phosphocreatine and Cardiomyopathy--Hypertrophic

Magnetic resonance spectroscopy (MRS) can noninvasively provide a window into the metabolic status of the heart. This technique has shown abnormalities in the phosphocreatine-to-adenosine triphosphate ratio in patients with severe cardiomyopathies, either dilated or hypertrophic. Data indicate that abnormal metabolic parameters can risk stratify patients with dilated cardiomyopathy and provide independent prognostic information. Finally, the use of MRS in patients after cardiac transplantation is being explored. The information from cardiac MRS will likely provide the investigator and clinician with unique data and assist in the diagnosis and management of patients with various forms of heart disease.

Topics: Adenosine Triphosphate; Animals; Cardiomyopathy, Dilated; Cardiomyopathy, Hypertrophic; Heart Failure; Heart Transplantation; Humans; Magnetic Resonance Spectroscopy; Muscle, Skeletal; Phosphocreatine; Phosphorus Isotopes; Predictive Value of Tests; Risk Assessment

Hypertrophic cardiomyopathy (HCM) is the commonest cause of sudden cardiac death in the young, with an excess of exercise-related deaths. The HCM sarcomere mutations increase the energy cost of contraction and impaired resting cardiac energetics has been documented by measurement of phosphocreatine/ATP (PCr/ATP) using (31)Phosphorus MR Spectroscopy ((31)P MRS). We hypothesized that cardiac energetics are further impaired acutely during exercise in HCM and that this would have important functional consequences.. (31)P MRS was performed in 35 HCM patients and 20 age- and gender-matched normal volunteers at rest and during leg exercise with 2.5 kg ankle weights. Peak left-ventricular filling rates (PFRs) and myocardial perfusion reserve (MPRI) were calculated during adenosine stress. Resting PCr/ATP was significantly reduced in HCM (HCM: 1.71 ± 0.35, normal 2.14 ± 0.35 P < 0.0001). During exercise, there was a further reduction in PCr/ATP in HCM (1.56 ± 0.29, P = 0.02 compared with rest) but not in normals (2.16 ± 0.26, P = 0.98 compared with rest). There was no correlation between PCr/ATP reduction and cardiac mass, wall thickness, MPRI, or late-gadolinium enhancement. PFR and PCr/ATP were significantly correlated at rest (r = 0.48, P = 0.02) and stress (r = 0.53, P = 0.01).. During exercise, the pre-existing energetic deficit in HCM is further exacerbated independent of hypertrophy, perfusion reserve, or degree of fibrosis. This is in keeping with the change at the myofilament level. We offer a potential explanation for exercise-related diastolic dysfunction in HCM.

Topics: Adenosine Triphosphate; Adult; Blood Pressure; Cardiomyopathy, Hypertrophic; Case-Control Studies; Diastole; Energy Metabolism; Exercise; Female; Heart Rate; Humans; Magnetic Resonance Angiography; Magnetic Resonance Imaging, Cine; Magnetic Resonance Spectroscopy; Male; Phosphocreatine; Prospective Studies; Stroke Volume; Ventricular Dysfunction, Left

A lethal and extensively characterized familial form of hypertrophic cardiomyopathy (HC) is due to a point mutation (Arg403Gln) in the cardiac β-myosin heavy chain gene. Although this is associated with abnormal energy metabolism and progression to heart failure in an animal model, in vivo cardiac energetics have not been characterized in patients with this mutation. Noninvasive phosphorus saturation transfer magnetic resonance spectroscopy was used to measure the adenosine triphosphate supplied by the creatine kinase (CK) reaction and phosphocreatine, the heart's primary energy reserve, in 9 of 10 patients from a single kindred with HC caused by the Arg403GIn mutation and 17 age-matched healthy controls. Systolic and diastolic function was assessed by echocardiography in all 10 patients with HC. The patients with HC had impairment of diastolic function and mild systolic dysfunction, when assessed using global systolic longitudinal strain. Myocardial phosphocreatine was significantly decreased by 24% in patients (7.1 ± 2.3 μmol/g) compared with the controls (9.4 ± 1.2 μmol/g; p = 0.003). The pseudo-first-order CK rate-constant was 26% lower (0.28 ± 0.15 vs 0.38 ± 0.07 s⁻¹, p = 0.035) and the forward CK flux was 44% lower (2.0 ± 1.4 vs 3.6 ± 0.9 μmol/g/s, p = 0.001) than in the controls. The contractile abnormalities did not correlate with the metabolic indexes. In conclusion, myocardial phosphocreatine and CK-ATP delivery are significantly reduced in patients with HC caused by the Arg403Gln mutation, akin to previous results from mice with the same mutation. A lack of a relation between energetic and contractile abnormalities suggests the former result from the sarcomeric mutation and not a late consequence of mechanical dysfunction.

