Learning from failure: congestive heart failure in the postgenomic age

The prognosis of heart failure is worse than that of most cancers, but new therapeutic interventions using stem and other cell-based therapies are succeeding in the fight against it, and old drugs, with new twists, are making a comeback.Genetically engineered animal models are driving insights into the molecular mechanisms that cause hearts to fail, accelerating drug discoveries, and inspiring cell-based therapeutic interventions for both acquired and inheritable cardiac diseases.Heart failure threatens to eclipse infectious disease as the major cause of death worldwide, with the prevalence rising as populations age, Western diets are emulated, and the rate of acute mortality from myocardial infarction subsides (1-3).Given the pace of these 3 trends, recognition of the emerging heart failure epidemic by clinicians, patients, public health officials, the pharmaceutical and biotechnology industries, and policy makers, already long overdue, is crucial for coping with the medical and economic challenges that loom ahead.Thanks to the efforts of scientists worldwide, however, substantial progress is being made toward understanding the underlying etiology, pathogenesis, and mechanisms of heart failure, and, ultimately, toward the prevention of heart failure.This review series will address selected but complementary and intricately interrelated triggers, such as oxidative stress, nitrosative stress, signal transduction, alterations in intracellular calcium handling, mitochondrial dysfunction, inherited mutations, and myocyte loss, that culminate in heart failure (Figure 1).Emphasis is given, too, to the nodal control points in signal transduction and transcription, whose modulation holds especially salutary promise, and to the nascent field of cardiac regeneration as a therapeutic reality.