Pathological 99mTc-sestamibi myocardial perfusion scintigraphy is independently associated with emerging cardiac events in elderly patients with known or suspected coronary artery disease.

BACKGROUND: Only few data are available regarding the prognostic impact of myocardial perfusion scintigraphy with (99m)Tc-sestamibi (MPS) regarding emerging cardiac events in elderly patients PURPOSE: To evaluate the prognostic value of MPS regarding emerging cardiac events in patients aged ≥70 years with known or suspected coronary artery disease (CAD). MATERIAL AND METHODS: One hundred and thirty-three patients (74.6 ± 3.7 years) who underwent exercise or pharmacological stress/rest MPS were included in this analysis. Semi-quantitative visual interpretation of MPS images was performed and Summed-Stress- (SSS), Summed-Difference- (SDS), and Summed-Rest Scores (SRS) were calculated. Multivariate logistic regression analyses were calculated for evaluation of the independent prognostic impact of MPS results and several cardiac-related patient characteristics with regard to emerging cardiac events. Kaplan-Meier survival- and log rank analyses were calculated for assessment of cardiac event-free survival. RESULTS: Pathological SSS (OR: 3.3), angina (OR: 2.7) and ischemic ECG (OR: 3.0) were independently associated with cardiac events. Patients with pathological SSS (p=0.005) and ischemic ECG (p=0.012) had a significantly lower incidence of cardiac event-free survival. CONCLUSION: Pathological MPS is independently associated with emerging cardiac events predicting a significantly lower incidence of cardiac event-free survival in patients aged ≥70 years.

Significant association of female gender with lower degree of pathological 99mTc-sestamibi scintigraphy results as well as higher cardiac-related deaths free survival in elderly patients.

BACKGROUND: The aim of the present study was to assess the impact of female gender on the extent of myocardial perfusion defects as revealed by (99m)Tc-sestamibi myocardial perfusion scintigraphy (MPS) and on emerging cardiac events (CE) in patients aged ≥ 70 years. PATIENTS AND METHODS: 86 patients aged ≥ 70 years with known or suspected CAD undergoing MPS (74.4 ± 3.2 years; women: n = 46; 53.5%) were included in this study. Semiquantitative analysis of MPS was performed and summed stress (SSS), summed difference (SDS), and summed rest scores (SRS) were calculated. Emerging CE comprised myocardial revascularization and -infarction and cardiac-related death. Multivariate regression analysis was performed to assess the independent prognostic impact of several patient related variables on MPS results. Kaplan-Meier- and log rank analyses were calculated for assessment of CE free survival as related to gender. RESULTS: Normal SSS (87.0% vs. 27.5%; p < 0.0001), SDS (80.4% vs. 27.5%; p < 0.0001), and SRS (97.8% vs. 82.5%; p = 0.023) were significantly more often found in women, whereas incidence of mildly and severely impaired SSS (6.5% vs. 35%; p = 0.001 and 2.2% vs. 25%; p = 0.002, respectively) and SDS (15.2% vs. 52.5%; p < 0.0001 and 2.2% vs. 17.5%; p = 0.023, respectively) were significantly higher in men. Multivariate logistic regression analysis revealed female gender as an independent predictor of normal SSS (odds ratio/OR: 17.6) and SDS (OR: 53.3). Female gender was associated with a significant higher cardiac-death free survival compared to male patients (p = 0.031). CONCLUSION: Female gender is independently associated with a significantly lower degree of pathological MPS results and a higher cardiac-death free survival in elderly patients.

Hemodynamic variables during stress testing can predict referral to early catheterization but failed to show a prognostic impact on emerging cardiac events in patients aged 70 years and older undergoing exercise (99m)Tc-sestamibi myocardial perfusion scintigraphy.

