Abstract: Giant Cell Arteritis (GCA) is an autoimmune/autoinflammatory disease affecting large vessels in patients over 50 years old. The disease presents as an acute inflammatory response with two phenotypes, cranial-GCA and Large Vessel Vasculitis (LV)-GCA, involving the thoracic aor-ta and its branches. 18F-fluorodeoxyglucose positron emission tomography-computed tomogra-phy (18F-FDG PET-CT) is among the imaging techniques contributing to diagnosis of patients with systemic disease. However, its association with soluble inflammatory markers is still elu-sive. This proof-of-concept study aims to identify novel soluble serum biomarkers in PET/CT pos-itive patients with LV-GCA and associate them with active (0 months) and inactive disease (6 months following treatment), in sequential samples. The Most-Disease-Segment Target-to-Background Ratio (TBRMDS) was calculated for 9 LV-GCA patients, while 12 cranial-GCA and 7 Polymyalgia Rheumatica patients with negative initial PET/CT served as disease controls. Serum macrophage-related cytokines were evaluated by Cytometric Bead Array (CBA). Finally, previously published NMR-metabolomics data acquired at the same blood sampling were associated with PET/CT findings. TBRMDS was significantly increased in active versus inactive disease (3.45 vs. 2.55, p=0.008). The analysis identified 6 serum metabolites, as more sensitive to change from the active to inactive state. Among them, choline levels were exclusively altered in the LV-GCA group, but not the disease controls. Cytokine levels were not associated with PET/CT activity. Combining with CRP, ESR, and TBRMDS a composite index was generated to depict well the differences between active and inactive systemic LV-GCA (25.45 vs 11.45, p=0.0039). These preliminary results could pave the way for more extensive studies integrating serum metabolomic parameters with PET/CT imaging data to extract sensitive composite disease indexes useful for the everyday clinical practice.

Giant cell arteritis (GCA) is an autoimmune/autoinflammatory disease affecting large vessels in patients over 50 years old. The disease presents as an acute inflammatory response with two phenotypes, cranial GCA and large-vessel vasculitis (LV)-GCA, involving the thoracic aorta and its branches. 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET-CT) is among the imaging techniques contributing to diagnosing patients with systemic disease. However, its association with soluble inflammatory markers is still elusive. This proof-of-concept study aims to identify novel soluble serum biomarkers in PET/CT-positive patients with LV-GCA and associate them with active (0 months) and inactive disease (6 months following treatment), in sequential samples. The most-diseased-segment target-to-background ratio (TBRMDS) was calculated for 13 LV-GCA patients, while 14 cranial GCA and 14 Polymyalgia Rheumatica patients with negative initial PET/CT scans served as disease controls. Serum macrophage-related cytokines were evaluated by cytometric bead array (CBA). Finally, previously published NMR/metabolomics data acquired from the same blood sampling were analyzed along with PET/CT findings. TBRMDS was significantly increased in active versus inactive disease (3.32 vs. 2.65, p = 0.006). The analysis identified nine serum metabolites as more sensitive to change from the active to inactive state. Among them, choline levels were exclusively altered in the LV-GCA group but not in the disease controls. Cytokine levels were not associated with PET/CT activity. Combining CRP, ESR, and TBRMDS with choline levels, a composite index was generated to distinguish active and inactive LV-GCA (20.4 vs. 11.62, p = 0.001). These preliminary results could pave the way for more extensive studies integrating serum metabolomic parameters with PET/CT imaging data to extract sensitive composite disease indexes useful for everyday clinical practice.

BACKGROUND Despite advances in the treatment of oncology patients, therapy-related side effects may lead to premature morbidity. Inflammatory activation that has been linked to cardiovascular disease is crucial for the pathogenesis of both Hodgkin (HL) and non-Hodgkin lymphoma (NHL). OBJECTIVES The purpose of this study was to assess the vascular effects of chemotherapy in patients with HL and NHL by positron emission tomography/computed tomography with 18-fluorodeoxyglucose (18-FDG PET/CT) and to investigate interactions with systemic inflammation as assessed by circulating inflammatory markers. METHODS Between July 2015 and July 2019, 65 consecutive patients (mean age 56 f 17.78 years) with confirmed diagnosis of either HL (n = 33) or NHL (n = 32) were prospectively studied. PET/CT imaging was performed at baseline, at an interim phase, and after first-line treatment. Aortic FDG uptake was assessed by measuring global aortic target-to-background ratio (GLA-TBR). Serum biomarkers interleukin (IL)-6 and IL-1b were measured at each phase. RESULTS Patients with HL demonstrated significant reduction in aortic TBR after first-line treatment (median GLA-TBR baseline: 1.98, median GLA-TBR third scan: 1.75, median difference =-0.20, 95% CI:-0.07 to-0.33, P = 0.006), which remained significant after adjustment for confounders (adj. R2 of model = 0.53). In contrast, patients with NHL did not demonstrate a significant aortic inflammation response (P = 0.306). Furthermore, patients with HL demonstrated a significant reduction in IL-6 (P = 0.048) and IL-1b (P = 0.045), whereas patients with NHL did not demonstrate significant reduction in IL-6 (P = 0.085) and IL-1b levels (P = 0.476). CONCLUSIONS Aortic inflammation, as assessed by 18-FDG PET/CT, is reduced in HL patients after first-line treatment but not in NHL patients. These findings imply that different pathophysiological pathways and different therapies might affect the arterial bed in different ways for patients with lymphoma. (c) 2023 The Authors. Published by Elsevier on behalf of the American College of Cardiology Foundation. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).

