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Background: 123 I-meta-iodobenzylguanidine (mIBG) has been applied to patients with chronic heart failure (CHF). However, the relationship between 123 I-mIBG activity and lethal arrhythmic events (ArE) is not well defined. This study aimed to determine this relationship in Japanese and European cohorts., Results: We calculated heart-to-mediastinum (H/M) count ratios and washout rates (WRs) of 827 patients using planar 123 I-mIBG imaging. We defined ArEs as sudden cardiac death, arrhythmic death, and potentially lethal events such as sustained ventricular tachycardia, cardiac arrest with resuscitation, and appropriate implantable cardioverter defibrillator (ICD) discharge, either from a single ICD or as part of a cardiac resynchronization therapy device (CRTD). We analyzed the incidence of ArE with respect to H/M ratios, WRs and New York Heart Association (NYHA) functional classes among Japanese (J; n = 581) and European (E; n = 246) cohorts. We also simulated ArE rates versus H/M ratios under specific conditions using a machine-learning model incorporating 13 clinical variables. Consecutive patients with CHF were selected in group J, whereas group E comprised candidates for cardiac electronic devices. Groups J and E mostly comprised patients with NYHA functional classes I/II (95%) and II/III (91%), respectively, and 21% and 72% were respectively implanted with ICD/CRTD devices. The ArE rate increased with lower H/M ratios in group J, but the relationship was bell-shaped, with a high ArE rate within the intermediate H/M range, in group E. This bell-shaped curve was also evident in patients with NYHA classes II/III in the combined J and E groups, particularly in those with a high (> 15%) mIBG WR and with ischemic, but not in those with non-ischemic etiologies. Machine learning-based prediction of ArE risk aligned with these findings, indicating a bell-shaped curve in NYHA class II/III but not in class I., Conclusions: The relationship between cardiac 123 I-mIBG activity and lethal arrhythmic events is influenced by the background of patients. The bell-shaped relationship in NYHA classes II/III, high WR, and ischemic etiology likely aids in identifying patients at high risk for ArEs., (© 2024. The Author(s).)

Aims/hypothesis: Inflammation is a core component of residual cardiovascular risk in type 2 diabetes. With new anti-inflammatory therapeutics entering the field, accurate markers to evaluate their effectiveness in reducing cardiovascular disease are paramount. Gallium-68-labelled DOTATATE ( 68 Ga-DOTATATE) has recently been proposed as a more specific marker of arterial wall inflammation than 18 F-fluorodeoxyglucose ( 18 F-FDG). This study set out to investigate whether 68 Ga-DOTATATE uptake is amenable to therapeutic intervention in individuals with type 2 diabetes., Methods: Individuals aged >50 years with type 2 diabetes underwent 68 Ga-DOTATATE positron emission tomography (PET)/computed tomography (CT) at baseline and after 3 months treatment with atorvastatin 40 mg once daily. Primary outcome was the difference in coronary 68 Ga-DOTATATE uptake, expressed as target-to-background ratio (TBR). The secondary outcome was difference in bone marrow and splenic uptake, expressed as the standardised uptake value (SUV)., Results: Twenty-two individuals with type 2 diabetes (mean age 63.2±6.4 years, 82% male, LDL-cholesterol 3.42±0.81 mmol/l, HbA 1c 55±12 mmol/mol [7.2%±3.2%]) completed both 68 Ga-DOTATATE PET/CT scans. The maximum TBR was -31% (95% CI -50, -12) lower in the coronary arteries, and bone marrow and splenic 68 Ga-DOTATATE uptake was also significantly lower post statin treatment, with a mean percentage reduction of -15% (95% CI -27, -4) and -17% (95% CI -32, -2), respectively., Conclusions/interpretation: 68 Ga-DOTATATE uptake across the cardio-haematopoietic axis was lower after statin therapy in individuals with type 2 diabetes. Therefore, 68 Ga-DOTATATE is promising as a metric for vascular and haematopoietic inflammation in intervention studies using anti-inflammatory therapeutics in individuals with type 2 diabetes., Trial Registration: ClinicalTrials.gov NCT05730634., (© 2023. The Author(s).)

