Myocarditis

Overview 
Theory 
Diagnosis 
Management 
Follow up 
Resources 

The mainstay of therapy for myocarditis is supportive care and conventional heart failure therapy.[15][58][59][60][79] There can be considerable overlap between dilated cardiomyopathy and myocarditis; as many as 16% of patients presenting with acute dilated cardiomyopathy who undergo endomyocardial biopsy are found to have biopsy-confirmed myocarditis.[74] Treatment is therefore aimed at management of both the cardiomyopathy and myocarditis in those patients with concomitant cardiomyopathy.[80]

Haemodynamically unstable with or without cardiogenic shock

A small proportion of patients with acute myocarditis will present with fulminant heart failure, sustained ventricular arrhythmias, or cardiogenic shock requiring invasive haemodynamic monitoring and aggressive pharmacological therapy.[21] A pulmonary artery catheter may be inserted to help optimise cardiac filling pressures and for rapid titration of cardiovascular therapies. Pharmacological therapy for adults may include vasodilators such as sodium nitroprusside, vasopressors such as noradrenaline (norepinephrine), and positive inotropes such as dobutamine.[81] An intra-aortic balloon pump or left ventricular assist device (LVAD) may be required as a bridge to recovery or heart transplantation.[59][82] In children, inotropic support may be provided by milrinone or dobutamine, with early escalation to mechanical circulatory support (such as LVAD or extracorporeal membrane oxygenation [ECMO]) if required.[15]

Haemodynamically stable with left ventricular (LV) systolic dysfunction

An ACE inhibitor, angiotensin-II receptor antagonist, or sacubitril/valsartan should be started as early as possible. A sodium-glucose cotransporter-2 (SGLT2) inhibitor is recommended once the patient is stable. Diuretic therapy, vasodilators, and inotropes are used in both the acute and chronic setting with the goal of optimising intracardiac filling pressures and increasing cardiac output. Long-term anticoagulation therapy may be needed to reduce risk of stroke or other arterial embolism. Patients with symptomatic myocarditis should refrain from exercise for 3-6 months.[21][56]

ACE inhibitor, angiotensin-II receptor antagonist, or sacubitril/valsartan:

In addition to the demonstrated efficacy in chronic heart failure, animal studies suggest that when started early in the course of acute myocarditis, renin-angiotensin antagonists improve survival and inhibit progression to dilated cardiomyopathy.[83]
The efficacy of sacubitril/valsartan for the treatment of heart failure has been well documented, and may be superior to ACE inhibitors, although data specifically for myocarditis are lacking. Sacubitril is a neprilysin inhibitor.[84]

SGLT2 inhibitor:

SGLT2 inhibitors are recommended for adults who have been hospitalised with heart failure, once they are clinically stable.[85] SGLT2 inhibitors are recommended in adults with symptomatic chronic heart failure, regardless of the presence of diabetes, to reduce cardiovascular mortality and hospitalisation for heart failure.[59][86]
Pre-clinical studies suggest an anti-inflammatory role for SGLT2 inhibitors in myocarditis.[87][88]

Vasodilator or inotrope:

Oral arterial (hydralazine) and venous (nitrates such as isosorbide dinitrate) vasodilators acutely improve cardiac output and decrease pulmonary and LV filling pressures.[81] This combination of therapy may also reduce morbidity and mortality in patients with heart failure who cannot tolerate ACE inhibitors, angiotensin-II receptor antagonists, or sacubitril/valsartan.[59]
Oral hydralazine and nitrates are rarely used in paediatric care. If vasodilators are required in children, ACE inhibitors and related agents are often most appropriate.
Milrinone (a parenteral positive inotrope and vasodilator) is often used early in the treatment course in children with evidence of left ventricular systolic dysfunction, even if they are haemodynamically stable. Milrinone may cause hypotension or, rarely, ventricular arrhythmias.

Beta-blocker:

Similarly, beta-blockers (e.g., carvedilol, metoprolol, bisoprolol) should be started once the patient is no longer in acutely decompensated heart failure
In animal models of acute myocarditis, the early initiation of beta-adrenergic blockers has been shown to reduce myocardial inflammation.[89][90]
Carvedilol is often the preferred beta-blocker in children.

Aldosterone antagonist:

An aldosterone antagonist (e.g., spironolactone, eplerenone) should be started in patients with New York Heart Association class II to IV heart failure.[59]
Eplerenone is not recommended in children.

Diuretic:

Diuretics improve haemodynamics and patient comfort.[59]
Volume status should be monitored.
Dual therapy with a thiazide (or thiazide-like) diuretic (e.g., hydrochlorothiazide, chlorothiazide, metolazone) and a loop diuretic (e.g., furosemide) may be required in some patients for augmented therapeutic effect.[59] The thiazide diuretic should be administered at the same time as or 30 minutes prior to the loop diuretic.

Anticoagulant:

Patients with left ventricular antero-apical akinesis or aneurysm as a result of cardiomyopathy are at increased risk for stroke or other arterial embolism secondary to left ventricular thrombus formation.[59]
Warfarin is appropriate to reduce risk in both children and adults.