Abstract Background The role of inflammation in Marfan Syndrome (MS) has been well studied in current research. These studies have investigated the role of serum Interleukin 6 (IL-6), Transforming Growth Factor-b (TGF-b) and Macrophage Colony Stimulating Factor (MCSF) as biomarkers of disease severity and progression. Surgical repair is the recommended treatment of aortic aneurysms when aortic diameter reaches the indication threshold. It has been observed however that dissection may occur even before this threshold is reached. 18-fluorodeoxyglucose (18 F-FDG) positron emission tomography / computed tomography (PET/CT) is the gold standard imaging modality to noninvasively assess vascular inflammation. Purpose Our aim was to investigate whether MS patients have increased aortic wall inflammation as assessed by 18F-FDG PET/CT, and the relationship between aortic wall inflammation with serum levels of IL-6, TGF-b and MCSF. Methods The study population consisted of fifteen MS patients and seventeen sex and age matched controls. In all subjects, serum levels of circulating IL-6, TGF-b and MCSF were measured. In PET/CT, the arterial target-to-background ratio (TBR) was calculated for aortic root (AR), ascending aorta(As), aortic arch (AA) and descending aorta (DA). Also, all patients were assessed with transthoracic echocardiography where the diameters of AR, As, AA, and DA were estimated at baseline and were reexamined at the end of the follow up period. Results TBR for MS vs. controls was 2.17±0.75 vs 2.01±0.36, p=0.75 at AR; 2.15±0.67 vs 1.84±0.35, p=0.040 at As; 2.16±0.64 vs 1.70±0.25, p=0.03 at AA and 1.97±0.52 vs 1.83±0.42, p=0.23 at DA respectively. Additionally, Marfan patients had increased levels of serum biomarkers. However, this difference was statistically significant (SS) only for IL-6 serum levels; 2.17±0.46 vs 1.08±0.12 p=0.011 and IL-6 was SS associated with AR TBR (rho=0.572, p=0.033), As TBR (rho=0.604, p=0.022) and DA TBR (rho=0.714, p=0.004). Two of our patients were operated due to severe dilatation of the aortic root and the surgical specimens showed aortic wall inflammation of moderate severity along with fibrosis. Conclusion MS patients have increased of aortic wall inflammation as assessed by 18F-FDG PET/CT, a finding that highlights the role of inflammation in the pathway of disturbed TGF signaling. Further research is needed to determine its prognostic role and value in identifying patients with an indication for early intervention.

Aim Arterial involvement has been implicated in the coronavirus disease of 2019 (COVID-19). 18F-fluoro-2-deoxy-d-glucose positron emission tomography/computed tomography (18F-FDG PET/CT) imaging is a valuable tool for the assessment of disease severity in different types of vasculitis and is a predictor of outcome. We sought to prospectively assess the presence of aortic inflammation and its time-dependent trend by measuring the 18-FDG uptake in PET/CT in patients with severe or critical COVID-19. Methods In this pilot case control study, we recruited 20 patients, who were admitted with severe or critical COVID-19 illness. Patients underwent imaging between 20 to 120 days after hospital admission. Ten age- and sex-matched individuals with prior history of malignancy but free of active disease served as the control group. Arterial inflammation was assessed by measuring 18-FDG uptake in PET/CT and calculating aortic target to blood ratio (TBR). Results There was a significant correlation between aortic TBR values and time distance from diagnosis to 18F-FDG PET/CT scan (-rho- =0.547, p=0.015) even after adjustment for confounders (p=0.002). Patients who were scanned less than 60 days (median) from diagnosis had significantly higher TBR values compared to patients examined more than 60 days post-diagnosis (1.55 [1.47-1.61] vs 1.40 [1.33-1.45], respectively, p=0.013). Conclusion This is the first study suggesting that 18 FDG PET/CT imaging could be used for assessment of arterial inflammation in patients with severe/critical COVID-19. These findings may have important implications for the understanding of the pathophysiology and the course of the disease and for improving our preventive and therapeutic strategies.

Abstract Background Despite advances in the treatment of oncology patients, therapy-related side effects may lead to premature morbidity among cancer survivors. Inflammatory activation that has been linked to cardiovascular disease is particularly crucial for the pathogenesis of both Hodgkin (HL) and non-Hodgkin lymphoma (NHL). Objectives To assess the vascular effects of chemotherapy in patients with HL and NHL by 18-Fluorodeoxyglucose (FDG PET/CT) and to investigate possible interactions with systemic inflammation as assessed by circulating inflammatory markers. Methods Between July 2015 and July 2019, sixty-five consecutive patients (37 males, mean age 56±17.8 years) with histologically confirmed new diagnosis of either HL (n=33) or NHL (n=32), were prospectively studied. PET/CT imaging was performed at baseline, at an interim phase and after 1st line treatment. Aortic FDG uptake was assessed by measuring global aortic TBR. Serum interleukin-6 (IL6) and interleukin-1b (IL1b) were measured at each phase for all patients and served as circulating inflammatory markers. Results Patients with HL demonstrated significant reduction in aortic TBR after 1st line treatment (aortic TBRbaseline=1.98, aorticTBR3rdscan=1.75, p=0.001, F=8.335), which remained significant after adjustment for 10-year cardiovascular risk (Framingham risk score), dyslipidemia, hypertension and diabetes (p=0.002, F=7.664). In contrast, patients with NHL did not demonstrate a significant aortic inflammation response (aortic TBRbaseline = 2.13, aorticTBR3rd scan=2.015, p=0.596, F=0.527), Figure 1. Regarding inflammatory markers, after 1st line treatment IL6 levels were reduced significantly in both HL and NHL groups (IL6baseline HL=3.25, IL6 post 1st line treatment HL=0.448, p=0.00; IL6baseline NHL=0.475, IL6 post 1st line treatment NHL=0.144, p=0.001); IL1b levels did not change significantly in either group, Table 1. Conclusions We demonstrate for the first time that aortic inflammation as assessed by 18-FDG PET-CT is reduced in HL patients after 1st line treatment but not in NHL patients. These findings imply that different pathophysiological pathways and different therapies might affect the arterial bed in different ways in lymphoma patients. Further, a strong potential role of molecular imaging in cardio-oncology emerges, offering valuable information on disease prognosis and progression with a single examination. Funding Acknowledgement Type of funding sources: Foundation. Main funding source(s): Hellenic Society of Hypertension

