Iodine-123 Metaiodobenzylguanidine Research Articles

Utility of Combining Transcranial Sonography and MIBG Myocardial Scintigraphy to Evaluate Substantia Nigra in Patients with Parkinson's Disease.

The utility of transcranial sonography (TCS) remains unclarified for the auxiliary diagnosis of Parkinson's disease (PD). We investigated iodine-123 metaiodobenzylguanidine (MIBG) and TCS during the examination and diagnosis of high-signal-intensity substantia nigra lesion (HSI-SNL) incidence in PD patients previously diagnosed with dopamine transporter scintigraphy (DAT). The subjects were 67 patients with definitively diagnosed PD after DAT evaluation. Patients with midbrain substantia nigra visible during TCS who previously underwent MIBG were analyzed. The SN+ group comprised patients with extensive pathological HSI-SNL of Okawa class III/IV observed during TCS. The MIBG+ group comprised patients with a heart-to-mediastinum ratio of ≤2.2 during MIBG. TCS was performed to divide patients into the SN+ and SN- groups, and patient characteristics and MIBG findings were compared between the groups. PD was definitively diagnosed in 67 patients, among whom midbrain was visualized during TCS in 43 (64.1%) patients and pathological HSI-SNL was observed in 24 (35.8%). The MIBG findings were normal in six patients (27.3%) with HSI-SNL, and abnormal in seven (63.6%) without HSI-SNL. No significant differences were noted by Okawa classification in clinical characteristics based on the presence or absence of HSI-SNL. Multiple patients with normal findings during MIBG may have HSI-SNL. Thus, confirmatory imaging of HSI-SNL with TCS may be useful for diagnosis.

Blood glucose level affects iodine-123 labeled MIBG uptake in the lung

The aim of this study was to evaluate the correlation of blood glucose and the metaiodobenzylguanidine (MIBG) uptake in lung and compare the difference between the lung uptake of MIBG in diabetic and non-diabetic patients. Patients who underwent iodine-123 MIBG whole-body scan (WBS) in the Department of Nuclear Medicine Seoul National University Hospital between January 2014 and July 2022 were recruited and analyzed. Semi-quantitative analysis of the mean value of lung-to-mediastinum ratio (LMR) was performed. Correlation was analyzed with Pearson correlation test and mean difference was analyzed with independent t-test. There were 36 patients in diabetic group and 57 patients in non-diabetic group with mean age of 56 ± 14.1 and 52 ± 14.6 years, respectively. The mean 24-h LMRs in diabetic and non-diabetic groups were 1.38 ± 0.20 and 1.17 ± 0.14, respectively. Fasting glucose showed a mean value of 136 ± 37.7 and 96 ± 8.2 mg/dL, respectively. There was a significant positive correlation in diabetic (r = 0.397; P = 0.016) and non-diabetic groups (r = 0.579; P <0.001) with significant mean difference (0.21; P <0.001). In conclusion, lung uptake of MIBG is positively correlated with blood sugar level, with diabetic patients displaying higher lung uptake of MIBG compared with non-diabetic patients. In addition, higher lung uptake of MIBG is evident in patients with higher fasting glucose level and even in non-diabetic patients. Thus, in the situations where MIBG therapy is required, the radiation dose to the lungs must be carefully adjusted for patients with high blood sugar level.

The prognostic impact of cardiac Metaiodobenzylguanidine imaging related to left ventricular geometry in patients with acute decompensated heart failure: a prospective study

