A simplified wall-based model for regional innervation/perfusion mismatch assessed by cardiac 123I-mIBG and rest 99mTc-tetrofosmin SPECT to predict arrhythmic events in ischaemic heart failure.

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.

Analysis of Differences in Assessment of Left Ventricular Function on Echocardiography and Nuclear Perfusion Imaging.

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.

Noradrenergic uptake in the liver on 123 I-mIBG imaging: Influence of heart failure and diabetes.

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 planar mIBG 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/m2 ) 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, liver mIBG activity decreased over time (early: 2.78 vs late: 2.43 cpp/MBq/m2 , P < 0.0001); in HF subjects, activity increased during this interval (HF without DM: 2.85 vs 2.93 [P = 0.005]; HF with DM: 2.37 vs 2.43 [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 cardiac mIBG uptake, HF subjects had higher and control subjects lower liver activity than comparable subjects with decreased cardiac innervation. CONCLUSIONS: In HF subjects, liver mIBG 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 liver mIBG uptake in HF.

Validation of 2-year 123I-meta-iodobenzylguanidine-based cardiac mortality risk model in chronic heart failure.

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.

Beta blocker dose and markers of sympathetic activation in heart failure patients: interrelationships and prognostic significance.

AIMS: 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. METHODS AND RESULTS: A post hoc analysis of 858 heart failure subjects in the ADMIRE-HF trial was performed. Variables related to sympathetic activity were plasma norepinephrine, baseline heart rate, the heart to mediastinum (H/M) ratio of 123 I-mIBG uptake, and beta blocker dose. Univariate and multivariate analyses for occurrence of mortality (all-cause and cardiac) and arrhythmic events were performed. Beta blocker dose was significantly related to age, heart rate, b-type natriuretic peptide (negatively), body mass index, body weight and plasma norepinephrine. Univariate predictors of all-cause and cardiac mortality were baseline heart rate (χ2  = 4.5, P = 0.029 and χ2  = 5 .2, P = 0.022, respectively), plasma norepinephrine level (χ2  = 8.9, P = 0.0006 and χ2  = 8.6, P = 0.003, respectively), and H/M (χ = 22.4, P < 0.0001 and χ2  = 17.8, P < 0.0001, respectively). In multivariate analyses, carvedilol-equivalent dose (P = 0.017), plasma norepinephrine (P = 0.002), and H/M (P = 0.0001) were significant predictors of all-cause mortality. In separate analyses using multiple measurements of heart rate, mean heart rate >67 b.p.m. was associated with significantly higher cardiac mortality. CONCLUSIONS: Higher beta blocker dose was associated with lower mortality, but of the variables associated with sympathetic activity examined, cardiac 123 I-mIBG uptake was the most powerful prognostic marker in heart failure patients. Elevated heart rate was associated with greater risk for cardiac death.

Assessment of 123I-mIBG and 99mTc-tetrofosmin single-photon emission computed tomographic images for the prediction of arrhythmic events in patients with ischemic heart failure: Intermediate severity innervation defects are associated with higher arrhythmic risk.

RATIONALE: 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). METHODS: 123I-mIBG SPECT images from 622 patients with ischemic HF were presented in standard displays alongside 99mTc-tetrofosmin images. Consensus interpretations using a 17-segment model produced summed scores. Cox proportional hazards analyses related findings to adjudicated ArEs over 2 years. RESULTS: 471 patients had images adequate for total 17-segment scoring. There were 48 ArEs (10.2%). Neither 123I-mIBG nor 99mTc-tetrofosmin SPECT summed scores were univariate predictors. On multivariate proportional hazards analysis, the 123I-mIBG SPECT score was independently predictive of ArEs (HR: 0.975, 95% CI 0.951-0.999, P = 0.042), but HR<1 indicated that risk decreased with increasing score. This occurred because patients with intermediately abnormal SPECT studies had a higher likelihood of ArEs compared to patients with extensive abnormalities. CONCLUSIONS: The presumption of a monotonic increase in ArE risk with increasing summed 123I-mIBG SPECT score may not be correct as ischemic HF patients with abnormalities of intermediate extent appear at highest risk.

