(Circulation. 1997;96:2190-2196.)
© 1997 American Heart Association, Inc.
Articles |
Myocardial Phosphocreatine-to-ATP Ratio Is a Predictor of Mortality in Patients With Dilated Cardiomyopathy
From the Departments of Medicine and Radiology (S.N., M.H., M.C., K.H., W.P., T.P., G.E., D.H., K.K.), Würzburg University, Germany; the Cardiac Computer Center, Massachusetts General Hospital, Boston (J.B.N.); and the NMR Laboratory for Physiological Chemistry (J.S.I.), Harvard Medical School, Boston Mass. Dr Ertl's present address is II Medizinischen Klinik, Klinikum Mannheim, Universität Heidelberg, Theodor-Kutzer-Ufer, 68135 Mannheim, Germany.
Correspondence to Stefan Neubauer, MD, Medizinische Universitätsklinik, Josef-Schneider-Straße 2, 97080 Würzburg, Germany. E-mail s.neubauer{at}rzbox.uni-wuerzburg.de
 |
Abstract |
|---|
 Top Abstract IntroductionMethodsResultsDiscussionReferences |
|---|
Background In patients with heart failure due to dilated cardiomyopathy, cardiac energy metabolism is impaired, as indicated by a reduction of the myocardial phosphocreatine-to-ATP ratio, measured noninvasively by 31P-MR spectroscopy. The purpose of this study was to test whether the phosphocreatine-to-ATP ratio also offers prognostic information in terms of mortality prediction as well as how this index compares with well-known mortality predictors such as left ventricular ejection fraction (LVEF) or New York Heart Association (NYHA) class.
Methods and Results Thirty-nine patients with dilated cardiomyopathy were followed up for 928±85 days (2.5 years). At study entry, LVEF and NYHA class were determined, and the cardiac phosphocreatine-to-ATP ratio was measured by localized 31P-MR spectroscopy of the anterior myocardium. During the study period, total mortality was 26%. Patients were divided into two groups, one with a normal phosphocreatine-to-ATP ratio (>1.60; mean±SE, 1.98±0.07; n=19; healthy volunteers: 1.94±0.11, n=30) and one with a reduced phosphocreatine-to-ATP ratio (<1.60; 1.30±0.05; n=20). At reevaluation (mean, 2.5 years), 8 of 20 patients with reduced phosphocreatine-to-ATP ratios had died, all of cardiovascular causes (total and cardiovascular mortality, 40%). Of the 19 patients with normal phosphocreatine-to-ATP ratios, 2 had died (total mortality, 11%), one of cardiovascular causes (cardiovascular mortality, 5%). Kaplan-Meier analysis showed significantly reduced total (P=.036) and cardiovascular (P=.016) mortality for patients with normal versus patients with low phosphocreatine-to-ATP ratios. A Cox model for multivariate analysis showed that the phosphocreatine-to-ATP ratio and NYHA class offered significant independent prognostic information on cardiovascular mortality.
Conclusions The myocardial phosphocreatine-to-ATP ratio, measured noninvasively with 31P-MR spectroscopy, is a predictor of both total and cardiovascular mortality in patients with dilated cardiomyopathy.
Key Words: spectroscopy, magnetic resonance • mortality • heart failure • metabolism
|
Introduction |
|---|
|
TopAbstractIntroductionMethodsResultsDiscussionReferences |
|---|
The tissue contents of the high-energy phosphate compounds ATP and phosphocreatine in normal and diseased human myocardium can be determined noninvasively by 31P-MR spectroscopy.1 2 3 4 5 6 7 8 9 10 In heart failure due to dilated cardiomyopathy, we11 12 and others13 have described an impairment of energy metabolism as attested to by reduced myocardial phosphocreatine/ATP ratios, which correlated with the degree of failure.11 12
On the basis of these observations of altered high-energy phosphate metabolism in human dilated cardiomyopathy as well as experimental findings in animal models of cardiac failure,14 15 16 17 18 19 it has been suggested that an impaired energetic state of the myocardium contributes to the development and progression of heart failure.20 Because ATP and its energy-reserve phosphocreatine are essential for normal cardiac function, alterations in these high-energy phosphate compounds such as occur in heart failure may be predictors of mortality. In patients with heart failure, a number of clinical, hemodynamic, biochemical, and electrophysiological predictors of mortality have been described (for a review, see Reference 2121 ) that include, among others, NYHA class,21 exercise capacity,22 LVEF,23 plasma norepinephrine,24 and atrial natriuretic peptide25 levels or hypokalemia.26 The purpose of the present study was to test whether the myocardial phosphocreatine/ATP ratio, measured by 31P-MR spectroscopy, is a significant long-term predictor of mortality in patients with heart failure due to dilated cardiomyopathy and, if so, how phosphocreatine/ATP ranks in its predictive power among traditional indices such as LVEF and NYHA class. In this way, we can assess whether the phosphocreatine/ATP ratio provides independent information on mortality.
|
Methods |
|---|
|
TopAbstractIntroductionMethodsResultsDiscussionReferences |
|---|
Patient Characteristics
All studies were approved by the Ethics Committee of the University of Würzburg. Thirty-nine patients with dilated cardiomyopathy (Table 1
) had a reduced LVEF of <50%. Of these
patients, 34 were male and 5 were female; mean age was 50±2 years
(range, 26 to 66 years). The presumed origin of dilated
cardiomyopathy was alcoholic in 12, myocarditis in
3, and idiopathic in 24 patients. In all patients, LVEF was determined
by radiocontrast left ventriculography (34) or radionuclide scan (5)
averaging 30±2%. In all patients, coronary artery disease was
ruled out by coronary angiography. On the day of spectroscopy,
the NYHA status of each patient was evaluated by an independent
cardiologist. At study entry, 37 patients received a diuretic,
37 received digitalis, 37 received an ACE inhibitor, 10
received ß-blockers, and 1 received amiodarone.
|
For an analysis of mortality prediction, patients were divided into two groups based on the myocardial phosphocreatine/ATP ratio: 19 patients had a phosphocreatine/ATP ratio >1.60, considered "normal," and 20 had a ratio of <1.60, considered "low." The cutoff point of 1.60 was chosen because it divided the 39 patients into two groups of nearly equal (19 versus 20 patients) size, and it created one patient group with a "normal" (1.98±0.7) mean phosphocreatine/ATP ratio not different from healthy volunteers (1.94±0.11) and another patient group with a phosphocreatine/ATP ratio that was significantly lower (1.30±0.05; P<.03) than for healthy volunteers. Similar to the strategy for phosphocreatine/ATP ratios, patients were split into two groups for analysis of mortality prediction by LVEF (cutoff point, LVEF=30%; n=21 versus 18 patients; normal=39±2%; low=22±1%) and by NYHA class (NYHA I+II [n=23] versus NYHA III [n=16]). Because short-term changes of phosphocreatine/ATP ratio can occur during clinical recompensation,11 we included only patients who had been recompensated to at least NYHA class III by a minimum of 6 weeks of standard medical therapy for heart failure. Patients were reevaluated after 928±85 days (2.5 years), when a survey was conducted with the general practitioners of the patients. Physicians were asked the following questions: (1) Is the patient alive, and if not, what was his or her date of death? (2) If the patient died, what was the cause of death, ie, cardiovascular (progressive heart failure or sudden death) or noncardiovascular? and (3) What medication is the patient taking? On the basis of the initial measurements of phosphocreatine/ATP ratios, LVEF, NYHA class and the mortality data of the survey, we performed a Kaplan-Meier survival analysis for phosphocreatine/ATP ratios, LVEF, and NYHA class and a multivariate analysis of survival including phosphocreatine/ATP, LVEF, and NYHA class as variables.