The aim of the present study was to evaluate the prognostic value of hemodynamic variables during ergometric stress testing for (99m)Tc-sestamibi myocardial perfusion scintigraphy (MPS) as compared to several patient-related variables and MPS results with regard to referral to early coronary angiography (<3 months after MPS; CA) as well as cardiac event (CE) free survival in a study population aged > or =70 years. About 90 patients aged > or =70 years (74.5 +/- 3.6 years) who underwent ergometric stress/rest MPS were included in this study. About 19 hemodynamic variables during stress testing were assessed. Semiquantitative visual interpretation of MPS images were performed and Summed-Stress-(SSS), Summed-Difference-, and Summed-Rest-Scores were calculated. Emerging CE comprised myocardial revascularization and -infarction as well as cardiac-related death. Multivariate logistic regression analyses were performed for evaluation of independent prognostic impact of hemodynamic-, MPS- and clinical-variables with regard to referral to early catheterization as well as emerging CE. Kaplan-Meier survival- and log rank analyses were calculated for assessment of CE free survival. History of CAD (Odds ratio; OR: 99.3), low rest heart rate (OR: 14.9) and low peak systolic blood pressure (OR: 15.4) during ergometric stress testing as well as pathological SSS (OR: 48.4) were significantly associated with referral to CA. History of ischemic ECG (OR: 4.7) and pathological SSS (OR: 3.7) independently predicted emerging CE and were associated with a lower CE free survival. In patients aged > or =70 years, CA is independently predicted by clinical variables, pathological results of MPS and hemodynamic variables. In contrast, hemodynamic response to stress testing failed to show any predictive impact on emerging CE.

Subclinical hyperthyroidism seems not to have a significant impact on systemic anticoagulation in patients with coumarin therapy.

There is little data regarding the impact of subclinical hyperthyroidism on coagulation metabolism in patients undergoing systemic anticoagulation therapy with coumarin derivates. In this retrospective analysis we studied 233 patients with benign thyroid disorders receiving therapeutic iodine-131, as well as concomitant systemic anticoagulation therapy (subclinical hyperthyroidism: n = 178; overt hyperthyroidism: n = 15; euthyroidism: n = 40). Multivariate regression analyses were performed in the total study population as well as in the subgroup of patients with subclinical hyperthyroidism to identify the possible impact of several variables on anticoagulation therapy, large enough to push the International Normalized Ratio (INR) level out of the therapeutic range (INR <2.0 or >3.0). Therapy with antibiotics or nitrates was significantly associated with INR-values >3.0 in the total population, while ACE inhibitors were associated with lower incidence of INR-values <2.0. In patients with subclinical hyperthyroidism, therapy with antibiotics was predictive of INR-values >3.0, whereas therapy with thyroid suppressive drugs or TSH-values <0.1 mU/l was associated with INR-values <2.0. Moreover, in a subgroup of 40 patients with the positive history of both subclinical hyperthyroidism and euthyroidism intraindividual comparison with regard to the possible impact on anticoagulation therapy was performed which failed to show any significant differences in INR-values between the two thyroid metabolic conditions. In conclusion, subclinical hyperthyroidism seems to have no significant impact on coagulation metabolism in patients receiving anticoagulation therapy.

Rhenium-186 hydroxyethylidenediphosphonate (186Re HEDP) for the treatment of hemophilic arthropathy: first results.

OBJECTIVES: The aim of this study was to evaluate the efficacy of a systemic application of rhenium-186 hydroxyethylidenediphosphonate (Re HEDP) for pain treatment in patients with hemophilic arthropathies. METHODS: Twelve patients with hemophilic arthropathy with at least 3 involved joints with persistent pain were included in this prospective study. A single dose of 15 mCi (555 MBq) Re HEDP was administered intravenously. Before and 12 weeks after treatment, pain assessment was performed using the visual analog scale (VAS). The pain status assessment included the general status, pain of all joints affected, and pain of the 3 mostly involved joints. Furthermore, quality of life was assessed. RESULTS: With regard to the 3 most involved joints, an improvement of the pain symptoms in 25 of 36 (69.4%) joints was observed. With regard to all involved joints a median of 3 joints per patient improved after Re HEDP therapy. General pain status after treatment was 2.0 VAS points lower as compared with pretreatment. The total number of involved joints remained unchanged in 7 patients, increased in 1 patient, and decreased in the remaining 4 patients. CONCLUSIONS: The results of this study show an improvement of the pain symptoms of the involved joints 12 weeks after therapy with Re HEDP in patients with hemophilic arthropathy. The only moderate success regarding a reduction of the total number of involved joints is by the fact that despite this improvement most affected joints remained still painful on a lower level after the therapy or due to newly affected joints not painful before initiation of the radionuclide therapy.