Persistence of 123I-mIBG Prognostic Capability in Relation to Medical Therapy in Heart Failure (from the ADMIRE-HF Trial).

123I-mIBG imaging has been evaluated to assess sympathetic function and prognosis in heart failure (HF). However, the effect of combined HF medical therapies on 123I-mIBG uptake and its prognostic significance has not been previously examined. This analysis examined the relation between the intensity of guideline-directed HF medical therapy and global 123I-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 123I-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 ß 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 123I-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.

Impact of concomitant medication use on myocardial 123I-mIBG imaging results in patients with heart failure.

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, ß 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 ß 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, ß 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 ß agonist respiratory medications in HF patients referred for cardiac I-mIBG imaging.

Cost-Effectiveness Analysis of Iodine-123 Meta-Iodobenzylguanidine Imaging for Screening Heart Failure Patients Eligible for an Implantable Cardioverter Defibrillator in the USA.

BACKGROUND: 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. OBJECTIVE: To estimate the potential outcomes, costs, and cost effectiveness of using iodine-123 meta-iodobenzylguanidine (I-mIBG) to screen HF patients eligible for an ICD. METHODS: A decision-analytic model was developed to compare screening with I-mIBG imaging and no screening over 2-year and 10-year time horizons from a US payer perspective. Data on I-mIBG imaging and risk stratification were obtained from the ADMIRE-HF/HFX (AdreView Myocardial Imaging for Risk Evaluation in Heart Failure) trial. Data on ICD effectiveness for prevention of sudden cardiac death (SCD) were obtained from a meta-analysis. Costs of ICDs and costs of generator and lead procedures were obtained from the Agency for Healthcare Research and Quality National Inpatient Sample. Age-specific mortality was modeled using US life tables and data from the ACT (Advancements in ICD Therapy) Registry on risks of SCD and non-SCD mortality. Sensitivity analyses were conducted. RESULTS: In the analysis, screening with I-mIBG imaging was associated with a reduction in ICD utilization of 21 %, resulting in a number needed to screen to prevent 1 ICD implantation of 5. Screening reduced the costs per patient by US$5500 and US$13,431 (in 2013 dollars) over 2 and 10 years, respectively, in comparison with no screening and resulted in losses of 0.001 and 0.040 life-years, respectively, over 2 and 10 years. Screening was decrementally cost effective, with savings of US$5,248,404 and US$513,036 per quality-adjusted life-year lost over 2 and 10 years, respectively. In subgroup analyses, cost savings were greater for patients with an ejection fraction (EF) of 25-35 % than for those with an EF <25 %. CONCLUSIONS: According to the model, screening of guideline-eligible patients selected for ICDs with I-mIBG imaging may be cost effective and may help reduce costs associated with implantation of ICDs, with a minimal impact on survival.

Prognostic significance of (123)I-mIBG SPECT myocardial imaging in heart failure: differences between patients with ischaemic and non-ischaemic heart failure.

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.

Creation of mortality risk charts using 123I meta-iodobenzylguanidine heart-to-mediastinum ratio in patients with heart failure: 2- and 5-year risk models.

AIMS: (123)I 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 (123)I-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 sub-population 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 (123)I-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.

Quantitative iodine-123-metaiodobenzylguanidine (MIBG) SPECT imaging in heart failure with left ventricular systolic dysfunction: Development and validation of automated procedures in conjunction with technetium-99m tetrofosmin myocardial perfusion SPECT.

