Cytokines in heart failure.

The natural history of heart failure (HF) is not linear, because changes in the heart structure and function start long before the disease becomes clinically evident. Many different cytokines originating from intracardiac tissues (cardiomyocytes, cardiac endothelial cells, cardiac fibroblasts, and cardiac infiltrated immune cells) or extracardiac tissues (adipose tissue, gut, and lymphoid organs) have been identified in HF. Because the levels of circulating cytokines correlate with the development and severity of HF, these mediators may have both pathophysiological importance, through their ability to modulate inflammation, myocyte stress/stretch, myocyte injury and apoptosis, fibroblast activation and extracellular matrix remodeling, and utility as clinical predictive biomarkers. A greater understanding of the mechanisms mediated by the multifaceted network of cytokines, leading to distinct HF phenotypes (HF with reduced or preserved ejection fraction), is urgently needed for the development of new treatment strategies. In this chapter, all these issues were thoroughly discussed, pointing on the practical considerations concerning the clinical use of the cytokines as prognostic biomarkers and potential therapeutic targets in HF.