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Positron emission tomography / computed tomography (PET/CT) plays a pivotal role in the assessment of cardiovascular diseases (CVD), particularly in the context of ischemic heart disease. Nevertheless, its application in other forms of CVD, such as infiltrative, infectious, or inflammatory conditions, remains limited. Recently, PET/CT systems with an extended axial field of view (LAFOV) have been developed, offering greater anatomical coverage and significantly enhanced PET sensitivity. These advancements enable head-to-pelvis imaging with a single bed position, and in systems with an axial field of view (FOV) of approximately 2 meters, even total body (TB) imaging is feasible in a single scan session. The application of LAFOV PET/CT in CVD presents a promising opportunity to improve systemic cardiovascular assessments and address the limitations inherent to conventional short axial field of view (SAFOV) devices. However, several technical challenges, including procedural considerations for LAFOV systems in CVD, complexities in data processing, arterial input function extraction, and artefact management, have not been fully explored. This review aims to discuss the technical aspects of LAFOV PET/CT in relation to CVD by highlighting key opportunities and challenges and examining the impact of these factors on the evaluation of most relevant CVD., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Riemer H. J. A. Slart reports a relationship with Siemens Healthineers that includes: funding grants. Riemer H. J. A. Slart reports a relationship with Pfizer that includes: funding grants. Andor W. J. M. Glaudemans reports a relationship with Siemens Healthineers that includes: funding grants. Charalampos Tsoumpas reports a relationship with Siemens Healthineers that includes: funding grants. Charalampos Tsoumpas reports a relationship with Positrigo that includes: funding grants. Charalampos Tsoumpas reports a relationship with General Electric Healthcare that includes: funding grants. Charalampos Tsoumpas reports a relationship with Positrigo that includes: consulting or advisory. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: The aim of our current systematic dynamic phantom study was first, to optimize reconstruction parameters of coronary CTA (CCTA) acquired on photon counting CT (PCCT) for coronary artery calcium (CAC) scoring, and second, to assess the feasibility of calculating CAC scores from CCTA, in comparison to reference calcium scoring CT (CSCT) scans., Methods: In this phantom study, an artificial coronary artery was translated at velocities corresponding to 0, < 60, and 60-75 beats per minute (bpm) within an anthropomorphic phantom. The density of calcifications was 100 (very low), 200 (low), 400 (medium), and 800 (high) mgHA/cm 3 , respectively. CCTA was reconstructed with the following parameters: virtual non-iodine (VNI), with and without iterative reconstruction (QIR level 2, QIR off, respectively); kernels Qr36 and Qr44f; slice thickness/increment 3.0/1.5 mm and 0.4/0.2 mm. The agreement in risk group classification between CAC CCTA and CAC CSCT scoring was measured using Cohen weighted linear κ with 95% CI., Results: For CCTA reconstructed with 0.4 mm slice thickness, calcium detectability was perfect (100%). At < 60 bpm, CAC CCTA of low, and medium density calcification was underestimated by 53%, and 15%, respectively. However, CAC CCTA was not significantly different from CAC CSCT of very low, and high-density calcifications. The best risk agreement was achieved when CCTA was reconstructed with QIR off, Qr44f, and 0.4 mm slice thickness (κ = 0.762, 95% CI 0.671-0.853)., Conclusion: In this dynamic phantom study, the detection of calcifications with different densities was excellent with CCTA on PCCT using thin-slice VNI reconstruction. Agatston scores were underestimated compared to CSCT but agreement in risk classification was substantial., Clinical Relevance Statement: Photon counting CT may enable the implementation of coronary artery calcium scoring from coronary CTA in daily clinical practice., Key Points: Photon-counting CTA allows for excellent detectability of low-density calcifications at all heart rates. Coronary artery calcium scoring from coronary CTA acquired on photon counting CT is feasible, although improvement is needed. Adoption of the standard acquisition and reconstruction protocol for calcium scoring is needed for improved quantification of coronary artery calcium to fully employ the potential of photon counting CT., (© 2024. The Author(s).)

Introduction: Prosthetic valve endocarditis (PVE) is a serious complication of prosthetic valve implantation, with an estimated yearly incidence of at least 0.4-1.0%. The Duke criteria and subsequent modifications have been developed as a diagnostic framework for infective endocarditis (IE) in clinical studies. However, their sensitivity and specificity are limited, especially for PVE. Furthermore, their most recent versions (ESC2015 and ESC2023) include advanced imaging modalities, e.g., cardiac CTA and [ 18 F]FDG PET/CT as major criteria. However, despite these significant changes, the weighing system using major and minor criteria has remained unchanged. This may have introduced bias to the diagnostic set of criteria. Here, we aimed to evaluate and improve the predictive value of the modified Duke/ESC 2015 (MDE2015) criteria by using machine learning algorithms., Methods: In this proof-of-concept study, we used data of a well-defined retrospective multicentre cohort of 160 patients evaluated for suspected PVE. Four machine learning algorithms were compared to the prediction of the diagnosis according to the MDE2015 criteria: Lasso logistic regression, decision tree with gradient boosting (XGBoost), decision tree without gradient boosting, and a model combining predictions of these (ensemble learning). All models used the same features that also constitute the MDE2015 criteria. The final diagnosis of PVE, based on endocarditis team consensus using all available clinical information, including surgical findings whenever performed, and with at least 1 year follow up, was used as the composite gold standard., Results: The diagnostic performance of the MDE2015 criteria varied depending on how the category of 'possible' PVE cases were handled. Considering these cases as positive for PVE, sensitivity and specificity were 0.96 and 0.60, respectively. Whereas treating these cases as negative, sensitivity and specificity were 0.74 and 0.98, respectively. Combining the approaches of considering possible endocarditis as positive and as negative for ROC-analysis resulted in an excellent AUC of 0.917. For the machine learning models, the sensitivity and specificity were as follows: logistic regression, 0.92 and 0.85; XGBoost, 0.90 and 0.85; decision trees, 0.88 and 0.86; and ensemble learning, 0.91 and 0.85, respectively. The resulting AUCs were, in the same order: 0.938, 0.937, 0.930, and 0.941, respectively., Discussion: In this proof-of-concept study, machine learning algorithms achieved improved diagnostic performance compared to the major/minor weighing system as used in the MDE2015 criteria. Moreover, these models provide quantifiable certainty levels of the diagnosis, potentially enhancing interpretability for clinicians. Additionally, they allow for easy incorporation of new and/or refined criteria, such as the individual weight of advanced imaging modalities such as CTA or [ 18 F]FDG PET/CT. These promising preliminary findings warrant further studies for validation, ideally in a prospective cohort encompassing the full spectrum of patients with suspected IE., (© 2024. The Author(s).)

Cardiovascular imaging has rapidly advanced over the past decades. Traditional imaging techniques such as echocardiography, computed tomography, and cardiovascular magnetic resonance are essential for assessing the structural and functional aspects of the cardiovascular system but often fall short in providing direct insights into disease activity. This gap is increasingly being bridged by molecular nuclear imaging techniques, including positron emission tomography and single-photon emission computed tomography, which enable the visualization of disease processes at the molecular and cellular levels. This review highlights the role of cardiovascular molecular imaging, emphasizing its current and potential applications in diagnosing and managing cardiovascular disease. With advancements in positron emission tomography scanners, novel radiotracers, and sophisticated imaging software, molecular imaging is set to play an essential role in precision medicine by enhancing our understanding of disease mechanisms, accelerating the development of targeted therapies, and facilitating personalized patient care., Competing Interests: None.

Methods to shorten [ 18 F]FDG Patlak PET imaging procedures ranging from 65-90 to 20-30 min after injection, using a population-averaged input function (PIF) scaled to patient-specific image-derived input function (IDIF) values, were recently evaluated. The aim of the present study was to explore the feasibility of ultrashort 10-min [ 18 F]FDG Patlak imaging at 55-65 min after injection using a PIF combined with direct Patlak reconstructions to provide reliable quantitative accuracy of lung tumor uptake, compared with a full-duration 65-min acquisition using an IDIF. Methods: Patients underwent a 65-min dynamic PET acquisition on a long-axial-field-of-view (LAFOV) Biograph Vision Quadra PET/CT scanner. Subsequently, direct Patlak reconstructions and image-based (with reconstructed dynamic images) Patlak analyses were performed using both the IDIF (time to relative kinetic equilibrium between blood and tissue concentration (t*) = 30 min) and a scaled PIF at 30-60 min after injection. Next, direct Patlak reconstructions were performed on the system console using only the last 10 min of the acquisition, that is, from 55 to 65 min after injection, and a scaled PIF using maximum crystal ring difference settings of both 85 and 322. Tumor lesion and healthy-tissue uptake was quantified and compared between the differently obtained parametric images to assess quantitative accuracy. Results: Good agreement was obtained between direct- and image-based Patlak analyses using the IDIF (t* = 30 min) and scaled PIF at 30-60 min after injection, performed using the different approaches, with no more than 8.8% deviation in tumor influx rate value ( K i ) (mean difference ranging from -0.0022 to 0.0018 mL/[min × g]). When direct Patlak reconstruction was performed on the system console, excellent agreement was found between the use of a scaled PIF at 30-60 min after injection versus 55-65 min after injection, with 2.4% deviation in tumor K i (median difference, -0.0018 mL/[min × g]; range, -0.0047 to 0.0036 mL/[min × g]). For different maximum crystal ring difference settings using the scan time interval of 55-65 min after injection, only a 0.5% difference (median difference, 0.0000 mL/[min × g]; range, -0.0004 to 0.0013 mL/[min × g]) in tumor K i was found. Conclusion: Ultrashort whole-body [ 18 F]FDG Patlak imaging is feasible on an LAFOV Biograph Vision Quadra PET/CT system without loss of quantitative accuracy to assess lung tumor uptake compared with a full-duration 65-min acquisition. The ultrashort 10-min direct Patlak reconstruction with PIF allows for its implementation in clinical practice., (© 2024 by the Society of Nuclear Medicine and Molecular Imaging.)

