Introduction

Myocarditis is an inflammatory disease of the myocardium and is relatively common. Lymphocytic myocarditis has been recorded in 1.06 % of 12,747 unselected routine autopsies performed over a 10-year period [1]. The prevalence is much higher (8.6 %) in the autopsies of adult victims of sudden death [2], especially when less than 30 years of age (22 %) [3].

Many cases are asymptomatic and are under-diagnosed, which makes it difficult to estimate true incidence. Evidence of myocardial injury during viral infection was present in 11.4 % of patients with H3N2 influenza who did not have any cardiac symptoms [4]. Mild troponin I elevation was found in asymptomatic individuals after smallpox vaccination [5].

From a practical standpoint, two aspects are of particular importance: (1) some forms of myocarditis cause serious symptoms and require treatment; (2) some cases progress to permanent myocardial damage and contribute to the burden of non-ischemic cardiomyopathy, a condition with high morbidity and mortality. What proportion of myocarditis progresses to cardiomyopathy is not well established, but signs of myocarditis were found in 89 % of patients with recent (1 month) onset of heart failure (HF) who had an endomyocardial biopsy [7].

Diagnosis of Myocarditis

The etiology of myocarditis includes infection, hypersensitivity to drugs or other substances, or autoimmune process which may be limited to the myocardium, or be a part of a more generalized autoimmune condition.

  • In the USA, infectious agents causing myocarditis are usually viruses, entero-and adenovirus being most common in the past, shifting to parvovirus and herpesvirus lately [8].

  • Non-viral infections like Lyme disease (Borrelia burgdorferi), or Chagas disease (Trypanosoma cruzi) are less common.

  • An inflammatory response in the myocardium may originate from hypersensitivity reactions to various medications or other substances (sulfa, antibiotics, cocaine).

  • Myocarditis may be part of hypereosinophilic syndrome (Loeffler’s disease) [9] or Churg-Strauss disease [10] (eosinophilic myocarditis).

  • Giant cell myocarditis is an autoimmune disease.

  • Autoimmune diseases include systemic lupus erythematous, Wegener's granulomatosis, and giant cell arteritis, Takayasu arteritis may have myocarditis as one of its manifestations.

  • Celiac disease may be accompanied by autoimmune myocarditis [11].

The stages of myocarditis include:

  1. 1.

    Acute injury and necrosis due to virus entry and replication within cardiomyocytes.

  2. 2.

    Activation of the immune system.

  3. 3.

    Autoimmune reaction with cytokine activation and antibody formation.

The role of the immune system in protection from viral myocarditis is best demonstrated by the human immunodeficiency virus. Before highly active antiviral therapy was used, myocarditis was present in 50 % of autopsies in patients with this infection, while currently cardiac manifestations occur only in 18.6 % [12, 13].

On pathology obtained from endomyocardial biopsy, myocarditis has well-defined features which until recently were the mainstay of the diagnosis.

Endomyocardial Biopsy

Endomyocardial biopsy is still considered the gold standard in diagnosis of myocarditis. Contrary of popular belief, this procedure when performed by an experienced operator is very safe, with a complication rate of under 1 % [14]. According to the Dallas criteria proposed in 1986, acute myocarditis is defined by lymphocytic infiltrates in association with myocyte necrosis not characteristic for ischemic damage. Borderline myocarditis is characterized by inflammatory infiltrates without evidence of necrosis [15].

Several factors limit the utilization of morphologic criteria:

  1. (1)

    Endomyocardial biopsy is rarely performed.

    Not many cases of myocarditis meet the criteria for biopsy, but there are clinical scenarios when it should be performed (Table 1).

  2. (2)

    Interobserver variability in reading samples.

    Biopsy specimens from 16 patients with dilated cardiomyopathy, read by seven cardiac pathologists, were interpreted as myocarditis in 11 patients, with three pathologists agreeing about three and two pathologists agreeing about five patients [16].

  3. (3)

    Sampling error.

    Inflammation may be focal, and random samples do not represent the entire myocardium. As a result, diagnostic findings can be missed [17]. Thus, among 38 hearts from autopsies in which lymphocytic myocarditis was diagnosed clinically and by myocardial slices, endomyocardial specimens were also obtained. Right ventricular biopsy specimens, which are routinely obtained during endomyocardial biopsy, were positive in only 63 % of the 38 cases. Even when 10 biopsy specimens per ventricle were evaluated, the frequency of false-negative results was 37 % for the right ventricle [18]. In practice, the number of specimens obtained is usually less than 10 (four or five) and therefore sampling error is even higher.

