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J Am Coll Cardiol, 2006; 48:2397-2409, doi:10.1016/j.jacc.2006.08.039 (Published online 28 November 2006).
© 2006 by the American College of Cardiology Foundation
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Emerging Therapies for the Management of Decompensated Heart Failure

From Bench to Bedside

Emil M. deGoma, MD, Randall H. Vagelos, MD, FACC, Michael B. Fowler, MB, MRCP, FACC and Euan A. Ashley, MRCP, DPhil*

Stanford University, Stanford, California


Figure 1
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  		Figure 1 Overview of emerging pharmacotherapies for the management of acute decompensated heart failure. ADP = adenosine diphosphate; AQP = aquaporin-2; AVP = arginine vasopressin; cAMP = cyclic adenosine monophosphate; cGMP = cyclic guanosine monophosphate; CPT-1 = carnitine palmitoyl transferase-1; Gs = stimulatory G-protein; Na/K-ATPase = adenosine triphosphate-dependent transmembrane sodium-potassium pump; PKA = protein kinase A. Illustration by Rob Flewell.

 

Figure 2
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  		Figure 2 The myosin ATPase cycle. Cardiac myosin activators appear to accelerate the rate-limiting step, hastening the transition of myosin from the weakly filament-bound to the strongly filament-bound state. ADP = adenosine diphosphate; ATP = adenosine triphosphate. Illustration by Rob Flewell.

 

Figure 3
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  		Figure 3 Change in left ventricular dP/dtmax comparing istaroxime (PST-2744) to dobutamine in 5 dogs with chronic ischemic heart failure. No difference was found between PST-2744 and 5 µg/kg/min dobutamine. Both significantly increased dP/dtmax (p < 0.05). Reproduced with permission (26).

 

Figure 4
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  		Figure 4 Adenosine antagonist BG9719 augments diuresis and preserves glomerular filtration rate (GFR) when administered alone or in combination without furosemide. Reproduced with permission (25).

 

Figure 5
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  		Figure 5 Vasopressin (AVP) stimulates synthesis of aquaporin-2 (AQP) water channel proteins and their transport to the apical surface of collecting duct principal cells. Other abbreviations as in Figure 1. Illustration by Rob Flewell.

 

Figure 6
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  		Figure 6 Tolvaptan therapy increased 24-h urine volume compared with placebo in patients hospitalized for decompensated heart failure. Reproduced with permission (77).

 

Figure 7
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  		Figure 7 Changes from baseline during 24-h placebo or urodilatin infusion, and after discontinuation. *p < 0.05 versus placebo; {dagger}p < 0.05 versus baseline. NT-pro-BNP = N-terminal pro-B-type natriuretic peptide; PCWP = pulmonary capillary wedge pressure; RAP = right atrial pressure. Reproduced with permission (101).

 

Figure 8
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  		Figure 8 Effect of perhexiline treatment on peak exercise oxygen consumption (VO2 max) and left ventricular ejection fraction (LVEF) in congestive heart failure patients. p < 0.001 in both cases. Reproduced with permission (134).

 




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