Abstract Background Computed Tomography Coronary Angiography (CTCA) is an effective non-invasive imaging modality for anatomo-functional assessment of coronary artery disease (CAD). Radiomics features have been used for diagnosis or outcome prediction, however, their potential value for characterizing flow limiting coronary lesions has not been explored. Purpose To assess whether application of novel radiomics and machine learning (ML) techniques on CTCA derived datasets improves characterization of functionally significant coronary lesions. Methods Consecutive patients with stable chest pain and intermediate pre-test likelihood for CAD, who underwent CTCA and PET-or SPECT-Myocardial Perfusion Imaging (MPI) respectively, were prospectively evaluated and included in the analysis. PET-MPI was considered abnormal when >1 contiguous segments showed both stress Myocardial Blood Flow ≤2.3mL/g/min and Myocardial Flow Reserve (MFR) ≤2.5 for 15O-water or <1.79 mL/g/min and ≤2.0 for 13N-ammonia respectively. Defect reversibility (DR) was defined as a summed difference score (SDS) between stress and rest images ≥2. CTCA and functional images were fused to assign each myocardial segment to the pertinent coronary territory. Stenosis severity, plaque characteristics and radiomic plaque features were assessed in the total length of the 3 main coronary vessels. In total, 1765 features were extracted from each vessel and a feature reduction and model creation pipeline was constructed [Figure 1]. Two separate datasets: a) coronary stenosis (≥50%) + plaque characteristics and b) coronary stenosis (≥50%) + plaque characteristics + radiomics were formulated and compared in terms of AUCs accordingly. Results A total of 292 coronary vessels (140 with corresponding PET-MPI data and 152 with SPECT MPI data) were analysed. Plaque burden and stenosis severity were the only independent predictors of impaired myocardial perfusion on PET-MPI, with an AUC = 0.749, (95% CI: 0.658–0.826). Stenosis severity, kurtosis, contrast, interquartile range and entropy were predictors of an abnormal PET-MPI result and their combination resulted in an AUC = 0.854, (95% CI: 0.775–0.914). The difference between the 2 models was statistically significant (p-diff: 0.02, 95% CI: 0.0165–0.194). Stenosis severity was the only predictor of a DR on SPECT-MPI, AUC = 0.624 (95% CI: 0.542–0.702). Small Dependence High Gray Level Emphasis, Cluster Prominence, Region Length, wavelet Median and square Median were predictors of a positive SPECT result, with AUC = 0.816, (95% CI: 0.745–0.875). The difference between the two models was statistically significant (p-diff: 0.006, 95% CI: 0.152–0.329) Conclusion Radiomic futures can be combined with anatomical and morphological characteristics of coronary lesions in CTCA imaging and provide valuable complementary information for characterizing functionally significant coronary lesions. Funding Acknowledgement Type of funding sources: Public grant(s) – EU funding. Main funding source(s): This work was supported from European Regional Development Fund, Operational Programme “Competitiveness, Entrepreneurship and Innovation 2014-2022 (EPAnEK)”, titled: The Greek Research Infrastructure for Personalized Medicine (pMED-GR)

The role of adipose tissue (AT) in arterial inflammation in familial dyslipidaemias is poorly studied. We investigated the relationship between AT and arterial inflammation in patients with heterozygous familial hypercholesterolemia (heFH) and familial combined hyperlipidemia (FCH). A total of 40 patients (20 heFH/20 FCH) and a subgroup of 20 of non-heFH/FCH patients were enrolled. Participants underwent blood sampling for serum adipokine measurements and Fluorine-18 fluorodeoxyglucose (18F-FDG) PET/CT imaging. Abdominal visceral (VAT) and subcutaneous (SAT) AT volumes and AT and abdominal aorta 18F-FDG uptake were quantified. FCH patients had increased VAT (pANOVA = 0.004) and SAT volumes (pANOVA = 0.003), lower VAT metabolic activity (pANOVA = 0.0047), and lower adiponectin levels (pANOVA = 0.007) compared to heFH or the control group. Log(Serum adiponectin) levels were correlated with aortic TBR (b = − 0.118, P = 0.038). In mediation analysis, VAT volume was the major determinant of circulating adiponectin, an effect partly mediated via VAT TBR. Clustering of the population of heFH/FCH by VAT volume/TBR and serum adiponectin identified two distinct patient clusters with significant differences in aortic TBR levels (2.11 ± 0.06 vs 1.89 ± 0.05, P= 0.012). VAT phenotype (increased VAT volume and/or high VAT TBR) and hypoadiponectinemia may account for the observed differences in arterial inflammation levels between heFH and FCH patients.