Abstract Background It is known that changes in the geometry of the left ventricle (LV), such as dilation or hypertrophy, are associated with cardiovascular events. The sympathetic nervous system also plays a crucial role in exacerbating these changes. Cardiac iodine-123 metaiodobenzylguanidine (MIBG) imaging can evaluate cardiac sympathetic neuronal activity and has been strongly associated with poor clinical outcomes in heart failure (HF). However, the prognostic significance of cardiac MIBG imaging related to LV geometry is still unclear, particularly in patients admitted for acute decompensated HF (ADHF). Methods We studied consecutive 575 patients admitted for ADHF and echocardiography were performed just before discharge. In cardiac MIBG imaging, the heart-to-mediastinum ratio (HMR) was measured on the delayed image. We divided the patients into four groups according to the relative wall thickness (RWT) and LV mass index (LVMI) based on the ASE/EACVI classification as follows: normal (n=75), normal RWT and LVMI; concentric remodeling (n=56), high RWT and normal LVMI; eccentric hypertrophy (n=298), normal RWT and high LVMI; and concentric hypertrophy (n=146), high RWT and LVMI. The endpoint of this study was all cause death (ACD). Results During a follow-up period of 4.2 ± 2.5 years, 272 patients had ACDs (normal [n=32], concentric remodeling [n=28], eccentric hypertrophy [n=137] and concentric hypertrophy [n=75]). There was no significant association between LV geometry and ACDs. At univariate Cox analysis, late HMR was significantly and independently associated with ACDs in the subgroup of patients with eccentric hypertrophy (p=0.0004). However, there was no significant association between late HMR and ACDs in those with other subgroups of LV geometry. At multivariate Cox analysis, late HMR was also significantly associated with ACDs even after adjusting for major HF confounders in the subgroup of patients with eccentric hypertrophy (p=0.0042). Furthermore, Kaplan-Meier analysis revealed that patients with lower late HMR (<1.524: determined by ROC curve analysis) had a significantly higher risk of ACDs in the subgroup with eccentric hypertrophy (61% vs 37%, p<0.0001). Conclusions LV geometry has an impact on the prognostic value of cardiac MIBG imaging in patients admitted for ADHF.

Adrenal Incidentaloma With the Diagnosis of Normotensive Pheochromocytoma: A Case Report

Background: Pheochromocytomas (PCCs) are catecholamine-producing neuroendocrine tumors that originate from the adrenal medulla. Their clinical presentations most commonly include hypertension, headache, palpitations, and sweating; however, PCCs are sometimes normotensive and clinically silent. Case Presentation: A female patient with abdominal pain as well as persistent and crushing left flank pain for the past six months was examined. The imaging studies revealed a mass in the upper pole of the left kidney indicative of a potential adrenal gland tumor; however, she had normal blood pressure (BP). Histopathologic examination of the mass from exploratory laparotomy showed that it was a PCC. Findings from sonography and computed tomography (CT) scan of the left adrenal tumor, along with elevated urinary normetanephrine level and positive iodine-123 metaiodobenzylguanidine (MIBG) scan led to preoperative diagnosis of PCC in our case. Conclusion: This study highlighted the importance of imaging and biochemical testing in diagnosing PCCs in patients with adrenal incidentalomas (AIs), even though they were normotensive and entirely asymptomatic.

ODP549 From Positive to Negative, a Histidine to Aspartic Acid Change in SDHB is Breaking Bad in Cardiac Paraganglioma

Abstract Introduction Cardiac paraganglioma (PGL) are extremely rare tumors. They are derived from chromaffin cells of the neural crest. Up to 40% of PGL foster germline mutations, while some bear somatic mutations. Here, we describe a sympathetic paraganglioma presenting as a cardiac mass, found to have a novel mutation of SDHB. Clinical Case A 64-year-old man with uncontrolled type 2 diabetes mellitus presented with chest pain, progressive fatigue and unintentional weight loss. An echocardiogram demonstrated a right atrial mass. Cardiac magnetic resonance imaging showed a 6.9×5.8×4.9 cm mass in the lateral right atrial wall and right atrioventricular groove, encasing the right coronary artery. Surgical removal was attempted and aborted due to involvement of the tricuspid valve. Incisional biopsy was consistent with paraganglioma. Plasma free normetanephrine was elevated at 1.87 nmol/L (ULN 0.89 nmol/L) and plasma free metanephrine was normal at 0.14 nmol/L (ULN 0.49 nmol/L). Chromogranin A was elevated at 1,038 ng/mL (normal <93 ng/mL). Iodine-123 meta-iodobenzylguanidine scan demonstrated increased and persistent MIBG activity of the cardiac mass. Ga-68 DOTATATE PET/CT scan revealed DOTATATE avidity of the mass without evidence of distant metastatic disease. Next-generation sequencing of the specimen revealed a variant of unknown significance of SDHB H244D at a variant allele frequency of 62.2%. This missense mutation replaces the histidine to aspartic acid, resulting in changes in charge of the side chain from positive to negative. Systemic treatment with tyrosine kinase inhibitor (TKI) cabozantinib was initiated due to unresectable tumor. Three month surveillance with Ga-68 PET/CT DOTATATE scan revealed partial response to treatment. Chromogranin A and normetanephrine are trending down, suggesting biochemical response. Conclusion Cardiac PGL are rare and SDHB mutations are associated with worse prognosis. This is the first case of a missense mutation of SDHB at H244D, which may be clinically relevant in characterizing cardiac paraganglioma and potential response to TKI therapy. Presentation: No date and time listed

Ventricular Arrhythmia Substrate Distribution and Its Relation to Sympathetic Innervation in Nonischemic Cardiomyopathy Patients.

