Treatment and prognosis of myocarditis in children

INTRODUCTION — Myocarditis is an inflammatory disease of the myocardium. Myocardial inflammation results in ventricular dysfunction, which can cause heart failure symptoms, hemodynamic compromise, and life-threatening arrhythmias. Children with myocarditis are at risk for considerable morbidity and mortality.

The natural course, management, and prognosis of myocarditis in children are reviewed here. The causes, incidence, clinical manifestations, and diagnosis of myocarditis in children are discussed separately. (See "Myocarditis: Causes and pathogenesis" and "Clinical manifestations and diagnosis of myocarditis in children".)

Myocarditis related to coronavirus disease 2019 (COVID-19) infection and vaccination is discussed in depth elsewhere. (See "COVID-19: Vaccines", section on 'Myocarditis' and "COVID-19: Multisystem inflammatory syndrome in children (MIS-C) clinical features, evaluation, and diagnosis" and "COVID-19: Cardiac manifestations in adults", section on 'Myocarditis'.)

NATURAL COURSE — Viral myocarditis can be considered a continuum of two or three disease processes that transition from one to another in a seamless manner [1,2]. (See "Myocarditis: Causes and pathogenesis", section on 'Role of viral myocarditis as a cause of dilated cardiomyopathy'.)

●Viral infection phase is often reported as a prodromal presentation of fever, myalgia, and malaise several days prior to the onset of symptoms of heart dysfunction. Respiratory and gastrointestinal symptoms are also common in this phase. Viral infection may result in direct myocyte injury. (See "Clinical manifestations and diagnosis of myocarditis in children", section on 'Presentation'.)

The use of antiviral agents has been proposed; however, their efficacy is unproven in the treatment of myocarditis [3]. (See 'Antiviral therapies' below.)

●Autoimmunity and inflammatory phase is caused by activation of the host immune system by the primary viral infection. Myocyte injury results from inflammation triggered by T cell and cytokine activation, which can be detected by endomyocardial biopsy. (See "Clinical manifestations and diagnosis of myocarditis in children", section on 'Endomyocardial biopsy'.)

Myocyte injury leads to impaired ventricular function, heart failure, and/or arrhythmias. In most patients, the acute immune response declines with viral elimination and left ventricular function recovers without sequelae within the first two to four weeks [3]. During this phase, a minority of patients will develop life-threatening arrhythmias, conduction disturbances, or circulatory collapse. (See "Clinical manifestations and diagnosis of myocarditis in children", section on 'Presentation'.)

Management during this phase usually includes supportive care. Immunosuppressive or immune modulatory therapies to reduce inflammation (ie, intravenous immune globulin [IVIG]) are also commonly used, but the data are inadequate to determine whether or not they are efficacious. Specific intervention for complications is required in more severely affected patients (eg, those with arrhythmias, conduction disturbances, or near circulatory collapse). (See 'Acute management' below.)

●Dilated cardiomyopathy (DCM) phase occurs in a subset of patients. It remains uncertain why these patients develop chronic dilation. One proposed mechanism is based on a predisposing immunogenetic background that renders the individual more susceptible to a prolonged autoimmune response due to incomplete clearance of cardiac viral genomes or self-myocardial antigens.

Management during this phase is continuation of medical management for patients with heart failure and, in some patients, cardiac transplantation. (See 'Chronic heart disease' below.)

ACUTE MANAGEMENT

Overview — Because of the high risk of arrhythmias and hemodynamic compromise during the acute inflammatory phase of the disease, children with myocarditis who present with severely depressed ventricular function or rhythm disturbances should be cared for in a pediatric intensive care unit. All patients require ongoing cardiorespiratory monitoring as the hemodynamic status of the patient may quickly deteriorate even if cardiac function is initially intact.

Therapy for pediatric myocarditis during the acute phase includes:

●Supportive care to maintain hemodynamic stability and adequate systemic perfusion. In cases of fulminant disease, this may necessitate the use of mechanical support of the circulation using extracorporeal membrane oxygenation (ECMO) or a ventricular assist device (VAD), followed by cardiac transplantation. (See 'Hemodynamic support' below.)