  4. (4)

    Pathological changes may be transient. When Dec et al. [7] studied 27 patients with recent onset HF, biopsy revealed myocarditis in 18 patients (66.7 %). However, in the subset of patients who became symptomatic only less than 1 month prior to the procedure, biopsy was positive in 89 % of cases.

Table 1 Indications for endomyocardial biopsy [64]
Full size table

All these limitations were summarized by Baughman in 2006 in his article “Diagnosis of myocarditis: Death of Dallas criteria” [19], where he stated that these criteria are no longer adequate.

Evidence of Viral Presence

Another diagnostic approach is identification and quantification of viral infection markers with immunohistochemical and polymerase chain reaction techniques. In one study of 50 patients with histologically proven myocarditis or dilated cardiomyopathy, 28 (56 %) had an endomyocardial biopsy specimen positive for the presence of viral genome, while 22 patients with other non-viral cardiac diseases were all negative [17]. This approach, however, is even less reliable than biopsy: viral genomes were detected at best in half of the patients with myocarditis. Moreover, they can be identified much more often during the first 2 weeks of the disease (40.0 % versus 19.4 %; P = 0.013) [20••]. Viral serology has a sensitivity and specificity of 9 % and 77 %, respectively. Even more importantly, there is no correlation between viral serology and the findings on endomyocardial biopsy, as only 4 % of patients have the same viral genome detected by both tests [21, 22]. Even among patients with positive viral genome findings, clinical presentation is mixed with both acute and chronic HF and variable ventricular function. Overall, the data discourages routine use of tests for viral presence as a diagnostic strategy, and challenges the hypothesis of antiviral therapies in patients with cardiomyopathy, and persistent viral genome [23••].

Because of the limitations and uncertainty regarding the results of these tests, diagnostic work-up of myocarditis is shifting towards non-invasive imaging.

Diagnostic Imaging

The value of diagnostic imaging has grown significantly over the past decade. Cardiac magnetic resonance imaging (CMR), in particular, provides an alternative to invasive tests and plays an important role in the early diagnosis of myocarditis.

There are three MRI sequences that are critical in the diagnosis of myocarditis. They can identify

  • edema (T2 weighted images)

  • hyperemia (T1 weighted images, early gadolinium enhancement)

  • necrosis (late gadolinium enhancement (LGE)

While the first two methods mostly reflect reversible injury related to inflammation, LGE identifies irreversible damage such as necrosis and fibrosis.

  • T2 weighted images

This sequence is designed to detect free water content as hyper-intense (bright) signal and is indicative of myocardial edema, inflammation, or necrosis. Myocarditis first results in edema and therefore this sequence is able to demonstrate abnormalities early on in the disease process.

  • Early T1-weighted enhanced images obtained one minute post contrast.

Gadolinium is an extracellular MRI contrast agent. In myocarditis, the inflammatory reaction in the myocardium results in tissue hyperemia. This early gadolinium enhancement sequence shows affected areas as hyper-intense (bright) signal due to increased cell-membrane permeability and capillary blood flow.

  • Late gadolinium enhancement images obtained 10–20 minutes post contrast.

In areas of tissue necrosis, there is accumulation of gadolinium due to the destruction of tissue cell membranes. As a result, gadolinium does not remain in the extra-cellular space and passively diffuses into the intracellular space. In areas of significant inflammation in myocarditis, there are concomitant areas of myocardial necrosis. These areas accumulate gadolinium on delayed images and appear as mid-myocardial or subepicardial hyper-intense (bright) signal. This technique delineates areas of injury, and when interpreted with T2 weighted images which delineate areas of edema and inflammation, the acuity of myocarditis can be determined. T2 mapping provides accurate quantification of areas of edema/necrosis and can be used for follow-up after treatment to ensure favorable response. In addition, T1-weighted mapping depicts areas of fibrosis in heart failure and has initial favorable results in evaluating myocarditis [24, 25].

According to a consensus paper and recommendations on the use of CMR for myocarditis [26••], the “Lake Louise criteria” require that two of the three above-mentioned sequences need to be positive to make the diagnosis.

