Hein J Verberne

University of Amsterdam, Amsterdamo, North Holland, Netherlands

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Publications (106)423.15 Total impact

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    ABSTRACT: Drug delivery to atherosclerotic plaques via liposomal nanoparticles may improve therapeutic agents' risk-benefit ratios. Our paper details the first clinical studies of a liposomal nanoparticle encapsulating prednisolone (LN-PLP) in atherosclerosis. First, PLP's liposomal encapsulation improved its pharmacokinetic profile in humans (n=13) as attested by an increased plasma half-life of 63 hours (LN-PLP 1.5 mg/kg). Second, intravenously infused LN-PLP appeared in 75% of the macrophages isolated from iliofemoral plaques of patients (n=14) referred for vascular surgery in a randomized, placebo-controlled trial. LN-PLP treatment did however not reduce arterial wall permeability or inflammation in patients with atherosclerotic disease (n=30), as assessed by multimodal imaging in a subsequent randomized, placebo-controlled study. In conclusion, we successfully delivered a long-circulating nanoparticle to atherosclerotic plaque macrophages in patients, whereas prednisolone accumulation in atherosclerotic lesions had no anti-inflammatory effect. Nonetheless, the present study provides guidance for development and imaging-assisted evaluation of future nanomedicine in atherosclerosis. Copyright © 2015. Published by Elsevier Inc.
    Nanomedicine: nanotechnology, biology, and medicine 03/2015; DOI:10.1016/j.nano.2015.02.021 · 5.98 Impact Factor
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    ABSTRACT: The objective of this study was to determine the predictive value of C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) to a positive fluorine-18 fluorodeoxyglucose (F-FDG) PET/computed tomography (CT) result in patients with inflammation of unknown origin and fever of unknown origin. Individual data of 498 patients were retrieved from three retrospective studies. Receiver operating characteristic derived areas under the curve were used to assess F-FDG PET/CT versus age, CRP, and ESR. The discriminative value of age, CRP, and ESR related to F-FDG PET/CT was examined using the net reclassification improvement (NRI). A diagnosis was established in 331 patients; F-FDG PET/CT had a diagnostic accuracy of 89%. F-FDG PET/CT had the highest area under the curve (0.89, P<0.001). The addition of F-FDG PET/CT to a diagnosis prediction model including age, CRP, and ESR resulted in an NRI of 42% (P<0.001). In the same model with CRP values below 20 mg/l or ESR values below 20 mm/h, the NRI was 64% (P<0.001) and 29% (P=0.059), respectively. In 30 of 91 patients with CRP less than 10 mg/l, a diagnosis could be established; F-FDG PET/CT was 100% true negative only in patients with CRP levels less than 5 mg/l. In patients with fever of unknown origin or inflammation of unknown origin, compared with elevated ESR levels, elevated CRP levels more often indicate a true positive F-FDG PET/CT outcome.In addition, F-FDG PET/CT, compared with CRP and ESR, shows the highest discrimination of patients with possible disabling disease.
    Nuclear Medicine Communications 03/2015; DOI:10.1097/MNM.0000000000000300 · 1.37 Impact Factor
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    ABSTRACT: Patients with increased inflammatory parameters, nonspecific signs and symptoms without fever and without a diagnosis after a variety of diagnostic procedures are a diagnostic dilemma and are referred to as having inflammation of unknown origin (IUO). The objective of this pilot study was to compare the cost-effectiveness of a diagnostic work-up/strategy with and without (18)F-FDG PET/CT in patients with IUO using a published dataset as a reference. IUO patients without (18)F-FDG PET/CT (group A, 46 patients) and IUO patients referred for (18)F-FDG PET/CT (group B, 46 patients) were selected. IUO was defined as the combination of nonspecific signs and symptoms and a prolonged erythrocyte sedimentation rate (ESR), defined as ≥age/2 in men and ≥(age + 10)/2 in women (ESR in millimetres per hour and age in years), and/or C-reactive protein (CRP) ≥15 mg/l. The costs of all tests and procedures and the number of hospitalization days in each patient to reach a diagnosis were calculated using current Dutch tariffs. In group A a diagnosis was reached in 14 of the 46 patients. The mean cost per patient of all the diagnostic procedures was 2,051, and including the cost of hospitalization was 12,614. In group B a diagnosis was reached in 32 of the 46 patients. The mean cost per patient of all the diagnostic procedures was 1,821, significantly lower than in group A (p < 0.0002), and including the cost of hospitalization was 5,298. In IUO (18)F-FDG PET/CT has the potential to become a cost-effective routine imaging technique indicating the direction for further diagnostic decisions thereby allowing unnecessary, invasive and expensive diagnostic investigations to be avoided and possibly the duration of hospitalization to be reduced. However, a prospective multicentre "bottom-up microcosting" cost-effectiveness study is warranted before these preliminary data can be extrapolated to clinical practice.
