Efficacy of [177Lu]Lu-DOTATATE in metastatic neuroendocrine neoplasms of different locations: data from the SEPTRALU study.

BACKGROUND: Peptide receptor radionuclide therapy (PRRT) is one of the most promising therapeutic strategies in neuroendocrine neoplasms (NENs). Nevertheless, its role in certain tumor sites remains unclear. This study sought to elucidate the efficacy and safety of [177Lu]Lu-DOTATATE in NENs with different locations and evaluate the effect of the tumor origin, bearing in mind other prognostic variables. Advanced NENs overexpressing somatostatin receptors (SSTRs) on functional imaging, of any grade or location, treated at 24 centers were enrolled. The protocol consisted of four cycles of 177Lu-DOTATATE 7.4 GBq iv every 8 weeks (NCT04949282). RESULTS: The sample comprised 522 subjects with pancreatic (35%), midgut (28%), bronchopulmonary (11%), pheochromocytoma/ paraganglioma (PPGL) (6%), other gastroenteropancreatic (GEP) (11%), and other non-gastroenteropancreatic (NGEP) (9%) NENs. The best RECIST 1.1 responses were complete response, 0.7%; partial response, 33.2%; stable disease, 52.1%; and tumor progression, 14%, with activity conditioned by the tumor subtype, but with benefit in all strata. Median progression-free survival (PFS) was 31.3 months (95% CI, 25.7-not reached [NR]) in midgut, 30.6 months (14.4-NR) in PPGL, 24.3 months (18.0-NR) in other GEP, 20.5 months (11.8-NR) in other NGEP, 19.8 months (16.8-28.1) in pancreatic, and 17.6 months (14.4-33.1) in bronchopulmonary NENs. [177Lu]Lu-DOTATATE exhibited scant severe toxicity. CONCLUSION: This study confirms the efficacy and safety of [177Lu]Lu-DOTATATE in a wide range of SSTR-expressing NENs, regardless of location, with clinical benefit and superimposable survival outcomes between pNENs and other GEP and NGEP tumor subtypes different from midgut NENs.

Audiovisual intervention alleviates anxiety of patients during PET/CT imaging.

AIM: to assess if the use of an audiovisual intervention in the uptake room and/or in the scanning room, could help to reduce anxiety during [18F]FDG PET/CT imaging. METHODS: We prospectively studied 120 patients referred for [18F]FDG PET/CT imaging. Patients were allocated in 4 groups of 30 patients depending on the use of the audiovisual intervention: (1) no audiovisual intervention; (2) audiovisual intervention only in the uptake room; (3) audiovisual intervention only in the scanning room; (4) audiovisual intervention in the uptake and the scanning rooms. In order to measure the anxiety levels of the patients before and after the scan, all patients answered the State-Trait Anxiety Inventory (STAI). RESULTS: The anxiety status across typical situations on a daily basis (STAI-T) of the 4 groups of patients was comparable with no significant differences. The mean State Anxiety (STAI-S) sum-score at prescan and postscan among groups was: (1) 17.5±8.7 vs. 17.3±8.6, p=0.834; (2) 17.4±10.5 vs. 15.8±9.6, p=0.110; (3) 17.5±11.7 vs. 15.1±9.8, p= 0.013; (4) 17.4±9.7 vs. 14.9±8.1, p= 0.009. The percentage of patients with reduction of the STAI-S score among groups 1-4 was 17%, 47%, 50%, and 66%, respectively. The variation of the percentage of patients with lower scores after intervention among groups was statistically significant (p<0.001). CONCLUSION: Audiovisual intervention decreases anxiety levels of patients referred for PET/CT imaging. The results of our study support a beneficial effect of the audiovisual intervention and its potential to alleviate the anxiety of oncological patients who undergo a PET/CT scan.

Brain metabolic changes in patients with disseminated malignant melanoma under immunotherapy.

