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(Circulation. 2001;104:1494.)
© 2001 American Heart Association, Inc.

Clinical Investigation and Reports

Complement Activation in Patients With Congestive Heart Failure

Effect of High-Dose Intravenous Immunoglobulin Treatment

Pål Aukrust, MD, PhD; Lars Gullestad, MD, PhD; Knut T. Lappegård, MD; Thor Ueland, BS; Halfdan Aass, MD, PhD; Lisbeth Wikeby, RN; Svein Simonsen, MD, PhD; Stig S. Frøland, MD, PhD; Tom E. Mollnes, MD, PhD

From the Section of Clinical Immunology and Infectious Diseases (P.A., S.S.F.), Research Institute for Internal Medicine (P.A., S.S.F., T.U.), Section of Endocrinology (T.U.), Medical Department and Department of Cardiology (L.G., H.A., L.W., S.S.), Rikshospitalet, University of Oslo, and Department of Immunology and Transfusion Medicine (K.T.L., T.E.M.) and Department of Medicine (K.T.L.), Nordland Central Hospital and University of Tromsø, Bodø, Norway.

Correspondence to Pål Aukrust, Section of Clinical Immunology and Infectious Diseases, Medical Department, Rikshospitalet, Sognsvannsveien 20, 0027 Oslo, Norway. E-mail pal.aukrust{at}rikshospitalet.no

Background— Increasing evidence implicates innate immunity in the pathogenesis 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 coronary circulation in 39 patients with CHF and 20 healthy control subjects. In a double-blind, placebo-controlled study, we have recently reported that high-dose intravenous immunoglobulin (IVIG) improves left ventricular ejection fraction (LVEF) in these patients. To examine if this improvement was related to IVIG-induced effects on complement, we also examined complement activation during induction (first week) and maintenance therapy (6 months) with IVIG or placebo. Our main findings were: (1) We found enhanced systemic complement activation involving classic, alternative, as well as terminal pathway in patients with CHF compared with healthy control subjects. (2) Particularly enhanced complement activation was found in coronary sinus, representing venous drainage from the heart. (3) The systemic complement activation was further enhanced during IVIG but not during placebo therapy, particularly during induction therapy. (4) Although IVIG improved LVEF in patients with CHF, the degree of IVIG-mediated complement activation was negatively 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 added to the list of possible therapeutic targets in CHF and that future studies with specific complement inhibitors may be of interest in this disorder.

Key Words: heart failure • inflammation • leukocytes • immunology

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