    European journal of nuclear medicine and molecular imaging 02/2015; DOI:10.1007/s00259-015-3010-0 · 5.22 Impact Factor
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    ABSTRACT: Abstract Objective: Patients treated for childhood craniopharyngioma often develop hypothalamic obesity (HO), which has a huge impact on the physical condition and quality of life of these patients. Treatment for HO thus far has been disappointing, and although several different strategies have been attempted, all interventions had only transient effects. Since thyroid hormones increase energy expenditure metabolism (thyroid hormone induced thermogenesis), it was speculated that treatment with tri-iodothyronine (T3) may be beneficial. In 2002, a case report was published on reduction of body weight after T3 treatment for HO. No studies have been reported since. Recent experimental studies in rodents showed that T3 increases brown adipose tissue (BAT) activity via (pre)sympathetic pathways between the hypothalamus and BAT. Our aim was to investigate whether T3 treatment increases BAT activity in a patient with HO resulting from (treatment of) childhood craniopharyngioma. Methods: Thyroxine treatment for central hypothyroidism was switched to T3 monotherapy. Serum T3 and free thyroxine (FT4) concentrations were measured twice weekly for 2 months. 123I-MIBG and 18F-FDG-PET after induction of non-shivering thermogenesis for the assessment of sympathetic and metabolic activity of BAT as well as indirect calorimetry for assessment of resting energy expenditure were performed before and during T3 treatment. Results: No change in sympathetic and metabolic BAT activity, energy expenditure, or BMI was seen during T3 treatment despite the expected changes in thyroid hormone plasma concentrations. Conclusion: We conclude that T3 monotherapy does not seem to be effective in decreasing HO in childhood craniopharyngioma.
    Journal of pediatric endocrinology & metabolism: JPEM 12/2014; 28(1-2). DOI:10.1515/jpem-2014-0337 · 0.71 Impact Factor
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    ABSTRACT: The I-metaiodobenzylguanidine (I-MIBG) late heart-to-mediastinum ratio (H/M) is a well-established prognostic parameter in patients with chronic heart failure (CHF). However, I presents imaging problems owing to high-energy photon emission leading to penetration of collimator septa and subsequent reduction in image quality. Most likely this affects the H/M ratio and may subsequently lead to incorrect patient risk classification. In this prospective study we assessed the intrapatient variation in late H/M ratio between low-energy high-resolution (LEHR) and medium-energy (ME) collimators in patients with CHF. Fifty-three patients with CHF (87% male, age 63±8.3 years, left ventricular ejection fraction 29±7.8) referred for I-MIBG scintigraphy were enrolled in the study. In each patient, after the administration of 185 MBq I-MIBG, early (15 min after injection) and late (4 h after injection) planar anterior thoracic images were acquired with both LEHR and ME collimators. Early and late H/M ratios were calculated on the basis of the mean count densities from the manually drawn regions of interest (ROIs) over the left ventricle and a predefined fixed ROI placed in the upper mediastinum. Additional ROIs were drawn over the liver and lungs. Liver/lung to myocardium and liver/lung to mediastinal ratios were calculated to estimate the effect of collimator septa penetration from liver and lung activity on the myocardial and mediastinal ROIs. The mean LEHR collimator-derived parameters were lower compared with those from the ME collimator (late H/M 1.41±0.18 vs. 1.80±0.41, P<0.001). Moreover, Bland-Altman analysis showed that with increasing late H/M ratios the difference between the ratios from the two collimator types increased (R=0.73, P=0.001). Multivariate regression analysis showed that almost 90% of the variation in the difference between ME and LEHR late H/M ratios could be explained by scatter from the liver in both the mediastinal and myocardial ROIs (R=0.90, P=0.001). Independent predictors for the difference in the late H/M between ME and LEHR were the liver-to-heart ratio and the liver-to-mediastinum ratio assessed by ME (standardized coefficient of -1.69 and 1.16, respectively) and LEHR (standardized coefficient of 1.24 and -0.90, respectively) (P<0.001 for all). Intrapatient comparison in H/M between the ME and LEHR collimators in patients with CHF showed that with increasing H/M the difference between the ratios increased in favour of the ME collimator. These differences could be explained by septal penetration of high-energy photons from both the liver and the lung in the mediastinum and myocardium, being lowest when using the ME collimator. These results strengthen the importance of the recommendation to use ME collimators in semiquantitative I-MIBG studies.
