Exercise-Induced Decrease in Myocardial High-Energy Phosphate Metabolites in Patients With Chagas Heart Disease

Leme, Ana Maria Betim Paes; Salemi, Vera Maria Cury; Weiss, Robert G.; Filho, José Rodrigues; Ianni, Bárbara Maria; Mady, Charles; Kalil‐Filho, Roberto

doi:10.1016/j.cardfail.2013.05.008

Cited by 13 publications

(11 citation statements)

References 34 publications

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“…Exercise‐induced changes in patients with disease are known to be more substantial, perhaps because their hearts have only a limited energetic reserve because of having to compensate for disease at rest. For example, Betim Paes Leme et al observed a 57% decrease in PCr/ATP in patients with Chagas heart disease on exercise . Such changes would be clearly detectable at 7 T. It is an open question whether 7 T 31 P‐MRS can be made sensitive enough to detect changes in high‐energy phosphate energetics in healthy subjects during exercise.…”

Section: Discussionmentioning

confidence: 99%

Reproducibility of human cardiac phosphorus MRS (³¹P‐MRS) at 7 T

et al. 2019

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Purpose We test the reproducibility of human cardiac phosphorus MRS ( 31 P‐MRS) at ultra‐high field strength (7 T) for the first time. The primary motivation of this work was to assess the reproducibility of a ‘rapid’ 6½ min 31 P three‐dimensional chemical shift imaging (3D‐CSI) sequence, which if sufficiently reproducible would allow the study of stress‐response processes. We compare this with an established 28 min protocol, designed to record high‐quality spectra in a clinically feasible scan time. Finally, we use this opportunity to compare the effect of per‐subject B 0 shimming on data quality and reproducibility in the 6½ min protocol. Methods 10 healthy subjects were scanned on two occasions: one to test the 28 min 3D‐CSI protocol, and one to test the 6½ min protocol. Spectra were fitted using the OXSA MATLAB toolbox. The phosphocreatine to adenosine triphosphate concentration ratio (PCr/ATP) from each scan was analysed for intra‐ and intersubject variability. The impact of different strategies for voxel selection was assessed. Results There were no significant differences between repeated measurements in the same subject. For the 28 min protocol, PCr/ATP in the midseptal voxel across all scans was 1.91 ± 0.36 (mean ± intersubject SD). For the 6½ min protocol, PCr/ATP in the midseptal voxel was 1.76 ± 0.40. The coefficients of reproducibility (CRs) were 0.49 (28 min) and 0.67 (6½ min). Per‐subject B 0 shimming improved the fitted PCr/ATP precision (for 6½ min scans), but had negligible effect on the CR (0.67 versus 0.66). Conclusions Both 7 T protocols show improved reproducibility compared with a previous 3 T study by Tyler et al. Our results will enable informed power calculations and protocol selection for future clinical research studies.

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Section: Discussionmentioning

confidence: 99%

Reproducibility of human cardiac phosphorus MRS (³¹P‐MRS) at 7 T

et al. 2019

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“…This response improved after successful revascularization, suggesting clinical potential for this methodology in myocardial ischemia. Similarly, cardiac 31 P-MRS exercise stress testing has been proposed as a means to noninvasively test therapeutic strategies in Chagas disease, where a reduction in the PCr/ATP ratio may be indicative of microvascular disease caused by a Trypanosoma cruzi parasite infection (Betim Paes Leme et al, 2013 ).…”

Section: Discussionmentioning

confidence: 99%

“…Instead, 31 P-MRS measurements of the myocardial PCr/ATP ratio at multiple steady-states of cardiac work rates are feasible. Pioneered almost three decades ago (Conway et al, 1988 , 1991 ; Weiss et al, 1990 ; Kuno et al, 1994 ), 31 P-MRS measurements of the in vivo human heart during exercise have recently regained interest (Hudsmith et al, 2009 ; Betim Paes Leme et al, 2013 ; Dass et al, 2015 ; Levelt et al, 2016 ). These studies typically consisted of steady-state 31 P-MRS data acquisition at rest and at one additional steady-state of low-intensity exercise (heart rates of 60–100 beats min −1 ) or pharmacologically induced stress (Figure 1 ).…”

Section: Introductionmentioning

confidence: 99%

“…Note the large variability in the reported PCr/ATP ratios, both within as well as between studies. See literature for individual study details (Weiss et al, 1990 ; Conway et al, 1991 ; Kuno et al, 1994 ; Yabe et al, 1994 ; Lamb et al, 1997 , 1999 ; Pluim et al, 1998 ; Hudsmith et al, 2009 ; Holloway et al, 2012 ; Rider et al, 2012 ; Betim Paes Leme et al, 2013 ; Dass et al, 2015 ; Levelt et al, 2016 ). ATP, adenosine triphosphate; PCr, phosphocreatine.…”