MR Data Acquisition and Processing
Measurements were performed with the patient in a prone position
on a 1.5-T whole-body Philips Gyroscan MR system, as described
previously.11 12 A 15-cm-diameter surface coil served as
both transmitter and receiver. Localization was achieved with the ISIS
technique27 as previously described.11 12 On
the basis of spin-echo 1H scout images, the ISIS volume was
positioned over the anteroseptal region of the heart. Volume size for
spectroscopy (mean, 84±2 cm3) ranged from 73 to 114
cm3; the spectroscopic volume was 85±2 cm3 in
patients with normal phosphocreatine/ATP ratios and 83±3
cm3 in patients with low phosphocreatine/ATP ratios
(P=NS). We used adiabatic pulses (flip angles of 180°),
ECG-triggered acquisition, a TR of 15 seconds, 128 averages per
spectrum, a scan time/spectrum of 
32 minutes, and a total patient
examination time of 50 to 60 minutes. Phosphocreatine/ATP ratios were
corrected for partial saturation as described
previously.11 12 With a TR of 15 seconds, the applied
saturation correction was minimal (1.05). 31P-spectra were
processed with zero shift, direct-current correction (30%),
exponential multiplication (7 Hz), and individual phase correction.
Peak areas for 2,3-DPG, phosphodiesters, phosphocreatine, and
[
-P]-, [
-P]-, and [ß-P]-ATP (Fig 1) were obtained by lorentzian line fits
in the time domain as previously described11 using 400
iterations. Phosphocreatine/[-P]-ATP and
phosphodiester/[-P]-ATP ratios were calculated. Because of
bandwidth limitations of the transmitter, we chose to use the
[-P] instead of the [ß-P] resonance of ATP to avoid
off-resonance effects.3 11 The phosphocreatine/ATP ratio
is an index of the energetic state of the heart (see Reference 2020 for
review), and changes in the phosphodiester/ATP ratio have been
suggested to possibly indicate cardiomyocyte membrane
damage in heart failure.6
|
All 31P-spectra exhibit resonances for 2,3-DPG. We
therefore corrected spectra for blood contamination, as described
previously in detail,11 28 on the basis of
[-P]-ATP/2,3-DPG (0.11±0.02) and phosphodiester/2,3-DPG area
ratios (0.19±0.03) in human blood 31P-spectra. For
patients with normal and low phosphocreatine/ATP ratios, the degree of
blood contamination, spectroscopic volumes, and saturation correction
were all similar.
Statistical Analysis
Phosphocreatine/ATP and phosphodiester/ATP ratios calculated for
each metabolite were averaged to yield mean±SE values. Variables
from patients with normal and patients with low phosphocreatine/ATP
ratios were compared by use of an unpaired t test. Mortality
analysis was performed with the Statistical Package of the
Social Sciences.29 Continuous variables
(phosphocreatine/ATP and LVEF) were converted into dichotomous
variables according to their median (phosphocreatine/ATP, 1.60;
LVEF, 30%). For the clinical parameter of NYHA status,
patients in classes I and II were compared with those in class III.
Cumulative probabilities of total and cardiovascular
mortality were constructed by use of the Kaplan-Meier life-table method
and were compared in a univariate fashion by use of the
log-rank test. The Cox regression model with forward stepwise
variable selection was used to test the relationship between total
or cardiovascular mortality and the set of three
predictor variables (phosphocreatine/ATP, LVEF, or NYHA class) in a
multivariate fashion. Variables were entered into a
stepwise model if their level of significance was P<.05
(overall 
2 statistic) and removed if
P>.10 as determined by the likelihood-ratio
statistic.29
|
Results |
|---|
|
TopAbstractIntroductionMethodsResultsDiscussionReferences |
|---|
Characteristics of Patients With Normal and Reduced Phosphocreatine/ATP Ratios
Characteristics of patients with dilated cardiomyopathy grouped for normal and low phosphocreatine/ATP ratios are shown in Table 2
. Mean age, duration of follow-up, and
sex distribution (most patients were male) were similar between the two
patient groups. The presumed origin of the dilated
cardiomyopathy suggested a certain preponderance of
idiopathic cases in the group with low phosphocreatine/ATP ratios and
of alcoholic cases in the group with normal phosphocreatine/ATP
ratios.
|
Mean LVEF was significantly lower (27±2%) in the low phosphocreatine/ATP ratio group than in the normal phosphocreatine/ATP ratio group (33±2%; P<.03). The mean NYHA functional class was not significantly different between groups. Per group definition, the phosphocreatine/ATP ratio was different between groups (1.30±0.05 versus 1.98±0.07). In addition, the normal phosphocreatine/ATP ratio group was not significantly different from healthy volunteers (phosphocreatine/ATP ratio of 1.94±0.11, n=30, P=.96) whereas the low phosphocreatine/ATP ratio group was (P=.0002). The myocardial phosphodiester/ATP ratio was similar for patients with low versus normal phosphocreatine/ATP ratios as well as for healthy volunteers (1.34±0.07). Mortality analysis of phosphodiester/ATP ratio was therefore not performed in more detail.
Medications of patients with dilated cardiomyopathy
and normal versus low phosphocreatine/ATP ratios are shown in Table 3. In general, medications taken by both
groups were similar. There was a slight excess of treatment with ACE
inhibitors and diuretics in the low
phosphocreatine/ATP ratio group, which persisted to the end of the
study, and a slight excess of treatment with digitalis in the normal
phosphocreatine/ATP ratio group, a trend that was reversed at the end
of the study. At study entry, approximately one fourth of patients from
both groups received ß-blockers, whereas at the end of the study,
more patients with low than with normal phosphocreatine/ATP ratios were
still treated with ß-blockers.
|
Total Mortality
Total mortality of all 39 patients during 928±85 days of
follow-up is shown in Fig 2. Ten of 39
patients had died at the end of follow-up, ie, the total mortality rate
was 26%.
