Five-year survival and biomarkers of sympatho-adrenal, neurohumoral, immune activation, fibrosis in patients with early and late superresponse to cardiac resynchronization therapy

Abstract

Methods. 82 SR (80.5% men; mean age 60.4±9.3; 45 (54.9%) with CAD) were divided according to period of LVESV maximum decrease: Gr.1 (n=19)- <24months (14.0 [8.0; 21.0]), Gr.2 (n=63)->24 months (59[43.0; 84.0]). Dynamics of echocardiography, adrenaline (ADR) plasma levels, norepinephrine (NE), interleukins (IL) 1β, 6, 10, TNF-α, NT-proBNP, MMP-9, TIMP-1, 4, were examined. Five-year survival was estimated by Kaplan-Meier method. ROC analysis and logistic regression were applied to identify late CRT response factors.Results. Initially, groups didn’t differ by clinical and echocardiographic findings. At baseline, Gr.2 had larger ADR (p=0.049) and NE (p=0.061). Rate of change in NE was opposite in groups during CRT: ΔNE increased in Gr.1 and decreased in Gr.2. (p=0.015), which was associated with better reverse cardiac remodeling (lower LV end systolic diameter, LV end diastolic diameter, LVESV, LV end diastolic volume), decrease in activity of immune inflammation (decrease in levels of IL-1β, 6, 10, TNF-α) and fibrosis formation (decrease in TIMP- 1, enhancement of MMP-9/TIMP-1). Cut-off value of 2.55 ng/ml for NE complied with the highest sensitivity (80%), specificity (60%), AUC=0.693 (p=0.011) for predicting late CRT response. Proportion of patients with NE<2.55 ng/ml was 21.1% in Gr.1 and 59.7% in Gr.2, (p=0.003), mean follow-up period was 45.8±0.3 and 94.9±35.9 months (p<0.001), respectively All SR of Gr.2 were alive within 5 years, survival rate was 50% in Gr.1 (Log-Rank test<0.001). NE was associated with late CRT response (OR 8.0 (95%CI 1.5-42.8), p=0.015).Conclusion. Late CRT response was accompanied by increased life expectancy, better 5-year survival, associated with greater reverse cardiac remodeling, decreased fibrosis activity, immune, neurohumoral, sympathoadrenal activation. When NE level was less than 2.55 ng/ml, probability of late response increased 8-fold.