Purpose: To ensure comparable PET/CT image quality between or within centres, clinical inter-system performance comparisons following European Association of Nuclear Medicine Research Ltd. (EARL) guidelines is required. In this work the performance of the long axial field-of-view Biograph Vision Quadra is compared to its predecessor, the short axial field-of-view Biograph Vision., Procedures: To this aim, patients with suspected tumour lesions received a single weight-based (3 MBq/kg) 2-deoxy-2-[ 18 F]fluoro-D-glucose injection and underwent routine clinical ( ∼ 15 min) scans on the Vision and 3-min scans on the Quadra in listmode in balanced order. Image quality (IQ), image noise (IN), and tumour demarcation (TD) were assessed visually by four nuclear medicine physicians using a 5-point Likert scale and semiquantitative analysis was performed using standardised uptake values (SUVs). Inter-reader agreement was tested using Wilcoxon's signed rank test and the SUVs were statistically compared using a paired t-test., Results: Twenty patients (mean age, 60 years ± 8.8 [standard deviation], 16 male) were enrolled. Inter-reader agreement ranged from good to very good for IQ and IN (0.62 ≤ W ≤ 0.81), and fair for TD (0.29 ≤ W ≤ 0.39). Furthermore, a significant difference was found for TD (p = 0.015) between the systems, showing improved TD for the Quadra., Conclusion: This study demonstrates that the Quadra can be used in routine clinical practice with multiple PET/CT systems or in multicentre studies. This system provides comparable diagnostic image quality and semiquantitative accuracy, improved TD, and has the advantage of shorter scan durations., (© 2024. The Author(s).)

The introduction of dual-energy X-ray absorptiometry (DXA) technology in the 1980s revolutionized the diagnosis, management and monitoring of osteoporosis, providing a clinical tool which is now available worldwide. However, DXA measurements are influenced by many technical factors, including the quality control procedures for the instrument, positioning of the patient, and approach to analysis. Reporting of DXA results may be confounded by factors such as selection of reference ranges for T-scores and Z-scores, as well as inadequate knowledge of current standards for interpretation. These points are addressed at length in many international guidelines but are not always easily assimilated by practising clinicians and technicians. Our aim in this report is to identify key elements pertaining to the use of DXA in clinical practice, considering both technical and clinical aspects. Here, we discuss technical aspects of DXA procedures, approaches to interpretation and integration into clinical practice, and the use of non-bone mineral density measurements, such as a vertebral fracture assessment, in clinical risk assessment., (© 2024. The Author(s).)

Purpose: Sodium[ 18 F]fluoride (Na[ 18 F]F) used in positron emission tomography (PET) binds to active calcification and correlates consistently with higher cardiovascular risk. This study aims to investigate the feasibility of aortic Na[ 18 F]F-PET in hybrid combination with low-dose computed tomography (CT) as a risk model for major adverse cardiovascular events (MACE)., Methods: Patient data and Na[ 18 F]F-PET/CT scans from January 2019 to February 2022 were retrospectively collected at the University Medical Center Groningen (UMCG), the Netherlands. MACE-outcome was a composite of time to first documented myocardial infarction, cerebral vascular accident (CVA), acute heart failure hospitalization, and aortic aneurysms. MACE dates were recorded from the day of the scan until follow-up in December 2023. The aorta was manually segmented in all low-dose CT scans. To minimize spill-over effects from the vertebrae, the vertebrae were automatically segmented using an open-source model, dilated with 10 mm, and subtracted from the aortic mask. The total aortic Na[ 18 F]F corrected maximum standardized uptake value (cSUV max ) and total aortic Agatston score were automatically calculated using SEQUOIA. Kaplan-Meier and Cox regression survival analysis were performed, stratifying patients into high, medium, and low cSUV max and Agatston categories. Cox regression models were adjusted for age., Results: Out of 280 identified scans, 216 scans of unique patients were included. During a median follow-up of 3.9 years, 12 MACE occurred. Kaplan-Meier survival analysis demonstrated a significant difference in MACE-free survival among the high cSUV max group compared to the medium and low groups (p = 0.03 and p < 0.01, respectively). Similarly, patients with high Agatston scores had a significantly lower MACE-free survival probability compared to those with medium and low scores (both p < 0.01)., Conclusion: This study highlights the potential clinical utility of Na[ 18 F]F-PET/CT as an imaging tool to predict the risk of MACE. Clinical validation of this novel proof-of-concept method is needed to confirm these results and expand the clinical context., (© 2024. The Author(s).)

Aims: Wild-type transthyretin cardiac amyloidosis (ATTRwt-CM) is an under-recognized aetiology of heart failure (HF), necessitating early detection for timely treatment. Our study aimed to differentiate patients with ATTRwt-CM from ATTRwt-negative HFpEF/HFmrEF patients by identifying and validating circulating protein biomarkers. In addition, we measured the same biomarkers in patients with cardiomyopathy due to light chain amyloidosis (AL)-CM to gain disease-specific insights., Methods and Results: In this observational study, serum concentrations of 363 protein biomarkers were measured in a discovery cohort consisting of 73 ATTRwt-CM, 55 AL-CM, and 59 ATTRwt-negative HFpEF/HFmrEF patients, using multiplex proximity extension assays. Sparse partial least squares analyses showed overlapping ATTRwt-CM and AL-CM biomarker profiles with clear visual differentiation from ATTRwt-negative patients. Pathway analyses with g:Profiler revealed significantly up-regulated proteoglycans (PG) and cell adhesion pathways in both ATTRwt-CM and AL-CM. Penalized regression analysis revealed that the proteoglycan decorin (DCN), lysosomal hydrolase alpha-L-iduronidase (IDUA) and glycosyl hydrolase galactosidase β-1 (GLB-1) most effectively distinguished ATTRwt-CM from ATTRwt-negative patients (R2 = 0.71). In a prospective validation cohort of 35 ATTRwt-CM patients and 25 ATTRwt-negative patients, DCN and IDUA significantly predicted ATTRwt-CM in the initial analysis (DCN: OR 3.3, IDUA: OR 0.4). While DCN remained significant after correcting for echocardiographic parameters, IDUA did not. DCN showed moderate discriminative ability (AUC, 0.74; 95% CI, 0.61-0.87; sensitivity, 0.91; specificity, 0.52) as did IDUA (AUC, 0.78; 95% CI, 0.65-0.91; sensitivity, 0.91; specificity, 0.61). A model combining clinical factors (AUC 0.92) outperformed DCN but not IDUA, a combination of the biomarkers was not significantly better. Neither DCN nor IDUA correlated with established disease markers., Conclusion: ATTRwt-CM has a distinctly different biomarker profile compared with HFpEF/HFmrEF, while ATTRwt-CM patients share a similar biomarker profile with AL-CM patients characterized by up-regulation of proteoglycans and cell-adhesion pathways. The biomarkers DCN and IDUA show the potential to serve as an initial screening tool for ATTTRwt-CM. Further research is needed to determine the clinical usefulness of these and other extracellular matrix components in identifying ATTRwt-CM., Competing Interests: Conflict of interest: Alwin Tubben: none. George Markousis-Mavrogenis: none. Laura M.G. Meems: none. Bart van Essen: none. Lukas Baumhove: none. Milou Berends: none. Hendrea S.A. Tingen: none. Johan Bijzet: none. Bouke P.C. Hazenberg: none. Adriaan A. Voors: The UMCG, which employs AAV, received consultancy fees or research support from Anacardio, AstraZeneca, BMS, Bayer, Boehringer Ingelheim, Cytokinetics, Corteria, EliLilly, Merck, Moderna, Novartis, NovoNordisk, Roche Diagnostics. Dirk-Jan van Veldhuisen: none. Riemer H.J.A. Slart: The UMCG, which employs RHJAS, received grant support of Pfizer and Siemens Healthineers. Hans L.A. Nienhuis: The UMCG, which employs HLAN, received consultancy fees and speaking honorarium from Pfizer and Alnylam. Peter van der Meer: PvdM is supported by a grant from the European Research Council (ERC CoG 101045236, DISSECT-HF). The UMCG, which employs PvdM, received consultancy fees and/or grants from Novartis, Pharmacosmos, Vifor Pharma, Astra Zeneca, Pfizer, Pharma Nord, BridgeBio, Novo Nordisk, Boehringer Ingelheim and Ionis., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Imaging water pathways in the human body provides an excellent way of measuring accurately the blood flow directed to different organs. This makes it a powerful diagnostic tool for a wide range of diseases that are related to perfusion and oxygenation. Although water PET has a long history, its true potential has not made it into regular clinical practice. The article highlights the potential of water PET in molecular imaging and suggests its prospective role in becoming an essential tool for the 21st century precision medicine in different domains ranging from preclinical to clinical research and practice. The recent technical advances in high-sensitivity PET imaging can play a key accelerating role in empowering this technique, though there are still several challenges to overcome., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

