ABSTRACT
Heart failure is a heterogeneous clinical syndrome but is fundamentally characterized by a
decrease in myocardial performance with a resultant decrease in cardiac output. As cardiac
output declines, a variety of compensatory mechanisms are activated, with both beneficial
and harmful acute and long-term effects. Peripheral vasoconstriction, a physiologic
response designed to maintain systemic perfusion pressure in response to a drop in cardiac
output, is a hallmark of the heart failure syndrome. Regulation of vascular tone is
controlled by complex neurohormonal and hemodynamic processes, including the
sympathetic nervous system, the renin-angiotensin system, and multiple endogenous
vasoconstrictive/vasodilatory factors. Vasoconstriction is functionally important in the
setting of trauma, severe hemorrhage, or short term decrease in cardiac performance,
acting to maintain arterial pressure and perfusion of the brain and other vital organs.
However, in the setting of heart failure, chronic vasoconstriction leads to reduced cardiac
output, increased myocardial oxygen consumption, decreased coronary perfusion, and
increased cell death (Fig. 1). This fundamental observation establishes the rationale for the
use of vasodilator agents in heart failure, a heterogeneous class of drugs that have become
mainstays in the management of acute and chronic heart failure.