Although there is evidence that chemotherapy can have side effects on metabolism and brain function, there are few studies on the occurrence of these side effects with immunotherapy. The present study was conducted to assess whether brain metabolic changes occur in patients with malignant melanoma under immunotherapy. Thirty-nine patients after surgical intervention and with a diagnosis of malignant melanoma were retrospectively included and were divided into two groups: one group under the first-line therapy with anti-programmed cell death-1 ± anti-cytotoxic T lymphocyte antigen-4 monoclonal antibodies and the other group without any treatment after surgery, which served as a control. Basal and follow-up whole body and brain 2-[ 18 F]fluoro-2-deoxy-D-glucose ( 18 F]FDG) PET/computed tomography (CT) studies were performed. Changes in brain glucose metabolism after treatment initiation of the immunotherapy group were compared with the findings in the control group. In addition, longitudinal regression analysis to investigate whether the time under immunotherapy influenced the changes of brain metabolism was performed. None of the patients presented cognitive impairment or other neurological alterations between basal and follow-up brain [ 18 F]FDG PET/CT examinations. The statistical analysis revealed a significant relative SUV (SUVr)-loss in the left frontal region in patients of the immunotherapy group compared with the control group, with radjusted = -0.62 and P = 0.008. Severity of SUVr-loss was correlated with duration of treatment. Patients with disseminated malignant melanoma receiving immunotherapy may present a decrease of brain metabolism in the left frontal region, which is related with time-under-treatment, without any clinical evidence of neurological disorder.

Digital versus analog PET/CT in patients with known or suspected liver metastases.

AIM: To assess if digital PET/CT improves liver lesion detectability compared to analog PET/CT in patients with known or suspected liver metastases. MATERIALS AND METHODS: We prospectively included 83 cancer patients, with one or more of these conditions: history of liver metastases, clinical risk of having liver metastases or presence of suspected liver metastases on the first of the two PET/CTs. All patients were consecutively scanned on each PET/CT on the same day after a single [18F]fluorodeoxyglucose dose injection. The order of acquisition was randomly assigned. Three nuclear medicine physicians assessed both PET/CTs by counting the foci of high uptake suspicious of liver metastases. Findings were correlated with appropriate reference standards; 19 patients were excluded from the analysis due to insufficient lesion nature confirmation. The final sample consisted of 64 patients (34 women, mean age 68 ± 12 years). RESULTS: As per-patient analysis, the mean number of liver lesions detected by the digital PET/CT (3.84 ± 4.25) was significantly higher than that detected by the analog PET/CT (2.91 ± 3.31); P < 0.001. Fifty-five patients had a positive PET/CT study for liver lesions. In 26/55 patients (47%), the digital PET/CT detected more lesions; 7/26 patients (27%) had detectable lesions only by the digital system and had <10 mm of diameter. Twenty-nine patients had the same number of liver lesions detected by both systems. In nine patients both PET/CT systems were negative for liver lesions. CONCLUSION: Digital PET/CT offers improved detectability of liver lesions over the analog PET/CT in patients with known or suspected liver metastases.

Future Challenges of Multimodality Imaging.

During the last decade, positron emission tomography/computed tomography (PET/CT) and single-photon emission computed tomography/computed tomography (SPECT/CT) have procured advances in research and clinical application of fusion imaging. The recent introduction of digital PET/CT opens new horizons for multimodality molecular imaging. This system offers more precise, simultaneous morphologic, functional, and molecular information of a living system. Moreover, other combinations of anatomic and functional imaging modalities hold promise in basic medical research or in clinical medicine. These developments are paralleled by advances in the field of biomolecules and particles that will provide new agents useful for more than one imaging modality and will facilitate the study of the same target by different imaging devices. Digital PET/CT may emerge as a powerful multimodality technique with great clinical impact on the diagnosis and therapy assessment of oncological diseases due to its enhanced sensitivity.

Correction to: Superior performance of 18F-fluorocholine digital PET/CT in the detection of parathyroid adenomas.

The correct administered activity of 18F-FCH is 0.1-0.14 mCi/Kg, which is equivalent to 3.7-5.2 MBq/kg.

Superior performance of 18F-fluorocholine digital PET/CT in the detection of parathyroid adenomas.

