Mammalian cardenolides as biomarkers in congestive heart failure

Congestive heart failure (CHF) afflicts over 5 million individuals in the United States, and most die within 5 yr of diagnosis. Because of the high morbidity and mortality associated with CHF, the search for biomarkers to predict, diagnose, and manage this disease has intensified. Calcium homeostasis and alterations in intracellular concentrations of this cation have been implicated in both hypertrophy as well as the adaptive mechanisms observed in CHF. In this article, we discuss the roles of the sodium pump and the endogenous mammalian cardenolides and their involvement in the pathophysiology of this disease in view of the regulation of intracellular calcium. Understanding the mechanisms for the release of mammalian cardenolides in plasma, the alterations in sodium pump isoforms and function, and the modulation of pathways involving calcium in hypertrophy and CHF may assist in the development of new biological markers capable of predicting the disease before significant progression and irreversible heart failure.