Eva Fricke

Myocardial Sympathetic Innervation in Patients with Symptomatic Coronary Artery Disease: Follow-up After 1 Year with Neurostimulation

In both diabetic and nondiabetic patients, there is a loose correlation between coronary flow reserve (CFR) and sympathetic innervation in viable myocardial segments. The loose correlation implies that sympathetic innervation may be preserved even with major impairment of myocardial blood supply. In some patients, denervation is due to repetitive episodes of ischemia in areas with severely reduced CFR. We investigated the long-term effect of reduced CFR on myocardial sympathetic innervation in diabetic and nondiabetic patients with spinal cord stimulation. Methods: We analyzed 23 patients (10 diabetic and 13 nondiabetic) with coronary artery disease and without known cardiac autonomic neuropathy. At baseline, we determined quantitative myocardial blood flow using 13N-ammonia PET, myocardial viability using 18F-FDG PET, and cardiac innervation using 11C-hydroxyephedrine (HED) PET. At the 1-y follow-up we measured CFR and 11C-HED retention. During follow-up, no cardiac intervention was performed and no myocardial infarction occurred. In all patients, spinal cord stimulation was performed for relief of angina. Results: There was no significant difference in segmental 11C-HED retention between baseline and follow-up in the whole patient group. In diabetic patients, as well as in segments with severely reduced CFR (<1.5), 11C-HED retention showed a small but significant decrease (P < 0.05). Linear regression of segmental 11C-HED retention between baseline and follow-up was high (r2 = 0.81), confirming good reproducibility of the investigation on the one hand and little change in regional sympathetic innervation on the other hand. Conclusion: In patients with stable chronic coronary artery disease, sympathetic innervation of the myocardium is almost unchanged in both diabetic and nondiabetic patients in a 1-y follow-up. In myocardial segments with severely altered blood supply, a small but significant decrease in 11C-HED retention most probably reflects ischemic neuronal damage. The prognostic relevance of sympathetic denervation in viable myocardium still has to be determined.

Myocardial perfusion after one year of spinal cord stimulation in patients with refractory angina.

AIM Spinal cord stimulation (SCS) is recommended for patients with coronary artery disease (CAD) and refractory angina. We used positron emission tomography (PET) to investigate the long-term effect of SCS on regional myocardial perfusion in patients suffering from angina pectoris refractory to medical treatment and without option for coronary intervention. PATIENTS, METHODS We analyzed data of 44 patients with stable CAD (91% three vessel disease). At baseline, we determined coronary flow reserve (CFR) using 13N-ammonia-PET and myocardial viability with 18F-FDG. SCS was performed for one year (Medtronic Itrell III or Synergy, Düsseldorf, Germany). During follow-up, no cardiac interventions were necessary and no myocardial infarctions occurred. At one year follow-up, CFR was measured again. RESULTS In the majority of patients (77%), SCS led to an improvement of clinical symptoms. CFR did not change significantly during follow-up. Subjective improvement did not correlate with an increase of CFR. CONCLUSIONS Despite its clinical effect, SCS does not have a direct impact on CFR in patients with stable CAD. According to our results, the pain relief is not due to an improvement of the myocardial blood supply.

Comparison of 99mTc- and 18F-Ubiquicidin Autoradiography to Anti–Staphylococcus aureus Immunofluorescence in Rat Muscle Abscesses

99mTc-ubiquicidin (UBI) 29-41 is under clinical evaluation for discrimination between bacterial infection and unspecific inflammation. We compared the distribution of 99mTc-UBI 29-41, the potential PET tracers 18F-UBI 29-41 and 18F-UBI 28-41, and 3H-deoxyglucose (DG) in rat muscle abscesses to that of anti–Staphylococcus aureus immunofluorescent imaging. Methods: Calf abscesses were induced in 15 CDF-Fischer rats after inoculation of Staphylococcus aureus. One to 6 d later, either 18F-UBI 29-41 and 3H-DG (n = 5) or 18F-UBI 28-41 and 3H-DG (n = 6) or 99mTc-UBI 29-41 and 3H-DG (n = 4) were injected simultaneously. Dual-tracer autoradiography of the abscess area was compared with the distribution of bacteria and macrophages. Results: The UBI derivates exhibited increased uptake in the abscess area that partly matched 3H-DG uptake and macrophage infiltration but showed no congruity with areas that were highly positive for bacteria. Conclusion: A specific binding of UBI derivatives to Staphylococcus aureus in vivo could not be confirmed in this study.

Respiratory resistance of patients during cardiac stress testing with adenosine: Is dyspnea a sign of bronchospasm?

