Sex differences in coronary atherosclerotic plaque activity using 18F-sodium fluoride positron emission tomography.

INTRODUCTION: There are sex differences in the extent, severity, and outcomes of coronary artery disease. We aimed to assess the influence of sex on coronary atherosclerotic plaque activity measured using coronary 18F-sodium fluoride (18F-NaF) positron emission tomography (PET), and to determine whether 18F-NaF PET has prognostic value in both women and men. METHODS: In a post-hoc analysis of observational cohort studies of patients with coronary atherosclerosis who had undergone 18F-NaF PET CT angiography, we compared the coronary microcalcification activity (CMA) in women and men. RESULTS: Baseline 18F-NaF PET CT angiography was available in 999 participants (151 (15%) women) with 4282 patient-years of follow-up. Compared to men, women had lower coronary calcium scores (116 [interquartile range, 27-434] versus 205 [51-571] Agatston units; p = 0.002) and CMA values (0.0 [0.0-1.12] versus 0.53 [0.0-2.54], p = 0.01). Following matching for plaque burden by coronary calcium scores and clinical comorbidities, there was no sex-related difference in CMA values (0.0 [0.0-1.12] versus 0.0 [0.0-1.23], p = 0.21) and similar proportions of women and men had no 18F-NaF uptake (53.0% (n = 80) and 48.3% (n = 73); p = 0.42), or CMA values > 1.56 (21.8% (n = 33) and 21.8% (n = 33); p = 1.00). Over a median follow-up of 4.5 [4.0-6.0] years, myocardial infarction occurred in 6.6% of women (n = 10) and 7.8% of men (n = 66). Coronary microcalcification activity greater than 0 was associated with a similarly increased risk of myocardial infarction in both women (HR: 3.83; 95% CI:1.10-18.49; p = 0.04) and men (HR: 5.29; 95% CI:2.28-12.28; p < 0.001). CONCLUSION: Although men present with more coronary atherosclerotic plaque than women, increased plaque activity is a strong predictor of future myocardial infarction regardless of sex.

Noninvasive In Vivo Thrombus Imaging in Patients With Ischemic Stroke or Transient Ischemic Attack-Brief Report.

BACKGROUND: 18F-GP1 is a novel positron-emitting radiotracer that is highly specific for activated platelets and thrombus. In a proof-of-concept study, we aimed to determine its potential clinical application in establishing the role and origin of thrombus in ischemic stroke. METHODS: Eleven patients with recent ischemic stroke (n=9) or transient ischemic attack (n=2) underwent 18F-GP1 positron emission tomography and computed tomography angiography at a median of 11 (range, 2-21) days from symptom onset. 18F-GP1 uptake (maximum target-to-background ratio) was assessed in the carotid arteries and brain. RESULTS: 18F-GP1 uptake was identified in 10 of 11 patients: 4 in the carotid arteries only, 3 in the brain only, and 3 in both the brain and carotid arteries. In those with carotid uptake, 4 participants had >50% stenosis and 3 had nonstenotic disease. One case had bilateral stenotic disease (>70%), but only the culprit carotid artery demonstrated 18F-GP1 uptake. The average uptake was higher in the culprit (median maximum target-to-background ratio, 1.55 [interquartile range, 1.26-1.82]) compared with the contralateral nonculprit carotid artery (maximum target-to-background ratio, 1.22 [1.19-1.6]). In those with brain 18F-GP1 uptake (maximum target-to-background ratio, 6.45 [4.89-7.65]), areas of acute infarction on computed tomography correlated with brain 18F-GP1 uptake in 6 cases. Ex vivo autoradiography of postmortem infarcted brain tissue showed focal uptake corresponding to intraluminal thrombus within the culprit vessel and downstream microvasculature. There was also evidence of diffuse uptake within some of the infarcted brain tissue reflecting parenchymal petechial hemorrhage. CONCLUSIONS: 18F-GP1 positron emission tomography and computed tomography angiography is a novel noninvasive method of identifying in vivo cerebrovascular thrombosis, which holds major promise in understanding the role and origin of thrombosis in stroke. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT03943966.

