema to outright cardiovascular collapse (8). Unfortunately, as patients often present with non-specific symptoms such as generalized malaise, myalgias, or gastrointestinal symptoms, the diagnosis of myocarditis can be easily missed (8). In cases of myocarditis triggered by exposures to medications, associated skin manifestations can be present and may provide a clue towards an inciting factor (9).

Diagnostic Testing

Because of the wide range of possible presentations, testing for myocarditis overlaps with diagnostic testing for other cardiopulmonary complaints. A screening electrocardiogram is commonly ordered but of limited specificity, though patients often display EKG abnormality in some form. Potential abnormalities include sinus tachycardia, ST-segment elevations which may be concave and without reciprocal changes, T-wave inversions, AV blocks, widened QRS durations, or prolonged QT intervals; however, these changes may neither be specific or sensitive (5, 26).  There may be a prognostic role for the EKG, as several studies have identified QRS prolongation > 120msec, QTc prolongation > 440msec, ventricular ectopy, and an abnormal QRS axis as predictive of poor clinical outcomes, such as the need for a cardiac transplant. (10)

Troponin assays are frequently but not universally elevated (11). In one small study examining the role of high-sensitivity troponin T in the diagnosis of patients with suspected myocarditis, patients with biopsy-proven acute myocarditis demonstrated significant elevations in their serum troponin levels compared to patients whose biopsies revealed either chronic myocarditis or normal myocardium. (12).  In a related study of 80 patients with suspected myocarditis, patients with elevated troponin levels were found to have myocarditis confirmed on immunohistological studies at a rate of 93% vs. 44% for those patients with normal troponin levels (13).  As such, while elevated serum troponin levels definitely suggest the presence of acute myocarditis, a normal serum troponin level cannot be used to definitively rule it out. Furthermore, there is a lack of evidence regarding disparities in troponin elevations among the different subsets of myocarditis (ie. viral, toxic, bacterial, inflammatory).

In cases with decompensated CHF, brain natriuretic peptide (BNP) assays will be elevated. Additional blood tests including a CBC, CRP, and ESR are often abnormal, but again non-specific. In severe cases associated with global hypoperfusion, evidence of acute end-organ failure can manifest with elevated transaminases and/or serum creatinine levels. Chest radiography in myocarditis can yield a variety of results ranging from completely normal to pronounced cardiomegaly plus or minus the presence of associated pulmonary edema (15).  Echocardiography may demonstrate a decreased left ventricular ejection fraction, regional wall-motion abnormalities, and/or global hypokinesis and can be used to help identify alternative conditions including pulmonary embolism, pericardial effusion, or cardiac tamponade.

Myocardial biopsy remains the traditional diagnostic gold standard but carries the inherent risk of complications including infection, hemorrhage, and pericardial tamponade.  Furthermore, false negative studies can result when unaffected areas of the heart are biopsied (16).  Consequently, given its non-invasive nature, diagnostic accuracy, and prognostic implications, cardiac MRI is emerging as the study of choice in patients with suspected myocarditis (23).  That said, both of these studies are well beyond the standard realm of the ED.

Treatment

The treatment of myocarditis is mainly supportive and aimed at mitigating further damage to the heart. As always, stabilizing the patient’s ABCs should be the priority. The ideal management of patients with secondary congestive heart failure depends upon the overall stability of the patient (15). Patients with hypoxia or pulmonary edema require supplemental oxygen, and non-invasive positive pressure ventilation may be necessary (15). Standard heart failure therapy including diuretics and nitroglycerin should be given to patients whose systemic perfusion can tolerate it (8). Transcutaneous or transvenous pacing may be required in patients with symptomatic bradycardia or advanced heart blocks.  Cardiac dysrhythmias may require treatment with antidysrhythmic medications including amiodarone.  Finally, patients with myocarditis presumed secondary to bacterial or parasitic infections require the appropriate antimicrobial therapy (8,15).

