Immunosupressive therapy in myocarditis: background for use in clinical practice

Abstract

The aim – to evaluate the efficacy and safety of immunosuppressive glucocorticoid therapy in patients with myocarditis.
Materials and methods. 145 patients with myocarditis who in accordance with the presence of preserved (> 40 %) or reduced (≤ 40 %) left ventricular (LV) ejection fraction (EF) were divided into 2 groups: the 1st group included 90 patients with myocarditis and reduced LV EF who were characterized by severe course of disease; the 2nd group consisted of 55 patients with myocarditis and preserved LV EF. Depending on the immunosuppressive therapy, patients in groups 1 and 2 were divided into subgroups 1A (50 patients) and 2A (30 patients) in which glucocorticoids (GC) were not used, and 1B (40 patients) and 2B (25 patients) who underwent a 6-month course of GC treatment. Patients of 1B and 2B subgroups received methylprednisolone at a dose of 0.25 mg/kg per day or prednisolone at a comparable dose for 3 months, followed by a gradual dose reduction by 1 mg per week until complete discontinuation of the drug after 6 months from the start of treatment. The analyses of the results of examinations were performed in the 1st month from the debut of myocarditis before the prescription of GC, after 6 and after 24 months of observation. All patients underwent comprehensive clinical examination, Holter ECG monitoring, echocardiography, cardiac magnetic resonance imaging, and immune status studies. After 24 months of observation, the incidence of cardiovascular events and adverse events of GC therapy was evaluated.
Results and discussion. In patients of 1B subgroup after 6 months we observed an improvement of the LV contractile function (an increase in the EF value by 19.1 %, longitudinal global systolic deformation – by 27.2 %), and a decrease in its end-diastolic volume (by 20.1 %) on the background of decrease in the number of LV segments in which inflammatory changes were found, as also a decrease in the content of proinflammatory cytokines and cardiospecific autoantibodies compared with patients in subgroup 1A. In patients of 2B subgroup GC treatment was not associated with an improvement in contractility and LV volumes or decrease in the frequency of rhythm and conduction disturbances, and in the number of LV segments affected by inflammatory and fibrotic changes after 6 months of follow-up compared with 2A subgroup patients. However typical for GC side effects (obesity in 12.0 %, hypertension in 8.0 %, diabetes in 8.0 %, erosive lesions of the stomach and gastrointestinal bleeding in 16.0 %, functional hypercorticism in 36.0 % cases) were documented within 24 months of their application. According to multivariate regression analysis, predictors of the immunosuppressive therapy effectiveness for the presence of LV EF > 40 % after 6 months of treatment in patients with severe acute myocarditis were established: values of longitudinal and circumferential global systolic LV strain ≥ 8.0 % and ≥ 7.5 %, respectively, absence of delayed contrast enhancement during cardiac MRI, level of expression of type 2 toll-like receptors ≥ 8 CIF and type 4 toll-like receptors ≥ 15 CIF.
Conclusions. The use of GC immunosuppressive therapy may be appropriate in patients with severe acute myocarditis with decreased LV EF in order to reduce LV volume indexes and improve its contractile function after 6 months of observation. In patients with preserved LV EF the use of GC in routine clinical practice is not advisable as their use is not associated with improvement of the structural and functional heart condition or reducing the frequency of heart rhythm and conduction, but instead leads to the appearance of typical side effects.