●Detection and treatment of arrhythmias. (See 'Arrhythmia management' below.)

●Immunomodulatory therapy. (See 'Immunomodulatory therapy' below.)

Hemodynamic support — At presentation, infants and children with myocarditis usually have signs and symptoms of heart failure. Supportive care interventions depend upon the degree of symptoms:

●Initial supportive treatment consists of supplemental oxygen and careful fluid resuscitation.

●Children with mild symptoms can generally be managed with oral diuretics and afterload-reducing agents (eg, angiotensin-converting enzyme inhibitors). (See 'Medical therapy for heart failure' below.)

●Children with more severe symptoms (ie, decompensated heart failure or cardiogenic shock) may require intravenous inotropic support, mechanical ventilation, and even mechanical circulatory support. (See 'Decompensated heart failure/cardiogenic shock' below.)

Medical therapy for heart failure — In patients who are asymptomatic or mildly symptomatic with evidence of depressed ventricular function, medical management with oral therapy generally includes:

●Diuretics

●Afterload-reducing agents (eg, angiotensin-converting enzyme inhibitors)

These agents and other pharmacologic agents for management of heart failure in children are discussed in greater detail separately. (See "Heart failure in children: Management", section on 'Pharmacologic therapy'.)

Decompensated heart failure/cardiogenic shock — Severely affected patients are at risk for circulatory collapse. Medical intervention for these patients includes:

●Intensive management of heart failure – This includes intravenous diuretics and inotropic agents, such as milrinone, dopamine, and dobutamine. (See "Heart failure in children: Management", section on 'Inotropes'.)

●Positive pressure ventilation – Positive pressure ventilation can improve cardiac function by reducing work of breathing, reducing left ventricular afterload, and increasing systemic oxygen levels. Positive pressure ventilation can be provided noninvasively (eg, bilevel positive airway support) or via an endotracheal tube. Intubation and sedation have the additional benefit of further reducing metabolic demand, which may be beneficial for patients with cardiogenic shock.

Although positive pressure ventilation may provide hemodynamic benefit, induction of anesthesia and intubation in a patient with severely depressed ventricular function carries considerable risks of hemodynamic deterioration and even cardiac arrest. Practitioners should choose induction agents with minimal cardiodepressant or vasodilatory effects and should be prepared to institute resuscitative efforts, including mechanical support of the circulation with ECMO where available. (See "Rapid sequence intubation (RSI) in children for emergency medicine: Approach" and "Rapid sequence intubation (RSI) in children for emergency medicine: Medications for sedation and paralysis".)

●Mechanical support – Infants and children with severe circulatory compromise despite medical management may need temporary mechanical circulatory support using ECMO or VAD [2,4,5]. ECMO is used more frequently than VAD support for acute myocarditis in children [6]. Temporary mechanical circulatory support is used to allow time for recovery of cardiac function. Less commonly, it serves as a bridge to transplantation [6-14].

In a report from the multicenter Extracorporeal Life Support Organization registry of 255 pediatric patients with myocarditis supported with ECMO, survival to hospital discharge was 61 percent [11]. Most survivors recovered cardiac function and were successfully separated from ECMO. ECMO was used as a bridge to transplantation in only seven patients (3 percent), of whom six survived to hospital discharge. Among nonsurvivors in this cohort, ECMO support was withdrawn in 70 percent, most of whom had multiple organ failure.

In another review of 514 pediatric hospital admissions for acute myocarditis from the Pediatric Health Information System (PHIS) database, 20 percent received ECMO or VAD support during the hospitalization, of whom 16 percent underwent cardiac transplantation [6]. Of the remaining patients who required temporary circulatory support, 24 percent died and the remaining patients (60 percent) had recovery of cardiac function and survived to discharge after separation from VAD or ECMO support.

Patients who require mechanical support are more likely to have ventricular arrhythmia, bradyarrhythmia, and/or evidence of other organ dysfunction (eg, acute kidney injury, elevated transaminases) at the time of presentation compared with patients managed without mechanical support [15-17].

