Inflammation in Chronic Heart Failure

Abstract

Objective: To summarize findings regarding the association of inflammatory processes with chronic heart failure (HF). Data Sources: We conducted PubMed/MEDLINE searches (1966–January 2006) of primary literature using the following key words: ACE inhibitors, allopurinol, angiotensin-receptor antagonists, cardiomyopathy, chemokines, cytokines, diuretics, heart failure, Inflammation, interleukins, HMG-CoA reductase inhibitors, immunotherapy, medications used In heart failure, thalidomide, tumor necrosis (actor, and uric acid. Study Selection and Data Extraction: All articles that appeared to be relevant were read; of 305 articles examined, 87 were selected for discussion. Articles were selected if they were written in English and focused on any of the key words or appeared to have substantial content addressing inflammation in HF. Data Synthesis: Cytokines, uric acid, and other inflammatory mediators are associated with physiologic effects that are also prominent features of HF (eg, reduced contractility and cardiac output, endothelial dysfunction, hypercoagulability, autonomic dysfunction as evidenced by reduced resting heart rate variability, insulin resistance). With the exception of elevated tumor necrosis factor-α as a cause of insulin resistance, it is not clear whether elevated inflammatory mediators directly cause HF signs and symptoms or whether they are incidental markers. Awareness of these associations has occurred relatively recently; there have been few clinical studies of efforts to directly modify inflammatory mediators. Most currently accepted drug therapies of HF reduce concentrations of circulating cytokines, but the significance of these findings awaits directed study. Conclusions: Loss of myocardial function, autonomic dysfunction, and glucose intolerance are interrelated and linked by underlying chronic low-grade inflammation. Drug therapy with statins, pentoxifylline, and perhaps urate-lowering agents, in addition to current therapies, holds promise for treatment of HF.