Nonischemic cardiomyopathy patients referred for catheter ablation of ventricular arrhythmias (VAs) typically have either inferolateral (ILS) or anteroseptal (ASS) VA substrate locations, with poorer outcomes for ASS. Sympathetic denervation is an important determinant of arrhythmogenicity. Its relation to nonischemic fibrosis in general and to the different VA substrates is unknown. This study sought to evaluate the association between VA substrates, myocardial fibrosis, and sympathetic denervation. Thirty-five patients from the Leiden Nonischemic Cardiomyopathy Study, who underwent electroanatomic voltage mapping and iodine-123 metaiodobenzylguanidine imaging between 2011 and 2018 were included. Late gadolinium-enhanced cardiac magnetic resonance data were collected when available. The relation between global cardiac sympathetic innervation and area-weighted unipolar voltage (UV) as a surrogate for diffuse fibrosis was evaluated. For regional analysis, patients were categorized as ASS or ILS. The distribution of low UV, sympathetic denervation, and late gadolinium enhancement (LGE) scar were compared using the 17-segment model. Median area-weighted UV was 12.3mV in patients with normal sympathetic innervation and 8.7mV in patients with sympathetic denervation. Global sympathetic denervation correlated with diffuse myocardial fibrosis (R=0.53; P=0.02). ILS (n=13) matched with low UV, sympathetic denervation, and LGE scar in all patients, whereas ASS (n=11) matched with low UV in all patients, with LGE scar in 63% (P=0.20), but with sympathetic denervation in only 27% of patients (P=0.0002). Global cardiac sympathetic denervation is related to fibrosis in nonischemic cardiomyopathy patients with VA. The mismatch between regional fibrosis and preserved innervation for ASS may contribute to a VA substrate difficult to control by catheter ablation.

Early-phase clinical trial eligibility and response evaluation criteria for refractory, relapsed, or progressive neuroblastoma: A consensus statement from the National Cancer Institute Clinical Trials Planning Meeting.

International standardized criteria for eligibility, evaluable disease sites, and disease response assessment in patients with refractory, progressive, or relapsed high-risk neuroblastoma enrolled in early-phase clinical trials are lacking. A National Cancer Institute-sponsored Clinical Trials Planning Meeting was convened to develop an international consensus to refine the tumor site eligibility criteria and evaluation of disease response for early-phase clinical trials in children with high-risk neuroblastoma. Standardized data collection of patient and disease characteristics (including specified genomic data), eligibility criteria, a definition of evaluable disease, and response evaluations for primary and metastatic sites of disease were developed. Eligibility included two distinct patient groups: progressive disease and refractory disease. The refractory disease group was subdivided into responding persistent disease and stable persistent disease to better capture the clinical heterogeneity of refractory neuroblastoma. Requirements for defining disease evaluable for a response assessment were provided; they included requirements for biopsy to confirm viable neuroblastoma and/or ganglioneuroblastoma in those patients with soft tissue or bone disease not avid for iodine-123 meta-iodobenzylguanidine. Standardized evaluations for response components and time intervals for response evaluations were established. The use of international consensus eligibility, evaluability, and response criteria for early-phase clinical studies will facilitate the collection of comparable data across international trials and promote more rapid identification of effective treatment regimens for high-risk neuroblastoma.

Complementary Role of Combined Indirect and Direct Cardiac Sympathetic (Hyper)Activity Assessment in Patients with Heart Failure by Spectral Analysis of Heart Rate Variability and Nuclear Imaging: Possible Application in the Evaluation of Exercise Training Effects.