Echocardiography

The typical findings on echocardiography are LV dilation and regional or global hypokinesis. Wall thickness may also increase due to myocardial edema. These findings are non-specific and have to be correlated with a convincing clinical scenario. There have been few case report studies which suggest strain Doppler echocardiography may be able to detect myocardial dysfunction in myocarditis [27]. However, there is still not sufficient data to support these diagnostic criteria in routine clinical practice.

Cardiac Computed Tomography Angiography

There is limited research on findings of acute myocarditis on computed tomography. Few case studies have shown hypodense (dark) areas corresponding with fluid/edema in affected myocardial segments on early enhancement images [28]. Currently, computed tomography is not routinely used for the diagnosis of myocarditis due to patient radiation exposure and lack of supporting research.

Nuclear Imaging

Nuclear imaging is no longer used in routine clinical practice for evaluation of myocarditis due to poor specificity, high radiation exposure, and prolonged procedures.

In summary, CMR is currently the best non-invasive test for diagnosing myocarditis.

  • Taking endomyocardial biopsy as gold standard, CMR demonstrated overall diagnostic sensitivity, specificity, and accuracy of 76 %, 54 %, and 68 %, respectively.

  • The best diagnostic performance was observed in patients with recent (2 weeks) onset of the disease (sensitivity, 81 %; specificity, 71 %; and accuracy, 79 %).

  • The diagnostic performance was found to be unsatisfactory (sensitivity, 63 %; specificity, 40 %; and accuracy, 52 %) if the imaging was done after 14 days [20••].

  • When "any-two" of the three CMR criteria were positive in the same patient, they yielded a 76 % sensitivity, 95.5 % specificity, and 85 % diagnostic accuracy.

  • In a smaller series of patients with suspected acute myocarditis, CMR yielded the diagnosis with a 76 % sensitivity, 95.5 % specificity, and 85 % diagnostic accuracy [29].

Studies have also shown that when endomyocardial biopsies are guided by CMR, the diagnostic yield is much higher. CMR-guided biopsies were positive in 19 of 21 patients, while in the remaining seven patients, in whom biopsy could not be taken from the region of contrast enhancement, myocarditis was found only in one case [30]. While the typical location of endomyocardial sampling is septal, CMR demonstrated that inflammatory changes are more often located in the lateral wall of the ventricle, which is rarely sampled due to safety considerations. This raises the question whether biopsy or CMR should be considered the gold standard in the diagnosis of acute myocarditis. At least, as a non-invasive method with good diagnostic yield, CMR should be done first to assess inflammation of the myocardium, and we suggest using it before the biopsy in diagnostic work-up (Fig. 1). However, if the patient was not seen early enough in the course of the disease and presented several months later, the CMR yield is expected to be low. In the presence of high risk features such as high degree atrioventricular blocks, malignant ventricular arrhythmias, or poor response to treatment, endomyocardial biopsy is warranted.

Fig. 1
figure 1

Algorithm for diagnostic work-up and treatment of myocarditis. If CMR cannot be done, or the patient presented later than 3 months from the onset of the disease but has high risk features, such as high degree atrioventricular block or malignant ventricular arrhythmias, endomyocardial biopsy should be performed bypassing the CMR. CMR cardiac magnetic resonance, LVEF left ventricular ejection fraction, EMB endomyocardial biopsy.

Full size image

Although CMR provides valuable information regarding the stage, acuity, location, and distribution of inflammation in the myocardium, it does not differentiate between infectious and autoimmune processes. In other words, acute viral myocarditis, eosinophilic myocarditis, and giant cell myocarditis appear similar on CMR. Meanwhile, from a clinician’s standpoint, these are different entities.

Criticizing Dallas criteria, Baughman proposed to classify myocarditis into clinicopathological types with distinct clinical and/or histologic features [19].

Lymphocytic Myocarditis

This is the most common form of myocarditis. Viral symptoms usually precede the onset of cardiac manifestations. The rapidity of onset and duration of cardiac complaints vary greatly, ranging from asymptomatic cases to acute catastrophic HF with malignant arrhythmias, or conduction disorders and hemodynamic compromise (fulminant myocarditis).

Pathology typically reveals cellular infiltrates with histiocytic, mononuclear, and myocyte damage. In subacute or chronic forms, fibrous tissue can be seen.