Arrhythmia management — Clinicians should maintain a high level of vigilance around monitoring for arrhythmias. Loss of sinus rhythm may lead to acute deterioration or may exacerbate the symptoms of heart failure. Arrhythmias are also a harbinger of severely depressed ventricular function and poor outcome. In one series of 85 pediatric patients hospitalized with myocarditis, 38 (45 percent) had clinically significant arrhythmias, with ventricular arrhythmias and complete heart block being the most common. The presence of arrhythmias conferred an eightfold increase in risk of need for mechanical support, heart transplant, or death [18]. In a study using data from the PHIS database on 2014 children with myocarditis, patients with tachyarrhythmias had a 2.3-fold increase in the odds of death and 58 percent increase in length of stay compared with those without tachyarrhythmias [19].

Since most antiarrhythmic drugs have negative inotropic effects with potential to cause acute hemodynamic instability, these drugs should be used only when the expected benefit exceeds the risk. Consultation with a pediatric cardiologist or a clinician with experience in managing arrhythmias in children is strongly advised.

Our approach is as follows:

●Supraventricular or ventricular arrhythmias associated with acute hemodynamic instability should be converted electrically without delay. (See "Management of supraventricular tachycardia (SVT) in children", section on 'Unstable patients' and "Management and evaluation of wide QRS complex tachycardia in children", section on 'Unstable patient'.)

●Supraventricular arrhythmias, particularly when associated with a rapid ventricular response, may induce or aggravate heart failure. These arrhythmias should be converted promptly, either with drugs or with electrical cardioversion if medical therapy is unsuccessful. An individualized approach is essential because the mechanisms of atrial arrhythmias in acute myocarditis are diverse (they may be automatic or reentrant in nature) and, thus, a single treatment strategy will not work for all patients. Electrical cardioversion and adenosine are generally less effective for terminating automatic atrial arrhythmias (eg, ectopic atrial ectopic tachycardia, focal atrial tachycardia) as compared with reentrant arrhythmias. A limited attempt at vagal maneuvers (Valsalva) may be utilized in stable, cooperative patients but not in unstable patients. In these patients, rapidly moving to more advanced therapy is warranted and is discussed separately. (See "Focal atrial tachycardia", section on 'Acute treatment' and "Management of supraventricular tachycardia (SVT) in children", section on 'Acute management'.)

●High-grade ventricular ectopy should be treated cautiously with antiarrhythmic drugs. All antiarrhythmic drugs have significant side effects, and many have negative inotropic, vasodilatory, or proarrhythmic effects. Therefore, our choice of antiarrhythmic therapy is highly individualized based on patient characteristics. Lidocaine is our preferred agent for treatment of ventricular ectopy in this setting. Although intravenous amiodarone is widely used to treat ventricular ectopy in adults and is included as a first-line therapy in Pediatric Advanced Life Support algorithms, the potential for serious adverse effects such as hypotension and atrioventricular block is considerable [20]. Thus, extreme caution should be used when administering this agent, particularly in young patients. This agent should be used only in collaboration with an experienced clinician. (See "Management and evaluation of wide QRS complex tachycardia in children", section on 'Management'.)

●Complete heart block with compromised cardiac output is an indication for transvenous pacing. This conduction abnormality is often transient. Thus, use of a temporary pacemaker should be the first step. (See "Third-degree (complete) atrioventricular block", section on 'Management'.)

Providing complete mechanical support of the circulation with ECMO or a VAD can be lifesaving in children with acute fulminant myocarditis and hemodynamically significant arrhythmias. Since many patients with fulminant disease recover completely if they can be supported through their acute illness, we use ECMO in the setting of a significant and persistent arrhythmia to allow myocardial recovery and safe pharmacologic therapy for the rhythm disturbance.

