Recent advances in metabolic imaging

Journal of Nuclear Cardiology

Volumn 20, Issue 6, 2013, Pages 1147-1172

  Gropler, Robert J ^a  

^a WASHINGTON UNIVERSITY SCHOOL OF MEDICINE   (United States)

Author keywords

cardiovascular disease; imaging; Metabolism

Indexed keywords

1 ACETATE C 11; 1 PALMITATE C 11; 1 PYRUVATE C 13; 14 FLUORO 6 THIAHEPTADECANOIC ACID F 18; 15 [4 (2 FLUOROETHOXY)PHENYL]PENTADECANOIC ACID F 18; 16 FLUORO 4 THIAPALMITATE F 18; 18 FLUORO 4 THIAOLEATE F 18; 6 (2 FLUOROPROPYL) 4 METHYLPYRIDIN 2 AMINE F 18; BICARBONATE C 13; CARBON 11; CARVEDILOL; FATTY ACID; FLUORINE 18; FLUORODEOXYGLUCOSE F 18; GLUCAGON LIKE PEPTIDE 1; GLUCOSE; GLUCOSE TRANSPORTER 4; HEMOGLOBIN A1C; INSULIN; IODINE 131; METFORMIN; OXYGEN 15; OXYGEN 17; PEROXISOME PROLIFERATOR ACTIVATED RECEPTOR ALPHA; PHOSPHORUS 31; PIOGLITAZONE; RADIOISOTOPE; RADIOPHARMACEUTICAL AGENT; ROSIGLITAZONE; UNCLASSIFIED DRUG; UNINDEXED DRUG;

CARDIOMYOPATHY; CELL METABOLISM; CELL VIABILITY; CLINICAL RESEARCH; COMPUTER ASSISTED EMISSION TOMOGRAPHY; DIABETES MELLITUS; DRUG DESIGN; DRUG DEVELOPMENT; DRUG TARGETING; ENERGY TRANSFER; EQUIPMENT; GENE EXPRESSION; GENETIC MODEL; HEART DEVELOPMENT; HEART DISEASE; HEART FAILURE; HEART MUSCLE METABOLISM; HUMAN; HYPERTENSIVE HEART DISEASE; IMAGING; IN VITRO STUDY; ISCHEMIC HEART DISEASE; METABOLIC IMAGING; MOLECULAR IMAGING; NONHUMAN; OBESITY; PRIORITY JOURNAL; RADIOCARDIOGRAPHY; REVIEW; SIGNAL TRANSDUCTION; SINGLE PHOTON EMISSION COMPUTER TOMOGRAPHY; SMALL ANIMAL IMAGING;

CARDIOVASCULAR DISEASES; FATTY ACIDS; HUMANS; INSULIN RESISTANCE; MAGNETIC RESONANCE IMAGING; MAGNETIC RESONANCE SPECTROSCOPY; MYOCARDIAL ISCHEMIA; MYOCARDIUM; NITRIC OXIDE SYNTHASE TYPE II; OXYGEN CONSUMPTION; POSITRON-EMISSION TOMOGRAPHY; PPAR ALPHA; TOMOGRAPHY, EMISSION-COMPUTED, SINGLE-PHOTON;

EID: 84891029326     PISSN: 10713581     EISSN: 15326551     Source Type: Journal    
DOI: 10.1007/s12350-013-9786-z     Document Type: Review

References (173)

1. Stanley WC, Lopaschuk GD, McCormack JG. Regulation of energy substrate metabolism in the diabetic heart. Cardiovasc Res 1997;34:25-33.
2. Neely JR, Morgan HE. Relationship between carbohydrate and lipid metabolism and the energy balance of heart muscle. Ann Rev Physiol 1974;36:413-59.
3. Finck BN, et al. A critical role for PPARα-mediated lipotoxicity in the pathogenesis of diabetic cardiomyopathy: Modulation by dietary fat content. Proc Natl Acad Sci USA 2003;100:1226-31.
4. Depre C, et al. Unloaded heart in vivo replicates fetal gene expression of cardiac hypertrophy. Nat Med 1998;4:1269-75.
5. Taegtmeyer H, Dilsizian V. Imaging myocardial metabolism and ischemic memory. Nat Clin Pract Cardiovasc Med 2008;5(Suppl 2):S42-8.
