verbatim): A critical untested biochemical hypothesis of human heart failure, as specifically emphasized by the NHLBI Special Emphasis Panel (SEP) on Heart Failure Research, is the Contribution of Energy Depletion to Heart Failure. This hypothesis suggests that energy transfer is reduced in congestive heart failure (CHF) and may limit contractile function. ATP is the biochemical fuel that sustains normal contractile function and creatine phosphate (Pcr) rapidly re-generates ATP via the creatine kinase (CK) reaction and is the major energy reserve in cardiac tissues. 31P magnetic resonance spectroscopy (MRS) is the only non-invasive means for directly studying cardiac biochemical energy metabolism. The investigators developed many of the 31P MRS techniques used today to quantify human cardiac CK metabolites and recent MRS techniques capable of detecting more subtle limitations in energy transfer. We propose here a close collaboration among experts in bioenergetics and novel imaging techniques with heart failure clinicians to combine for the first time biochemical investigations under physiological conditions with state-of-the-art assessments of contractile function and robust clinical correlates to evaluate whether energy depletion is present and contributes mechanistically to human heart failure progression. The three specific aims are: 1. To test the hypothesis that the myocardial metabolite concentrations of the CK energy reserve system are reduced in proportion to heart failure severity and predict its progression. 2. To evaluate energy reserve in heart failure, we will test the hypothesis that the response of the cardiac creatine kinase energy reserve to modulations of myocardial energy demand differs in normal and failing human myocardium. 3.To evaluate a metabolic intervention, we will test the hypothesis that oral creatine supplementation can improve myocardial energetics and thereby improve contractile function, symptoms and exercise tolerance of patients with chronic congestive heart failure.

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National Heart, Lung, and Blood Institute (NHLBI)
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Cardiovascular and Pulmonary Research A Study Section (CVA)
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Johns Hopkins University
Internal Medicine/Medicine
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Bonanno, Gabriele; Hays, Allison G; Weiss, Robert G et al. (2018) Self-gated golden angle spiral cine MRI for coronary endothelial function assessment. Magn Reson Med 80:560-570
Weiss, Kilian; Schär, Michael; Panjrath, Gurusher S et al. (2017) Fatigability, Exercise Intolerance, and Abnormal Skeletal Muscle Energetics in Heart Failure. Circ Heart Fail 10:
Hays, Allison G; Iantorno, Micaela; Schär, Michael et al. (2017) Local coronary wall eccentricity and endothelial function are closely related in patients with atherosclerotic coronary artery disease. J Cardiovasc Magn Reson 19:51
Iantorno, Micaela; Hays, Allison G; Schär, Michael et al. (2016) Simultaneous Noninvasive Assessment of Systemic and Coronary Endothelial Function. Circ Cardiovasc Imaging 9:e003954
Weiss, Kilian; Bottomley, Paul A; Weiss, Robert G (2015) On the theoretical limits of detecting cyclic changes in cardiac high-energy phosphates and creatine kinase reaction kinetics using in vivo ³¹P MRS. NMR Biomed 28:694-705
Zhang, Yi; Zhou, Jinyuan; Bottomley, Paul A (2015) Minimizing lipid signal bleed in brain (1) H chemical shift imaging by post-acquisition grid shifting. Magn Reson Med 74:320-9
Schär, Michael; Gabr, Refaat E; El-Sharkawy, AbdEl-Monem M et al. (2015) Two repetition time saturation transfer (TwiST) with spill-over correction to measure creatine kinase reaction rates in human hearts. J Cardiovasc Magn Reson 17:70
Soleimanifard, Sahar; Stuber, Matthias; Hays, Allison G et al. (2014) Robust volume-targeted balanced steady-state free-precession coronary magnetic resonance angiography in a breathhold at 3.0 Tesla: a reproducibility study. J Cardiovasc Magn Reson 16:27
Strauss, David G; Loring, Zak; Selvester, Ronald H et al. (2013) Right, but not left, bundle branch block is associated with large anteroseptal scar. J Am Coll Cardiol 62:959-67
Akki, Ashwin; Gupta, Ashish; Weiss, Robert G (2013) Magnetic resonance imaging and spectroscopy of the murine cardiovascular system. Am J Physiol Heart Circ Physiol 304:H633-48

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