Cardiac metabolism in patients with dilated and hypertrophic cardio‐myopathy: Assessment with proton‐decoupled P‐31 MR spectroscopy

Roos, Albert de; Doornbos, Joost; Luyten, Peter R.; Oosterwaal, Lambère J. M. P.; Hollander, Jan A. den; Wall, Ernst E. van der

doi:10.1002/jmri.1880020616

Cited by 121 publications

(57 citation statements)

References 22 publications

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“…39 Because CK is relatively abundant even in the failing heart, 25,28 -32,38,40 a lower total creatine pool means that [PCr] must also be lower. 31 P NMR studies in the early 1990s by several groups [41][42][43][44] showed that [PCr]/[ATP] is lower in dilated cardiomyopathy and heart failure. In Figure 2, typical 31 P NMR spectra obtained noninvasively from normal and failing human hearts illustrate the changes in [ATP] and [PCr] that characterize the failing heart.…”

Section: Pcr and The Failing Heartmentioning

confidence: 99%

Is the Failing Heart Energy Starved?

Ingwall

Weiss

2004

Circulation Research

546

281

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Abstract-The requirement of chemical energy in the form of ATP to support systolic and diastolic work of the heart is absolute. Because of its central role in cardiac metabolism and performance, the subject of this review on energetics in the failing heart is ATP. We briefly review the basics of myocardial ATP metabolism and describe how this changes in the failing heart. We present an analysis of what is now known about the causes and consequences of these energetic changes and conclude by commenting on unsolved problems and opportunities for future basic and clinical research. Key Words: adenosine triphosphate Ⅲ phosphocreatine Ⅲ creatine kinase Ⅲ familial hypertrophic cardiomyopathy Ⅲ heart failure T he energy starvation hypothesis suggesting that the failing heart is energy-starved is decades old. 1,2 Because ATP is required for normal systolic and diastolic contractile performance, the idea that the failing heart is unable to meet the hemodynamic requirements of the body because there is not enough chemical energy available is logical. The hypothesis was initially set aside for several reasons. First, it was unclear whether the concentration of ATP ([ATP]) decreased. Second, it was reasoned that even if there were decreases in [ATP] in the failing heart, the remaining ATP should be sufficient to supply the ATP-requiring reactions in the myocyte. Third, our understanding of how ATP synthesis and use are regulated was remarkably incomplete. A good example of our ignorance about cardiac energetics was the use of inotropic agents to increase performance of the failing human heart. While increasing performance, these agents did so at great energetic cost and often resulted in increased, rather than decreased, heart failure mortality.There is now renewed interest in the energy-starvation hypothesis. 3,4 New biophysical tools such as nuclear magnetic resonance (NMR) spectroscopy, positron emission tomography (PET), and transgenesis using the mouse have allowed old questions to be revisited and new ones to be formulated. Combining old and new strategies to address the "energy starvation" hypothesis, we have learned much. We now know when and by how much [ATP] decreases in the hypertrophied and failing heart. We now know that despite increases in some ATP synthesizing pathways such as glycolysis, other pathways such as the creatine kinase (CK)-phosphocreatine (PCr) system decrease. Finally, we now have a better understanding of how the myocyte accomplishes the tasks of maintaining (near) normal ATP supply Original

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Section: Pcr and The Failing Heartmentioning

confidence: 99%

Is the Failing Heart Energy Starved?

Ingwall

Weiss

2004

Circulation Research

546

281

View full text Add to dashboard Cite

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“…We corrected ATP for the contribution originated from blood in the cardiac chambers based on a previous study (13). We corrected PCr/ATP ratios for partial saturation effects using T1 values obtained from inversion recovery experiments.…”

Section: Mrs Analysismentioning

confidence: 99%

Abnormal Left Ventricular Energy Metabolism in Obese Men With Preserved Systolic and Diastolic Functions Is Associated With Insulin Resistance

Perseghin

Ntali²,

Cobelli

et al. 2007

Diabetes Care

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OBJECTIVE -Perturbations in cardiac energy metabolism might represent early alterations in diabetes preceding functional and pathological changes. We evaluated left ventricular (LV) structure/geometry and function in relation to energy metabolism and cardiovascular risk factors in overweight/obese men using magnetic resonance techniques. RESULTS -LV mass increased across quartiles of BMI; meanwhile, the volumes did not differ. Parameters of LV systolic and diastolic function were not different among quartiles. The phosphocreatine-to-ATP ratio was reduced across increasing quartiles of mean Ϯ SD BMI (2.25 Ϯ 0.52, 1.89 Ϯ 0.26, 1.99 Ϯ 0.38, and 1.79 Ϯ 0.29; P Ͻ 0.006) in association with insulin sensitivity (computer homeostasis model assessment 2 model); this relation was independent of age, BMI, blood pressure, wall mass, HDL cholesterol, triglycerides, smoking habits, and metabolic syndrome. RESEARCH DESIGN AND METHODSCONCLUSIONS -Abnormal LV energy metabolism was detectable in obese men in the presence of normal function, supporting the hypothesis that metabolic remodeling in insulin resistant states precedes functional and structural/geometrical remodeling of the heart regardless of the onset of overt hyperglycemia. Diabetes Care 30:1520-1526, 2007C ardiovascular disease is the leading cause of death in patients with type 2 diabetes (1,2). The existence of a diabetic cardiomyopathy distinct from ischemic injury was confirmed, but the challenge of recognizing its specific features remained unresolved because diabetes could also provoke cardiac damage via coronary macrovascular disease, autonomic dysfunction, and coronary microvascular disease (3). It was proposed that altered metabolism and impaired insulin action in the heart might be cause and consequence of altered cardiac function (4) and that metabolic remodeling in diabetes might precede, cause, and sustain the functional and structural/geometrical remodeling of the heart (5). In keeping with this hypothesis, cardiac energy metabolism was found to be abnormal in patients with type 2 diabetes despite the lack of major cardiac dysfunctions (6) or the presence of diastolic dysfunction (7). Those studies were performed in middleage individuals (52-57 years old) in whom diabetes was diagnosed 1 (7) to 3 (6) years earlier. Therefore, the question whether the alterations of cardiac energy metabolism were due to the hyperglycemic state itself or whether they were secondary to the metabolic features characterizing the prediabetic state remained unanswered.This study was undertaken to assess whether obesity was associated with impaired cardiac structure/geometry, function, and energy metabolism and to establish whether these potential alterations were associated with the cardiovascular and metabolic risk factors accompanying insulin resistance conditions. RESEARCH DESIGN AND METHODSWe selected 81 apparently healthy men with no previous history of diabetes, hypertension, dyslipidemias, coronary, cerebral, or peripheral vascular events, no history of dilated cardiomy...

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“…Reduced CR appeared to reflect disease severity. There were previous reports examining myocardial PCr and ATP in patients with LV hypertrophy of HHD or HCM by 31 P MRS. 18 Some reports indicated that myocardial PCr/ATP ratios decreased, 19,20 while others did not. 21,22 The discrepancy may be due to differences in the Scatterplots showing the total creatine (CR) concentration in the myocardium of patients with heart disease, graded according to the New York Heart Association (NYHA) classification.…”

Section: Creatine In the Diseased Myocardiummentioning

confidence: 99%