6. Taegtmeyer H, McNulty P, Young ME. Adaptation and maladaptation of the heart in diabetes: Part I: General concepts. Circulation 2002;105:1727-33.
7. Boudina S, Abel ED. Diabetic cardiomyopathy revisited. Circulation 2007;115:3213-23.
8. Thorn SL, et al. Repeatable noninvasive measurement of mouse myocardial glucose uptake with 18F-FDG: Evaluation of tracer kinetics in a type 1 diabetes model. J Nucl Med 2013;54:1637-44.
9. Shoghi KI, et al. In vivo metabolic phenotyping of myocardial substrate metabolism in rodents: Differential efficacy of metformin and rosiglitazone monotherapy. Circ Cardiovasc Imaging 2009;2:373-81.
10. Sharp TL, et al. Techniques necessary for multiple tracer quantitative small-animal imaging studies. Nucl Med Biol 2005;32:875-84.
11. Su Y, Welch MJ, Shoghi KI. The application of maximum likelihood factor analysis (MLFA) with uniqueness constraints on dynamic cardiac microPET data. Phys Med Biol 2007;52:2313-34.
12. Shoghi KI, Welch MJ. Hybrid image and blood sampling input function for quantification of small animal dynamic PET data. Nucl Med Biol 2007;34:989-94.
13. Kim J, et al. Minimally invasive method of determining blood input function from PET images in rodents. J Nucl Med 2006;47:330-6.
14. Shoghi KI, et al. Time course of alterations in myocardial glucose utilization in the Zucker diabetic fatty rat with correlation to gene expression of glucose transporters: A small-animal PET investigation. J Nucl Med 2008;49:1320-7.
15. 11C-acetate in rats with small-animal PET. J Nucl Med 2006;47:477-85.
16. (18)F-labeled 4-thia palmitate as a PET tracer of myocardial fatty acid oxidation. Nucl Med Biol 2000;27:221-31.
17. 18F-fluoro-4-thia-palmitate as a PET probe for myocardial fatty acid oxidation: Effects of hypoxia and composition of exogenous fatty acids. J Nucl Med 2006;47:173-81.
18. (18)F-fluoro-4-thia-oleate as a PET probe of fatty acid oxidation. J Nucl Med 2010;51:1310-7.
19. Tu Z, et al. Synthesis and evaluation of 15-(4-(2-[(1)F]Fluoroethoxy) phenyl)pentadecanoic acid: A potential PET tracer for studying myocardial fatty acid metabolism. Bioconjug Chem 2010;21:2313-9.
20. Labbe SM, et al. Increased myocardial uptake of dietary fatty acids linked to cardiac dysfunction in glucose-intolerant humans. Diabetes 2012;61:2701-10.
21. Labbe SM, et al. Organ-specific dietary fatty acid uptake in humans using positron emission tomography coupled to computed tomography. Am J Physiol Endocrinol Metab 2011;300:E445-53.
22. O'Donnell JM, et al. The absence of endogenous lipid oxidation in early stage heart failure exposes limits in lipid storage and turnover. J Mol Cell Cardiol 2008;44:315-22.
23. Saddik M, Lopaschuk GD. Triacylglycerol turnover in isolated working hearts of acutely diabetic rats. Can J Physiol Pharmacol 1994;72:1110-9.
24. 14C-labeled substrates in humans. J Clin Invest 1987;79:359-66.
25. Wicklmayr M, et al. Inhibition of muscular triglyceride lipolysis by ketone bodies: a mechanism for energy-preservation in starvation. Horm Metab Res 1986;18:476-8.
26. 11C-palmitate. J Nucl Cardiol 2009;16:411-21.
27. Bucci M, et al. Trimetazidine reduces endogenous free fatty acid oxidation and improves myocardial efficiency in obese humans. Cardiovasc Ther 2012;30:333-41.
28. Banke NH, et al. Preferential oxidation of triacylglyceride-derived fatty acids in heart is augmented by the nuclear receptor PPARα. Circ Res 2010;107:233-41.
29. Finck BN. The PPAR regulatory system in cardiac physiology and disease. Cardiovasc Res 2007;73:269-77.
30. Brown PJ, et al. Identification of a subtype selective human PPARα agonist through parallel-array synthesis. Bioorg Med Chem Lett 2001;11:1225-7.
31. (11)C]KSM-01 for imaging PPAR-alpha receptors. Bioorg Med Chem Lett 2012;22:6233-6.