|
Mortality Prediction by Phosphocreatine/ATP Ratio, Ejection
Fraction, and NYHA Status
Fig 1
shows representative myocardial
31P-MR spectra of a healthy volunteer, patients with
phosphocreatine/ATP ratios >1.6 or <1.6, and a patient who died 7
days after MR spectroscopy was performed; the severe reduction of the
phosphocreatine/ATP ratio in this latter patient is apparent. Fig 3 shows Kaplan-Meier life-table
analyses of total and cardiovascular mortality
rates for patient groups split by phosphocreatine/ATP ratios, NYHA
class, or LVEF. There were eight deaths, all of
cardiovascular causes, in the group with reduced
phosphocreatine/ATP ratios (total and cardiovascular
mortality rate, 40%) and two deaths in the group with normal
phosphocreatine/ATP ratios (total mortality rate, 11%); in this latter
group, one patient died of bronchial carcinoma
(cardiovascular mortality rate, 5%). For patients with
normal phosphocreatine/ATP ratios, Kaplan-Meier analysis showed
significantly reduced total (P=.036) and
cardiovascular (P=.016) mortality rates
compared with patients with low phosphocreatine/ATP ratios. Thus, the
myocardial phosphocreatine/ATP ratio was a significant predictor of
both total and cardiovascular mortality.
|
Fig 3 also shows mortality analysis for patients with lower (I
and II) versus higher (III) NYHA classes and for patients with higher
(39±2%) versus lower (22±1%) LVEFs. NYHA class III predicted both
total (P=.041) and cardiovascular
(P=.022) mortality compared with NYHA classes I and II. For
mortality prediction by LVEF, significance was not reached but a clear
trend was apparent (total mortality P=.328;
cardiovascular mortality P=.243).
For multivariate analysis of cardiovascular mortality, phosphocreatine/ATP ratio, NYHA class, and LVEF were entered into a Cox regression analysis model. Both phosphocreatine/ATP ratio (P=.016) and NYHA class (P=.022) were found to provide significant independent prognostic information on cardiovascular mortality, whereas ejection fraction did not offer additional independent information. Because age is known as a predictor of mortality and mean age was slightly yet not significantly different between groups (53 versus 48 years), the same analysis was repeated after forcing age into the model. Age adjustment did not alter these findings (phosphocreatine/ATP ratio: P=.017; NYHA class: P=.022).
|
Discussion |
|---|
|
TopAbstractIntroductionMethodsResultsDiscussionReferences |
|---|
In the present report, the myocardial phosphocreatine/ATP ratio was a significant multivariate predictor of cardiovascular mortality in patients with dilated cardiomyopathy. Moreover, in the present group of 39 patients, phosphocreatine/ATP ratio was the predictor with the highest statistical significance, and LVEF showed only a trend to predict cardiovascular mortality. This suggests that the phosphocreatine/ATP ratio is a very sensitive predictor of mortality and may also suggest that a reduction in the phosphocreatine/ATP ratio is by itself a risk factor for death.
How could the derangement of energy metabolism be a sensitive predictor of mortality? ATP is the sole substrate for the myofibrillar ATPase and thus is absolutely required for muscle contraction. According to the creatine kinase–phosphocreatine energy-shuttle hypothesis,30 phosphocreatine serves to transfer the high-energy phosphate bond from the site of ATP production (mitochondria) to the site of ATP utilization (myofibrils). During metabolic stress, this energy shuttle becomes essential for maintaining high-performance states. Inhibition of creatine kinase31 or depletion of creatine with poorly hydrolyzable creatine analogues32 limits the ability of the heart to increase its workload in response to inotropic stimulation. The essential role of high-energy phosphate metabolism for maintenance of high-performance states is underscored by recent findings in transgenic mice with a knockout of the creatine kinase M gene and thus the M-line protein in the sarcomere. Skeletal muscle from these animals lacks the ability to perform burst activity.33
There is ample evidence, both experimentally and clinically, that myocardial high-energy phosphate metabolism is substantially deranged in chronic heart failure (see Reference 2020 for review). Depletion of phosphocreatine and free creatine levels has been described as a uniform phenomenon occurring in animal models of heart failure of various origins, such as aortic banding34 and heredity,15 17 18 as well as in the DC-shock dog model19 and in intact left ventricle of rats with chronic myocardial infarction.14 35 Total creatine content is also reduced in human dilated cardiomyopathy,36 as is total creatine kinase activity16 ; the decrease of both creatine content and creatine kinase activity has been shown to correlate with the degree of left ventricular dysfunction.16 36 Using 31P-MR spectroscopy, we11 12 and others10 13 have found reduced myocardial phosphocreatine/ATP ratios in heart failure due to dilated cardio-myopathy, aortic valve disease,10 or coronary artery disease,13 attesting to the depletion of phosphocreatine under these conditions. Although the question of whether altered high-energy phosphate metabolism contributes directly to pump failure is still not completely resolved,20 it is likely that in heart failure, reduced energy reserve via creatine kinase, as indicated by reduced phosphocreatine/ATP ratios, limits cardiac performance during metabolic stress conditions.37 38 This may be one explanation for the reduced exercise capacity that occurs with heart failure.22 On the basis of these experimental and clinical findings, we speculate that impairment of high-energy phosphate metabolism in heart failure may be a sensitive index that reflects the degree of physiological and biochemical derangement of the heart and the ability to increase work in response to stress better than the purely hemodynamic parameter of ejection fraction or the clinical estimation by NYHA, both of which are only measured at rest.
If reduced phosphocreatine/ATP ratio is a significant predictor of cardiovascular mortality and possibly by itself a risk factor for death, attempts to improve phosphocreatine/ATP ratios in heart failure are to be encouraged. In chronically infarcted rat hearts, ACE inhibitor treatment with quinapril was shown to improve phosphocreatine/ATP ratios in concert with the preservation of mechanical function.39 Furthermore, in rats after myocardial infarction, the decrease of total creatine content was prevented by long-term treatment with the ß-blocker bisoprolol.40 Thus, we may speculate that the beneficial effects of ACE inhibitors and ß-blockers on mortality seen in clinical trials41 42 43 are, at least in part, related to changes in cardiac high-energy phosphate metabolism.
In the present study, the total mortality rate was 26% during a mean follow-up period of 2.5 years. Thus, mortality of dilated cardiomyopathy patients selected for LVEF <50% was in the expected range.41 42 43 44 The inclusion criteria of LVEF <50% and NYHA classes I through III were chosen because we aimed to include the entire spectrum of disease severity that occurs in patients with dilated cardiomyopathy. Patients with NYHA class IV were not directly included in the study, however. In our previous work, we showed that significant improvements of myocardial energy metabolism may be achieved during weeks of medical treatment for heart failure leading to clinical recompensation. Thus, short-term, reversible reductions of the phosphocreatine/ATP ratio can occur during short-term decompensation, most likely due to exacerbation of left ventricular dilatation, increased wall stress, and neurohumoral stimulation, that would probably not be predictive of long-term survival. For this reason, it was important to include only patients who were recompensated to at least NYHA class III by a minimum of 6 weeks of standard medical therapy for heart failure.
