HOME SUBSCRIPTIONS CURRENT ISSUE PAST ISSUES CARDIOSOURCE SEARCH HELP FEEDBACK		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Figures Only Full Text Full Text (PDF) All Versions of this Article: j.jacc.2006.08.039v1 48/12/2397    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via ISI Web of Science (6) Citing Articles via Google Scholar Google Scholar Articles by deGoma, E. M. Articles by Ashley, E. A. Search for Related Content PubMed Articles by deGoma, E. M. Articles by Ashley, E. A.

STATE-OF-THE-ART PAPER

Emerging Therapies for the Management of Decompensated Heart Failure

From Bench to Bedside

Stanford University, Stanford, California.

Manuscript received May 18, 2006; revised manuscript received July 6, 2006, accepted July 31, 2006.

^_* Reprint requests and correspondence: Dr. Euan A. Ashley, Division of Cardiovascular Medicine, Falk CVRC, Stanford University, 300 Pasteur Drive, Stanford, California 94305. (Email: euan{at}stanford.edu).

While pharmaceutical innovation has been highly successful in reducing mortality in chronic heart failure, this has not been matched by similar success in decompensated heart failure syndromes. Despite outstanding issues over definitions and end points, we argue in this paper that an unprecedented wealth of pharmacologic innovation may soon transform the management of these challenging patients. Agents that target contractility, such as cardiac myosin activators and novel adenosine triphosphate-dependent transmembrane sodium-potassium pump inhibitors, provide inotropic support without arrhythmogenic increases in cytosolic calcium or side effects of more traditional agents. Adenosine receptor blockade may improve glomerular filtration and diuresis by exerting a direct beneficial effect on glomerular blood flow while vasopressin antagonists promote free water excretion without compromising renal function and may simultaneously inhibit myocardial remodeling. Urodilatin, the renally synthesized isoform of atrial natriuretic peptide, may improve pulmonary congestion via vasodilation and enhanced diuresis. Finally, metabolic modulators such as perhexiline may optimize myocardial energy utilization by shifting adenosine triphosphate production from free fatty acids to glucose, a unique and conceptually appealing approach to the management of heart failure. These advances allow optimism not only for the advancement of our understanding and management of decompensated heart failure syndromes but for the translational research effort in heart failure biology in general.

Abbreviations and Acronyms   ANP = atrial natriuretic peptide   ATP = adenosine triphosphate   AVP = arginine vasopressin   BNP = brain natriuretic peptide   cAMP = cyclic adenosine monophosphate   CI = confidence interval   DHF = decompensated heart failure   FFA = free fatty acid   LTCC = L-type calcium channel   NYHA = New York Heart Association   PCWP = pulmonary capillary wedge pressure   PKA = protein kinase A   RyR = ryanodine receptor

This article has been cited by other articles:

				H. Tuunanen, E. Engblom, A. Naum, K. Nagren, M. Scheinin, B. Hesse, K.E. Juhani Airaksinen, P. Nuutila, P. Iozzo, H. Ukkonen, et al. Trimetazidine, a Metabolic Modulator, Has Cardiac and Extracardiac Benefits in Idiopathic Dilated Cardiomyopathy Circulation, September 16, 2008; 118(12): 1250 - 1258. [Abstract] [Full Text] [PDF]

				G. W. Dec Istaroxime in heart failure new hope or more hype. J. Am. Coll. Cardiol., June 10, 2008; 51(23): 2286 - 2288. [Full Text] [PDF]

				F. L. Martin, T. Supaporn, H. H. Chen, S. M. Sandberg, Y. Matsuda, M. Jougasaki, and J. C. Burnett Jr. Distinct roles for renal particulate and soluble guanylyl cyclases in preserving renal function in experimental acute heart failure Am J Physiol Regulatory Integrative Comp Physiol, October 1, 2007; 293(4): R1580 - R1585. [Abstract] [Full Text] [PDF]