Aggressive stabilization with intraaortic balloon pumps, extracorporeal membrane oxygenation (ECMO), and/or ventricular assist devices (VAD’s) may be necessary for patients who present with cardiovascular collapse (24).  While VAD’s are more often used in non-acute presentations while preparing for definitive heart transplantation, ECMO has been used successfully in patients with fulminant presentations who require either continuous CPR or those with either persistent hypotension or high vasopressor or inotrope requirements.  Growing evidence suggests that ECMO is more successful for said patients when started earlier in their resuscitations (25).  A 2014 meta-analysis looking at the use of ECMO for a total of 170 patients with severe myocarditis showed survival to discharge rates of 46% for patients in whom ECMO was initiated after the onset of cardiac arrest versus 66% for those in whom ECMO was initiated prior to arrest (17).

The use of intravenous immunoglobulin (IVIG) in the treatment of myocarditis from various etiologies including post-viral and immune-mediated cases has also been studied.  Proposed to have a role in tempering the inflammatory response that helps drive the development of myocarditis, clinical studies have been mixed.  While an earlier retrospective study showed improvements in both left ventricular ejection fraction (LVEF) and serious dysrhythmia rates for those patients treated with IVIG, a more recent randomized controlled trial has failed to show any significant improvement in patient mortality (18,19).  Finally, for patients with proven or suspected giant cell myocarditis, the use of high dose steroids and immunosuppressive agents such as cyclosporine has been shown to improve outcomes in some studies (20).

Prognosis

The overall prognosis for patients with myocarditis is difficult to assess given the variability in clinical presentation, severity, and inciting factor(s).  Predictors of poor clinical outcomes in patients with viral myocarditis include a lower LVEF, higher New York Heart Association (NYHA) class, and the presence of immunohistological signs of inflammation on biopsy (21). One study found an all-cause mortality rate of 19.7% within 5 years of diagnosis, with nearly 10% of patients experiencing sudden cardiac death (22). The prognosis for other types of myocarditis such as giant cell myocarditis or toxin-mediated is not clear.

Case Continued

An immediate EKG, portable chest x-ray, and basic labs including cardiac markers were ordered.  The EKG was significant for isolated sinus tachycardia, while the chest radiograph demonstrated cardiomegaly with associated pulmonary edema. Bedside echocardiography revealed global depressed ejection fraction. The patient’s labs were notable for a leukocytosis of 14.3*10³/μL, a mildly elevated serum creatinine of 1.8mg/dL, and a troponin I level of 4.4ng/mL.  She was started on supplemental oxygen via a non-rebreather and diuresed with intravenous furosemide.  Given her response to therapy in the emergency department, she was admitted to the cardiac unit for further evaluation, monitoring, and treatment.

Pearls & Pitfalls

-Myocarditis remains a challenging diagnosis given its wide range in clinical presentation, from a subtle picture of mild dyspnea and malaise following a recent viral illness to fulminant congestive heart failure and sudden cardiac death.

-Clinicians should investigate for clues including travel or immigration history, illicit drug use, underlying autoimmune conditions, transplant status, co-infections such as hepatitis or HIV, or treatment with chemotoxic or new antibiotic agents.

-Physical exam findings may include tachycardia disproportionate to body temperature, a toxic appearance without a clear source of infection, or dyspnea with signs of circulatory overload in a patient with no known cardiac history.

-Patients with myocarditis should be admitted to a setting capable of cardiac monitoring. Treatment in the ED is mainly supportive with careful attention to airway, breathing, and circulation.

