Dynamics of global longitudinal strain of the left ventricular myocardium and blood biomarker levels in patients with rheumatoid arthritis treated with biologic disease-modifying antirheumatic drugs or Janus kinase inhibitors

Abstract

   Objective: to study the dynamics of global longitudinal myocardial strain (GLS) using echocardiography (speckle tracking method) and blood biomarker levels (NT -proBNP, soluble ST2, sST2) in RA patients against a background of 12 months of therapy with biological disease-modifying antirheumatic drugs (bDMARDs) or Janus kinase inhibitors (JAKi).   Material and methods. The study included 50 patients with RA (ACR/EULAR criteria, 2010): 84 % were women, median age 51.0 [40.0; 59.0] years, median duration of RA was 4.5 [3.0; 14.0] years, median DAS28 5.7 [5.2; 6.4] points. 78 % of patients were positive for IgM rheumatoid factor, 66 % for antibodies to cyclic citrullinated peptide. At the time of inclusion in the study, 38% of patients were receiving methotrexate, 38 % – leflunomide, 10 % – sulfasalazine, 12 % – hydroxychloroquine, 70 % – glucocorticoids, 82 % – nonsteroidal anti-inflammatory drugs. 60 % of patients with RA had a history of inadequate efficacy of two or more DMARDs. After examination, all patients were prescribed bDMARDs or JAKi. TNF-α inhibitors were given to 38% of patients, anti-B-cell therapy – to 50% of patients, IL-6 inhibitors – to 4%, T-lymphocyte costimulation blockers – to 2 %, JAKi – to 6 % of RA patients. All patients with RA were examined before administration of bDMARDs and in dynamics after 12 months of treatment. Echocardiography was performed – tissue Dopplerography and evaluation by speckle tracking method of left ventricular myocardium GLS (GLD LVM); in blood serum the levels of NT-proBNP, sST2 were determined. The normal range for NT-proBNP was less than 125 pg/ml, and for sST2 less than 17.65 ng/ml. The control group consisted of 20 healthy subjects who were comparable in sex and age. RA patients and subjects in the control group had no cardiovascular disease.   Results and discussion. After 12 months of bDMARDs therapy, GLS LVM increased and the frequency of reduced GLS LVM decreased by 47 % (p < 0.05). The indexed end-systolic volume of the left atrium also decreased. RA patients had higher values of NT-proBNP and sST2 compared to the control group (p < 0.05). The variations of NT-proBNP level in blood serum of RA patients after 12 months of therapy were statistically insignificant (p = 0.5). The level of sST2 in the serum of patients with RA decreased significantly after 12 months of therapy compared to baseline (p < 0.01). Direct correlations were found between the delta (Δ) of the level of sST2 and ΔDAS28, the level of ΔsST2 and ΔCRP, and ΔACCP. After 12 months of therapy, RA patients with persistent moderate/high disease activity had higher levels of systolic blood pressure and serum levels of NT-proBNP, lower left ventricular (LV) ejection fraction (LVEF) and GLS LVM than patients who had remission/low RA activity. There were no differences between groups in LVEF, LV size, LV myocardial mass index, and NT-proBNP levels. Negative correlations were observed between ΔGLD LVM and ΔESR and ΔsST2.   Conclusion. In patients with RA, a decrease in disease activity on a background of therapy with bDMARDs and JAKi leads to an improvement in GLS LVM. Administration of bDMARDs in patients with active RA and established LV subclinical myocardial dysfunction may slow the progression of myocardial dysfunction. Serum sST2 and NT-proBNP levels were increased in patients with RA compared with the control group. After 12 months of therapy with bDMARDs, the level of sST2 in the serum of RA patients decreased significantly, and the level of NT-proBNP did not change in dynamics.