Purpose: A high SUV max tumor-to-liver ratio (TLR) of 68 Ga-DOTATATE can be used to select patients with neuroendocrine tumors (NETs) for peptide receptor radionuclide therapy (PRRT). In addition, an SUV max TLR ≥ 8.1 is associated with increased progression-free survival in NET patients treated with somatostatin analogs (SSAs). To avoid a theoretical interaction, several guidelines recommend performing PET/CT just before the monthly administration of long-acting SSAs. We aimed to investigate the effect of SSA on the SUV max of 68 Ga-DOTATATE in patients with NET and to identify independent predictors for high SUV max TLR., Patients and Methods: For this retrospective study, 192 68 Ga-DOTATATE PET/CT scans of 165 patients without (n = 115) and with (n = 77) SSA (octreotide or lanreotide) in the 3 months before PET/CT were collected and reviewed. The effect of SSA on SUV max values was analyzed by a maximum likelihood mixed model., Results: Patients with SSA had a significantly higher median SUV max TLR than patients without SSA (4.7 [IQR], 3.1-7.7) versus 3.2 [IQR, 2.0-5.4]; P < 0.001). Multivariable logistic regression analysis showed that SSA use was an independent predictor for SUV max TLR ≥ 8.1 (odds ratio, 2.91; 95% confidence interval, 1.26-6.72; P = 0.012)., Conclusions: Our data suggest that higher SSA concentrations do not have a negative effect on 68 Ga-DOTATATE uptake in tumor lesions. In addition, we found that only SSA use was associated with SUV max TLR ≥ 8.1. Our results are consistent with previously conducted studies and in line with the recently published guideline that suggests that the relatively recent use of SSA does not necessitate any delay in 68 Ga-DOTATATE PET/CT imaging., Competing Interests: Conflicts of interest and sources of funding: none declared., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc.)

Background : Cross-calibration of 123 I-labeled meta -iodobenzylguanidine ( m IBG) myocardial-derived indices is essential to extrapolate findings from several clinical centers. Here, we conducted a phantom study to generate conversion coefficients for the calibration of heart-to-mediastinum ratios and compare them between Taiwan and Europe. Methods : We used an acrylic phantom dedicated to 123 I- m IBG planar imaging to calculate the conversion coefficients of 136 phantom images derived from 36 Taiwanese institutions. A European phantom image database including 191 images from 27 institutions was used. Conversion coefficients were categorized into five collimator types: low-energy (LE) high-resolution (LEHR), LE general-purpose (LEGP), extended LEGP (ELEGP), medium-energy (ME) GP (MEGP), and ME low-penetration (MELP) collimators. Results : The conversion coefficients were 0.53 ± 0.039, 0.59 ± 0.032, 0.79 ± 0.032, 0.96 ± 0.038, and 0.99 ± 0.050 for LEHR, LEGP, ELEGP, MEGP, and MELP collimators, respectively. The Taiwanese and European conversion coefficients for the LEHR, LEGP, and MELP collimators did not significantly differ. The coefficient of variation was slightly higher for the Taiwanese than the European conversion coefficients (3.7%-7.5% vs. 2.3%-5.6%). Conclusions : We calculated conversion coefficients for various types of collimators used in Taiwan using a 123 I- m IBG phantom. In general, the Taiwanese and European conversion coefficients were comparable. These findings further corroborated and highlighted the need for 123 I- m IBG standardization using the phantom-determined conversion coefficients., Competing Interests: K. Nakajima and K. Okuda collaborate with PDRadiopharma Inc., Tokyo, Japan, and K. Nakajima belongs to an endowed department partly funded by PDRadiopharma Inc. C. Kitamura is an employee of PDRadiopharma Inc., Tokyo, Japan., (© The Japanese Society of Nuclear Cardiology 2023.)