    Nuclear Medicine Communications 11/2014; DOI:10.1097/MNM.0000000000000238 · 1.37 Impact Factor
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    ABSTRACT: Patients with familial hypercholesterolemia (FH) are characterized by elevated atherogenic lipoprotein particles, predominantly low-density lipoprotein cholesterol (LDL-C), which is associated with accelerated atherogenesis and increased cardiovascular risk.
    Journal of the American College of Cardiology 10/2014; 64(14):1418-26. DOI:10.1016/j.jacc.2014.01.088 · 15.34 Impact Factor
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    ABSTRACT: Objective Hypoglycemia is associated with increased heat production and, despite of this, hypothermia. Heat production is likely to be mediated by sympathetic innervation. Brown adipose tissue is activated by cold exposure and stimulated by the sympathetic nervous system. We therefore examined the effect of hypoglycemia on uptake of the labeled glucose analogue 18 F-fluorodeoxyglucose in brown adipose tissue using positron emission tomography and computer tomography. Methods In nine healthy adults 18 F-fluorodeoxyglucose uptake as measure of brown adipose tissue activity was assessed in a cold environment (17 °C) during euglycemia (blood glucose 4.5 mmol/L) and hypoglycemia (2.5 mmol/L) using a hyperinsulinemic glucose clamp. Results Brown adipose tissue activity was observed in all participants. No difference was observed in the median (range) maximal standardized uptake values of 18 F-fluorodeoxyglucose in brown adipose tissue between euglycemia and hypoglycemia: 4.2 (1.0-7.7) versus 3.1 (2.2-12.5) g/mL (p = 0.7). Similarly there were no differences in mean standardized 18 F-fluorodeoxyglucose uptake values or total brown adipose tissue volume between euglycemia and hypoglycemia. Body temperature dropped by 0.6 °C from baseline during the hypoglycemic condition and remained unchanged during the euglycemic condition. There was no correlation between the maximal standardized uptake values of 18 F-fluorodeoxyglucose in brown adipose tissue and levels of counterregulatory hormones. Conclusions This study shows that there is a similar amount of 18 F-fluorodeoxyglucose uptake in brown adipose tissue during hypoglycemia when compared to euglycemia, which makes a role for systemic catecholamines in brown adipose tissue activation and a role for brown adipose tissue thermogenesis in hypoglycemia associated hypothermia unlikely. Future studies in humans should determine whether hypoglycemia indeed increases energy expenditure, and if so which alternative source can explain this increase.
