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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

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