The GLP-1 receptor agonist Semaglutide decreases vascular inflammation in a rabbit model of advanced atherosclerosis

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
J Kildevang Jensen ◽  
C Grandjean Poulsen ◽  
T Binderup ◽  
S Bentsen ◽  
B Follin ◽  
...  
Keyword(s):  
Molecular Imaging ◽  
Receptor Agonist ◽  
Vascular Inflammation ◽  
Rabbit Model ◽  
Public Institution ◽  
Ct Scans ◽  
Control Group ◽  
Funding Source ◽  
Pet Ct

Abstract Introduction Atherosclerosis is one of the most common inflammatory disorders leading to cardiovascular disease. Incretin therapies such as Glucagon like peptide 1 (GLP-1) receptor agonists has demonstrated efficacy in reducing major adverse cardiovascular events among high risk populations, possibly due to a reduction in vascular inflammation. Positron emission tomography (PET) is a promising modality in the study of atherosclerosis since it has the ability to evaluate physiological processes in vivo. The somatostaton receptor 2 (SSTR2) targeting tracer [64Cu]Cu-DOTA-TATE (DOTATATE) has high specificity for activated macrophages, which are one on the key instigators of atherosclerosis. Two other radiotracers, more commonly used to study atherosclerosis are Na[18F]F (NaF) a radiotracer used for detection of vascular microcalcifications, and [18F]FDG (FDG) used for visualization of inflammatory metabolic activity. Purpose The purpose of this study was to evaluate the anti-atherosclerotic and anti-inflammatory effects of the GLP-1 receptor agonist Semaglutide, using molecular imaging with DOTATATE, NaF and FDG, in a rabbit model of advanced atherosclerosis. Methods A total of 23 female New Zealand White rabbits were fed a high cholesterol diet for 4 months and endothelial denudation of the aorta was performed twice (Fig 1A). The animals underwent baseline PET/CT scans using DOTATATE and FDG. They were then randomly allocated to an intervention group (n=12) or control group (n=11) receiving bi- weekly subcutaneous injections of either Semaglutide in a dose escalating regimen up to 44 μg/kg/week, or placebo (n=11). The intervention period was 16 weeks for both groups. At follow-up, the animals underwent PET/CT scans with DOTATATE, FDG and NaF. Regions of interest were drawn on all CT scans of the aorta from the right renal artery to the iliac bifurcation, and SUVmax was measured from the superimposed PET scans. Data are presented as means ± SEM. Results SUVmax for FDG and DOTATATE were similar in the 2 groups at baseline (DOTATATE: 7.59±0.48 vs 6.69±0.28, P=0.13 and FDG: 2.63±0.12 vs 2.86±0.19 P=0.29). At follow-up, the Semaglutide group had a significantly lower uptake of both DOTATATE and FDG, although the largest difference was observed for DOTATATE (DOTATATE: 5.83±0.24 vs 7.10±0.33, P=0.001 and FDG: 2.49±0.13 vs 2.99±0.15, P=0.034) (Fig 1BC). Microcalcifications visualized using NaF PET, showed no difference at follow-up between the Semaglutide and the control group (4.15±0.30 vs 3.92±0.34, P=0.62) (Fig 1D). Increase in body weight was significantly attenuated in the Semaglutide group compared to the control group at follow-up (0.25±3.29% vs 10.68±3.01%, P=0.0016). Conclusions Semaglutide decreases vascular uptake of the SSTR2 tracer, DOTATATE, and FDG but not NaF. This supports the hypothesis that Semaglutide reduces inflammation by means of decreased macrophage activity and metabolism in the arterial wall. Figure 1 Funding Acknowledgement Type of funding source: Public Institution(s). Main funding source(s): Department of Clinical Physiology, Nuclear Medicine & PET and Cluster for Molecular Imaging, Rigshospitalet and University of Copenhagen, Copenhagen, Denmark

