Concentration of BNP, endothelin 1, pro-inflammatory cytokines (TNF-alpha, IL-6) and exercise capacity in patients with heart failure treated with carvedilol

Abstract

Background: Recent studies on the pathophysiology of heart failure indicate the role of neurohormones and immune and inflammatory processes as potential mechanisms involved in the pathogenesis and clinical course of chronic heart failure (CHF).

Aim: To analyse the relationship between concentrations of brain natriuretic peptide (BNP), endothelin-1 (ET-1), inflammatory cytokines (TNF-alpha, IL-6) and cardiopulmonary stress test parameters, and to evaluate their changes during carvedilol treatment.

Methods: The study included 86 patients (81 men and 5 women) aged from 35 to 70 years (56.8+/-9.19) with symptomatic heart failure and left ventricular ejection fraction <40%, receiving an inhibitor of angiotensin II converting enzyme, diuretic and/or digoxin but not beta-blockers. All patients at baseline, and then at 3 and 12 months after treatment, underwent a panel of studies to assess functional capacity according to NYHA, echocardiographic and cardiopulmonary stress test (CPX) parameters, and serum concentrations of BNP, ET-1, TNF-alpha and IL-6. Before introducing carvedilol we found a weak relationship between concentrations of BNP, ET-1, IL-6 and decreased VO2 peak.

Results: At 12 months exercise tolerance was significantly improved (exercise stress testing prolonged by 143.9 s, p=0.001) and an increase in metabolic equivalent (MET) by 1.41 (p=0.001) was observed. The VO2 peak was nonsignificantly increased by a mean of 0.9 ml/kg/min. In patients with baseline VO2 peak <14 ml/kg/min the concentrations of ET-1 and TNF-alpha were significantly higher than in the remaining ones, and after treatment they were significantly reduced. In these patients VO2 peak%N was also significantly increased (39.5+/-7.5 vs. 50.1+/-15,0; p=0.013). The number of patients with VO2 peak <14 ml/kg/min also significantly decreased from 39 to 21 (p=0.013).

Conclusions: In patients with HF decreased value of VO2 peak is associated with LV systolic function disorders and increased levels of BNP, ET-1, TNF-alpha and IL-6. Chronic treatment with carvedilol improves LV systolic function, exercise tolerance and peak oxygen consumption and is associated with significant decrease of BNP, ET-1, TNF-alpha and IL-6 concentrations.