Atorvastatin lowers 68Ga-DOTATATE uptake in coronary arteries, bone marrow and spleen in individuals with type 2 diabetes.

AIMS/HYPOTHESIS: Inflammation is a core component of residual cardiovascular risk in type 2 diabetes. With new anti-inflammatory therapeutics entering the field, accurate markers to evaluate their effectiveness in reducing cardiovascular disease are paramount. Gallium-68-labelled DOTATATE (68Ga-DOTATATE) has recently been proposed as a more specific marker of arterial wall inflammation than 18F-fluorodeoxyglucose (18F-FDG). This study set out to investigate whether 68Ga-DOTATATE uptake is amenable to therapeutic intervention in individuals with type 2 diabetes. METHODS: Individuals aged >50 years with type 2 diabetes underwent 68Ga-DOTATATE positron emission tomography (PET)/computed tomography (CT) at baseline and after 3 months treatment with atorvastatin 40 mg once daily. Primary outcome was the difference in coronary 68Ga-DOTATATE uptake, expressed as target-to-background ratio (TBR). The secondary outcome was difference in bone marrow and splenic uptake, expressed as the standardised uptake value (SUV). RESULTS: Twenty-two individuals with type 2 diabetes (mean age 63.2±6.4 years, 82% male, LDL-cholesterol 3.42±0.81 mmol/l, HbA1c 55±12 mmol/mol [7.2%±3.2%]) completed both 68Ga-DOTATATE PET/CT scans. The maximum TBR was -31% (95% CI -50, -12) lower in the coronary arteries, and bone marrow and splenic 68Ga-DOTATATE uptake was also significantly lower post statin treatment, with a mean percentage reduction of -15% (95% CI -27, -4) and -17% (95% CI -32, -2), respectively. CONCLUSIONS/INTERPRETATION: 68Ga-DOTATATE uptake across the cardio-haematopoietic axis was lower after statin therapy in individuals with type 2 diabetes. Therefore, 68Ga-DOTATATE is promising as a metric for vascular and haematopoietic inflammation in intervention studies using anti-inflammatory therapeutics in individuals with type 2 diabetes. TRIAL REGISTRATION: ClinicalTrials.gov NCT05730634.

Simultaneous assessment of myocardial perfusion and adrenergic innervation in patients with heart failure by low-dose dual-isotope CZT SPECT imaging.

BACKGROUND: In patients with heart failure (HF) sequential imaging studies have demonstrated a relationship between myocardial perfusion and adrenergic innervation. We evaluated the feasibility of a simultaneous low-dose dual-isotope 123I/99mTc-acquisition protocol using a cadmium-zinc-telluride (CZT) single-photon emission computed tomography (SPECT) camera. METHODS AND RESULTS: Thirty-six patients with HF underwent simultaneous low-dose 123I-metaiodobenzylguanidine (MIBG)/99mTc-sestamibi gated CZT-SPECT cardiac imaging. Perfusion and innervation total defect sizes and perfusion/innervation mismatch size (defined by 123I-MIBG defect size minus 99mTc-sestamibi defect size) were expressed as percentages of the total left ventricular (LV) surface area. LV ejection fraction (EF) significantly correlated with perfusion defect size (P < .005), innervation defect size (P < .005), and early (P < .05) and late (P < .01) 123I-MIBG heart-to-mediastinum (H/M) ratio. In addition, late H/M ratio was independently associated with reduced LVEF (P < .05). Although there was a significant relationship (P < .001) between perfusion and innervation defect size, innervation defect size was larger than perfusion defect size (P < .001). At multivariable linear regression analysis, 123I-MIBG washout rate (WR) correlated with perfusion/innervation mismatch (P < .05). CONCLUSIONS: In patients with HF, a simultaneous low-dose dual-isotope 123I/99mTc-acquisition protocol is feasible and could have important clinical implications.

EANM procedural guidelines for PET/CT quantitative myocardial perfusion imaging.