The vegf-a gene polymorphism in prognosis of outcomes in patients with stemi

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
I Kutya ◽  
Y Hilova ◽  
J Rodionova ◽  
M Kopytsya ◽  
O Petyunina
Keyword(s):  
Gene Polymorphism ◽  
Cardiovascular Death ◽  
Adverse Outcomes ◽  
Public Institution ◽  
Control Group ◽  
Case Group ◽  
Funding Source ◽  
Polymerase Chain

Abstract   One of the promising parameter for the prognosis in patients with STEMI can be suggested the VEGF-A gene polymorphism. Purpose Estimate the role of the VEGF-A gene polymorphism in the prediction of outcomes in patients with STEMI. Methods The study involved 135 STEMI patients (80.7% male and 19.3% female) with an average age of 59.21±8.92 years. Control group of 30 healthy volunteers included. Patients were divided into two groups: the first one – “case” group, those who reached the end point, and the second group – “control”, those who did not reached. The combined endpoint included cardiovascular death, recurrent myocardial infarction, the occurrence / progression of heart failure that required hospitalization. The study of the VEGF-A gene polymorphism (rs 2010963) was carried out by polymerase chain reaction (PCR). Follow-up period was 6 month. VEGF-A level was measured by ELISA. Results The patients from the “case” group had significantly elevated VEGF-A levels compared to controls (217.40 [102.54–473.78] pg/ml; 311.45 [204.20–680.86] pg/ml; p=0.046). Multivariate linear regression analyses demonstrated that polymorphism G634C (rs2010963) of VEGF-A gene (G634C+C634C) – β=0.8079, CI [1.1907 to 5.6490] p=0.0465; and LVEF <50.60% – β=0.0488 CI [0.9179 to 0.9882], p=0.0096 are significantly associated with negative outcomes (combined endpoints). Conclusions STEMI patients with G634C+C634C polymorphism G634C (rs2010963) of VEGF-A gene, and with LVEF <50.60% have greater chances for adverse outcomes. Further investigations of the VEGF-A gene polymorphism are the perspective direction in the development of prevention and treatment of STEMI. Funding Acknowledgement Type of funding source: Public Institution(s). Main funding source(s): GI “L.T. Malaya Therapy National Institute NAMSU”

Coronary sinus catalase and ceruloplasmin levels predict all-cause mortality in patients with end-stage heart failure awaiting heart transplantation

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
W Szczurek ◽  
M Gasior ◽  
M Skrzypek ◽  
G Kubiak ◽  
A Kuczaj ◽  
...  
Keyword(s):  
Heart Failure ◽  
Heart Transplantation ◽  
Coronary Sinus ◽  
Public Institution ◽  
Funding Source ◽  
Organ Shortage ◽  
Number Of Patients ◽  
End Stage ◽  
Medical University

Abstract   Background, As a consequence of the worldwide increase in life expectancy and due to significant progress in the pharmacological and interventional treatment of heart failure (HF), the proportion of patients that reach an advanced phase of disease is steadily growing. Hence, more and more numerous group of patients is qualified to the heart transplantation (HT), whereas the number of potential heart donors has remained invariable since years. It contributes to deepening in disproportion between the demand for organs which can possibly be transplanted and number of patients awaiting on the HT list. Therefore, accurate identification of patients who are most likely to benefit from HT is imperative due to an organ shortage and perioperative complications. Purpose The aim of this study was to identify the factors associated with reduced survival during a 1.5-year follow-up in patients with end-stage HF awating HT. Method We propectively analysed 85 adult patients with end-stage HF, who were accepted for HT at our institution between 2015 and 2016. During right heart catheterization, 10 ml of coronary sinus blood was additionally collected to determine the panel of oxidative stress markers. Oxidative-antioxidant balance markers included glutathione reductase (GR), glutathione peroxidase (GPx), glutathione transferase (GST), superoxide dismutase (SOD) and its mitochondrial isoenzyme (MnSOD) and cytoplasmic (Cu/ZnSOD), catalase (CAT), malondialdehyde (MDA), hydroperoxides lipid (LPH), lipofuscin (LPS), sulfhydryl groups (SH-), ceruloplasmin (CR). The study protocol was approved by the ethics committee of the Medical University of Silesia in Katowice. The endpoint of the study was mortality from any cause during a 1.5 years follow-up. Results The median age of the patients was 53.0 (43.0–56.0) years and 90.6% of them were male. All included patients were treated optimally in accordance with the guidelines of the European Society of Cardiology. Mortality rate during the follow-up period was 40%. Multivariate logistic regression analysis showed that ceruloplasmin (odds ratio [OR] = 0.745 [0.565–0.981], p=0.0363), catalase (OR = 0.950 [0.915–0.98], p=0.0076), as well as high creatinine levels (OR = 1.071 [1.002–1.144], p=0.0422) were risk factors for death during 1.5 year follow-up. Conclusions Coronary sinus lower ceruloplasmin and catalase levels, as well as higher creatinine level are independently associated with death during 1.5 year follow-up. Funding Acknowledgement Type of funding source: Public Institution(s). Main funding source(s): Medical University of SIlesia, Katowice, POland

