Journal
CANADIAN JOURNAL OF CARDIOLOGY
Volume 23, Issue 5, Pages 369-376Publisher
PULSUS GROUP INC
DOI: 10.1016/S0828-282X(07)70770-5
Keywords
heart failure; immune modulation; ventricular dysfunction
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BACKGROUND: Evidence has accumulated regarding the importance of inflammatory mediators in the development and progression of heart failure (HF). Although targeted anticytokine treatment strategies, specifically antitumour necrosis factor,alpha, have yielded disappointing results, this may simply reflect the redundancy of the cytokine cascade and the fact that antitumour necrosis factor-alpha therapies do not stimulate increased activity of the anti-inflammatory arm of the immune system. Ex vivo exposure of autologous blood to controlled oxidative stress and subsequent intramuscular administration is a device-based procedure shown in experimental studies to have a broad-spectrum effect on a number of immune mediators. These studies have demonstrated that this approach downregulates inflammatory cytokines, whereas several anti-inflammatory cytokines are increased. In a feasibility study of 73 patients with moderate to severe HF, active therapy (versus placebo) had a significant benefit on both mortality and hospitalization, and was not associated with adverse hemodynamic or metabolic effects. METHODS: The Advanced Chronic heart failure CLinical Assessment of Immune Modulation therapy (ACCLAIM) trial is a multicentre, randomized, double-blind, placebo-controlled clinical trial of New York Heart Association functional class 11 to IV chronic HF patients with left ventricular ejection fraction of 30% or less. Enrolling approximately 2400 subjects at 177 sites, the primary end point of the study was the cumulative incidence (time to first event) of the combined end point of total mortality or hospitalization for cardiovascular causes. The study was completed in late 2005, when 701 primary end point events had occurred and all patients had been treated for six months. CONCLUSIONS: If the ACCLAIM trial confirms earlier results, this approach represents a novel nonpharmacological treatment for HF that targets a pathogenic mechanism contributing to progression of this syndrome not addressed by current therapies.
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