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Background: Previous reports had emphasized the importance of humoral immunity in heart failure in humans, primarily determined by the presence of circulating antibodies. However, there is little or no information about the frequency of anticardiac antibodies present in failing human myocardium., Methods: Clinical data and myocardial tissue samples were analyzed to determine the role of humoral immunity in patients with chronic heart failure (CHF) in different SETTINGS., Results: Anticardiac antibodies were found present in failing hearts but not in normal control hearts. Further, the level of expression of these anticardiac antibodies changed with the severity of the disease state; and in patients with acute heart failure, we found selective activation of B cells. Finally, treatment of CHF patients with therapeutic plasma exchange, a strategy that removes circulating antibodies, resulted in a reduction in anticardiac antibody deposition and improvements in cardiac function., Conclusion: These data collectively suggest a role of humoral immunity in the progression of heart failure., (Copyright © 2010 Wiley-Liss, Inc.)