OBJECTIVE: To compare detectability of hyperfunctioning parathyroid tissue (HPT) by digital and analog 18F-fluorocholine PET/CT in patients with primary hyperparathyroidism and negative/inconclusive 99mTc-MIBI scintigraphy-SPECT/CT. MATERIALS AND METHODS: Thirty-three patients with primary hyperparathyroidism and negative/inconclusive 99mTc-MIBI scintigraphy-SPECT/CT were prospectively included. All patients accepted to be scanned by digital and analog PET/CT in the same imaging session after a single injection of 18F-fluorocholine. Three nuclear medicine physicians evaluated the digital and analog PET/CT datasets to assess the detection rate of HPT. Maximum standard uptake values (SUVmax) of HPT and locoregional lymph nodes were measured in both systems. RESULTS: HPT was detected in 30/33 patients by the digital system, whereas it was detected in 22/33 patients by the analog system (p < 0.01). Moreover, in 21 of these 33 patients, both systems detected one focal 18F-fluorocholine uptake, and in one patient the digital system detected two foci. Histopathology demonstrated HPT in 32 patients and it was inconclusive in one patient. The digital PET/CT detected HPT in 29 of the 32 patients, and the analog system in 22 of the 32 (p < 0.01). All HPT suspected lesions resected and detected only by the digital system (n = 8) were < 10 mm (7.5 ± 1.3 mm), while those detected by both systems (n = 22) were > 10 mm (13 ± 3.8 mm). SUVmax of HPT lesions was significantly higher than SUVmax of locoregional lymph node independently of the PET/CT system used (4.5 ± 1.9 vs. 2.9 ± 1.3, p < 0.0001). CONCLUSIONS: Digital PET/CT offers superior performance over analog system in patients with suspected HPT and previous negative/inconclusive imaging examinations, particularly in sub-centimeter lesions. SUVmax can help in the differentiation between HTP and locoregional lymph nodes.

Correction to: Digital vs. analog PET/CT: intra-subject comparison of the SUVmax in target lesions and reference regions.

The article Digital vs. analog PET/CT: intra-subject comparison of the SUVmax in target lesions and reference regions, written by Francisco Fuentes-Ocampo, Diego Alfonso López-Mora, Albert Flotats, Gabriela Paillahueque.

Comparison of image quality and lesion detection between digital and analog PET/CT.

OBJECTIVE: The purpose of this study was to compare image quality and lesion detection capability between a digital and an analog PET/CT system in oncological patients. MATERIALS AND METHODS: One hundred oncological patients (62 men, 38 women; mean age of 65 ± 12 years) were prospectively included from January-June 2018. All patients, who accepted to be scanned by two systems, consecutively underwent a single day, dual imaging protocol (digital and analog PET/CT). Three nuclear medicine physicians evaluated image quality using a 4-point scale (-1, poor; 0, fair; 1, good; 2, excellent) and detection capability by counting the number of lesions with increased radiotracer uptake. Differences were considered significant for a p value <0.05. RESULTS: Improved image quality in the digital over the analog system was observed in 54% of the patients (p = 0.05, 95% CI, 44.2-63.5). The percentage of interrater concordance in lesion detection capability between the digital and analog systems was 97%, with an interrater measure agreement of κ = 0.901 (p < 0.0001). Although there was no significant difference in the total number of lesions detected by the two systems (digital: 5.03 ± 10.6 vs. analog: 4.53 ± 10.29; p = 0.7), the digital system detected more lesions in 22 of 83 of PET+ patients (26.5%) (p = 0.05, 95% CI, 17.9-36.7). In these 22 patients, all lesions detected by the digital PET/CT (and not by the analog PET/CT) were < 10 mm. CONCLUSION: Digital PET/CT offers improved image quality and lesion detection capability over the analog PET/CT in oncological patients, and even better for sub-centimeter lesions.

Digital vs. analog PET/CT: intra-subject comparison of the SUVmax in target lesions and reference regions.

PURPOSE: The purpose of this study was to assess whether digital photon counting technology in digital PET/CT influences the quantification of SUVmax in target lesions and regions of reference compared to analog PET/CT before an interchangeable use of either system in follow up studies. METHODS: From January to June of 2018, 100 oncological patients underwent successive PET/CT imaging with digital and analog systems in the same day. Fifty-eight patients underwent analog imaging first and digital imaging thereafter, and 42 patients the other way round. SUVmax was measured in reference regions (liver and mediastinal blood pool) and in the most metabolically active target lesion in each patient. According to the sequence order of PET/CT acquisition, two groups of SUVmax values were obtained, i.e. group 1: analog PET/CT performed first; group 2: digital PET/CT performed first. RESULTS: Mean SUVmax in the total sample (regardless of the order of PET/CT acquisition) in the target lesions with the analog PET/CT was 8.14 ± 6.39 and the digital 9.97 ± 6.14 (P = 0.000). Total mean SUVmax in the liver with the analog was 4.39 ± 2.59 and the digital 4.46 ± 3.18 (P = 0.477). Total mean SUVmax in the mediastinal blood pool with the analog was 2.30 ± 0.67 and the digital 2.54 ± 0.74 (P = 0.000). Group 1: mean SUVmax in the target lesions with the analog system was 6.64 ± 4.71 and the digital 9.48 ± 5.60 (P = 0.000). Mean liver SUVmax with the analog was 4.70 ± 2.90 and the digital 4.80 ± 3.72 (P = 0.088). Mediastinal blood pool SUVmax with the analog was 2.33 ± 0.66 and the digital 2.45 ± 0.73 (P = 0.041). Group 2: mean SUVmax in target lesions with the digital system was 10.63 ± 6.88 and the analog 10.16 ± 7.76 (P = 0.046). Mean liver SUVmax with the digital was 3.99 ± 2.20 and the analog 3.96 ± 2.04 (P = 0.218). Mediastinal blood pool SUVmax with the digital was 2.66 ± 0.75 and the analog 2.27 ± 0.68 (P = 0.000). No significant differences between both time delays were found. CONCLUSIONS: Improved photon counting technology in the digital PET/CT, and the effect of delayed increased uptake and retention significantly increases SUVmax values. This has to be taken into account before interchangeable use of either system in follow up studies.