Type of funding sources: Public grant(s) – EU funding. Main funding source(s): This work was supported in part from European Regional Development Fund, Operational Programme “Competitiveness, Entrepreneurship and Innovation 2014-2020 (EPAnEK)”, titled: The Greek Research Infrastructure for Personalized Medicine (pMED-GR) , no. GR 5002802 ,and by Greece and the European Union (European Social Fund-ESF) through the Operational Programme «Human Resources Development, Education and Lifelong Learning 2014-2020» in the context of the project “Assessment of coronary atherosclerosis: a new complete, anatomo-functional, morphological and biomechanical approach”, Project no. 504776 Computed Tomography Coronary Angiography (CTCA) is a non-invasive imaging modality, used effectively for anatomo-functional assessment of coronary artery disease (CAD). Machine learning (ML) processes can effectively allow the extraction of useful information from multidimensional feature spaces for evaluation of coronary lesions. To investigate the ability of ML for predicting impaired myocardial blood flow (MBF) by combining computational fluid dynamics (CFD) derived parameters with quantitative plaque burden, plaque morphology and anatomical characteristics obtained from CTCA. 53 patients (31 male, mean age 64.7 ± 7.1 years) with intermediate pre-test likelihood of CAD who underwent CTCA and PET-MPI were included. PET was considered positive when > 1 contiguous segment demonstrated MBF ≤ 2.3 mL/g/min for 15O-water or ≤ 1.79 for 13N-ammonia respectively. CFD derived parameters such as a previously validated, virtual functional assessment index (vFAI), segmental endothelial shear stress (ESS), as well as anatomical and plaque characteristics were assessed. Seven classifiers were implemented and internally validated using 5-fold cross validation, repeated 1000 times. Using sequential forward selection (SFS), the highest rank features combination, based on appearances in the highest mean area under curve (AUC) classification scheme, was selected and features performance was evaluated following exhaustive search (ES). 92 coronary segments were analyzed and 34 features derived from CTCA were extracted. Classifiers performance are depicted in Figure A. k-NN was the best classifier with AUCmean = 0.791 (SENSmean= 0.622, SPECmean = 0.840, p < 0.05). Clusters of features and number of appearances are presented in Figure B. The combination of vFAI, stenosis severity and lumen area demonstrated the highest AUC (1473 times). ES results are depicted in Figure C. The combination of vFAI and lumen area was the best predictor among all the combinations (AUCmean = 0.830, SENSmean =0.61, SPECmean =0.83, p < 0.05) followed by vFAI and stenosis severity (AUCmean = 0.81, SENSmean =0.72, SPECmean = 0.87, p < 0.05) and vFAI alone (AUCmean = 0.806, SENSmean =0.61, SPECmean =0.87, p < 0.05). ML analysis is feasible for predicting with reasonable specificity abnormal MBF by PET, using a combination of CFD derived parameters and anatomical features. vFAI as a single characteristic was a specific predictor of impaired MBF, whilst in combination with stenosis severity, maintained almost the same AUC and specificity values and resulted in improved sensitivity. On the other hand, addition of lumen area to vFAI, increases the AUC and provides a relatively good specificity but low  sensitivity. Abstract Figure 1

Abstract Introduction Inflammation plays a pivotal role in the pathogenesis of both Hodgkin and non-Hodgkin's lymphoma and it has been shown recently that disease burden is associated with arterial inflammation. This can be captured by 18F-fluorodeoxyglucose (18F-FDG) positron emission computed tomography (PET/CT), a commonly used imaging modality for staging and treatment response of patients with lymphoma, which has also been established as a reliable marker of arterial inflammation. Chemotherapy remains the cornerstone of lymphoma treatment; however, its direct effect on arterial 18F-FDG uptake is unknown. Purpose To investigate the effect of chemotherapy on arterial inflammation using 18F-FDG PET/CT imaging, in patients with lymphoma. Methods Sixty-six patients (22 male, mean age 56 years) with Hodgkin (n=34) or non-Hodgkin's lymphoma (n=32) underwent 18F-FDG PET/CT imaging at baseline, during and after completion of chemotherapy as part of their routine protocol. Arterial 18F-FDG uptake was assessed at the same time points by measuring the metabolic activity (maximum standardized uptake value (SUVmax) and the arterial target to background ratio (TBR)) of the aortic wall along the entire aorta. Patients with Hodgkin lymphoma underwent therapy with doxorubicin, bleomycin, vinblastine and dacarbazine (ABVD). The interim scan was performed at 1 to 3 days prior to initiating the 3rd chemotherapy cycle. Patients with non-Hodgkin's lymphoma underwent therapy with cyclophosphamide, doxorubicin, vincristine and prednisone+rituximab (R-CHOP). Their interim scan was obtained at 2 weeks post the 4th chemotherapy cycle. All patients were re-assessed with 18F-FDG PET/CT imaging 6–8 weeks after chemotherapy completion. Results Baseline total aortic TBR was not associated with the presence of diabetes, dyslipidaemia or smoking (p=0.258, p=0.302 and p=0.452, respectively). Twelve patients were receiving statin therapy, however, there was no significant difference in baseline aortic TBR between patients on statins and patients who were not on statin therapy (p=0.265). In the whole study sample, the index vessel TBR progressively decreased by 0.17 from baseline to 6 weeks following the end of treatment (p=0.013 ANOVA with Bonferroni Correction, Figure 1). Conclusion Our findings suggest that arterial inflammation is reduced during and post chemotherapy in patients with lymphoma. In addition, they indicate a potential role of molecular imaging in cardio-oncology, providing a longitudinal evaluation of disease severity and its consequences to the arterial wall metabolic activity with a single examination. Funding Acknowledgement Type of funding sources: None.