Immunosuppressive therapies and intravenous immunoglobulin (IVIG)

Immunosuppressive therapy is recommended for select patients with symptomatic myocarditis, particularly those with histologically confirmed, non-infectious immune-mediated conditions such as eosinophilic myocarditis, giant cell myocarditis (GCM), cardiac sarcoidosis, or associated systemic immune diseases.[1] While expert consensus on the use of immunosuppressive therapy remains variable, some evidence supports its application in lymphocytic myocarditis when endomyocardial biopsy (EMB) tests negative for viral DNA. This includes the findings of the TIMIC trial, which investigated immunosuppressive therapy in virus-negative inflammatory cardiomyopathy, and various single-centre studies.[91][92][93] In one propensity-weighted observational study, patients with biopsy-confirmed autoimmune myocarditis who underwent tailored long-term immunosuppressive therapy demonstrated comparable 5-year rates of mortality and heart transplant, despite having a higher-risk profile at baseline.[92]

A multidisciplinary team, including rheumatologists, is typically involved in managing complex inflammatory responses and mitigating drug-related adverse effects. Standard treatment often begins with high-dose intravenous methylprednisolone, followed by oral prednisolone, with subsequent tapering and the addition of corticosteroid-sparing agents. Specific treatment depends on the underlying cause and disease severity. When myocarditis presents with concurrent systemic inflammation, therapy should be adjusted to address multiple organ involvement.

One practice survey recommends viral polymerase chain reaction (PCR) testing of EMB samples before initiating immunosuppressive therapy to avoid exacerbating active infections.[94] However, given the lack of standardised protocols for viral PCR testing in many centres, referral to specialised myocarditis teams may be warranted. Evolving antiviral therapies offer alternative treatment options for viral myocarditis, emphasising the importance of consulting infectious disease specialists for appropriate management.

Additionally, IVIG may be beneficial for inflammatory or autoimmune-mediated myocarditis. It is more commonly used in paediatric patients than in adults, with a multicentre study reporting its administration in 51% of children with mild cardiac dysfunction and 88% of those with moderate-to-severe impairment. However, its use, along with corticosteroids, was not associated with mortality or heart transplantation in this study.[24]

Therapy targeted at specific cause of myocarditis

Lymphocytic (viral) myocarditis

Lymphocytic myocarditis is primarily treated with supportive care and standard heart failure therapies. As with all aetiologies of myocarditis, patients presenting with fulminant heart failure and cardiogenic shock may require invasive haemodynamic monitoring, aggressive therapy with intravenous diuretics or inotropes, and even mechanical haemodynamic support devices. Given the high rate of recovery, aggressive therapy is recommended, especially early in the course of the disease.
Some evidence supports the use of immunosuppressive therapy for lymphocytic myocarditis when EMB tests negative for viral DNA, but expert consensus remains variable.[91][92][93]
For the most part, immunosuppressive therapy has been shown to be ineffective in viral myocarditis.[95] [ ] Novel therapies with immune-modulating drugs such as interferon-beta have shown great promise in phase II trials.[96]
For those with documented influenza, antiviral agents may be beneficial. In those with SARS-CoV-2 infection, similarly, antiviral agents as well as monoclonal antibodies (if recommended in your region) may be used. For more information on the treatment of influenza infection and SARS-CoV-2 infection, see Influenza infection and Coronavirus disease 2019 (COVID-19).

GCM

This is a rare and rapidly progressive disease that is probably the most fatal of all causes of myocarditis.[9] Life-threatening ventricular arrhythmias are seen in 14% of patients with GCM at first presentation, progressing to refractory arrhythmias in more than half of the patients.[21] Although aggressive immunosuppressive regimens have been shown to only modestly improve survival, limited data suggest that it prolongs life sufficiently to enable more effective treatment with heart transplantation.[10][97][98]
For adults, standard immunosuppressive therapy for GCM typically includes intravenous methylprednisolone followed by a gradual tapering of prednisolone over 6-8 weeks. This regimen is often combined with either antithymocyte globulin (ATG) or alemtuzumab, along with ciclosporin.[99] Alternative options may include high-dose corticosteroids combined with either ciclosporin or tacrolimus plus azathioprine or mycophenolate.[99][100] High-dose corticosteroids plus ATG are commonly used for patients with recurrent disease and LV dysfunction.[99] A similar approach to immunosuppressive therapy may be used for children with GCM, but note that alemtuzumab is not approved for use in children and studies only support its use for GCM in adults.

Autoimmune-related myocarditis

Patients with myocarditis due to systemic autoimmune diseases generally have a significant response to aggressive immunosuppressive regimens including systemic corticosteroids. Animal studies with immune-modulating therapies such as rapamycin and mycophenolate are promising.[101]

Hypersensitivity myocarditis

Hypersensitivity myocarditis is thought to be related to an allergic reaction to a variety of drugs. With the removal of the offending agent and treatment with systemic corticosteroids, clinical improvement is the rule.[102]

Chagasic myocarditis

Chagas' disease is the most common cause of myocarditis in the world. Patients with chagasic myocarditis should be treated with an appropriate antiparasitic agent; see Chagas' disease for detailed information on management. Heart failure treatment of this disease is mainly symptom management. A permanent pacemaker with defibrillator is often necessary because of conduction abnormalities and ventricular arrhythmias. Immunosuppressive therapy is controversial; heart transplantation is often necessary for refractory heart failure.[33]

Immune checkpoint inhibitor (ICI)-related myocarditis[32]

The ICI should be discontinued immediately and treatment with high-dose intravenous methylprednisolone commenced. This can be switched to a weaning dose of oral prednisolone if patients show ongoing signs of clinical improvement. Corticosteroid-refractory patients or haemodynamically unstable patients with fulminant myocarditis should be treated with second-line immunosuppressive therapies. Various second-line agents are under investigation (e.g., mycophenolate, abatacept, IVIG) and specialist guidance is recommended. After recovery, a multidisciplinary team should review whether ICI therapy should be restarted.

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