32. 18F-labeled PPARgamma antagonists. Nucl Med Biol 2012;39:77-87.
33. Alderton WK, Cooper CE, Knowles RG. Nitric oxide synthases: Structure, function and inhibition. Biochem J 2001;357(Pt 3):593-615.
34. 18F]6-(2-fluoropropyl)-4-methyl-pyridin-2-amine as a potential PET tracer for inducible nitric oxide synthase. J Med Chem 2009;52:2443-53.
35. 18F]6-(2-fluoropropyl)-4-methyl-pyridin-2-amine as a potential PET tracer for inducible nitric oxide synthase. J Med Chem 2009;52:2443-53.
36. 18F-NOS as a potential PET radiopharmaceutical for inducible nitric oxide synthase in humans. J Nucl Med 2012;53:994-1001.
37. Holloway CJ, et al. Clinical cardiac magnetic resonance spectroscopy. Prog Cardiovasc Dis 2011;54:320-7.
38. Neubauer S, et al. Myocardial phosphocreatine-to-ATP ratio is a predictor of mortality in patients with dilated cardiomyopathy. Circulation 1997;96:2190-6.
39. Ingwall JS, Weiss RG. Is the failing heart energy starved? On using chemical energy to support cardiac function. Circ Res 2004;95:135-45.
40. Bizino MB, Hammer S, Lamb HJ. Metabolic imaging of the human heart: Clinical application of magnetic resonance spectroscopy. Heart 2013. doi: 10.1136/heartjnl-2012-302546.
41. Li D, et al. Myocardial signal response to dipyridamole and dobutamine: Demonstration of the BOLD effect using a double-echo gradient-echo sequence. Magn Reson Med 1996;36:16-20.
42. Zheng J, et al. Dynamic estimation of the myocardial oxygen extraction ratio during dipyridamole stress by MRI: A preliminary study in canines. Magn Reson Med 2004;51:718-26.
43. Fieno DS, et al. Myocardial perfusion imaging based on the blood oxygen level-dependent effect using T2-prepared steady-state free-precession magnetic resonance imaging. Circulation 2004;110:1284-90.
44. Karamitsos TD, et al. Relationship between regional myocardial oxygenation and perfusion in patients with coronary artery disease: Insights from cardiovascular magnetic resonance and positron emission tomography. Circ Cardiovasc Imaging 2010;3:32-40.
45. McCommis KS, et al. Quantification of regional myocardial oxygenation by magnetic resonance imaging: Validation with positron emission tomography. Circ Cardiovasc Imaging 2010;3:41-6.
46. McCommis KS, et al. Quantification of global myocardial oxygenation in humans: Initial experience. J Cardiovasc Magn Reson 2010;12:34.
47. 17O MRI: Toward direct quantification of myocardial oxygen consumption. Magn Reson Med 2010;63:1442-7.
48. Schroeder MA, et al. Hyperpolarized magnetic resonance: A novel technique for the in vivo assessment of cardiovascular disease. Circulation 2011;124:1580-94.
49. Ardenkjaer-Larsen JH, et al. Increase in signal-to-noise ratio of >10,000 times in liquid-state NMR. Proc Natl Acad Sci USA 2003;100:10158-63.
50. 13C allows a direct measure of flux through a single enzyme-catalyzed step by NMR. Proc Natl Acad Sci USA 2007;104:19773-7.
51. Schroeder MA, et al. In vivo assessment of pyruvate dehydrogenase flux in the heart using hyperpolarized carbon-13 magnetic resonance. Proc Natl Acad Sci USA 2008;105:12051-6.
52. 13C magnetic resonance spectroscopy. FASEB J 2009;23:2529-38.
53. 13C MRS. NMR Biomed 2011;24:201-8.
54. 13C-labelled bicarbonate. Nature 2008;453:940-3.
55. Desrois M, et al. Gender differences in hypertrophy, insulin resistance and ischemic injury in the aging type 2 diabetic rat heart. J Mol Cell Cardiol 2004;37:547-55.
56. Banke NH, et al. Sexual dimorphism in cardiac triacylglyceride dynamics in mice on long term caloric restriction. J Mol Cell Cardiol 2012;52:733-40.
57. Peterson LR, et al. Sex differences in myocardial oxygen and glucose metabolism. J Nucl Cardiol 2007;14:573-81.
58. Kakinuma Y, et al. The human female heart incorporates glucose more efficiently than the male heart. Int J Cardiol 2013. doi: 10.1016/j.ijcard.2013. 03.016.