Nanomedicine holds promise for the delivery of therapeutic and imaging agents to improve cancer treatment outcomes. Preclinical studies have demonstrated that high-density lipoprotein (HDL) nanoparticles accumulate in tumor tissue on intravenous administration. Whether this HDL-based nanomedicine concept is feasible in patients is unexplored. Using a multimodal imaging approach, we aimed to assess tumor uptake of exogenously administered HDL nanoparticles in patients with esophageal cancer. Methods: The HDL mimetic CER-001 was radiolabeled using 89 Zr to allow for PET/CT imaging. Patients with primary esophageal cancer staged T2 and above were recruited for serial 89 Zr-HDL PET/CT imaging before starting chemoradiation therapy. In addition, patients underwent routine 18 F-FDG PET/CT and 3-T MRI scanning (diffusion-weighted imaging/intravoxel incoherent motion imaging and dynamic contrast-enhanced MRI) to assess tumor glucose metabolism, tumor cellularity and microcirculation perfusion, and tumor vascular permeability. Tumor biopsies were analyzed for the expression of HDL scavenger receptor class B1 and macrophage marker CD68 using immunofluorescence staining. Results: Nine patients with adenocarcinoma or squamous cell carcinoma underwent all study procedures. After injection of 89 Zr-HDL (39.2 ± 1.2 [mean ± SD] MBq), blood-pool SUV mean decreased over time (11.0 ± 1.7, 6.5 ± 0.6, and 3.3 ± 0.5 at 1, 24, and 72 h, respectively), whereas liver and spleen SUV mean remained relatively constant (4.1 ± 0.6, 4.0 ± 0.8, and 4.3 ± 0.8 at 1, 24, and 72 h, respectively, for the liver; 4.1 ± 0.3, 3.4 ± 0.3, and 3.1 ± 0.4 at 1, 24, and 72 h, respectively, for the spleen) and kidney SUV mean markedly increased over time (4.1 ± 0.9, 9.3 ± 1.4, and 9.6 ± 2.0 at 1, 24, and 72 h, respectively). Tumor uptake (SUV peak ) increased over time (3.5 ± 1.1 and 5.5 ± 2.1 at 1 and 24 h, respectively [ P = 0.016]; 5.7 ± 1.4 at 72 h [ P = 0.001]). The effective dose of 89 Zr-HDL was 0.523 ± 0.040 mSv/MBq. No adverse events were observed after the administration of 89 Zr-HDL. PET/CT and 3-T MRI measures of tumor glucose metabolism, tumor cellularity and microcirculation perfusion, and tumor vascular permeability did not correlate with tumor uptake of 89 Zr-HDL, suggesting that a specific mechanism mediated the accumulation of 89 Zr-HDL. Immunofluorescence staining of clinical biopsies demonstrated scavenger receptor class B1 and CD68 positivity in tumor tissue, establishing a potential cellular mechanism of action. Conclusion: To our knowledge, this was the first 89 Zr-HDL study in human oncology. 89 Zr-HDL PET/CT imaging demonstrated that intravenously administered HDL nanoparticles accumulated in tumors of patients with esophageal cancer. The administration of 89 Zr-HDL was safe. These findings may support the development of HDL nanoparticles as a clinical delivery platform for drug agents. 89 Zr-HDL imaging may guide drug development and serve as a biomarker for individualized therapy., (© 2022 by the Society of Nuclear Medicine and Molecular Imaging.)

Background: In patients with heart failure (HF) sequential imaging studies have demonstrated a relationship between myocardial perfusion and adrenergic innervation. We evaluated the feasibility of a simultaneous low-dose dual-isotope 123 I/ 99m Tc-acquisition protocol using a cadmium-zinc-telluride (CZT) single-photon emission computed tomography (SPECT) camera., Methods and Results: Thirty-six patients with HF underwent simultaneous low-dose 123 I-metaiodobenzylguanidine (MIBG)/ 99m Tc-sestamibi gated CZT-SPECT cardiac imaging. Perfusion and innervation total defect sizes and perfusion/innervation mismatch size (defined by 123 I-MIBG defect size minus 99m Tc-sestamibi defect size) were expressed as percentages of the total left ventricular (LV) surface area. LV ejection fraction (EF) significantly correlated with perfusion defect size (P < .005), innervation defect size (P < .005), and early (P < .05) and late (P < .01) 123 I-MIBG heart-to-mediastinum (H/M) ratio. In addition, late H/M ratio was independently associated with reduced LVEF (P < .05). Although there was a significant relationship (P < .001) between perfusion and innervation defect size, innervation defect size was larger than perfusion defect size (P < .001). At multivariable linear regression analysis, 123 I-MIBG washout rate (WR) correlated with perfusion/innervation mismatch (P < .05)., Conclusions: In patients with HF, a simultaneous low-dose dual-isotope 123 I/ 99m Tc-acquisition protocol is feasible and could have important clinical implications., (© 2022. The Author(s).)