    Metabolism 10/2014; 63(10). DOI:10.1016/j.metabol.2014.06.017 · 3.61 Impact Factor
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    ABSTRACT: Background Understanding how leukocytes impact atherogenesis contributes critically to our concept of atherosclerosis development and the identification of potential therapeutic targets. Objectives The study evaluates an in vivo imaging approach to visualize peripheral blood mononuclear cell (PBMC) accumulation in atherosclerotic lesions of cardiovascular (CV) patients using hybrid single-photon emission computed tomography/computed tomography (SPECT/CT). Methods At baseline, CV patients and healthy controls underwent 18fluorodeoxyglucose positron emission tomography-computed tomography and magnetic resonance imaging to assess arterial wall inflammation and dimensions, respectively. For in vivo trafficking, autologous PBMCs were isolated, labeled with technetium-99m, and visualized 3, 4.5, and 6 h post-infusion with SPECT/CT. Results Ten CV patients and 5 healthy controls were included. Patients had an increased arterial wall inflammation (target-to-background ratio [TBR] right carotid 2.00 ± 0.26 in patients vs. 1.51 ± 0.12 in controls; p = 0.022) and atherosclerotic burden (normalized wall index 0.52 ± 0.09 in patients vs. 0.33 ± 0.02 in controls; p = 0.026). Elevated PBMC accumulation in the arterial wall was observed in patients; for the right carotid, the arterial-wall-to-blood ratio (ABR) 4.5 h post-infusion was 2.13 ± 0.35 in patients versus 1.49 ± 0.40 in controls (p = 0.038). In patients, the ABR correlated with the TBR of the corresponding vessel (for the right carotid: r = 0.88; p < 0.001). Conclusions PBMC accumulation is markedly enhanced in patients with advanced atherosclerotic lesions and correlates with disease severity. This study provides a noninvasive imaging tool to validate the development and implementation of interventions targeting leukocytes in atherosclerosis.
    Journal of the American College of Cardiology 09/2014; 64(10):1019–1029. DOI:10.1016/j.jacc.2014.06.1171 · 15.34 Impact Factor
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    ABSTRACT: Aims: We sought to compare the diagnostic accuracy of basal stenosis resistance index (BSR), instantaneous wave-free ratio (iFR) and fractional flow reserve (FFR) for stenosis-specific myocardial ischaemia identified by means of a combined reference standard of myocardial perfusion scintigraphy and the hyperaemic stenosis resistance index. Methods and results: BSR and FFR were determined for 299 coronary stenoses, iFR was determined for 85 coronary stenoses (iFR cohort). The discriminative value for stenosis-specific myocardial ischaemia was compared by means of the area under the receiver operating characteristic (ROC) curves (AUC). Classification agreement with the reference standard was determined according to ROC curve-derived ischaemic cut-off values, as well as according to clinical cut-off values, equivalent to the 0.80 FFR cut-off. Across all stenoses, the discriminative value of BSR and FFR was equivalent (AUC: 0.90 and 0.91, respectively, p=0.46). In the iFR cohort, the discriminative value was equivalent for BSR, iFR, and FFR (AUC: 0.88, 0.84, and 0.88, respectively; p≥0.20 for all). At both ischaemic as well as clinical cut-off values, classification agreement with the reference standard was equivalent for BSR and FFR across all stenoses, as well as for BSR, iFR, and FFR in the iFR cohort. Conclusions: BSR, iFR, and FFR have equivalent diagnostic accuracy for the detection of ischaemia-generating coronary stenoses.
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    ABSTRACT: Cellular imaging modalities are important for revealing the behavior and role of monocytes in response to neovascularization progression in coronary artery disease. In this study we aimed to develop methods for high-resolution three-dimensional (3D) imaging and quantification of monocytes relative to the entire coronary artery network using a novel episcopic imaging modality. In a series of ex vivo experiments, human umbilical vein endothelial cells and CD14 + monocytes were labeled with fluorescent live cell tracker probes and infused into the coronary artery network of excised rat hearts by a Langendorff perfusion method. Coronary arteries were subsequently infused with fluorescent vascular cast material and processed with an imaging cryomicrotome, whereby each heart was consecutively cut (5 μm slice thickness) and block face imaged at appropriate excitation and emission wavelengths. The resulting image stacks yielded 3D reconstructions of the vascular network and the location of cells administered. Successful detection and quantification of single cells and cell clusters were achieved relative to the coronary network using customized particle detection software. These methods were then applied to an in vivo rabbit model of chronic myocardial ischemia in which autologous monocytes were isolated from peripheral blood, labeled with a fluorescent live cell tracker probe and re-infused into the host animal. The processed 3D image stacks revealed homing of monocytes to the ischemic myocardial tissue. Monocytes detected in the ischemic tissue were predominantly concentrated in the mid-myocardium. Vessel segmentation identified coronary collateral connections relative to monocyte localization. This study established a novel imaging platform to efficiently determine the localization of monocytes in relation to the coronary microvascular network. These techniques are invaluable for investigating the role of monocyte populations in the progression of coronary neovascularization in animal models of chronic and sub-acute myocardial ischemia.