It is unlikely that our results are affected by accumulation of fibroblast or other nonmuscle cells in dilated cardiomyopathy. Quantitatively, such tissue contains negligible amounts of ATP and phosphocreatine. We previously reported that scar tissue in the chronically infarcted rat heart has <1% of ATP and phosphocreatine concentrations of normal myocardium.14 Thus, nonmuscle tissue will contribute to the 31P-MR signal to a negligible extent. Because we evaluated high-energy phosphate concentrations in relative terms only (phosphocreatine/ATP), nonmuscle tissue should not affect our results significantly.
A limitation of our study is the relatively small number of patients (n=39). However, at our hospital, the accumulation of this number of patients required a period of close to 7 years. With the current complexity of MR spectroscopy methodology and suitability requirements for the patients, it is impossible to amass a substantially larger number of patients during a reasonable study duration in a single-center approach. Furthermore, the number of patients in the study does not allow us to determine whether reductions in the phosphocreatine/ATP ratio are stronger indicators of one of the two main causes of cardiovascular death in dilated cardiomyopathy: progressively worsening heart failure or sudden death. It is conceivable, however, that reduced energy metabolism is not only predictive of progressive pump failure but also of sudden death: in isolated perfused hearts made hypoxic, the extent of myocardial phosphocreatine depletion was predictive of the occurrence of ventricular fibrillation.45 Thus, in a large-scale, multicenter study of dilated cardiomyopathy patients, it will be critical to examine whether phosphocreatine/ATP ratio reductions are predictors of both of the main causes of cardiovascular death. In such a study, it will also be interesting to evaluate whether phosphocreatine/ATP is a stronger predictor of early or late cardiovascular death. A statistical limitation of our study is that the cutoff levels for phosphocreatine/ATP ratios (>1.60 and <1.60), which were established retrospectively, need to be evaluated prospectively.
In conclusion, the myocardial phosphocreatine/ATP ratio, measured noninvasively at a compensated stage of heart failure, may be a guide to prognosis in patients with dilated cardiomyopathy. Long-term, multicenter studies during various forms of medical therapy with follow-up measurements of energy metabolism, cardiac function, clinical indices, and other traditionally recognized mortality predictors such as plasma catecholamine levels are required to further analyze how phosphocreatine/ATP changes can be used to predict the efficacy of drug therapy as well as prognosis.
|
Selected Abbreviations and Acronyms |
|---|
|
|
Acknowledgments |
|---|
This study was supported by grant SFB 355/A3 from the Deutsche Forschungsgemeinschaft.
Received April 2, 1997; revision received May 5, 1997; accepted May 15, 1997.
|
References |
|---|
|
TopAbstractIntroductionMethodsResultsDiscussionReferences |
|---|
1. Ingwall JS. Phosphorus nuclear magnetic resonance spectroscopy of cardiac and skeletal muscles. Am J Physiol. 1982;242:H729-H744.
2.
Bottomley PA. MR spectroscopy of the human
heart: the status and the challenges. Radiology. 1994;191:593-612.
3. Schaefer S, Gober JR, Schwartz GG, Twieg DB, Weiner MW, Massie B. In vivo phosphorus-31 spectroscopic imaging in patients with global myocardial disease. Am J Cardiol. 1990;65:1154-1161.[Medline] [Order article via Infotrieve]
4.
Blackledge MJ, Rajagopalan B, Oberhaensli RD, Bolas
NM, Styles P, Radda G. Quantitative studies of human cardiac
metabolism by 31P rotating-frame NMR.
Proc Natl Acad Sci U S A. 1987;84:4283-4287.
5.
Grist TM, Kneeland JB, Rilling WR, Jesmanowicz A,
Froncisz W, Hyde JS. Gated cardiac MR imaging and P-31 MR
spectroscopy in humans at 1.5 T. Radiology. 1989;170:357-361.
6.
Auffermann W, Chew W, Wolfe CL, Tavares NJ, Parmley
WW, Semelka RC, Donnelly T, Chatterjee K, Higgins CB. Normal and
diffusely abnormal myocardium in humans: functional and
metabolic characterization with P-31 MR spectroscopy and
cine MR imaging. Radiology. 1991;179:253-259.
7. de Roos A, Doornbos J, Luyten PR, Oosterwaal LJMP, van der Waal EE, den Hollander JA. Cardiac metabolism in patients with dilated and hypertrophic cardiomyopathy: assessment with proton-decoupled P-31 MR spectroscopy. J Magn Reson Imaging. 1992;2:711-719.[Medline] [Order article via Infotrieve]
8. Weiss RG, Bottomley PA, Hardy CJ, Gerstenblith G. Regional myocardial metabolism of high-energy phosphates during isometric exercise in patients with coronary artery disease. N Engl J Med. 1990;323:1593-1600.[Abstract]
9.
Yabe T, Mitsunami K, Inubushi T, Kinoshita M.
Quantitative measurements of cardiac phosphorus metabolites in
coronary artery disease by 31P magnetic resonance
spectroscopy. Circulation. 1995;92:15-23.
10. Conway MA, Allis J, Ouwerkerk R, Niioka T, Rajagopalan B, Radda GK. Detection of low phosphocreatine to ATP ratio in failing hypertrophied human myocardium by 31P magnetic resonance spectroscopy. Lancet. 1991;338:973-976.[Medline] [Order article via Infotrieve]
11.
Neubauer S, Krahe T, Schindler R, Hillenbrand H,
Entzeroth C, Horn M, Bauer WR, Stephan T, Lackner K, Haase A, Ertl
G. Cardiac 31P-magnetic resonance spectroscopy of
volunteers and patients with coronary artery disease and
dilated cardiomyopathy: altered cardiac high-energy
phosphate metabolism in heart failure.
Circulation. 1992;86:1810-1818.
12. Neubauer S, Horn M, Pabst T, Gödde M, Lübke D, Illing B, Hahn D, Ertl G. Contributions of 31P-magnetic resonance spectroscopy to the understanding of dilated heart muscle disease. Eur Heart J. 1995;16(suppl O):115-118.
13. Hardy CJ, Weiss RG, Bottomley PA, Gerstenblith G. Altered myocardial high-energy phosphate metabolites in patients with dilated cardiomyopathy. Am Heart J. 1991;122:795-801.[Medline] [Order article via Infotrieve]
14. Neubauer S, Horn M, Naumann A, Tian R, Hu K, Laser M, Friedrich J, Gaudron P, Schnackerz K, Ingwall JS, Ertl G. Impairment of energy metabolism in intact residual myocardium of rat hearts with chronic myocardial infarction. J Clin Invest. 1995;95:1092-1100.
15.
Markiewicz W, Wu SS, Parmley WW, Higgins CB, Sievers R,
James TL, Wikman-Coffelt J, Jasmin G. Evaluation of the
hereditary Syrian hamster cardiomyopathy by
31P nuclear magnetic resonance spectroscopy: improvement
after acute verapamil therapy. Circ Res. 1986;59:597-604.