BACKGROUND: The purpose of this study was to develop and validate new approaches to quantitative MIBG myocardial SPECT imaging in heart failure (HF) subjects. METHODS AND RESULTS: Quantitative MIBG myocardial SPECT analysis methods, alone and in conjunction with 99mTc-tetrofosmin perfusion SPECT, were adapted from previously validated techniques for the analysis of SPECT and PET perfusion imaging. To account for underestimation of MIBG defect severity in subjects with global reduction in uptake, a mixed reference database based on planar heart/mediastinum (H/M) ratio categories was used. Extent and severity of voxel-based defects and number of myocardial segments with significant dysinnervation (derived score ≥2) were determined. MIBG/99mTc-tetrofosmin mismatch was quantified using regions with preserved innervation as the reference for scaling 99mTc-tetrofosmin voxel maps. Quantification techniques were tested on studies of 619 ischemic (I) and 319 non-ischemic (NI) HF subjects. Using all analytical techniques, IHF subjects had significantly greater and more severe MIBG SPECT abnormalities compared with NIHF subjects. Innervation/perfusion mismatches were also larger in IHF subjects. Findings were consistent between voxel- and myocardial-segment-based quantitation methods. CONCLUSIONS: Multiple objective methods for quantitation of MIBG SPECT imaging studies provided internally consistent results for distinguishing the different patterns of uptake between IHF and NIHF subjects.

¹²³I-MIBG Imaging for Prediction of Mortality and Potentially Fatal Events in Heart Failure: The ADMIRE-HFX Study.

UNLABELLED: ADMIRE-HF (AdreView Myocardial Imaging for Risk Evaluation in Heart Failure) established the prognostic significance of (123)I-metaiodobenzylguanidine ((123)I-MIBG) imaging in heart failure subjects (median follow-up, 17 mo) using a composite endpoint dominated by heart failure progression. The ADMIRE-HF extension (ADMIRE-HFX) extended follow-up to a median of 24 mo and used mortality as the primary endpoint. The objective of these analyses was to use multiple multivariate risk modeling techniques to determine the independent predictive ability of (123)I-MIBG imaging for mortality outcomes. METHODS: Data from 964 New York Heart Association class II-III subjects in ADMIRE-HFX were included. All-cause mortality and a composite endpoint of death or death-equivalent events (resuscitated arrest, successful defibrillation for ventricular tachycardia or ventricular fibrillation) were analyzed with multivariate Cox proportional hazards and logistic regression techniques using demographic and clinical variables and the (123)I-MIBG heart-to-mediastinum ratio (H/M). The incremental value of H/M was also examined for the logistic regression models using receiver-operating-characteristic curve methods and for the proportional hazards models using net reclassification improvement. RESULTS: There were 101 deaths, and 136 subjects had a composite event during follow-up. H/M was significant in all multivariate proportional hazards and logistic regression models for the 2 mortality endpoints, both models developed with only clinical variables and those including left ventricular ejection fraction and b-type natriuretic peptide (BNP). For baseline models including BNP, the addition of H/M did not significantly increase receiver-operating-characteristic curve area. However, there was significant net reclassification improvement with the addition of H/M to a proportional hazards model containing BNP and left ventricular ejection fraction. CONCLUSION: The multivariate Cox proportional hazards and logistic regression analyses demonstrated consistent significance for H/M when added to the baseline risk models for mortality and mortality-equivalent events.

123I-MIBG SPECT for Evaluation of Patients with Heart Failure.

Heart failure (HF) is characterized by activation of the sympathetic cardiac nerves. The condition of cardiac sympathetic nerves can be evaluated by (123)I-metaiodobenzylguanidine ((123)I-MIBG) imaging. Most cardiac (123)I-MIBG studies have relied on measurements from anterior planar images of the chest. However, it has become progressively more common to include SPECT imaging in clinical and research protocols. This review examines recent trends in (123)I-MIBG SPECT imaging and evidence that provides the basis for the increased use of the procedure in the clinical management of patients with HF. (123)I-MIBG SPECT has been shown to be complementary to planar imaging in patients with HF in studies of coronary artery disease after an acute myocardial infarction. Moreover, (123)I-MIBG SPECT has been used in numerous studies to document regional denervation for arrhythmic event risk assessment. For better quantification of the size and severity of innervation abnormalities in (123)I-MIBG SPECT, programs and protocols specifically for (123)I have been developed. Also, the introduction of new solid-state cameras has created the potential for more rapid SPECT acquisitions or a reduction in radiopharmaceutical activity. Although PET imaging has superior quantitative capabilities, (123)I-MIBG SPECT is, for the foreseeable future, the only widely available nuclear imaging method for assessing regional myocardial sympathetic innervation.

