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(Circulation. 2002;105:2099.)
© 2002 American Heart Association, Inc.

Clinical Cardiology: New Frontiers

New Therapeutic Options in Congestive Heart Failure: Part I

John McMurray, MD, FRCP, FESC; Marc A. Pfeffer, MD, PhD

From the Clinical Research Initiative in Heart Failure, University of Glasgow, Scotland (J.M.), and the Cardiovascular Division, Brigham and Women’s Hospital, Boston, Mass (M.A.P.).

Correspondence to Dr. John J.V. McMurray, Clinical Research Initiative in Heart Failure, University of Glasgow, Wolfson Building, Glasgow G12 8QQ, Scotland.

	Introduction

 
The need for new treatments for congestive heart failure (CHF) is clear. Population morbidity and mortality, although they are improving, remain high.^1,2 In this article, we review potential future therapies for CHF, building on our understanding of pathophysiological mechanisms and insights gained from previous studies of therapeutic interventions. The focus is on ambulatory CHF associated with left ventricular (LV) systolic dysfunction, although heart failure with preserved systolic function is also discussed. Given the broad scope of this review, individual areas can be addressed only briefly. The first part of this review deals with the pathophysiological basis of therapy and the use of neurohumoral antagonists in CHF with low LV ejection fraction (LVEF).

	Pathophysiological Basis of Treatment

 
Although the pathophysiology of CHF has recently been reviewed in detail, it is important to mention key concepts as the basis of therapy.^3,4

Neurohumoral Pathways
Over the past 20 years, the "neurohumoral hypothesis" has evolved to focus less on the impact of these pathways on the blood vessels and kidneys and more on the heart (Figure 1, and see below).⁵ This in part reflects the benefit of ß-blockers and spironolactone, treatments that are not vasodilators.^6–10 New peptides, such as the endothelins, and other mediators that are not conventional endocrine, autocrine, or paracrine factors, such as cytokines and free radicals, have also been postulated to play a role in CHF.^11,12 These, in turn, are now thought to set into motion pathophysiological processes, such as apoptosis, that had not yet been recognized when the neurohumoral model was originally postulated (. . . [Full Text of this Article]

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