Myocarditis is an inflammatory process of the myocardium. It can present as an acute, subacute, or chronic disease phase and may present with either focal or diffuse involvement of the myocardium. In symptomatic patients, the presentation can be highly variable from generalized fatigue, malaise, chest pain, congestive heart failure (CHF), cardiogenic shock, arrhythmias and even 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 also provide important causes of myocarditis. Other causes include toxic myocarditis, which is related to drugs that may cause an insidious form of the disease.
Myocarditis is diagnosed based on clinical presentation. Diagnosis is classically confirmed by endomyocardial biopsy (EMB) via established histologic, immunologic, and immunohistochemical criteria.
The etiology is thought to be caused by a variety of infectious and non-infectious causes. Among the infectious causes, viruses are presumed to be the most common pathogen. In North America and Europe the most frequently implicated viruses include enteroviruses, including coxsackievirus. Parvovirus B-19 and human herpesvirus 6 are frequent culprits as well. Other pathogens that have been implicated include various bacteria, fungi, protozoa, and helminths. Other common but non-infectious causes of myocarditis include autoimmune disorders such as systemic lupus erythematosus (SLE), Wegener’s granulomatosis, and giant cell arteritis.
The incidence of myocarditis is approximately 1.5 million cases worldwide per year. Incidence is usually estimated between 10 to 20 cases per 100,000 persons. 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 the majority of Coxsackie B virus infections, an important 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.
This leads to the destruction of the cardiac tissue from the infiltration and replication of the infectious agent. Later, the host cellular immune responds and the cytotoxic effects of host immunity are activated by the offending agent.
There may also be a toxic effect of exogenous or endogenous chemicals produced by the systemic pathogen directly on the myocyte.
Three stages of the disease process:
Endomyocardial biopsy (EMB) typically is recommended after other causes of heart failure such 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 the endomyocardial biopsy will reveal cellular infiltrates, which are usually histiocytic and mononuclear with or without associated myocyte damage. Specific findings include eosinophilic, granulomatous, and giant cell myocarditis. The infiltrates are highly variable, often associated with varying degrees 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 such as cocaine, phenothiazines, alcohol, TCA antidepressants, and lithium to name a few, are known to cause myocarditis over time. Frequently, toxic myocarditis will run an insidious course resulting in CHF and dilated cardiomyopathy, often irreversible.
Myocarditis is also a common autopsy finding in patients with cocaine abuse. While the mechanism is largely unknown, many largely believe it is due to its increased sympathomimetic effect, severe oxidative stress, and even metabolite interactions with ion channels. Myocarditis may account for the myocardial anatomic changes that predispose the patient to ventricular dysrhythmias associated with sudden death.
Patients typically will present with a flu-like illness, including fever, malaise, myalgias, vomiting, and diarrhea.
Most patients will present with abnormal ECG that are widely variable. This included sinus tachycardia, widened QRS patterns, low voltage, prolonged QT, variable atrioventricular (AV) blocks, and even acute myocardial infarction (AMI) pattern.
Cardiac markers, such as troponin, may be elevated, but during which course of the disease process is mostly unknown. Higher levels of troponin likely correlate with more myocardial damage as it is indicative of myonecrosis, but negative values do not rule out the diagnosis. Other tests that should be ordered include complete blood count (CBC), erythrocyte sedimentation rate (ESR), and c-reactive protein (CRP). The white count, ESR, and CRP may be elevated but are not diagnostic in any way.
Viral antibody titers should also be ordered and should include coxsackievirus group B, HIV, CMV, Ebstein-Barr virus, hepatitis and influenza viruses. Titers will typically increase by four-fold during the acute phase with gradual fall with the progression of the disease process. Serial titers may be helpful.
Cardiac ECHO should be ordered and may show nonspecific findings such as reduced left the ventricular function, global hypokinesis, and even regional wall motion abnormalities.
Contrast MRI or nuclear studies can show the extent of inflammation and cellular edema, although this may still be non-specific.
Endomyocardial biopsy (EMB), while considered the “gold standard” for diagnosis, is rarely utilized as it 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.
Treatment, for the most part, is supportive and aimed at preserving left ventricular function and can range from a simple limitation of activity to rhythm and CHF management, ventricular assist devices and even cardiac transplantation down the road. Multicenter trials evaluating immunosuppressive therapies have shown no benefit at this time. In the chronic stage, CHF symptoms tend to predominate, and standard pharmacologic treatments for CHF are indicated.
All patients diagnosed or suspected to have acute myocarditis should be admitted to the hospital and be monitored for hemodynamic instability. Immediate complications of myocarditis include ventricular dysrhythmias, left ventricular aneurysm, CHF, and dilated cardiomyopathy. The mortality rate is up to 20% at 1 year and 50% at 5 years. Despite optimal medical management, overall mortality has not changed in the last 30 years.
The diagnosis and management of viral myocarditis is complex and is best done with an interprofessional team that includes a cardiologist, intensivist, nurse practitioner, cardiac surgeon, an internist, and an infectious disease expert. Once the diagnosis is made, the treatment is largely supportive. All symptomatic patients need ICU monitoring. Immediate complications of myocarditis include ventricular dysrhythmias, left ventricular aneurysm, CHF, and dilated cardiomyopathy. The mortality rate is up to 20% at 1 year and 50% at 5 years. Despite optimal medical management, overall mortality has not changed in the last 30 years. (Level V)
|||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; [PubMed PMID: 30740183]|
|||Price JF, Congestive Heart Failure in Children. Pediatrics in review. 2019 Feb; [PubMed PMID: 30709972]|
|||Seo KW,Park JS, Sinus of Valsalva Aneurysm and Multiple Aortic Aneurysms Provoked by Viral Myocarditis. Korean circulation journal. 2019 Feb; [PubMed PMID: 30693683]|
|||Mavrogeni SI,Tsarouhas K,Spandidos DA,Kanaka-Gantenbein C,Bacopoulou F, Sudden cardiac death in football players: Towards a new pre-participation algorithm. Experimental and therapeutic medicine. 2019 Feb; [PubMed PMID: 30679986]|
|||Filipowicz A,Coca MN,Blair BM,Chang PY, ACUTE MYOCARDITIS WITH CARDIOGENIC SHOCK AND MULTIPLE ORGAN FAILURE, FOLLOWED BY BILATERAL PANUVEITIS MASQUERADING AS ENDOGENOUS ENDOPHTHALMITIS, DUE TO TOXOPLASMA GONDII IN AN IMMUNOCOMPETENT PATIENT. Retinal cases [PubMed PMID: 30664080]|
|||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 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; [PubMed PMID: 30619368]|
|||Bailey JR,Loftus A,Allan RJC, Myopericarditis: recognition and impact in the military population. Journal of the Royal Army Medical Corps. 2018 Nov 14; [PubMed PMID: 30429297]|
|||Tselios K,Urowitz MB, Cardiovascular and Pulmonary Manifestations of Systemic Lupus Erythematosus. Current rheumatology reviews. 2017; [PubMed PMID: 28675998]|
|||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; [PubMed PMID: 27858465]|
|||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; [PubMed PMID: 26622337]|
|||Casadonte JR,Mazwi ML,Gambetta KE,Palac HL,McBride ME,Eltayeb OM,Monge MC,Backer CL,Costello JM, Risk Factors for Cardiac Arrest or Mechanical Circulatory Support in Children with Fulminant Myocarditis. Pediatric cardiology. 2017 Jan; [PubMed PMID: 27826709]|