Abstract 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.

Two widely used methods for left ventricular (LV) ejection fraction (EF) determination, echocardiography (echo) and gated single-photon emission computed tomography (SPECT) myocardial perfusion imaging (MPI), often have wide limits of agreement. Factors influencing discrepancies between core laboratory echo and MPI LVEF determinations were examined in a large series of heart failure (HF) subjects and normal controls. 879 HF and 101 control subjects had core lab analyses of echo and MPI (mean time between procedures 7-8 days). LVEF differences were analyzed using one-way analysis of variance and Bland-Altman plots. Relationships between LVEF differences and patient characteristics and outcome endpoints (mortality and arrhythmias) were explored with logistic regression, Cox proportional hazards models, and Kaplan-Meier survival analyses. There was a systematic difference between the 2 modalities; echo LVEF was higher with more severe LV dysfunction, MPI LVEF higher when systolic function was normal. LVEF results were within +/- 5% in only 37% of HF and 23% of control subjects. Considering discordance around the LVEF threshold 35%, there was disagreement between the 2 methods in 305 HF subjects (35%). Male gender (odds ratio (OR) = 0.200), atrial fibrillation (OR = 2.314), higher body mass index (OR = 1.051) and lower LV end-diastolic volume (OR = 0.985) were the strongest predictors of methodologic discordance. Cardiac event rates were highest if both LVEF values were <= 35% and lowest when both LVEF values were >35%. In conclusion, substantial disagreements between LVEF results by echo and MPI are common. HF patients with LVEF <= 35% by both techniques have the highest 2-year event risk. (C) 2021 Elsevier Inc. All rights reserved.

This narrative review reflects on the body of evidence on cardiac 123I-mIBG imaging that has accumulated since the introduction in the late 1970s and focusses on to what extent cardiac 123I-mIBG imaging has fulfilled its potential in cardiology especially. In contrast to the linear relationship between 123I-mIBG-derived parameters and overall prognosis in heart failure, there seems a “bell-shape” curve for 123I-mIBG-derived parameters and arrhythmic events. In addition, there is a potential clinical role for cardiac 123I-mIBG in optimizing patient selection for expensive devices (i.e., ICD and CRT). This needs of course to be established in future trials. Cardiac 123I-mIBG imaging is, despite the numerous of studies, sometimes mistakenly seen as a nice to have technique rather than a must have imaging modality. Although cardiac 123I-mIBG imaging has grown and matured over the years, its full clinical potential has still not been tested to the maximum.

Background and Aim Imaging noradrenergic uptake in the liver with norepinephrine analog(123)I-meta-iodobenzylguanidine (mIBG) was explored in normal controls and patients with heart failure (HF). Methods A total of 961 HF (343 with diabetes mellitus [DM]) and 94 control subjects underwent anterior planarmIBG images including upper abdomen at 15 min (early) and 3 h 50 min (late) post-injection. Decay-corrected liver activity normalized to injected activity and body surface area (counts/pixel [cpp]/MBq/m(2)) was compared in three groups: HF with DM; HF without DM; and controls. Associations with plasma norepinephrine, liver function tests, and level of cardiac innervation were explored. Results In controls, livermIBG activity decreased over time (early: 2.78vslate: 2.43 cpp/MBq/m(2),P < 0.0001); in HF subjects, activity increased during this interval (HF without DM: 2.85vs2.93 [P = 0.005]; HF with DM: 2.37vs2.43 [P = 0.054]). Early liver activity was lower in HF with DM subjects than in the other groups (P < 0.001); late liver activity was higher in HF without DM than in the other two groups (P < 0.01). Subjects with elevated plasma norepinephrine (> 520 pg/mL) or >= 1 abnormal liver function test had lower early and late liver activity. In subjects with preserved cardiacmIBG uptake, HF subjects had higher and control subjects lower liver activity than comparable subjects with decreased cardiac innervation. Conclusions In HF subjects, livermIBG activity increased over time, reversing the normal washout pattern, suggesting a compensatory change in sympathetic nerve function. DM, abnormal liver function tests, and decreased cardiac innervation were associated with decreased livermIBG uptake in HF.

Molecular imaging supplies specific information on the functional and metabolic behavior of myocardial tissues at the cellular level, providing unique insights into susceptibility to cardiac arrhythmias. This chapter examines recent molecular imaging research related to the origin and treatment of cardiac arrhythmias. Most of this work involved radionuclide imaging agents with both planar and single-photon emission computed tomography and positron emission tomography. Advances in molecular imaging relevant to arrhythmias support the need for change. The autonomic nervous system plays a significant role in the genesis and maintenance of arrhythmias. The state of the myocardial interstitium plays a significant role in the functional behavior of the heart, particularly in the conduction of electrical signals and the production of a coordinated contraction. Molecular imaging provides valuable insights on the interstitium, particularly in assessing the quantity and distribution of scar.