Anticoagulation — Practice varies with regard to anticoagulation in children with acute myocarditis. For most patients with mild myocarditis, anticoagulation to prevent venous thromboembolism is not routinely necessary unless there are other indications or additional risk factors (eg, obesity, oral contraceptive use). However, patients with severe ventricular dysfunction are at increased risk for thrombus formation and anticoagulation with aspirin, unfractionated heparin, low molecular weight heparin, direct oral anticoagulant, or warfarin can be considered [21]. There is no standard approach. In our practice, we typically use unfractionated heparin during the acute phase while the patient is in the intensive care unit and then transition to aspirin once the clinical status has improved. Aspirin is continued until ventricular function has improved (eg, left ventricular ejection fraction [LVEF] >40 percent). If thrombus is documented, we typically treat with low molecular weight heparin. (See "Venous thrombosis and thromboembolism (VTE) in children: Treatment, prevention, and outcome" and "Heart failure in children: Management", section on 'Thromboembolism'.)

Immunomodulatory therapy — Data are limited and inconclusive as to whether intravenous immune globulin (IVIG) or glucocorticoids improve outcomes in pediatric myocarditis [2,5]. Nevertheless, IVIG has been used commonly because myocarditis is associated with considerable risk of mortality and morbidity and the risks associated with IVIG are usually small in comparison.

In multicenter observational studies in the United States from the mid-2000s to mid-2010s, approximately 70 percent of pediatric patients with myocarditis were treated with IVIG and 20 to 30 percent received glucocorticoids [6,22]. Similar rates were reported in a nationwide study from Japan [23]. However, use of IVIG and glucocorticoids for children with myocarditis has become more common in the coronavirus disease 2019 (COVID-19) era since these therapies are first-line treatments for patients with COVID-19-related multisystem inflammatory syndrome in children (MIS-C), which often presents similarly to acute myocarditis. Based on the experience using these therapies in COVID-19-related illness, many experts apply this practice to patients with myocarditis due to other etiologies. (See "COVID-19: Multisystem inflammatory syndrome in children (MIS-C) management and outcome", section on 'Immunomodulatory therapy'.)

Intravenous immune globulin — For most children diagnosed with acute myocarditis, we suggest treatment with IVIG. This applies to patients diagnosed based upon clinical findings, cardiac magnetic resonance imaging, or endomyocardial biopsy. We feel that, given the considerable risks of death and morbidity associated with myocarditis, the potential side effects associated with IVIG are justified in this setting. It is reasonable to omit IVIG therapy in patients who are not severely affected.

The dosing for IVIG in this setting is 2 g/kg administered in a single infusion over 8 to 24 hours. In obese patients, the dose should be based upon ideal body weight. For patients with significant cardiac dysfunction, if there is concern that the patient will not tolerate the volume load of the full dose in a single infusion, it can be given in divided doses over two days.

The use of IVIG to treat myocarditis was suggested by its efficacy in other immune-mediated diseases. Randomized-controlled trial data of IVIG for the treatment of myocarditis are limited. A 2020 systematic review identified two small adult trials and one small pediatric trial that were deemed to be at high risk of bias [24]. In the pediatric trial, there was a trend toward improved transplant-free survival, but it did not reach statistical significance [25]. LVEF at hospital discharge was higher in the IVIG group compared with control. The adult trials are discussed separately. (See "Treatment and prognosis of myocarditis in adults", section on 'Intravenous immune globulin'.)

Observational studies on the efficacy of IVIG have reached variable conclusions [6,22,24,26-30]. In a meta-analysis of 13 observational studies (1404 pediatric patients), IVIG therapy was associated with better survival (odds ratio 2.13, 95% CI 1.32-3.43) [30]. However, after adjusting for important confounders, the difference was no longer statistically significant (odds ratio 1.4, 95% CI 0.83-2.35). It is difficult to draw firm conclusions from these retrospective studies since they are highly susceptible to selection bias.

Additional details on IVIG administration, including adverse effects and premedication, are provided separately. (See "Overview of intravenous immune globulin (IVIG) therapy".)