Introduction to cardiac neuronal imaging: a clinical perspective.

Procedures for noninvasive and minimally invasive imaging of cardiac neurons and neuronal function using radiolabeled compounds were developed in the second half of the 20th century. The foundation for these procedures was several centuries of research that identified the structural components of the autonomic nervous system and explored the means by which neurotransmitters such as acetylcholine and norepinephrine contributed to neuronal control of target organ effector cells. This article provides a brief clinical overview of modern approaches to the assessment of cardiac neurons as an introduction to the in-depth articles on the current status of cardiac neuronal imaging presented in this supplement.

Impact of medications on mIBG uptake, with specific attention to the heart: Comprehensive review of the literature.

BACKGROUND: A critical review of the literature on drug interactions with mIBG uptake was performed to allow formulation of contemporary guidance regarding withholding medications prior to clinical imaging studies. METHODS: Published information was extracted on the experimental system used, the quantitative characteristics of the measurements, and whether any data directly examining cardiac tissues were included. Level of evidence for each medication category was assessed on a qualitative scale of very low, low, medium, or high. Strength of medication effect for inhibition of mIBG uptake was judged as none, weak, moderate, or strong. RESULTS: The only medications for which level of evidence was judged high were labetalol and reserpine. Level of evidence was judged medium for tricyclic antidepressants, calcium channel blockers, and antiarrhythmics (specifically amiodarone). Evidence was judged sufficient to recommend withholding labetalol and the tricyclic antidepressants prior to mIBG cardiac imaging. Mechanistic evidence was sufficient to suggest consideration of withdrawal of sympathomimetic amines and serotonin-norepinephrine reuptake inhibitors (SNRIs). CONCLUSIONS: As there is strong evidence for inhibition of mIBG uptake in only a small number of compounds, clinical decisions regarding withdrawal of concomitant medications should be individualized by considering the potential consequences of a false-positive (artificially low cardiac uptake) imaging result.

The utility of ADMIRE-HF risk score in predicting serious arrhythmic events in heart failure patients: incremental prognostic benefit of cardiac 123I-mIBG scintigraphy.

BACKGROUND: A minority of heart failure (HF) patients who undergo implantable cardioverter defibrillator (ICD) implantation for primary prevention of sudden cardiac death (SCD) receive device therapy. Whether the addition of mIBG scintigraphy to conventional markers of arrhythmic risk can provide incremental risk stratification in HF patients has not been investigated. METHODS: We identified 778 patients from the ADMIRE-HF study with LVEF < 35% and class II or III HF symptoms who did not have an ICD at the time of enrollment. Patients were followed up prospectively (median 5 17 months) for occurrence of arrhythmic events (ArE). Heart-to-mediastinum ratio (HMR) was determined as a measure of relative myocardial sympathetic nerve activity at baseline using 123I-mIBG. The primary endpoint was the first occurrence of ArE: a composite of SCD, appropriate ICD therapy, resuscitated cardiac arrest or sustained ventricular tachycardia. Multivariate regression was used to determine independent predictors of ArE and to derive a risk score for ArE prediction. The score was used to group patients according to their risk for ArE. Integrated discrimination improvement (IDI) was used to quantify improvement in risk assessment with addition of HMR. RESULTS: ArE occurred in 54 patients (6.9%). ArE predictors were:HMR < 1.6 (HR 3.5, 95%CI [1.52-8], P 5 .02), LVEF < 25% (HR 2.0, 95% CI [1.28-3.05], P 5 .04) and SBP < 120 (HR 1.2,95%CI [1.03-1.39], P 5 .02). Event rates in the low-, intermediate-, and high risk groups were 2, 10 and 16%, respectively (P 5 .001). The score significantly improved risk prediction(IDI 5 45%, P 0.03). CONCLUSION: 123I-mIBG significantly provides incremental risk stratification for ArE in HF patients.