Kerstin Harre

Myocardial Phosphocreatine-to-ATP Ratio Is a Predictor of Mortality in Patients With Dilated Cardiomyopathy

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 re-evaluation (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.

Absolute concentrations of high-energy phosphate metabolites in normal, hypertrophied, and failing human myocardium measured noninvasively with 31P-SLOOP magnetic resonance spectroscopy☆

OBJECTIVE The purpose of the present study was to measure absolute concentrations of phosphocreatine (PCr) and adenosine triphosphate (ATP) in normal, hypertrophied, and failing human heart. BACKGROUND Conflicting evidence exists on the extent of changes of high-energy phosphate metabolites in hypertrophied and failing human heart. Previous reports using phosphorus-31 magnetic resonance spectroscopy ((31)P-MRS) have quantified metabolites in relative terms only. However, this analysis cannot detect simultaneous reductions. METHODS Four groups of subjects (n = 10 each), were studied: volunteers and patients with hypertensive heart disease (HHD), aortic stenosis, and dilated cardiomyopathy (DCM). Left ventricular (LV) function and mass were measured by cine magnetic resonance imaging. Absolute and relative concentrations of PCr and ATP were determined by (31)P-MRS with spatial localization with optimum point spread function. RESULTS Left ventricular ejection fraction remained normal in HHD and aortic stenosis, but was severely reduced to 18% in DCM; LV mass was increased by 55%, 79%, and 68% respectively. In volunteers, PCr and ATP concentrations were 8.82 +/- 1.30 mmol/kg wet weight and 5.69 +/- 1.02 mmol/kg wet weight, and the PCr/ATP ratio was 1.59 +/- 0.33. High-energy phosphate levels were unaltered in HHD. In aortic stenosis, PCr was decreased by 28%, whereas ATP remained constant. In DCM, PCr was reduced by 51%, ATP by 35%, and reduction of the PCr/ATP ratio by 25% was of borderline significance (p = 0.06). Significant correlations were observed among energetic and functional variables, with the closest relations for PCr. CONCLUSIONS In human heart failure due to DCM, both PCr and ATP are significantly reduced. Ratios of PCr to ATP underestimate changes of high-energy phosphate levels.

Effect of additional temporary glycoprotein IIb/IIIa receptor inhibition on troponin release in elective percutaneous coronary interventions after pretreatment with aspirin and clopidogrel (TOPSTAR trial).

OBJECTIVES The Troponin in Planned PTCA/Stent Implantation With or Without Administration of the Glycoprotein IIb/IIIa Receptor Antagonist Tirofiban (TOPSTAR) trial investigated: 1) the amount of troponin T (TnT) release after nonacute, elective percutaneous coronary intervention (PCI) in patients pretreated with aspirin and clopidogrel; and 2) the effect of additional glycoprotein (GP) IIb/IIIa receptor inhibiton on postinterventional TnT release. BACKGROUND No data are available yet as to whether additional administration of a GP IIb/IIIa receptor antagonist might be beneficial in patients undergoing elective PCI already pretreated with aspirin and clopidogrel. METHODS After bolus application of the study medication (tirofiban [T] or placebo [P]), PCI was performed followed by an 18-h continuous infusion of T/P. Primary end point of the study was incidence and amount of TnT release after elective PCI after 24 h. RESULTS A total of 12 h after PCI troponin release was detected in 63% of the patients receiving P and in 40% of the patients receiving T (p < 0.05), after 24 h in 69% (P) and 48% (T) (p < 0.05) and after 48 h in 74% (P) versus 58% (T) (p < 0.08) of the patients. No differences were observed regarding major bleeding, intracranial bleeding or nonhemorrhagic strokes. After nine months a reduction of combined death/myocardial infarction/target vessel revascularization could be observed in the tirofiban group ([T] 2.3% vs. [P] 13.04%, p < 0.05). CONCLUSIONS Troponin T release occurs after successful intervention in 74% of the patients undergoing elective PCI after 48 h even after pretreatment with aspirin and clopidogrel. The GP IIb/IIIa receptor antagonist tirofiban is able to decrease the incidence of troponin release significantly in this patient population.

Changes in left and right ventricular cardiac function after valve replacement for aortic stenosis determined by cine MR imaging.

