Effects of carvedilol on right ventricular ejection fraction and cytokines levels in patients with systolic heart failure

Background: Right ventricular (RV) dysfunction frequently complicates advanced left ventricular (LV) heart failure and contributes to an unfavorable prognosis. It is known that carvedilol increases left ventricular ejection fraction (LVEF) significantly, and carvedilol reduces mortality by associating with improvement in LV function. However, the effect of carvedilol on RV function in heart failure has not adequately been studied, so far. The objective is to establish whether the addition of carvedilol has an additive beneficial effect on RVEF and cytokines levels in patients with heart failure who are already receiving treatment with angiotensin-converting enzyme (ACE) inhibitors, digoxin and diuretics. Methods: In this single-centre, prospective, randomized study, 74 patients with heart failure with an LVEF less than 40% and already receiving digoxin, ACE inhibitors and diuretics for 6 months as the standard therapy were randomly assigned to receive either carvedilol (n= 44) or placebo (n= 30). Patients received an initial dosage of 6.25 mg carvedilol or placebo twice daily for 2 weeks, which was then increased at 2-week intervals (if tolerated), first to 12.5 mg and, finally, to a target dosage of 25 mg twice daily. Clinical examinations, radionuclide studies, and determinations of plasma levels of tumour necrosis factor-alpha (TNF-alpha), interleukin (IL)-2 and IL-6 were performed at baseline and repeated 4 months after random assignment. Primary end points were New York Heart Association functional class, RVEF and plasma cytokines levels. Results: Patients treated with carvedilol had a significant improvement in functional class compared with the baseline values (P = 0.001), with a decrease in the levels of cytokines (IL-6 [P=0.02] and TNF-alpha [P= 0.02]). LVEF increased from 21.4 +/- 8.8% to 27.8 +/- 10.8% and RVEF increased from 28.8 +/- 4.2% to 36.3 +/- 2.6% in the carvedilol group (P= 0.003). Conclusions: Carvedilol treatment for 4 months resulted in a significant improvement of RVEF, which paralleled the improvement of LVEF and the decreasing of TNF-alpha and IL-6 levels in patients with systolic HF. Published by Elsevier Ireland Ltd.