    Journal of Molecular and Cellular Cardiology 08/2014; 76:196–204. DOI:10.1016/j.yjmcc.2014.08.019 · 5.22 Impact Factor
  • Atherosclerosis 08/2014; 235(2):e184. DOI:10.1016/j.atherosclerosis.2014.05.536 · 3.97 Impact Factor
  • Atherosclerosis 08/2014; 235(2):e20. DOI:10.1016/j.atherosclerosis.2014.05.026 · 3.97 Impact Factor
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    ABSTRACT: Brown adipose tissue (BAT) has emerged as a novel player in energy homeostasis in humans and is considered a potential new target for combating obesity and related diseases. The current 'gold standard' for quantification of BAT volume and activity is cold-induced 18F-FDG uptake in BAT. However, use of this technique is limited by cost and radiation exposure. Given the fact that BAT is a thermogenic tissue, mainly located in the supraclavicular region, the aim of the current study was to investigate whether cold-induced supraclavicular skin temperature and core body temperature may be alternative markers of BAT activation in humans.
    PLoS ONE 06/2014; 9(6):e98822. DOI:10.1371/journal.pone.0098822 · 3.53 Impact Factor
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    ABSTRACT: Cardiac imaging now provides a range of anatomical and functional information with some overlap in the ability of individual techniques to guide diagnosis and management. This report summarizes the conclusions of a panel of cardiac imagers who assembled to discuss the current state of the field. It focuses principally on options for nuclear cardiology, the choice between individual techniques, and areas where further advances would benefit patient management.
    05/2014; 15(9). DOI:10.1093/ehjci/jeu060
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    ABSTRACT: Aims: It has been argued that hyperaemic microvascular resistance (HMR), defined as the ratio of mean distal coronary pressure to flow velocity, is overestimated in the presence of a coronary stenosis compared to actual microvascular resistance (MR), due to neglecting collateral flow. We aimed to test the hypothesis that HMR allows accurate identification of microvascular functional abnormalities by evaluating the association between high or low HMR and the presence of myocardial ischaemia on non-invasive stress testing. Methods and results: Myocardial perfusion scintigraphy was performed in 228 patients, with 299 lesions to identify reversible myocardial ischaemia. Intracoronary distal pressure and flow velocity were assessed during adenosine-induced hyperaemia (20-40 µg, intracoronary) to determine hyperaemic stenosis resistance (HSR) and HMR. HMR >1.9 mmHg/cm/s was defined as high. The diagnostic odds ratio (OR) for myocardial ischaemia for lesions associated with high compared to low HMR was 2.6 (95% confidence interval [CI]: 1.5-4.4; p<0.001) overall, 3.3 (95% CI: 1.2-9.0; p=0.02) for lesions with HSR >0.8 mmHg/cm/s, and 1.3 (95% CI: 0.6-2.9; p=0.52) for lesions with HSR ≤0.8 mmHg/cm/s. Conclusions: The increased risk of myocardial ischaemia in the presence of high HMR, uncorrected for collateral flow, demonstrates that HMR is reflective of an increase in actual MR, identifying pertinent pathophysiological alterations in the microvasculature.
