Emerging therapies for the management of decompensated heart failure: from bench to bedside.
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.
deGoma
Emil M
EM
Stanford University, Stanford, California 94305, USA.
Vagelos
Randall H
RH
Fowler
Michael B
MB
Ashley
Euan A
EA
D065092:Antidiuretic Hormone Receptor Antagonists; D009320:Atrial Natriuretic Factor / Q000627:therapeutic use; D024722:Cardiac Myosins / Q000187:drug effects; D002316:Cardiotonic Agents / Q000627:therapeutic use*; D002317:Cardiovascular Agents / Q000627:therapeutic use*; D005043:Etiocholanolone / Q000031:analogs & derivatives / Q000627:therapeutic use; D006333:Heart Failure / Q000188:drug therapy*; D006801:Humans; D045283:Natriuretic Agents / Q000627:therapeutic use*; D010446:Peptide Fragments / Q000627:therapeutic use; D010480:Perhexiline / Q000627:therapeutic use; D058915:Purinergic P1 Receptor Antagonists; D000254:Sodium-Potassium-Exchanging ATPase / Q000037:antagonists & inhibitors
D065092:Antidiuretic Hormone Receptor Antagonists; D002316:Cardiotonic Agents; D002317:Cardiovascular Agents; D045283:Natriuretic Agents; D010446:Peptide Fragments; D058915:Purinergic P1 Receptor Antagonists; C056452:Ularitide; D009320:Atrial Natriuretic Factor; D005043:Etiocholanolone; D024722:Cardiac Myosins; D000254:Sodium-Potassium-Exchanging ATPase; D010480:Perhexiline; C468128:Istaroxime