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

Objective: Accurate sentinel lymph node (SLN) staging is essential for both prognosis and treatment in patients with breast cancer. However, the preoperative lymphoscintigraphy may fail to visualize the SLN. The aim of this retrospective study was to investigate whether parameters derived from anatomical breast imaging can predict SLN nonvisualization on lymphoscintigraphy., Methods: For this retrospective study, all data of mammography, breast MRI, and lymphoscintigraphy of SLN procedures from January 2016 to April 2021 were collected and reviewed from the Amsterdam UMC database., Results: A total of 758 breast cancer patients were included in this study. SLN nonvisualization on planar lymphoscintigraphy at 2-h postinjection (pi) was 29.7% and was reduced after a second injection to 7.5% at late lymphoscintigraphy 4-h pi. Multivariable analysis showed that age ≥ 70 years ( P = 0.019; OR, 1.82; 95% CI, 1.10-3.01), BMI ≥ 30 kg/m 2 ( P = 0.031; OR, 1.59; 95% CI, 1.04-2.43), and nonpalpable tumors ( P = 0.034; OR, 1.54; 95% CI, 1.03-2.04) were independent predictors of SLN nonvisualization. Differences in tumor size, Breast Imaging-Reporting and Data System classification, or breast density were not significantly associated with SLN nonvisualization., Conclusion: This study shows that, by using a multivariable analysis, risk factors for SLN nonvisualization in breast cancer patients during preoperative lymphoscintigraphy at 2-h pi are age ≥ 70 years, BMI ≥ 30 kg/m 2 , and nonpalpable tumors. Parameters derived from mammography or breast MRI, however, are not useful to predict SLN nonvisualization on lymphoscintigraphy., (Copyright © 2022 The Author(s). Published by Wolters Kluwer Health, Inc.)

Aortic valve stenosis (AVS) is an increasingly prevalent disease in our aging population. Although multiple risk factors for AVS have been elucidated, medical therapies capable of slowing down disease progression remain unavailable. Molecular imaging technologies are opening up avenues for the non-invasive assessment of disease progression, allowing the assessment of (early) medical interventions. This review will focus on the role of positron emission tomography of the aortic valve with 18 F-fluorodeoxyglucose and 18 F-sodium fluoride but will also shed light on novel tracers which have potential in AVS, ranging from the healthy aortic valve to end-stage valvular disease.

Cardiac sympathetic upregulation is one of the neurohormonal compensation mechanisms that play an important role in the pathogenesis of chronic heart failure (CHF). In the past decades, cardiac 123 I- m IBG scintigraphy has been established as a feasible technique to evaluate the global and regional cardiac sympathetic innervation. Although cardiac 123 I- m IBG imaging has been studied in many cardiac and neurological diseases, it has extensively been studied in ischemic and non-ischemic CHF. Therefore, this review will focus on the role of 123 I- m IBG imaging in CHF. This non-invasive, widely available technique has been established to evaluate the prognosis in CHF. Standardization, especially among various combinations of gamma camera and collimator, is important for identifying appropriate thresholds for adequate risk stratification. Interestingly, in contrast to the linear relationship between 123 I- m IBG-derived parameters and overall prognosis, there seems to be a "bell-shape" curve for 123 I- m IBG-derived parameters in relation to ventricular arrhythmia or appropriate implantable cardioverter defibrillator (ICD) therapy in patients with ischemic CHF. In addition, there is a potential clinical role for cardiac 123 I- m IBG imaging in optimizing patient selection for implantation of expensive devices such as ICD and cardiac resynchronization therapy (CRT). Based on cardiac 123 I- m IBG data risk models and machine learning, models have been developed for appropriate risk assessment in CHF.