Latent Coronary Plaque Morphology From Computed Tomography Angiography, Molecular Disease Activity on Positron Emission Tomography, and Clinical Outcomes.

BACKGROUND: Assessments of coronary disease activity with 18F-sodium fluoride positron emission tomography and radiomics-based precision coronary plaque phenotyping derived from coronary computed tomography angiography may enhance risk stratification in patients with coronary artery disease. We sought to investigate whether the prognostic information provided by these 2 approaches is complementary in the prediction of myocardial infarction. METHODS: Patients with known coronary artery disease underwent coronary 18F-sodium fluoride positron emission tomography and coronary computed tomography angiography on a hybrid positron emission tomography/computed tomography scanner. Coronary 18F-NaF uptake was determined by the coronary microcalcification activity. We performed quantitative plaque analysis of coronary computed tomography angiography datasets and extracted 1103 radiomic features for each plaque. Using weighted correlation network analysis, we derived latent morphological features of coronary lesions which were aggregated to patient-level radiomics nomograms to predict myocardial infarction. RESULTS: Among 260 patients with established coronary artery disease (age, 65±9 years; 83% men), 179 (69%) participants showed increased coronary 18F-NaF activity (coronary microcalcification activity>0). Over 53 (40-59) months of follow-up, 18 patients had a myocardial infarction. Using weighted correlation network analysis, we derived 15 distinct eigen radiomic features representing latent morphological coronary plaque patterns in an unsupervised fashion. Following adjustments for calcified, noncalcified, and low-density noncalcified plaque volumes and 18F-NaF coronary microcalcification activity, 4 radiomic features remained independent predictors of myocardial infarction (hazard ratio, 1.46 [95% CI, 1.03-2.08]; P=0.03; hazard ratio, 1.62 [95% CI, 1.04-2.54]; P=0.02; hazard ratio, 1.49 [95% CI, 1.07-2.06]; P=0.01; and hazard ratio, 1.50 (95% CI, 1.05-2.13); P=0.02). CONCLUSIONS: In patients with established coronary artery disease, latent coronary plaque morphological features, quantitative plaque volumes, and disease activity on 18F-sodium fluoride positron emission tomography are additive predictors of myocardial infarction.

Translational molecular imaging: Thrombosis imaging with positron emission tomography.

A key focus of cardiovascular medicine is the detection, treatment, and prevention of disease, with a move towards more personalized and patient-centred treatments. To achieve this goal, novel imaging approaches that allow for early and accurate detection of disease and risk stratification are needed. At present, the diagnosis, monitoring, and prognostication of thrombotic cardiovascular diseases are based on imaging techniques that measure changes in structural anatomy and biological function. Molecular imaging is emerging as a new tool for the non-invasive detection of biological processes, such as thrombosis, that can improve identification of these events above and beyond current imaging modalities. At the forefront of these evolving techniques is the use of high-sensitivity radiotracers in conjunction with positron emission tomography imaging that could revolutionise current diagnostic paradigms by improving our understanding of the role and origin of thrombosis in a range of cardiovascular diseases.

Atorvastatin lowers 68Ga-DOTATATE uptake in coronary arteries, bone marrow and spleen in individuals with type 2 diabetes.

