ABSTRACT

Activation of the sympathetic nervous system in congestive heart failure was initially

described in 1962 by Chidsey et al. who found that heart failure patients had

augmented norepinephrine responses at rest and during exercise (1). The significance

of the sympathetic nervous system in the pathophysiology of heart failure became

increasingly more apparent as circulating catecholamine levels were found to correlate

with disease severity and mortality in heart failure patients (2,3). While

sympathoadrenergic activation initially improves and maintains cardiac function, the

compensatory response eventually turns pathologic and maladaptive. The mechanisms

by which sustained sympathoadrenergic activation leads to declining cardiac function

are complex, involving deleterious alterations in the b-adrenergic receptor signaling pathway as well as direct cardiotoxic effects of norepinephrine. That b-adrenergic receptor antagonists, b-blockers, would have a role in the treatment for heart failure may now seem rudimentary. However, early paradigms of heart failure focused

primarily on reduced systolic function and regarded negative inotropes such as

b-blockers as intuitively contraindicated. It is only after nearly half a century of basic science investigations establishing biological rationale, mechanistic studies showing

physiologic effects, and large randomized clinical trials (4-12) demonstrating

morbidity and mortality benefits that b-blockers are now accepted as a weapon in

the standard armamentarium against heart failure.