59. Ren J. Influence of gender on oxidative stress, lipid peroxidation, protein damage and apoptosis in hearts and brains from spontaneously hypertensive rats. Clin Exp Pharmacol Physiol 2007;34:432-8.
60. Mendelsohn ME, Karas RH. Molecular and cellular basis of cardiovascular gender differences. Science 2005;308:1583-7.
61. Grist M, et al. Estrogen replacement stimulates fatty acid oxidation and impairs post-ischemic recovery of hearts from ovariectomized female rats. Can J Physiol Pharmacol 2002;80:1001-7.
62. Yoon M. The role of PPARα in lipid metabolism and obesity: Focusing on the effects of estrogen on PPARα actions. Pharmacol Res 2009;60:151-9.
63. Herrero P, et al. Impact of hormone replacement on myocardial fatty acid metabolism: potential role of estrogen. J Nucl Cardiol 2005;12:574-81.
64. Peterson LR, et al. Impact of gender on the myocardial metabolic response to Obesity. J Am Coll Cardiol Imaging 2008;1:424-33.
65. McMillin JB, et al. Mitochondrial metabolism and substrate competition in the aging Fischer rat heart. Cardiovasc Res 1993;27:2222-8.
66. Abu-Erreish GM, et al. Fatty acid oxidation by isolated perfused working hearts of aged rats. Am J Physiol 1977;232:E258-62.
67. Paradies G, et al. The effect of aging and acetyl-l-carnitine on the activity of the phosphate carrier and on the phospholipid composition in rat heart mitochondria. Biochim Biophys Acta 1992;1103:324-6.
68. Odiet JA, Boerrigter ME, Wei JY. Carnitine palmitoyl transferase-I activity in the aging mouse heart. Mech Ageing Dev 1995;79:127-36.
69. Iemitsu M, et al. Aging-induced decrease in the PPAR-alpha level in hearts is improved by exercise training. Am J Physiol Heart Circ Physiol 2002;283:H1750-60.
70. Kates AM, et al. Impact of aging on substrate metabolism by the human heart. J Am Coll Cardiol 2003;41:293-9.
71. Soto PF, et al. Impact of aging on myocardial metabolic response to dobutamine. Am J Physiol Heart Circ Physiol 2003;285:H2158-64.
72. van der Meer RW, et al. The ageing male heart: Myocardial triglyceride content as independent predictor of diastolic function. Eur Heart J 2008;29:1516-22.
73. Hollingsworth KG, et al. Left ventricular torsion, energetics, and diastolic function in normal human aging. Am J Physiol Heart Circ Physiol 2012;302:H885-92.
74. Soto PF, et al. Exercise training impacts the myocardial metabolism of older individuals in a gender-specific manner. Am J Physiol Heart Circ Physiol 2008;295:H842-50.
75. Lopaschuk G. Regulation of carbohydrate metabolism in ischemia and reperfusion. Am Heart J 2000;139(2 Pt 3):S115-9.
76. Araujo LI, et al. Abnormalities in myocardial metabolism in patients with unstable angina as assessed by positron emission tomography. Cardiovasc Drugs Ther 1988;2:41-6.
77. 18F-fluorodeoxyglucose in postischemic myocardium of patients with exercise-induced angina. Circulation 1986;74:81-8.
78. Tamaki N, et al. The role of fatty acids in cardiac imaging. J Nucl Med 2000;41:1525-34.
79. 99mTc-tetrofosmin SPECT and coronary angiography. Circ J 2004;68:547-52.
80. Kontos MC, et al. Iodofiltic acid I 123 (BMIPP) fatty acid imaging improves initial diagnosis in emergency department patients with suspected acute coronary syndromes: A multicenter trial. J Am Coll Cardiol 2010;56:290-9.
81. Moroi M, et al. Association between abnormal myocardial fatty acid metabolism and cardiac-derived death among patients undergoing hemodialysis: Results from a cohort study in Japan. Am J Kidney Dis 2013;61:466-75.
82. He ZX, et al. Direct imaging of exercise-induced myocardial ischemia with fluorine-18-labeled deoxyglucose and Tc-99m-sestamibi in coronary artery disease. Circulation 2003;108:1208-13.