Background: Accurate scar assessment is crucial in cardiac resynchronization therapy (CRT) candidates, since its presence is a negative predictor for CRT response. Therefore, we assessed the performance of different PET parameters to detect scar in CRT candidates., Methods: Twenty-nine CRT candidates underwent 18F-fluorodeoxyglucose (18F-FDG)-PET/computed tomography (CT), resting 13N-NH3-PET/CT and cardiac magnetic resonance (CMR) prior to CRT implantation. Segmental 18F-FDG uptake, late 13N-NH3 uptake and absolute myocardial blood flow (MBF) were evaluated for scar detection using late gadolinium enhancement (LGE) CMR as reference. A receiver operator characteristic (ROC) area under the curve (AUC) ≥0.8 indicated a good accuracy of the methods evaluated., Results: Scar was present in 111 of 464 segments. None of the approaches could reliably identify segments with nontransmural scar, except for 18F-FDG uptake in the lateral wall (AUC 0.83). Segmental transmural scars could be detected with all methods (AUC ≥ 0.8), except for septal 18F-FDG uptake and MBF in the inferior wall (AUC < 0.8). Late 13N-NH3 uptake was the best parameter for transmural scar detection, independent of its location, with a sensitivity of 80% and specificity of 92% using a cutoff of 66% of the maximum tracer activity., Conclusions: Late 13N-NH3 uptake is superior to 13N-NH3 MBF and 18F-FDG in detecting transmural scar, independently of its location. However, none of the tested PET parameters was able to accurately detect nontransmural scar., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Background and Aims: Severe obstructive sleep apnea (OSA) is associated with an increased risk of cardiovascular disease. Experimental evidence suggests that this risk may be mediated by chronic sympathetic hyperactivation and systemic inflammation, but the precise mechanisms remain to be unraveled. Our aim was to evaluate whether severe OSA patients are characterized by increased sympathetic and hematopoietic activity, potentially driving atherosclerosis., Methods: Untreated patients with severe OSA (apnea-hypopnea index (AHI) > 30 per hour) were matched with mild OSA patients (AHI<15 & >5 per hour) according to age, sex, and body mass index. Study objectives were to assess baroreflex sensitivity (BRS) and heart-rate variability (HRV) using continuous finger blood pressure measurements, hematopoietic activity in the bone marrow and spleen, and arterial inflammation with 18 F-fluorodeoxyglucose positron emission tomography/computed tomography ( 18 F-FDG PET/CT)., Results: A total of 34 subjects, 17 per group, were included in the analysis. Mean age was 60.7 ± 6.2 years, 24 (70.6%) were male. Mean AHI was 40.5 ± 12.6 per hour in the severe OSA group, and 10.5 ± 3.4 per hour in the mild OSA group. Participants with severe OSA were characterized by reduced BRS (5.7 [4.6-7.8] ms/mmHg in severe vs 8.2 [6.9-11.8] ms/mmHg in mild OSA, p = 0.033) and increased splenic activity (severe OSA 18 F-FDG uptake 3.56 ± 0.77 vs mild OSA 3.01 ± 0.68; p = 0.036). HRV, bone marrow activity and arterial inflammation were comparable between groups., Conclusions: Patients with severe OSA are characterized by decreased BRS and increased splenic activity. Randomized controlled trials are warranted to assess whether OSA treatment reduces sympathetic and splenic activity., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Background: A recently discovered sudden cardiac arrest (SCA) syndrome is linked to a risk haplotype that harbors the dipeptidyl-peptidase 6 (DPP6) gene as a plausible culprit., Objective: Because DPP6 impacts both cardiomyocyte and neuronal function, we hypothesized that ventricular fibrillation (VF) in risk haplotype carriers arises from functional changes in both the heart and autonomic nervous system., Methods: We studied 6 risk haplotype carriers with previous VF (symptomatic), 8 carriers without VF (asymptomatic), and 7 noncarriers (controls). We analyzed supine and standing heart rate variability, baroreflex sensitivity, pre-VF heart rate changes, and myocardial 123 I-meta-iodobenzylguanide ( 123 I-mIBG) scintigraphy., Results: Carriers had longer interbeat intervals than controls (1.03 ± 0.11 seconds vs 0.81 ± 0.07 seconds; P <.001), lower low-frequency (LF) and higher high-frequency (HF) activity, and lower LF/HF ratio (0.68 ± 0.50 vs 2.11 ± 1.10; P = .013) in the supine position. Upon standing up, carriers had significantly larger decrease in interbeat interval and increase in LF than controls (standing-to-supine ratio: 0.78 ± 0.07 vs 0.90 ± 0.07; P = .002; and 1.94 ± 1.03 vs 1.17 ± 0.34; P = .022, respectively), and nonsignificantly larger decrease in HF (0.62 ± 0.36 vs 0.97 ± 0.42; P = .065) and increase in LF/HF ratio (5.55 ± 6.79 vs 1.62 ± 1.24; P = .054). Sixteen of 17 VF episodes occurred at rest. Heart rate immediately before VF was 110 ± 25 bpm. Symptomatic carriers had less heterogeneous 123 I-mIBG distribution in the left ventricle than asymptomatic carriers (single-photon emission computed tomography score ≥3 in 7 asymptomatic and 1 symptomatic carrier; P = .008)., Conclusion: It can be speculated that these data are consistent with more labile autonomic tone in carriers, suggesting that the primary abnormalities may reside in both the heart and the autonomic nervous system., (Copyright © 2021 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