Topics: Adenosine Triphosphate; Adult; Cardiomyopathy, Hypertrophic; Creatine Kinase; Disease Progression; DNA; DNA Mutational Analysis; Echocardiography; Energy Metabolism; Female; Heart Ventricles; Humans; Magnetic Resonance Spectroscopy; Male; Mutation; Myosin Heavy Chains; Phosphocreatine; Prognosis

Areas of intramyocardial late enhancement (LE) at delayed enhanced magnetic resonance imaging (DE-MRI) and reduction of myocardial phosphocreatine (PCr)/ATP-ratio at phosphorus magnetic resonance spectroscopy ((31)P-MRS) are both reported in hypertrophic cardiomyopathy (HCM) and indicate areas of increased interstitial myocardial space with fibrosis and impairment of myocardial energy metabolism, respectively. We sought to ascertain whether in HCM patients the abnormal features of left ventricular (LV) interstitial space revealed by DE-MRI correlated with impaired LV energy metabolism shown at (31)P-MRS.. 19 patients with HCM proved by histological analysis of multiple endomyocardial biopsies and with normal coronary arteries, underwent cardiac MRI including DE-MRI and (31)P-MRS. DE-MRI for detection and quantification of late enhancement (LE) and (31)P-MRS to assess the myocardial PCr/ATP-ratio were performed by means of a 1.5-T magnet. 19 healthy subjects, matched for gender and age were studied by (31)P-MRS as control group.. LE areas in the LV wall were found in 17 out of 19 patients with an extension ranging from 0.8% to 19.5% of the LV-mass (mean value 7.6% (SD 5.6%). The PCr/ATP-ratio was lower in HCM patients than in control subjects (2.18 (0.41) vs 2.41 (0.30); p<0.05). LE% and PCr/ATP-ratio were inversely related (R = -0.57; p<0.05) and LE% was the stronger predictor of PCr/ATP-ratio by multivariate analysis.. This study demonstrated that the known alteration of the PCr/ATP-ratio observed in HCM patients is correlated with the presence of fibrotic areas in the myocardium of the left ventricle.

Topics: Adenosine Triphosphate; Adolescent; Adult; Cardiomyopathy, Hypertrophic; Case-Control Studies; Contrast Media; Early Diagnosis; Endomyocardial Fibrosis; Energy Metabolism; Female; Fibrosis; Gadolinium; Heart Ventricles; Humans; Magnetic Resonance Spectroscopy; Male; Middle Aged; Myocardium; Phosphocreatine; Stroke Volume

Hypertrophic cardiomyopathy (HCM) is associated with cardiac hypertrophy, diastolic dysfunction, and sudden death. Recently, it has been suggested that inefficient energy utilization could be a common molecular pathway of HCM-related mutations. We have previously generated transgenic Sprague-Dawley rats overexpressing a truncated cardiac troponin T (DEL-TNT) molecule, displaying typical features of HCM such as diastolic dysfunction and an increased susceptibility to ventricular arrhythmias. We now studied these rats using 31P magnetic resonance spectroscopy (MRS). MRS demonstrated that cardiac energy metabolism was markedly impaired, as indicated by a decreased phosphocreatine to ATP ratio (-31%, p < 0.05). In addition, we assessed contractility of isolated cardiomyocytes. While DEL-TNT and control cardiomyocytes showed no difference under baseline conditions, DEL-TNT cardiomyocytes selectively exhibited a decrease in fractional shortening by 28% after 1 h in glucose-deprived medium (p < 0.05). Moreover, significant decreases in contraction velocity and relaxation velocity were observed. To identify the underlying molecular pathways, we performed transcriptional profiling using real-time PCR. DEL-TNT hearts exhibited induction of several genes critical for cardiac energy supply, including CD36, CPT-1/-2, and PGC-1alpha. Finally, DEL-TNT rats and controls were studied by radiotelemetry after being stressed by isoproterenol, revealing a significantly increased frequency of arrhythmias in transgenic animals. In summary, we demonstrate profound energetic alterations in DEL-TNT hearts, supporting the notion that inefficient cellular ATP utilization contributes to the pathogenesis of HCM.