Systemic vasculitides are autoimmune diseases characterized by inflammation of blood vessels. They are categorized based on the size of the preferentially affected blood vessels: large-, medium-, and small-vessel vasculitides. The main forms of large-vessel vasculitis include giant cell arteritis (GCA) and Takayasu arteritis (TAK). Depending on the location of the affected vessels, various imaging modalities can be employed for diagnosis of large vessel vasculitis: ultrasonography (US), magnetic resonance angiography (MRA), computed tomography angiography (CTA), and [ 18 F]-fluoro-2-deoxy-d-glucose positron emission tomography/computed tomography (FDG-PET/CT). These imaging tools offer complementary information about vascular changes occurring in vasculitis. Recent advances in PET imaging in large vessel vasculitis include the introduction of digital long axial field-of-view PET/CT, dedicated acquisition, quantitative methodologies, and the availability of novel radiopharmaceuticals. This review aims to provide an update on the current status of PET imaging in large vessel vasculitis and to share the latest developments on imaging vasculitides., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Aims: The study aimed, firstly, to validate automatically and visually scored coronary artery calcium (CAC) on low-dose computed tomography (CT) (LDCT) scans with a dedicated calcium scoring CT (CSCT) scan and, secondly, to assess the added value of CAC scored from LDCT scans acquired during [15O]-water-positron emission tomography (PET) myocardial perfusion imaging (MPI) on prediction of major adverse cardiac events (MACE)., Methods and Results: Five hundred seventy-two consecutive patients with suspected coronary artery disease, who underwent [15O]-water-PET MPI with LDCT and a dedicated CSCT scan were included. In the reference CSCT scans, manual CAC scoring was performed, while LDCT scans were scored visually and automatically using deep learning approach. Subsequently, based on CAC score results from CSCT and LDCT scans, each patient's scan was assigned to one out of five cardiovascular risk groups (0, 1-100, 101-400, 401-1000, >1000), and the agreement in risk group classification between CSCT and LDCT scans was investigated. MACE was defined as a composite of all-cause death, non-fatal myocardial infarction, coronary revascularization, and unstable angina. The agreement in risk group classification between reference CSCT manual scoring and visual/automatic LDCT scoring from LDCT was 0.66 [95% confidence interval (CI): 0.62-0.70] and 0.58 (95% CI: 0.53-0.62), respectively. Based on visual and automatic CAC scoring from LDCT scans, patients with CAC > 100 and CAC > 400, respectively, were at increased risk of MACE, independently of ischaemic information from the [15O]-water-PET scan., Conclusion: There is a moderate agreement in risk classification between visual and automatic CAC scoring from LDCT and reference CSCT scans. Visual and automatic CAC scoring from LDCT scans improve identification of patients at higher risk of MACE., Competing Interests: Conflict of interest: N.R.v.d.W. is an employee of Philips. I.I. received institutional research grants from Dutch Technology Foundation (P15–26) with participation of Philips Healthcare and Pie Medical Imaging BV and institutional research grant from Pie Medical Imaging BV., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Background: Kidney transplantation provides substantial benefits in extending survival and improving quality of life for patients with end-stage renal disease. The incidence of major adverse cardiac events (MACE) increases with a decline of kidney function in patients with chronic kidney disease. After kidney transplantation, the incidence of MACE remains high. The objective of this study was to assess the prognostic significance of pre-transplant single-photon emission computed tomography (SPECT) myocardial perfusion imaging (MPI) in kidney transplant recipients., Methods: A systematic literature search was performed between January 1st 2015 and March 26th 2024 in PubMed, EMBASE, Web of Science and The Cochrane Library to identify the prognostic value of SPECT MPI for developing MACE (primary outcome) and mortality (secondary outcome) in kidney transplant recipients (PROSPERO CRD42020188610). Risk of bias was assessed. Meta-analyses and subgroup analyses were performed using random-effects models., Results: Six studies comprising 2090 SPECT MPI scans were included. Abnormal SPECT MPI scans were associated with an increased risk of MACE post-transplantation (HR 1.62, 95% CI 1.27-2.06, p < 0.001). Subgroup analyses showed consistent findings across various patient populations and methodological differences. Sensitivity analyses supported the robustness of our findings., Conclusions: Current evidence showed that pre-transplant SPECT MPI has significant prognostic value in identifying kidney transplant candidates at risk for MACE post-transplantation. Integrating SPECT MPI into preoperative assessments might enhance risk stratification and guide clinical decision-making. Prospective studies are needed to refine risk prediction models., Competing Interests: Declaration of competing interest The authors of this manuscript have no conflicts of interest to declare., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Objective: To investigate the diagnostic performance of liver stiffness for detecting liver involvement in immunoglobulin light chain (AL) amyloidosis., Methods: Liver stiffness was measured using transient elastography in 71 patients with systemic AL amyloidosis and 18 patients with wild type transthyretin (ATTRwt) amyloidosis with cardiomyopathy. Both non-invasive consensus criteria and serum amyloid P component (SAP) scintigraphy were used as substitute standards instead of liver biopsy for establishing liver involvement., Results: Liver stiffness was higher in AL amyloidosis patients with liver involvement than in those without: this was observed using both consensus criteria (median 14.4 kPa vs. 8.1 kPa; p = 0.001) and SAP scintigraphy (median 20.9 kPa vs. 6.2 kPa; p < 0.001). Liver stiffness was also higher in AL amyloidosis patients with liver involvement compared to AL and ATTRwt amyloidosis patients with cardiac involvement. Based on receiver operating characteristic (ROC) curves a cut-off value of 14.4 kPa for stiffness was optimal to indicate liver involvement, providing sensitivity and specificity of 50% and 74%, respectively, using the consensus criteria and 63% and 90%, respectively, using SAP scintigraphy as standard., Conclusion: Liver stiffness is a promising tool to establish liver involvement in AL amyloidosis having potential to become part of updated criteria for liver involvement., (© 2024. The Author(s).)

Purpose: Bone scintigraphy is key to non-invasively diagnosing wild-type transthyretin (ATTRwt) amyloidosis, and is mainly used to assess cardiac radiotracer uptake. However, extracardiac radiotracer uptake is also observed. We investigated whether intensity of soft tissue radiotracer uptake is associated with amyloid load in subcutaneous abdominal fat tissue and with mortality., Methods: This prospective cohort study included 94 ATTRwt amyloidosis patients and 26 amyloid-negative heart failure controls who underwent whole-body [ 99m Tc]Tc-hydroxydiphosphonate scintigraphy. Site-to-background ratios were calculated for heart, elbows, subcutaneous tissue, shoulders and wrists on anterior planar bone scintigraphy images using rib and whole-body radiotracer uptake as background. Fat tissue aspirates were stained with Congo red to grade amyloid load. Site-to-rib ratios were compared between ATTRwt amyloidosis patients and controls, and associations of site-to-background ratio with Congo red score and all-cause mortality were studied., Results: ATTRwt amyloidosis patients had higher soft tissue-to-rib, heart-to-rib and heart-to-whole body ratios compared with controls. The intensity of soft tissue uptake was positively associated with amyloid load in fat tissue in ATTRwt amyloidosis patients. Estimated glomerular filtration rate, N-terminal brain natriuretic propeptide, high-sensitivity cardiac troponin T (hs-cTnT), and the prognostic Mayo and NAC staging system were associated with all-cause mortality in univariable models. Soft tissue/rib ratio, hs-cTnT and the prognostic staging systems were the only two variables that were independently associated withall-cause mortality., Conclusion: Soft tissue radiotracer uptake on bone scintigraphy in ATTRwt amyloidosis patients is positively associated with amyloid load in abdominal fat tissue and is independently associated with mortality., (© 2024. The Author(s).)

Aims: Calciprotein particles (CPPs) are circulating calcium and phosphate nanoparticles associated with development of vascular calcification (VC) in chronic kidney disease (CKD). Although recent studies have been focusing on associations of CPPs with presence of VC in CKD, insights in the underlying processes and mechanisms by which CPPs might aggravate VC and vascular dysfunction in vivo are currently lacking. Here, we assessed overall burden of abdominal VC in healthy kidney donors and CKD patients, and subsequently performed transcriptome profiling in vascular tissue obtained from these subjects, linking outcome to CPP counts and calcification propensity., Methods and Results: Calcification scores were quantified in renal arteries, iliac arteries and abdominal aorta, using computed tomography (CT) scans of kidney donors and CKD patients. Vascular tissue was collected from kidney donors (renal artery) and CKD patients (iliac artery), after which bulk RNA sequencing and gene set enrichment analysis (GSEA) was performed on a subset of patients. Calcification propensity (crystallization time, T50) was measured using nephelometry, and CPP counts with microparticle flow cytometric analysis. Increased calcification scores (based on CT) were found in CKD patients compared to kidney donors. Transcriptome profiling revealed enrichment for processes related to endothelial activation, inflammation, extracellular matrix (ECM) remodelling and ossification in CKD vascular biopsies compared to kidney donors. Calcification propensity was increased in CKD, as well as CPP counts, of which the latter significantly associated with markers of vascular remodelling., Conclusions: Our findings reveal that CKD is characterized by systemic VC with increased calcification propensity and CPP counts. Transcriptome profiling showed altered vascular gene expression with enrichment for endothelial activation, inflammation, ECM remodelling and ossification. Moreover, we demonstrate for the first time that vascular remodelling processes are associated with increased circulating CPP counts. Interventions targeting CPPs are promising avenues for alleviating vascular remodelling and VC in CKD., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Objectives: Cardiac motion artifacts hinder the assessment of coronary arteries in coronary computed tomography angiography (CCTA). We investigated the impact of motion compensation reconstruction (MCR) on motion artifacts in CCTA at various heart rates (HR) using a dynamic phantom., Materials and Methods: An artificial hollow coronary artery (5-mm diameter lumen) filled with iodinated contrast agent (400 HU at 120 kVp), positioned centrally in an anthropomorphic chest phantom, was scanned using a dual-layer spectral detector CT. The artery was translated at constant horizontal velocities (0-80 mm/s, increment of 10 mm/s). For each velocity, five CCTA scans were repeated using a clinical protocol. Motion artifacts were quantified using the in-plane motion area. Regression analysis was performed to calculate the reduction in motion artifacts provided by MCR, by division of the slopes of non-MCR and MCR fitted lines., Results: Reference mean (95% confidence interval) motion artifact area was 24.9 mm 2 (23.8, 26.0). Without MCR, motion artifact areas for velocities exceeding 20 mm/s were significantly larger (up to 57.2 mm 2 (40.1, 74.2)) than the reference. With MCR, no significant differences compared to the reference were shown for all velocities, except for 70 mm/s (29.0 mm 2 (27.0, 31.0)). The slopes of the fitted data were 0.44 and 0.04 for standard and MCR reconstructions, respectively, resulting in an 11-time motion artifact reduction., Conclusion: MCR may improve CCTA assessment in patients by reducing coronary artery motion artifacts, especially in those with elevated HR who cannot receive beta blockers or do not attain the targeted HR., Clinical Relevance Statement: This vendor-specific motion compensation reconstruction may improve coronary computed tomography angiography assessment in patients by reduction of coronary artery motion artifacts, especially in those with elevated various heart rates (HR) who cannot receive beta blockers or do not attain the targeted HR., Key Points: • Motion artifacts are known to hinder the assessment of coronary arteries on coronary CT angiography (CCTA), leading to more non-diagnostic scans. • This dynamic phantom study shows that motion compensation reconstruction (MCR) reduces motion artifacts at various velocities, which may help to decrease the number of non-diagnostic scans. • MCR in this study showed to reduce motion artifacts 11-fold., (© 2024. The Author(s), under exclusive licence to European Society of Radiology.)