In chronic heart failure (CHF), abnormalities in cardiac autonomic control, characterized by sympathetic overactivity, contribute to the progression of the disease and are associated with an unfavorable prognosis. Assessing cardiac autonomic status is clinically important in the management of patients with CHF. To this aim, heart rate variability (HRV) analysis has been extensively used as a non-invasive tool for assessing cardiac autonomic regulation, and has been shown to predict the clinical outcome in patients with CHF. Adrenergic nerve activity has also been estimated using iodine-123 (I-123) metaiodobenzylguanidine (MIBG), a noradrenaline analogue. MIBG is an analogue of norepinephrine sharing the same cellular mechanism of uptake, storage, and release in presynaptic sympathetic neurons. As an innervation tracer, 123I-MIBG allows for the evaluation of cardiac sympathetic neuronal function. Cardiac MIBG imaging has also been reported to predict a poor clinical outcome in CHF. MIBG provides direct information on the function of the presynaptic sympathetic nerve endings, whereas HRV, which depends on postsynaptic signal transduction, reflects the end-organ response of the sinus node. The aim of this brief review is to provide the reader with some basic concepts regarding the spectral analysis of HRV and MIBG, highlighting what is known about their respective roles in detecting cardiac sympathetic hyperactivity in CHF and, in perspective, their possible combined use in assessing non-pharmacological treatments in patients with CHF and reduced ejection fraction, with a particular focus on the effects of exercise training.

Sympathetic Reinnervation After Heart Transplantation Assessed by Iodine-123 Metaiodobenzylguanidine (123I-MIBG) Imaging and Heart Rate Response to Exercise

<h3>Purpose</h3> The extent of sympathetic reinnervation of transplanted hearts varies among recipients. The purpose of this study is to investigate the relation between the functional response of the left ventricular (LV) myocardium to adrenergic stimulation and the findings of [¹²³I]metaiodobenzylguanidine (MIBG) scintigraphy in cardiac transplant recipients. <h3>Methods</h3> MIBG scintigraphy was performed in 20 heart transplant recipients (mean of 7.6 years after transplantation) and in 20 age-matched individuals with hemodynamically stable (NYHA functional class I) dilated cardiomyopathy (DCM). Heart rate and blood pressure as well as the ECG during exercise- or dobutamine-induced stress tests were measured in all patients. All patients also underwent endomyocardial biopsy, and some of the biopsy specimens were subjected to mRNA analysis. LV isovolumic contraction (<i>dP/dt</i>_max) and relaxation (tau) were measured simultaneously during stress tests in six transplant recipients and five patients with DCM. <h3>Results</h3> MIBG uptake was virtually undetectable in transplant recipients, with the exception of one individual who showed evidence of reinnervation in the anteroseptal region. The heart-to-mediastinum ratio was significantly smaller in transplant recipients than in patients with DCM (1.32 ± 0.6. vs. 2.22 ± 0.3, <i>p</i> < 0.0001). The change in <i>dP/dt</i>_max at peak heart rate during stress tests did not differ significantly between the two groups (83 ± 26 vs. 93 ± 20%, <i>p</i> = 0.335), whereas that in tau was smaller in transplant recipients than in DCM patients (31 ± 8 vs. 42 ± 9%, <i>p</i> < 0.05). RT-PCR analysis revealed that the amount of β-adrenergic receptor kinase-1 mRNA in the ventricular myocardium tended to be smaller in recipients who showed an attenuated response in stress tests than in those with a good response <h3>Conclusion</h3> LV contractility during adrenergic stimulation by dobutamine or exercise was preserved, whereas LV relaxation was attenuated, in transplant recipients. The discrepancy between the responses of LV myocardial contractility and relaxation to adrenergic stimulation and MIBG scintigraphic findings may provide insight into the reinnervation of transplanted hearts.

Usefulness of the 2-year iodine-123 metaiodobenzylguanidine-based risk model for post-discharge risk stratification of patients with acute decompensated heart failure.