Topics: Adenosine Triphosphate; Animals; Arrhythmias, Cardiac; Cardiomyopathy, Hypertrophic; Cell Size; Cells, Cultured; Disease Models, Animal; Energy Metabolism; Gene Expression Profiling; Genetic Predisposition to Disease; Humans; Magnetic Resonance Imaging; Microscopy, Electron; Mitochondria, Heart; Muscle Contraction; Mutation; Myocardium; Myocytes, Cardiac; Phosphocreatine; Rats; Rats, Sprague-Dawley; Rats, Transgenic; Reverse Transcriptase Polymerase Chain Reaction; Troponin T

To study the role of early energetic abnormalities in the subsequent development of heart failure, we performed serial in vivo combined magnetic resonance imaging (MRI) and (31)P magnetic resonance spectroscopy (MRS) studies in mice that underwent pressure-overload following transverse aorta constriction (TAC). After 3 wk of TAC, a significant increase in left ventricular (LV) mass (74 +/- 4 vs. 140 +/- 26 mg, control vs. TAC, respectively; P < 0.000005), size [end-diastolic volume (EDV): 48 +/- 3 vs. 61 +/- 8 microl; P < 0.005], and contractile dysfunction [ejection fraction (EF): 62 +/- 4 vs. 38 +/- 10%; P < 0.000005] was observed, as well as depressed cardiac energetics (PCr/ATP: 2.0 +/- 0.1 vs. 1.3 +/- 0.4, P < 0.0005) measured by combined MRI/MRS. After an additional 3 wk, LV mass (140 +/- 26 vs. 167 +/- 36 mg; P < 0.01) and cavity size (EDV: 61 +/- 8 vs. 76 +/- 8 microl; P < 0.001) increased further, but there was no additional decline in PCr/ATP or EF. Cardiac PCr/ATP correlated inversely with end-systolic volume and directly with EF at 6 wk but not at 3 wk, suggesting a role of sustained energetic abnormalities in evolving chamber dysfunction and remodeling. Indeed, reduced cardiac PCr/ATP observed at 3 wk strongly correlated with changes in EDV that developed over the ensuing 3 wk. These data suggest that abnormal energetics due to pressure overload predict subsequent LV remodeling and dysfunction.

Topics: Adenosine Triphosphate; Animals; Cardiomyopathy, Hypertrophic; Energy Metabolism; Hypertrophy, Left Ventricular; Male; Metabolic Clearance Rate; Mice; Mice, Inbred C57BL; Myocardial Contraction; Phosphocreatine; Ventricular Dysfunction, Left; Ventricular Remodeling

We investigated cardiac energetics in subjects with mutations in three different familial hypertrophic cardiomyopathy (HCM) disease genes, some of whom were nonpenetrant carriers without hypertrophy, using phosphorus-31 magnetic resonance spectroscopy.. Familial hypertrophic cardiomyopathy is caused by mutations in sarcomeric protein genes. The mechanism by which these mutant proteins cause disease is uncertain. A defect of myocyte contractility had been proposed, but in vitro studies of force generation have subsequently shown opposing results in different classes of mutation. An alternative hypothesis of "energy compromise" resulting from inefficient utilization of adenosine triphosphate (ATP) has been suggested, but in vivo data in humans with genotyped HCM are lacking.. The cardiac phosphocreatine (PCr) to ATP ratio was determined at rest in 31 patients harboring mutations in the genes for either beta-myosin heavy chain, cardiac troponin T, or myosin-binding protein C, and in 24 controls. Transthoracic echocardiography was used to measure left ventricular (LV) dimensions and maximal wall thickness.. The PCr/ATP was reduced in the HCM subjects by 30% relative to controls (1.70 +/- 0.43 vs. 2.44 +/- 0.30; p < 0.001), and the reduction was of a similar magnitude in all three disease-gene groups. The PCr/ATP was equally reduced in subjects with (n = 24) and without (n = 7) LV hypertrophy.. Our data provide evidence of a bioenergetic deficit in genotype-confirmed HCM, which is present to a similar degree in three disease-gene groups. The presence of energetic abnormalities, even in those without hypertrophy, supports a proposed link between altered cardiac energetics and development of the disease phenotype.