Background Advances in three-dimensional reconstruction techniques and computational fluid dynamics of coronary CT angiography (CCTA) data sets make feasible evaluation of endothelial shear stress (ESS) in the vessel wall. Purpose To investigate the relationship between CCTA-derived computational fluid dynamics metrics, anatomic and morphologic characteristics of coronary lesions, and their comparative performance in predicting impaired coronary vasodilating capability assessed by using PET myocardial perfusion imaging (MPI). Materials and Methods In this retrospective study, conducted between October 2019 and September 2020, coronary vessels in patients with stable chest pain and with intermediate probability of coronary artery disease who underwent both CCTA and PET MPI with oxygen 15-labeled water or nitrogen 13 ammonia and quantification of myocardial blood flow were analyzed. CCTA images were used in assessing stenosis severity, lesion-specific total plaque volume (PV), noncalcified PV, calcified PV, and plaque phenotype. PET MPI was used in assessing significant coronary stenosis. The predictive performance of the CCTA-derived parameters was evaluated by using area under the receiver operating characteristic curve (AUC) analysis. Results There were 92 coronary vessels evaluated in 53 patients (mean age, 65 years ± 7; 31 men). ESS was higher in lesions with greater than 50% stenosis versus those without significant stenosis (mean, 15.1 Pa ± 30 vs 4.6 Pa ± 4 vs 3.3 Pa ± 3; P = .004). ESS was higher in functionally significant versus nonsignificant lesions (median, 7 Pa [interquartile range, 5-23 Pa] vs 2.6 Pa [interquartile range, 1.8-5 Pa], respectively; P ≤ .001). Adding ESS to stenosis severity improved prediction (change in AUC, 0.10; 95% CI: 0.04, 0.17; P = .002) for functionally significant lesions. Conclusion The combination of endothelial shear stress with coronary CT angiography (CCTA) stenosis severity improved prediction of an abnormal PET myocardial perfusion imaging result versus CCTA stenosis severity alone. © RSNA, 2021 Online supplemental material is available for this article. See also the editorial by Kusmirek and Wieben in this issue.

Abstract Introduction Arterial stiffness independently predicts cardiovascular risk and has been associated with the presence of inflammation. Chemotherapy-induced cardiac dysfunction is a major contributor to adverse morbidity and mortality rates in cancer patients. There is extensive literature describing the cardiotoxic effects of anti-cancer treatment on left ventricular systolic function, that may be the result of direct effects of the cancer treatment on heart function, or due to an indirect acceleration of atherosclerosis. However there is only little evidence regarding chemotherapy effects on arterial elastic properties. The gold standard for measuring arterial stiffness is carotid femoral pulse wave velocity (cfPWV) and it is calculated as a function of transit time and distance of the pulse wave derived from the carotid and femoral arteries. Purpose Our aim was to investigate the effect of chemotherapy in aortic stiffness in patients with lymphoma, a malignancy with known high metabolic burden. Methods Sixty-six patients (22 male, mean age 56 years) with Hodgkin (n=34) or non-Hodgkin lymphoma (n=32) were enrolled in the study. Patients with Hodgkin Lymphoma underwent therapy with Doxorubicin, bleomycin, vinblastine and dacarbazine (ABVD). The interim of their treatment was set at 1 to 3 days prior to initiating the 3rd chemotherapy cycle. Patients with non Hodgkin Lymphoma underwent therapy with cyclophosphamide, doxorubicin, vincristine, and prednisone+rituximab (R-CHOP). Blood pressure (BP) and carotid-femoral pulse wave velocity (c-f PWV) were measured at baseline, interim and after completion of chemotherapy. Results Changes in systolic and diastolic BP from baseline, to interim phase and 6 weeks post therapy were insignificant (decrease by 3.87±1.37 mmHg p-0.277 and 3.05±0.92 mmHg p-0.422 respectively). Figure illustrates c-f PWV changes from baseline to interim and 6 weeks after completion of chemotherapy. As figure shows, c-f PWV progressively decreased at the interim phase and at 6–8 weeks after chemotherapy completion (by 0.37±0.14 m/s), (overall P-0.010, by ANOVA) The progressive decrease in c-f PWV remained statistically significant after adjustment for age, systolic BP and diabetes (F=5.173, P-0.009). Patients' baseline characteristics are demonstrated in table 1. Conclusion Carotid-Femoral PWV decreased at 6–8 weeks post chemotherapy in patients with lymphoma, suggesting that aortic elastic properties improve with chemotherapy in these patients. Considering that aortic stiffness increases due to systemic inflammation and that lymphomas are increased metabolic burden tumors, the significant improvement in arterial stiffness implies that the presence of inflammation caused by the malignancy may play a significant role in the arterial stiffness progression. Funding Acknowledgement Type of funding sources: None.