Purpose: In routine care, clinicians may employ 2-[18F]fluoro-2-deoxy-D-glucose (FDG) positron emission tomography (PET) computed tomography (CT) to validate their initial clinical diagnosis of polymyalgia rheumatica (PMR). Nevertheless, the diagnostic utility of combining FDG-PET/CT findings with clinical presentation has not been explored. Therefore, this study aimed to investigate whether the diagnostic accuracy for PMR could be enhanced by combining FDG-PET/CT findings with the clinical baseline diagnosis or the 2012 ACR/EULAR clinical classification criteria for PMR., Methods: An investigation and a validation cohort were included from two countries, encompassing 66/27 and 36/21 PMR/non-PMR patients, respectively. The cohorts comprised treatment-naïve patients suspected of PMR, who initially received a clinical baseline diagnosis and underwent FDG-PET/CT scans. The FDG-PET/CT Leuven-score was applied to classify patients as either PMR or non-PMR and combined with the clinical baseline diagnosis. Final diagnoses were established through clinical follow-up after twelve or six months in the investigation and validation cohorts, respectively., Results: In the investigation cohort, a clinical baseline diagnosis yielded a sensitivity/specificity of 94%/82%, compared with 78%/70% using the ACR/EULAR criteria. Combining the clinical baseline diagnosis with a positive Leuven-score showed a sensitivity/specificity of 80%/93%, compared with 80%/82% for an ACR/EULAR-Leuven-score. In the validation cohort, the baseline diagnosis revealed a sensitivity/specificity of 100%/91%, compared with 92%/76% using the ACR/EULAR criteria. Combining FDG-PET/CT with the baseline diagnosis demonstrated a sensitivity/specificity of 83%/95% compared with 89%/81% for the ACR/EULAR-Leuven-score., Conclusion: Combining FDG-PET/CT findings with the clinical baseline diagnosis or ACR/EULAR clinical classification criteria can improve the diagnostic specificity for PMR., (© The Author(s) 2024. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Osteoporotic fractures, also known as fragility fractures, are reflective of compromised bone strength and are associated with significant morbidity and mortality. Such fractures may be clinically silent, and others may present clinically with pain and deformity at the time of the injury. Unfortunately, and even at the time of detection, most individuals sustaining fragility fractures are not identified as having underlying metabolic bone disease and are not evaluated or treated to reduce the incidence of future fractures. A multidisciplinary international working group with representation from international societies dedicated to advancing the care of patients with metabolic bone disease has developed best practice recommendations for the diagnosis and evaluation of individuals with fragility fractures. A comprehensive narrative review was conducted to identify key articles on fragility fractures and their impact on the incidence of further fractures, morbidity, and mortality. This document represents consensus among the supporting societies and harmonizes best practice recommendations consistent with advances in research. A fragility fracture in an adult is an important predictor of future fractures and requires further evaluation and treatment of the underlying osteoporosis. It is important to recognize that most fragility fractures occur in patients with bone mineral density T scores higher than -2.5, and these fractures confirm the presence of skeletal fragility even in the presence of a well-maintained bone mineral density. Fragility fractures require further evaluation with exclusion of contributing factors for osteoporosis and assessment of clinical risk factors for fracture followed by appropriate pharmacological intervention designed to reduce the risk of future fracture. Because most low-trauma vertebral fractures do not present with pain, dedicated vertebral imaging and review of past imaging is useful in identifying fractures in patients at high risk for vertebral fractures. Given the importance of fractures in confirming skeletal fragility and predicting future events, it is recommended that an established classification system be used for fracture identification and reporting., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Purpose: Consensus on the choice of the most accurate imaging strategy in diabetic foot infective and non-infective complications is still lacking. This document provides evidence-based recommendations, aiming at defining which imaging modality should be preferred in different clinical settings., Methods: This working group includes 8 nuclear medicine physicians appointed by the European Association of Nuclear Medicine (EANM), 3 radiologists and 3 clinicians (one diabetologist, one podiatrist and one infectious diseases specialist) selected for their expertise in diabetic foot. The latter members formulated some clinical questions that are not completely covered by current guidelines. These questions were converted into statements and addressed through a systematic analysis of available literature by using the PICO (Population/Problem-Intervention/Indicator-Comparator-Outcome) strategy. Each consensus statement was scored for level of evidence and for recommendation grade, according to the Oxford Centre for Evidence-Based Medicine (OCEBM) criteria., Results: Nine clinical questions were formulated by clinicians and used to provide 7 evidence-based recommendations: (1) A patient with a positive probe-to-bone test, positive plain X-rays and elevated ESR should be treated for presumptive osteomyelitis (OM). (2) Advanced imaging with MRI and WBC scintigraphy, or [ 18 F]FDG PET/CT, should be considered when it is needed to better evaluate the location, extent or severity of the infection, in order to plan more tailored treatment. (3) In a patient with suspected OM, positive PTB test but negative plain X-rays, advanced imaging with MRI or WBC scintigraphy + SPECT/CT, or with [ 18 F]FDG PET/CT, is needed to accurately assess the extent of the infection. (4) There are no evidence-based data to definitively prefer one imaging modality over the others for detecting OM or STI in fore- mid- and hind-foot. MRI is generally the first advanced imaging modality to be performed. In case of equivocal results, radiolabelled WBC imaging or [ 18 F]FDG PET/CT should be used to detect OM or STI. (5) MRI is the method of choice for diagnosing or excluding Charcot neuro-osteoarthropathy; [ 18 F]FDG PET/CT can be used as an alternative. (6) If assessing whether a patient with a Charcot foot has a superimposed infection, however, WBC scintigraphy may be more accurate than [ 18 F]FDG PET/CT in differentiating OM from Charcot arthropathy. (7) Whenever possible, microbiological or histological assessment should be performed to confirm the diagnosis. (8) Consider appealing to an additional imaging modality in a patient with persisting clinical suspicion of infection, but negative imaging., Conclusion: These practical recommendations highlight, and should assist clinicians in understanding, the role of imaging in the diagnostic workup of diabetic foot complications., (© 2024. The Author(s).)

Background and Aims: Sodium [ 18 F]fluoride (Na [ 18 F]F) positron emission tomography imaging allows detailed visualization of early arterial micro-calcifications. This study aims to investigate atherosclerosis manifested by micro-calcification, macro-calcification, and aortic stiffness in patients with type 2 diabetes mellitus (T2DM) with and without albuminuria and severely decreased kidney function., Methods: A cohort was stratified in four groups (N = 10 per group), based on KDIGO categories (G1-5 A1-3). G1-2A1 non-diabetic controls (median [IQR] estimated glomerular filtration rate (eGFR) in mL/min/1.73 m 2 91 [81-104]), G1-2A1 with T2DM (eGFR 87 [84-93], and albumin-creatinin-ratio (ACR) in mg/mmol 0.35 [0.25-0.75]), G1-2A3 with T2DM (eGFR 85 [60-103], and ACR 74 [62-122], and G4A3 with T2DM (eGFR 19 [13-27] and ACR 131 [59-304])., Results: Na [ 18 F]F femoral artery grading score differed significantly in the groups with the highest Na [ 18 F]F activity in A3 groups with T2DM (G1-2A3 with T2DM 228 [100-446] and G4A3 with T2DM 198 [113-578]) from the lowest groups of the G1-2A1 with T2DM (33 [0-93]) and in G1-2A1 non-diabetic controls (75 [0-200], p = 0.001). Aortic Na [ 18 F]F activity and femoral artery computed tomography (CT)-assessed macro-calcification was increased in G4A3 with T2DM compared with G1-2A1 with T2DM (47.5 [33.8-73.8] vs. 17.5 [8.8-27.5] (p = 0.006) and 291 [170-511] vs. 12.2 [1.41-44.3] mg (p = 0.032), respectively). Carotid-femoral pulse wave velocity (PWV)-assessed aortic stiffness was significantly higher in both A3 groups with T2DM compared with G1-2A1 with T2DM (11.15 and 12.35 vs. 8.86 m/s, respectively (p = 0.009))., Conclusions: This study indicates that the presence of severely increased albuminuria in patients with T2DM is cross-sectionally associated with subclinical arterial disease in terms of micro-calcification and aortic stiffness. Additional decrease in kidney function was associated with advanced macro-calcifications., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

Objectives: This study aimed to evaluate the level of evidence of expert recommendations and guidelines for clinical indications and procedurals in hybrid nuclear cardiovascular imaging., Methods: From inception to August 2023, a PubMed literature analysis of the latest version of guidelines for clinical hybrid cardiovascular imaging techniques including SPECT(/CT), PET(/CT), and PET(/MRI) was performed in two categories: (1) for clinical indications for all-in primary diagnosis; subgroup in prognosis and therapy evaluation; and for (2) imaging procedurals. We surveyed to what degree these followed a standard methodology to collect the data and provide levels of evidence, and for which topic systematic review evidence was executed., Results: A total of 76 guidelines, published between 2013 and 2023, were included. The evidence of guidelines was based on systematic reviews in 7.9% of cases, non-systematic reviews in 47.4% of cases, a mix of systematic and non-systematic reviews in 19.7%, and 25% of guidelines did not report any evidence. Search strategy was reported in 36.8% of cases. Strengths of recommendation were clearly reported in 25% of guidelines. The notion of external review was explicitly reported in 23.7% of cases. Finally, the support of a methodologist was reported in 11.8% of the included guidelines., Conclusion: The use of evidence procedures for developing for evidence-based cardiovascular hybrid imaging recommendations and guidelines is currently suboptimal, highlighting the need for more standardized methodological procedures., (© 2024. The Author(s).)