Selection of Reference Regions to Model Neurodegeneration in Huntington Disease by 18F-FDG PET/CT Using Imaging and Clinical Parameters.

OBJECTIVE: Normalization to an appropriate reference region in F-FDG PET imaging may enhance diagnostic performance in Huntington disease (HD). We aimed to identify stable brain areas that could be used to model neurometabolic degeneration in HD correlating imaging (SUVrvalues at the basal ganglia [BBGG]) and clinical parameters (disease burden score [DBS]). MATERIALS AND METHODS: We performed brain F-FDG PET/CT in 38 manifest HD patients (meanage ± SD, 54 ± 14.3 years; CAGrepeats ± SD, 44.2 ± 3.1), 20 premanifest HD patients (meanage ± SD, 42.7 ± 11.7 years; CAGrepeats ± SD, 40 ± 3.8), and 18 healthy controls (NC; meanage ± SD, 45 ± 13.2 years). For quantitative analysis, we selected (a) defined reference regions from the Montreal Neurological Institute space atlas (pons, whole cerebellum, cerebral white matter, thalamus, and a pons-cerebellar vermis region of interest), and (b) reference clusters obtained by voxelwise statistical comparison across groups (P < 0.05 FWE; extent voxel threshold k = 200). Each candidate reference region and reference cluster was quantitatively assessed using imaging and clinical parameters. RESULTS: Comparing HD and NC groups, we obtained a reference cluster in the cerebellum, and in temporal and frontal lobes. Comparing manifest HD and premanifest HD patients, we observed reference clusters in the cerebellum, pons, thalamus, parietal lobe, and cuneus. The set of reference regions showed a significant correlation between SUVrvalues at the BBGG and DBS in all HD patients. In premanifest HD patients, the correlation between SUVrvalues at the BBGG and DBS was significant using the pons-cerebellar vermis region of interest, the thalamus as defined reference regions, and the pons and thalamus as reference clusters. In manifest HD patients, the correlation was significant using the temporal and white matter frontal lobe clusters. Variance between SUVrvalues in the set of reference regions and reference clusters was minimal within NC. CONCLUSIONS: The pons may be a stable and reliable region to calculate SUVrvalues to model the neurometabolic degeneration in quantitative F-FDG PET imaging in HD.

Future challenges of multimodality imaging.

During the last decade, positron emission tomography/computed tomography (PET/CT) and single-photon emission computed tomography/computed tomography (SPECT/CT) have procured advances in research and clinical application of fusion imaging. The recent introduction of systems that combine PET and MRI opens new horizons for multimodality molecular imaging. These systems offer simultaneous morphologic, functional, and molecular information of a living system. Moreover, other combinations of anatomic and functional imaging modalities (for example CT and MRI or PET and optical imaging) are emerging, holding promise in basic medical research or in clinical medicine. These developments are paralleled by advances in the field of biomolecules and particles, to provide new agents useful for more than one imaging modality and to facilitate the study of the same target by different imaging devices. In the near future PET/MRI may emerge as a new powerful multimodality technique in clinical oncology, offering considerable potential for imaging applications beyond correlation of functional and anatomic images. Future developments should include the simultaneous acquisition of multifunctional data such as PET tracer uptake, MR spectroscopy, or fMRI along with high-resolution anatomic MRI.

[Multidimensional alcohol craving scale and [123I] iodobenzamide SPECT as predictors of early relapse in alcohol-dependent patients]. / La Escala Multidimensional de Craving de Alcohol y el SPECT con yodobenzamida[I123] como predictores de recaída precoz en pacientes que presentan dependencia del alcohol.