Resolution of vascular inflammation in patients with new-onset giant cell arteritis: data from the RIGA study

Rheumatology ◽  
2021 ◽  
Author(s):  
Verena Schönau ◽  
Jessica Roth ◽  
Koray Tascilar ◽  
Giulia Corte ◽  
Bernhard Manger ◽  
...  
Keyword(s):  
Giant Cell Arteritis ◽  
Giant Cell ◽  
Vascular Inflammation ◽  
Efficacy Evaluation ◽  
Glucocorticoid Treatment ◽  
Pet Ct ◽  
Sparing Effect ◽  
Fdg Pet Ct ◽  
New Onset

Abstract Objectives Efficacy evaluation of giant cell arteritis (GCA) treatment is primarily based on non-specific symptoms and laboratory markers. We aimed to assess the change in vascular inflammation in patients with large vessel (LV)-GCA under different treatments using [18F]FDG PET/CT. Methods Observational study on patients with new-onset, active LV-GCA starting treatment with either prednisolone monotherapy (PRED) or combination with methotrexate (MTX) or tocilizumab (TOC). All patients underwent baseline and follow-up PET/CT. The aorta and its major branches were assessed using PET vascular activity score (PETVAS) by independent readers. Cumulative glucocorticoid doses and cessation of glucocorticoid treatment were documented in all patients. Results We included 88 LV-GCA patients, 27 were treated with PRED, 42 with MTX, and 19 with TOC. PETVAS decreased from 18.9–8.0 units at follow-up in the overall population (p< 0.001). PETVAS changes were numerically higher in patients receiving MTX (-12.3 units) or TOC (-11.7 units) compared with PRED (-8.7). Mean cumulative prednisolone dosages were 5637, 4418, and 2984 mg in patients treated with PRED, MTX, and TOC (p= 0.002). Risk ratios for glucocorticoid discontinuation at the time of follow-up PET/CT were 6.77 (95%CI 1.01–45.29; p= 0.049) and 16.25 (95%CI 2.60–101.73; p= 0.003) for MTX and TOC users compared with PRED users. Conclusion Treatment of LV-GCA inhibits vascular inflammation in the aorta and its major branches. While similar control of vascular inflammation was achieved with PRED, MTX, and TOC treatments, TOC showed a strong glucocorticoid sparing effect, supporting the concept of initial combination therapy.

scholarly journals Patients with recurrent syncope and implantable loop recorder exhibit better survival than the control group without implantable loop recorder

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
C Perings ◽  
C Wolff ◽  
A Wilk ◽  
A Witthohn ◽  
R Voss ◽  
...  
Keyword(s):  
Life Expectancy ◽  
Control Group ◽  
Funding Source ◽  
Implantable Loop Recorder ◽  
Loop Recorder ◽  
Cardiac Device ◽  
Unexplained Syncope ◽  
Care Costs