Different types of vasculitis can be distinguished according to the blood vessel's size that is preferentially affected: large-vessel, medium-vessel, and small-vessel vasculitides. Giant cell arteritis (GCA) and Takayasu's arteritis (TAK) are the main forms of large-vessel vasculitis, and may lead to lumen narrowing. Clinical manifestations of arterial narrowing on the short- and long term include vision loss, stroke, limb ischemia, and heart failure. Imaging tools are well established diagnostic tests for large-vessel vasculitis and may aid therapy monitoring in selected cases while providing important information regarding the occurrence of vascular damage, tissue and organ complications. This review aims to provide the current status of multimodality imaging for the diagnosis and identification of vascular complications in the field of large vessel vasculitis., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: LV geometry with shape index (SI) and eccentricity index (EI) measured by myocardial perfusion positron emission tomography/computed tomography (PET/CT) may allow the evaluation of left ventricular (LV) adverse remodeling. This first study aims to explore the relationship of SI and EI values acquired by Nitrogen-13 ammonia PET/CT in patients with normal perfusion, ischemia, and myocardial infarction. And evaluate the correlations between the variables of LV geometry, and with the variables of LV function., Methods and Results: One hundred and forty patients who underwent an electrocardiogram (ECG)-gated PET/CT were selected and classified into 4 groups according to ischemia or infarction burden (normal perfusion, mild ischemia, moderate-severe ischemia, and infarction). The variables were automatically retrieved using dedicated software (QPS/QGS; Cedars-Sinai, Los Angeles, CA, USA). On multicomparison analysis (one-way ANOVA and Dunnett's Test), subjects in the infarction group had significant higher values of SI end-diastolic rest (P < 0.001), and stress (P = 0.003), SI end-systolic rest (P = 0.002) and stress (P < 0.001) as well as statistically significant lower values of EI rest (P < 0.001) and stress (P < 0.001) when compared with all other groups. Regarding Pearson correlation, in the infarcted group all the variables of SI and EI were significantly correlated (P < 0.001) with strong correlation coefficients (>0.60). SI end-systolic correlated significantly with the variables of LV function independently of the group of patients (P < 0.05)., Conclusions: Shape and eccentricity indices differ in patients with myocardial infarction as compared to patients with ischemia or normal perfusion. This encourage further research in their potential for detecting LV adverse remodeling., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

This document on cardiovascular infection, including infective endocarditis, is the first in the American Society of Nuclear Cardiology Imaging Indications (ASNC I 2 ) series to assess the role of radionuclide imaging in the multimodality context for the evaluation of complex systemic diseases with multisocietal involvement including pertinent disciplines. A rigorous modified Delphi approach was used to determine consensus clinical indications, diagnostic criteria, and an algorithmic approach to diagnosis of cardiovascular infection including infective endocarditis. Cardiovascular infection incidence is increasing and is associated with high morbidity and mortality. Current strategies based on clinical criteria and an initial echocardiographic imaging approach are effective but often insufficient in complicated cardiovascular infection. Radionuclide imaging with fluorine-18 fluorodeoxyglucose ( 18 F-FDG) positron emission tomography/computed tomography (CT) and single photon emission computed tomography/CT leukocyte scintigraphy can enhance the evaluation of suspected cardiovascular infection by increasing diagnostic accuracy, identifying extracardiac involvement, and assessing cardiac implanted device pockets, leads, and all portions of ventricular assist devices. This advanced imaging can aid in key medical and surgical considerations. Consensus diagnostic features include focal/multifocal or diffuse heterogenous intense 18 F-FDG uptake on valvular and prosthetic material, perivalvular areas, device pockets and leads, and ventricular assist device hardware persisting on non-attenuation corrected images. There are numerous clinical indications with a larger role in prosthetic valves, and cardiac devices particularly with possible infective endocarditis or in the setting of prior equivocal or non-diagnostic imaging. Illustrative cases incorporating these consensus recommendations provide additional clarification. Future research is necessary to refine application of these advanced imaging tools for surgical planning, to identify treatment response, and more., (Copyright © 2024 by the American Society of Nuclear Cardiology, the American College of Cardiology, Heart Rhythm Society, and the Infectious Diseases Society of America. Published by Elsevier on behalf of the American Society of Nuclear Cardiology, the American College of Cardiology, Heart Rhythm Society, and by Oxford University Press on behalf of the Infectious Diseases Society of America. Published by Elsevier Inc. All rights reserved.)

Background: Cardiovascular disease is the most common cause of death worldwide, including infection and inflammation related conditions. Multiple studies have demonstrated potential advantages of hybrid positron emission tomography combined with computed tomography (PET/CT) as an adjunct to current clinical inflammatory and infectious biochemical markers. To quantitatively analyze vascular diseases at PET/CT, robust segmentation of the aorta is necessary. However, manual segmentation is extremely time-consuming and labor-intensive., Purpose: To investigate the feasibility and accuracy of an automated tool to segment and quantify multiple parts of the diseased aorta on unenhanced low-dose computed tomography (LDCT) as an anatomical reference for PET-assessed vascular disease., Methods: A software pipeline was developed including automated segmentation using a 3D U-Net, calcium scoring, PET uptake quantification, background measurement, radiomics feature extraction, and 2D surface visualization of vessel wall calcium and tracer uptake distribution. To train the 3D U-Net, 352 non-contrast LDCTs from (2-[ 18 F]FDG and Na[ 18 F]F) PET/CTs performed in patients with various vascular pathologies with manual segmentation of the ascending aorta, aortic arch, descending aorta, and abdominal aorta were used. The last 22 consecutive scans were used as a hold-out internal test set. The remaining dataset was randomly split into training (n = 264; 80%) and validation (n = 66; 20%) sets. Further evaluation was performed on an external test set of 49 PET/CTs. The dice similarity coefficient (DSC) and Hausdorff distance (HD) were used to assess segmentation performance. Automatically obtained calcium scores and uptake values were compared with manual scoring obtained using clinical softwares (syngo.via and Affinity Viewer) in six patient images. intraclass correlation coefficients (ICC) were calculated to validate calcium and uptake values., Results: Fully automated segmentation of the aorta using a 3D U-Net was feasible in LDCT obtained from PET/CT scans. The external test set yielded a DSC of 0.867 ± 0.030 and HD of 1.0 [0.6-1.4] mm, similar to an open-source model with a DSC of 0.864 ± 0.023 and HD of 1.4 [1.0-1.8] mm. Quantification of calcium and uptake values were in excellent agreement with clinical software (ICC: 1.00 [1.00-1.00] and 0.99 [0.93-1.00] for calcium and uptake values, respectively)., Conclusions: We present an automated pipeline to segment the ascending aorta, aortic arch, descending aorta, and abdominal aorta on LDCT from PET/CT and to accurately provide uptake values, calcium scores, background measurement, radiomics features, and a 2D visualization. We call this algorithm SEQUOIA (SEgmentation, QUantification, and visualizatiOn of the dIseased Aorta) and is available at https://github.com/UMCG-CVI/SEQUOIA. This model could augment the utility of aortic evaluation at PET/CT studies tremendously, irrespective of the tracer, and potentially provide fast and reliable quantification of cardiovascular diseases in clinical practice, both for primary diagnosis and disease monitoring., (© 2024 The Authors. Medical Physics published by Wiley Periodicals LLC on behalf of American Association of Physicists in Medicine.)

