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Aim: Planar myocardial 123 I-meta-iodobenzylguanidine ( 123 I-mIBG) scintigraphy is a highly reproducible technique. However, differences in collimator use are one of the most important factors that cause variation among institutions and studies in heart-to-mediastinum (H/M) ratio. Therefore, standardization among various gamma camera-collimator combinations is needed. Previously, a phantom has been developed to cross-calibrate different acquisition conditions in Japan. For further cross-calibration of European myocardial 123 I-mIBG imaging, the aim of this study was to collect 123 I-mIBG data for H/M ratios from common European gamma camera vendors., Methods: 210 experiments were performed in 27 European institutions. Based on these experiments, conversion coefficients for each gamma camera-collimator combination were calculated. An averaged conversion coefficient of 0.88 was used to calculate a standardized H/M ratio., Results: On average, LE-collimator-derived H/M ratios were significantly lower compared to ME-collimator-derived H/M ratios. The mean conversion coefficients ranged from 0.553 to 0.605 for the LE-collimator group and from 0.824 to 0.895 for the ME-collimator group., Conclusion: Clinically established H/M ratios can be converted into standardized H/M ratios using cross-calibrated conversion coefficients. This standardization is important for identifying appropriate thresholds for adequate risk stratification. In addition, this cross-calibration enables comparison between different national and international data.

Aim: The NET, encoded by SLC6A2, is responsible for presynaptic NE-reuptake. 123 I-mIBG is clinically used to evaluate cardiac sympathetic function. However, it is unknown if polymorphism of SLC6A2 influences cardiac sympathetic activity as assessed with 123 I-mIBG. Therefore we studied the influence of SLC6A2 SNPs on myocardial 123 I-mIBG parameters in CHF., Materials and Methods: Forty-nine adults with stable CHF (age 66.5 ± 8.1 years, LVEF 22.3 ± 6.4) were enrolled. Fifteen minutes (early) and 4 hours (late) after administration of 123 I-mIBG planar images were acquired. The H/M ratio was calculated from the manually drawn ROI over the left ventricle and a fixed mediastinal ROI. Fourteen exons of the SLC6A2 gene were analyzed from whole blood samples., Results: We found 6 different SLC6A2 SNPs, although none were functional. LVEF was the only independent predictor for early (adjusted R 2  = 0.063, p = 0.045) and late H/M ratio (adjusted R 2  = 0.116, p = 0.010). NT-proBNP was the only independent predictor for 123 I-mIBG WO (adjusted R 2  = 0.074, p = 0.032). SLC6A2 SNPs were not associated with any myocardial 123 I-mIBG-derived parameter., Conclusion: In this specific CHF population polymorphism of SLC6A2 gene was not associated with any 123 I-mIBG derived parameters.

Aim: Chronic heart failure (CHF) results in both increased cardiac sympathetic activity and myocardial inflammation. The aim of this study was to identify the relationship between severity of heart failure (i.e., NT-proBNP and LVEF), cardiac sympathetic activity ( 123 I-mIBG scintigraphy), and measures of inflammation in subjects with stable, optimally treated CHF. In addition, the predictive value for cardiac events (i.e., ventricular arrhythmia, progression of CHF and cardiac death) of 123 I-mIBG parameters and these inflammatory markers was evaluated., Materials and Methods: Fifty-five CHF patients (age 66.3 ± 8.0 years, 78% male, LVEF 22.4 ± 6.3) referred for cardiac 123 I-mIBG imaging were included. At 15 minutes (early) and 4 hours (late) after i.v. administration of 123 I-mIBG (185 MBq), planar images were acquired. Early Heart/Mediastinum (H/M) ratio, late H/M ratio, and 123 I-mIBG washout (WO) were calculated. NT-proBNP and markers of inflammation (i.e., C-reactive protein (CRP), IL-1β, IL-6, IL-8, IL-10, IL-12p40, tumor necrosis factor-α (TNF-α), soluble (s)E-selectin, myeloperoxidase (MPO), plasminogen activator inhibitor-1 (PAI-1), tPA, tumor necrosis factor receptor (TNFR) 1 and 2, and interferon (IFN) α and β) were measured in blood plasma samples, taken just before 123 I-mIBG administration., Results: Mean early H/M ratio was 2.12 ± 0.39, late H/M ratio was 1.84 ± 0.40, and 123 I-mIBG WO was 13.0 ± 10.9. LVEF was the only independent predictor of late H/M ratio (adjusted R 2 = 0.100, p = 0.011). NT-proBNP was an independent predictor of 123 I-mIBG WO (adjusted R 2 = 0.090, p = 0.015). CRP, IL12p40, TNF-α, sE-selectin, MPO, PAI-1, tPA, and TNFR2 were not related to late H/M ratio and 123 I-mIBG WO. During a median follow-up of 34 months (2-58 months), 13 patients experienced a cardiac event [ventricular arrhythmia (4), progression of CHF (4), and cardiac death (5)]. Univariate Cox regression analysis showed that the risk of a cardiac event was associated with CRP (HR 1.047 [1.013-1.081]), NT-proBNP (HR 1.141 [1.011-1.288]), MPO (HR 0.998 [0.996-1.000]), and late H/M ratio (HR 0.182 [0.035-0.946]). Multivariate Cox regression analysis showed that only CRP, NT-proBNP, MPO, and IL-12p40 were predictors of a cardiac event., Conclusion: Inflammation and cardiac sympathetic activity seem not to be related in stable CHF patients. This is corroborated by the finding that they both provide prognostic information in this specific CHF population. The current findings should be regarded as insightful but preliminary.

