What does this research mean for the field?

Current evidence does not support the routine use of immunosuppression in traditional lymphocytic myocarditis, as it does not significantly improve left ventricular ejection fraction, though combined therapy may benefit high-risk, virus-negative patients. Novelty: ClaimNovelty.SYNTHESIS. Consensus alignment: ConsensusAlignment.CHALLENGES_CONSENSUS.

June 3, 2018Open Access

Immunomodulatory treatment for lymphocytic myocarditis—a systematic review and meta-analysis

MWMax‐Paul WinterGoethe University Frankfurt PSPatrick SulzgruberGeneral Cardiology LKLorenz KollerMedical University of Vienna

Structured PICO

Does immunomodulatory treatment improve left ventricular ejection fraction in patients with endomyocardial biopsy-proven lymphocytic myocarditis and LVEF < 45%?

Population

612 patients across 9 randomized controlled trials with endomyocardial biopsy (EMB)-proven traditional lymphocytic myocarditis and at least moderately decreased left ventricular ejection fraction (LVEF < 45%).

Intervention

Immunomodulatory treatments at any dose targeting the cause of myocarditis, including corticosteroids alone, combination of immunosuppressants (azathioprine or cyclosporine) and corticosteroids, intravenous immunoglobulin (IVIG) alone, immunoadsorption + IVIG, statins (atorvastatin), or interferon/thymomodulin.

Comparator

Standard heart failure therapy with or without placebo.

Outcome

Change in left ventricular ejection fraction (LVEF) measured by echocardiography or scintigraphy.surrogate

Current evidence does not support the routine use of immunosuppression in traditional lymphocytic myocarditis, as combined therapy did not significantly improve LVEF, though selected high-risk patients with virus-negative myocarditis might benefit.

Abstract

Deleterious inflammatory responses are seen to be the trigger of heart failure in myocarditis and therapies directed towards immunomodulation have been assumed to be beneficial. The objective of the present review was to systematically assess the effect of immunomodulation in lymphocytic myocarditis. Studies were included if diagnosis of lymphocytic myocarditis was based on EMB as well as on the exclusion of other etiologies of heart failure and if the patients had at least moderately decreased left ventricular ejection fraction (< 45%). All immunomodulatory treatments at any dose that target the cause of myocarditis leading to cardiomyopathy were included. Retrieval of PUBMED, SCOPUS, Cochrane Central Register of Controlled Trials, and LILACs from January 1950 to January 2016 revealed 444 abstracts of which nine studies with a total of 612 patients were included. As primary effectivity endpoint, a change in left ventricular ejection was chosen. No benefits of corticosteroids or intravenous immunoglobulin alone were reported. Immunoadsorption and subsequent IVIG substitution was associated with a greater improvement in left ventricular ejection fraction (LVEF) in one study. Single studies found a beneficial effect of interferon and statins on LVEF. We performed a meta-analysis for the combination of corticosteroids with immunosuppressants and found a non-significant increase of LVEF of + 13.06% favoring combined treatment (95%CI 1.71 to + 27.84%, p = 0.08). The current evidence does not support the routine use of immunosuppression in traditional lymphocytic myocarditis. Nevertheless, in histologically proven virus-negative myocarditis of high-risk patients, combined immunosuppression might be beneficial. Future research should focus on translation of these effects to clinical outcome.

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