Abstract Introduction In 30% of patients with syncope, the underlying cause remains unexplained after clinical investigations. Unexplained syncope tends to recur, significantly impacting patients' quality of life of patients and mortality. Thus, there is a need for timely and more accurate diagnosis to initiate treatment. Dedicated care pathways are recommended by ESC guidelines. Purpose Patients with recurrent syncope were followed over time and patient outcomes with ILR were compared to patients with the same syncope burden, age, gender and mortality risk score who did not receive an ILR. Method A representative database of 4.9 million patients insured by German company statuary health insurances (BKK) was analysed over a time period of 10 years, 2007–17. Patients with recurrent syncope (two times ICD-10 GM diagnosis codes R55), age between 45–84 and no diagnosis code for the syncope were included in the analysis and followed for at least 2 years. Patients with ILR were matched to patients without ILR based on age, gender and Charlson Comorbidity index (CCI) using mahalanobis distances. The index event was the device implant in the ILR group and the second syncope event in the control group. Life expectancy, syncope hospitalisations, fall related injuries, health care costs, diagnoses and treatment rates were compared between the groups. Results A total of 412 patients with ILR for recurrent unexplained syncope were matched to the control group. Overall mean age was 68, mean was CCI 2.7, 42% were females. The risk of death was 2.35 times higher in the control group during follow up as shown in Figure 1 (p-value logrank test <0.0001). Cardiovascular related diagnosis and treatment rates were higher in the ILR group with 69% of patients having a cardiology diagnosis compared to 41% in the control group. Over a quarter (27%) of ILR patients received an implantable cardiac device compared to 5% in the control group. Ablation rates were 7% in the ILR group compared to 0% in the control group. Median health care costs were € 3,847 higher in the ILR group including the costs of the ILR implant, follow up and higher rates of cardiac treatments. These extra costs appear moderate given the substantially higher mortality risk in the control group. Conclusion This study of patients with recurrent unexplained syncope shows a remarkable difference in life expectancy in patients with ILR compared to a matched control group. Two large claim data analysis have recently shown higher rates of cardiovascular death as well as all-cause mortality in patients with unexplained syncope. A more vigilant cardiac workup might be needed to identify a possible underlying cardiac condition. Higher rates of cardiac device therapy in the ILR group were likely to play an important role for their better life expectancy. Cardiac therapies such as pacemakers, defibrillators and ablation have also been shown to significantly improve patients' quality of life. Life Expectancy Comparison Funding Acknowledgement Type of funding source: Private company. Main funding source(s): The data analysis was funded by Medtronic

Benefit of Static FET PET in Pretreated Pediatric Brain Tumor Patients with Equivocal Conventional MRI Results

2021 ◽  
Author(s):  
Frederik Grosse ◽  
Florian Wedel ◽  
Ulrich-Wilhelm Thomale ◽  
Ingo Steffen ◽  
Arend Koch ◽  
...  
Keyword(s):  
Brain Tumor ◽  
Tumor Tissue ◽  
Pediatric Brain Tumor ◽  
Ct Scans ◽  
Tumor Patients ◽  
Fet Pet ◽  
Conventional Mri ◽  
Pet Ct ◽  
Pediatric Brain