83. 18F-FDG uptake after exercise-induced myocardial ischemia in patients with coronary artery disease. J Nucl Med 2008;49:1986-91.
84. Rupp H, Jacob R. Metabolically-modulated growth and phenotype of the rat heart. Eur Heart J 1992;13(Suppl D):56-61.
85. Barger PM, Kelly DP. Fatty acid utilization in the hypertrophied and failing heart: Molecular regulatory mechanisms. Am J Med Sci 1999;318:36-42.
86. Jamshidi Y, et al. Peroxisome proliferator-activated receptor alpha gene regulates left ventricular growth in response to exercise and hypertension. Circulation 2002;105:950-5.
87. Blair E, et al. Mutations in the gamma(2) subunit of AMP-activated protein kinase cause familial hypertrophic cardiomyopathy: Evidence for the central role of energy compromise in disease pathogenesis. Hum Mol Genet 2001;10:1215-20.
88. Handa N, et al. Quantitative FDG-uptake by positron emission tomography in progressive hypertrophy of rat hearts in vivo. Ann Nucl Med 2007;21:569-76.
89. Zhong M, et al. Quantitative PET imaging detects early metabolic remodeling in a mouse model of pressure-overload left ventricular hypertrophy in vivo. J Nucl Med 2013;54:609-15.
90. Sen S, et al. Glucose regulation of load-induced mTOR signaling and ER stress in mammalian heart. J Am Heart Assoc 2013;2:e004796.
91. De Las Fuentes L, et al. Myocardial fatty acid metabolism: Independent predictor of left ventricular mass in hypertensive heart disease. Hypertension 2003;41:83-7.
92. De las Fuentes L, et al. Hypertensive left ventricular hypertrophy is associated with abnormal myocardial fatty acid metabolism and myocardial efficiency. J Nucl Cardiol 2006;13:369-77.
93. Tuunanen H, et al. Myocardial perfusion, oxidative metabolism, and free fatty acid uptake in patients with hypertrophic cardiomyopathy attributable to the Asp175Asn mutation in the alpha-tropomyosin gene: A positron emission tomography study. J Nucl Cardiol 2007;14:354-65.
94. Razeghi P, et al. Downregulation of myocardial myocyte enhancer factor 2C and myocyte enhancer factor 2C-regulated gene expression in diabetic patients with nonischemic heart failure. Circulation 2002;106:407-11.
95. Buttrick PM, et al. Alterations in gene expression in the rat heart after chronic pathological and physiological loads. J Mol Cell Cardiol 1994;26:61-7.
96. Ouwens DM, et al. Cardiac contractile dysfunction in insulin-resistant rats fed a high-fat diet is associated with elevated CD36-mediated fatty acid uptake and esterification. Diabetologia 2007;50:1938-48.
97. Tuunanen H, et al. Decreased myocardial free fatty acid uptake in patients with idiopathic dilated cardiomyopathy: Evidence of relationship with insulin resistance and left ventricular dysfunction. J Card Fail 2006;12:644-52.
98. Sharma S, et al. Intramyocardial lipid accumulation in the failing human heart resembles the lipotoxic rat heart. FASEB J 2004;18:1692-700.
99. Davila-Roman VG, et al. Altered myocardial fatty acid and glucose metabolism in idiopathic dilated cardiomyopathy. J Am Coll Cardiol 2002;40:271-7.
100. Ardehali H, et al. Targeting myocardial substrate metabolism in heart failure: Potential for new therapies. Eur J Heart Fail 2012;14:120-9.
101. Fragasso G, et al. Metabolic therapy of heart failure. Curr Pharm Des 2008;14:2582-91.
102. Beanlands RS, et al. The effects of beta(1)-blockade on oxidative metabolism and the metabolic cost of ventricular work in patients with left ventricular dysfunction: A double-blind, placebo-controlled, positron-emission tomography study. Circulation 2000;102:2070-5.
103. Al-Hesayen A, et al. Selective versus nonselective beta-adrenergic receptor blockade in chronic heart failure: Differential effects on myocardial energy substrate utilization. Eur J Heart Fail 2005;7:618-23.
104. Fragasso G, et al. A randomized clinical trial of trimetazidine, a partial free fatty acid oxidation inhibitor, in patients with heart failure. J Am Coll Cardiol 2006;48:992-8.
