J Nucl Med. Markus Schwaiger István Kósa, Rudolf Blasini, Jan Schneider-Eicke, Franz J. Neumann, Ichiro Matsunari, Jodi Neverve, Albert Schömig and Implantation Myocardial Perfusion Scintigraphy to Evaluate Patients After Coronary Stent http://jnm.snmjournals.org/content/39/8/1307 This article and updated information are available at: http://jnm.snmjournals.org/site/subscriptions/online.xhtml Information about subscriptions to JNM can be found at: http://jnm.snmjournals.org/site/misc/permission.xhtml Information about reproducing figures, tables, or other portions of this article can be found online at:

Aims To evaluate effects of the oral antidiabetic insulinotropic agent nateglinide on myocardial blood flow (MBF) and microvascular reactivity in Type 2 diabetic patients.Methods Forty-seven Type 2 diabetic patients were randomly assigned 2 : 1 to nateglinide 120 mg (t.i.d., n = 33) or placebo (n = 14). At baseline and after 16 weeks of treatment, MBF was quantified using positron emission tomography with N-13 ammonia at rest, during endothelial-dependent stimulation by cold pressor test and during adenosine-mediated vasodilation. Additional blood samples were taken to assess glycaemic control and lipid profile.Results MBF at rest and during adenosine did not change during the study. The percentage of flow increase from rest during cold pressor test did not improve significantly in the nateglinide group vs. placebo (from 26.1 +/- 37.2% to 29.1 +/- 27.8% between week 0 to week 16 for nateglinide vs. 14.9 +/- 37.1% to 18.1 +/- 28.4% for placebo; P = 0.07 for nateglinide when adjusted for higher baseline values). Nateglinide decreased HbA1c by 0.4% (from 7.6 +/- 0.9% to 7.2 +/- 1.3%) compared to an increase of 0.5% in the placebo group (from 7.9 +/- 0.8% to 8.4 +/- 1.7%; P = 0.02 for nateglinide). No differences between the two groups were observed in insulin levels and lipid status.Conclusions Nateglinide neither improved, nor impaired myocardial blood flow in Type 2 diabetic patients. Potential effects on endothelial-dependent myocardial blood flow remain to be investigated further. Positron emission tomography is a sensitive approach to assess the effects of therapeutic agents on myocardial blood flow in patients with diabetes.

Considering the low mortality rate related to cardiovascular diseases achieved by the currently available therapeutic options, proving the superiority of a new drug/intervention over standard treatment using mortality as the end point requires the inclusion of several thousands of patients in a prospective randomized clinical trial. The high costs involved in such trials represent a severe limitation for the development of new therapeutic strategies. At the same time, however, there is increasing acceptance that cardiac functional parameters, changes in which are directly related to the beneficial effect of an intervention, can be used as surrogate end points in small-sample size pilot-phase studies. This study design has been shown to be advantageous not only regarding cost-saving aspects but also for providing objective evaluation of the beneficial effect of a new treatment. In addition, the design helps in establishing the number of patients to be included in the definitive trial as well as determining the best dosage to be used. This review describes the available information supporting the use of nuclear cardiology imaging to reliably assess multiple cardiac function parameters constituting adequate surrogate end points for the assessment of therapeutic effects in several cardiovascular diseases. In addition, the technical aspects, feasibility and clear advantages of the use of nuclear cardiology core laboratories for centralized imaging processing/analysis in the context of multicenter clinical trials are also presented.

OBJECTIVES:We sought to assess the relationship between the Thrombolysis In Myocardial Infarction (TIMI) myocardial perfusion (TMP) grade and myocardial salvage as well as the usefulness of TMP grade in comparing two different reperfusion strategies. BACKGROUND:The angiographic index of TMP grade correlates with infarct size and mortality after thrombolysis for acute myocardial infarction (AMI). Its relationship to myocardial salvage and its usefulness in comparing different reperfusion strategies are not known. METHODS:We analyzed the TMP grade on angiograms obtained at one to two weeks after treatment in 267 patients enrolled in two randomized trials that compared stenting with thrombolysis in AMI. Patients were classified into two groups: 159 patients with TMP grade 2/3 and 108 patients with TMP grade 0/1. Two scintigraphic studies were performed: before and one to two weeks after reperfusion. The salvage index was calculated as the proportion of the area at risk salvaged by reperfusion. RESULTS:Patients with TMP grade 2/3 had a higher salvage index (0.49 +/- 0.42 vs. 0.34 +/- 0.49, p = 0.01), a smaller final infarct size (15.4 +/- 15.5% vs. 22.1 +/- 16.2% of the left ventricle, p = 0.001), and a trend toward lower one-year mortality (3.8% vs. 8.3%, p = 0.11) than patients with TMP grade 0/1. The relationship between TMP and salvage index was independent of the form of reperfusion therapy. The proportion of patients with TMP grade 2/3 was significantly higher after stenting than after thrombolysis (70.9% vs. 48.1%, p = 0.001). CONCLUSIONS:These findings show that the TMP grade is a useful marker of the degree of myocardial salvage achieved with reperfusion and a sensitive indicator of the efficacy of reperfusion strategies in patients with AMI.