The use of cardiac PET, and in particular of quantitative myocardial perfusion PET, has been growing during the last years, because scanners are becoming widely available and because several studies have convincingly demonstrated the advantages of this imaging approach. Therefore, there is a need of determining the procedural modalities for performing high-quality studies and obtaining from this demanding technique the most in terms of both measurement reliability and clinical data. Although the field is rapidly evolving, with progresses in hardware and software, and the near perspective of new tracers, the EANM Cardiovascular Committee found it reasonable and useful to expose in an updated text the state of the art of quantitative myocardial perfusion PET, in order to establish an effective use of this modality and to help implementing it on a wider basis. Together with the many steps necessary for the correct execution of quantitative measurements, the importance of a multiparametric approach and of a comprehensive and clinically useful report have been stressed.

Procedural recommendations of cardiac PET/CT imaging: standardization in inflammatory-, infective-, infiltrative-, and innervation (4Is)-related cardiovascular diseases: a joint collaboration of the EACVI and the EANM.

With this document, we provide a standard for PET/(diagnostic) CT imaging procedures in cardiovascular diseases that are inflammatory, infective, infiltrative, or associated with dysfunctional innervation (4Is). This standard should be applied in clinical practice and integrated in clinical (multicenter) trials for optimal procedural standardization. A major focus is put on procedures using [18F]FDG, but 4Is PET radiopharmaceuticals beyond [18F]FDG are also described in this document. Whilst these novel tracers are currently mainly applied in early clinical trials, some multicenter trials are underway and we foresee in the near future their use in clinical care and inclusion in the clinical guidelines. Finally, PET/MR applications in 4Is cardiovascular diseases are also briefly described. Diagnosis and management of 4Is-related cardiovascular diseases are generally complex and often require a multidisciplinary approach by a team of experts. The new standards described herein should be applied when using PET/CT and PET/MR, within a multimodality imaging framework both in clinical practice and in clinical trials for 4Is cardiovascular indications.

Position paper of the EACVI and EANM on artificial intelligence applications in multimodality cardiovascular imaging using SPECT/CT, PET/CT, and cardiac CT.

In daily clinical practice, clinicians integrate available data to ascertain the diagnostic and prognostic probability of a disease or clinical outcome for their patients. For patients with suspected or known cardiovascular disease, several anatomical and functional imaging techniques are commonly performed to aid this endeavor, including coronary computed tomography angiography (CCTA) and nuclear cardiology imaging. Continuous improvement in positron emission tomography (PET), single-photon emission computed tomography (SPECT), and CT hardware and software has resulted in improved diagnostic performance and wide implementation of these imaging techniques in daily clinical practice. However, the human ability to interpret, quantify, and integrate these data sets is limited. The identification of novel markers and application of machine learning (ML) algorithms, including deep learning (DL) to cardiovascular imaging techniques will further improve diagnosis and prognostication for patients with cardiovascular diseases. The goal of this position paper of the European Association of Nuclear Medicine (EANM) and the European Association of Cardiovascular Imaging (EACVI) is to provide an overview of the general concepts behind modern machine learning-based artificial intelligence, highlights currently prefered methods, practices, and computational models, and proposes new strategies to support the clinical application of ML in the field of cardiovascular imaging using nuclear cardiology (hybrid) and CT techniques.

Impact of left bundle branch block on myocardial perfusion and metabolism: A positron emission tomography study.