105. Fragasso G, et al. Effects of metabolic modulation by trimetazidine on left ventricular function and phosphocreatine/adenosine triphosphate ratio in patients with heart failure. Eur Heart J 2006;27:942-8.
106. Tuunanen H, et al. Trimetazidine, a metabolic modulator, has cardiac and extracardiac benefits in idiopathic dilated cardiomyopathy. Circulation 2008;118:1250-8.
107. Tuder RM, et al. Exuberant endothelial cell growth and elements of inflammation are present in plexiform lesions of pulmonary hypertension. Am J Pathol 1994;144:275-85.
108. Tuder RM, Davis LA, Graham BB. Targeting energetic metabolism: A new frontier in the pathogenesis and treatment of pulmonary hypertension. Am J Respir Crit Care Med 2012;185:260-6.
109. Taraseviciene-Stewart L, et al. Inhibition of the VEGF receptor 2 combined with chronic hypoxia causes cell death-dependent pulmonary endothelial cell proliferation and severe pulmonary hypertension. FASEB J 2001;15:427-38.
110. Sakao S, et al. Initial apoptosis is followed by increased proliferation of apoptosis-resistant endothelial cells. FASEB J 2005;19:1178-80.
111. Tuder RM, et al. Expression of angiogenesis-related molecules in plexiform lesions in severe pulmonary hypertension: Evidence for a process of disordered angiogenesis. J Pathol 2001;195:367-74.
112. 18F]fluoro-d-glucose positron emission tomography to detect metabolic changes in pulmonary arterial hypertension hearts over 1 year. Ann Am Thorac Soc 2013;10:1-9.
113. Bokhari S, et al. PET imaging may provide a novel biomarker and understanding of right ventricular dysfunction in patients with idiopathic pulmonary arterial hypertension. Circ Cardiovasc Imaging 2011;4:641-7.
114. 18F-FDG uptake by right ventricular myocardium in idiopathic pulmonary arterial hypertension and pulmonary arterial hypertension associated with congenital heart disease. Pulm Circ 2012;2:365-72.
115. 18F]fluorodeoxyglucose accumulation in right ventricular free wall in patients with pulmonary hypertension and the effect of epoprostenol. J Am Coll Cardiol 2005;45:1849-55.
116. 18F]fluorodeoxyglucose accumulation in patients with heart failure. Circ Cardiovasc Imaging 2011;4:59-66.
117. Kenchaiah S, et al. Obesity and the risk of heart failure. N Engl J Med 2002;347:305-13.
118. Wong CY, et al. Alterations of left ventricular myocardial characteristics associated with obesity. Circulation 2004;110:3081-7.
119. Zhou YT, et al. Lipotoxic heart disease in obese rats: Implications for human obesity. Proc Natl Acad Sci USA 2000;97:1784-9.
120. Commerford SR, et al. Fat oxidation, lipolysis, and free fatty acid cycling in obesity-prone and obesity-resistant rats. Am J Physiol Endocrinol Metab 2000;279:E875-85.
121. Peterson LR, et al. Effect of obesity and insulin resistance on myocardial substrate metabolism and efficiency in young women. Circulation 2004;109:2191-6.
122. Iozzo P, et al. Contribution of glucose tolerance and gender to cardiac adiposity. J Clin Endocrinol Metab 2009;94:4472-82.
123. Viljanen AP, et al. Effect of caloric restriction on myocardial fatty acid uptake, left ventricular mass, and cardiac work in obese adults. Am J Cardiol 2009;103:1721-6.
124. Hammer S, et al. Prolonged caloric restriction in obese patients with type 2 diabetes mellitus decreases myocardial triglyceride content and improves myocardial function. J Am Coll Cardiol 2008;52:1006-12.
125. Lin CH, et al. Myocardial oxygen consumption change predicts left ventricular relaxation improvement in obese humans after weight loss. Obesity (Silver Spring) 2011;19:1804-12.
126. Domanski M, et al. The effect of diabetes on outcomes of patients with advanced heart failure in the BEST trial. J Am Coll Cardiol 2003;42:914-22.
127. Eguchi K, et al. Association between diabetes mellitus and left ventricular hypertrophy in a multiethnic population. Am J Cardiol 2008;101:1787-91.
128. Kannel WB. Incidence and epidemiology of heart failure. Heart Fail Rev 2000;5:167-73.
129. Kannel WB, Hjortland M, Castelli WP. Role of diabetes in congestive heart failure: The Framingham study. Am J Cardiol 1974;34:29-34.