16. Ingwall JS, Atkinson DE, Clarke K, Fetters JK. Energetic correlates of cardiac failure: changes in the creatine kinase system in the failing myocardium. Eur Heart J. 1990;II(suppl C):108-115.
17. Shimamoto N, Goto N, Tanabe M, Imamoto T, Fujiwara S, Hirata M. Myocardial energy metabolism in the hypertrophied hearts of spontaneously hypertensive rats. Basic Res Cardiol. 1982;77:359-371.[Medline] [Order article via Infotrieve]
18.
Nascimben L, Friedrich J, Liao R, Pauletto P, Pessina
AC, Ingwall JS. Enalapril treatment increases cardiac
performance and energy reserve via the creatine kinase reaction
in myocardium of Syrian myopathic hamsters with advanced
heart failure. Circulation. 1995;91:1824-1833.
19.
Zhang J, McDonald KM. Bioenergetic consequences
of left ventricular remodeling.
Circulation. 1995;92:1011-1019.
20. Ingwall JS. On the hypothesis: cardiac failure is due to decreased energy reserve. Circulation. 1993;87[suppl VII]:VII-58-VII-62.
21. Cohn JN, Rector TS. Prognosis of congestive heart failure and predictors of mortality. Am J Cardiol. 1988;62:25A-30A.[Medline] [Order article via Infotrieve]
22. Slachcic J, Massie BM, Kramer BL, Topic N, Tubau J. Correlates and prognostic implication of exercise capacity in chronic congestive heart failure. Am J Cardiol. 1985;55:1037-1042.[Medline] [Order article via Infotrieve]
23. Gradman A, Deedwania P, Cody R, Massie B, Packer M, Pitt B, Goldstein S. Predictors of total mortality and sudden death in mild to moderate heart failure. J Am Coll Cardiol. 1989;14:564-570.[Abstract]
24. Cohn J, Levine B, Olivari MT, Garberg V, Lura D, Francis GS, Simon AB, Rector T. Plasma norepinephrine as a guide to prognosis in patients with chronic congestive heart failure. N Engl J Med. 1984;311:819-923.[Abstract]
25. Gottlieb SS, Kukin ML, Ahern D, Packer M. Prognostic importance of atrial natriuretic peptide in patients with chronic heart failure. J Am Coll Cardiol. 1989;13:1534-1539.[Abstract]
26. Packer M. Potential role of potassium as a determinant of morbidity and mortality in patients with systemic hypertension and congestive heart failure. Am J Cardiol. 1990;65:45E-51E.[Medline] [Order article via Infotrieve]
27. Ordidge RJ, Connelly A, Lohman JAB. Image-Selected In vivo Spectroscopy (ISIS): a new technique for spatially selective NMR spectroscopy. J Magn Reson. 1985;66:283-294.
28. Horn M, Neubauer S, Bomhard M, Kadgien M, Schnackerz K, Ertl G. 31P-NMR spectroscopy of human blood and serum: first results from volunteers and patients with congestive heart failure, diabetes mellitus and hyperlipidemia. MAGMA. 1993;1:55-60.
29. Norusis M. SPSS Advanced Statistics Version 6.1. Chicago, Ill: SPSS Inc; 1994.
30. Wallimann T, Wyss M, Brdiczka D, Nicolay K, Eppenberger HM. Intracellular compartmentation, structure and function of creatine kinase isoenzymes in tissues with high and fluctuating energy demands: the phosphocreatine circuit for cellular energy homeostasis. Biochem J. 1992;281:21-40.
31.
Hamman BL, Bittl JA, Jacobus WE, Ingwall JS.
Inhibition of the creatine kinase reaction decreases the contractile
reserve of isolated rat hearts. Am J Physiol. 1995;269:H1030-H1036.
32.
Zweier JL, Jacobus WE, Korecky B, Brandejs-Barry
Y. Bioenergetic consequences of cardiac phosphocreatine
depletion induced by creatine analogue feeding. J
Biol Chem. 1991;266:20296-20304.
33. van Deussen J, Heerschap A, Oerlemans F, Ruitenbeek W, Jap P, ter Laak H, Wieringa B. Skeletal muscles of mice deficient in muscle creatine kinase lack burst activity. Cell. 1993;74:621-631.[Medline] [Order article via Infotrieve]
34. Zhang J, Merkle H, Hendrich K, Garwood M, From AHL, Ugurbil K, Bache RJ. Bioenergetic abnormalities associated with severe left ventricular hypertrophy. J Clin Invest. 1993;92:993-1003.
35. Sanbe A, Tanonaka K, Hanaoka Y, Katoh T, Takeo S. Regional energy metabolism of failing hearts following myocardial infarction. J Mol Cell Cardiol. 1993;25:995-1013.[Medline] [Order article via Infotrieve]
36.
Nascimben L, Ingwall JS, Pauletto P, Friedrich J,
Gwathmey JK, Saks V, Pessina AC, Allen PD. The creatine kinase
system in failing and nonfailing human myocardium.
Circulation. 1996;94:1894-1901.
37. Tian R, Nascimben L, Daouk R, Ingwall JS. Depletion of energy reserve via creatine kinase reaction during the evolution of heart failure in cardiomyopathic hamsters. J Mol Cell Cardiol. 1996;28:755-765.[Medline] [Order article via Infotrieve]
38.
Liao R, Nascimben L, Friedrich J, Gwathmey JK, Ingwall
JS. Decreased energy reserve in an animal model of dilated
cardiomyopathy. Circ Res. 1996;78:893-902.
39. Horn M, Neubauer S, Frantz S, Hügel S, Hu K, Gaudron P, Schnackerz K, Ertl G. Preservation of left ventricular mechanical function and energy metabolism in rats post myocardial infarction by the angiotensin converting enzyme inhibitor quinapril. J Cardiovasc Pharmacol. 1996;27:201-210.[Medline] [Order article via Infotrieve]
40. Laser A, Neubauer S, Tian R, Hu K, Gaudron P, Ingwall J, Ertl G. Long-term beta-blocker treatment prevents chronic creatine kinase and lactate dehydrogenase system changes in rat hearts post-myocardial infarction. J Am Coll Cardiol. 1996;27:487-493.[Abstract]
41. Pfeffer MA, on behalf of the SAVE Investigators. Effect of captopril on mortality and morbidity in patients with left ventricular dysfunction after myocardial infarction. N Engl J Med. 1992;327:669-677.[Abstract]
42. Consensus Trial Study Group. Effects of enalapril on mortality in severe congestive heart failure. N Engl J Med. 1987;316:1429-1435.[Abstract]
43.
Swedberg K, Hjalmarson A, Waagstein F, Wallentin
I. Beneficial effects of long-term beta-blockade in congestive
cardiomyopathy. Br Heart J. 1980;44:117-133.
44.
CIBIS Investigators and Committees. A randomized trial
of ß-blockade in heart failure: the Cardiac Insufficiency BIsoprolol
Study (CIBIS). Circulation. 1994;90:1765-1773.
45.
