Differential long-term effects of carvedilol on proinflammatory and antiinflammatory cytokines, asymmetric dimethylarginine, and left ventricular function in patients with heart failure.

Neuroendocrine/inflammatory and endothelial functions have been indicated as crucial for heart failure (HF) patients. We evaluated relation in HF patients among cytokines and asymmetric dimethylarginine (ADMA) and left ventricular ejection fraction (LVEF) at baseline and after long-term administration of carvedilol. Interleukin 10 (IL-10), interleukin 18 (IL-18), and ADMA were measured in 22 NYHA class II to IV HF patients at baseline and after 40 +/- 14 months of carvedilol treatment. Patients were divided into 2 groups according to whether, after treatment with carvedilol, LVEF had increased at least 5% (responders) or less than 5% (non-responders). In responders (11 of 22 patients), LVEF increased from 38 +/- 6% to 50 +/- 7%, (P < 0.001); in non-responders, it decreased from 36 +/- 9% to 31 +/- 6%, (P = 0.02); NYHA class significantly decreased in both groups. IL-18 decreased in responders (from 586.4 +/- 128 to 183.13 +/- 64.4 pg/mL; P < 0.001) and in non-responders (from 529.3 +/- 116.25 to 142.4 +/- 58.9 pg/mL; P < 0.001). IL-10 increased in responders (from 0.49 +/- 0.25 to 2.01 +/- 1.01 pg/mL; P < 0.001) and in non-responders (from 0.64 +/- 0.31 to 1.33 +/- 0.59 pg/mL; P < 0.001). Conversely, ADMA levels decreased only in responders (from 0.67 +/- 0.16 to 0.44 +/- 0.15 micromol/L; P < 0.001), and an inverse correlation was observed between basal ADMA levels and changes in LVEF after treatment. In HF patients, carvedilol appears to reduce symptoms and the expression of inflammation, regardless of the LV functional response. In those patients showing improvement of LVEF, the reduction of inflammation is paralleled by a reduction of ADMA. We surmise that carvedilol could be effective at various independent levels as a result of possible pleiotropic effects of this agent.