Abstract Aims The aim of this study was to validate a four-parameter risk model including 123I-meta-iodobenzylguanidine (MIBG) imaging, which was previously developed for predicting cardiac mortality, in a new cohort of patients with chronic heart failure (CHF). Methods and results Clinical and outcome data were retrospectively obtained from 546 patients (age 66 ± 14 years) who had undergone 123I-MIBG imaging with a heart-to-mediastinum ratio (HMR). The mean follow-up time was 30 ± 20 months, and the endpoint was cardiac death. The mortality outcome predicted by the model was compared with actual 2-year event rates in pre-specified risk categories of three or four risk groups using Kaplan–Meier survival analysis for cardiac death and receiver-operating characteristic (ROC) analysis. Cardiac death occurred in 137 patients, including 105 (68%) patients due to heart-failure death. With a 2-year mortality risk from the model divided into three categories of low- (<4%), intermediate- (4–12%), and high-risk (>12%), 2-year cardiac mortality was 1.1%, 7.9%, and 54.7%, respectively in the validation population (P < 0.0001). In a quartile analysis, although the predicted numbers of cardiac death was comparable with actual number of cardiac death for low- to intermediate-risk groups with a mortality risk <13.8%, it was underestimated in the high-risk group with a mortality risk ≥13.8%. The ROC analysis showed that the 2-year risk model had better (P < 0.0001) diagnostic ability for predicting heart failure death than left ventricular ejection fraction, natriuretic peptides or HMR alone. Conclusion The 2-year risk model was successfully validated particularly in CHF patients at a low to intermediate cardiac mortality risk.

INTRODUCTION:Medications that interfere with sympathetic neuronal norepinephrine uptake and storage, such as neuropsychiatrics (NP) and sympathomimetic amines, are most likely to affect cardiac uptake of iodine-123 metaiodobenzylguanidine (I-mIBG). The present study examined these and other medications reported to affect I-mIBG uptake using measurements of cardiac I-mIBG uptake on the heart failure (HF) patients in the ADMIRE-HF extension (X) study. METHODS:Baseline concomitant medications taken by the 961 HF patients were categorized into five groups: calcium channel blockers, NP medications, β agonists and sympathomimetics, α antagonists, and other antihypertensives. NP medications were further subcategorized into those expected to have high and low impact on norepinephrine transporter (NET) function. Myocardial I-mIBG heart/mediastinum (H/M) uptake ratios on 4 h planar images were compared among the groups. Impact of medication group on the prognostic value of the H/M ratio for all-cause (AC) and cardiac death during a median 2-year follow-up was also examined. RESULTS:A total of 283 (29%) patients were using at least one calcium channel blocker, NP medication, or β agonist or sympathomimetic. These patients had a lower mean H/M ratio than the other study patients (1.42±0.20 vs. 1.45±0.20; P=0.022). However, the 2-year AC mortality rates in the two groups were the same [11.3% (95% confidence interval: 7.5-15.2%) vs. 11.8% (95% confidence interval: 9.2-14.4%)]. In terms of medication categories, there were no significant differences in the mean H/M ratios between patients who did and did not use NP medications, β agonists, calcium channel blockers, and α antagonists. Across all categories, patients with H/M ratio greater than or equal to 1.60 had lower AC and cardiac mortality. Patients using higher potency (for NET inhibition) NP medications had significantly lower H/M ratio values, but the prognostic significance of H/M ratio greater than or equal to 1.60 was unchanged. CONCLUSION:Only a small number of higher potency NET-inhibiting NP medications have a measurable effect on the results of I-mIBG myocardial imaging. There appears to be no basis for restricting the use of calcium channel blockers and β agonist respiratory medications in HF patients referred for cardiac I-mIBG imaging.

123I-mIBG planar image heart-to-mediastinum ratios effectively risk-stratify heart failure (HF) patients. The value of single-photon emission computed tomographic (SPECT) imaging for identifying increased risk of ventricular arrhythmias is less clear. This study sought to determine if findings from simultaneous interpretation of 123I-mIBG and 99mTc-tetrofosmin SPECT are predictive of arrhythmic events (ArEs).

Extent of cardiac sympathetic activation can be estimated from physiological parameters, blood biomarkers, and imaging findings. This study examined the prognostic value of three markers of sympathetic activity and their relationship to beta blocker dose in heart failure patients.