Type of funding sources: Public grant(s) – EU funding. Main funding source(s): This work was supported in part from European Regional Development Fund, Operational Programme “Competitiveness, Entrepreneurship and Innovation 2014-2020 (EPAnEK)”, titled: The Greek Research Infrastructure for Personalized Medicine (pMED-GR) , no. GR 5002802 ,and by Greece and the European Union (European Social Fund-ESF) through the Operational Programme «Human Resources Development, Education and Lifelong Learning 2014-2020» in the context of the project “Assessment of coronary atherosclerosis: a new complete, anatomo-functional, morphological and biomechanical approach”, Project no. 504776 EVINCI-SMARTOOL Background/Objectives: The relationship between biomechanical characteristics of a coronary lesion with myocardial blood flow has not been studied. We investigated the relationship between local endothelial shear stress (ESS) and computed tomography coronary angiography (CTCA)-derived anatomical and plaque characteristics data with impaired vasodilating capability assessed by positron emission tomography myocardial perfusion imaging (PET-MPI). A total of 92 coronary vessels of 53 patients who have undergone both CTCA and PET-MPI with 15O-water or 13N-ammonia were analysed. PET was considered abnormal when > 1 contiguous segments showed both stress Myocardial Blood Flow (MBF) ≤2.3mL/g/min and Myocardial Flow Reserve (MFR) ≤2.5 for 15O-water or <1.79 mL/g/min and ≤2.0 for 13N-ammonia respectively.  CTCA images were used to assess stenosis severity, lesion specific total plaque volume (PV), non-calcified PV and calcified PV as well as plaque phenotype. ESS was calculated for the full length of a lesion (total), as well as in the proximal, minimum lumen area and distal lesion segments. ESS was weakly correlated with total PV (rho = 0.273, p = 0.008), non-calcified PV (rho = 0.247, p = 0.017) and the volume of necrotic core (rho = 0.242, p = 0.02). ESS increased progressively with stenosis severity (p ≤ 0.001). ΕSS was also higher in functionally significant vs. non-significant lesions (10.4 [8.04-54.4] Pa vs. 3.9 [2.32-7.29] Pa, p ≤0.001). Addition of ESS to stenosis severity improved prediction (Δ[AUC]:0.113, 95% CI: 0.055 to 0.171, p = 0.0001) of functionally significant lesions. There is a weak positive association between lesion-specific ESS and plaque volume. ESS increases progressively with stenosis severity and is higher in functionally significant lesions by PET-MPI. The addition of ESS to CTCA-anatomical information improves prediction of an abnormal PET-MPI result.

Background: Chemotherapy regimens for breast cancer treatment can promote vascular dysfunction and lead to high cardiovascular risk. Purpose: To investigate the cardiovascular burden and vascular inflammation in metastatic breast cancer patients receiving CDK 4/6 inhibitors or everolimus in addition to standard hormonal treatment. Methods: 22 consecutive female patients with metastatic breast cancer were enrolled. Relative wall thickness (RWT) and left ventricle mass (LVM) measurements by transthoracic echocardiography were obtained followed by 24-h ambulatory blood pressure monitoring, and 18F-fluorodeoxyglucose positron-emission tomography/computed tomography imaging. Uptake of the radiotracer in the aortic wall was estimated as tissue-to-background ratio (TBR). Each patient was assessed for the aforementioned parameters before the initiation and after 6 months of treatment. Results: At follow up, patients assigned to CDK 4/6 treatment demonstrated increased 24-h systolic blood pressure (SBP) (p = 0.004), daytime SBP (p = 0.004) and night time SBP (p = 0.012) (Group effect). The 24-h mean arterial pressure measurements were also higher in CDK 4/6 population, in comparison to everolimus that displayed firm values (Group effect- p = 0.035, Interaction effect-p = 0.023). Additionally, 24 h diastolic blood pressure recordings in CDK 4/6 therapy were higher opposed to everolimus that remained consistent (Interaction effect- p = 0.010). In CDK 4/6 group, TBR aorta also increased significantly, whereas TBR values in everolimus remained stable (Interaction effect-p = 0.049). Both therapeutic regimens displayed statistically significant damaging effect to RWT and LVM. Conclusion: CDK 4/6 inhibitors and hormonal treatment can lead to increased vascular inflammation, and higher blood pressure compared to the combination of everolimus and hormonal treatment. Moreover, both treatment strategies promoted left ventricle remodeling.

BACKGROUND:There is evidence that metabolic disease burden in lymphoma influences patient outcome. However, the impact of disease severity on the cardiovascular system is unknown. OBJECTIVES:The aim of this study was to examine whether lymphoma is associated with arterial inflammation by investigating the relationship between disease metabolic burden and arterial fluorodeoxyglucose (FDG) uptake. METHODS:Sixty-two chemotherapy-naïve patients with active Hodgkin's or non-Hodgkin's lymphoma were matched (2:1) to individual control groups of lymphoma patients previously treated and free of active disease. All groups underwent 18F-FDG position emission tomography-computed tomography imaging. Disease severity was quantified by metabolic tumor volume (MTV) and total lesion glycolysis corresponding to standardized uptake values (SUVs) ≥41% or ≥2.5 of the maximum SUV within lymphoma regions, and aortic FDG uptake was quantified through the target-to-background ratio (TBR). Inflammatory and disease severity biomarkers were also measured. RESULTS:MTV and total lesion glycolysis measurements were significantly correlated with inflammatory and disease biomarkers. Aortic TBR was higher in patients with active non-Hodgkin's lymphoma compared with control subjects (median difference 0.51; 95% confidence interval [CI]: 0.28 to 0.78; p < 0.001). Similarly, patients with active Hodgkin's lymphoma had higher values of aortic TBR compared with control subjects (median difference 0.31; 95% CI: 0.15 to 0.49; p < 0.001). In addition, aortic TBR was modestly increased in patients with stage III to IV disease compared with those with stage I to II disease (median aortic TBR: 2.23 [interquartile range: 2.01 to 2.54] vs. 2.06 [interquartile range: 1.83 to 2.27; p = 0.050). In multivariable analysis, aortic FDG uptake and MTV≥2.5 values were independently associated (β = 0.425; 95% CI: 0.189 to 0.662; p = 0.001; R2 = 0.208), as were aortic FDG uptake and MTV≥41% (β = 0.407; 95% CI: 0.167 to 0.649, p = 0.001; R2 = 0.191). CONCLUSIONS:Aortic wall FDG uptake is related with disease severity indicative of a possible vascular effect of lymphoma. This work highlights a new potential role of molecular imaging in cardio-oncology for evaluating disease severity and its consequences on the vasculature.

