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.

The value of HMPAO SPECT in predicting treatment response to citalopram in patients with major depression.

Alterations of regional cerebral blood flow (rCBF) in prefrontal cortex and the anterior cingulate cortex are conspicuous imaging findings in patients with major depression (MD). While these rCBF changes have been suggested as functional disease markers, data in large patient samples examining treatment response prediction to antidepressant therapy are limited. This study examined the predictive value of Tc-99m-HMPAO-SPECT for subsequent treatment response to antidepressant therapy with citalopram in an unprecedented large collective of patients. Ninety-three patients with MD were examined with Tc-99m-HMPAO-SPECT twice, at the beginning of citalopram-treatment (T1) and after 4 weeks of treatment (T2). To determine the impact of rCBF changes associated with treatment response, the patient sample was divided into two subgroups: responders (44 patients) and non-responders (49 patients). A two-sample t-test was used to determine group-specific rCBF-differences. Age, gender and initial Hamilton Rating Scale for Depression (HRSD) were treated as regressors of no interest. The responder group revealed significant relative rCBF increases at T1 in a large region en-compassing predominantly prefrontal and temporal cortices as well as subgenual cingulate cortex. No relative rCBF decreases were detected in this group. The comparison between T1 and T2 revealed trends of rCBF decreases in inferior frontal gyrus and rCBF increases in premotor cortex in the responder group. Our data show that rCBF measurements with TC-99M-HMPAO-SPECT provide a predictor estimate for subsequent treatment response in depressed patients undergoing antidepressant therapy with citalopram. This effect is highly significant and, most notably, independent of the initial HRSD score.

Deep brain stimulation to reward circuitry alleviates anhedonia in refractory major depression.

Deep brain stimulation (DBS) to different sites allows interfering with dysfunctional network function implicated in major depression. Because a prominent clinical feature of depression is anhedonia--the inability to experience pleasure from previously pleasurable activities--and because there is clear evidence of dysfunctions of the reward system in depression, DBS to the nucleus accumbens might offer a new possibility to target depressive symptomatology in otherwise treatment-resistant depression. Three patients suffering from extremely resistant forms of depression, who did not respond to pharmacotherapy, psychotherapy, and electroconvulsive therapy, were implanted with bilateral DBS electrodes in the nucleus accumbens. Stimulation parameters were modified in a double-blind manner, and clinical ratings were assessed at each modification. Additionally, brain metabolism was assessed 1 week before and 1 week after stimulation onset. Clinical ratings improved in all three patients when the stimulator was on, and worsened in all three patients when the stimulator was turned off. Effects were observable immediately, and no side effects occurred in any of the patients. Using FDG-PET, significant changes in brain metabolism as a function of the stimulation in fronto-striatal networks were observed. No unwanted effects of DBS other than those directly related to the surgical procedure (eg pain at sites of implantation) were observed. Dysfunctions of the reward system--in which the nucleus accumbens is a key structure--are implicated in the neurobiology of major depression and might be responsible for impaired reward processing, as evidenced by the symptom of anhedonia. These preliminary findings suggest that DBS to the nucleus accumbens might be a hypothesis-guided approach for refractory major depression.

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.

Integrated PET/CT in differentiated thyroid cancer: diagnostic accuracy and impact on patient management.