Aims To evaluate whether C-reactive protein (CRP) levels on admission are predictive of myocardial salvage achieved with different reperfusion strategies in patients with acute myocardial infarction (AMI).Methods and results Patients with AMI treated with stenting plus abciximab (n=125) and thrombolysis alone (n=54) or with abciximab (n=71) were prospectively studied. CRP levels were measured by a high sensitivity assay. The threshold of the upper quartile (12 mg/l) was used to divide patients into two groups: 60 patients with high CRP (>12 mg/l) and 190 patients with tow CRP (less than or equal to12 mg/l). Myocardial salvage was measured by technetium (Tc)-99(m) sestamibi scintigraphy. Patients in the high CRP group had a significantly tower salvage index (0.35+/-0.42 vs 0.48+/-0.34, p=0.01) and higher 18-month mortality (11.7 vs; 3.2%, p=0.03) compared to those in the tow CRP group. White basal CRP was not related to myocardial salvage in patients treated with stenting plus abciximab (p=0.89) or thrombolysis plus abciximab (p=0.43), a high CRP on admission was associated with a significantly lower salvage index (0.09+/-0.48 vs 0.42+/-0.37 in the tow CRP group, p=0.006) among patients treated with thrombolysis alone.Conclusion CRP levels on admission may predict the efficacy of reperfusion in patients with AMI. The predictive ability is dependent on the form of reperfusion therapy. (C) 2003 The European Society of Cardiology. Published by Elsevier Science Ltd. All rights reserved.

In diabetic patients, a number of studies have suggested an impairment of vascular reactivity in response to vasodilatory stimuli. The pattern of dysregulation at the coronary microcirculatory level, however, has not been clearly defined. Thus, it was the aim of this study to characterise coronary microvascular function non-invasively in a homogeneous group of asymptomatic type 2 diabetic patients. In 46 patients with type 2 diabetes, myocardial blood flow (MBF) was quantified at baseline, in response to cold pressor test (CPT) and during adenosine-mediated vasodilation using positron emission tomography and nitrogen-13 ammonia. None of the patients had been treated with insulin, and none had symptoms of cardiac disease. Decreased MBF during CPT, indicating microvascular dysregulation, was observed in 16 patients (CPT–), while 30 patients demonstrated increased MBF during CPT (CPT+). Response to CPT was mildly, but significantly correlated with response to adenosine (r=0.44, P=0.0035). There was no difference in HbA1c, serum lipid levels or serum endothelial markers between the groups. Microvascular dysregulation in the CPT– group was associated with elevated baseline MBF (P<0.0001), reduced baseline vascular resistance (P=0.0026) and an abnormal increase in resistance during CPT (P=0.0002). In conclusion, coronary microvascular dysregulation is present in approximately one-third of asymptomatic, non-insulin-treated type 2 diabetic patients. Elevated baseline blood flow and reduced microvascular resistance at rest are characteristics of this dysregulation. These data suggest a state of activation of endothelial-dependent vasodilation at baseline which appears to limit the flow response to stress conditions.

Background: Positron emission tomography (PET) determines therapy-induced changes in tumour glucose utilization. Experimental data indicate that cholecystokinin (CCK) stimulates pancreatic cancer growth. In this study in patients with advanced pancreatic cancer, we evaluated the use of fluorodeoxyglucose (FDG) PET compared with magnetic resonance imaging (MRI) in monitoring hormonal therapy using a highly selective, non-peptide CCK receptor antagonist (SR 27897B). Methods: Nineteen patients were enrolled on a 28-day course of SR 27897B. Initially, 4 patients received 20 mg of SR 27897B; 9 patients received 40 mg; and 6 patients 80 mg. Imaging studies, including FDG-PET and MRI, were performed at baseline and on days 14 and 28. Results: No significant changes in FDG uptake by the primary tumours were observed. Rate of progression of disease was 11 (61%) of 18 evaluable patients by MRI. Median survival of all patients enrolled was 2.7 months. SR 27897B was fairly well tolerated at all doses tested. The most common side effects were gastrointestinal disorders such as diarrhoea, flatulence and nausea. Conclusion: SR 27897B, when used alone at the limited doses employed, led neither to an impairment of tumour glucose metabolism nor to a reduction of tumour size in advanced pancreatic cancer.