A four-parameter risk model that included cardiac iodine-123 metaiodobenzylguanidine (MIBG) imaging and readily available clinical parameters was recently developed for prediction of 2-year cardiac mortality risk in patients with chronic heart failure. We sought to validate the ability of this risk model to predict post-discharge clinical outcomes in patients with acute decompensated heart failure (ADHF) and to compare its prognostic value with that of the Acute Decompensated Heart Failure National Registry (ADHERE) and Get With The Guidelines-Heart Failure (GWTG-HF) risk scores. We studied 407 consecutive patients who were admitted for ADHF and survived to discharge, with definitive 2-year outcomes (death or survival). Cardiac MIBG imaging was performed just before discharge. The 2-year cardiac mortality risk was calculated using four parameters, namely age, left ventricular ejection fraction, New York Heart Association functional class, and cardiac MIBG heart-to-mediastinum ratio on delayed images. Patients were stratified into three groups based on the 2-year cardiac mortality risk: low- (< 4%), intermediate- (4-12%), and high-risk (> 12%) groups. The ADHERE and GWTG-HF risk scores were also calculated. There was a significant difference in the incidence of cardiac death among the three groups stratified using the 2-year cardiac mortality risk model (p < 0.0001). The 2-year cardiac mortality risk model had a higher C-statistic (0.732) for the prediction of cardiac mortality than the ADHERE and GWTG-HF risk scores. The 2-year MIBG-based cardiac mortality risk model is useful for predicting post-discharge clinical outcomes in patients with ADHF. UMIN000015246, 25 September 2014.

The utility of heart-to-mediastinum ratio using a planar image created from IQ-SPECT with Iodine-123 meta-iodobenzylguanidine

Aims123I-labeled meta-iodobenzylguanidine (MIBG) has used a planar image to measure the heart-to-mediastinum ratio (HMR). However, planar images are not available from IQ-SPECT with SMARTZOOM collimator due to its multi-focal collimation. Since we created the planar-equivalent (IQ-planar) images by adding all slices of the IQ-SPECT coronal image. The aim of this study was to demonstrate the utility of the new method for calculating HMR. MethodsThe planar image and transverse images of IQ-SPECT with attenuation and scatter corrections (ACSC) and without ACSC (NC) were obtained. Multi-planar reconstruction and ray-summation processing were applied to create IQ-planar images with NC and ACSC. Linear regression between the measured HMR from the planar image and the mathematically calculated HMR was used to calibrate HMR to standardized values. ResultsScatterplots and linear regression lines between planar and IQ-planar HMRs before and after cross-calibration showed systematic differences in both NC and ACSC conditions. The IQ-planar HMR with NC and ACSC was significantly higher compared with that of the conventional planar image. However, the IQ-planar HMR with NC and ACSC after cross-calibration was similar to the standardized HMR calculated by planar image. ConclusionThe IQ-planar HMR using the new ray-summation processing method could be used along with the conventional planar HMR.

Endovascular renal sympathetic denervation to improve heart failure with reduced ejection fraction: the IMPROVE-HF-I study.

IntroductionThe aim of the present study was to assess the safety and efficacy of renal sympathetic denervation (RDN) in patients with heart failure with reduced ejection fraction (HFrEF).MethodsWe randomly assigned 50 patients with a left ventricular ejection fraction (LVEF) ≤ 35% and NYHA class ≥ II, in a 1:1 ratio, to either RDN and optimal medical therapy (OMT) or OMT alone. The primary safety endpoint was the occurrence of a combined endpoint of cardiovascular death, rehospitalisation for heart failure, and acute kidney injury at 6 months. The primary efficacy endpoint was the change in iodine-123 meta-iodobenzylguanidine (123I‑MIBG) heart-to-mediastinum ratio (HMR) at 6 months.ResultsMean age was 60 ± 9 years, 86% was male and mean LVEF was 33 ± 8%. At 6 months, the primary safety endpoint occurred in 8.3% vs 8.0% in the RDN and OMT groups, respectively (p = 0.97). At 6 months, the mean change in late HMR was −0.02 (95% CI: −0.08 to 0.12) in the RDN group, versus −0.02 (95% CI: −0.09 to 0.12) in the OMT group (p = 0.95) whereas the mean change in washout rate was 2.34 (95% CI: −6.35 to 1.67) in the RDN group versus −2.59 (95% CI: −1.61 to 6.79) in the OMT group (p-value 0.09).ConclusionRDN with the Vessix system in patients with HFrEF was safe, but did not result in significant changes in cardiac sympathetic nerve activity at 6 months as measured using 123I‑MIBG.Supplementary InformationThe online version of this article (10.1007/s12471-021-01633-z) contains supplementary material, which is available to authorized users.

