The FAR NHL register and humoral activation

Czech version

Authors: Špinarová L. ¹; Špinar J. ¹; Pařenica J. ²; Ludka O. ¹; Málek F. ³; Lábr K. ¹; Špinarová M. ¹; Krejčí J. ¹; Jarkovský J. ⁴; Goldbergová-Pávková M. ⁵; Tomandl J. ⁶
Authors‘ workplace: I. interní kardioangiologická klinika LF MU a FN u sv. Anny v Brně ¹; Interní kardiologická klinika LF MU a FN Brno ²; kardiologické oddělení, Nemocnice Na Homolce, Praha ³; Institut biostatistiky a analýz, LF a PřF MU, Brno ⁴; Ústav patofyziologie, LF MU, Brno ⁵; Ústav lékařské chemie a biochemie, LF MU, Brno ⁶
Published in: Kardiol Rev Int Med 2020, 22(2): 51-57

Overview

Chronic heart failure is a clinical syndrome with the activation of various pathophysiological mechanisms. Some of them are vasoconstrictive: sympathetic system, renin angiotensin system, aldosterone, vasopressin and endothelin. Counterbalancing vasodilating agents are: natriuretic peptides, endothelium-dependent relaxation factor and adrenomedullin. The elevation of cytokines or markers of oxidative stress also plays a role. The FAR NHL (FARmacology and NeuroHumoraL activation) register is a database of patients with chronic heart failure (CHF) and is focused on pharmacology and humoral activation. A total of 1,100 patients have been included, the most frequent aetiology of CHF was ischaemic heart disease 49.7%. Routine biochemistry and NT-proBNP was evaluated in all patients. Novel humoral substances and markers of oxidative stress: copeptin, MR-proadrenomedullin (MR-proADM), pentraxin (PTX3), galectin3, soluble lectin-like oxidised LDL receptor-1 (sLOX-1) and 3-Nitrotyrosin (3-NT) were measured in a part of the study population. The primary endpoint after a 1-year follow-up was: death or hospitalisation for decompensation of HF or heart transplantation (HTX) or LVAD implantation. More than 50% of the patients with stable CHF showed a level of NT-proBNP higher than 600 pg/ml. The level of NT-proBNP increased with the NYHA class. Patients without a primary endpoint (death or hospitalisation for decompensation of HF or heart transplantation or LVAD implantation) were assigned as group A, those with a primary endpoint as group B. There were statistically significant differences between the groups in the levels of copeptin, MR-proADM and PTX3 (p < 0.001 for all substances). There were no differences in the levels of other substances: galectin3, NGAL, sLOX-1 and 3-NT. When evaluating comorbidities using the AHEAD score, patients with a higher AHEAD score (more comorbidities) achieved the primary endpoint more often. For both humoral agents: copeptin and MR-proADM, there was a statistically significant importance for achieving the primary endpoint in patients with lower AHEAD scores (p < 0.006 and p < 0.003), however, neither agent showed a significant predictive value in patients with higher AHEAD scores. Higher levels of the new humoral agents (copeptin and MR-proADM) could differentiate CHF patients at a higher risk of adverse events. The predictive value of these agents is also affected by the patient's comorbidities as assessed by the AHEAD score. New humoral agents could thus have an additional value for the already traditional and routinely used natriuretic peptides.

Keywords:

Prognosis – chronic heart failure – humoral activation – FAR NHL registry – AHEAD score

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