Cardiac models in drug discovery and development: a review.

Cardiovascular diseases are among the leading causes of death in the developed world. Developing novel therapies for diseases like heart failure is crucial, but this is hampered by the high attrition rate in drug development. The withdrawal of drugs at the final hurdle of approval is mostly because of their unpredictable effects on normal cardiac rhythm. The advent of cardiac computational modeling in the last 5 decades has aided the understanding of heart function significantly. Recently, these models increasingly have been applied toward designing and understanding therapies for cardiac disease. This article will discuss how cellular models of electrophysiology, cell signaling, and metabolism have been used to investigate pharmacologic therapies for cardiac diseases including arrhythmia, ischemia, and heart failure.