References/Further Reading

1. Baughman, Kenneth L. “Diagnosis of myocarditis: death of Dallas criteria.” Circulation 113.4 (2006): 593-595.
2. Basso, Cristina, et al. “Postmortem diagnosis in sudden cardiac death victims: macroscopic, microscopic and molecular findings.” Cardiovascular research 50.2 (2001): 290-300.
3. Sagar, Sandeep, Peter P. Liu, and Leslie T. Cooper Jr. “Myocarditis.” The Lancet 379.9817 (2012): 738-747.
4. Punukollu, Gopikrishna, et al. “Clinical aspects of the Chagas’ heart disease.” International journal of cardiology 115.3 (2007): 279-283.
5. Cooper Jr, Leslie T. “Myocarditis.” New England Journal of Medicine 360.15 (2009): 1526-1538.
6. Hufnagel, Günther, et al. “The European Study of Epidemiology and Treatment of Cardiac Inflammatory Diseases (ESETCID) First Epidemiological Results.” Herz 25.3 (2000): 279-285.
7. Dec, G. William, et al. “Viral myocarditis mimicking acute myocardial infarction.” Journal of the American College of Cardiology 20.1 (1992): 85-89.
8. Caforio, Alida LP, 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.” European heart journal 34.33 (2013): 2636-2648.
9. Martinez, Soledad, et al. “Giant cell myocarditis associated with amoxicillin hypersensitivity reaction.” Forensic science, medicine, and pathology 9.3 (2013): 403-406.
10. Ukena, Christian, et al. “Prognostic electrocardiographic parameters in patients with suspected myocarditis.” European journal of heart failure 13.4 (2011): 398-405.
11. Caforio, Alida LP, et al. “A prospective study of biopsy-proven myocarditis: prognostic relevance of clinical and aetiopathogenetic features at diagnosis.” European heart journal 28.11 (2007): 1326-1333
12. Ukena, Christian, et al. “Diagnostic and prognostic validity of different biomarkers in patients with suspected myocarditis.” Clinical Research in Cardiology 103.9 (2014): 743-751.
13. Lauer, Bernward, et al. “Cardiac troponin T in patients with clinically suspected myocarditis.” Journal of the American College of Cardiology 30.5 (1997): 1354-1359.
14. Escher, Felicitas, et al. “New echocardiographic findings correlate with intramyocardial inflammation in endomyocardial biopsies of patients with acute myocarditis and inflammatory cardiomyopathy.” Mediators of inflammation 2013 (2013).
15. Brady, William J., et al. “Myocarditis: emergency department recognition and management.” Emergency Medicine Clinics 22.4 (2004): 865-885.
16. Friedrich, Matthias G., et al. “Cardiovascular magnetic resonance in myocarditis: A JACC White Paper.” Journal of the American College of Cardiology 53.17 (2009): 1475-1487.
17. Cheng, Richard, et al. “Clinical outcomes in fulminant myocarditis requiring extracorporeal membrane oxygenation: a weighted meta-analysis of 170 patients.” Journal of cardiac failure 20.6 (2014): 400-406.
18. Yu, Dan‑Qing, et al. “Intravenous immunoglobulin in the therapy of adult acute fulminant myocarditis: A retrospective study.” Experimental and therapeutic medicine 7.1 (2014): 97-102.
19. Isogai, Toshiaki, et al. “Effect of intravenous immunoglobulin for fulminant myocarditis on in-hospital mortality: propensity score analyses.” Journal of cardiac failure 21.5 (2015): 391-397.
20. Cooper Jr, Leslie T., et al. “Usefulness of immunosuppression for giant cell myocarditis.” The American journal of cardiology 102.11 (2008): 1535-1539.
21. Kindermann, Ingrid, et al. “Predictors of outcome in patients with suspected myocarditis.” Circulation 118.6 (2008): 639-648.
22. Grün, Stefan, et al. “Long-term follow-up of biopsy-proven viral myocarditis: predictors of mortality and incomplete recovery.” Journal of the American College of Cardiology 59.18 (2012): 1604-1615.
23. Grigoratos, C et al. “Diagnostic and prognostic role of cardiac magnetic resonance in acute myocarditis”. Heart Failure Review, Epub ahead of print (2018)
24. Murray, LK et al. “Ventricular assist device support as a bridge to heart transplantation in patients with giant cell myocarditis”. Eur J Heart Fail 2012 Mar;14(3):312-8
25. Asaumi, Y et al. “Favourable clinical outcome in patients with cardiogenic shock due to fulminant myocarditis supported by percutaneous extracorporeal membrane oxygenation”. Eur Heart J 2005 Oct 26(20):2185-92
26. Kindermann, Ingrid. “Update on Myocarditis”.  Journal of the American College of Cardiology 59.9(2012): 779-792