BACKGROUND: Better understanding of pathophysiological changes, induced by left bundle branch block (LBBB), may improve patient selection for cardiac resynchronization therapy (CRT). Therefore, we assessed the effect of LBBB on regional glucose metabolism, 13N-NH3-derived absolute and semiquantitative myocardial blood flow (MBF), and their relation in non-ischemic CRT candidates. METHODS: Twenty-five consecutive non-ischemic patients with LBBB underwent 18F-FDG and resting dynamic 13N-NH3 PET/CT prior to CRT implantation. Regional 18F-FDG uptake, absolute MBF, and late 13N-NH3 uptake were analyzed and corresponding septal-to-lateral wall ratios (SLR) were calculated. Segmental analysis was performed to evaluate "reverse mismatch," "mismatch," and "match" patterns, based on late 13N-NH3/18F-FDG uptake ratios. RESULTS: A significantly lower 18F-FDG uptake was observed in the septum compared to the lateral wall (SLR 0.53 ± 0.17). A similar pattern was observed for MBF (SLR 0.68 ± 0.18), whereas late 13N-NH3 uptake showed a homogeneous distribution (SLR 0.96 ± 0.13). 13N-NH3/18F-FDG "mismatch" and "reverse mismatch" segments were predominantly present in the lateral (52%) and septal wall (61%), respectively. CONCLUSIONS: Non-ischemic CRT candidates with LBBB demonstrate lower glucose uptake and absolute MBF in the septum compared to the lateral wall. However, late static 13N-NH3 uptake showed a homogenous distribution, reflecting a composite measure of altered regional MBF and metabolism, induced by LBBB.

Left ventricular ischemia after arterial switch procedure: Role of myocardial perfusion scintigraphy and cardiac CT.

Transposition of the great arteries is a congenital heart defect defined by an abnormal connection between the aorta, pulmonary artery, and the ventricles, resulting in parallel systemic and pulmonary circulations. Long-term follow-up data of patients who underwent correction via an arterial switch operation have recently shown that as a result of re-implantation of the coronary arteries in the neo-aorta, coronary stenosis and occlusion are relatively common complications. In this report, we discuss two cases illustrating the added value of myocardial perfusion imaging (MPI) and cardiac CT for the assessment of these patients. Based on the available literature we conclude that MPI and cardiac CT are excellent non-invasive methods to evaluate coronary anatomy and myocardial function also in this specific group of patients.

ASNC/AHA/ASE/EANM/HFSA/ISA/SCMR/SNMMI expert consensus recommendations for multimodality imaging in cardiac amyloidosis: Part 2 of 2-Diagnostic criteria and appropriate utilization.

Cardiac amyloidosis is emerging as an underdiagnosed cause of heart failure and mortality. Growing literature suggests that a noninvasive diagnosis of cardiac amyloidosis is now feasible. However, the diagnostic criteria and utilization of imaging in cardiac amyloidosis are not standardized. In this paper, Part 2 of a series, a panel of international experts from multiple societies define the diagnostic criteria for cardiac amyloidosis and appropriate utilization of echocardiography, cardiovascular magnetic resonance imaging, and radionuclide imaging in the evaluation of patients with known or suspected cardiac amyloidosis.

ASNC/AHA/ASE/EANM/HFSA/ISA/SCMR/SNMMI Expert Consensus Recommendations for Multimodality Imaging in Cardiac Amyloidosis: Part 2 of 2-Diagnostic Criteria and Appropriate Utilization.

Cardiac amyloidosis is emerging as an underdiagnosed cause of heart failure and mortality. Growing literature suggests that a noninvasive diagnosis of cardiac amyloidosis is now feasible. However, the diagnostic criteria and utilization of imaging in cardiac amyloidosis are not standardized. In this paper, Part 2 of a series, a panel of international experts from multiple societies define the diagnostic criteria for cardiac amyloidosis and appropriate utilization of echocardiography, cardiovascular magnetic resonance imaging, and radionuclide imaging in the evaluation of patients with known or suspected cardiac amyloidosis.

EANM guideline for ventilation/perfusion single-photon emission computed tomography (SPECT) for diagnosis of pulmonary embolism and beyond.

These guidelines update the previous EANM 2009 guidelines on the diagnosis of pulmonary embolism (PE). Relevant new aspects are related to (a) quantification of PE and other ventilation/perfusion defects; (b) follow-up of patients with PE; (c) chronic PE; and (d) description of additional pulmonary physiological changes leading to diagnoses of left ventricular heart failure (HF), chronic obstructive pulmonary disease (COPD) and pneumonia. The diagnosis of PE should be reported when a mismatch of one segment or two subsegments is found. For ventilation, Technegas or krypton gas is preferred over diethylene triamine pentaacetic acid (DTPA) in patients with COPD. Tomographic imaging with V/PSPECT has higher sensitivity and specificity for PE compared with planar imaging. Absence of contraindications makes V/PSPECT an essential method for the diagnosis of PE. When V/PSPECT is combined with a low-dose CT, the specificity of the test can be further improved, especially in patients with other lung diseases. Pitfalls in V/PSPECT interpretation are discussed. In conclusion, V/PSPECT is strongly recommended as it accurately establishes the diagnosis of PE even in the presence of diseases like COPD, HF and pneumonia and has no contraindications.