Giant Adrenal Pheochromocytoma Presenting With Stroke

Background: Pheochromocytomas and paragangliomas (PPGLs) are rare neuroendocrine tumours arising from the adrenal medulla or from paravertebral ganglia of the sympathetic chain(1). The tumours commonly produce one or more catecholamines: epinephrine, norepinephrine, and dopamine leading to a classic triad of presentation with pounding headache, profuse sweating, and palpitations occurs in spells; However, one in 10 patients may be completely asymptomatic and the diagnosis of PPGL is frequently missed(2). Care Report: A 29 years old African female presented with one-month history of throbbing headache, palpitations, profuse sweating, and unintentional weight loss. Her previous medical history and family history was unremarkable. She was found to have accelerated hypertension and a small lacunar infarct and some suspected subarachnoid hemorrhage on MRI head but was clinically silent. Investigation for secondary causes of hypertension revealed high metanephrine in urine and her imaging showed giant adrenal mass suggestive of pheochromocytoma.CT Abdomen of large left adrenal necrotic solid mass lesion with heterogenous enhancement of its solid components measuring 6.5 x 6.1 x 7 cm in maximum AP, TR and CC dimensions respectively.She was scheduled for open resection and left adrenalectomy after approximatly10 day and was treated with high-sodium diet, alpha blockers, and beta blockers perioperatively. Histopathology examination revealed Pheochromocytoma measuring 8 x 7 x 5 cm with diffuse growth >10% of tumor volume with central necrosis; PASS =4, which has malignant potential. She recovered well post operatively and required no further antihypertensive therapy or hormonal replacement, follow up hormonal profile and imaging with Iodine-123 metaiodobenzylguanidine (MIBG) scintigraphy were negative for remnants or metastasis,further evaluation with gallium DOTATATE PET CT and molecular genetic testing was considered, but it was not available. Conclusion: Pheochromocytoma is a rare cause of secondary hypertension with a variable clinical presentation. Episodes of tumoral catecholamine release, are thought to be responsible for the high prevalence of cardiovascular emergencies, such as myocardial infarction, heart failure, and stroke as a complication of hypertensive crisis. Timely diagnosis and treatment are crucial to prevent life-threatening complications.

Incremental prognostic value of cardiac metaiodobenzylguanidine imaging over the co‐morbid burden in acute decompensated heart failure

AimsCo‐morbidities are associated with poor clinical outcomes in patients with chronic heart failure, while cardiac iodine‐123 (I‐123) metaiodobenzylguanidine (MIBG) imaging provides prognostic information in such patients. We sought to prospectively investigate the incremental prognostic value of cardiac MIBG imaging over the co‐morbid burden, in patients admitted for acute decompensated heart failure (ADHF).Methods and resultsIn 433 consecutive ADHF patients with survival to discharge, we measured the co‐morbidity using age‐adjusted Charlson co‐morbidity index (ACCI), commonly employed to evaluate a weighted and scored co‐morbid condition, adding additional points for age. In cardiac MIBG imaging, the cardiac MIBG heart‐to‐mediastinum ratio (late HMR) was measured on the delayed image. Over a follow‐up period of 2.9 ± 1.5 years, 160 patients had a cardiac event (a composite of cardiac death and unplanned hospitalization for worsening heart failure). Patients with high ACCI (≥6: median value) had a significantly greater risk of a cardiac event. In multivariate Cox analysis, the ACCI and late HMR were significantly and independently associated with a cardiac event. In both high and low ACCI subgroups (ACCI ≥ 6 and <6, respectively), patients with low late HMR had a significantly greater risk of a cardiac event (high ACCI: 51% vs. 34% P = 0.0026, adjusted HR 1.74 [1.21–2.51]; low ACCI: 34% vs. 17%, P = 0.0228, adjusted HR 2.19 [1.10–4.37]).ConclusionsCardiac MIBG imaging could provide additional prognostic information over ACCI, which was also promoted to be a useful risk model, in patients admitted for ADHF.

Abstract 13677: Usefulness of 2-year Iodine-123 Metaiodobenzylguanidine-based Risk Model for the Post-discharge Risk Stratification in Acute Decompensated Heart Failure Patients With Preserved Left Ventricular Ejection Fraction