Tako-tsubo cardiomyopathy (TCM) is an increasingly recognized clinical syndrome characterized by acute reversible apical ventricular dysfunction, commonly preceded by exposure to severe physical or emotional stress. In this review, we give a short overview on clinical presentation and treatment of TCM and discuss the possible pathophysiological mechanisms of TCM and the role of various non-invasive imaging modalities in TCM with a focus on the potential role of (123)I-meta-iodobenzylguanidine (MIBG) scintigraphy. Currently, the dominating hypothesis on the pathophysiology of TCM postulates that high levels of the neurotransmitter epinephrine may trigger a change in intracellular signaling in ventricular myocytes. More specific, epinephrine stimulates G-protein coupled β2 adenoreceptors (β2AR) which are located on ventricular myocytes. Normal levels of this neurotransmitter predominantly stimulate the intracellular G-protein, and induce a positive inotropic effect. However, with significant increasing levels of epinephrine, the predominance of stimulation is shifted from G-stimulating to the G-inhibitor protein coupling, which leads to a negative inotropic effect. Interestingly, this negative inotropic effect is the largest in the apical myocardium where the β2AR:β1AR ratio is the highest within the heart. Echocardiography and ventriculography are essential to diagnose TCM, but new imaging tools are promising to diagnose TCM and to evaluate therapeutic efficacy. Cardiovascular magnetic resonance can be used to differentiate TCM from other myocardial diseases, such as myocarditis. (123)I-meta-iodobenzylguanidine ((123)I-MIBG) scintigraphy can be used to assess ventricular adrenergic activity and may guide optimization of individual (pharmacological) therapy. These new insights into the possible pathophysiological mechanisms and novel diagnostic imaging modalities can be used as starting point for the development of international guidelines of TCM which may increase the awareness, and optimize the treatment of TCM.

Aim: Purpose of this study was to assess the impact of mediastinal region of interest (ROI) definition on intra- and inter-observer variability in relation to collimator type., Methods: Thirty-five subjects with CHF (80% men, mean age 66 ± 9 years, NYHA 2.4 ± 0.5, LVEF 29 ± 8.4%) were enrolled. 15 minutes and 4 hours post-injection (p.i.) of (123)I-MIBG, planar images were sequentially acquired with low energy high energy (LEHR) and medium energy (ME) collimators. In the first analysis, observer-defined mediastinal ROI was used. In the second analysis, a predefined mediastinal ROI was used. Intra- and inter-observer variability of late H/M was assessed using Lin's concordance coefficient (LCC)., Results: There was substantial agreement between all three observers using predefined mediastinum ROI. LCCs for LEHR were 0.98, 0.96, and 0.95, for ME 0.98, 0.97, and 0.97. However, observer-defined mediastinal ROI resulted in poor-moderate agreement. LCCs for LEHR were 0.82, 0.94, and 0.70, for ME 0.77, 0.91, and 0.80. Intra-observer analysis using predefined mediastinal ROI showed substantial agreement. LCC was 0.97 for LEHR and 0.96 for ME., Conclusion: Predefined mediastinal ROI results in low intra- and inter-observer variability of late H/M and is, therefore, to be preferred over observer-defined mediastinal ROI. Intra- and inter-observer variability of late H/M is not influenced by collimator choice.

Background: Although several myocardial iodine 123 metaiodobenzylguanidine (MIBG) indices are increasingly used to detect alterations in myocardial sympathetic activity in various forms of cardiac pathology, published measurements of normal values and within-subject variability are lacking., Methods and Results: Twenty-five healthy volunteers underwent planar and single photon emission computed tomography (SPECT) imaging. Heart-mediastinum ratio (H/M) and myocardial washout were calculated from planar images comparing three different methods for the assessment of myocardial activity: (1) global region over the myocardium (cavity included), (2) global region over the myocardium (cavity excluded), and (3) fixed small myocardial region. Segmental (relative) uptake and washout were assessed by SPECT. For all MIBG indices, the interindividual variation was the lowest for methods 1 and 2. In SPECT this variation was low for relative segmental uptake compared with washout. In 9 subjects a second MIBG scintigraphy was performed after 3 months. The within-subject variability of H/M and washout assessed by planar methods 1 and 2 was 5%, whereas it was approximately 9% for planar method 3. For relative segmental uptake from SPECT, this variability was 5%., Conclusion: MIBG H/M (planar) and relative segmental uptake (SPECT) show a low interindividual and within-subject variability. This enables the detection of small (regional) variations in myocardial sympathetic nervous function, especially to monitor the effect of therapeutic interventions in patients with various cardiac diseases.

Background: There is inconsistency in reported patient characteristics associated with differences in basal and poststress left ventricular function (delta ejection fraction [DeltaEF]) assessed by gated single photon emission computed tomography (SPECT). This inconsistency may therefore hamper adequate interpretation. In this study we first determined the reproducibility of serial gated SPECT-assessed left ventricular function. Second, we determined whether left ventricular ejection fraction (LVEF) assessed directly after stress reflects basal LVEF and, if not, what patient characteristics were associated with this discrepancy in LVEF., Methods and Results: Serial reproducibility of technetium 99m tetrofosmin gated SPECT-assessed LVEF in 22 patients showed a mean difference between two sequential measurements at rest of 0.09% EF units, with a 95% limit of agreement (2 SDs) at 5.8% EF units. In 229 patients Tc-99m tetrofosmin gated SPECT was performed after stress and at rest. Independent predictors of DeltaEF were the presence of scintigraphically proven ischemia (standardized coefficient, -1.256; P =.003) and difference in heart rate at the time of acquisition (standardized coefficient, 0.121; P =.001)., Conclusions: Gated SPECT-assessed LVEF at rest is reproducible under standard clinical conditions. However, LVEF assessed after stress does not represent LVEF at rest in patients with scintigraphically proven ischemia and in patients with increased heart rate after stress compared with heart rate at rest.