Glucocorticoids — Use of glucocorticoids for the treatment of acute myocarditis is generally limited to patients who are refractory to IVIG and patients in whom myocarditis is associated with systemic autoimmune or inflammatory conditions (eg, COVID-19-related MIS-C, systemic lupus erythematosus). (See "Systemic lupus erythematosus (SLE) in children: Treatment, complications, and prognosis".)

Evidence remains inconclusive on the benefit of glucocorticoid therapy in patients with myocarditis. In a meta-analysis of trials that included children and adults, mortality rates were similar in patients treated with and without glucocorticoids (relative risk 0.93, 95% CI 0.70-1.24) [31]. At one to three months follow-up, the group that received steroids had higher LVEF (mean difference 7.4 percent, 95% CI 4.9-9.8). However, there was a substantial amount of heterogeneity among the studies. In a subgroup analysis of pediatric patients (n = 200), the degree of improvement in LVEF associated with steroid therapy was greater than in the overall cohort (mean difference 9 percent, 95% CI 7.5-10.5).

Observational studies evaluating the efficacy of glucocorticoids in acute myocarditis have reached variable conclusions [32,33]. One study reported that combination therapy with IVIG plus glucocorticoids is associated with recovery of ventricular function and high rates of transplant-free survival [32]. Another study failed to detect a meaningful difference in mortality or cardiovascular complications in patients treated with or without glucocorticoids [33].

Antiviral therapies — Although viral infection is the most common identified cause of myocarditis in children, the efficacy of antiviral therapy for myocarditis is uncertain. Thus, antiviral therapy is not a routine component of treatment for myocarditis in children.

Considerations and evidence regarding antiviral therapy for specific viral infections are discussed in separate topics:

●Enterovirus (see "Enterovirus and parechovirus infections: Clinical features, laboratory diagnosis, treatment, and prevention", section on 'Antiviral therapy for severe cases')

●Adenovirus (see "Diagnosis, treatment, and prevention of adenovirus infection", section on 'Treatment')

●Parvovirus B19 (see "Treatment and prevention of parvovirus B19 infection", section on 'Treatment')

●Cytomegalovirus (see "Overview of cytomegalovirus infections in children", section on 'Treatment')

●Human herpes 6 (see "Human herpesvirus 6 infection in children: Clinical manifestations, diagnosis, and treatment", section on 'Treatment')

●Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) (see "COVID-19: Management in children")

Limited data suggest potential benefit of interferon beta therapy in adult patients with chronic dilated cardiomyopathy (DCM) and confirmed myocardial viral infection [34,35]. However, similar findings have not been reported in children.

CHRONIC MANAGEMENT

Chronic heart disease — For patients who progress from acute myocarditis to chronic heart failure, diuretics, angiotensin-converting enzyme inhibitors, digoxin, beta blockers, and aldosterone inhibitors (ie, spironolactone) are well-accepted therapies and are discussed in greater detail separately. (See "Heart failure in children: Management", section on 'Pharmacologic therapy'.)

Recurrent disease — Some patients may relapse after the first episode, sometimes many years later [3]. Relapses should be managed in a similar manner to the initial episode [3].

ROUTINE FOLLOW-UP ISSUES

Activity — Although data are limited, experts in the field suggest that strenuous physical activity and exercise be restricted in patients with complete resolution of myocarditis for at least six months after the onset of the disease [2,3]. Preparticipation screening should be performed prior to resuming athletic competition. This may entail exercise testing in patients after the acute phase of their disease. (See "Sports participation in children and adolescents: The preparticipation physical evaluation" and "Exercise testing in children and adolescents: Principles and clinical application".)

Patients who continue to have impaired ventricular function may benefit from exercise rehabilitation. (See "Heart failure in children: Management", section on 'Exercise and physical activity'.)

Immunization — Live-virus vaccination may have diminished immunogenicity when given to a child who has recently received intravenous immune globulin (IVIG). Based on the recommendations from the American Academy of Pediatrics, we suggest that immunization with live vaccine be delayed for 11 months for children who receive IVIG for myocarditis [36]. For patients undergoing heart transplant, live vaccines should be given prior to transplantation, despite concerns of decreased efficacy, given that live vaccines are contraindicated with the administration of immunosuppressive therapy following transplantation. (See "Measles, mumps, and rubella immunization in infants, children, and adolescents", section on 'Recent receipt of blood or immune globulin'.)

