Heart Failure: From Gene to Therapy

Abstract

Congestive heart failure is the final endstage of various cardiac diseases with varying pathologies resulting in impaired systolic and diastolic function, activation of neurohumoral pathways, and high morbidity and mortality. The pathogenic processes leading to altered structure of the heart in the development of heart failure with systolic dysfunction has been termed “ventricular remodeling”. This concept relates to a complex of anatomical, physiological, histological and molecular changes of the myocardium in response to injury and increased wall stress (Fig. 1). Our understanding of ventricular remodeling has rapidly progressed from initial bedside observation of large hearts and edema in patients with heart disease to studies of the mechanical consequences of increased volumes, hemodynamic changes and wall stress in the failing left ventricle. Following the discovery of the neurohumoral activation in heart failure, more recently, attention has been attracted to the molecular and genetic alterations that promote further detoriation of the function of the heart and that determine the inexorable course to end-stage heart failure.