BACKGROUND: The Multidimensional Alcohol Craving Scale (MACS) and Single Photon Emission Computerized Tomography (SPECT) with (123)I-iodobenzamide ((123)I-IBZM) can be useful tools for assessing relapse risk in early recovery from alcohol-dependency. The aim of this study was to assess possible relationships between MACS score, (123)I-IBZM binding and time to first heavy drinking day (TFHD) after detoxification treatment. METHODS: Nineteen alcohol-dependent in-patients were evaluated by MACS scale and an 123I-IBZM-SPECT, performed following alcohol detoxification treatment. At discharge, participants were advised to take naltrexone 50 mg/day for relapse prevention. TFHD was assessed over a 12-week follow up. RESULTS: The MACS score at the beginning of the detoxification process and naltrexone treatment after detoxification were independent predictive factors for TFHD. CONCLUSIONS: The MACS scale is a better predictor of TFHD than IBZM binding. It is simple, non-invasive and inexpensive and appears to be a useful instrument both for clinical practice and for research.

La Escala Multidimensional de Craving de Alcohol y el SPECT con yodobenzamida[I123] como predictores de recaída precoz en pacientes que presentan dependencia del alcohol / Multidimensional alcohol craving scale and [123I] lodobenzamide SPECT as predictors of early relapse in alcohol-dependent patients

Objetivos: La Escala Multidimensional de Craving de Alcohol (EMCA) yla Tomografía Computarizada por emisión de Fotón Simple (SPECT) con123I-yodobenzamida (IBZM) pueden ser instrumentos válidos para evaluar el riesgo de recaída, durante la etapa inicial de la recuperación del trastorno por dependencia del alcohol. El objetivo de este estudio es evaluarlas posibles relaciones entre la escala EMCA y la captación de IBZM y el tiempo hasta el primer consumo excesivo de alcohol (TPCEA) una vez finalizado el tratamiento de desintoxicación. Metodología: Diecinueve pacientes hospitalizados han sido evaluados mediante la escala EMCA y la SPECT con IBZM al finalizar el tratamiento de desintoxicación del alcohol. En el momento del alta se les aconsejó seguir un tratamiento con naltrexona 50 mg/día para la prevención de recaídas. El TPCEA ha sido evaluado durante 12 semanas de seguimiento. Resultados: La puntuación de la escala EMCA, al inicio del proceso de desintoxicación, y el seguimiento de un tratamiento con naltrexona, posteriormente a dicho proceso, fueron factores predictivos independientes del TPCEA. Conclusiones: La escala EMCA se ha mostrado como un buen predictor del TPCEA mientras que la captación de IBZM parece no serlo. La escala EMCA parece presentar una mayor utilidad, tanto clínica como para la investigación, frente a evaluaciones más complejas, invasivas y costosas (AU)

Background: The Multidimensional Alcohol Craving Scale (MACS) and Single Photon Emission Computerized Tomography (SPECT) with 123I-iodobenzamide (123I-IBZM) can be useful tools for assessing relapse risk in early recovery from alcohol-dependency. The aim of this study was to assess possible relationships between MACS score, 123I-IBZM binding and time to first heavy drinking day (TFHD) after detoxification treatment. Methods: Nineteen alcohol-dependent in-patients were evaluated by MACS scale and an 123I-IBZM-SPECT, performed following alcohol detoxification treatment. At discharge, participants were advised to take naltrexone 50 mg/day for relapse prevention. TFHD was assessed over a 12-week follow up. Results: The MACS score at the beginning of the detoxification process and naltrexone treatment after detoxification were independent predictive factors for TFHD. Conclusions: The MACS scale is a better predictor of TFHD than IBZM binding. It is simple, non-invasive and inexpensive and appears to be a useful instrument both for clinical practice and for research (AU)

Early-onset familial lewy body dementia with extensive tauopathy: a clinical, genetic, and neuropathological study.