Advances in CTCA imaging enable assessment of coronary plaque burden, a predictor of myocardial perfusion abnormalities and more recently, with the use of computational fluid dynamics (CFD) of endothelial shear stress (ESS), an established contributor to atherosclerotic plaque development and progression. To investigate the relationship of local endothelial shear stress (ESS) and plaque burden (PB) between them and with stenosis severity as well as their comparative performance in predicting impaired coronary vasodilating capability assessed by PET myocardial perfusion imaging (MPI). 49 patients (29 males, mean age 65.3±6.3 years, intermediate pre-test likelihood of coronary artery disease, CAD), who underwent PET-MPI with 15O-water or 13N-ammonia and CTCA were included. PET was considered abnormal when >1 contiguous segment showed both stress Myocardial Blood Flow ≤2.3 mL/g/min and Myocardial Flow Reserve ≤2.5 for 15O-water or <1.79 mL/g/min and ≤2.0 for 13N-ammonia respectively. On CTCA, stenosis (sten) severity was classified as: <30%, 31–50%, 51–70% and 71–90%. CFD were applied to every vessel, assuming a mean pressure of 100 mmHg as the inlet boundary condition and a coronary velocity profile of 1 ml/sec as the outlet. ESS was calculated for the full length of a stenosis (total), as well as in the proximal (prox), minimum lumen area (MLA) and distal (dist) stenotic segments. Atherosclerotic PB was defined as lesion plaque volume/lesion vessel volume ×100. 85 coronary vessels were evaluated. There was a positive correlation between ESS and PB (r(total)=0.544, r(prox)=0.528, r(MLA)=0.529, r(dist)=0.474, p<0.001 for all). All ESS indices and PB increased progressively with stenosis severity compared to segments with a <30% stenosis (p≤0.004 for all comparisons). ESS indices and PB were also higher in lesions demonstrating impaired vasodilating capacity compared to those without (p≤0.02 for all comparisons, figure 1). All ESS indices performed equally with PB and sten >50% in predicting an abnormal PET MPI, (AUC: from 0.682 to 0.780, p-diff >0.5 for all comparisons). The pairwise combination of sten >50% with the ESS segments, except the distal one, increased the predictive ability of the model over stenosis alone (AUC (sten >50% + ESS(total)) = 0.80, AUC (sten >50% + ESS(prox)) = 0.797, AUC (sten >50% + ESS(MLA)) = 0.822, p-diff ≤0.01 for all comparisons, AUC (sten >50% + ESS(dist)) = 0.768, p-diff=0.07). There is a low to moderate positive association between lesion plaque burden and ESS indices. Like PB, ESS increases progressively with stenosis severity and is higher in lesions paired with abnormal PET results. ESS is a moderate predictor of impaired vasodilating capability, performing equally with PB and stenosis severity. The addition of ESS to stenosis severity can improve prediction of an abnormal PET result. Figure 1 Type of funding source: Public grant(s) – EU funding. Main funding source(s): This study is co-financed by Greece and the European Union (European Social Fund-ESF) through the Operational Programme “Human Resources Development, Education and Lifelong Learning 2014-2020” in the context of the project “Assessment of coronary atherosclerosis: a new complete, anatomo-functional, morphological and biomechanical approach” and from p-Med GR 5002802

Abstract Background The adipose tissue is now established as a major regulator of cardiovascular status, mediated by the secretion of several bioactive molecules, including adipocytokines. Individuals with genetic dyslipidaemias of either familial combined hyperlipidemia (FCH) or heterozygous familial hypercholesterolemia (heFH) subtype are characterized by accelerated atherosclerosis. Nonetheless, limited data exists on the relationship between adiposity and arterial inflammation, a marker of cardiovascular risk, in this setting. Purpose To investigate the relationship between adiposity indices and arterial inflammation evaluated by 18F fluorodeoxyglycose positron emission tomography (PET/CT) in patients with hereditary lipid metabolism disorders. Methods Consecutive patients with either FCH or heFH, free of statin therapy, and normolipidaemic individuals underwent PET/CT imaging. Arterial FDG uptake was estimated as the average value of target-to-background ratio (TBR) within aortic and carotid wall. Volumes of subcutaneous adipose tissue (SAT) and visceral adipose tissue (VAT) were measured from CT images between the proximal (cephalic) end of the L1 and distal (caudal) end of the L3 vertebrae by selecting all voxels with attenuation between −190 and −30 Hounsfield Units (HU). Serum adiponectin and leptin levels were measured with ELISA by available commercial kits. For comparisons with arterial TBR, adiponectin and leptin concentrations above and below the 25th percentile, were stratified as high and low, respectively. Results In total, 60 individuals (20 FCH, 20 heFH and 20 controls) were included. A modest but significant correlation between SAT volume and arterial TBR (R=0.386, p=0.004) was detected. This relationship did not remain significant after controlling for VAT volume (p=0.303). A strong correlation between VAT volume and arterial TBR (R=0.621, p=0.001) was observed. This relationship remained significant after controlling for SAT volume (R=0.541, p<0.001). Arterial TBR values were higher in individuals with low plasma adiponectin levels (p=0.010). In addition, patients with higher leptin levels exhibited increased arterial FDG uptake compared to subjects with low serum leptin concentrations (p=0.05) Conclusions Abdominal adipose tissue imaging markers and serum adipocytokines correlate with arterial inflammation as assessed by PET/CT in patients with familial dyslipidaemias highlighting the role of abdominal adipose tissue for atherosclerosis progression in this population.