Background: A four-parameter risk model including cardiac iodine-123 metaiodobenzylguanidine (MIBG) imaging and readily available clinical parameters has been recently developed for the prediction of 2-year cardiac mortality risk in patients with chronic heart failure (CHF) using a Japanese CHF database consisting of 1322 patients. However, there is no information available on the usefulness of 2-year MIBG-based cardiac mortality risk score for the prediction of post-discharge prognosis in patients with heart failure with preserved LVEF (HFpEF) who are admitted with acute decompensated heart failure (ADHF). Methods and Results: Patients' data were extracted from The Prospective mUlticenteR obServational stUdy of patIenTs with Heart Failure with Preserved Ejection Fraction (PURSUIT-HFpEF) study, which is a prospective multicenter observational registry for ADHF patients with LVEF ≥50% in Osaka. We studied 239 patients who survived to discharge. Cardiac MIBG imaging was performed just before discharge. The 2-year cardiac mortality risk score was calculated using four parameters, including age, LVEF, NYHA functional class, and the cardiac MIBG heart-to-mediastinum ratio on delayed image. The patients were stratified into three groups based on the 2-year cardiac mortality risk score: low- (&lt;4%), intermediate- (4-12%), and high-risk (&gt;12%) groups. The endpoint was all-cause death. During a follow-up period of 1.6±0.8 years, 33 patients had all-cause death. Multivariate Cox analysis showed that 2-year MIBG-based cardiac mortality risk score was an independent predictor of all-cause death (p=0.0009). There was significant difference in the rate of all-cause death among the three groups stratified by 2-year cardiac mortality risk score (Figure). Conclusions: In this multicenter study, the 2-year MIBG-based cardiac mortality risk score was shown to be useful for the prediction of post-discharge clinical outcome in HFpEF patients admitted for ADHF.

Renal 123I-MIBG Uptake before and after Live-Donor Kidney Transplantation.

Increased sympathetic activity is suggested to be part of the pathogenesis in several diseases. Methods to evaluate sympathetic activity and renal nervous denervation procedural success are lacking. Scintigraphy using the norepinephrine analog Iodine-123 Metaiodobenzylguanidine (123I-MIBG) might provide information on renal sympathetic nervous activity. Renal transplantation induces complete denervation of the kidney and as such represents an ideal model to evaluate the renal 123I-MIBG scintigraphy method. The aim of this study was to evaluate whether renal 123I-MIBG scintigraphy can detect changes in renal sympathetic nervous activity following renal transplantation. Renal 123I-MIBG scintigraphy was performed in eleven renal transplant recipients at 1, 3, and 6 months following transplantation and in their respective living donors prior to their kidney donation. Relative uptake as well as washout was obtained. In transplanted patients, the relative 4 h uptake of 123I-MIBG, as measured by the kidney/background ratio, was 2.7 (0.4) (mean (SD)), 2.7 (0.5), and 2.5 (0.4) at 1, 3, and 6 months post-transplantation, respectively, as compared with the 4.0 (0.4) value in the donor kidney before donor nephrectomy (p < 0.01). There was no significant change in washout-rate between pre-transplantation and any of the follow-up time points. Living donor kidney transplantation was at 6 months post transplantation, associated with an almost 40% reduction in the relative 4 h 123I-MIBG uptake of the kidney. Further studies will help to fully establish its implications as a marker of renal innervation or denervation.

Incremental prognostic value of myocardial neuroadrenergic damage in patients with chronic congestive heart failure: An iodine-123 meta-iodobenzylguanidine scintigraphy study

BackgroundICD in primary prevention reduced mortality in patients with heart failure (HF); however, in about 80% of the ICD recipients an event requiring a device intervention will never occur. Thus, a reliable screening test included in a multiparametric approach to appropriately select patients to ICD implantation is increasingly required. Aim of the work was to assess if the Iodine-123 Meta-Iodobenzylguanidine scintigraphy (123I-mIBG) could be useful to identify patients with HF who would not benefit from the ICD implantation because at low risk of arrhythmias. Methods and resultsThis is a retrospective multicentre study on patients undergoing 123I-mIBG from February 2012 to December 2015. Inclusion criteria where: age ≥ 18 years old, LVEF ≤ 35% with idiopathic or ischemic heart disease, no previous malignant ventricular arrhythmias. Patients were divided in two groups based on of late H/M < or ≥ 1.60 on 123I-mIBG. Primary end-point was occurrence of malignant arrhythmias. Secondary end-point was occurrence of cardiac death and hospitalization for worsening HF. MACE were mortality and malignant arrhythmias. Eighty-one patients were enrolled (mean age: 69 years). On 123I-mIBG, 54 patients had late H/M < 1.6 and 27 patients had late H/M ≥ 1.60. After a mean follow-up of 13.3 (± 9.7) months, the primary end-point occurred in 13 patients out of 81. No arrhythmias occurred in patients with H/M late ≥ 1.6. Nineteen patients out of 20 with MACE showed an H/M late < 1.6. Death in group with H/M ≥ 1.6 occurred for worsening HF. A late H/M ≥ 1.60 showed a very high NPV for arrhythmia (100%) and for death (96.3%). Conclusion123I-mIBG imaging has the capability to identify patients at low risk of events.