PROGNOSIS — Studies examining outcomes in children with myocarditis are limited by small numbers of patients, limited duration of follow-up, variability in case definition (biopsy confirmed versus clinical diagnosis), and inclusion of patients with other diagnoses (eg, dilated cardiomyopathy [DCM]). Based on the available evidence, it appears that the risk of morbidity and mortality is greatest during the acute illness. Most survivors recover ventricular function without long-term cardiac impairment (including arrhythmias), though a small subset develop DCM [18,26,37-40].

●Mortality – Reported mortality rates during the acute illness for children with myocarditis range from 6 to 14 percent [6,17,19,27,37,38,41,42]. Late deaths are uncommon, occurring in <5 percent of patients [17,42]. Most late deaths are due to persistent ventricular dysfunction, heart failure, or complications following heart transplantation [42].

Factors associated with increased risk of death include [6,15,19,22,42-47]:

•Fulminant presentation

•Severely depressed left ventricular function (eg, left ventricular ejection fraction [LVEF] <30 percent or fractional shortening Z-score <-2)

•Need for mechanical support (extracorporeal membrane oxygenation [ECMO] or ventricular assist device [VAD])

•Need for intravenous inotropic therapy (eg, milrinone, dopamine, and dobutamine)

•Tachyarrhythmias

•Peak B-type natriuretic peptide level >10,000 pg/mL

●Heart transplantation – Approximately 5 to 20 percent of children with acute myocarditis require heart transplantation [6,22,42]. Risk factors are similar to the mortality risk factors listed above. Severely affected patients often require mechanical support (ECMO or VAD) as a bridge to transplant. (See 'Decompensated heart failure/cardiogenic shock' above.)

It is unclear if patients with myocarditis are at risk for poor outcome following transplantation compared with children who undergo cardiac transplantation for other reasons (eg, DCM, congenital heart disease [CHD]). Compared with children with idiopathic DCM, patients with myocarditis may have more severe heart failure and require a greater degree of hemodynamic support at the time of transplant (including inotropes and in some cases, mechanical support) [48]. In a registry study that evaluated transplant outcomes in 221 children with myocarditis and 1583 children with idiopathic DCM, after adjustment for severity of illness, myocarditis was not independently associated with waitlist mortality or post-transplant graft loss [48]. Another registry study evaluating transplant outcomes in 709 patients with myocarditis and 1631 patients with CHD found that graft survival varied with age [49]. Among patients with myocarditis, median graft survival was 14.1 years for school-age children (6 to 12 years old) and 6.9 years for adolescents (13 to 18 years old). Among patients with CHD, median graft survival was 9 years for school-age children and 7.4 years for adolescents.

●Long-term morbidity – Though most children ultimately have complete or partial recovery of left ventricular function, a subset of patients develop chronic DCM [37-39,41,42,50,51]. Recovery of cardiac function tends to be gradual, occurring over months to years.

Most patients have evidence of ongoing left ventricular dysfunction at the time of discharge from the hospital. In a retrospective multicenter study of 171 children with acute myocarditis diagnosed from 2008 to 2012, 55 percent were discharged on heart failure medications and 16 percent were readmitted to the hospital for heart failure symptoms during the first year following discharge [22]. In a report of 372 children with myocarditis, 53 percent had normal echocardiographic parameters at three years after presentation [42]. In another study of 70 children with myocarditis who were treated with immunomodulatory therapy, the rate of complete recovery of ventricular function at a median follow-up of six years was 70 percent [37].

In a small series of 36 children with histologically confirmed myocarditis with median follow-up of 19 months, approximately one-half of patients recovered normal left ventricular function within three months [38]. None of the survivors reported cardiac symptoms or restrictions in physical activity, and none required antiarrhythmic treatment.