I-123-mIBG imaging has been evaluated to assess sympathetic function and prognosis in heart failure (HF). However, the effect of combined HF medical therapies on I-123-mIBG uptake and its prognostic significance has not been previodsly examined. This analysis examined the relation between the intensity of guideline-directed HF medical therapy and global I-123-mIBG cardiac uptake in the AdreView Myocardial Imaging for Risk Evaluation in Heart Failure (ADMIRE-HF) database. A second objective was to investigate whether this guideline-based therapy, measured by total medication doses, had the expected effect on outcome, that is, that patients with higher I-123-mIBG cardiac uptake and more intensive medical therapy had the fewest outcome events. Three HF cardiologists developed an HF Medication Score (HFMS) to quantify adequacy of dosages of beta blockers, angiotensin-converting enzyme inhibitors, and angiotensin II receptor blockers and mineralocorticoid receptor antagonists. A Cox model was used to investigate the predictive ability. of the HFMS for mortality events during median 17 months follow-up. Multiple regression and Cox models assessed the usefulness of the HFMS relative to the planar heart/mediastinum ratio (H/Mp) from I-123-mIBG imaging in prediction of an event and to characterize the interaction of HFMS and H/M in predicting an event. HFMS was not a significant predictor of all-cause or cardiac death in either univariate or multivariate Cox models; H/Mp was highly significant for both event categories (p <0.0001). Mean H/Mp did not differ among HFMS ranges 0 to 3, 4 to 6, and 7 to 9. However, within each category, the mean H/Mp for subjects with events, was significantly lower than that of subjects without events, with the exception of cardiac mortality in those with highest scores. In conclusion, intensity of medical therapy is not predictive of short-term mortality in HF patients. H/Mp is a good predictor for both cardiac and overall mortality regardless of medical therapy levels. (C) 2016 Elsevier Inc. All rights reserved.

AIMS:The purpose of this study was to examine the prognostic significance of uptake patterns on quantitative myocardial (123)I-mIBG and (99m)Tc-tetrofosmin SPECT imaging in heart failure (HF) subjects and to assess the differences between patients with ischaemic and non-ischaemic HF.METHODS AND RESULTS:Results of quantitative analyses of (123)I-mIBG myocardial SPECT, alone and in combination with (99m)Tc tetrofosmin SPECT, were studied in 619 ischaemic (I) and 319 non-ischaemic (NI) HF subjects from the ADMIRE-HF trial. Cardiac and all-cause mortality data for 2-year follow-up were collected in the extension study (ADMIRE-HFX) and were examined in relation to extent and severity of voxel-based defects, the number of myocardial segments with significant dysinnervation (derived score ≥2), and (123)I-mIBG/(99m)Tc tetrofosmin mismatch quantitation. Cox proportional hazards and survival analyses were used to identify higher and lower risk groups and to define thresholds for optimal discrimination between the two. Two-year all-cause and cardiac mortality were not significantly different between IHF and NIHF subjects. Mortality was higher in patients with dysinnervation involving >50% of the myocardium. Highest cardiac mortality risk for IHF subjects was seen with perfusion defects involving 20-40% of the myocardium. By comparison, NIHF subjects with smaller perfusion abnormalities (<20% of myocardium), but with a large discrepancy between (123)I-mIBG and (99m)Tc tetrofosmin defect sizes, were at highest risk of cardiac death.CONCLUSIONS:Prognostic significance of patterns of (123)I-mIBG and MPI uptake differ between IHF and NIHF subjects. SPECT imaging may provide new insights into underlying disease processes in HF, including the degree of dysinnervation in areas with preserved myocardial perfusion in non-ischaemic HF patients.

Aims I-123 meta-iodobenzylguanidine (MIBG) imaging has been extensively used for prognostication in patients with chronic heart failure (CHF). The purpose of this study was to create mortality risk charts for short-term (2 years) and long-term (5 years) prediction of cardiac mortality.Methods and results Using a pooled database of 1322 CHF patients, multivariate analysis, including I-123-MIBG late heart-to-mediastinum ratio (HMR), left ventricular ejection fraction (LVEF), and clinical factors, was performed to determine optimal variables for the prediction of 2- and 5-year mortality risk using subsets of the patients (n = 1280 and 933, respectively). Multivariate logistic regression analysis was performed to create risk charts. Cardiac mortality was 10 and 22% for the subpopulation of 2- and 5-year analyses. A four-parameter multivariate logistic regression model including age, New York Heart Association (NYHA) functional class, LVEF, and HMR was used. Annualized mortality rate was,1% in patients with NYHA Class I-II and HMR >= 2.0, irrespective of age and LVEF. In patients with NYHA Class III-IV, mortality rate was 4-6 times higher for HMR <1.40 compared with HMR >= 2.0 in all LVEF classes. Among the subset of patients with b-type natriuretic peptide (BNP) results (n = 491 and 359 for 2- and 5-year models, respectively), the 5-year model showed incremental value of HMR in addition to BNP.Conclusion Both 2-and 5-year risk prediction models with I-123-MIBG HMR can be used to identify low-risk as well as high-risk patients, which can be effective for further risk stratification of CHF patients even when BNP is available.

Many guideline-eligible heart failure (HF) patients do not receive a survival benefit from implantable cardioverter defibrillators (ICDs). Improved risk stratification may help to reduce costs and improve the cost effectiveness of ICDs.