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(Circulation. 2002;105:1753.)
© 2002 American Heart Association, Inc.

Editorial

The "Unsympathetic" Nervous System of Heart Failure

John S. Floras, MD, DPhil

From University Health Network and Mount Sinai Hospital, Department of Medicine, and the University of Toronto, Toronto, Canada.

Correspondence to Dr John S. Floras, 1614–600 University Ave, Toronto, ON M5G 1X5 Canada. E-mail john.floras@utoronto.ca

Key Words: Editorials • nervous system, sympathetic • norepinephrine • heart failure

Sympathetic activation in heart failure is intimately linked to disease progression and to adverse outcome.^1–3 Contemporary management of heart failure relies on three antiadrenergic strategies, predicated on the hypothesis that interventions that counter sympathetic overactivity will improve both symptoms and prognosis. First, excessive central sympathetic outflow to the heart and periphery can be reduced by normalizing elevated cardiac filling pressures,⁴ by abolishing coexisting obstructive sleep apnea with nocturnal continuous positive airway pressure,⁵ or by attenuating sympathoexcitatory reflexes activated by exercising muscle through conditioning. Although rational, thus far these interventions have not been proven to improve survival.

See p 1797

A second approach has been to modulate the neural regulation of norepinephrine (NE) release. Examples include digitalis glycosides, which appear to sensitize acutely and therefore increase the discharge of arterial baroreceptors, and ACE inhibitors, which should diminish or block the prejunctional facilitatory effects of angiotensin II on NE release. However, the impact of ACE inhibitors on plasma NE (PNE) concentrations is relatively modest,^6,7 suggesting that their mortality benefit accrues primarily through nonadrenergic mechanisms.

Third, sympathetic activation may be addressed indirectly, by blocking the actions of catecholamines on postjunctional adrenergic receptors. A series of placebo-controlled trials has demonstrated the symptomatic, hemodynamic, and mortality benefits of ß-adrenoceptor antagonists.^8–10 ß₁ blockade, as exerted by metoprolol or bisoprolol, may be sufficient to achieve these effects. Whether concomitant ß₂-adrenoceptor antagonism, as with carvedilol or bucindolol, confers any additional benefit is the subject of an ongoing comparative mortality trial. Although carvedilol is also classified as an ₁ . . . [Full Text of this Article]

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