Topics: Adenosine Triphosphate; Adolescent; Adult; Aged; Cardiac Myosins; Cardiomyopathy, Hypertrophic; Carrier Proteins; Child; Echocardiography, Transesophageal; Energy Metabolism; Female; Humans; Magnetic Resonance Spectroscopy; Male; Middle Aged; Mutation; Mutation, Missense; Myocardium; Phosphocreatine; Troponin T; Ventricular Myosins

Topics: Adenosine Triphosphate; Cardiac Myosins; Cardiomyopathy, Hypertrophic; Energy Metabolism; Humans; Mutation; Myocardial Contraction; Myocardium; Phosphocreatine

Topics: Adenosine Triphosphate; Adult; Cardiomyopathy, Hypertrophic; Energy Metabolism; Humans; Magnetic Resonance Spectroscopy; Mutation, Missense; Myocardium; Myosin Heavy Chains; Nonmuscle Myosin Type IIB; Phosphocreatine

Impaired energy metabolism in the failing human heart could be an important mechanism of functional deterioration. The purpose of this study was to assess the changes of myocardial energy metabolism in the human heart at end-stage heart failure.. The left ventricular myocardium of patients undergoing heart transplantation due to dilated (DCM, n = 14) or hypertrophic cardiomyopathy (HCM, n = 5) and non-diseased donor heart samples (n = 4) were analysed for citrate synthase (CS), enzymes of the glycolytic pathway as well as concentrations of phosphocreatine (PCr), creatine (Cr), adenine and guanine nucleotides.. Total creatine levels (phosphocreatine + creatine) were significantly decreased (P < 0.05) in both groups of diseased hearts (3.87 +/- 0.57 in DCM, 5.09 +/- 1.23 in HCM compared with control 10. 7 +/- 3.5 micromol g-1 wet weight). There was a trend for higher guanine nucleotide content in failing hearts, but no significant differences were observed in total adenine nucleotides and total NAD content. CS was markedly reduced (P < 0.05) in both groups of diseased hearts: in the DCM to 13.8 +/- 1.3 micromol min-1 g-1 wet weight, and in HCM to 11.9 +/- 2.4 compared with the control 29.2 +/- 2.2. Glycolytic enzymes were decreased compared with the control, and this decrease was greater in DCM than in HCM. Echocardiographic indices of contractility were considerably better in hypertrophic cardiomyopathy.. Despite the different mechanisms of cardiac failure and the differences in contractility of the heart we have observed, metabolic changes are very similar in hypertrophic and dilated cardiomyopathy. Depletion of the creatine pool suggests an alteration in the intracellular energy reserves and transfer, whereas the decrease in citrate synthase activity suggests reduced oxidative capacity in both dilated and hypertrophic cardiomyopathy.

Topics: Adenine Nucleotides; Adult; Cardiomyopathy, Dilated; Cardiomyopathy, Hypertrophic; Citrate (si)-Synthase; Creatine; Echocardiography; Energy Metabolism; Female; Glycolysis; Guanine Nucleotides; Heart; Heart Failure; Heart Transplantation; Hemodynamics; Humans; Male; Myocardium; Phosphocreatine

Although both aging and hypertrophy are extremely important factors for cardiac performance, their influence on cardiac metabolism, especially that of high-energy phosphates, has not been fully elucidated as yet. Quantitative measurements of high-energy phosphates were attempted by comparing myocardial 31P NMR spectra with an external reference using depth-resolved surface-coil spectroscopy. The voxel size of the region of interest (ROI) was disk-shaped with 15-cm diameter and 25-mm thickness, but the left ventricular weight actually involved in the ROI was estimated to be between 22 and 66 g using MRI. Myocardial phosphocreatine (PCr) content and adenosine triphosphate (ATP) content for the 30 normal volunteers showed significant age dependence since both decreased in relation to increasing age. Myocardial PCr content and ATP content in patients with hypertension did not differ significantly from the age-matched control group. PCr content (6.1 +/- 2.2 micromol/g wet tissue, n = 10) and ATP content (4.1 +/- 1.3 micromol/g wet tissue) in patients with hypertrophic cardiomyopathy were less than the age-matched control group (n = 15; PCr: 9.7 +/- 2.5 micromol/g wet tissue, P < 0.01; ATP: 6.4 +/- 1.8 micromol/g wet tissue, P < 0.05), respectively. These results indicate that quantitative 31P MRS may be valuable in the assessment of changes in high-energy phosphate metabolism caused by aging or hypertrophy.