130. Bahrami H, et al. Novel metabolic risk factors for incident heart failure and their relationship with obesity: The MESA (Multi-Ethnic Study of Atherosclerosis) study. J Am Coll Cardiol 2008;51:1775-83.
131. Okin PM, et al. Impact of diabetes mellitus on regression of electrocardiographic left ventricular hypertrophy and the prediction of outcome during antihypertensive therapy: The Losartan Intervention For Endpoint (LIFE) Reduction in Hypertension Study. Circulation 2006;113:1588-96.
132. Dries DL, et al. Prognostic impact of diabetes mellitus in patients with heart failure according to the etiology of left ventricular systolic dysfunction. J Am Coll Cardiol 2001;38:421-8.
133. Ryden L, et al. Efficacy and safety of high-dose lisinopril in chronic heart failure patients at high cardiovascular risk, including those with diabetes mellitus. Results from the ATLAS trial. Eur Heart J 2000;21:1967-78.
134. Young ME, McNulty P, Taegtmeyer H. Adaptation and maladaptation of the heart in diabetes: Part II: Potential mechanisms. Circulation 2002;105:1861-70.
135. Itani SI, et al. Involvement of protein kinase C in human skeletal muscle insulin resistance and obesity. Diabetes 2000;49:1353-8.
136. Ruderman NB, et al. Malonyl-CoA, fuel sensing, and insulin resistance. Am J Physiol 1999;276:E1-18.
137. Schmitz-Peiffer C, Craig DL, Biden TJ. Ceramide generation is sufficient to account for the inhibition of the insulin-stimulated PKB pathway in C2C12 skeletal muscle cells pretreated with palmitate. J Biol Chem 1999;274:24202-10.
138. Finck BN, et al. The cardiac phenotype induced by PPARα overexpression mimics that caused by diabetes mellitus. J Clin Invest 2002;109:121-30.
139. Burkart EM, et al. Nuclear receptors PPARα/δ and PPARα direct distinct metabolic regulatory programs in the mouse heart. J Clin Invest 2007;117:3930-9.
140. van den Brom CE, et al. Altered myocardial substrate metabolism is associated with myocardial dysfunction in early diabetic cardiomyopathy in rats: Studies using positron emission tomography. Cardiovasc Diabetol 2009;8:39.
141. van den Brom CE, et al. Diabetic cardiomyopathy in Zucker diabetic fatty rats: The forgotten right ventricle. Cardiovasc Diabetol 2010;9:25.
142. Herrero P, et al. Increased myocardial fatty acid metabolism in patients with type 1 diabetes mellitus. J Am Coll Cardiol 2006;47:598-604.
143. Herrero P, et al. PET detection of the impact of dobutamine on myocardial glucose metabolism in women with type 1 diabetes mellitus. J Nucl Cardiol 2008;15:791-9.
144. Peterson LR, et al. Fatty acids and insulin modulate myocardial substrate metabolism in humans with type 1 diabetes. Diabetes 2008;57:32-40.
145. Rijzewijk LJ, et al. Altered myocardial substrate metabolism and decreased diastolic function in nonischemic human diabetic cardiomyopathy: Studies with cardiac positron emission tomography and magnetic resonance imaging. J Am Coll Cardiol 2009;54:1524-32.
146. Peterson LR, et al. Sex and type 2 diabetes: Obesity-independent effects on left ventricular substrate metabolism and relaxation in humans. Obesity (Silver Spring) 2012;20:802-10.
147. Monti LD, et al. Myocardial insulin resistance associated with chronic hypertriglyceridemia and increased FFA levels in type 2 diabetic patients. Am J Physiol Heart Circ Physiol 2004;287:H1225-31.
148. McGill JB, et al. Potentiation of abnormalities in myocardial metabolism with the development of diabetes in women with obesity and insulin resistance. J Nucl Cardiol 2011;18:421-9.
149. Rijzewijk LJ, et al. Myocardial steatosis is an independent predictor of diastolic dysfunction in type 2 diabetes mellitus. J Am Coll Cardiol 2008;52:1793-9.
150. Rijzewijk LJ, et al. Effects of hepatic triglyceride content on myocardial metabolism in type 2 diabetes. J Am Coll Cardiol 2010;56:225-33.
