Efficiency of immunosuppressive therapy in virus-negative and virus-positive patients with morphologically verified lymphocytic myocarditis

Abstract

To evaluate the efficiency of immunosuppressive therapy (IST) in virus-negative (V-) and virus-positive (V+) patients with lymphocytic myocarditis (LM). 60 patients (45 males) (mean age 46.7±11.8 years) with dilated cardiomyopathy (mean left ventricular (LV) end diastolic size (EDS) 6.7±0.7 cm; ejection fraction (EF) 26.2±9.1%) were examined. The diagnosis of active/borderline LM was verified by right ventricular endomyocardial biopsy in 38 patients, by intraoperative LV biopsy in 10, in the study of explanted hearts from 3 patients and at autopsy in 9. The investigators determined the genomes of parvovirus B19, herpes viruses types 1, 2 and 6, Epstein-Barr (EBV), zoster, and cytomegalovirus in the blood and myocardium and, if antibodies were present in the blood, hepatitis B and C viruses, as well as antibodies against antigens in the endothelium, cardiomyocytes and their nuclei, smooth muscles, fibers of the conducting system. IST was used in terms of histological, immune, and viral activities. IST was performed in 22 V+ patients (Group 1) and in 24 V- patients (Group 2); this was not done in 10 V+ patients (Group 3) and V- patients (Group 4). IST comprised methylprednisolone at a mean dose of 24 mg/day (n=40), hydroxychloroquine 200 mg/day (n=20), azathioprine at a mean dose of 150 mg/day (n=21); antiviral therapy included acyclovir, ganciclovir, intravenous immunoglobulin (n=24). The follow-up period was 19 (7.3-40.3) months. The viral genome was detected in the myocardium of 32 patients who made up a V+ group. The degree of histological activity did not differ in relation to the presence of viral genome in the myocardium. The degree of immune activity (anticardiolipin antibody titers) in the V+ patients was as high as that in V- ones. At baseline, the V+ patients had a significantly higher LV EDS and a lower EF than the V- patients. Overall, IST only could lead to a significant increase in EF (from 26.5±0.9 to 36.0±10.8%; p<0.001) and reductions in NYHA functional class from III to II (p<0.001), LV EDS (from 6.7±0.7 to 6.4±0.8 cm; p<0.01), pulmonary artery systolic pressure (from 48.9±15.5 to 39.4±11.5 mm Hg (p<0.01); the IST group had significantly lower mortality rates than the non-IST group (23.9 and 64.3%; p<0.01). At the same time, a significant trend was seen in both V- and V+ patients. The mortality rate in the V+ patients, as a whole, was higher (46.9 and 17.9%; p<0.05). IST leads to a significant improvement of functional indices and it is associated with lower mortality rates in both myocardial V- and V+ patients with LM. A more than 10% EF increase in the first 2 months is associated with a good prognosis. The presence of viral genome in the myocardium (primarily herpesviruses rather than parvovirus-19) is accompanied by more severe initial dysfunction, a less pronounced effect of IST, and higher mortality rates. However, the positive effect of IST also persists in V+ patients. No positive changes (a decrease in EF was observed) were absent only in IST-naïve V+ patients.