Objective: To assess whether patients with aortic valve stenosis (AS) with elevated lipoprotein(a) (Lp(a)) are characterised by increased valvular calcification activity compared with those with low Lp(a)., Methods: We performed 18 F-sodium fluoride ( 18 F-NaF) positron emission tomography/CT in patients with mild to moderate AS (peak aortic jet velocity between 2 and 4 m/s) and high versus low Lp(a) (>50 mg/dL vs <50 mg/dL, respectively). Subjects were matched according to age, gender, peak aortic jet velocity and valve morphology. We used a target to background ratio with the most diseased segment approach to compare 18 F-NaF uptake., Results: 52 individuals (26 matched pairs) were included in the analysis. The mean age was 66.4±5.5 years, 44 (84.6%) were men, and the mean aortic valve velocity was 2.80±0.49 m/s. The median Lp(a) was 79 (64-117) mg/dL and 7 (5-11) mg/dL in the high and low Lp(a) groups, respectively. Systolic blood pressure and low-density-lipoprotein cholesterol (corrected for Lp(a)) were significantly higher in the low Lp(a) group (141±12 mm Hg vs 128±12 mm Hg, 2.5±1.1 mmol/L vs 1.9±0.8 mmol/L). We found no difference in valvular 18 F-NaF uptake between the high and low Lp(a) groups (3.02±1.26 vs 3.05±0.96, p=0.902). Linear regression analysis showed valvular calcium score to be the only significant determinant of valvular 18 F-NaF uptake (β=0.63; 95% CI 0.38 to 0.88 per 1000 Agatston unit increase, p<0.001). Lp(a) was not associated with 18 F-NaF uptake (β=0.17; 95% CI -0.44 to 0.88, p=0.305 for the high Lp(a) group)., Conclusion: Among patients with mild to moderate AS, calcification activity is predominantly determined by established calcium burden. The results do not support our hypothesis that Lp(a) is associated with valvular 18 F-NaF uptake., Competing Interests: Competing interests: ESGS has received research grants/support to his institution from Amgen, Sanofi, Resverlogix and Athera, and has served as a consultant for Amgen, Sanofi, Esperion, Novartis and Ionis Pharmaceuticals. All other authors report no conflict of interest., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY. Published by BMJ.)