Myocardial perfusion scintigraphy during chest pain: An atypical presentation of takotsubo cardiomyopathy?

Although Takotsubo cardiomyopathy (TCM) knowledge is increasing, the exact pathophysiology remains unclear. TCM represents 1%-2% of all troponin positive acute coronary syndromes, affects predominantly postmenopausal women, and is commonly preceded by exposure to severe physical or emotional stress. Transient wall motion abnormalities mimicking ST-elevation myocardial infarction is expected as well as increase of troponin levels and echocardiography alterations. This case report is about a patient that as far as we know is the first case that shows the use of myocardial perfusion imaging in the acute phase of TCM. In general, the TCM Mayo Clinic diagnostic criteria have been very helpful in the clinical setting. In this specific case, however, the presence of reduced myocardial perfusion in the acute phase combined with increased troponin levels seemed to be in contradiction with the exclusion of obstructive coronary artery disease.

Role of cardiac 123I-mIBG imaging in predicting arrhythmic events in stable chronic heart failure patients with an ICD.

BACKGROUND: Despite therapeutic improvement, the prognosis of chronic heart failure (CHF) remains unfavorable partly due to arrhythmia and sudden cardiac death (SCD). This prospective study evaluated myocardial 123I-meta-iodobenzylguanidine (123I-mIBG) scintigraphy as a predictor of arrhythmic events (AE) in CHF patients. METHODS: 170 CHF patients referred for implantable cardioverter-defibrillator (ICD) implantation for both primary and secondary prevention were enrolled. All patients underwent planar and SPECT imaging. Early and late heart-to-mediastinum (H/M) ratio, 123I-mIBG washout (WO), early and late summed SPECT scores were calculated The primary endpoint was an AE: sustained ventricular tachycardia, resuscitated cardiac arrest, appropriate ICD therapy or SCD. The secondary endpoint was appropriate ICD therapy. RESULTS: During a median follow-up of 23.3 months, 69 patients experienced an AE. Early summed score (ESS) was the only independent predictor of AE [HR 1.023 (1.003-1.043)]. Focussing on only patients with an ICD for primary prevention, ESS was the only independent predictor of AE [HR 1.028 (1.007-1.050)]. 123I-mIBG-derived parameters failed to be independent predictors of appropriate ICD therapy. However there was a "bell-shaped" relation between 123I-mIBG scintigraphy-derived parameters and AE and appropriate ICD therapy, i.e., those with intermediate 123I-mIBG abnormalities tended to be at higher risk of events. CONCLUSION: Although SPECT 123I-mIBG scintigraphy was associated with AE in CHF patients with ICD implantation for primary and secondary prevention, no association was found between 123I-mIBG scintigraphy-derived parameters and appropriate ICD therapy.

Prolonged hematopoietic and myeloid cellular response in patients after an acute coronary syndrome measured with 18F-DPA-714 PET/CT.