BACKGROUND:Patients with acute myocardial infarction might benefit from the addition of glycoprotein IIb/IIIa inhibitors to fibrinolytic or mechanical reperfusion strategies. We compared two strategies, stenting and fibrinolysis, both combined with abciximab, in terms of their ability to salvage myocardium in patients with acute myocardial infarction.METHODS:We enrolled 162 patients with acute myocardial infarction within 12 h of onset of symptoms, assigning 81 stenting plus abciximab and 81 alteplase plus abciximab. Technetium-99m sestamibi scintigraphy was done at admission and after a median of 11 days to calculate initial perfusion defect, final infarct size, and degree of myocardial salvage. The primary endpoint was the salvage index (the ratio of the degree of myocardial salvage to the initial perfusion defect). Major adverse clinical events within 6 months from randomisation were also compared between the two treatments.FINDINGS:Paired scintigraphic measurements were available for 70 patients in the stent group and 71 in the alteplase group. Stenting was associated with greater myocardial salvage than alteplase (median 13.6% [IQR 5.9-23.9] vs 8.0% [2.5-16.0] of the left ventricle; p=0.007). Salvage index was greater in the stent group than in the alteplase group (median 0.60 [0.37-0.82] vs 0.41 [0.13-0.58]; p=0.001). The 6-month mortality rate was 5% (four deaths) in the stent group and 9% (seven deaths) in the alteplase group (relative risk 0.56 [95% CI 0.17-1.88]; p=0.35).INTERPRETATION:In patients with acute myocardial infarction, a reperfusion strategy based on stenting with abciximab produced more myocardial salvage than the combination of fibrinolysis plus abciximab. Larger studies are needed to assess whether these effects translate into clinical benefit.

The strength of PET imaging in nuclear cardiology relies significantly on the usage of physiological contrast agents such as water or glucose analogues in very small doses in order to assess function, perfusion and metabolism. However, one is continually challenged with maintaining a balance between acquisition capabilities, physiological knowledge and applications in patient care. The more recent use of dynamic studies with high temporal resolution or as function of the heart phases has extended the spectrum of functional, non-invasive cardiac imaging. However, this is paralleled with a drastic increase in data and lack of sufficient means of data analysis. In order to cope with these demands of extracting physiological information from vast amounts of physical data, the analysis environment `MunichHeart' was developed. Three quantitative analysis modules from this tool box are investigated with respect to intra- and interobserver variability: the assessment of myocardial viability, the delineation of absolute myocardial blood flow and the measurement of left ventricular ejection fraction. The results demonstrate that reproducibility, stability and flexibility can be achieved both in a research oriented environment as well as for routine applications. This is the necessary prerequisite to facilitate the transfer of new methods into clinical reality

Die Stärke der modernen nuklearmedizinischen Diagnostik mit Hilfe der Positronen-Emissions-Tomographie (PET) ist der Einsatz physiologischer „Kontrastmittel“ in sehr geringen Konzentrationen. Allerdings sieht man sich zunehmend mit der Problematik konfrontiert, die Balance zwischen Akquisitionstechnologien, physiologisch-methodischem Wissen und Umsetzung in der Routine zu bewahren. Insbesondere die Möglichkeit, Studien zeitaufgelöst (dynamisch) oder in Abhängigkeit der Herzphasen (getriggert) zu messen, erweitert das Spektrum der funktionellen, nichtinvasiven Herzbildgebung - allerdings geht dies mit einem drastischen Anstieg der auszuwertenden Datenmengen einher. Um die Extraktion der physiologischen Informationen zu vereinfachen, wurde daher das Werkzeug “MunichHeart” entwickelt, das insbesondere die Gesichtspunkte Reproduzierbarkeit, Stabilität und Flexibilität im Forschungs- und Routineumfeld beinhaltet.