Section: Introductionmentioning

confidence: 99%

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Human Cardiac 31P-MR Spectroscopy at 3 Tesla Cannot Detect Failing Myocardial Energy Homeostasis during Exercise

et al. 2017

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Phosphorus-31 magnetic resonance spectroscopy (31P-MRS) is a unique non-invasive imaging modality for probing in vivo high-energy phosphate metabolism in the human heart. We investigated whether current 31P-MRS methodology would allow for clinical applications to detect exercise-induced changes in (patho-)physiological myocardial energy metabolism. Hereto, measurement variability and repeatability of three commonly used localized 31P-MRS methods [3D image-selected in vivo spectroscopy (ISIS) and 1D ISIS with 1D chemical shift imaging (CSI) oriented either perpendicular or parallel to the surface coil] to quantify the myocardial phosphocreatine (PCr) to adenosine triphosphate (ATP) ratio in healthy humans (n = 8) at rest were determined on a clinical 3 Tesla MR system. Numerical simulations of myocardial energy homeostasis in response to increased cardiac work rates were performed using a biophysical model of myocardial oxidative metabolism. Hypertrophic cardiomyopathy was modeled by either inefficient sarcomere ATP utilization or decreased mitochondrial ATP synthesis. The effect of creatine depletion on myocardial energy homeostasis was explored for both conditions. The mean in vivo myocardial PCr/ATP ratio measured with 3D ISIS was 1.57 ± 0.17 with a large repeatability coefficient of 40.4%. For 1D CSI in a 1D ISIS-selected slice perpendicular to the surface coil, the PCr/ATP ratio was 2.78 ± 0.50 (repeatability 42.5%). With 1D CSI in a 1D ISIS-selected slice parallel to the surface coil, the PCr/ATP ratio was 1.70 ± 0.56 (repeatability 43.7%). The model predicted a PCr/ATP ratio reduction of only 10% at the maximal cardiac work rate in normal myocardium. Hypertrophic cardiomyopathy led to lower PCr/ATP ratios for high cardiac work rates, which was exacerbated by creatine depletion. Simulations illustrated that when conducting cardiac 31P-MRS exercise stress testing with large measurement error margins, results obtained under pathophysiologic conditions may still lie well within the 95% confidence interval of normal myocardial PCr/ATP dynamics. Current measurement precision of localized 31P-MRS for quantification of the myocardial PCr/ATP ratio precludes the detection of the changes predicted by computational modeling. This hampers clinical employment of 31P-MRS for diagnostic testing and risk stratification, and warrants developments in cardiac 31P-MRS exercise stress testing methodology.

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“…Another possible exercise paradigm is isometric stress (i.e., static muscular contraction), which raises blood pressure (BP), heart rate (HR) and cardiac output (CO) [7]. Isometric exercise has previously been shown to be useful in the assessment of endothelial function, great vessel haemodynamics and left ventricular (LV) dysfunction [8][9][10]. The lack of motion during exercise makes it compatible with standard breath-hold CMR [11].…”

Section: Introductionmentioning

confidence: 99%

Isometric stress in cardiovascular magnetic resonance—a simple and easily replicable method of assessing cardiovascular differences not apparent at rest

et al. 2015

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Exercise-Induced Decrease in Myocardial High-Energy Phosphate Metabolites in Patients With Chagas Heart Disease

Cited by 13 publications

References 34 publications

Reproducibility of human cardiac phosphorus MRS (³¹P‐MRS) at 7 T

Reproducibility of human cardiac phosphorus MRS (³¹P‐MRS) at 7 T

Human Cardiac 31P-MR Spectroscopy at 3 Tesla Cannot Detect Failing Myocardial Energy Homeostasis during Exercise

Isometric stress in cardiovascular magnetic resonance—a simple and easily replicable method of assessing cardiovascular differences not apparent at rest

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Exercise-Induced Decrease in Myocardial High-Energy Phosphate Metabolites in Patients With Chagas Heart Disease

Cited by 13 publications

References 34 publications

Reproducibility of human cardiac phosphorus MRS (31P‐MRS) at 7 T

Reproducibility of human cardiac phosphorus MRS (31P‐MRS) at 7 T

Human Cardiac 31P-MR Spectroscopy at 3 Tesla Cannot Detect Failing Myocardial Energy Homeostasis during Exercise

Isometric stress in cardiovascular magnetic resonance—a simple and easily replicable method of assessing cardiovascular differences not apparent at rest

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Reproducibility of human cardiac phosphorus MRS (³¹P‐MRS) at 7 T

Reproducibility of human cardiac phosphorus MRS (³¹P‐MRS) at 7 T