Myocarditis medical therapy


 * Associate Editor(s)-In-Chief: Varun Kumar, M.B.B.S.

Overview
Insofar as most viral infections cannot be treated with directed therapy, symptomatic treatment is the mainstay of therapy for patients with viral myocarditis. Supportive therapy includes diuretics and inotropes for left ventricular failure. ACE inhibitor therapy may aid in left ventricular remodeling after the inflammation has begun to resolve. in patients with fulminant myocarditis, placement of an intra-aortic balloon pump or a left ventricular assist device may be necessary as bridge to recovery.

According to 2010 HFSA guidelines, routine use of immunosuppressive therapies in management of myocarditis is not recommended (Strength of Evidence A). Immunotherapy is beneficial in giant cell myocarditis. Finally, cardiac transplantation can be performed in patients with severe myocarditis who fail to recover.

Bacterial infections are treated with antibiotics the selection of which is based upon the nature of the pathogen and its sensitivity to antibiotics.

Lymphocytic Myocarditis

 * Lymphocytic myocarditis is usually of viral origin . Animal studies have demonstrated better outcomes in viral myocarditis with the use of antiviral agents and interferon early in the course of infection prior to inoculation . The use of antiviral therapy may be limited since patients with viral myocarditis are usually not seen in the early stages. However, it may be used in acute, fulminant myocarditis and in institutional outbreaks. In a series, 6 months of beta interferon in patients with myocarditis secondary to enterovirus or adenovirus infection resulted in elimination of viral genomes in all patients and improvement of LV function in 68% of the patients.


 * Immunotherapy was thought to be a treatment option for myocarditis as they suppress the activity of immunologic agents mediating myocardial inflammation. 2 randomized trials reported that there were no significant change in mortality rate with immunotherapy . However, improvement in LV function was noted in patients with chronic inflammatory dilated cardiomyopathy  . Heart failure society of America recommends against the routine use of immunosuppressive agents in treatment of myocarditis.


 * Intravenous immunoglobulin (IVIG) is known to have both antiviral and immunologic properties. However, its use in treatment of myocarditis has not yet been established as of yet. In a small placebo-controlled trial, there was no significant differences in survival or improvement of LV ejection fraction among patients receiving IVIG or placebo at 6 and 12months . Few case reports and series suggest improvement of cardiac function with use of IVIG in patients with myocarditis. A dramatic clinical improvement was noted in two children with fulminant myocarditis with 10 hour infusion of high-dose IVIG . In another series, a tendency towards improved 1 year survival among 21 children with myocarditis was demonstrated with the use of high-dose IVIG . A recent multicentric nonconcurrent cohort study which analyzed 216 myocarditis patients reported that the IVIG did not affect survival rates, even in patients with extreme illness scores . As illustrated above, a systematic review concluded that there are isufficient data from methodologically strong studies to recommend routine use of IVIG in patients with myocarditis and emphasized the need of future randomized studies that take into account the etiology of acute myocarditis.


 * NSAIDs in myocarditis may actually worsen the condition as they inhibit the natural healing process, and may exacerbate inflammatory process .  NSAIDs have been associated with an increased risk of mortality in animal models of myocarditis  and hence are not recommended.

Giant Cell Myocarditis
Giant cell myocarditis is a rare form of myocarditis and is generally associated with a poor prognosis. Immunosuppressive therapy directed at T-cells may be beneficial as T-cells mediate myocardial inflammation. In a non-randomized series, 22 patients with giant cell myocarditis who were treated with corticosteroids and cyclosporine/azathioprine, survived for an average of 12.3 months. In contrast, those patients who were not treated with immunosuppressants survived for an average of 3 months. Use of immunosuppressive therapy was further strengthened by a prospective, multicenter observational study which reported an improved survival of 6 years among patients receiving high dose steroids and cyclosporine with or without muromonab-CD3. Of the 11 patients studied, two patients underwent cardiac transplantation early in the course of the study and one patient died. The study also reported that withdrawal of immunosuppression was associated with a recurrence of giant cell myocarditis in some patients which in some cases was fatal.