PURPOSE: An acute coronary syndrome (ACS) is characterized by a multi-level inflammatory response, comprising activation of bone marrow and spleen accompanied by augmented release of leukocytes into the circulation. The duration of this response after an ACS remains unclear. Here, we assessed the effect of an ACS on the multi-level inflammatory response in patients both acutely and after 3 months. METHODS: We performed 18F-DPA-714 PET/CT acutely and 3 months post-ACS in eight patients and eight matched healthy controls. DPA-714, a PET tracer binding the TSPO receptor and highly expressed in myeloid cells, was used to assess hematopoietic activity. We also characterized circulating monocytes and hematopoietic stem and progenitor cells (HSPCs) by flow cytometry in 20 patients acutely and 3 months post-ACS and in 19 healthy controls. RESULTS: In the acute phase, patients displayed a 1.4-fold and 1.3-fold higher 18F-DPA-714 uptake in, respectively, bone marrow (p = 0.012) and spleen (p = 0.039) compared with healthy controls. This coincided with a 2.4-fold higher number of circulating HSPCs (p = 0.001). Three months post-ACS, 18F-DPA-714 uptake in bone marrow decreased significantly (p = 0.002), but no decrease was observed for 18F-DPA-714 uptake in the spleen (p = 0.67) nor for the number of circulating HSPCs (p = 0.75). CONCLUSIONS: 18F-DPA-714 PET/CT reveals an ACS- triggered hematopoietic organ activation as initiator of a prolonged cellular inflammatory response beyond 3 months, characterized by a higher number of circulating leukocytes and their precursors. This multi-level inflammatory response may provide an attractive target for novel treatment options aimed at reducing the high recurrence rate post-ACS.

Microvascular Permeability after an Acute and Chronic Salt Load in Healthy Subjects: A Randomized Open-label Crossover Intervention Study.

BACKGROUND: Sodium-induced microcirculatory changes, endothelial surface layer alterations in particular, may play an important role in sodium-mediated blood pressure elevation. However, effects of acute and chronic sodium loading on the endothelial surface layer and microcirculation in humans have not been established. The objective of this study was to assess sodium-induced changes in blood pressure and body weight as primary outcomes and also in microvascular permeability, sublingual microcirculatory dimensions, and urinary glycosaminoglycan excretion in healthy subjects. METHODS: Twelve normotensive males followed both a low-sodium diet (less than 50 mmol/day) and a high-sodium diet (more than 200 mmol/day) for eight days in randomized order, separated by a crossover period. After the low-sodium diet, hypertonic saline (5 mmol sodium/liter body water) was administered intravenously in 30 min. RESULTS: Both sodium interventions did not change blood pressure. Body weight increased with 2.5 (95% CI, 1.7 to 3.2) kg (P < 0.001) after dietary sodium loading. Acute intravenous sodium loading resulted in increased transcapillary escape rate of I-labeled albumin (2.7 [0.1 to 5.3] % cpm · g · h; P = 0.04), whereas chronic dietary sodium loading did not affect transcapillary escape rate of I-labeled albumin (-0.03 [-3.3 to 3.2] % cpm · g · h; P = 1.00), despite similar increases of plasma sodium and osmolality. Acute intravenous sodium loading coincided with significantly increased plasma volume, as assessed by the distribution volume of albumin, and significantly decreased urinary excretion of heparan sulfate and chondroitin sulfate. These changes were not observed after dietary sodium loading. CONCLUSIONS: Our results suggest that intravenous sodium loading has direct adverse effects on the endothelial surface layer, independent of blood pressure.

Pharmacodynamics and Pharmacokinetics of Lidocaine in a Rodent Model of Diabetic Neuropathy.

BACKGROUND: Clinical and experimental data show that peripheral nerve blocks last longer in the presence of diabetic neuropathy. This may occur because diabetic nerve fibers are more sensitive to local anesthetics or because the local anesthetic concentration decreases more slowly in the diabetic nerve. The aim of this study was to investigate both hypotheses in a rodent model of neuropathy secondary to type 2 diabetes. METHODS: We performed a series of sciatic nerve block experiments in 25 Zucker Diabetic Fatty rats aged 20 weeks with a neuropathy component confirmed by neurophysiology and control rats. We determined in vivo the minimum local anesthetic dose of lidocaine for sciatic nerve block. To investigate the pharmacokinetic hypothesis, we determined concentrations of radiolabeled (C) lidocaine up to 90 min after administration. Last, dorsal root ganglia were excised for patch clamp measurements of sodium channel activity. RESULTS: First, in vivo minimum local anesthetic dose of lidocaine for sciatic nerve motor block was significantly lower in diabetic (0.9%) as compared to control rats (1.4%). Second, at 60 min after nerve block, intraneural lidocaine was higher in the diabetic animals. Third, single cell measurements showed a lower inhibitory concentration of lidocaine for blocking sodium currents in neuropathic as compared to control neurons. CONCLUSIONS: We demonstrate increased sensitivity of the diabetic neuropathic nerve toward local anesthetics, and prolonged residence time of local anesthetics in the diabetic neuropathic nerve. In this rodent model of neuropathy, both pharmacodynamic and pharmacokinetic mechanisms contribute to prolonged nerve block duration.

