The effectiveness of azathioprine in the treatment of patients with severe myocarditis: the single center experience

Abstract

The aim – to evaluate the efficacy of combined immunosuppressive therapy with azathioprine and methylprednisolone in patients with severe myocarditis who did not improve left ventricular (LV) systolic function after 6 months of glucocorticoid (GC) therapy.
Materials and methods. The study included 26 patients with chronic myocarditis, disease duration of more than 6 months and lack of efficacy of previous GC administration: functional class (FC) of HF remained at level II or higher, LV ejection fraction (EF) remained <40% at the time of inclusion in the study. All patients on the background of HF therapy according to modern standards were prescribed combined immunosuppressive therapy: azathioprine at a dose of 1 mg/kg of body weight for 6 months in combination with methylprednisolone at a dose of 0.25 mg/kg per day for 3 months with a gradual dose reduction of 1 mg per week until complete drug withdrawal 6 months after the start of treatment. Determination of the content of immunological biomarkers in the blood, cardiac magnetic resonance imaging (CMR) with intravenous contrast, transthoracic echocardiography and a 6-minute walk test were performed before the appointment of combined immunosuppressive therapy and after 6 months of treatment.
Results. Before the appointment of combined immunosuppressive therapy, the average number of LV segments in which signs of inflammation were determined in the form of early contrast and/or T2 signal intensity enhancement was 7.25±0.36 segments, and the number of segments with fibrotic myocardial damage was 5.81±0.32 on average. After 6 months, inflammatory changes were detected only in 2.20±0.17 LV segments, while the volume of fibrotic LV damage did not significantly change compared to the initial examination. When analyzing echocardiography data after 6 months of observation, a significant decrease in the LV end-diastolic volume index by 15.6% (p<0.05) and an increase in LV EF by 16.7% (p<0.05) were found. Also, after 6 months of observation, a significant decrease in the content of systemic inflammation markers was detected: the level of ferritin decreased by 41.5% (p<0.01), C-reactive protein – by 34.2% (p<0.01), the content of interleukin-6 and tumor necrosis factor α decreased by 93.8% and 33.3%, respectively (p<0.01), and the content of troponin I decreased 3 times compared to the baseline level before the appointment of azathioprine. According to the results of the 6-minute test, before the appointment of azathioprine, patients with FC III HF predominated, only a third had FC II, and 20% – FC IV. After 6 months of treatment, more than half of the studied patients had FC II HF, every fourth – FC I, and FC IV was not diagnosed in any patient.
Conclusions. In patients with severe myocarditis, combined immunosuppressive therapy with azathioprine and glucocorticoids for 6 months was accompanied by a decrease in dilatation and improving the contractility of the left ventricle, improving the functional class of heart failure, reducing the number of myocardial segments affected by inflammatory changes as well as reducing the content of systemic inflammation markers.