To develop and test a model predicting 2-deoxy-2-[18F]fluoro-d-glucose ([18F]FDG) standardized uptake value (SUV) changes over time in the aorta and the superior vena cava (SVC). Maximum aortic SUV and mean SVC SUV were determined at two time points (T1 and T2) in the ascending (ASC), descending (DSC), abdominal (ABD) aorta, aortic arch (ARC) and SVC of patients who have undergone [18F]FDG PET/CT for clinical purposes. For SUV prediction at T2, linear and non-linear models of SUV difference for a given time change were developed in a derivation group. The results were tested in an independent validation group, whilst model reproducibility was tested in patients of the validation group who have undergone a second clinically indicated scan. Applying the linear model in the derivation group, there were no statistically significant differences in measurements obtained in the examined segments: mean differences ranged from 0 ± 0.10 in SVC to 0.01 ± 0.13 in ARC between measured and predicted SUV. In contrast, in the non-linear model, there were statistically significant differences in measurements, except in ARC, with mean differences ranging from 0.04 ± 0.14 in ARC to 0.28 ± 0.13 in ABD. In the validation group using the linear model, there were no statistically significant differences, with mean differences ranging from − 0.01 ± 0.08 in ASC to − 0.03 ± 0.11 in ABD. Regarding reproducibility, mean differences were no statistically significant, ranging from 0.004 ± 0.06 in ASC to − 0.02 ± 0.16 in ABD. We have developed a linear model allowing accurate and reproducible prediction of SUV changes over time in the aorta and SVC.

Abstract Background The feasibility of assessing endothelial shear stress (ESS) in coronary lesions by non-invasive imaging and its potential role in different clinical settings has been recently explored. However, the relationship of ESS with functional indices derived by computed tomography coronary angiography (CTCA) and its value in predicting perfusion changes by quantitative positron emission tomography (PET) downstream stenotic vessels has not been assessed. Purpose To investigate the feasibility of calculating local ESS, its relationship with stenosis severity as well as with virtual functional assessment index (vFAI), and the comparative performance of the two parameters for predicting impaired coronary vasodilating capability in terms both of stress myocardial blood flow (MBF) and myocardial flow reserve (MFR) in patients submitted to CTCA. Methods Thirty-two patients (23 male-9 female, mean age 65.6±7.2 years) with intermediate pre-test likelihood of coronary artery disease (CAD), who were enrolled in the EVINCI and SMARTool projects, and had undergone CTCA with vFAI and PET myocardial perfusion imaging with 15 O-water or 13 N-ammonia were included in the study. PET was considered positive when >1 contiguous segments showed both stress MBF ≤2.3 mL/g/min and MFR ≤2.5 for 15 O-water or ≤1.79 mL/g/min and ≤2.0, for 13 N-ammonia respectively. A vFAI threshold of 0.85 was used as predictor of impaired vasodilating capability. ESS computation was based on a mean aortic pressure of 100 mmHg for the inlet and a mean blood flow at rest of 0.00105 kg/s for the outlet. ESS was calculated (Pa) in the full length of the stenosis and the mean value was obtained. Results Hybrid imaging analysis was performed in CTCA and PET datasets. 51 coronary segments were assessed. There were 27 lesions with stenosis 31–50% and 24 lesions with stenosis 51–70%. ESS was higher in the latter (20.4, IQ: 11.4–32.1 vs. 10.4, IQ: 5.5–15.7, p=0.04). Similarly, ESS was higher in stenoses with impaired vasodilating capacity compared to those without, although this difference did not reach statistical significance (22.8, IQ: 13.2–35.1 vs. 10.6, IQ: 5.7–22.1, p=0.10). The ROC curve analysis for prediction of both abnormal stress MBF and MFR followed the same pattern (AUC=0.668, 95% confidence interval (CI): 0.490–0.810, p=0.11).On the other hand, there was a moderate negative correlation (r=−0.41, p=0.004) between ESS and vFAI and the former was lower in stenoses with vFAI >0.85 compared to those below this threshold (7.35, IQ: 3.2–13.9 vs. 19.1, IQ: 14.1–32.8, p=0.012). vFAI was a good predictor of coronary flow capacity (AUC=0.737, CI: 0.58–0.85, p=0.02). Conclusion Calculation of ESS is feasible in CTCA datasets. ESS was related with stenosis severity and there was a trend to be higher in lesions with impaired coronary vasodilating capability. ESS is modestly related with vFAI and may also be an additional predictor of impaired regional myocardial flow obtained by PET imaging. Acknowledgement/Funding This study has received funding from the EU H2020 research and innovation programme under grant agreement No 689068 and from p-Med GR 5002802