151. Ng AC, et al. Myocardial steatosis and biventricular strain and strain rate imaging in patients with type 2 diabetes mellitus. Circulation 2010;122:2538-44.
152. MacDonald MR, et al. Discordant short- and long-term outcomes associated with diabetes in patients with heart failure: Importance of age and sex: a population study of 5.1 million people in Scotland. Circ Heart Fail 2008;1:234-41.
153. Ho KK, et al. The epidemiology of heart failure: The Framingham Study. J Am Coll Cardiol 1993;22(4 Suppl A):6A-13A.
154. Gu K, Cowie CC, Harris MI. Diabetes and decline in heart disease mortality in US adults. JAMA 1999;281:1291-7.
155. van der Meer RW, et al. Pioglitazone improves cardiac function and alters myocardial substrate metabolism without affecting cardiac triglyceride accumulation and high-energy phosphate metabolism in patients with well-controlled type 2 diabetes mellitus. Circulation 2009;119:2069-77.
156. Hallsten K, et al. Enhancement of insulin-stimulated myocardial glucose uptake in patients with type 2 diabetes treated with rosiglitazone. Diabet Med 2004;21:1280-7.
157. Lyons MR, Peterson LR, McGill JB, Herrero P, Coggan AR, Saeed IM, et al. Impact of sex on the heart's metabolic and functional responses to diabetic therapies. Am J Physiol Heart Circ Physiol., under review.
158. 18F-fluorodeoxyglucose positron emission tomography imaging provides a noninvasive measure of carotid plaque inflammation in patients. J Am Coll Cardiol 2006;48:1818-24.
159. Tahara N, et al. Simvastatin attenuates plaque inflammation: Evaluation by fluorodeoxyglucose positron emission tomography. J Am Coll Cardiol 2006;48:1825-31.
160. 18F]-fluorodeoxyglucose positron emission tomography. Circulation 2002;105:2708-11.
161. (18)F-FDG accumulation in atherosclerotic plaques: Immunohistochemical and PET imaging study. J Nucl Med 2004;45:1245-50.
162. 18F-FDG for the detection of atherosclerosis in ApoE-/- mice. Eur J Nucl Med Mol Imaging 2007;34:1747-55.
163. Tawakol A, et al. Noninvasive in vivo measurement of vascular inflammation with F-18 fluorodeoxyglucose positron emission tomography. J Nucl Cardiol 2005;12:294-301.
164. 18F-Choline images murine atherosclerotic plaques ex vivo. Arterioscler Thromb Vasc Biol 2006;26:584-9.
165. 18F-FDG PET/CT in patients with carotid atherosclerosis and correlation with matrix metalloproteinase-1. J Nucl Med 2007;48:227-33.
166. 18F]- fluorodeoxyglucose positron emission tomography is associated with the metabolic syndrome. J Am Coll Cardiol 2007;49:1533-9.
167. 18F-FDG PET/CT identifies patients at risk for future vascular events in an otherwise asymptomatic cohort with neoplastic disease. J Nucl Med 2009;50:1611-20.
168. Tawakol A, et al. Intensification of statin therapy results in a rapid reduction in atherosclerotic inflammation: Results of a multicenter fluorodeoxyglucose-positron emission tomography/computed tomography feasibility study. J Am Coll Cardiol 2013;62:909-17.
169. Mizoguchi M, et al. Pioglitazone attenuates atherosclerotic plaque inflammation in patients with impaired glucose tolerance or diabetes a prospective, randomized, comparator-controlled study using serial FDG PET/CT imaging study of carotid artery and ascending aorta. JACC Cardiovasc Imaging 2011;4:1110-8.
170. Rogers IS, et al. Feasibility of FDG imaging of the coronary arteries: comparison between acute coronary syndrome and stable angina. JACC Cardiovasc Imaging 2010;3:388-97.
171. 18F-FDG uptake by fusion of PET and coronary CT angiography at sites of percutaneous stenting for acute myocardial infarction and stable coronary artery disease. J Nucl Med 2012;53:575-83.
172. Aragno MMG, Vercellinatto I, Bardini P, Raimondo S, Peiretti PG, Vercelli A, et al. Cardiac impairment in rabbits fed a high-fat diet is counteracted by dehydroepiandrosterone supplementation. Life Sci 2009;85:77-84.
173. (123)I]-iodophenyl-pentadecanoic acid identifies ischemic memory after demand ischemia. Circulation 2005;112:2169-74.