The purpose of this study was to determine the changes in function of both the left and the right ventricles (LV, RV) before and after aortic valve replacement (AVR), compared with age‐matched healthy volunteers using magnetic resonance (MR) imaging. Fourteen patients with aortic stenosis underwent MR imaging (1.5 T) before and 3 (n = 14) and 12 (n = 9) months after surgical valve replacement. An electrocardiographically triggered two‐dimensional cine fast low‐angle shot sequence was used for the evaluation of absolute values and indices related to 1 m 2 body surface area for function, mass, and LV wall thickening. Fourteen age‐matched healthy volunteers served as controls. Before surgery, all patients showed significant abnormalities of LV mass and function, whereas RV mass and function were not different from those of volunteers and remained mostly unchanged. After surgery, normalization of LV ejection fraction, absolute mass, and end‐systolic wall thickness was observed, whereas the LV mass index failed to normalize, and LV volumes remained elevated. Aortic stenosis combined with a significant, but not severe reduction in LV function only affects the LV, whereas the RV remains unaffected at this stage of disease. AVR leads to improved LV function and reduced hypertrophy, but without normalization of LV volumes or the LV mass index within 1 year. J. Magn. Reson. Imaging 2000;12:240–246.

Altered energy metabolism after myocardial infarction assessed by 31P-MR-spectroscopy in humans

Abstract. The value of 31P-magnetic resonance spectroscopy (MRS) as a possible tool to distinguish viable from non-viable tissue after myocardial infarction was analysed in humans. Fifteen patients 3 weeks after anterior myocardial infarction were studied with breath-hold cine MRI and 3D-CSI MRS (1.5 T system). 31P-spectra were obtained from infarcted as well as non-infarcted myocardium (voxel size 25 cm3 each). Gold standard for viability was recovery of regional function, as determined by a control MRI 6 months after revascularization. Ten age-matched healthy volunteers served as control group. No significant difference was found between the phosphocreatine to adenosinetriphosphate (PCr/ATP) ratio of volunteers (SD 1.72 ± 0.31) and non-infarcted septal myocardium of patients. Cine MRI demonstrated recovery of regional function in 10 patients, i. e. 10 patients showed viable and 5 non-viable myocardium. In viable myocardium, the PCr/ATP ratio was 1.47 ± 0.38 (non-significant vs volunteers; p > 0.05). In the 5 patients with akinetic myocardium, PCr peaks could not be detected. Therefore, calculation of PCr/ATP ratios was not possible. However, a significant reduction of the ATP signal-to-noise ratio (SNR) was observed (2.92 ± 0.73 vs 6.68 ± 0.80; patients vs volunteers; p <0.05). The SNR of ATP of akinetic regions may predict recovery of function after revascularization in patients with myocardial infarction.

Advances in human cardiac 31P-MR spectroscopy: SLOOP and clinical applications.

Phosphorus magnetic resonance spectroscopy (31P‐MRS) has revealed a lot about the biochemistry of physiological and pathological processes in the heart. Nevertheless, until today, cardiac 31P‐MRS has not had any clinical impact, albeit some pioneering studies demonstrated that 31P‐MRS can indeed provide diagnostic information. In this paper, the development of techniques for human cardiac 31P‐MRS over the past decade is reviewed, and the requirements for a reliable clinical measurement protocol are discussed. Spatial localization with optimal pointspread function (SLOOP) is a new method to achieve spatial localization and absolute quantitation. Its properties are detailed, and preliminary findings in patients with dilated cardiomyopathy or myocardial infarction are presented. J. Magn. Reson. Imaging 2001;13:521–527.

Time course of contrast enhancement patterns after Gd-BOPTA in correlation to myocardial infarction and viability: a feasibility study.

Our objective was to analyze contrast enhancement patterns (CEP) and their time course after myocardial infarction (MI) following injection of Gd‐BOPTA in correlation with recovery of regional function. Seven patients with subacute MI (18 ± nine days) were examined before, as well as three and six (n = six) months after, revascularization of the infarct‐related artery. Regional wall motion abnormalities were assessed by cine‐MRI, and repetitive images of one representative slice were acquired up to 45 minutes after 0.05 mmol/kg Gd‐BOPTA using a T1‐w TSE‐sequence. Two patients showed mid‐wall/subendocardial, one patient subendocardial enhancement of MI associated with mechanical improvement after revascularization. Three patients without improvement revealed a mid‐wall hypoenhanced zone within the first five minutes after injection, which was unchanged at follow‐up. One patient with partial functional improvement showed transmural enhancement and a mid‐wall hypoenhanced zone in adjacent areas. With this feasibility study, we concluded that mid‐wall and/or subendocardial enhancement after Gd‐BOPTA was associated with viable myocardium, whereas detection of microvascular obstruction correlating with scar formation is suggested by mid‐wall hypoenhancement within the first five minutes after injection. J. Magn. Reson. Imaging 2001;14:789–794.