UNLABELLED: The aim of this study was to investigate the diagnostic accuracy and impact on patient management of the new integrated PET/CT modality in patients with suspected iodine-negative, differentiated thyroid carcinoma (DTC). METHODS: Forty patients with DTC and a suggestion of iodine-negative tumor tissue underwent PET/CT examination (370 MBq (18)F-FDG, coregistered PET/CT whole-body images). As the first step of analysis, PET and CT images were scored blindly and independently by 2 nuclear medicine physicians and 2 radiologists. A 5-point scale was used. The second step consisted of a consensus reading, during which a virtual side-by-side fusion of PET and CT images was initially evaluated and afterward the "real" fusion (i.e., coregistered) PET/CT images were also scored with the same 5-point scale. The imaging results were compared with histopathologic findings and the course of disease during further follow-up examinations. RESULTS: One hundred twenty-seven lesions in 40 patients were evaluated. Diagnostic accuracy was 93% and 78% for PET/CT and PET, respectively (P = 0.049, per-patient analysis). In 17 (74%) of 23 patients with suspicious (18)F-FDG foci, integrated PET/CT added relevant information to the side-by-side interpretation of PET and CT images by precisely localizing the lesion(s). In tumor-positive PET patients, PET/CT fusion by coregistration led to a change of therapy in 10 (48%) patients. Futile surgery was prevented in an additional 3 patients. CONCLUSION: Integrated PET/CT is able to improve diagnostic accuracy in a therapeutically relevant way in patients with iodine-negative DTC. By precisely localizing tumor tissue, image fusion by integrated PET/CT is clearly superior to side-by-side interpretation of PET and CT images.

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.

In vitro evaluation of nicotinic acetylcholine receptors with 2-[18F]F-A85380 in Parkinson's disease.

Nicotinic acetylcholine receptors (nAChR) are involved in many physiological functions and appear to be affected in neurodegenerative diseases like Alzheimer's disease and Parkinson's disease (PD). Here, we describe the in vitro evaluation of nAChRs in PD with 2-[18F]F-A85380, a ligand with high affinity to the beta2 nAChR subunit. Autoradiography with 2-[18F]F-A85380 in untreated rat brain corresponded to the known distribution of alpha4beta2 nAChRs with high uptake in the thalamus, moderate uptake in the striatum and cortex and low uptake in the cerebellum (47%, 43% and 19% of the thalamus, respectively). The localization of alpha4beta2 nAChRs in the striatum was investigated in rodents with unilateral lesion of the substantia nigra. 2-[18F]F-A85380 binding was significantly reduced in the striatum ipsilateral to the lesion side (to 64% of the contralateral side), indicating that a fraction of alpha4beta2 nAChRs is located on dopaminergic terminals, whereas another fraction resides on striatal interneurons or cortical afferents. Similarly, in human brain sections of PD patients, 2-[18F]F-A85380 uptake was significantly reduced not only in the caudate and putamen but also in the thalamus (approximately 30% of the binding of control brain in all three regions); within the striatum, nAChRs in the putamen were significantly more severely affected as in the caudate. The observed pattern of alpha4beta2* nAChR loss demonstrates the potential of 2-[18F]F-A85380 for further investigations of this positron emission tomography ligand for in vivo studies of alpha4beta2* nAChRs in PD.

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.

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.

Repeated bone-targeted therapy for hormone-refractory prostate carcinoma: tandomized phase II trial with the new, high-energy radiopharmaceutical rhenium-188 hydroxyethylidenediphosphonate.

PURPOSE: We investigated the effect of repeated bone-targeted therapy with rhenium-188 hydroxyethylidenediphosphonate (HEDP) in patients with progressive, hormone-resistant prostate carcinoma and bone pain. The aim of this study was to determine the pain palliation and the antitumor effect of rhenium-188 HEDP treatments. PATIENTS AND METHODS: Sixty-four patients were randomly assigned to one of two groups for radionuclide therapy with rhenium-188 HEDP; patients of group A received a single injection, patients of group B received two injections (interval, 8 weeks). After therapy, patients were followed-up by assessment of pain palliation and clinical outcome until death. RESULTS: In both groups, toxicity was low, with moderate thrombopenia and leukopenia (maximum common toxicity criteria grade of 2). The effectiveness of rhenium-188 HEDP for pain palliation was better in the repeated treatment group (group B), with a response rate and time of response of 92% and 5.66 months, respectively (P =.006 and P =.001). In group B, 11 (39%) of 28 patients had a prostate-specific antigen decrease of more than 50% for at least 8 weeks, compared with two (7%) of 30 patients in the single-injection group (group A). The median times to progression of group A and group B were 2.3 months (range, 0 to 12.2 months) and 7.0 months (range, 0 to 24.1 months), respectively (P =.0013), and the median overall survival times were 7.0 months (range, 1.3 to 36.7 months) and 12.7 months (range, 4.1 to 32.2 months), respectively (P =.043). CONCLUSION: Compared with single-injection therapy, repeated bone-targeted therapy with rhenium-188 HEDP administered to patients with advanced progressive hormone-refractory prostate carcinoma enhanced pain palliation and improved progression-free and overall survival. Larger studies are justified to further evaluate the use of rhenium-188 HEDP.