Remnant Cholesterol Elicits Arterial Wall Inflammation and a Multilevel Cellular Immune Response in Humans.

OBJECTIVE: Mendelian randomization studies revealed a causal role for remnant cholesterol in cardiovascular disease. Remnant particles accumulate in the arterial wall, potentially propagating local and systemic inflammation. We evaluated the impact of remnant cholesterol on arterial wall inflammation, circulating monocytes, and bone marrow in patients with familial dysbetalipoproteinemia (FD). APPROACH AND RESULTS: Arterial wall inflammation and bone marrow activity were measured using 18F-FDG PET/CT. Monocyte phenotype was assessed with flow cytometry. The correlation between remnant levels and hematopoietic activity was validated in the CGPS (Copenhagen General Population Study). We found a 1.2-fold increase of 18F-FDG uptake in the arterial wall in patients with FD (n=17, age 60±8 years, remnant cholesterol: 3.26 [2.07-5.71]) compared with controls (n=17, age 61±8 years, remnant cholesterol 0.29 [0.27-0.40]; P<0.001). Monocytes from patients with FD showed increased lipid accumulation (lipid-positive monocytes: Patients with FD 92% [86-95], controls 76% [66-81], P=0.001, with an increase in lipid droplets per monocyte), and a higher expression of surface integrins (CD11b, CD11c, and CD18). Patients with FD also exhibited monocytosis and leukocytosis, accompanied by a 1.2-fold increase of 18F-FDG uptake in bone marrow. In addition, we found a strong correlation between remnant levels and leukocyte counts in the CGPS (n=103 953, P for trend 5×10-276). In vitro experiments substantiated that remnant cholesterol accumulates in human hematopoietic stem and progenitor cells coinciding with myeloid skewing. CONCLUSIONS: Patients with FD have increased arterial wall and cellular inflammation. These findings imply an important inflammatory component to the atherogenicity of remnant cholesterol, contributing to the increased cardiovascular disease risk in patients with FD.

Polymorphism of SLC6A2 gene does not influence outcome of myocardial 123I-mIBG scintigraphy in patients with chronic heart failure.

AIM: The NET, encoded by SLC6A2, is responsible for presynaptic NE-reuptake. 123I-mIBG is clinically used to evaluate cardiac sympathetic function. However, it is unknown if polymorphism of SLC6A2 influences cardiac sympathetic activity as assessed with 123I-mIBG. Therefore we studied the influence of SLC6A2 SNPs on myocardial 123I-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 123I-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 123I-mIBG WO (adjusted R 2 = 0.074, p = 0.032). SLC6A2 SNPs were not associated with any myocardial 123I-mIBG-derived parameter. CONCLUSION: In this specific CHF population polymorphism of SLC6A2 gene was not associated with any 123I-mIBG derived parameters.

Myocardial 123I-mIBG scintigraphy in relation to markers of inflammation and long-term clinical outcome in patients with stable chronic heart failure.

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 (123I-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 123I-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 123I-mIBG imaging were included. At 15 minutes (early) and 4 hours (late) after i.v. administration of 123I-mIBG (185 MBq), planar images were acquired. Early Heart/Mediastinum (H/M) ratio, late H/M ratio, and 123I-mIBG washout (WO) were calculated. NT-proBNP and markers of inflammation (i.e., C-reactive protein (CRP), IL-1ß, 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 ß) were measured in blood plasma samples, taken just before 123I-mIBG administration. RESULTS: Mean early H/M ratio was 2.12 ± 0.39, late H/M ratio was 1.84 ± 0.40, and 123I-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 123I-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 123I-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.