Background: Hereditary Multiple Exostoses (HME) is a rare autosomal disorder characterized by the presence of multiple exostoses (osteochondromas) caused by a heterozygous loss of function mutation in EXT1 or EXT2 ; genes involved in heparan sulfate (HS) chain elongation. Considering that HS and other glycosaminoglycans play an important role in sodium and water homeostasis, we hypothesized that HME patients have perturbed whole body volume regulation and osmolality in response to high sodium conditions., Methods: We performed a randomized cross-over study in 7 male HME patients and 12 healthy controls, matched for age, BMI, blood pressure and renal function. All subjects followed both an 8-day low sodium diet (LSD, <50 mmol/d) and high sodium diet (HSD, >200 mmol/d) in randomized order. After each diet, blood and urine samples were collected. Body fluid compartment measurements were performed by using the distribution curve of iohexol and 125 I-albumin., Results: In HME patients, HSD resulted in significant increase of intracellular fluid volume (ICFV) (1.2 L, p  = 0.01). In this group, solute-mediated water clearance was significantly lower after HSD, and no changes in interstitial fluid volume (IFV), plasma sodium, and effective osmolality were observed. In healthy controls, HSD did not influence ICFV, but expanded IFV (1.8 L, p  = 0.058) and increased plasma sodium and effective osmolality., Conclusion: HME patients show altered body fluid distribution and osmoregulation after HSD compared to controls. Our results might indicate reduced interstitial sodium accumulation capacity in HME, leading to ICFV increase. Therefore, this study provides additional support that HS is crucial for maintaining constancy of the internal environment., Competing Interests: All authors have read the journals policy on disclosure of potential conflicts of interest. There are no conflicts of interest to declare., (© 2021 The Authors.)

Background: Better understanding of pathophysiological changes, induced by left bundle branch block (LBBB), may improve patient selection for cardiac resynchronization therapy (CRT). Therefore, we assessed the effect of LBBB on regional glucose metabolism, 13 N-NH 3 -derived absolute and semiquantitative myocardial blood flow (MBF), and their relation in non-ischemic CRT candidates., Methods: Twenty-five consecutive non-ischemic patients with LBBB underwent 18 F-FDG and resting dynamic 13 N-NH 3 PET/CT prior to CRT implantation. Regional 18 F-FDG uptake, absolute MBF, and late 13 N-NH 3 uptake were analyzed and corresponding septal-to-lateral wall ratios (SLR) were calculated. Segmental analysis was performed to evaluate "reverse mismatch," "mismatch," and "match" patterns, based on late 13 N-NH 3 / 18 F-FDG uptake ratios., Results: A significantly lower 18 F-FDG uptake was observed in the septum compared to the lateral wall (SLR 0.53 ± 0.17). A similar pattern was observed for MBF (SLR 0.68 ± 0.18), whereas late 13 N-NH 3 uptake showed a homogeneous distribution (SLR 0.96 ± 0.13). 13 N-NH 3 / 18 F-FDG "mismatch" and "reverse mismatch" segments were predominantly present in the lateral (52%) and septal wall (61%), respectively., Conclusions: Non-ischemic CRT candidates with LBBB demonstrate lower glucose uptake and absolute MBF in the septum compared to the lateral wall. However, late static 13 N-NH 3 uptake showed a homogenous distribution, reflecting a composite measure of altered regional MBF and metabolism, induced by LBBB., (© 2019. American Society of Nuclear Cardiology.)

Background: Accurate sentinel lymph node (SLN) staging is essential for both prognosis and treatment in patients with breast cancer. However, the preoperative lymphoscintigraphy may fail to visualize the SLN in some patients. The purpose of this retrospective study was to identify risk factors associated with SLN nonvisualization on lymphoscintigraphy. For this single-center retrospective study, all data of lymphoscintigraphy of SLN procedures from March 2011 to April 2021 were collected and reviewed from the Amsterdam UMC database., Results: A total of 1886 SLN procedures were included in this study. The SLN nonvisualization rate was 25.1% on lymphoscintigraphy at 4 h post-injection. The SLN nonvisualization rate decreased to 9.4% after reinjection. Multivariable analysis showed that age ≥ 70 years (P < 0.001; OR: 2.27; 95% CI: 1.46-3.53), BMI ≥ 30 kg/m 2 (P = 0.031; OR: 1.48; 95% CI: 1.04-2.12) and nonpalpable tumors (P = 0.004; OR: 1.54; 95% CI: 1.15-2.07) were independent predictors of SLN nonvisualization. Tumor location, brand of radiopharmaceutical, injected dose and volume, experience of preparer and administrator were not associated with SLN nonvisualization. None of the patient, tumor or tracer characteristics were associated with SLN nonvisualization after radiotracer reinjection., Conclusions: This study shows that risk factors for SLN nonvisualization in breast cancer patients during preoperative lymphoscintigraphy are age ≥ 70 years, BMI ≥ 30 kg/m 2 and nonpalpable tumors. Our results support the notion that SLN lymphoscintigraphy is a very robust technique that does not depend on the experience of the preparer or administrator of the radiotracer.