Topics: Adenosine Triphosphate; Adult; Aged; Aged, 80 and over; Aging; Cardiomyopathy, Hypertrophic; Case-Control Studies; Electrocardiography; Exercise Test; Female; Humans; Hypertension; Magnetic Resonance Imaging; Magnetic Resonance Spectroscopy; Male; Middle Aged; Myocardium; Phosphocreatine

Proton-decoupled 31P NMR spectroscopy at 1.5 T of the anterior left ventricular myocardium was used to monitor myocardial phosphate metabolism in asymptomatic patients with hypertrophic cardiomyopathy (HCM, n = 14) and aortic stenosis (AS, n = 12). In addition to the well-known phosphorus signals a phosphomonoester (PME) signal was detected at about 6.9 ppm in 7 HCM and 2 AS patients. This signal was not observed in the spectra of normal controls (n = 11). We suggest that in spectra of patients with myocardial hypertrophy the presence of a PME signal reflects alterations in myocardial glucose metabolism.

Topics: 2,3-Diphosphoglycerate; Adenosine Triphosphate; Adolescent; Adult; Aortic Valve Stenosis; Cardiomyopathy, Hypertrophic; Female; Glucose; Heart Ventricles; Humans; Magnetic Resonance Spectroscopy; Male; Myocardium; NAD; Organophosphates; Phosphates; Phosphocreatine; Phosphorus

Topics: 2,3-Diphosphoglycerate; Adenosine Triphosphate; Cardiomyopathy, Hypertrophic; Child; Humans; Myocardium; Nuclear Magnetic Resonance, Biomolecular; Organophosphates; Phosphocreatine; Phosphorus; Signal Processing, Computer-Assisted

Disturbed myocardial energy metabolism may occur in patients with primary hypertrophic cardiomyopathy (HCM). A noninvasive way to gain insight into cardiac energy metabolism is provided by in vivo 31P nuclear magnetic resonance (NMR) spectroscopy. 31P NMR spectroscopy with proton decoupling was performed in 13 patients aged 13-36 years with HCM on a 1.5 T Magnetom with a double resonant surface coil. A 2D chemical shift imaging (CSI) sequence in combination with slice selective excitation was used to acquire spectra of the anteroseptal region of the left ventricle (volume element: 38 mL). The chemical shifts of the phosphorus metabolites, intracellular pHi, and coupling constants J(alphabeta) and J(gammabeta) were calculated. Peak areas of 2,3-diphosphoglycerate (DPG), Pi, and adenosine triphosphate (ATP) were determined and corrected for blood contamination, saturation, and differences in nuclear Overhauser enhancements (NOE). The maximum thickness of the interventricular septum (IVSmax) was determined from tomographic long-axis images and expressed as number of standard deviations above the mean of the normal population (Z score). The patients were then divided into 2 groups: 6 patients with moderate HCM (HCMm, Z score < or = 5) and 7 patients with severe HCM (HCMs, Z score > 5). No differences between both groups and a control group of healthy volunteers (n = 16) were found with respect to phosphocreatine (PCr)/gamma-ATP ratio, pHi, or the coupling constants. Only the PCr/Pi ratio differed significantly from the control group (HCM(all), alpha < 0.05, HCMs, alpha < 0.02, 2-sided U test). The decrease of the PCr/Pi ratio in patients with HCM is probably caused by ischemically decreased oxygen supply in the severely hypertrophied myocardium.