Single- vs. dual-head SPECT for detection of myocardial ischemia and viability in a large study population.

BACKGROUND: As single-head data acquisition for thallium-201 myocardial SPECT is a frequently used method mainly in the outpatient medical care as well as in smaller hospitals, comparison to dual-head data collection is a still discussed issue mainly with regard to quality control and -assurance. METHODS: A total of 1334 patients undergoing thallium-201 myocardial SPECT for diagnosis of myocardial ischemia and/or viability have been retrospectively analyzed. In 554 patients, a single-head gamma camera (360 degrees rotation) has been applied, whereas a dual-head gamma camera (180 degrees rotation) has been used in 780 patients. Four hundred twenty-six patients received both myocardial SPECT as well as coronary angiography. The diagnostic value of both applied acquisition techniques has been analyzed. RESULTS: Regarding myocardial viability, positive predictive value for the diagnosis of myocardial scar tissue was significantly higher for dual-head- as compared to single-head acquisition. Among the 426 patients undergoing diagnosis of myocardial ischemia, significant differences have only been found with regard to specificity being higher in the single-head acquisition. Diagnosis of myocardial ischemia related to a distinct myocardial perfusion region showed a significantly higher sensitivity of dual-head acquisition for the left anterior descending perfusion area, whereas specificity was significantly higher for single-head acquisition. CONCLUSIONS: Our results indicate a beneficial effect of dual-head data collection with regard to sensitivity of the diagnosis of myocardial ischemia. In contrast, single-head data acquisition was superior with regard to specificity. However, it is justified to preferably apply dual-head data collection in clinical routine due to the shorter acquisition time leading to an evident time benefit of this acquisition technique.

Response-dependent differences in regional cerebral blood flow changes with citalopram in treatment of major depression.

UNLABELLED: Major depression (MD) is the most frequent psychiatric disorder with a predicted increase within the next decade. The understanding of the neurobiologic basis of its cause, antidepressive treatment effects, and identification of treatment outcome predictors is of crucial importance to warrant efficient medical care. The aim of our study was to investigate differences of regional cerebral blood flow (rCBF) in MD between responders and nonresponders in the beginning and differences during the course of treatment. METHODS: 99mTc-Labeled d,l-hexamethylpropyleneamine oxime brain scans under resting conditions were performed on 65 patients with MD. All patients were treated with citalopram as an antidepressive monotherapy. SPECT scans were performed 2 times, at the beginning (t1) and after 4 wk of medication (t2). Voxel-by-voxel analyses were performed using SPM. Unpaired t test, paired t test, and multigroup analysis were used on a significance threshold of P < 0.005 (uncorrected) to identify significant differences in rCBF between responders and nonresponders at t1, within both groups over time of treatment (t2-t1), as well as a group x time interactions. RESULTS: Thirty-five patients responded after 4 wk of treatment. Distinct differences between responders and nonresponders were found at the beginning of treatment and also relating to changes in rCBF during treatment. Responders showed a higher posterior cingulate activity at t1. Furthermore, an opposite direction of rCBF changes during treatment could be observed in this area. CONCLUSION: The differences in rCBF in responders and nonresponders in the posterior cingulate at t1 and the opposite directed changes in rCBF in both groups during treatment in this region suggest that the posterior cingulate function plays a key role in the pathophysiology of depression and may have a predictive value for antidepressive treatment outcome.

Impact of short-term hypothyroidism on systemic anticoagulation in patients with thyroid cancer and coumarin therapy.