31P-MR Spectroscopy for the evaluation of energy metabolism in intact residual myocardium after acute myocardial infarction in humans

Objectiveexperimental studies have demonstrated that acute myocardial infarction (MI) alters energy metabolism even in non-infarcted adjacent tissue. In patients with subacute MI, the influence of the regional ischemie insult on energy metabolism of intact septal myocardium was analyzed using31P-Magnetic resonance spectroscopy (MRS).Patients and Methodsin eight patients with wall motion abnormalities in the anterior wall31P-spectra were obtained from non-infarcted adjacent scptal myocardium, as well as infarcted anterior myocardium (voxel size 25 ccm each) 29 ±8 days after MI using a 3D-CSI technique. Additionally, cardiac function was analyzed using breath-hold cine MRI. MR1 was repeated 6 months after revascularization to assess viability of infarcted segments. Eight age-matched healthy volunteers served as control group.Resultsaccording to follow-up MRI 4/8 patients showed regional wall motion recovery. Here, PCr/ATP-ratios were not significantly reduced in intact septal myocardium as well as infarcted anterior myocardium compared to healthy volunteers (1.28 ±0.10 and 1.14 ±0.09 vs. 1.45 ±0.29). No recovery of regional function was detected in 4/8 patients with —therefore—non-viable anterior myocardium. PCr/ATP-ratios were significantly reduced in intact and infarcted myocardium compared with healthy volunteers as well as to patients with wall motion recovery (0.77 ±0.17 and 0.49 ±0.23;P < 0.05).Discussionthese preliminary results indicate that energy metabolism is reduced in patients with persisting wall motion abnormalities after myocardial infarction and revascularization in ischemically injured as well as in adjacent non-injured myocardium.

Assessment of myocardial viability by 31P-MR-spectroscopy and 23Na-MR imaging

An exact differentiation between viable (hibernating or stunned) and non-viable (scar) tissue is crucial for the decision whether revascularisation is required after myocardial infarction [I]. Former studies demonstrated altered energy metabolism in ischemic myocardium [2]. 3~p-MR-Spectroscopy offers the unique possibility for non-invasive study of cardiac energy metabolism. Aim of the present work was to analyze whether a reliable detection of myocardial viability is possible by 3tp-MRSpectroscopy. All examinations were performed on a 1.5 Tesla clinical MR system (Magnetom VISION, Siemens, Erlangen). 3~p-spectra were acquired using a double-resonant 3~p/~H-surface coil and a double-angulated 3D-CSI-technique (voxelsize 25 ccm). Due to the limited sensitivity for the deeper parts of the heart only patients with anterior wall infarction were included (n=20) . For each patient 3~P-spectra from the infarcted area were compared to 3~p-spectra from non-infarcted septat myocardium (internal reference). Additionally, left ventricular function was analyzed by short axis cine-MRI breath-hold sequences (slice thickness 8 mm). Both examinations were performed at study entry (3 weeks after acute myocardial infarction) and 3 months after revascularization. Improvement of regional function in MRI was used as gold standard for viability [3]. Aged-matched healthy volunteers (n = 10) served as control group. Using the AMARES software

Assessment of myocardial viability by 31 P-MR-spectroscopy and 23 Na-MR imaging

An exact differentiation between viable (hibernating or stunned) and non-viable (scar) tissue is crucial for the decision whether revascularisation is required after myocardial infarction [I]. Former studies demonstrated altered energy metabolism in ischemic myocardium [2]. 3~p-MR-Spectroscopy offers the unique possibility for non-invasive study of cardiac energy metabolism. Aim of the present work was to analyze whether a reliable detection of myocardial viability is possible by 3tp-MRSpectroscopy. All examinations were performed on a 1.5 Tesla clinical MR system (Magnetom VISION, Siemens, Erlangen). 3~p-spectra were acquired using a double-resonant 3~p/~H-surface coil and a double-angulated 3D-CSI-technique (voxelsize 25 ccm). Due to the limited sensitivity for the deeper parts of the heart only patients with anterior wall infarction were included (n=20) . For each patient 3~P-spectra from the infarcted area were compared to 3~p-spectra from non-infarcted septat myocardium (internal reference). Additionally, left ventricular function was analyzed by short axis cine-MRI breath-hold sequences (slice thickness 8 mm). Both examinations were performed at study entry (3 weeks after acute myocardial infarction) and 3 months after revascularization. Improvement of regional function in MRI was used as gold standard for viability [3]. Aged-matched healthy volunteers (n = 10) served as control group. Using the AMARES software