Effects of a novel Immune modulation therapy in patients with advanced chronic heart failure: Results of a randomized, controlled, phase II trial

• Published in: Journal of the American College of Cardiology 2004-09, Vol.44 (6), p.1181-1186
• Main Authors: TORRE-AMIONE, Guillermo, SESTIER, Francois, RADOVANCEVIC, Branislav, YOUNG, James
• Format: Article
• Language: English
• Subjects: Aged; Angina pectoris; Biological and medical sciences; Biomarkers - blood; Cardiology; Cardiology. Vascular system; Chronic Disease; Cytokines; Drug therapy; Female; Heart; Heart attacks; Heart failure; Heart Failure - immunology; Heart Failure - physiopathology; Heart Failure - therapy; Heart failure, cardiogenic pulmonary edema, cardiac enlargement; Heart rate; Hospitalization; Humans; Immunotherapy; Male; Medical sciences; Middle Aged; Mortality; Oxidative stress; Patients; Quality of life; Stroke Volume - physiology; Survival Analysis; Treatment Outcome; Variance analysis
• ISSN: 0735-1097; 1558-3597
• DOI: 10.1016/j.jacc.2004.06.047

We sought to determine whether a novel, non-pharmacological form of immune modulation therapy (IMT), shown experimentally to reduce inflammatory and increase anti-inflammatory cytokines, improved outcomes in patients with advanced heart failure (HF). Immune activation contributes to the progression of HF, but treatments directed against inflammation have been largely unsuccessful. Seventy-five HF patients (New York Heart Association [NYHA] functional class III to IV) were randomized to receive either IMT (n = 38) or placebo (n = 37) in a double-blind trial for six months, with continuation of standard HF therapy. Patients were evaluated using the 6-min walk test, changes in NYHA functional class, cardiac function, and quality of life assessments, as well as occurrence of death and hospitalization. There was no between-group difference in 6-min walk test, but 15 IMT patients (compared with 9 placebo) improved NYHA functional classification by at least one class (p = 0.140). The Kaplan-Meier survival analysis showed that IMT significantly reduced the risk of death (p = 0.022) and hospitalization (p = 0.008). Analysis of a clinical composite score demonstrated a significant between-group difference (p = 0.006). There was no difference in left ventricular ejection fraction, but there was a trend toward improved quality of life (p = 0.110). These preliminary findings are consistent with the hypothesis that immune activation is important in the pathogenesis of HF and establish the basis for a phase III trial to define the benefit of IMT in chronic HF.