Heart Failure and Changes at the Periphery: Vascular, Inflammation, Neurohormonal, and Renal Systems

Abstract

Again, the clinical syndrome of chronic heart failure (HF) has traditionally been linked to malfunction of the heart as a pump, usually caused by insults to the myocardium. In recent years, there is mounting evidence to support the concept that the complex pathophysiology of heart failure begins with an abnormality of the heart, but then involves dysfunction of most body organs, including the cardiac, peripheral vascular, renal, neurohormonal, immune, as well as the inflammatory systems. The magnitude of these abnormalities has been related to disease progression and subsequent mortality. Less clear, however, is the origin of these derangements and the sequence of triggering mechanisms in the course of the natural history of HF. One of the known abnormalities associated with the complex clinical syndrome of HF is the profound disturbance in the regulation of the autonomic nervous system. The link between peripheral systems activated in HF and the central nervous system as a source of neurohumoral drive has therefore received increasing attention. The key abnormality in HF is the kidneys’ perception of an inadequate circulating volume by various sensors located on critical sites within the circulation. As a result, the normal relationship between intravascular volume and holding capacity, as perceived by these sensing mechanisms, is perturbed. This leads to the activation of various effector mechanisms whose aim is to increase intravascular volume and maintain blood pressure. The kidney is therefore the central site of action for these effectors that increase intravascular volume, and therefore plays a major pathogenetic role in the sodium and water retention in HF. Renal insufficiency is common in patients with HF and is an adverse prognostic factor.