    EuroIntervention: journal of EuroPCR in collaboration with the Working Group on Interventional Cardiology of the European Society of Cardiology 04/2014; 9(12):1423-31. DOI:10.4244/EIJV9I12A240 · 3.76 Impact Factor
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    ABSTRACT: Fractional flow reserve (FFR) aims to identify the extent of epicardial disease, but may be obscured by involvement of the coronary microvasculature. We documented the impact of hyperaemic stenosis resistance (HSR) and hyperaemic microvascular resistance (HMR) on FFR, and its relationship with myocardial ischaemia in patients with stable coronary artery disease. We evaluated 255 coronary arteries with stenoses of intermediate severity by means of intracoronary pressure and flow measurements to determine FFR, HSR and HMR. Myocardial perfusion scintigraphy (MPS) was performed to identify inducible myocardial ischaemia. In 178 patients, HMR was additionally determined in a reference coronary artery. Target vessel HMR was stratified according to reference vessel HMR tertiles. The diagnostic OR for inducible ischaemia on MPS of a positive compared with a negative FFR was significantly higher only in the presence of a high HMR (at the 0.75 and 0.80 FFR cut-off). Among stenoses with a positive FFR, the prevalence of ischaemia was significantly higher when HMR was high despite equivalent FFR across the HMR groups. This was paralleled by a concomitant significant increase in HSR with increasing HMR across groups. The relation between FFR and HSR (r(2)=0.54, p<0.001) was modulated by the magnitude of HMR, and improved substantially after adjustment for HMR (adjusted-r(2)=0.73, p<0.001), where, for epicardial disease of equivalent severity, FFR increased with increasing HMR. Identification of epicardial disease severity by FFR is partly obscured by the microvascular resistance, which illustrates the necessity of combined pressure and flow measurements in daily practice.
    Heart (British Cardiac Society) 04/2014; 100(12). DOI:10.1136/heartjnl-2013-305124 · 6.02 Impact Factor
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    ABSTRACT: Nitric oxide (NO) is essential for the optimal perfusion of the heart and its vasculature. NO may be insufficient in surgical patients because its precursor arginine is decreased, and the inhibitor of NO synthesis asymmetric dimethylarginine (ADMA) is increased. Besides arginine, the presence of other amino acids essential for the proper metabolism of cardiac cells may be decreased too. Supplementation of these amino acids with enteral and parenteral nutrition before, during, and after surgery may augment the myocardial and plasma arginine:ADMA ratio and availability of amino acids. Myocardial glucose metabolism and nutritional conditioning may result in a reduction of cardiac injury and support rapid recovery after major surgery. We investigated the effect of nutrition before, during, and after surgery on amino acids and the myocardial arginine:ADMA ratio and its relation to myocardial glucose metabolism. In this trial, 33 patients who were undergoing off-pump coronary artery bypass grafting (CABG) were randomly assigned between enteral, parenteral, or no nutrition (control) from 2 d before, during, and until 2 d after surgery. Both enteral and parenteral solutions were prepared with commercial available products and included proteins or amino acids, glucose, vitamins, and minerals. Concentrations of amino acids including ADMA were analyzed in myocardial tissue and plasma samples. (18)F-fluorodeoxyglucose positron emission tomography was performed before and after surgery to assess myocardial glucose metabolism. The myocardial arginine:ADMA ratio increased during surgery and was significantly higher in the enteral and parenteral groups than in the control group [median (IQR): 115.0 (98.0-142.2) (P = 0.012), 116.9 (100.3-135.3) (P = 0.004), and 93.3 (82.7-101.1), respectively]. Furthermore, the change in the preoperative to postoperative plasma arginine:ADMA ratio correlated with the change in myocardial glucose metabolism in positron emission tomography (r = 0.427, P = 0.033). Enteral or parenteral nutrition before, during, and after CABG may positively influence myocardial glucose metabolism by increasing the plasma and myocardial arginine:ADMA ratio. This trial was registered at http://www.trialregister.nl as NTR2183.