Neubauer S, Newell JB, Ingwall JS.
Ventricular fibrillation in hypoxia:
metabolic consequences and predictability—a
31P- and 23Na-NMR study of the isolated rat
heart. Circulation. 1992;86:302-310.
This article has been cited by other articles:
 |
|
 |
|
  V. Soukoulis, J. B. Dihu, M. Sole, S. D. Anker, J. Cleland, G. C. Fonarow, M. Metra, E. Pasini, T. Strzelczyk, H. Taegtmeyer, et al. Micronutrient deficiencies an unmet need in heart failure. J. Am. Coll. Cardiol., October 27, 2009; 54(18): 1660 - 1673. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. W.-K. Yip, M. Frenneaux, and J. E Sanderson Heart failure with a normal ejection fraction: new developments Heart, October 1, 2009; 95(19): 1549 - 1552. [Full Text] [PDF]
|
|
|
|
|
|
G Perseghin, F De Cobelli, A Esposito, E Belloni, G Lattuada, T Canu, P L Invernizzi, F Ragogna, A La Torre, P Scifo, et al. Left ventricular function and energy metabolism in middle-aged men undergoing long-lasting sustained aerobic oxidative training Heart, April 1, 2009; 95(8): 630 - 635. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 X. Chen, K. Wang, J. Chen, J. Guo, Y. Yin, X. Cai, X. Guo, G. Wang, R. Yang, L. Zhu, et al. In Vitro Evidence Suggests That miR-133a-mediated Regulation of Uncoupling Protein 2 (UCP2) Is an Indispensable Step in Myogenic Differentiation J. Biol. Chem., February 20, 2009; 284(8): 5362 - 5369. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. van Bilsen, F. A. van Nieuwenhoven, and G. J. van der Vusse Metabolic remodelling of the failing heart: beneficial or detrimental? Cardiovasc Res, February 15, 2009; 81(3): 420 - 428. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. S. Ingwall Energy metabolism in heart failure and remodelling Cardiovasc Res, February 15, 2009; 81(3): 412 - 419. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. E. Hudsmith and S. Neubauer Magnetic resonance spectroscopy in myocardial disease. J. Am. Coll. Cardiol. Img., January 1, 2009; 2(1): 87 - 96. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 F. Joubert, J. R. Wilding, D. Fortin, V. Domergue-Dupont, M. Novotova, R. Ventura-Clapier, and V. Veksler Local energetic regulation of sarcoplasmic and myosin ATPase is differently impaired in rats with heart failure J. Physiol., November 1, 2008; 586(21): 5181 - 5192. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F. Wu, E. Y. Zhang, J. Zhang, R. J. Bache, and D. A. Beard Phosphate metabolite concentrations and ATP hydrolysis potential in normal and ischaemic hearts J. Physiol., September 1, 2008; 586(17): 4193 - 4208. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Beer, D. Wagner, J. Myers, J. Sandstede, H. Kostler, D. Hahn, S. Neubauer, and P. Dubach Effects of Exercise Training on Myocardial Energy Metabolism and Ventricular Function Assessed by Quantitative Phosphorus-31 Magnetic Resonance Spectroscopy and Magnetic Resonance Imaging in Dilated Cardiomyopathy J. Am. Coll. Cardiol., May 13, 2008; 51(19): 1883 - 1891. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. J. Eisen Exercise Training and Myocardial Energetics in Patients With Heart Failure: When More Is Less J. Am. Coll. Cardiol., May 13, 2008; 51(19): 1892 - 1895. [Full Text] [PDF]
|
|
|
|
 |
|
 J. Feygin, Q. Hu, C. Swingen, and J. Zhang Relationships between regional myocardial wall stress and bioenergetics in hearts with left ventricular hypertrophy Am J Physiol Heart Circ Physiol, May 1, 2008; 294(5): H2313 - H2321. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. F. Kelly, W. Sluiter, and E. O. McFalls Hibernating Myocardium: Is the Program to Survive a Pathway to Failure? Circ. Res., January 4, 2008; 102(1): 3 - 5. [Full Text] [PDF]
|
|
|
|
|
|
E. O. McFalls, R. F. Kelly, Q. Hu, A. Mansoor, J. Lee, M. Kuskowski, J. Sikora, H. B. Ward, and J. Zhang The energetic state within hibernating myocardium is normal during dobutamine despite inhibition of ATP-dependent potassium channel opening with glibenclamide Am J Physiol Heart Circ Physiol, November 1, 2007; 293(5): H2945 - H2951. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Feygin, A. Mansoor, P. Eckman, C. Swingen, and J. Zhang Functional and bioenergetic modulations in the infarct border zone following autologous mesenchymal stem cell transplantation Am J Physiol Heart Circ Physiol, September 1, 2007; 293(3): H1772 - H1780. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. G. Koch and S. L. Britton Evolution, atmospheric oxygen, and complex disease Physiol Genomics, August 20, 2007; 30(3): 205 - 208. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Ashrafian, M. P. Frenneaux, and L. H. Opie Metabolic Mechanisms in Heart Failure Circulation, July 24, 2007; 116(4): 434 - 448. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. Peluffo and R. Radi Biochemistry of protein tyrosine nitration in cardiovascular pathology Cardiovasc Res, July 15, 2007; 75(2): 291 - 302. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. N. Finck and D. P. Kelly Peroxisome Proliferator-Activated Receptor {gamma} Coactivator-1 (PGC-1) Regulatory Cascade in Cardiac Physiology and Disease Circulation, May 15, 2007; 115(19): 2540 - 2548. [Full Text] [PDF]
|
|
|
|
 |
|
 S. Neubauer The Failing Heart -- An Engine Out of Fuel N. Engl. J. Med., March 15, 2007; 356(11): 1140 - 1151. [Full Text] [PDF]
|
|
|
|
|
|
R. Ventura-Clapier, B. Mettauer, and X. Bigard Beneficial effects of endurance training on cardiac and skeletal muscle energy metabolism in heart failure Cardiovasc Res, January 1, 2007; 73(1): 10 - 18. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y J. Woo, T. J Grand, G. P Liao, and C. M Panlilio Off-pump revascularization for significant left ventricular dysfunction. Asian Cardiovasc Thorac Ann, August 1, 2006; 14(4): 306 - 309. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. J. Murray, C. A. Lygate, M. A. Cole, C. A. Carr, G. K. Radda, S. Neubauer, and K. Clarke Insulin resistance, abnormal energy metabolism and increased ischemic damage in the chronically infarcted rat heart Cardiovasc Res, July 1, 2006; 71(1): 149 - 157. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. Fragasso, G. Perseghin, F. De Cobelli, A. Esposito, A. Palloshi, G. Lattuada, P. Scifo, G. Calori, A. Del Maschio, and A. Margonato Effects of metabolic modulation by trimetazidine on left ventricular function and phosphocreatine/adenosine triphosphate ratio in patients with heart failure Eur. Heart J., April 2, 2006; 27(8): 942 - 948. