Myocardial remodeling and immunologic activation in patients with heart failure

Introduction and objectives. Immune responsemediated regulation of myocardial collagen remains poorly understood. Our objective was to investigate the relationship between ventricular remodeling and immunologic activation in patients with heart failure (HF) by comparing dilated and ischemic cardiomyopathy. Methods. We studied 94 patients with HF and dilated cardiomyopathy (n=46) or ischemic cardiomyopathy (n=48). We recorded left ventricular (LV) volumes, E/A ratio, and ejection fraction. Plasma concentrations of tumor necrosis factor α (TNFα), soluble TNFα receptor I (sTNF-RI), sTNF-RII, interleukin-6 (IL-6), and IL-10 were measured. The serum procollagen type-III amino-terminal propeptide (PIIINP) level was also obtained. Results. Ventricular volumes were greater in the dilated cardiomyopathy than in the ischemic cardiomyopathy group (P<.05). However, sTNF-RI, sTNF-RII, and PIIINP levels were higher in the ischemic group (P<.05). In this group, there were significant correlations between ventricular volumes and IL-10 and sTNF-RII levels. There was also a significant correlation between PIIINP and sTNF-RII levels (r=0.30; P<.05). In the dilated cardiomyopathy group, there was a significant correlation between ventricular volumes and IL-10 level, and between PIIINP level and IL-6 (r=0.32; P<.05) and sTNF-RII levels (r=0.32; P<.05). Multiple linear regression analysis, which included cytokine levels, age, sex and ventricular function, showed that the sTNF-RII level was an independent predictor of the PIIINP level (adjusted r 2 =0.16; P<.0001) and of ventricular volumes (LV end-systolic volume index, adjusted r 2 =0.034; P<.05; and LV end-diastolic volume index, adjusted r 2 =.048; P<.05) in both groups. Conclusions. In HF, there is an interaction between proinflammatory cytokines and the extracellular matrix.