Clinically, new onset HF, exertional dyspnea, fatigue, syncope, palpitations, cardiac arrhythmias, or conduction disorders are typical manifestations. Pericardial involvement may bring up chest pain provoked by inspiration or position, and relieved by leaning forward. Pericardial friction rub and ECG changes typical for pericarditis (PR depression and diffuse ST elevation) may help the diagnosis. Otherwise, the complaints, history, and physical exam are often non-specific and diagnosis of myocarditis on purely clinical grounds is difficult. Elevated biomarkers like natriuretic peptides and troponin are of some help but are also non-specific. In patients enrolled into the Myocarditis Treatment trial, troponin I was elevated in 34 % of patients with myocarditis and in only 11 % of 35 controls (P = 0.01) [31]. Although the difference is statistically significant, sensitivity and specificity are certainly not sufficient for the diagnosis.

Serum markers of inflammation including leukocytosis and C-reactive protein can be elevated but are even less specific.

Changes on electrocardiogram are common, but the overall sensitivity of the electrocardiogram for myocarditis is low (47 %) [6]. In 45 consecutive patients with a histologic diagnosis of active myocarditis, atrioventricular block and repolarization abnormalities were the prevailing features in the acute phase of the disease. Later, left atrial enlargement, atrial fibrillation, left ventricular hypertrophy, and left bundle branch block become more common. Wide QRS and left bundle branch block are poor prognostic signs like in any other form of cardiomyopathy [32, 33]. A pseudoinfarction pattern (Q waves plus ST-segment elevation) heralds a rapid and sometimes fatal course (fulminant myocarditis) [33].

The Natural History

Natural course of symptomatic forms is not too favorable. When 222 patients with biopsy-proven viral myocarditis were followed for 4.7 years, long term mortality was quite high (19.2 % all cause, 15 % cardiac, and 9.9 % sudden cardiac death). The presence of LGE on MRI yielded a hazard ratio of 8.4 for all-cause mortality and 12.8 for cardiac mortality, independent of clinical symptoms. It was superior to left ventricular ejection fraction (LVEF), LV end-diastolic volume, or New York Heart Association functional class. None of the patients without LGE experienced sudden cardiac death [34••].

The rate and mechanism of transition of acute myocarditis into chronic irreversible non-ischemic cardiomyopathy is probably the most important question in myocarditis. The possibility of this transition has been proven in animal experiments. For instance, in mice infected with encephalomyocarditis virus, acute changes of myocardial necrosis and mononuclear cell infiltration were gradually replaced by fibrotic changes, with concomitant dilation of the ventricle. These changes were very similar to dilated cardiomyopathy [35]. Other animal studies demonstrated that persistence of viral genome can trigger chronic immune activation and eventually result in development of dilated cardiomyopathy [36].

Unfortunately, the rate of such transition can be studied only on longitudinal follow-up of patients with histologically proven acute myocarditis. In patients with pre-existing dilated cardiomyopathy, viral origin of initial damage is very difficult to prove. Keeling et al. [37] demonstrated the presence of viral genome in 12 % patients with dilated cardiomyopathy and in 17 % of the controls with known ischemic or valvular cardiomyopathy. They could not find any difference in risk factors, natural course, or prognosis in patients with and without persistent viral presence. On the other hand, Why et al. [38] found that patients with persistent viral presence have poor outcomes despite negative biopsies.

The most detailed literature review on the transition to dilated cardiomyopathy was published by D’Ambrosio [39]. In their own experience of 54 patients with biopsy proven acute myocarditis, the overall incidence of spontaneous improvement was 50 %. In the experience of other authors, evolution to dilated cardiomyopathy ranged 11 %–52 %, with a mean of 21 %, in the series with mean follow-up of three years. Such rates make acute myocarditis a very important cause of non-ischemic cardiomyopathy, especially since the most extensive diagnostic work-up cannot identify the etiology in about half of cases of dilated cardiomyopathy [19].

Eosinophilic Myocarditis

Eosinophilic myocarditis is characterized by the presence of eosinophilic infiltrates on histology. Clinically, it is still a heterogenous group. It can be caused by hypersensitivity to drugs (clozapine, sulfonamide antibiotics, methyldopa, furosemide, and some anti-seizure drugs), vaccines, or cocaine. In some cases, clinical features of hypersensitivity reaction (skin rash, fever) in conjunction with cardiac symptoms may help to recognize this condition, but these features may be absent. Even eosinophilia is not uniformly present. Identification and discontinuation of the offender drug is critical, but high dose steroid therapy is also indicated.

