Approach

The mainstay of therapy for myocarditis is supportive care and conventional heart failure therapy.[15][55][57][58]​​​[75]​​ 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.[70] Treatment is therefore aimed at management of both the cardiomyopathy and myocarditis in those patients with concomitant cardiomyopathy.[76]​ ​

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.[77] An intra-aortic balloon pump or left ventricular assist device (LVAD) may be required as a bridge to recovery or heart transplantation.[57][78]​ 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 LV dysfunction should avoid exercise.[21]

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.[79]

  • 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.[80]

SGLT2 inhibitor:

  • SGLT2 inhibitors are recommended for adults who have been hospitalised with heart failure, once they are clinically stable.[81] 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.[57][82]

  • Pre-clinical studies suggest an anti-inflammatory role for SGLT2 inhibitors in myocarditis.[83][84]​​

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.[77] 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.[57]

  • 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.[85][86]

  • 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.[57]

  • Eplerenone is not recommended in children.

Diuretic:

  • Diuretics improve haemodynamics and patient comfort.[57]

  • 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.[57] 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.[57]

  • Warfarin is appropriate to reduce risk in both children and adults.

Immunosuppressive therapies and intravenous immunoglobulin (IVIG)

Because the long-term myocardial changes associated with myocarditis seem to be mediated by abnormal cellular and humoral immune activation, it is hypothesised that immunosuppression should be an effective form of treatment. Despite this rationale, immune suppression trials aimed at attenuating the inflammatory response in myocarditis in adults have been largely disappointing. Well-designed prospective randomised controlled trials (RCTs) involving immune suppression with corticosteroids with or without ciclosporin or azathioprine for the treatment of biopsy-confirmed myocarditis showed no long-term improvement in LV ejection fraction (LVEF) or survival benefit.[87][88]

Similarly, the use of IVIG for treatment of acute myocarditis has been evaluated in several small studies. An RCT of patients with newly diagnosed acute dilated cardiomyopathy found no benefit in mortality or improvement in LVEF in those treated with IVIG as compared with standard care.[89] This lack of benefit persisted in those patients with biopsy-confirmed myocarditis. A Cochrane review evaluating IVIG for presumed viral myocarditis in children and adults could not draw certain conclusions about its efficacy due to paucity of data.[90] Compared to adults, IVIG is used very frequently in paediatric patients with myocarditis. In one multicentre study, IVIG was used as a therapeutic agent in 51% of children admitted with mild cardiac dysfunction, and in 88% of those admitted with moderate or worse function.[24]

Overall, standard immunosuppressive regimens and IVIG cannot be recommended for the routine treatment of myocarditis due to lack of robust evidence. The decision to use them or not should be determined on a case-by-case basis. Exceptions to this include patients with giant cell myocarditis or myocarditis secondary to autoimmune diseases; both of these patient populations have been shown to benefit from aggressive early immune suppression.[33]​​[91]

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.

  • For the most part, immunosuppressive therapy has been shown to be ineffective in viral myocarditis.[92] [ Cochrane Clinical Answers logo ] There are insufficient data to support a benefit of intravenous gamma globulin.[90] Novel therapies with immune-modulating drugs such as interferon-beta have shown great promise in phase II trials.[93]

  • 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 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).

Giant cell myocarditis

  • 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 giant cell myocarditis 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][91][94]

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 mofetil are promising.

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.[95]

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.

Use of this content is subject to our disclaimer