Topics: Adenosine Triphosphate; Adolescent; Adult; Cardiomyopathy, Hypertrophic; Humans; Hydrogen-Ion Concentration; Magnesium; Magnetic Resonance Spectroscopy; Myocardium; Phosphocreatine; Phosphorus Isotopes; Protons

It was the aim of this study to evaluate the effects of hyperthyroidism on heart function and cardiac energy metabolism of spontaneously hypertensive (SHR) rats. Hyperthyroidism was induced by daily injections of T3 (0.2 mg/kg s.c.) for 14 days. The hearts were then isolated and perfused in the Langendorff mode. ATP, phosphocreatine (PCr), and inorganic phosphate (Pi) were measured continuously by means of 31P-nuclear magnetic resonance (NMR) spectroscopy. Work load was altered by varying stepwise the Ca++ concentration in the perfusion fluid from 0.5 to 1.0, 1.5, and 2.0 mM, respectively. At every elevation of the Ca++ concentration, the increase in left ventricular developed pressure (LVDP) was higher in the hyperthyroid SHR than in the untreated SHR hearts. The ATP and PCr concentrations were lower in the hyperthyroid SHR compared to the untreated SHR hearts throughout the perfusion period. PCr decreased at every Ca++ elevation in both the untreated and hyperthyroid SHR hearts. The PCr/ATP ratio was not altered at any Ca++ concentration neither in the untreated SHR nor in the hyperthyroid SHR hearts. The Ca(++)-induced stepwise elevation in LVDP was higher at any given PCr/Pi ratio in the hyperthyroid SHR than in the untreated SHR hearts. Thus, the Ca(++)-inducible contractile reserve was greater in the hyperthyroid SHR heart.

Topics: Adenosine Triphosphate; Animals; Calcium; Cardiomyopathy, Hypertrophic; Disease Models, Animal; Energy Metabolism; Female; Heart; Hyperthyroidism; Magnetic Resonance Spectroscopy; Myocardial Contraction; Perfusion; Phosphocreatine; Rats; Rats, Inbred SHR

Abnormal phosphate metabolism of the myocardium was evaluated in patients with hypertrophic cardiomyopathy (HCM) using 31P magnetic resonance (MR) spectroscopy. The results were compared with those from left ventricular function and thallium 201 (Tl-201) perfusion scintigraphy. Six normal volunteers and 19 patients with HCM were studied with a 1.5 T MR system. The spectra were localized to the myocardium using volume selection with the depth-resolved surface coil spectroscopy (DRESS) technique. Peak areas of 2,3-diphosphoglycerate (DPG), phosphodiesters (PDE), phosphocreatine (PCr), and beta-ATP were determined by fitting Gaussian functions to the phased spectra. The peak areas were corrected for contamination of blood adenosine triphosphate (ATP) and PDE. The corrected PCr/beta-ATP ratio in patients (1.07 +/- 0.10, mean +/- SE) was significantly lower compared with that in normal volunteers (1.71 +/- 0.13, p < .01). The PCr/beta-ATP ratio showed an abnormal decrease (< mean -2 SD of the controls) in 11 (58%) of 19 patients. The averaged PCr/beta-ATP ratio in 15 patients with normal left ventricular ejection fraction (LVEF) was 1.14 +/- 0.10, significantly lower than in healthy subjects. By contrast, the corrected PDE/PCr ratio in HCM did not differ significantly compared with that in healthy subjects (0.46 +/- 0.09 vs 0.36 +/- 0.09). The PDE/PCr ratio was abnormally elevated (> mean + 2 SD of the controls) in only four (21%) of the patients. On Tl-201 myocardial single-photon emission computed tomography (SPECT) imaging, the perfusion of the left ventricular wall looked normal in 6 and abnormal in 5 of 11 HCM patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adenosine Triphosphate; Adult; Aged; Cardiomyopathy, Hypertrophic; Case-Control Studies; Echocardiography; Heart; Humans; Magnetic Resonance Spectroscopy; Middle Aged; Myocardium; Phosphates; Phosphocreatine; Thallium Radioisotopes; Tomography, Emission-Computed, Single-Photon

Phosphorus-31 magnetic resonance spectroscopy can be used to study intracellular biochemistry non-invasively by measuring the relative proportions of high energy phosphates. Study of deteriorating cardiac metabolism might be useful in the management of hypertrophy and heart failure. 31P magnetic resonance spectroscopy was carried out in fourteen patients with aortic valve disease (six with aortic stenosis, eight with aortic incompetence). Six patients were receiving treatment for symptoms of heart failure. The phosphocreatine (PCr) to ATP ratio in these patients (1.1 [SD 0.32]) was significantly lower than that in thirteen controls (1.5 [0.2], p less than 0.001) or in the eight patients who did not have symptoms of heart failure (1.56 [0.15], p less than 0.0035). These findings indicate that heart failure in aortic valve disease is associated with low PCr, which could be due to loss of intracellular creatine. The measurement could eventually have a role in helping to determine the optimum timing for aortic valve replacement.