Abstract Background MRI has shortcomings in differentiation between tumor tissue and post-therapeutic changes in pretreated brain tumor patients. Patients We assessed 22 static FET-PET/CT-scans of 17 pediatric patients (median age 12 years, range 2–16 years, ependymoma n=4, medulloblastoma n=4, low-grade glioma n=6, high-grade glioma n=3, germ cell tumor n=1, choroid plexus tumor n=1, median follow-up: 112 months) with multimodal treatment. Method FET-PET/CT-scans were analyzed visually by 3 independent nuclear medicine physicians. Additionally quantitative FET-Uptake for each lesion was determined by calculating standardized uptake values (SUVmaxT/SUVmeanB, SUVmeanT/SUVmeanB). Histology or clinical follow-up served as reference. Results Static FET-PET/CT reliably distinguished between tumor tissue and post-therapeutic changes in 16 out of 17 patients. It identified correctly vital tumor tissue in 13 patients and post-therapeutic changes in 3 patients. SUV-based analyses were less sensitive than visual analyses. Except from a choroid plexus carcinoma, all tumor entities showed increased FET-uptake. Discussion Our study comprises a limited number of patients but results corroborate the ability of FET to detect different brain tumor entities in pediatric patients and discriminate between residual/recurrent tumor and post-therapeutic changes. Conclusions We observed a clear benefit from additional static FET-PET/CT-scans when conventional MRI identified equivocal lesions in pretreated pediatric brain tumor patients. These results warrant prospective studies that should include dynamic scans.

scholarly journals Value of fourth and subsequent post-therapy follow-up 18F-FDG PET/CT scans in patients with breast cancer

2016 ◽  
Vol 37 (6) ◽  
pp. 602-608
Author(s):  
Mehdi Taghipour ◽  
Sara Sheikhbahaei ◽  
Tyler J. Trahan ◽  
Rathan M. Subramaniam
Keyword(s):  
Breast Cancer ◽  
Fdg Pet ◽  
Ct Scans ◽  
Pet Ct ◽  
18F Fdg ◽  
Fdg Pet Ct ◽  
Post Therapy

Diagnostic and prognostic value of neopterin and RNA-ase in patients with STEMI and NSTEMI

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
L Ciobanu ◽  
I Popovici ◽  
V Ivanov ◽  
V Cobet ◽  
M Ivanov ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Diagnostic Value ◽  
Public Institution ◽  
Funding Source ◽  
Extracellular Rna ◽  
Diagnosis And Prognosis ◽  
Markers Of Inflammation ◽  
Neopterin Level ◽  
Diagnostic And Prognostic Value

Abstract Background Neopterin and RNA-ase are markers of inflammation with low disclosed role in diagnosis and prognosis of either STEMI or NSTEMI, although inflammation is well documented as a leader pathogenic mechanism in these pathologies. Aim Evaluation of serum admission levels of neopterin and ARN-ase in pts with STEMI and NSTEMI and their prediction value concerning the risk of MACE in 1 year of follow up period. Material and methods The admission serum concentration of neopterin and ARN-ase was determined by ELISA in 94 pts with STEMI and 92 pts with NSTEMI which was compared with normal markers appreciated in 32 healthy persons. Likewise, the rate of MACE in both groups was estimated during 1 year of post-infarction period. Diagnostic worth and MACE prediction power of markers have been established using respectively ROC curve and odds ratio. Results In patients with STEMI the serum level of neopterin was significantly increased compared with normal index by 3,5 times (11,6±3,4 vs 3,3±1,4 nM/L), but RNA-ase was significantly decreased by 43,4% (24,1±3,2 vs 42,6±5,2 nM/ml). In pts with NSTEMI neopterin level was lesser than STEMI, but significantly elevated by 39% (4,6±2,5 vs 3,3±1,4 nM/L) vs normal marker. RNA-ase level didn't significantly differ from normal level. However, adjusted to diabetes mellitus established in 19 pts, RNA-ase significantly diminished (36,4±3,9 vs 42,6±5,2 nM/ml), and its diagnostic value of NSTEMI according to ROC was 69,6% (RNA-ase level indicates inversely inflammation response, such as it breaks down extracellular RNA which has proinflammatory ability). Both markers in pts with NSTEMI and diabetes mellitus demonstrated a diagnostic value of 77,6%. In pts with STEMI highest tertile level of neopterin and lowest tertile level of ARN-ase had 2,8fold (adds ratio=2,8; CI=1,98–4,62; p<0,05) and 2,3fold (adds ratio=2,3; CI=1,71–3,89; p<0,05) higher risk of MACE development. In pts with NSTEMI the combination of these markers (highest and lowest quartile levels) also had a significant prediction regarding MACE risk (adds ratio=2,1; CI=1,86–3,77; p=0,029). Conclusions 1. In STEMI both neopterin and RNA-ase could be as diagnostic markers, due to their significant change. In NSTEMI neopterin significantly elevated, but RNA-ase didn't shift from normal. In diabetic pts with NSTEMI, however, their combination demonstrated in ROC estimation a diagnostic value of 77,6%. 2. Prediction value of markers combination regarding MACE risk in pts with NSTEMI is significant and close to each marker in partly prediction of MACE for pts with STEMI. Funding Acknowledgement Type of funding source: Public Institution(s). Main funding source(s): Research Institute of Cardiology, Moldova Republic of