Impact of adjunctive tolvaptan on sympathetic activity in acute heart failure with preserved ejection fraction

AimsAcute decompensated heart failure (ADHF) is generally treated by decongestion using diuretic therapy. However, the use of loop diuretics is associated with increased cardiac sympathetic nerve activity (CSNA). We aimed to evaluate the effect of adjunctive tolvaptan therapy on CSNA in ADHF patients with preserved left ventricular ejection fraction (LVEF).Methods and resultsWe enrolled 51 consecutive ADHF patients with LVEF ≥45%. Patients were randomly assigned to receive either tolvaptan add‐on (n = 25) or conventional diuretic therapy (n = 26). Cardiac iodine‐123 metaiodobenzylguanidine (MIBG) imaging was performed after stabilisation of heart failure symptoms, and the cardiac MIBG heart‐to‐mediastinum ratio (HMR) and washout rate (WR) were calculated. There were no significant differences in the body weight change and total urine volume during 2 days after randomisation or in the HMR on delayed image (HMR(d)) and WR between the tolvaptan and conventional groups. After stratification based on the median change in body weight, the patients with higher weight reduction had a significantly lower HMR(d) (P = 0.0128) and tended to have a higher WR (P = 0.0786) in the conventional group, whereas the cardiac MIBG imaging results were not influenced by body weight reduction in the tolvaptan group.ConclusionsAdjunctive tolvaptan therapy may provide rapid decongestion without a harmful effect on CSNA in ADHF patients with preserved LVEF.

MULTIMODALITY IMAGING IN IMPLANTABLE CARDIOVERTER DEFIBRILLATOR IMPLANTATION DECISION MAKING IN HEART FAILURE PATIENTS: ROLE OF 123-IODINE METAIODOBENZYLGUANITIDINE IMAGING AND CARDIAC MAGNETIC RESONANCE

Guidelines for ICD implantation have limitations as implant indication is mainly based on LVEF.CMR and more recently 123-iodine metaiodobenzylguanidine imaging(MIBG)seems to identify patients(pts) at high risk of sudden cardiac death. The aim was to assess the impact of MIBG alone and combined with

Impact of body mass index on cardiac adrenergic derangement in heart failure patients: a 123I-mIBG imaging study.

To assess the impact of body mass index (BMI) on cardiac adrenergic derangement, measured by iodine-123 meta-iodobenzylguanidine (123I-mIBG) imaging in heart failure (HF) patients. Overweight and obesity represent relevant health issues, and augmented sympathetic tone has been described in patients with increased BMI. An extensive literature supports that HF-dependent cardiac denervation, measured through mIBG parameters, is an independent predictor of cardiovascular outcomes and mortality. However, the influence of BMI on cardiac mIBG uptake has not been largely investigated. We prospectively enrolled patients with systolic HF, collecting demographic, clinical, echocardiographic data, and mIBG imaging parameters. In order to detect the factors associated with mIBG parameters, a model building strategy, based on the Multivariable Fractional Polynomial algorithm, has been employed. We studied 249 patients with systolic HF, mean age of 66.4 ± 10.6years, and mean left ventricular ejection fraction (LVEF) of 30.7% ± 6.4, undergoing cardiac 123I-mIBG imaging to assess HF severity and prognosis. Seventy-eight patients (31.3%) presented a BMI ≥ 30kg/m2 and obese patients showed a significant reduction in early heart to mediastinum (H/M) ratio (1.66 ± 0.19 vs. 1.75 ± 0.26; p = 0.008) and a trend to reduction in washout rate (33.6 ± 18.3 vs. 38.1 ± 20.1; p= 0.092) compared with patients with BMI < 30kg/m2. Multiple regression analysis revealed that BMI, age, and LVEF were significantly correlated with early and late H/M ratios. Results of the present study indicate that BMI, together with LVEF and age, is independently correlated with cardiac mIBG uptake in HF patients.