Unlike hyperthyroidism, few data exist regarding the impact of hypothyroidism on systemic anticoagulation with coumarin derivates. Therefore, we evaluated a potential impact of short-term hypothyroid conditions on systemic anticoagulation with coumarin derivates in patients after complete thyroidectomy for treatment of thyroid cancer. Fifteen patients with differentiated thyroid cancers and continued international normalized ratio (INR)-adjusted therapy with coumarin derivates were included in this retrospective analysis. A total of 88 laboratory tests was analyzed. INR values were compared between thyroid-stimulating hormone (TSH) values greater than 10 and 10 mU/L or less. An INR value of less than 2.0 was defined as being out of the therapeutic range. Analysis of significant differences between categorized TSH and INR values were performed by using X(2) analysis, correlation of continuous TSH and INR values by using the Pearson's analysis. When TSH was greater than 10 mU/L (n = 50) the INR value was less than 2.0 in 76.0% (n = 38) cases. In contrast, the INR value was less than 2.0 in only 21.1% (n = 8; p < 0.0001) of patients with TSH of 10 mU/L or less (n = 38). Correlation between continuous TSH and INR values was r = -0.589 (p < 0.0001). Based on the results of the present study, it seems to be necessary to monitor the anticoagulation parameters more often in patients with hypothyroidism and either to correct the hypothyroid state, or in cases of desired hypothyroid conditions, to adjust the therapy with coumarin derivates in order to ensure a sufficient anticoagulation.

Feasibility of 2-deoxy-2-[18F]fluoro-D-glucose- A85380-PET for imaging of human cardiac nicotinic acetylcholine receptors in vivo.

Nicotinic acetylcholine receptors mediate the parasympathetic autonomic control of cardiac function. Aim of this study was the assessment of cardiac nicotinic acetylcholine receptor distribution with a novel (alpha4beta2) nicotinic acetylcholine receptor PET ligand (2-deoxy-2- [18F]fluoro-D-glucose-A85380) in humans. Five healthy volunteers without cardiac disease and six patients with either Parkinson's disease or multiple system atrophy without additional overt cardiac disease were evaluated with 2-deoxy-2-[18F]fluoro-D-glucose-A85380 PET-imaging to assess the cardiac parasympathetic innervation and the putative impact of both disorders. 2-deoxy-2- [18F]fluoro-D-glucose-A85380 whole body PET-scans were performed on a Siemens PET/CT biograph(TM) 75.4 min +/- 6.7 after i.v. injection of 371.2 +/- 58.1 MBq. Average count rate density of left ventricle ROI's and a standard ROI in the right lung were measured within three consecutive slices of 10.0 mm thickness. Heart-to-lung ratios were calculated in each volunteer and patient. Tracer uptake in the left ventricle could be measured in all of the five volunteers and the six patients. Heart-to-lung ratios in the volunteer group were not different from patients suffering from Parkinson's disease or MSA (3.2 +/- 0.5 vs 3.2 +/- 0.8 and 2.96+/-0.7, mean +/- SD), respectively. Human cardiac nicotinic acetylcholine receptors can be visualized and measured by 2-deoxy-2- [18F]fluoro-D-glucose-A85380 PET scans both in cardiac-healthy subjects and patients suffering from Parkinson's disease or multiple system atrophy. The heart- as well as the lung-tracer uptake was almost constant throughout all subjects leading to a good target-to-background ratio. These first results suggest no impact of either PD or MSA on cardiac nicotinic acetylcholine receptors.

Diagnostic performance of whole body dual modality 18F-FDG PET/CT imaging for N- and M-staging of malignant melanoma: experience with 250 consecutive patients.