Changes in regional cerebral blood flow by therapeutic vagus nerve stimulation in depression: an exploratory approach.

Abnormalities in regional cerebral blood flow (rCBF) have been reported to characterize depressive episodes; they are at least partly reversed by antidepressant treatment. Treatment-specific as well as response-related changes in rCBF have been reported. We explored the changes in rCBF induced by vagus nerve stimulation (VNS), a recently proposed antidepressant strategy, by application of single photon emission-computed tomography with (99m)Tc-hexamethyl-propylene amine oxime in otherwise treatment-refractory patients. Both region-of-interest (ROI) and statistical parametric mapping (SPM) analytic approaches were used. Decreases of rCBF in the amygdala, left hippocampus, left subgenual cingulate cortex, left and right ventral anterior cingulum, right thalamus and brain stem were observed; the only increase of rCBF was found by SPM analysis in the middle frontal gyrus. This pattern shares features with changes of rCBF previously associated with the administration of selective serotonin reuptake inhibitors. Similarities to other brain-stimulation strategies in antidepressant treatment were less pronounced.

Nasolacrimal drainage obstruction after radioiodine therapy: case report and a review of the literature.

The authors report a 54-year-old woman with papillary thyroid carcinoma (Lindsay type, pT2 N0 M1) with pulmonary metastases. After a total thyroidectomy, a series of 3 radioiodine therapies were performed with a cumulative dose of 700 mCi I-131. After termination of the therapy, the patient was initially without complaints, but approximately 6 months later, epiphora was noted, first only of the right eye and eventually of both eyes. A whole-body I-131 scan performed 1 year after final radioiodine therapy showed atypical tracer accumulation in both medial orbital regions. This finding was new compared with the scan that was done 1 year before. Dacryocystography revealed bilateral occlusion of the lacrimal drainage system. A review of the literature shows that epiphora and lacrimal duct alterations are rarely investigated and potentially underestimated side effects after high-dose radioiodine therapy.

Verbal memory deficits are correlated with prefrontal hypometabolism in (18)FDG PET of recreational MDMA users.

INTRODUCTION: 3,4-Methylenedioxymethamphetamine (MDMA, "ecstasy") is a recreational club drug with supposed neurotoxic effects selectively on the serotonin system. MDMA users consistently exhibit memory dysfunction but there is an ongoing debate if these deficits are induced mainly by alterations in the prefrontal or mediotemporal cortex, especially the hippocampus. Thus, we investigated the relation of verbal memory deficits with alterations of regional cerebral brain glucose metabolism (rMRGlu) in recreational MDMA users. METHODS: Brain glucose metabolism in rest was assessed using 2-deoxy-2-((18)F)fluoro-D-glucose positron emission tomography ((18)FDG PET) in 19 male recreational users of MDMA and 19 male drug-naïve controls. (18)FDG PET data were correlated with memory performance assessed with a German version of the Rey Auditory Verbal Learning Test. RESULTS: As previously shown, MDMA users showed significant impairment in verbal declarative memory performance. PET scans revealed significantly decreased rMRGlu in the bilateral dorsolateral prefrontal and inferior parietal cortex, bilateral thalamus, right hippocampus, right precuneus, right cerebellum, and pons (at the level of raphe nuclei) of MDMA users. Among MDMA users, learning and recall were positively correlated with rMRGlu predominantly in bilateral frontal and parietal brain regions, while recognition was additionally related to rMRGlu in the right mediotemporal and bihemispheric lateral temporal cortex. Moreover, cumulative lifetime dose of MDMA was negatively correlated with rMRGlu in the left dorsolateral and bilateral orbital and medial PFC, left inferior parietal and right lateral temporal cortex. CONCLUSIONS: Verbal learning and recall deficits of recreational MDMA users are correlated with glucose hypometabolism in prefrontal and parietal cortex, while word recognition was additionally correlated with mediotemporal hypometabolism. We conclude that memory deficits of MDMA users arise from combined fronto-parieto-mediotemporal dysfunction.

