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

Yu. N. Gorbunova, I. G. Kirillova, T. V. Popkova, M. E. Diatroptov, T. I. Nevretdinov, A. M. Lila
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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.
类风湿关节炎患者接受生物疾病改善抗风湿药物或Janus激酶抑制剂治疗时左心室心肌整体纵向应变和血液生物标志物水平的动态变化
目的:利用超声心动图(斑点追踪法)和血液生物标志物水平(NT -proBNP、可溶性ST2、sST2)研究RA患者在接受生物疾病改善抗风湿药物(bDMARDs)或Janus激酶抑制剂(JAKi)治疗12个月背景下的全局纵向心肌应变(GLS)动态。材料和方法。该研究纳入了50例RA患者(ACR/EULAR标准,2010年):84%为女性,中位年龄51.0 [40.0;59.0年,RA的中位病程为4.5年[3.0年;14.0]年,中位DAS28 5.7 [5.2;6.4)点。类风湿因子IgM阳性占78%,环瓜氨酸肽抗体阳性占66%。在纳入研究时,38%的患者正在接受甲氨蝶呤、38%的来氟米特、10%的磺胺氮嗪、12%的羟氯喹、70%的糖皮质激素、82%的非甾体类抗炎药。60%的RA患者有两种或两种以上dmard疗效不足的病史。检查后,所有患者均开bdmard或JAKi。38%的患者使用TNF-α抑制剂,50%的患者使用抗b细胞治疗,4%的患者使用IL-6抑制剂,2%的患者使用t淋巴细胞共刺激阻滞剂,6%的患者使用JAKi。所有RA患者在服用bDMARDs前和治疗12个月后进行动态检查。行超声心动图-组织多普勒成像及斑点跟踪法评价左心室心肌GLS (GLD LVM);测定血清NT-proBNP、sST2水平。NT-proBNP正常值范围小于125 pg/ml, sST2正常值范围小于17.65 ng/ml。对照组由20名性别和年龄相当的健康受试者组成。RA患者和对照组均无心血管疾病。结果和讨论。bDMARDs治疗12个月后,GLS LVM升高,GLS LVM降低的频率降低了47% (p <0.05)。左心房收缩期终末容积指数也下降。RA患者NT-proBNP和sST2值高于对照组(p <0.05)。治疗12个月后RA患者血清NT-proBNP水平变化无统计学意义(p = 0.5)。治疗12个月后,RA患者血清中sST2水平与基线相比显著下降(p <0.01)。sST2水平与ΔDAS28的Δ (Δ)、ΔsST2与ΔCRP的Δ (Δ)、ΔACCP的Δ (Δ)呈直接相关。治疗12个月后,与缓解/低RA活动度的患者相比,持续中高疾病活动度的RA患者的收缩压水平和血清NT-proBNP水平、低左心室射血分数(LVEF)和GLS LVM水平更高。各组间LVEF、左室大小、左室心肌质量指数、NT-proBNP水平均无差异。ΔGLD LVM与ΔESR、ΔsST2呈负相关。结论。在RA患者中,在bDMARDs和JAKi治疗的背景下,疾病活动性的降低导致GLS LVM的改善。活动期RA和已建立的左室亚临床心肌功能障碍患者给予bDMARDs可减缓心肌功能障碍的进展。与对照组相比,RA患者血清sST2和NT-proBNP水平升高。bDMARDs治疗12个月后,RA患者血清中sST2水平明显下降,NT-proBNP水平无动态变化。
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