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 F. C. Chen and O. Ogut Decline of contractility during ischemia-reperfusion injury: actin glutathionylation and its effect on allosteric interaction with tropomyosin Am J Physiol Cell Physiol, March 1, 2006; 290(3): C719 - C727. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. V. Naumova, V. P. Chacko, R. Ouwerkerk, L. Stull, E. Marban, and R. G. Weiss Xanthine oxidase inhibitors improve energetics and function after infarction in failing mouse hearts Am J Physiol Heart Circ Physiol, February 1, 2006; 290(2): H837 - H843. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. J. Kang Cardiac Hypertrophy: A Risk Factor for QT-Prolongation and Cardiac Sudden Death Toxicol Pathol, January 1, 2006; 34(1): 58 - 66. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. J. Murray, M. Panagia, D. Hauton, G. F. Gibbons, and K. Clarke Plasma Free Fatty Acids and Peroxisome Proliferator-Activated Receptor {alpha} in the Control of Myocardial Uncoupling Protein Levels Diabetes, December 1, 2005; 54(12): 3496 - 3502. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Maloyan, A. Sanbe, H. Osinska, M. Westfall, D. Robinson, K.-i. Imahashi, E. Murphy, and J. Robbins Mitochondrial Dysfunction and Apoptosis Underlie the Pathogenic Process in {alpha}-B-Crystallin Desmin-Related Cardiomyopathy Circulation, November 29, 2005; 112(22): 3451 - 3461. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. J. Woo, T. J. Grand, M. F. Berry, P. Atluri, M. A. Moise, V. M. Hsu, J. Cohen, O. Fisher, J. Burdick, M. Taylor, et al. Stromal cell-derived factor and granulocyte-monocyte colony-stimulating factor form a combined neovasculogenic therapy for ischemic cardiomyopathy J. Thorac. Cardiovasc. Surg., August 1, 2005; 130(2): 321 - 329. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 W. C. Stanley, F. A. Recchia, and G. D. Lopaschuk Myocardial Substrate Metabolism in the Normal and Failing Heart Physiol Rev, July 1, 2005; 85(3): 1093 - 1129. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. G. Weiss, G. Gerstenblith, and P. A. Bottomley ATP flux through creatine kinase in the normal, stressed, and failing human heart PNAS, January 18, 2005; 102(3): 808 - 813. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. J. Pennell, U. P. Sechtem, C. B. Higgins, W. J. Manning, G. M. Pohost, F. E. Rademakers, A. C. van Rossum, L. J. Shaw, and E. K. Yucel Clinical indications for cardiovascular magnetic resonance (CMR): Consensus Panel report Eur. Heart J., November 1, 2004; 25(21): 1940 - 1965. [Full Text] [PDF]
|
|
|
|
|
|
S. Goffart, J.-C. von Kleist-Retzow, and R. J. Wiesner Regulation of mitochondrial proliferation in the heart: power-plant failure contributes to cardiac failure in hypertrophy Cardiovasc Res, November 1, 2004; 64(2): 198 - 207. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. S. Ingwall and R. G. Weiss Is the Failing Heart Energy Starved?: On Using Chemical Energy to Support Cardiac Function Circ. Res., July 23, 2004; 95(2): 135 - 145. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. D. Johnson, L. J. Shaw, S. D. Buchthal, C. N. Bairey Merz, H.-W. Kim, K. N. Scott, M. Doyle, M. B. Olson, C. J. Pepine, J. den Hollander, et al. Prognosis in Women With Myocardial Ischemia in the Absence of Obstructive Coronary Disease: Results From the National Institutes of Health-National Heart, Lung, and Blood Institute-Sponsored Women's Ischemia Syndrome Evaluation (WISE) Circulation, June 22, 2004; 109(24): 2993 - 2999. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Ventura-Clapier, A. Garnier, and V. Veksler Energy metabolism in heart failure J. Physiol., February 15, 2004; 555(1): 1 - 13. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. V. Gourine, Q. Hu, P. R. Sander, A. I. Kuzmin, N. Hanafy, S. A. Davydova, D. V. Zaretsky, and J. Zhang Interstitial purine metabolites in hearts with LV remodeling Am J Physiol Heart Circ Physiol, February 1, 2004; 286(2): H677 - H684. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. van Bilsen, P. J.H Smeets, A. J Gilde, and G. J van der Vusse Metabolic remodelling of the failing heart: the cardiac burn-out syndrome? Cardiovasc Res, February 1, 2004; 61(2): 218 - 226. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. Omerovic, E. Bollano, B. Soussi, and F. Waagstein Selective {beta}1-blockade attenuates post-infarct remodelling without improvement in myocardial energy metabolism and function in rats with heart failure Eur J Heart Fail, December 1, 2003; 5(6): 725 - 732. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
I. Nakae, K. Mitsunami, T. Omura, T. Yabe, T. Tsutamoto, S. Matsuo, M. Takahashi, S. Morikawa, T. Inubushi, Y. Nakamura, et al. Proton magnetic resonance spectroscopy can detect creatine depletion associated with the progression of heart failure in cardiomyopathy J. Am. Coll. Cardiol., November 5, 2003; 42(9): 1587 - 1593. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
O. Ogut and F. V. Brozovich Creatine Phosphate Consumption and the Actomyosin Crossbridge Cycle in Cardiac Muscles Circ. Res., July 11, 2003; 93(1): 54 - 60. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. Gong, J. Liu, P. Liang, T. Guo, Q. Hu, K. Ochiai, M. Hou, Y. Ye, X. Wu, A. Mansoor, et al. Oxidative capacity in failing hearts Am J Physiol Heart Circ Physiol, July 11, 2003; 285(2): H541 - H548. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Scheuermann-Freestone, P. L. Madsen, D. Manners, A. M. Blamire, R. E. Buckingham, P. Styles, G. K. Radda, S. Neubauer, and K. Clarke Abnormal Cardiac and Skeletal Muscle Energy Metabolism in Patients With Type 2 Diabetes Circulation, June 24, 2003; 107(24): 3040 - 3046. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. G. Crilley, E. A. Boehm, E. Blair, B. Rajagopalan, A. M. Blamire, P. Styles, W. J. McKenna, I. Ostman-Smith, K. Clarke, and H. Watkins Hypertrophic cardiomyopathy due to sarcomeric gene mutations is characterized by impaired energy metabolism irrespective of the degree of hypertrophy J. Am. Coll. Cardiol., May 21, 2003; 41(10): 1776 - 1782. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P.A. Poole-Wilson Who are the enemies? Lack of oxygen Eur. Heart J. Suppl., November 1, 2002; 4(suppl_G): G15 - G19. [Abstract] [PDF]
|
|
|
|
|
|