When eosinophilic myocarditis is associated with systemic disease such as Loffler’s endomyocardial fibrosis, hypereosinophilic syndrome, Churg-Strauss syndrome, and malignancies, it may gradually evolve over months. Eosinophilia is usually present. Clinically, patients present with biventricular failure, arrhythmia, or can even suffer sudden cardiac death [40]. Finally, such myocarditis can also be related to parasitic infections.

Giant Cell Myocarditis

Giant cell myocarditis presents with acute HF, which is frequently associated with ventricular arrhythmias or high grade heart block. On pathology, there are typical giant cells with extensive inflammation and necrosis. Prognosis without treatment is poor and the rate of death or cardiac transplantation may be as high as 89 percent, while median survival is only 5.5 months from the onset of symptoms [41]. Giant cell myocarditis may be associated with thymoma or autoimmune disorders but can be limited to the heart.

Aggressive immunosuppression with cyclosporine, high-dose steroids, and muromonab-CD3 was associated with a 91 % one-year survival [42]. Some patients require mechanical circulatory support or heart transplantation, and withdrawal of immunosuppression can results in recurrent, and sometimes fatal giant cell myocarditis [43].

Fulminant Myocarditis

The term “fulminant myocarditis” characterizes the clinical course rather than the specific etiology, although giant cell and hypersensitivity myocarditis more often have fulminant progression than viral lymphocytic myocarditis. Patients typically have acute viral prodrome with muscle aches, fever, joint pain, gastrointestinal or upper respiratory symptoms, followed by acute onset of HF within 2 weeks. On echocardiography, there is profound left ventricular dysfunction but usually not left ventricular dilatation. There may be increased left ventricular wall thickness due to inflammation. Endomyocardial biopsy shows multiple foci of active inflammation and necrosis. Patients either die or recover within 2 weeks with complete histological and functional recovery of the myocardium in survivors [44].

Interestingly, patients who survive fulminant myocarditis have better prognosis than those with acute but not fulminant course [45].

When there is hemodynamic compromise, fulminant myocarditis should be treated with heroic measures including short term or long term mechanical circulatory support.

  • Percutaneous extracorporeal membrane oxygenation.

In acute fulminant myocarditis, 60 %–70 % of patients who were supported by percutaneous extracorporeal membrane oxygenation were successfully weaned off the machine [46, 47]. Their further survival was not compromised by the fact that they required mechanical circulatory support. LVEF improved from 23 % to 53 % while on the device [48].

  • Paracorporeal biventricular assist device.

In a series of cases, five patients with fulminant myocarditis were successfully managed with a paracorporeal biventricular assist device. Support was required for a time period of 1 to 3 weeks. All completely recovered [49].

  • Short-term ventricular assist devices.

There are case reports of successful use of Levitronix CentriMag (Levitronix, Waltham, MA), Impella (Abiomed, Danvers, MA) and the TandemHeart (CardiacAssist, Inc., Pittsburg, PA) as bridges to recovery in fulminant myocarditis [50–52].

Treatment

Although management of cardiac conditions is usually based on the guidelines generated from randomized controlled clinical trials, it is difficult to perform trials with myocarditis because it is not as common as other cardiac conditions.

  • HF treatment.

It is uniformly recognized that in patients with myocarditis and LV systolic dysfunction, general principles of treatment apply. Patients should be given angiotensine converting enzyme inhibitors, beta-blockers, and spironolactone, as well as loop diuretics as needed. Persistent decrease in systolic function with LVEF ≤35 % should prompt the implantation of a cardioverter-defibrillator, and a combination of reduced LVEF with left bundle branch block on the electrocardiogram is an indication for cardiac resynchronization therapy [53]

  • Limitation of physical activity during the symptomatic phase of the disease and for several months during recovery is reasonable.

  • Antiviral therapy.

There is no data on antiviral drugs and they are not routinely recommended. There was only one uncontrolled study suggesting benefits of interferon in viral myocarditis [54].

  • Non-steroidal anti-inflammatory drugs

There is no evidence of benefit of nonsteroidal anti-inflammatory drugs or colchicine. In fact, in some animal models ibuprofen exacerbated the course of myocarditis and even increased mortality [55]. The only scenario when non-steroidal drugs may be justified is pericardial involvement with chest pain.