In daily clinical practice, clinicians integrate available data to ascertain the diagnostic and prognostic probability of a disease or clinical outcome for their patients. For patients with suspected or known cardiovascular disease, several anatomical and functional imaging techniques are commonly performed to aid this endeavor, including coronary computed tomography angiography (CCTA) and nuclear cardiology imaging. Continuous improvement in positron emission tomography (PET), single-photon emission computed tomography (SPECT), and CT hardware and software has resulted in improved diagnostic performance and wide implementation of these imaging techniques in daily clinical practice. However, the human ability to interpret, quantify, and integrate these data sets is limited. The identification of novel markers and application of machine learning (ML) algorithms, including deep learning (DL) to cardiovascular imaging techniques will further improve diagnosis and prognostication for patients with cardiovascular diseases. The goal of this position paper of the European Association of Nuclear Medicine (EANM) and the European Association of Cardiovascular Imaging (EACVI) is to provide an overview of the general concepts behind modern machine learning-based artificial intelligence, highlights currently prefered methods, practices, and computational models, and proposes new strategies to support the clinical application of ML in the field of cardiovascular imaging using nuclear cardiology (hybrid) and CT techniques.

Cardiac sympathetic activity plays a key role in supporting cardiac function in both health and disease conditions, and nuclear cardiac imaging has always represented the only way for the non-invasive evaluation of the functional integrity of cardiac sympathetic terminals, mainly through the use of radiopharmaceuticals that are analogues of norepinephrine and, in particular, with the use of 123I-mIBG imaging. This technique demonstrates the presence of cardiac sympathetic dysfunction in different cardiac pathologies, linking the severity of sympathetic nervous system impairment to adverse patient's prognosis. This article will outline the state-of-the-art of cardiac 123I-mIBG imaging and define the value and clinical applications in the different fields of cardiovascular diseases., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2021. For permissions, please email: journals.permissions@oup.com.)

With this document, we provide a standard for PET/(diagnostic) CT imaging procedures in cardiovascular diseases that are inflammatory, infective, infiltrative, or associated with dysfunctional innervation (4Is). This standard should be applied in clinical practice and integrated in clinical (multicenter) trials for optimal procedural standardization. A major focus is put on procedures using [ 18 F]FDG, but 4Is PET radiopharmaceuticals beyond [ 18 F]FDG are also described in this document. Whilst these novel tracers are currently mainly applied in early clinical trials, some multicenter trials are underway and we foresee in the near future their use in clinical care and inclusion in the clinical guidelines. Finally, PET/MR applications in 4Is cardiovascular diseases are also briefly described. Diagnosis and management of 4Is-related cardiovascular diseases are generally complex and often require a multidisciplinary approach by a team of experts. The new standards described herein should be applied when using PET/CT and PET/MR, within a multimodality imaging framework both in clinical practice and in clinical trials for 4Is cardiovascular indications.

The use of cardiac PET, and in particular of quantitative myocardial perfusion PET, has been growing during the last years, because scanners are becoming widely available and because several studies have convincingly demonstrated the advantages of this imaging approach. Therefore, there is a need of determining the procedural modalities for performing high-quality studies and obtaining from this demanding technique the most in terms of both measurement reliability and clinical data. Although the field is rapidly evolving, with progresses in hardware and software, and the near perspective of new tracers, the EANM Cardiovascular Committee found it reasonable and useful to expose in an updated text the state of the art of quantitative myocardial perfusion PET, in order to establish an effective use of this modality and to help implementing it on a wider basis. Together with the many steps necessary for the correct execution of quantitative measurements, the importance of a multiparametric approach and of a comprehensive and clinically useful report have been stressed.