PURPOSE: To assess the diagnostic performance of positron emission tomography/computed tomography (PET/CT) using (18)F-fluorodeoxyglucose (FDG) for N- and M-staging of cutaneous melanoma. PATIENTS AND METHODS: This is a retrospective and blinded study of 250 consecutive patients (105 women, 145 men; age 58 +/- 16 years) who underwent FDG-PET/CT for staging of cutaneous melanoma at different time points in the course of disease. Whole-body FDG-PET/CT was performed 101 +/- 21 minutes postinjection of 371 +/- 41 MBq FDG. Diagnostic accuracy for N- and M-staging was determined for CT alone, PET alone, and PET/CT. RESULTS: PET/CT detected significantly more visceral and nonvisceral metastases than PET alone and CT alone (98.7%, 88.8%, and 69.7%, respectively). PET/CT imaging thus provided significantly more accurate interpretations regarding overall N- and M-staging than PET alone and CT alone. Overall N- and M-stage was correctly determined by PET/CT in 243 of 250 patients (97.2%; 95% CI, 95.2% to 99.4%) compared with 232 patients (92.8%; 95% CI, 89.6% to 96.0%) by PET, and 197 patients (78.8%; 95% CI, 73.7% to 83.9%) by CT. All differences were significant. Accuracy of PET/CT was significantly higher than that of PET and CT for M-staging (0.98 v 0.93 and 0.84) and significantly higher than that of CT for N-Staging (0.98 v 0.86). Change of treatment according to PET/CT findings occurred in 121 patients (48.4%). CONCLUSION: The diagnostic performance of FDG-PET/CT for N- and M-staging of melanoma patients suggests its use for whole-body tumor staging, especially for detection or exclusion of distant metastases.

Dose selection for radioiodine therapy of borderline hyperthyroid patients according to thyroid uptake of 99mTc-pertechnetate: applicability to unifocal thyroid autonomy?

PURPOSE: The aim of this study was to evaluate the feasibility of applying a previously described dose strategy based on (99m)Tc-pertechnetate thyroid uptake under thyrotropin suppression (TcTU(s)) to radioiodine therapy for unifocal thyroid autonomy. METHODS: A total of 425 consecutive patients (302 females, 123 males; age 63.1+/-10.3 years) with unifocal thyroid autonomy were treated at three different centres with (131)I, using Marinelli's formula for calculation of three different absorbed dose schedules: 100-300 Gy to the total thyroid volume according to the pre-treatment TcTU(s) (n=146), 300 Gy to the nodule volume (n=137) and 400 Gy to the nodule volume (n=142). RESULTS: Successful elimination of functional thyroid autonomy with either euthyroidism or hypothyroidism occurred at a mean of 12 months after radioiodine therapy in 94.5% of patients receiving 100-300 Gy to the thyroid volume, in 89.8% of patients receiving 300 Gy to the nodule volume and in 94.4% receiving 400 Gy to the nodule volume. Reduction in thyroid volume was highest for the 100-300 Gy per thyroid and 400 Gy per nodule strategies (36+/-19% and 38+/-20%, respectively) and significantly lower for the 300 Gy per nodule strategy (28+/-16%; p<0.01). CONCLUSION: A dose strategy based on the TcTU(s) can be used independently of the scintigraphic pattern of functional autonomous tissue in the thyroid.

PET recognition of pulmonary metastases on PET/CT imaging: impact of attenuation-corrected and non-attenuation-corrected PET images.

PURPOSE: The aims of this study were to assess the performance of FDG PET at PET/CT imaging for the detection of pulmonary metastases and to evaluate differences in lesion detectability on attenuation-corrected (AC) and non-attenuation corrected (NAC) PET images. METHODS: The institutional PET/CT database was searched for patients with pulmonary metastases of 3-60 mm in diameter. Ninety-two patients with 438 metastases to the lungs were included in the study. The primary tumours were 33 malignant melanomas, 12 carcinomas of unknown primary, 11 colorectal carcinomas, eight differentiated thyroid carcinomas, seven aggressive non-Hodgkin's lymphomas, six head and neck cancers, three breast cancers, two prostate cancers and ten others. Lesion detectability was visually compared between PET and CT and between AC and NAC PET images using a five-point scale. RESULTS: Of the 438 pulmonary metastases, 174 were detected with FDG PET (39.7%), six of them on NAC images only (not significant). Visual scores were higher on NAC images in 41.4% and equal in 54.6% of lesions. The sensitivity of FDG PET increased significantly from 0.405 for metastases of 5-7 mm in diameter to 0.784 for lesions of 8-10 mm and to 0.935 for lesions measuring 11-29 mm in diameter. No metastases smaller than 5 mm in diameter were seen on PET images. CONCLUSION: FDG PET/CT is useful for the assessment of pulmonary metastases. The frequency of lesion detection is similar for AC and NAC PET images. A reduced sensitivity of FDG PET has to be considered for lesions smaller than 11 mm in diameter.