Regarding physical activity in patients with myocarditis, athletes deserve special attention.

Myocarditis in Athletes

Myocarditis can be the cause of sudden cardiac death, including young athletes [56]. It is recommended that athletes with definite or probable myocarditis are withdrawn from all competitive sports. They can be allowed to resume athletic activities after a minimum of at least 6 months, if their symptoms resolve completely, if the cardiac size and function returns to normal, and there are no major arrhythmias. Serum markers also have to return to normal. The recommendations include stress-testing, echocardiography, and Holter monitoring before resuming athletic activities [57].

Immunosuppressive Treatment

Because of the important role of autoimmune process in the pathogenesis of myocarditis, there were multiple attempts to treat this condition with immunosuppressive and immunomodulating therapy.

  • The Myocarditis Treatment Trial [58] enrolled 111 patients with a histopathological diagnosis of myocarditis and LVEF <45 %. The trial failed to demonstrate a mortality benefit of a combination of prednisone with either azathioprine or cyclosporine versus placebo in one year. There was also no improvement in LV systolic function.

  • In another study, Frustaci et al. [59] performed endomyocardial biopsy in patients with recent onset HF and found myocarditis in 112 patients. Those who did not respond to standard HF drugs were additionally treated with prednisone and azathioprine for 6 months. About half of them responded with an increase of LVEF from 23 % to 47 %. Interestingly, almost all responders had anticardiac antibodies, and non-responders had viral genome present in the myocardium. Because there was no control group, this study should be considered more hypothesis-generating than definitive.

  • Same authors later conducted a randomized, double-blind, placebo-controlled TIMIC study (The Tailored Immunosuppression in Inflammatory Cardiomyopathy) focusing on the type of patients that responded well to immunosuppression in their first study. This trial included 85 patients with lymphocytic myocarditis proven by biopsy, but without evidence of myocardial viral genomes. Besides usual HF therapies, they received prednisone 1 mg/kg per day for 4 weeks followed by a lower dose for 5 months, and azathioprine for 6 months, or placebo. Patients on immunosuppression showed a significant improvement of LVEF and a significant decrease in LV dimensions, while in the placebo arm the LVEF deteriorated compared with baseline. Specifically, 38 out of 43 patients (88 %) on immunosuppressive therapy showed a 10 % improvement of cardiac function and dimensions [60••].

  • Another randomized controlled trial studied patients with inflammatory cardiomyopathy diagnosed by presence of increased HLA expression on endomyocardial biopsy who received either immunosuppression or placebo for 3 months; they were then followed for two years. LVEF improved in 3 months, and continued to improve until the end of the follow-up [61].

Immudomodulation with intravenous immunoglobulin was tested in the Intervention in Myocarditis and Acute Cardiomyopathy trial. Patients with acute dilated cardiomyopathy, of which only 16 % had biopsy-proven myocarditis, did no better on immunoglobulin than on placebo [62].

Immunoadsorption is a procedure removing circulating anticardiac antibodies. This was associated with an increase in cardiac index and improvement in exercise capacity, and peak oxygen consumption, although patients had dilated cardiomyopathy, and did not have a confirmed diagnosis of myocarditis [63].

In summary, there is not enough evidence to currently recommend immunosuppressive treatment with corticosteroids and other agents for patients with lymphocytic myocarditis. Such therapies are justified only for biopsy proven eosinophilic or giant cell myocarditis. The only other scenario when empiric steroids might be reasonable is fulminant myocarditis with severe systolic dysfunction and hemodynamic instability, if there is no immediate access to cardiac MRI, endomyocardial biopsy, or mechanical circulatory support.

Conclusions

Diagnosis and treatment of myocarditis can be challenging. Symptomatic patients present with new onset heart failure, malignant arrhythmias, conduction abnormalities, and sometimes hemodynamic instability requiring mechanical circulatory support. Although infrequent, such cases should be promptly recognized and aggressively treated. Endomyocardial biopsy and cardiac magnetic resonance are the diagnostic modalities with the highest diagnostic yield. Transition of acute myocarditis to non-ischemic cardiomyopathies is currently a growing area of research. Understanding risk factors, mechanisms, and rate of this transition may potentially decrease the burden of non-ischemic cardiomyopathy and heart failure in general. Immunosuppressive therapies may modify and reverse the disease in selected subtypes of patients with myocarditis.