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.