Topics: Adenosine Triphosphate; Adult; Aged; Aortic Valve Insufficiency; Aortic Valve Stenosis; Cardiomyopathy, Hypertrophic; Humans; Magnetic Resonance Spectroscopy; Middle Aged; Myocardium; Phosphocreatine; Phosphorus

To investigate the cause for the greater susceptibility of hypertrophied hearts to ischemic injury, we determined the interrelations of total work output, contractile function and energy metabolism in isolated, perfused normal and hypertrophied rat hearts subjected to graded global ischemia. Cardiac hypertrophy was induced by giving rats seven daily injections of either triiodothyronine (0.2 mg/kg) or isoproterenol (5 mg/kg). All hearts were perfused at an aortic pressure of 100 mmHg in the isovolumic mode in an NMR spectrometer (7.05 Tesla). Heart rate, developed pressure, and coronary flow were monitored simultaneously with changes in pH, creatine phosphate, ATP and inorganic phosphate. During pre-ischemic perfusion, the total work output (rate-pressure product) of hyperthyroid hearts was 28% higher than that of control hearts, whereas hearts from isoproterenol-treated animals showed no difference. However, when related to unit muscle mass, work was normal in hyperthyroid hearts and 26% lower after isoproterenol. Contractile function per unit myocardium (developed pressure/g wet weight) was lower in the hypertrophied hearts. ATP content was the same in all groups. Creatine phosphate decreased 41% after triiodothyronine and 25% after isoproterenol. Inorganic phosphate levels and intracellular pH were similar in control and isoproterenol-treated rat hearts, but were higher in the hyperthyroid rat hearts. The phosphorylation potential and the free energy change of ATP hydrolysis were lowered by hypertrophy, the levels correlating with the depressed contractile function. At each ischemic flow rate, both work and contractile function per unit myocardium were the same for all hearts, but the relations between flow and phosphorylation potential were different for each type of heart. Thus, at low flow rates, hypertrophied hearts perform the same amount of work and have the same contractile function as control hearts, but with abnormal changes in energy metabolism, indicating that the relations of energy status to coronary flow, total work output and contractile function are altered during the process of hypertrophy.

Topics: Adenosine Triphosphate; Animals; Cardiomyopathy, Hypertrophic; Chromatography, High Pressure Liquid; Coronary Disease; Cytosol; Isoproterenol; Magnetic Resonance Spectroscopy; Male; Myocardial Contraction; Myocardium; Phosphocreatine; Phosphorylation; Rats; Rats, Inbred Strains; Triiodothyronine

Topics: Adenosine Triphosphatases; Amyloidosis; Biopsy, Needle; Cardiomyopathies; Cardiomyopathy, Hypertrophic; DNA; Echocardiography; Endocardium; Heart Transplantation; Humans; Myocardium; Myosins; Phosphocreatine

An 8 month old girl presented with undiagnosed non-anatomic congenital cardiomyopathy with massive cardiomegaly on chest X-ray film. Her older sibling had died suddenly at 6 months of age from what appeared to be a similar abnormality. Utilizing phosphorus-31 nuclear magnetic resonance (P-31 NMR) surface coil spectroscopy, a metabolic disorder was demonstrated in both her myocardium and skeletal muscle, revealing a phosphocreatine (PCr) to inorganic phosphate (Pi) ratio of half of that for a normal control infant. Manipulation of serum substrate availability indicated that medium chain triglycerides alone did not improve myocardial metabolism, but that intravenous glucose or oral carbohydrate loading raised the myocardial PCr/Pi ratio from 1.0 +/- 0.05 to 1.8 +/- 0.1 (p less than 0.01) without significantly affecting the PCr/Pi value of her resting skeletal muscle. This study demonstrates the feasibility of using P-31 nuclear magnetic resonance to evaluate the biochemistry of the human myocardium in vivo and to diagnose a metabolic abnormality. Phosphorus-31 nuclear magnetic resonance can thus be used to optimize therapy for human disease.

Topics: Cardiomegaly; Cardiomyopathy, Hypertrophic; Female; Humans; Infant; Magnetic Resonance Spectroscopy; Muscles; Myocardium; Phosphates; Phosphocreatine; Phosphorus; Time Factors