Ten-year survival and clinical biochemical status of nonprogressors and responders to cardiac resynchronization therapy

Abstract

Aim. To estimate the 10-year survival, clinical and biochemical status of responders and nonprogressors to cardiac resynchronization therapy (CRT) using biomarkers of fibrogenesis, neuro-humoral, immune, sympatho-adrenal activation.Methods. Eighty CRT patients (mean age 58.9±10.1 years; 90% men; 72.5% with coronary artery disease) with the best CRT response timing («best» timing), assessed by maximum decrease in left ventricle end-systolic volume (LVESV), were divided into groups: Gr.1 (n=42): non-progressors (decrease in LVESV by >0<15%), Gr.2 (n=38): responders (decrease in LVESV by >15<30%). At baseline, in the «best» timing and in the «end» timing (November 2020), parameters of echocardiography, NT-proBNP, epinephrine, norepinephrine (NAdr), IL 1β, 6, TNF-α, C-reactive protein, matrix metalloproteinase 9, tissue inhibitor of matrix metalloproteinases 1 in plasma were studied. Survival was estimated by Kaplan-Meier method. Logistic regression was used to assess relationship of studied factors with CRT efficacy, and Cox regression with survival.Results. In Gr.1, greater heart failure functional class was revealed (p=0.042). In Gr.1, there was less reverse cardiac remodeling in the «best» timing and greater pulmonary artery systolic pressure (p=0.029), NT-proBNP (p=0.020) in the «end» timing. Immune activation and imbalance of fibrogenesis were found across all time points of the study. In Gr.1, increase in NAdr level was revealed only in the «end» timing (p=0.017), but in Gr.2 it already was in the «best» timing (p=0.003). Correlations of NAdr «best» with ΔLVESV (r=-0.245; p=0.038), Δ left ventricle end-diastolic volume (LVEDV) (r=-0.293; p=0.013) in general group; and with IL-1β «best» (r=0.363; p=0.032), TNF-α «best» (r=0.360; p=0.034) in responders group were registered. Responder’s survival was the best only at 2 and 3 years after CRT implantation, with comparable survival between groups in subsequent years. In Gr.1, significant factors associated with 2-3-year survival were LVEDV «best» (RR 0.831 (0.713-0.967), p=0.017), LVESV «best» (RR 1.245 (1.040-1.492), p=0.017); in Gr.2, NT-proBNP «end» (RR 1.001 (1.000-1.001), p=0.024) related to 10-year survival in the absence of significant factors.Conclusion. Comparable 10-year survival rate of non-progressors and responders is probably due to immune, sympathetic-adrenal activation, fibrogenesis imbalance. In non-progressors group CRT response can be assessed as positive due to significant reverse cardiac remodeling and survival comparable to responders and associated with NT-proBNP level.