    American Journal of Clinical Nutrition 04/2014; DOI:10.3945/ajcn.113.075473 · 6.92 Impact Factor
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    ABSTRACT: The purpose of this study was to determine the most appropriate prognostic endpoint for myocardial (123)I-metaiodobenzylguanidine (MIBG) scintigraphy in patients with chronic heart failure (CHF) based on aggregate results from multiple studies published in the past decade. Original individual late (3-5 h) heart/mediastinum (H/M) ratio data of 636 CHF patients were retrieved from six studies from Europe and the USA. All-cause mortality, cardiac mortality, arrhythmic events, and heart transplantation were investigated to determine which provided the strongest prognostic significance for the MIBG imaging data. The majority of patients was male (78%), had a decreased left ventricular ejection fraction (31.1 ± 12.5%), and a mean late H/M of 1.67 ± 0.47. During follow-up (mean 36.9 ± 20.1 months), there were 83 deaths, 67 cardiac deaths, 33 arrhythmic events, and 56 heart transplants. In univariate regression analysis, late H/M was a significant predictor of all event categories, but lowest hazard ratios (HRs) were for the composite endpoint of any event (HR = 0.30, 95% CI 0.19-0.46), all-cause (HR = 0.29, 95% CI 0.16-0.53), and cardiac mortality (HR = 0.28, 95% CI 0.14-0.55). In multivariate analysis, late H/M was an independent predictor for all event categories, except for arrhythmias. This pooled individual patient data meta-analysis showed that, in CHF patients, the late H/M ratio is not only useful as a dichotomous predictor of events (high vs. low risk), but also has prognostic implication over the full range of the outcome value for all event categories except arrhythmias.
    03/2014; 15(9). DOI:10.1093/ehjci/jeu044
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    ABSTRACT: The goal of this multicenter retrospective study was to evaluate the contribution of F-FDG PET/CT in the diagnosis of patients with inflammation of unknown origin (IUO). In addition, C-reactive protein (CRP) level and erythrocyte sedimentation rate were assessed as possible predictors for the outcome of F-FDG PET/CT. Inflammation of unknown origin was defined as prolonged and perplexing inflammation, with repeated CRP levels more than 20 mg/L or erythrocyte sedimentation rate more than 20 mm/h, body temperature of less than 38.3°C, and without a diagnosis after a variety of conventional diagnostic procedures.A total of 140 patients with IUO (67 men, 73 women; mean age, 64.2 years; age range, 18-87 years) underwent F-FDG PET/CT. F-FDG PET/CT was considered helpful when the imaging findings led to a diagnosis, either confirmed by histopathology, microbiological assays, clinical and imaging follow-up, or response to treatment. In 104 patients (73%), a final diagnosis could be established as follows: infection in 35 patients, malignancy in 18 patients, noninfectious inflammatory disease in 44 patients, and a variety of uncommon conditions in 7 patients. F-FDG PET/CT was true positive in 95 patients, true negative in 30 patients (ie, self-limiting conditions), false positive in 6 patients, and false negative in 9 patients (predominantly systemic diseases). In this population, the positive predictive value, negative predictive value, and diagnostic accuracy of F-FDG PET/CT were 94%, 77%, and 89%, respectively. In a multivariate analysis, CRP was the only independent predictor for the outcome of F-FDG PET/CT. F-FDG PET/CT correctly identified or excluded a causal explanation in approximately 90% of patients with IUO. However, a negative F-FDG PET/CT is indicative for a self-limiting condition only after systemic diseases are excluded by other diagnostic tests.
    Clinical nuclear medicine 03/2014; DOI:10.1097/RLU.0000000000000423 · 2.86 Impact Factor

Publication Stats

1k Citations
423.15 Total Impact Points

Institutions

  • 2006–2014
    • University of Amsterdam
      • • Department of Nuclear Medicine
      • • Faculty of Medicine AMC
      Amsterdamo, North Holland, Netherlands
  • 1999–2014
    • Academisch Medisch Centrum Universiteit van Amsterdam
      • • Department of Nuclear Medicine
      • • Department of Endocrinology and Metabolism
      Amsterdamo, North Holland, Netherlands
  • 2013
    • Department of Nuclear Medicine
      Nyitra, Nitriansky, Slovakia
  • 2009
    • Oslo University Hospital
      Kristiania (historical), Oslo, Norway
  • 2001
    • Academic Medical Center (AMC)
      Amsterdamo, North Holland, Netherlands