Giant cell arteritis is the principal form of systemic vasculitis affecting people over 50. Large-vessel involvement, termed large vessel giant cell arteritis, mainly affects the aorta and its branches, often occurring alongside cranial giant cell arteritis, but large vessel giant cell arteritis without cranial giant cell arteritis can also occur. Patients mostly present with constitutional symptoms, with localising large vessel giant cell arteritis symptoms present in a minority of patients only. Large vessel giant cell arteritis is usually overlooked until clinicians seek to exclude it with imaging by ultrasonography, magnetic resonance angiography (MRA), computed tomography angiography (CTA), or [ 18 F]fluorodeoxyglucose-PET-CT. Although the role of imaging in treatment monitoring remains uncertain, imaging by MRA or CTA is crucial for identifying aortic aneurysm formation during patient follow up. In this Series paper, we define the large vessel subset of giant cell arteritis and summarise its clinical challenges. Furthermore, we identify areas for future research regarding the management of large vessel giant cell arteritis., Competing Interests: Declaration of interests KSMvdG reports a grant from FOREUM Foundation for Research in Rheumatology, speaker fees from Roche, and research support from AbbVie, all outside the submitted work and paid to the University Medical Center Groningen (UMCG). TAB reports research grants from Deutsche Forschungsgemeinschaft and Siemens Healthineers paid to his institution and personal consulting fees and honoraria for lectures from Bracco, BTR, Guerbet, Siemens Healthineers, Novartis, and Roche. RHJAS reports independent research grants from Siemens Healthineers and Pfizer. EB, as an employee of the UMCG, received grants from the Dutch Arthritis Society and the EU, European Federation of Pharmaceutical Industries and Associations, and Innovative Medicines Initiative 2 Joint Undertaking Immune-Image (grant no 831514), which were paid to the UMCG. All other authors declare no competing interests., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

The role of fibroblast activation protein inhibitor (FAPI) positron emission tomography/computed tomography (PET/CT) is emerging for the assessment of non-oncological diseases, such as inflammatory and infectious diseases, even if the evidence in the literature is still in its initial phases. We conducted a systematic search of Scopus, PubMed/MEDLINE, Embase, and Cochrane library databases for studies published before 31 December 2023 reporting infectious and inflammatory disease imaging with FAPI PET/CT. We included twenty-one studies for a total of 1046 patients. The most frequent disease studied was lung interstitial disease, investigated in six studies for a total of 200 patients, followed by bone and joint diseases in two studies and 185 patients, IgG4-related disease in 53 patients, and Crohn's disease in 30 patients. Despite the heterogeneity of studies in terms of study design and technical features, FAPI PET/CT showed a high detection rate and diagnostic role. Moreover, when compared with 2-[ 18 F]FDG PET/CT ( n = 7 studies), FAPI PET/CT seems to have better diagnostic performances. The presence of chronic inflammation and tissue remodeling, typical of immune-mediated inflammatory conditions, may be the underlying mechanism of FAPI uptake.

Objectives: To update the EULAR recommendations for the use of imaging modalities in primary large vessel vasculitis (LVV)., Methods: A systematic literature review update was performed to retrieve new evidence on ultrasound, MRI, CT and [ 18 F]-fluorodeoxyglucose positron emission tomography (FDG-PET) for diagnosis, monitoring and outcome prediction in LVV. The task force consisted of 24 physicians, health professionals and patients from 14 countries. The recommendations were updated based on evidence and expert opinion, iterating until voting indicated consensus. The level of agreement was determined by anonymous votes., Results: Three overarching principles and eight recommendations were agreed. Compared to the 2018 version, ultrasound is now recommended as first-line imaging test in all patients with suspected giant cell arteritis, and axillary arteries should be included in the standard examination. As an alternative to ultrasound, cranial and extracranial arteries can be examined by FDG-PET or MRI. For Takayasu arteritis, MRI is the preferred imaging modality; FDG-PET, CT or ultrasound are alternatives. Although imaging is not routinely recommended for follow-up, ultrasound, FDG-PET or MRI may be used for assessing vessel abnormalities in LVV patients with suspected relapse, particularly when laboratory markers of inflammation are unreliable. MR-angiography, CT-angiography or ultrasound may be used for long-term monitoring of structural damage, particularly at sites of preceding vascular inflammation., Conclusions: The 2023 EULAR recommendations provide up-to-date guidance for the role of imaging in the diagnosis and assessment of patients with LVV., Competing Interests: Competing interests: CDejaco has received consulting/speaker’s fees from Abbvie, Eli Lilly, Janssen, Novartis, Pfizer, Roche, Galapagos, Sparrow and Sanofi; grant support from AbbVie and Novartis, all unrelated to this manuscript. He is an editorial board member of ARD. SR has received research grants and/or consultancy fees From AbbVie, Eli Lilly, Galapagos, MSD, Novartis, Pfizer, Sanofi, UCB. MB: consultancy fees from AbbVie PB has received speaker fees by Janssen and project grants by Pfizer. CP has received research grants and/or consultancy fees from AbbVie, Vifor, Roche, GlaxoSmithKline and AstraZeneca, all unrelated to this manuscript. SLM reports: Consultancy on behalf of her institution for Roche/Chugai, Sanofi, AbbVie, AstraZeneca; Investigator on clinical trials for Sanofi, GSK, Sparrow; speaking/lecturing on behalf of her institution for Roche/Chugai, Vifor, Pfizer and Novartis; chief investigator on STERLING-PMR trial, funded by NIHR; patron of the charity PMRGCAuk. No personal remuneration was received for any of the above activities. Support from Roche/Chugai to attend EULAR2019 in person and from Pfizer to attend ACR Convergence 2021 virtually. SLM is supported in part by the NIHR Leeds Biomedical Research Centre. TAB reports research grants from Deutsche Forschungsgemeinschaft (DFG) and Siemens Healthineers on behalf of his Department. He has received consulting/speaker’s fees from BioTel Research, Chugai, Guerbet, Novartis, Roche, Sanofi and Siemens Healthineers. DB consultancy fees from Roche and GSKSara Brolin: Grant from Novartis. MCC has received consulting fees from GSK, SCL-Vifor, AbbVie, AstraZeneca and Janssen, and a research grant form Kiniksa Pharmaceuticals. JM-C has received consulting/speaker’s fees from Abbvie, Lilly, Janssen, Novartis, Pfizer, UCB, MSD, all unrelated to this manuscript. BD has received consultancies and educational grants from Novartis, Abbvie, Roche, Chugai, Sanofi. BDN has received consulting/speaker’s fees from Roche and Novartis all unrelated to this manuscript. EDM Research funding/consulting and conferences fees from: Abbvie, Novartis, Pfizer, Roche, Janssen, Lilly, MSD, BMS, UCB, Grunental and Sanofi. CDuftner has received consulting/speaker’s fees from Abbvie, AOP Orphan, Astra-Zeneca, Bristol-Myers-Squibb, Eli-Lilly, Janssen, Galapagos, Merck-Sharp-Dohme, Novartis, Pfizer, Roche, Sandoz, UCB, Vifor, and grant/research support from Eli-Lilly, Pfizer, UCBHaner Direskeneli is investigator in clinical trials for Abbvie and Novartis, had educational support from Pfizer, Amgene, Celltrion, UCB and Roche unrelated to this manuscript. AM has received research grants and/or consultancy fees From AbbVie, BMS, Biogen, Eli Lilly, Galapagos, Janssen, MSD, Novartis and UCB. LS has received grant support from the Swiss Society of Rheumatology, iQone and Sandoz and support for travel expenses from Sanofi; all unrelated to this manuscript. RHJAS has received independent research grants of Siemens Healtineers and WAS has received consultancy fees, honoraria and travel expenses from Abbvie, Chugai, GlaxoSmithKline, Medac, Novartis, Roche, and Sanofi and is principal investigator in trials sponsored by Abbvie, GlaxoSmithKline, Novartis and Sanofi., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

This document on cardiovascular infection, including infective endocarditis, is the first in the American Society of Nuclear Cardiology Imaging Indications (ASNC I 2 ) series to assess the role of radionuclide imaging in the multimodality context for the evaluation of complex systemic diseases with multi-societal involvement including pertinent disciplines. A rigorous modified Delphi approach was used to determine consensus clinical indications, diagnostic criteria, and an algorithmic approach to diagnosis of cardiovascular infection including infective endocarditis. Cardiovascular infection incidence is increasing and is associated with high morbidity and mortality. Current strategies based on clinical criteria and an initial echocardiographic imaging approach are effective but often insufficient in complicated cardiovascular infection. Radionuclide imaging with 18 F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (CT) and single photon emission computed tomography/CT leukocyte scintigraphy can enhance the evaluation of suspected cardiovascular infection by increasing diagnostic accuracy, identifying extracardiac involvement, and assessing cardiac implanted device pockets, leads, and all portions of ventricular assist devices. This advanced imaging can aid in key medical and surgical considerations. Consensus diagnostic features include focal/multi-focal or diffuse heterogenous intense 18 F-FDG uptake on valvular and prosthetic material, perivalvular areas, device pockets and leads, and ventricular assist device hardware persisting on non-attenuation corrected images. There are numerous clinical indications with a larger role in prosthetic valves, and cardiac devices particularly with possible infective endocarditis or in the setting of prior equivocal or non-diagnostic imaging. Illustrative cases incorporating these consensus recommendations provide additional clarification. Future research is necessary to refine application of these advanced imaging tools for surgical planning, to identify treatment response, and more., (Copyright © 2024 2024 The American Society of Nuclear Cardiology, the American College of Cardiology, Heart Rhythm Society, and the Infectious Diseases Society of America. Published by Elsevier on behalf of the American Society of Nuclear Cardiology, the American College of Cardiology, Heart Rhythm Society, and by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. Published by Elsevier Inc. All rights reserved.)