BackgroundA denosine is widely used for stress-testing in myocardial perfusion imaging. During adenosine infusion, dyspnea is one of the main complaints of patients. The aim of this study was to determine whether dyspnea during adenosine infusion is caused by bronchospasm.MethodsFifty-four patients were enrolled in the study. Seven of these 54 suffered from mild chronic obstructive pulmonary disease (COPD). We continuously measured respiratory resistance (Rrs), using impulse oscillometry. Respiratory resistance was measured before, during, and after a continuous infusion of 140 μg/kg/min adenosine.ResultsSixty-seven percent of patients suffered from dysnea during adenosine infusion. In patients with mild COPD, Rrs was higher compared with other patients (0.48 vs 0.27 kPa/L/s, P<.05). Neither patients with COPD nor those without COPD exhibited a significant increase in Rrs during adenosine infusion. The Rrs of patients with dyspnea was insignificantly lower compared with patients without dyspnea(P=.469).ConclusionsDyspnea as a side effect of adenosine infusion is not correlated with impaired respiratory resistance in nonasthmatic pattents and in patients with mild COPD. Thus bronchospasm is ruled out as cause of this clinical symptom. Despite the small number of COPD patients enrolled in the study, adenosine infusion might be possible in patients with mild COPD.

EANM guideline for radionuclide therapy with radium-223 of metastatic castration-resistant prostate cancer

Radium Ra-223 dichloride (radium-223, Xofigo®) is a targeted alpha therapy approved for the treatment of castration-resistant prostate cancer (CRPC) with symptomatic bone metastases and no known visceral metastatic disease. Radium-223 is the first targeted alpha therapy in this indication providing a new treatment option, with evidence of a significant survival benefit, both in overall survival and in the time to the first symptomatic skeletal-related event. The skeleton is the most common metastatic site in patients with advanced prostate cancer. Bone metastases are a clinically significant cause of morbidity and mortality, often resulting in bone pain, pathologic fracture, or spinal cord compression necessitating treatment. Radium-223 is selectively accumulated in the bone, specifically in areas of high bone turnover, by forming complexes with the mineral hydroxyapatite (the inorganic matrix of the bone). The alpha radiation generated during the radioactive decay of radium-223 produces a palliative anti-tumour effect on the bone metastases. The purpose of this guideline is to assist nuclear medicine specialists in evaluating patients who might be candidates for treatment using radium-223, planning and performing this treatment, understanding and evaluating its consequences, and improving patient management during therapy and follow-up.

ECHO-GUIDED EXTRACORPOREAL SHOCK WAVE THERAPY FOR REFRACTORY ANGINA IMPROVES REGIONAL MYOCARDIAL BLOOD FLOW AS ASSESSED BY PET IMAGING

Background: Medical therapy for refractory angina is limited and the prognosis is poor. Experimental data suggest that the use of extracorporeal shockwave myocardial revascularization (ESMR) can contribute to angiogenesis and improve symptoms of angina and left ventricular (LV) function. The objective of this study was to examine the effects of ESMR on clinical symptoms as well as LV function as assessed by cardiac MRI in patients with refractory angina. Methods: Patients with Canadian Cardiovascular Society (CCS) class III–IV angina despite medical therapy and ischemia documented on thallium or echo-dobutamine were eligible for the study. ESMR therapy was applied with a commercially available cardiac shockwave generator system under echocardiographic guidance. LV function was assessed before and 6 months after therapy by cardiac MRI. Results: Twenty patients (four women, 16 men; mean age 64 years, range 45–83) were included in the study. The CCS class after treatment improved in all patients (16 patients angina pectoris CCS from III to II and four patients from IV to III). The use of sublingual nitroglycerin was significantly reduced as well. There was a significant improvement in LV ejection fraction as assessed by blinded MRI following therapy in the overall population (51 vs. 59%, P<0.05). Conclusion: This study demonstrates the potential efficacy of ESMR for the treatment of refractory angina pectoris. The patients showed both a significant clinical response as well as improved LV ejection fraction on serial MRI imaging. Larger studies are needed to adequately define the clinical utility of this novel therapy.

Right atrial hemangioma in modern cardiac imaging

Dr. med. Andreas Peterschröder Dr. med. Eva Fricke Institut für Radiologie, Nuklearmedizin und molekulare Bildgebung Herzund Diabeteszentrum NRW Ruhr-Universität Bochum Georgstr. 11 32545 Bad Oeynhausen, Germany Tel.: +49-57 31 / 97 18 29 Fax: +49-57 31 / 97 18 62 E-Mail: apeterschroeder@hdz-nrw.de efricke@hdz.nrw.de Prof. Dr. med. Ute Raute-Kreinsen Städt. Kliniken Bielefeld Mitte Institut für Pathologie Teutoburger Str. 50 33604 Bielefeld, Germany Tel.: +49-5 21 / 58 10 Fax: +49-5 21 / 5 81 20 99

[Therapy of bone metastases with radium-223. German guidelines].