Cardiac transplantation is sometimes required to treat refractory giant cell myocarditis. However, the condition can recur in post-transplant patients. Recurrence of biopsy proven giant cell myocarditis between 3 weeks to 9 years was observed in 9 of 34 cardiac transplant patients.

Eosinophilic Myocarditis
Eosinophilic myocarditis as described before, can occur secondary to hypersensitivity to drugs, parasitic infestation or hypereosinophilic syndrome. The eosinophils which infiltrate the myocardium, degenerate leading to extracellular release of eosinophil granules which can contribute to death of myocytes. Usage of immunosuppressants such as high dose steroids (after excluding infections) and removal of offending drug (in drug induced hypersensitivity) is known to be beneficial in treatment of eosinophilic myocarditis. Immuno therapy may be tapered gradually after 1 year if normal cardiac function and cardiac enzymes levels are restored.

Autoimmune Myocarditis
Myocarditis can develop in autoimmune diseases such as celiac disease and sarcoidosis. Treatment with gluten-free diet and immunosuppressants in celiac disease improves cardiac function. Corticosteroids are found to be beneficial in patients with sarcoidosis related myocarditis, particularly during initial stages of the disease before development of extensive fibrosis of myocardium.

Treatment of Heart Failure
As heart failure in patients with myocarditis has poor prognosis, it is important to prevent progression or worsening of cardiac dysfunction. These patients should be treated with low sodium intake, diuretics and ACE inhibitors. Few animal studies report that mortality rate is high with digoxin in comparison to beta blocker in viral myocarditis. Studies have also demonstrated that usage of carvedilol during recovery phase decreases expression of several histochemicals and subsequently myocardial inflammation and there by improving survival. The Beta-blockers should however be avoided in the acutely decompensating phase of illness.

If heart failure or cardiogenic shock does not respond to medical therapy, circulatory support with an intraaortic balloon pump should be considered which could be used in fulminant myocarditis as a bridge to spontaneous recovery. Implantation of ICD in severe heart failure should be deferred for several months to allow sufficient time for recovery of ventricular function. Following the initial circulatory stabilization, further treatment of cardiac dysfunction should follow current ACC/AHA recommendations. Anticoagulation may be considered in patients with severe/chronic heart failure as they are at risk for developing thromboembolic complications.

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Treatment of Arrhythmia
Arrhythmias or conduction abnormalities can occur in patients with myocarditis. Treatment should be initiated only if arrhythmias are symptomatic or sustained. Caution should be observed while using antiarrhythmics as majority of these agents have negative inotropic property which may worsen heart failure. Regular monitoring with ECG is important as it enables early detection and treatment of asymptomatic yet life threatening arrhythmias.

Supraventricular tachycardia(SVT) can aggravate heart failure. Symptomatic and sustained SVT should be immediately converted electrically. While, patients with recurrent sustained SVT should be treated with antiarrhythmics and rate controlling agents. Implantation of ICD should be considered in patients with recurrent ventricular arrhythmia refractory to medical therapy.

Myocarditis patients presenting with conduction abnormalities, particularly Mobitz type II and complete heart block require temporary pacemaker usually during the acute phase. Implantation of permanent pacemaker or ICD may be necessary in few patients.

===Relevant ACC/AHA/ESC 2006 Guidelines for Management of Patients with Ventricular Arrhythmias and the Prevention of Sudden Cardiac Death === Class I

1. Temporary pacemaker insertion is indicated in patients with symptomatic bradycardia and/or heart block during the acute phase of myocarditis. (Level of Evidence: C)

Class IIa

1. ICD implantation can be beneﬁcial in patients with life-threatening ventricular arrhythmias who are not in the acute phase of myocarditis, as indicated in the ACC/AHA/NASPE 2002 Guideline Update for Implantation of Cardiac Pacemakers and Antiarrhythmia Devices who are receiving chronic optimal medical therapy, and who have reasonable expectation of survival with a good functional status for more than 1 year. (Level of Evidence: C)

2. Antiarrhythmic therapy can be useful in patients with symptomatic NSVT or sustained VT during the acute phase of myocarditis. (Level of Evidence: C)

Class III

1. ICD implantation is not indicated during the acute phase of myocarditis. (Level of Evidence: C)