Complement activation in patients with congestive heart failure - Effect of high-dose intravenous immunoglobulin treatment

Background-Increasing evidence implicates innate immunity in the pathogenes is of congestive heart failure (CHF). In the present study, we examined the possible role of complement, an important part of innate immunity, in CHF. Methods and Results-Complement activation was analyzed in systemic and coro nary circulation in 39 patients with CHF and 20 healthy control subjects. I n a double-blind, placebo-controlled study, we have recently reported that high-dose intravenous immunoglobulin (IVIG) improves left ventricular eject ion fraction (LVEF) in these patients. To examine if this improvement was r elated to IVIG-induced effects on complement, we also examined complement a ctivation during induction (first week) and maintenance therapy (6 months) with IVIG or placebo. Our main findings were: (1) We found enhanced systemi c complement activation involving classic, alternative, as well as terminal pathway in patients with CHF compared with healthy control subjects. (2) P articularly enhanced complement activation was found in coronary sinus, rep resenting venous drainage from the heart. (3) The systemic complement activ ation was further enhanced during IVIG but not during placebo therapy, part icularly during induction therapy. (4) Although IVIG improved LVEF in patie nts with CHF, the degree of IVIG-mediated complement activation was negativ ely correlated with this improvement of LVEF. Conclusions-This study further supports the involvement of innate immunity in the pathogenesis of CHF. Our findings suggest that complement may be add ed to the list of possible therapeutic targets in CHF and that future studi es with specific complement inhibitors may be of interest in this disorder.