Patients who do not fully recover cardiac function may develop DCM. DCM is preceded by myocarditis in 27 to 40 percent of cases in children [50,51].

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Heart failure in children" and "Society guideline links: Myocarditis" and "Society guideline links: Acute rheumatic fever and rheumatic heart disease".)

INFORMATION FOR PATIENTS — UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." The Basics patient education pieces are written in plain language, at the 5^th to 6^th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10^th to 12^th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.

Here are the patient education articles that are relevant to this topic. We encourage you to print or email these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient education" and the keyword[s] of interest.)

●Basics topic (see "Patient education: Myocarditis (The Basics)")

SUMMARY AND RECOMMENDATIONS

●Setting of care – Children with myocarditis are at risk for considerable morbidity and mortality. All patients require ongoing cardiorespiratory monitoring since the hemodynamic status of the patient may quickly deteriorate. Children who present with severely depressed ventricular function or rhythm disturbances should be cared for in a pediatric intensive care unit. (See 'Overview' above.)

●Acute management – Acute management includes the following (see 'Acute management' above):

•Supportive care – Initial supportive treatment consists of supplemental oxygen and careful fluid resuscitation. (See 'Hemodynamic support' above.)

•Management of ventricular dysfunction – Children with mild heart failure symptoms can generally be managed with oral diuretics and afterload-reducing agents (eg, angiotensin-converting enzyme [ACE] inhibitors). (See 'Medical therapy for heart failure' above and "Heart failure in children: Management", section on 'Pharmacologic therapy'.)

Children with more severe presentations (ie, decompensated heart failure or cardiogenic shock) may require intravenous inotropic support, positive pressure ventilation, and even mechanical circulatory support (eg, extracorporeal membrane oxygenation [ECMO] or a ventricular assist device [VAD]). (See 'Decompensated heart failure/cardiogenic shock' above.)

•Arrhythmia management – All children with acute myocarditis should be monitored for arrhythmias. Loss of sinus rhythm may lead to acute deterioration or may exacerbate the symptoms of heart failure. Because most antiarrhythmic drugs have negative inotropic effects and may aggravate heart failure, the management of patients who experience cardiac arrhythmias including choice of interventions should be performed in consultation with a clinician experienced in managing cardiac arrhythmias in children. (See 'Arrhythmia management' above.)

•Immunomodulatory therapy – For most children with acute myocarditis (diagnosed on the basis of clinical findings, cardiac magnetic resonance imaging, or endomyocardial biopsy), we suggest treatment with intravenous immune globulin (IVIG) (Grade 2C). The dose of IVIG for this indication is 2 g/kg over 8 to 24 hours. (See 'Intravenous immune globulin' above.)

We generally reserve glucocorticoid therapy for myocarditis that is refractory to IVIG or associated with systemic autoimmune or inflammatory diseases. (See 'Glucocorticoids' above.)

●Management of chronic heart failure – For patients who progress from acute myocarditis to chronic heart failure, well-accepted therapies include diuretics, ACE inhibitors, beta blockers, mineralocorticoid receptor antagonists, and digoxin. These are discussed in greater detail separately. (See "Heart failure in children: Management", section on 'Pharmacologic therapy'.)

●Follow-up issues

•Activity restrictions – For most patients recovering from myocarditis, strenuous physical activity is restricted for at least six months. Preparticipation screening should be performed prior to resuming athletic competition. (See 'Activity' above.)

•Immunizations – Immunization with live vaccine should be delayed for 11 months for children who have received IVIG (with the exception of children undergoing heart transplant, in whom live vaccines should be given prior to transplantation). (See "Measles, mumps, and rubella immunization in infants, children, and adolescents", section on 'Recent receipt of blood or immune globulin'.)

●Prognosis – In the contemporary era, mortality associated with myocarditis in children is approximately 5 to 10 percent. Approximately 5 to 20 percent of patients require cardiac transplantation. Most survivors recover ventricular function without long-term cardiac impairment, though a small subset develop dilated cardiomyopathy (DCM). (See 'Prognosis' above.)