We describe a Spanish family in which 3 of 4 siblings had dementia with Lewy bodies, 2 of them starting at age 26 years and the other at 29 years. The father has recently been diagnosed with Lewy body disease, with onset at 77 years. Neuropathological examination of the brain of the index patient disclosed unusual features characterized by diffuse Lewy body disease and generalized neurofibrillary tangle pathology but with no amyloid deposits in any region. Moreover, Lewy body pathology colocalized with neurofibrillary tangles in most affected neurons. Mutation screening that included all coding exons of presenilin 1 (PSEN1), presenilin 2 (PSEN2), alpha-synuclein (SNCA), beta-synuclein (SNCB), microtubule-associated protein tau (MAPT), leucine-rich repeat kinase 2 (LRRK2), glucocerebrosidase (GBA), and exons 16 and 17 of the amyloid precursor protein (APP) genes did not identify any mutation. Genome-wide single nucleotide polymorphism was performed in 4 family members and ruled out any pathogenic duplication or deletion in the entire genome. In summary, we report a unique family with pathologically confirmed early-onset dementia with Lewy bodies with widespread tau and alpha-synuclein deposition. The absence of mutations in genes known to cause Lewy body disease suggests that a novel locus or loci are implicated in this neurodegenerative disease.

Cardiac (123)I-metaiodobenzylguanidine imaging allows early identification of dementia with Lewy bodies during life.

PURPOSE: Differential diagnosis between dementia with Lewy bodies (DLB) and other neurodegenerative diseases with cognitive impairment represents a clinical challenge. Due to the overlapping of symptoms, the clinical diagnosis can be modified during the prolonged follow-up of these diseases. The purpose of this study was to assess the ability of cardiac metaiodobenzylguanidine (MIBG) imaging for early identification of DLB. MATERIALS AND METHODS: Since January 2003, all patients with neurodegenerative diseases with cognitive impairment at their first visit at the Memory Unit and clinical criteria of DLB were consecutively recruited and underwent a cardiac (123)I-MIBG study. The heart-to-mediastinum ratio (HMR) and the washout rate (WR) of cardiac MIBG uptake were obtained. RESULTS: Sixty-five patients were included. After a clinical follow-up of 4 years, the progress of the disease procured a definite diagnosis in 44 (68%) patients: 19 DLB, 12 Alzheimer disease (AD), and 13 other neurodegenerative diseases with cognitive impairment. HMR was significantly decreased in DLB with respect to the other neurodegenerative diseases. WR was only significantly different between DLB and AD. The HMR cut off point of 1.36 differentiated DLB from the other dementias with a sensitivity of 94% and a specificity of 96% with an accuracy of 95%. CONCLUSIONS: Cardiac MIBG imaging performed at the time of the first clinical diagnosis of DLB can help early clinical identification or exclusion of this disease.

I-123-mIBG myocardial imaging for assessment of risk for a major cardiac event in heart failure patients: insights from a retrospective European multicenter study.

PURPOSE: Single-center experiences have shown that myocardial meta-iodobenzylguanidine (mIBG) uptake has prognostic value in heart failure (HF) patients. To verify these observations using a rigorous clinical trial methodology, a retrospective review and prospective quantitative reanalysis was performed on a series of cardiac (123)I-mIBG scans acquired during a 10-year period at six centers in Europe. METHODS: (123)I-mIBG scans obtained on 290 HF patients [(262 with left ventricular ejection fraction (LVEF) < 50%)] from 1993 to 2002 were reanalyzed using a standardized methodology to determine the heart-to-mediastinum ratio (H/M) on delayed planar images. All image results were verified by three independent reviewers. Major cardiac events [MCEs; cardiac death, cardiac transplant, potentially fatal arrhythmia (including implantable cardioverter-defibrillator discharge)] during 24-month follow-up were confirmed by an adjudication committee. RESULTS: MCEs occurred in 67 patients (26%): mean H/M ratio was 1.51 +/- 0.30 for the MCE group and 1.97 +/- 0.54 for the non-MCE group (p < 0.001). Two-year event-free survival using an optimum H/M ratio threshold of 1.75 was 62% for H/M ratio less than 1.75, 95% for H/M ratio greater than or equal to 1.75 (p < 0.0001). Logistic regression showed H/M ratio and LVEF as the only significant predictors of MCE. Using the lower and upper H/M quartiles of 1.45 and 2.17 as high- and very low-risk thresholds, 2-year event-free survival rates were 52% and 98%, respectively. Among patients with LVEF < or = 35% and H/M > or = 1.75 (n = 73), there were nine MCEs because of progressive HF and only one because of an arrhythmia. CONCLUSION: Application of a clinical trial methodology via the retrospective reanalysis of (123)I-mIBG images confirms the previously reported prognostic value of this method in HF patients, including potential identification of a quantitative threshold for low risk for cardiac mortality and potentially fatal ventricular arrhythmias.