M. Spindler, R. Niebler, H. Remkes, M. Horn, T. Lanz, and S. Neubauer Mitochondrial creatine kinase is critically necessary for normal myocardial high-energy phosphate metabolism Am J Physiol Heart Circ Physiol, August 1, 2002; 283(2): H680 - H687. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
V.i. G. Davila-Roman, G. Vedala, P. Herrero, L. de las Fuentes, J. G. Rogers, D. P. Kelly, and R. J. Gropler Altered myocardial fatty acid and glucose metabolism in idiopathic dilated cardiomyopathy J. Am. Coll. Cardiol., July 17, 2002; 40(2): 271 - 277. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Watkins Hypertrophic cardiomyopathy: from molecular and genetic mechanisms to clinical management Eur. Heart J. Suppl., October 1, 2001; 3(suppl_L): L43 - L50. [Abstract] [PDF]
|
|
|
|
|
|
F. del Monte, E. Williams, D. Lebeche, U. Schmidt, A. Rosenzweig, J. K. Gwathmey, E. D. Lewandowski, and R. J. Hajjar Improvement in Survival and Cardiac Metabolism After Gene Transfer of Sarcoplasmic Reticulum Ca2+-ATPase in a Rat Model of Heart Failure Circulation, September 18, 2001; 104(12): 1424 - 1429. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Liu, C. Wang, Y. Murakami, G. Gong, Y. Ishibashi, C. Prody, K. Ochiai, R. J. Bache, C. Godinot, and J. Zhang Mitochondrial ATPase and high-energy phosphates in failing hearts Am J Physiol Heart Circ Physiol, September 1, 2001; 281(3): H1319 - H1326. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. J. Mihm, F. Yu, C. A. Carnes, P. J. Reiser, P. M. McCarthy, D. R. Van Wagoner, and J. A. Bauer Impaired Myofibrillar Energetics and Oxidative Injury During Human Atrial Fibrillation Circulation, July 10, 2001; 104(2): 174 - 180. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. P. Beyerbacht, H. J. Lamb, A. van der Laarse, H. W. Vliegen, F. Leujes, M. G. Hazekamp, A. de Roos, and E. E. van der Wall Aortic Valve Replacement in Patients with Aortic Valve Stenosis Improves Myocardial Metabolism and Diastolic Function Radiology, June 1, 2001; 219(3): 637 - 643. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. Braunwald Congestive heart failure: a half century perspective Eur. Heart J., May 2, 2001; 22(10): 825 - 836. [PDF]
|
|
|
|
 |
|
 E. Blair, C. Redwood, H. Ashrafian, M. Oliveira, J. Broxholme, B. Kerr, A. Salmon, I. Ostman-Smith, and H. Watkins 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., May 1, 2001; 10(11): 1215 - 1220. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Pennell IMAGING TECHNIQUES: Cardiovascular magnetic resonance Heart, May 1, 2001; 85(5): 581 - 589. [Full Text]
|
|
|
|
|
|
Y. Ye, G. Gong, K. Ochiai, J. Liu, and J. Zhang High-Energy Phosphate Metabolism and Creatine Kinase in Failing Hearts : A New Porcine Model Circulation, March 20, 2001; 103(11): 1570 - 1576. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. Omerovic, E. Bollano, R. Mobini, V. Kujacic, B. Madhu, B. Soussi, M. Fu, A. Hjalmarson, F. Waagstein, and J. Isgaard Growth Hormone Improves Bioenergetics and Decreases Catecholamines in Postinfarct Rat Hearts Endocrinology, December 1, 2000; 141(12): 4592 - 4599. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
V. P. Chacko, F. Aresta, S. M. Chacko, and R. G. Weiss MRI/MRS assessment of in vivo murine cardiac metabolism, morphology, and function at physiological heart rates Am J Physiol Heart Circ Physiol, November 1, 2000; 279(5): H2218 - H2224. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. H. Lorell and B. A. Carabello Left Ventricular Hypertrophy : Pathogenesis, Detection, and Prognosis Circulation, July 25, 2000; 102(4): 470 - 479. [Full Text] [PDF]
|
|
|
|
 |
|
 J. Irvine, A. Basinski, B. Baker, S. Jandciu, M. Paquette, J. Cairns, S. Connolly, R. Roberts, M. Gent, and P. Dorian Depression and Risk of Sudden Cardiac Death After Acute Myocardial Infarction: Testing for the Confounding Effects of Fatigue Psychosom Med, November 1, 1999; 61(6): 729 - 737. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. De Sousa, V. Veksler, A. Minajeva, A. Kaasik, P. Mateo, E. Mayoux, J. Hoerter, X. Bigard, B. Serrurier, and R. Ventura-Clapier Subcellular Creatine Kinase Alterations : Implications in Heart Failure Circ. Res., July 9, 1999; 85(1): 68 - 76. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B M Pluim, C A Swenne, A H Zwinderman, A C Maan, A van der Laarse, J Doornbos, and E E Van der Wall Correlation of heart rate variability with cardiac functional and metabolic variables in cyclists with training induced left ventricular hypertrophy Heart, June 1, 1999; 81(6): 612 - 617. [Abstract] [Full Text]
|
|
|
|
|
|
P. P. Dzeja, K. T. Vitkevicius, M. M. Redfield, J. C. Burnett, and A. Terzic Adenylate Kinase–Catalyzed Phosphotransfer in the Myocardium : Increased Contribution in Heart Failure Circ. Res., May 28, 1999; 84(10): 1137 - 1143. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Murakami, J. Zhang, M. H. J. Eijgelshoven, W. Chen, W. C. Carlyle, Y. Zhang, G. Gong, and R. J. Bache Myocardial creatine kinase kinetics in hearts with postinfarction left ventricular remodeling Am J Physiol Heart Circ Physiol, March 1, 1999; 276(3): H892 - H900. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. A. Conway, P. A. Bottomley, R. Ouwerkerk, G. K. Radda, and B. Rajagopalan Mitral Regurgitation : Impaired Systolic Function, Eccentric Hypertrophy, and Increased Severity Are Linked to Lower Phosphocreatine/ATP Ratios in Humans Circulation, May 5, 1998; 97(17): 1716 - 1723. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P Ruiz-Lozano, S. Smith, G Perkins, S. Kubalak, G. Boss, H. Sucov, R. Evans, and K. Chien Energy deprivation and a deficiency in downstream metabolic target genes during the onset of embryonic heart failure in RXRalpha-/- embryos Development, January 2, 1998; 125(3): 533 - 544. [Abstract] [PDF]
|
|
|
|
|
|
D. Pucar, E. Janssen, P. P. Dzeja, N. Juranic, S. Macura, B. Wieringa, and A. Terzic Compromised Energetics in the Adenylate Kinase AK1 Gene Knockout Heart under Metabolic Stress J. Biol. Chem., December 22, 2000; 275(52): 41424 - 41429. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Frederich and J. A. Balschi The Relationship between AMP-activated Protein Kinase Activity and AMP Concentration in the Isolated Perfused Rat Heart J. Biol. Chem., January 11, 2002; 277(3): 1928 - 1932. [Abstract] [Full Text] [PDF]
|
|
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||