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Aims: Cardiac 123iodine-meta-iodobenzylguanidine (123I-mIBG) single-photon emission computed tomography (SPECT) imaging provides information on regional myocardial innervation. However, the value of the commonly used 17-segment summed defect score (SDS) as a prognostic marker is uncertain. The present study examined whether a simpler regional scoring approach for evaluation of 123I-mIBG SPECT combined with rest 99mTc-tetrofosmin SPECT myocardial perfusion imaging could improve prediction of arrhythmic events (AEs) in patients with ischaemic heart failure (HF)., Methods and Results: Five hundred and two ischaemic HF subjects of the ADMIRE-HF study with complete cardiac 123I-mIBG and rest 99mTc-tetrofosmin SPECT studies were included. Both SPECT image sets were read together by two experienced nuclear imagers and scored by consensus. In addition to standard 17-segment scoring, the readers classified walls (i.e. anterior, lateral, inferior, septum and apex) as normal, matched defect, mismatched (innervation defect > perfusion defect), or reverse mismatched (perfusion defect > innervation defect). Cox proportional hazards ratios (HRs) were used to determine if age, body mass index, functional class, left ventricular ejection fraction (LVEF), B-type natriuretic peptide (BNP), norepinephrine, 123I-mIBG SDS, 99mTc-tetrofosmin SDS, innervation/perfusion mismatch SDS, and our simplified visual innervation/perfusion wall classification were associated with occurrence of AEs (i.e. sudden cardiac death, sustained ventricular tachycardia, resuscitated cardiac arrest, appropriate implantable cardioverter-defibrillator therapy). At 2-year median follow-up, 52 subjects (10.4%) had AEs. Subjects with 1 or 2 mismatched walls were twice as likely to have AEs compared with subjects with either 0 or 3-5 mismatched walls (16.3% vs. 8.3%, P = 0.010). Cox regression analyses showed that patients with a visual mismatch in 1-2 walls had an almost two times higher risk of AEs [HR 2.084 (1.109-3.914), P = 0.001]. None of the other innervation, perfusion and mismatch scores using standard 17 segments were associated with AEs. BNP (ng/L) was the only non-imaging parameter associated with AEs., Conclusion: A visual left ventricular wall-level based scoring method identified highest AE risk in ischaemic HF subjects with intermediate levels of innervation/perfusion mismatches. This simple technique for the evaluation of SPECT studies, which are often challenging in HF subjects, seems to be superior to the 17-segment scoring method., Competing Interests: Conflict of interest: A.F.J. was an employee at GE Healthcare during the conduct of the original ADMIRE-HF study. The other authors declare that they have no conflict of interest., (© The Author(s) 2021. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Aims: Cardiac resynchronization therapy (CRT) is a disease-modifying therapy in patients with chronic heart failure (CHF). Current guidelines ascribe CRT eligibility on three parameters only: left ventricular ejection fraction (LVEF), QRS duration, and New York Heart Association (NYHA) functional class. However, one-third of CHF patients does not benefit from CRT. This study evaluated whether 123I-meta-iodobenzylguanidine (123I-mIBG) assessed cardiac sympathetic activity could optimize CRT patient selection., Methods and Results: A total of 78 stable CHF subjects (age 66.8 ± 9.6 years, 73% male, LVEF 25.2 ± 6.7%, QRS duration 153 ± 23 ms, NYHA 2.2 ± 0.7) referred for CRT implantation were enrolled. Subjects underwent 123I-mIBG scintigraphy prior to implantation. Early and late heart-to-mediastinum (H/M) ratio and 123I-mIBG washout were calculated. CRT response was defined as either an increase of LVEF to >35%, any improvement in LVEF of >10%, QRS shortening to <150 ms, or improvement in NYHA class of >1 class. In 33 patients LVEF increased to >35%, QRS decreased <150 ms in 36 patients, and NYHA class decreased in 33 patients. Late H/M ratio and hypertension were independent predictors of LVEF improvement to >35% (P = 0.0014 and P = 0.0149, respectively). In addition, early H/M ratio, LVEF, and absence of diabetes mellitus (DM) were independent predictors for LVEF improvement by >10%. No independent predictors were found for QRS shortening to <150 ms or improvement in NYHA class., Conclusion: Early and late H/M ratio were independent predictors of CRT response when improvement of LVEF was used as measure of response. Therefore, cardiac 123I-mIBG scintigraphy may be used as a tool to optimize selection of subjects that might benefit from CRT., (© The Author(s) 2020. Published by Oxford University Press on behalf of the European Society of Cardiology.)

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 123 I-meta-iodobenzylguanidine ( 123 I-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, 123 I-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)]. 123 I-mIBG-derived parameters failed to be independent predictors of appropriate ICD therapy. However there was a "bell-shaped" relation between 123 I-mIBG scintigraphy-derived parameters and AE and appropriate ICD therapy, i.e., those with intermediate 123 I-mIBG abnormalities tended to be at higher risk of events., Conclusion: Although SPECT 123 I-mIBG scintigraphy was associated with AE in CHF patients with ICD implantation for primary and secondary prevention, no association was found between 123 I-mIBG scintigraphy-derived parameters and appropriate ICD therapy.

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.

Aim: Chronic heart failure (CHF) is a life-threatening clinical syndrome, partly due to sudden cardiac death (SCD). Implantable cardioverter defibrillators (ICD) for primary prevention of SCD have improved overall survival of CHF patients. However, a high percentage of patients never receives appropriate ICD therapy. This prospective multicentre study evaluated whether cardiac sympathetic activity assessed by 123 I-mIBG scintigraphy could be helpful in selecting patients for ICD implantation., Materials and Methods: 135 stable CHF subjects (age 64.5±9.3years, 79% male, LVEF 25±6%) referred for prophylactic ICD implantation were enrolled in 13 institutions. All subjects underwent planar and SPECT 123 I-mIBG scintigraphy. Early and late heart-to-mediastinum (H/M) ratio, 123 I-mIBG washout (WO) and late summed scores were calculated. The primary endpoint was appropriate ICD therapy. The secondary endpoint was defined as the combined endpoint of all first cardiac events: appropriate ICD therapy, progression of heart failure (HF) and cardiac death., Results: During a median follow-up of 30months (6-68months), 24 subjects (17.8%) experienced a first cardiac event (appropriate ICD therapy [12], HF progression [6], cardiac death [6]). Late H/M ratio and defect size of 123 I-mIBG SPECT were not associated with appropriate ICD therapy. However, late H/M ratio was independently associated with the combined endpoint (HR 0.135 [0.035-0.517], p=0.001). Post-hoc analysis showed that the combination of late H/M ratio (HR 0.461 [0.281-0.757]) and LVEF (HR 1.052 [1.021-1.084]) was significantly associated with freedom of appropriate ICD therapy (p<0.001)., Conclusion: 123 I-mIBG scintigraphy seems to be helpful in selecting CHF subjects who might not benefit from ICD implantation., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Aims: 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., Methods and Results: 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., Conclusions: 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., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2014. For permissions please email: journals.permissions@oup.com.)

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.