This document describes the guideline for therapy of bone metastases with radium-223 ((223)Ra) published by the Arbeitsgemeinschaft der Wissenschaftlichen Medizinischen Fachgesellschaften in Germany (AWMF) under the auspices of the Deutsche Gesellschaft für Nuklearmedizin (DGN), Östereichische Gesellschaft für Nuklearmedizin (OGN), and Schweizerische Gesellschaft für Nuklearmedizin (SGNM). This guidance is based on an interdisciplinary consensus. These recommendations are a prerequisite for the quality management in the treatment of patients with bone metastases from prostate cancer using (223)Ra. They are aimed at guiding nuclear medicine specialists in selecting candidates to receive therapy and to deliver the treatment in a safe and effective manner. The document contains background information and definitions. It covers the rationale, indications and contraindications for therapy with (223)Ra. Essential topics are the requirements for institutions performing the therapy, which patient data have to be available prior to performance of therapy, and how treatment has to be carried out technically and organisationally. Moreover, essential elements of follow-up and aftercare are specified. As a matter of principle, the treatment inclusive aftercare has to be realised in close cooperation with the involved medical disciplines.

Radionuklidtherapie von Knochenmetastasen mittels Radium-223

This document describes the guideline for therapy of bone metastases with radium-223 ((223)Ra) published by the Arbeitsgemeinschaft der Wissenschaftlichen Medizinischen Fachgesellschaften in Germany (AWMF) under the auspices of the Deutsche Gesellschaft für Nuklearmedizin (DGN), Östereichische Gesellschaft für Nuklearmedizin (OGN), and Schweizerische Gesellschaft für Nuklearmedizin (SGNM). This guidance is based on an interdisciplinary consensus. These recommendations are a prerequisite for the quality management in the treatment of patients with bone metastases from prostate cancer using (223)Ra. They are aimed at guiding nuclear medicine specialists in selecting candidates to receive therapy and to deliver the treatment in a safe and effective manner. The document contains background information and definitions. It covers the rationale, indications and contraindications for therapy with (223)Ra. Essential topics are the requirements for institutions performing the therapy, which patient data have to be available prior to performance of therapy, and how treatment has to be carried out technically and organisationally. Moreover, essential elements of follow-up and aftercare are specified. As a matter of principle, the treatment inclusive aftercare has to be realised in close cooperation with the involved medical disciplines.

Effect of caffeine on myocardial blood flow during pharmacological vasodilation

Pharmacologic stress with adenosine is frequently used for noninvasive detection of coronary artery disease. Dietary intake of caffeinated food, beverages or medications might alter adenosine-induced hyperemic blood flow, thereby compromising the diagnostic sensitivity of adenosine stress testing. In this case we report on a male patient with CAD. Mycardial blood flow at rest and during adenosine-induced hyperemia 2 hours after consumption of decaffeinated coffee and again without caffeine intake were quantified by ammonia PET. After caffeine intake there was a clearly diminished increase of myocardial blood flow during adenosine. The average coronary flow reserve in the myocardium was 1.3 after caffeine. In the baseline study without caffeine the coronary flow reserve has been improved to 2.3. Caffeine intake alters the coronary vasodilatory capacity. These findings emphasize the importance of carefully screening patients for intake of caffeinated food prior to adenosine stress testing. Die pharmakologische Belastung mit Adenosin ist eine häufig eingesetzte Methode zur nichtinvasiven Detektion der KHK mit der Emissionstomographie. Die Einnahme von koffeinhaltigen Lebensmitteln, Getränken oder Medikamenten kann den adenosininduzierten Blutflussanstieg beeinflussen. In diesem Fall berichten wir über einen Patienten mit KHK, bei dem der myokardiale Blutfluss in Ruhe und unter pharmakologischer Belastung mit Adenosin 2 Stunden nach Genuss einer 1 Tasse entkoffeinierten Kaffee und nochmals nach 24 Stunden ohne Koffeineinfluss mit der PET untersucht wurde. Unter Koffeinwirkung war die gemittelte koronare Flussreserve erheblich eingeschränkt [1, 3], während ohne Koffein die Flussreserve deutlich anstieg [2, 3]. Schon eine geringe Menge Koffein beeinflusst die Untersuchung der koronaren Vasodilatationskapazität. Der Fallbericht unterstreicht die Bedeutung einer genauen Koffeinanamnese, um konklusive Resultate in der Ischämiediagnostik zu erhalten.Pharmacologic stress with adenosine is frequently used for noninvasive detection of coronary artery disease. Dietary intake of caffeinated food, beverages or medications might alter adenosine-induced hyperemic blood flow, thereby compromising the diagnostic sensitivity of adenosine stress testing. In this case we report on a male patient with CAD. Myocardial blood flow at rest and during adenosine-induced hyperemia 2 hours after consumption of decaffeinated coffee and again without caffeine intake were quantified by ammonia PET. After caffeine intake there was a clearly diminished increase of myocardial blood flow during adenosine. The average coronary flow reserve in the myocardium was 1.3 after caffeine. In the baseline study without caffeine the coronary flow reserve has been improved to 2.3. Caffeine intake alters the coronary vasodilatory capacity. These findings emphasize the importance of carefully screening patients for intake of caffeinated food prior to adenosine stress testing.