Glucose metabolism, gray matter structure, and memory decline in subjective memory impairment.

OBJECTIVE: To identify biological evidence for Alzheimer disease (AD) in individuals with subjective memory impairment (SMI) and unimpaired cognitive performance and to investigate the longitudinal cognitive course in these subjects. METHOD: [¹8F]fluoro-2-deoxyglucose PET (FDG-PET) and structural MRI were acquired in 31 subjects with SMI and 56 controls. Cognitive follow-up testing was performed (average follow-up time: 35 months). Differences in baseline brain imaging data and in memory decline were assessed between both groups. Associations of memory decline with brain imaging data were tested. RESULTS: The SMI group showed hypometabolism in the right precuneus and hypermetabolism in the right medial temporal lobe. Gray matter volume was reduced in the right hippocampus in the SMI group. At follow-up, subjects with SMI showed a poorer performance than controls on measures of episodic memory. Longitudinal memory decline in the SMI group was associated with reduced glucose metabolism in the right precuneus at baseline. CONCLUSION: The cross-sectional difference in 2 independent neuroimaging modalities indicates early AD pathology in SMI. The poorer memory performance at follow-up and the association of reduced longitudinal memory performance with hypometabolism in the precuneus at baseline support the concept of SMI as the earliest manifestation of AD.

Influence of 5-HTTLPR polymorphism on resting state perfusion in patients with major depression.

Neuroimaging studies in major depressive disorder (MDD) have indicated dysregulation in a network involving prefrontal cortex, subgenual cingulate and the amygdalae, which is known to be modulated by serotonin. The serotonergic system is the principal target for pharmacological treatment in MDD and the functional variable serotonin promoter polymorphism (5-HTTLPR) influences susceptibility, course and treatment response of MDD. Using data from a previously published sample of 89 MDD-patients, we examined post hoc the effect of 5-HTTLPR status on resting state perfusion, as measured with (99m)Tc-HMPAO-SPECT. MDD patients were stratified according to receptor polymorphism, both using a bi-allelic (group A: L/L vs. group B: S/S and S/L genotype) and a tri-allelic approach (Group A': LA/LA vs. Group B': non-LA/LA genotype). There were no significant differences between both subgroups regarding age, gender, severity of depression, medication, or treatment response (p > 0.1). Using the bi-allelic approach, Group B, compared to group A, revealed a significantly higher resting state perfusion in medial prefrontal cortex (p(voxel) (FWE) < 0.05). Additional ROI analyses showed relative overactivity of the amygdalae in group B (p(voxel) (FWE) < 0.05). Similar effects were observed in the tri-allelic approach. The opposite contrasts (Group A > Group B) revealed no significant effects. We demonstrate that in patients with MDD, 5-HTTLPR gene polymorphism modulates resting state perfusion in key structures of mood processing. While the clinical impact of these findings will need to be further investigated in larger cohort studies, the necessity to monitor and to account for individual 5-HTTLPR-status in future MDD imaging studies is highly recommended.

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.