Chronic immune diseases mainly include autoimmune and inflammatory diseases. Managing chronic inflammatory and autoimmune diseases has become a significant public health concern, and therapeutic advancements over the past 50 years have been substantial. As therapeutic tools continue to multiply, the challenge now lies in providing each patient with personalized care tailored to the specifics of their condition, ushering in the era of personalized medicine. Precise and holistic imaging is essential in this context to comprehensively map the inflammatory processes in each patient, identify prognostic factors, and monitor treatment responses and complications. Imaging of patients with inflammatory and autoimmune diseases must provide a comprehensive view of the body, enabling the whole-body mapping of systemic involvement. It should identify key cellular players in the pathology, involving both innate immunity (dendritic cells, macrophages), adaptive immunity (lymphocytes), and microenvironmental cells (stromal cells, tissue cells). As a highly sensitive imaging tool with vectorized molecular probe capabilities, PET/CT can be of high relevance in the management of numerous inflammatory and autoimmune diseases. Relying on key molecular concepts of immunity, the clinical usefulness of FDG-PET/CT in several relevant inflammatory and immune-inflammatory conditions, validated or emerging, will be discussed in this review, together with radiolabeled probe perspectives., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Objectives: This study directly compares diagnostic performance of Colour Duplex Ultrasound (CDUS), Fluor-18-deoxyglucose Positron Emission Tomography Computed Tomography (FDG-PET/CT) and Magnetic Resonance Imaging (MRI) in patients suspected of giant cell arteritis (GCA)., Methods: Patients with suspected GCA were included in a nested-case control pilot study. CDUS, whole body FDG-PET/CT and cranial MRI were performed within 5 working days after initial clinical evaluation. Clinical diagnosis after six months follow-up by experienced rheumatologists in the field of GCA, blinded for imaging, was used as reference standard. Diagnostic performance of the imaging modalities was determined. Stratification for GCA subtype was performed and imaging results were evaluated in different risk stratification groups., Results: In total, 23 patients with GCA and 19 patients suspected of but not diagnosed with GCA were included. Sensitivity was 69.6% (95%CI 50.4%-88.8%) for CDUS, 52.2% (95%CI 31.4%-73.0%) for FDG-PET/CT and 56.5% (95%CI 35.8%-77.2%) for MRI. Specificity was 100% for CDUS, FDG-PET/CT and MRI. FDG-PET/CT was negative for GCA in all isolated cranial GCA patients (n = 8), while MRI was negative in all isolated extracranial GCA patients (n = 4). In 4 GCA patients with false-negative (n = 2; intermediate and high risk) or inconclusive (n = 2; low and intermediate risk) CDUS results, further imaging confirmed diagnosis., Conclusions: Sensitivity of CDUS was highest, while specificity was excellent in all imaging modalities. Nevertheless, confidence intervals of all imaging modalities were overlapping. Following EULAR recommendations, CDUS can be used as a first test to diagnose GCA. With insufficient evidence for GCA, further testing considering GCA subtype is warranted., (© The Author(s) 2024. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Objective: The aim of this study was to evaluate and compare reliability, costs, and radiation dose of dual-energy X-ray absorptiometry (DXA) to MRI and CT in measuring muscle mass for the diagnosis of sarcopenia., Methods: Thirty-four consecutive DXA scans performed in surgically menopausal women from November 2019 until March 2020 were analyzed by two observers. Observers analyzed muscle mass of the lower limbs in every scan twice. Reliability was assessed by calculating inter- and intra-observer variability. Reliability from CT and MRI as well as radiation dose from CT and DXA were collected from literature. Costs for each type of scan were calculated according to the guidelines for economic evaluation of the Dutch National Health Care Institute., Results: The 34 participants had a median age of 58 years (IQR 53-65) and a median body mass index of 24.6 (IQR 21.7-29.7). Inter-observer variability had an intraclass correlation coefficient (ICC) of 0.997 (95% CI 0.994-0.998) with a relative variability of 0.037 ± 0.022%. Regarding intra-observer variability, observer 1 had an ICC of 0.998 (95% CI 0.996-0.999) with a relative variability of 0.019 ± 0.016% and observer 2 had an ICC of 0.997 (95% CI 0.993-0.998) with a relative variability of 0.016 ± 0.011%. DXA costs were €62, CT €77, and MRI €195. The estimated radiation dose of CT was 2.5-3.0 mSv, for DXA this was 2-4 µSv., Conclusions: DXA has lower costs and a lower radiation dose, with low inter- and intra-observer variability, compared to CT and MRI for assessing lower limb muscle mass., Trial Registration: Netherlands Trial Register; NL8068., Critical Relevance Statement: DXA is a good alternative for CT and MRI in assessing lower limb muscle mass, with lower costs and lower radiation dose, while inter-observer and intra-observer variability are low., Key Points: • Screening for sarcopenia should be optimized as the population ages. • DXA outperformed CT and MRI in the measured metrics. • DXA validity should be further evaluated as an alternative to CT and MRI for sarcopenia evaluation., (© 2024. The Author(s).)

Background: Currently, computed tomography (CT) is used for risk profiling of (asymptomatic) individuals by calculating coronary artery calcium scores. Although this score is a strong predictor of major adverse cardiovascular events, this method has limitations. Sodium [ 18 F]fluoride (Na[ 18 F]F) positron emission tomography (PET) has shown promise as an early marker for atherosclerotic progression. However, evidence on Na[ 18 F]F as a marker for high-risk plaques is limited, particularly on its presentation in clinical PET/CT. Besides, the relationship between microcalcifications visualized by Na[ 18 F]F PET and macrocalcifications detectable on CT is unknown., Purpose: To establish a match/mismatch score in the aorta between macrocalcified plaque content on CT and microcalcification Na[ 18 F]F PET uptake., Methods: Na[ 18 F]F-PET/CT scans acquired in our centre in 2019-2020 were retrospectively collected. The aorta of each low-dose CT was manually segmented. Background measurements were placed in the superior vena cava. The vertebrae were automatically segmented using an open-source convolutional neural network, dilated with 10 mm, and subtracted from the aortic mask. Per patient, calcium and Na[ 18 F]F-hotspot masks were retrieved using an in-house developed algorithm. Three match/mismatch analyses were performed: a population analysis, a per slice analysis, and an overlap score. To generate a population image of calcium and Na[ 18 F]F hotspot distribution, all aortic masks were aligned. Then, a heatmap of calcium HU and Na[ 18 F]F-uptake on the surface was obtained by outward projection of HU and uptake values from the centerline. In each slice of the aortic wall of each patient, the calcium mass score and target-to-bloodpool ratios (TBR) were calculated within the calcium masks, in the aortic wall except the calcium masks, and in the aortic wall in slices without calcium. For the overlap score, three volumes were identified in the calcium and Na[ 18 F]F masks: volume of PET (PET+/CT-), volume of CT (PET-/CT+), and overlapping volumes (PET+/CT+). A Spearman's correlation analysis with Bonferroni correction was performed on the population image, assessing the correlation between all HU and Na[ 18 F]F vertex values. In the per slice analysis, a paired Wilcoxon signed-rank test was used to compare TBR values within each slice, while an ANOVA with post-hoc Kruskal-Wallis test was employed to compare TBR values between slices. p-values < 0.05 were considered significant., Results: In total, 186 Na[ 18 F]F-PET/CT scans were included. A moderate positive exponential correlation was observed between total aortic calcium mass and total aortic TBR (r = 0.68, p < 0.001). A strong positive correlation (r = 0.77, p < 0.0001) was observed between CT values and Na[ 18 F]F values on the population image. Significantly higher TBR values were found outside calcium masks than inside calcium masks (p < 0.0001). TBR values in slices where no calcium was present, were significantly lower compared with outside calcium and inside calcium (both p < 0.0001). On average, only 3.7% of the mask volumes were overlapping., Conclusions: Na[ 18 F]F-uptake in the aorta behaves similarly to macrocalcification detectable on CT. Na[ 18 F]F-uptake values are also moderately correlated to calcium mass scores (match). Higher uptake values were found just outside macrocalcification masks instead of inside the macrocalcification masks (mismatch). Also, only a small percentage of the Na[ 18 F]F-uptake volumes overlapped with the calcium volumes (mismatch)., (© 2023 The Authors. Medical Physics published by Wiley Periodicals LLC on behalf of American Association of Physicists in Medicine.)

Because of the limited axial field of view of conventional PET scanners, the internal carotid arteries are commonly used to obtain an image-derived input function (IDIF) in quantitative brain PET. However, time-activity curves extracted from the internal carotids are prone to partial-volume effects due to the limited PET resolution. This study aimed to assess the use of the internal carotids for quantifying brain glucose metabolism before and after partial-volume correction. Methods: Dynamic [ 18 F]FDG images were acquired on a 106-cm-long PET scanner, and quantification was performed with a 2-tissue-compartment model and Patlak analysis using an IDIF extracted from the internal carotids. An IDIF extracted from the ascending aorta was used as ground truth. Results: The internal carotid IDIF underestimated the area under the curve by 37% compared with the ascending aorta IDIF, leading to K i values approximately 17% higher. After partial-volume correction, the mean relative K i differences calculated with the ascending aorta and internal carotid IDIFs dropped to 7.5% and 0.05%, when using a 2-tissue-compartment model and Patlak analysis, respectively. However, microparameters ( K 1 , k 2 , k 3 ) derived from the corrected internal carotid curve differed significantly from those obtained using the ascending aorta. Conclusion: These results suggest that partial-volume-corrected internal carotids may be used to estimate K i but not kinetic microparameters. Further validation in a larger patient cohort with more variable kinetics is needed for more definitive conclusions., (© 2024 by the Society of Nuclear Medicine and Molecular Imaging.)

