Sympathetic activation in heart failure: A target of therapeutic approaches

In heart failure, decreased cardiac output leads to a number of adaptive mechanisms. Among these, neuroendocrine activation including activation of the renin-angiotensin-aldosterone system, augmentation of vasopressin and endothelin release, and activation of the sympathetic nervous system occur. The increase of adrenergic drive is characterized by decreased baroreceptor sensitivity, increased plasma norepinephrine levels and cardiac norepinephrine spillover, and desensitization of postsynaptic β-adrenergic signal transduction. While increased sympathetic drive initially helps to maintain contractile performance of the damaged heart, the above changes chronically result in catecholamine refractoriness and are associated with a poor prognosis.