FDG-PET/CT Is Superior to Anatomic Imaging for the Staging and Follow Up of Bony Involvement in Patients with Lymphoma.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 2330-2330 ◽  
Author(s):  
Rebecca L. Elstrom ◽  
Richard K.J. Brown
Keyword(s):  
Fdg Pet ◽  
Bone Involvement ◽  
Ct Scans ◽  
Bone Lesions ◽  
Pet Ct ◽  
Fdg Pet Ct ◽  
Bone Lymphoma ◽  
Diagnostic Ct ◽  
Ct And Mri

Abstract Background and Objectives: Positron tomission tomography using 18fluoro-2-deoxyglucose in combination with low dose non-enhanced computed tomography (FDG-PET/CT) is increasingly utilized in the management of patients with lymphoma. Numerous studies have demonstrated improved accuracy for both staging and restaging as compared to standard diagnostic CT. However, there is a paucity of data on the significance of bone uptake in patients with lymphoma. This is one area in which FDG-PET has the potential to dramatically influence care of lymphoma patients. However, false positive FDG-PET has been shown in patients with traumatic or benign bone lesions. The aim of this study was to evaluate the utility and accuracy of FDG-PET/CT in comparison with standard anatomic imaging with CT and MRI in the staging and follow up of patients with Hodgkin lymphoma (HL) or diffuse large B cell lymphoma (DLBCL). Design and Methods: We reviewed a database of 75 lymphoma patients who underwent concurrent FDG-PET/CT and standard diagnostic CT scans or MRI, and identified those with bone involvement by lymphoma. Involvement of bone was demonstrated by either biopsy of a bone lesion or radiologic appearance and clinical follow up highly suggestive of bone involvement. Follow up studies were evaluated for resolution of FDG avid lesions on PET, and anatomic lesions on CT or MRI. Results: Fourteen patients with either HL or DLBCL who underwent both FDG-PET/CT and diagnostic CT were identified to have bone involvement by lymphoma. FDG-PET identified bone involvement in all 14 patients, whereas CT imaging identified bone involvement in seven. One patient in whom CT did not detect bone involvement had evidence of bone lymphoma by MRI. Eight patients had confirmation of bone lymphoma by biopsy, while 6 were confirmed by clinical criteria (radiologic appearance and clinical follow up). Thirteen of the patients had follow up FDG-PET/CT scans, and 12 had follow up CT and/or MRI. All follow up FDG-PET scans showed resolution of FDG avid bone lesions after anti-lymphoma therapy. In contrast, all CT and MRI scans which originally showed evidence of bone involvement had persistent abnormality on follow up, with only 2 showing improvement. At a median follow up of 9 months (range 0–20 months), 11 patients remain in remission, while 2 patients subsequently showed progression by FDG-PET, CT and biopsy in soft tissue sites, but not bone. One patient remains on therapy. No patient in our series was found to have a benign etiology of a lesion initially thought due to lymphoma. Conclusion: FDG-PET/CT is useful in the staging and follow up of patients with lymphoma with bone involvement. The lack of sensitivity of CT combined with the delayed resolution of anatomic abnormalities limit the utility of standard anatomic imaging, making FDG-PET/CT the imaging modality of choice for patients with bone lymphoma.

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