This document on cardiovascular infection, including infective endocarditis, is the first in the American Society of Nuclear Cardiology Imaging Indications (ASNC I2) series to assess the role of radionuclide imaging in the multimodality context for the evaluation of complex systemic diseases with multi-societal involvement including pertinent disciplines. A rigorous modified Delphi approach was used to determine consensus clinical indications, diagnostic criteria, and an algorithmic approach to diagnosis of cardiovascular infection including infective endocarditis. Cardiovascular infection incidence is increasing and is associated with high morbidity and mortality. Current strategies based on clinical criteria and an initial echocardiographic imaging approach are effective but often insufficient in complicated cardiovascular infection. Radionuclide imaging with 18F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) and single photon emission computed tomography/CT leukocyte scintigraphy can enhance the evaluation of suspected cardiovascular infection by increasing diagnostic accuracy, identifying extracardiac involvement, and assessing cardiac implanted device pockets, leads, and all portions of ventricular assist devices. This advanced imaging can aid in key medical and surgical considerations. Consensus diagnostic features include focal/multi-focal or diffuse heterogenous intense 18F-FDG uptake on valvular and prosthetic material, perivalvular areas, device pockets and leads, and ventricular assist device hardware persisting on non-attenuation corrected images. There are numerous clinical indications with a larger role in prosthetic valves, and cardiac devices particularly with possible infective endocarditis or in the setting of prior equivocal or non-diagnostic imaging. Illustrative cases incorporating these consensus recommendations provide additional clarification. Future research is necessary to refine application of these advanced imaging tools for surgical planning, to identify treatment response, and more., (© 2024 The American Society of Nuclear Cardiology, The American College of Cardiology, Heart Rhythm Society, and the Infectious Disease Society of America. Published by Elsevier on behalf of the American Society of Nuclear Cardiology, the American College of Cardiology, Heart Rhythm Society, and by Oxford University Press on behalf of the Infectious Disease Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Reducing proteinuria is a crucial approach in preventing kidney function loss. Previous preclinical studies indicated that caloric restriction (CR) imposed at a young age protects against age-related proteinuria. However, these studies have not explored CR in established renal disease. Therefore, this study aimed to investigate the impact of CR on established proteinuria. Rats, aged 12 ± 2 weeks, were administered 2.1 mg/kg of Adriamycin. Six weeks after injection, protein excretion was measured, and a [ 13 N]ammonia positron emission tomography (PET) scan was conducted to assess kidney perfusion. After 7 weeks rats were divided into four groups: ad libitum (AL) and CR groups fed either a 12% or a 20% protein diet. All groups were treated for 12 weeks. Blood pressure was measured and a second PET scan was acquired at the end of the study. The animals subjected to CR exhibited a 20.3% decrease in protein excretion (p = 0.003) compared to those in the AL groups. Additionally, blood pressure in the CR group was 21.2% lower (p < 0.001) than in the AL groups. While kidney function declined over time in all groups, the 20% CR group demonstrated the smallest decline. Thus CR effectively reduces urinary protein excretion and lowers blood pressure in rats with established proteinuria., (© 2024 The Authors. Physiological Reports published by Wiley Periodicals LLC on behalf of The Physiological Society and the American Physiological Society.)

Digital PET/CT systems with a long axial field of view have become available and are emerging as the current state of the art. These new camera systems provide wider anatomic coverage, leading to major increases in system sensitivity. Preliminary results have demonstrated improvements in image quality and quantification, as well as substantial advantages in tracer kinetic modeling from dynamic imaging. These systems also potentially allow for low-dose examinations and major reductions in acquisition time. Thereby, they hold great promise to improve PET-based interrogation of cardiac physiology and biology. Additionally, the whole-body coverage enables simultaneous assessment of multiple organs and the large vascular structures of the body, opening new opportunities for imaging systemic mechanisms, disorders, or treatments and their interactions with the cardiovascular system as a whole. The aim of this perspective document is to debate the potential applications, challenges, opportunities, and remaining challenges of applying PET/CT with a long axial field of view to the field of cardiovascular disease., (© 2024 by the Society of Nuclear Medicine and Molecular Imaging.)

Objectives: To compare clinical characteristics, imaging findings and treatment requirements of patients with immune checkpoint inhibitor-mediated polymyalgia rheumatica (ICI-PMR) and primary PMR., Methods: This single centre, retrospective cohort study compared ICI-PMR in patients with cancer (n = 15) to patients with primary PMR (n = 37). A comparison was made between clinical symptoms, laboratory markers, ultrasonography,18F-FDG-PET/CT findings and treatment requirements related to PMR., Results: Patients with ICI-PMR less frequently fulfilled the EULAR/ACR classification criteria for PMR (66.7%) than patients with primary PMR (97.3%). Morning stiffness, weight loss and elevation of the ESR were less frequently seen in patients with ICI-PMR. No differences were observed regarding the presence of inflammatory lesions on ultrasound of the shoulders and hips between the two groups. The Leuven and the Leuven/Groningen 18F-FDG-PET/CT scores were significantly lower in the ICI-PMR group. Finally, the ICI-PMR group could be managed with less glucocorticoids than the primary PMR group., Conclusion: Our findings indicate that ICI-PMR may have a milder course with less inflammation than primary PMR on 18F-FDG-PET/CT. ICI-mediated PMR patients can be managed with a relatively low glucocorticoid dose. Our study underscores that ICI-PMR should be regarded as PMR-like syndrome., (© The Author(s) 2024. Published by Oxford University Press on behalf of the British Society for Rheumatology.)

Purpose: There is a need for early quantitative markers of potential treatment response in patients with hereditary transthyretin (ATTRv) amyloidosis to guide therapy. This study aims to evaluate changes in cardiac tracer uptake on bone scintigraphy in ATTRv amyloidosis patients on different treatments., Methods: In this retrospective cohort study, outcomes of 20 patients treated with the transthyretin (TTR) gene silencer patisiran were compared to 12 patients treated with a TTR-stabilizer. Changes in NYHA class, cardiac biomarkers in serum, wall thickness, and diastolic parameters on echocardiography and NYHA class during treatment were evaluated., Results: Median heart/whole-body (H/WB) ratio on bone scintigraphy decreased from 4.84 [4.00 to 5.31] to 4.16 [3.66 to 4.81] (p < .001) in patients treated with patisiran for 29 [15-34] months. No changes in the other follow-up parameters were observed. In patients treated with a TTR-stabilizer for 24 [20 to 30] months, H/WB ratio increased from 4.46 [3.24 to 5.13] to 4.96 [ 3.39 to 5.80] (p = .010), and troponin T increased from 19.5 [9.3 to 34.0] ng/L to 20.0 [11.8 to 47.8] ng/L (p = .025). All other parameters did not change during treatment with a TTR-stabilizer., Conclusion: A change in cardiac tracer uptake on bone scintigraphy may be an early marker of treatment-specific response or disease progression in ATTRv amyloidosis patients., (© 2023. The Author(s).)

Aim: Sodium-glucose co-transporter 2 inhibitors and mineralocorticoid receptor antagonists reduce albuminuria and the risk of kidney failure. The aim of this study was to investigate the effects of both agents alone and in combination on markers of the glomerular endothelial glycocalyx and tubular function., Methods: This post-hoc analysis utilized data of the ROTATE-3 study, a randomized cross-over study in 46 adults with chronic kidney disease and urinary albumin excretion ≥100 mg/24 h, who were treated for 4 weeks with dapagliflozin, eplerenone or its combination. The effects of dapagliflozin, eplerenone and the combination on outcome measures such as heparan sulphate, neuro-hormonal markers and tubular sodium handling were assessed with mixed repeated measures models., Results: The mean percentage change from baseline in heparan sulphate after 4 weeks treatment with dapagliflozin, eplerenone or dapagliflozin-eplerenone was -34.8% (95% CI -52.2, -10.9), -5.9% (95% CI -32.5, 31.3) and -28.1% (95% CI -48.4, 0.1) respectively. The mean percentage change from baseline in plasma aldosterone was larger with eplerenone [38.9% (95% CI 2.8, 87.7)] and dapagliflozin-eplerenone [32.2% (95% CI -1.5, 77.4)], compared with dapagliflozin [-12.5% (95% CI -35.0, 17.8)], respectively. Mean percentage change from baseline in copeptin with dapagliflozin, eplerenone or dapagliflozin-eplerenone was 28.4% (95% CI 10.7, 49.0), 4.2% (95% CI -10.6, 21.4) and 23.8% (95% CI 6.6, 43.9) respectively. Dapagliflozin decreased proximal absolute sodium reabsorption rate by 455.9 mmol/min (95% CI -879.2, -32.6), while eplerenone decreased distal absolute sodium reabsorption rate by 523.1 mmol/min (95% CI -926.1, -120.0). Dapagliflozin-eplerenone decreased proximal absolute sodium reabsorption [-971.0 mmol/min (95% CI -1411.0, -531.0)], but did not affect distal absolute sodium reabsorption [-9.2 mmol/min (95% CI -402.0, 383.6)]., Conclusions: Dapagliflozin and eplerenone exert different effects on markers of glomerular and tubular function supporting the hypothesis that different mechanistic pathways may account for their kidney protective effects., (© 2023 The Authors. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.)

(1) Background: Individuals carrying a pathogenic transthyretin gene variant ( TTRv ) are at high risk for developing hereditary transthyretin (ATTRv) amyloidosis and are routinely screened for the development of cardiomyopathy (ATTRv-CM). This study aims to evaluate whether the cardiac biomarkers N-terminal pro B-type natriuretic peptide (NT-proBNP) and high-sensitivity cardiac troponin T (hs-cTnT) can be used to rule out ATTRv-CM. (2) Methods: In this retrospective case-control study, data from 46 ATTRv-CM patients and 101 TTRv carriers and ATTRv amyloidosis patients without cardiomyopathy were included. Binary logistic regression models were used to assess the ability of NT-proBNP and hs-cTnT to predict the diagnosis of ATTRv-CM. An optimal cutoff for the relevant biomarker(s) was determined based on a sensitivity of ≥99% and the highest possible percentage of additional tests avoided (%ATA) in the index dataset. (3) Results: Hs-cTnT demonstrated the highest predictive capabilities for ATTRv-CM. The addition of NT-proBNP did not improve the predictive model. A hs-cTnT cutoff of <6 ng/L resulted in a 97% sensitivity and a negative predictive value of 95% with a %ATA of 30% in the validation dataset. (4) Conclusion: In conclusion, hs-cTnT is a useful biomarker for excluding cardiac involvement in TTRv carriers and ATTRv amyloidosis patients and it has the potential to prevent unnecessary diagnostic procedures.