Myocardial uptake characteristics of three 99mTc-labeled tracers for myocardial perfusion imaging one hour after rest injection.

OBJECTIVE: 99mTc-tetrofosmin and 99mTc-sestamibi are approved tracers for myocardial perfusion studies. Recently, a 99mTc-MIBI preparation from a different manufacturer (99mTc-cardiospect-MIBI) has been introduced to the market. Therefore, the aim of this study was the evaluation of 99mTc-tetrofosmin as well as of two different 99mTc-labeled MIBI tracers with regard to differences in imaging quality under resting conditions. METHODS: Sixty patients (mean age 63.8 years +/- 1.25) with known or suspected coronary artery disease but without evidence of rest-ischemia were included. Twenty patients in each group were examined by a two-day-rest-stress protocol using the three 99mTc-labeled tracers. Visual analysis of all images was performed by two experienced physicians blinded with regard to the applied tracer. Regions of interest (ROI) were defined over the heart, lung and whole body only in the rest imaging in order to calculate heart-to-lung, lung-to-whole body-, and heart-to-whole body-ratios. RESULTS: The heart-to-lung ratio was statistically significant higher for 99mTc-cardiospect-MIBI as compared to 99mTc-sestamibi as well as to 99mTc-tetrofosmin. Furthermore, a significantly higher heart-to-lung ratio was found for 99mTc-sestamibi as compared to 99mTc-tetrofosmin. The heart-to-whole body-ratio and the lung-to-whole body-ratio were equivalent between all tracers. Visual analysis revealed only slight differences regarding image quality between all tracers. CONCLUSIONS: ROI analysis surprisingly revealed a significant higher myocardial uptake and consequently a higher heart-to-lung ratio for 99mTc-cardiospect-MIBI. Whether this leads to a better visual image quality has to be evaluated in future studies with larger study populations as well as semiquantitative segmental analysis of the myocardial perfusion images.

Radioiodine therapy in Graves' disease based on tissue-absorbed dose calculations: effect of pre-treatment thyroid volume on clinical outcome.

This study was performed with three aims. The first was to analyse the effectiveness of radioiodine therapy in Graves' disease patients with and without goitres under conditions of mild iodine deficiency using several tissue-absorbed doses. The second aim was to detect further parameters which might be predictive for treatment outcome. Finally, we wished to determine the deviation of the therapeutically achieved dose from that intended. Activities of 185-2,220 MBq radioiodine were calculated by means of Marinelli's formula to deliver doses of 150, 200 or 300 Gy to the thyroids of 224 patients with Graves' disease and goitres up to 130 ml in volume. Control of hyperthyroidism, change in thyroid volume and thyrotropin-receptor antibodies were evaluated 15+/-9 months after treatment for each dose. The results were further evaluated with respect to pre-treatment parameters which might be predictive for therapy outcome. Thyroidal radioiodine uptake was measured every day during therapy to determine the therapeutically achieved target dose and its coefficient of variation. There was a significant dose dependency in therapeutic outcome: frequency of hypothyroidism increased from 27.4% after 150 Gy to 67.7% after 300 Gy, while the frequency of persistent hyperthyroidism decreased from 27.4% after 150 Gy to 8.1% after 300 Gy. Patients who became hypothyroid had a maximum thyroid volume of 42 ml and received a target dose of 256+/-80 Gy. The coefficient of variation for the achieved target dose ranged between 27.7% for 150 Gy and 17.8% for 300 Gy. When analysing further factors which might influence therapeutic outcome, only pre-treatment thyroid volume showed a significant relationship to the result of treatment. It is concluded that a target dose of 250 Gy is essential to achieve hypothyroidism within 1 year after radioiodine therapy in Graves' disease patients with goitres up to 40 ml in volume. Patients with larger goitres might need higher doses.