AIMS/HYPOTHESIS: Inflammation is a core component of residual cardiovascular risk in type 2 diabetes. With new anti-inflammatory therapeutics entering the field, accurate markers to evaluate their effectiveness in reducing cardiovascular disease are paramount. Gallium-68-labelled DOTATATE (68Ga-DOTATATE) has recently been proposed as a more specific marker of arterial wall inflammation than 18F-fluorodeoxyglucose (18F-FDG). This study set out to investigate whether 68Ga-DOTATATE uptake is amenable to therapeutic intervention in individuals with type 2 diabetes. METHODS: Individuals aged >50 years with type 2 diabetes underwent 68Ga-DOTATATE positron emission tomography (PET)/computed tomography (CT) at baseline and after 3 months treatment with atorvastatin 40 mg once daily. Primary outcome was the difference in coronary 68Ga-DOTATATE uptake, expressed as target-to-background ratio (TBR). The secondary outcome was difference in bone marrow and splenic uptake, expressed as the standardised uptake value (SUV). RESULTS: Twenty-two individuals with type 2 diabetes (mean age 63.2±6.4 years, 82% male, LDL-cholesterol 3.42±0.81 mmol/l, HbA1c 55±12 mmol/mol [7.2%±3.2%]) completed both 68Ga-DOTATATE PET/CT scans. The maximum TBR was -31% (95% CI -50, -12) lower in the coronary arteries, and bone marrow and splenic 68Ga-DOTATATE uptake was also significantly lower post statin treatment, with a mean percentage reduction of -15% (95% CI -27, -4) and -17% (95% CI -32, -2), respectively. CONCLUSIONS/INTERPRETATION: 68Ga-DOTATATE uptake across the cardio-haematopoietic axis was lower after statin therapy in individuals with type 2 diabetes. Therefore, 68Ga-DOTATATE is promising as a metric for vascular and haematopoietic inflammation in intervention studies using anti-inflammatory therapeutics in individuals with type 2 diabetes. TRIAL REGISTRATION: ClinicalTrials.gov NCT05730634.

Automated nonlinear registration of coronary PET to CT angiography using pseudo-CT generated from PET with generative adversarial networks.

BACKGROUND: Coronary 18F-sodium-fluoride (18F-NaF) positron emission tomography (PET) showed promise in imaging coronary artery disease activity. Currently image processing remains subjective due to the need for manual registration of PET and computed tomography (CT) angiography data. We aimed to develop a novel fully automated method to register coronary 18F-NaF PET to CT angiography using pseudo-CT generated by generative adversarial networks (GAN). METHODS: A total of 169 patients, 139 in the training and 30 in the testing sets were considered for generation of pseudo-CT from non-attenuation corrected (NAC) PET using GAN. Non-rigid registration was used to register pseudo-CT to CT angiography and the resulting transformation was used to align PET with CT angiography. We compared translations, maximal standard uptake value (SUVmax) and target to background ratio (TBRmax) at the location of plaques, obtained after observer and automated alignment. RESULTS: Automatic end-to-end registration was performed for 30 patients with 88 coronary vessels and took 27.5 seconds per patient. Difference in displacement motion vectors between GAN-based and observer-based registration in the x-, y-, and z-directions was 0.8 ± 3.0, 0.7 ± 3.0, and 1.7 ± 3.9 mm, respectively. TBRmax had a coefficient of repeatability (CR) of 0.31, mean bias of 0.03 and narrow limits of agreement (LOA) (95% LOA: - 0.29 to 0.33). SUVmax had CR of 0.26, mean bias of 0 and narrow LOA (95% LOA: - 0.26 to 0.26). CONCLUSION: Pseudo-CT generated by GAN are perfectly registered to PET can be used to facilitate quick and fully automated registration of PET and CT angiography.

Relationship between impaired myocardial blood flow by positron emission tomography and low-attenuation plaque burden and pericoronary adipose tissue attenuation from coronary computed tomography: From the prospective PACIFIC trial.

BACKGROUND: Positron emission tomography (PET) is the clinical gold standard for quantifying myocardial blood flow (MBF). Pericoronary adipose tissue (PCAT) attenuation may detect vascular inflammation indirectly. We examined the relationship between MBF by PET and plaque burden and PCAT on coronary CT angiography (CCTA). METHODS: This post hoc analysis of the PACIFIC trial included 208 patients with suspected coronary artery disease (CAD) who underwent [15O]H2O PET and CCTA. Low-attenuation plaque (LAP, < 30HU), non-calcified plaque (NCP), and PCAT attenuation were measured by CCTA. RESULTS: In 582 vessels, 211 (36.3%) had impaired per-vessel hyperemic MBF (≤ 2.30 mL/min/g). In multivariable analysis, LAP burden was independently and consistently associated with impaired hyperemic MBF (P = 0.016); over NCP burden (P = 0.997). Addition of LAP burden improved predictive performance for impaired hyperemic MBF from a model with CAD severity and calcified plaque burden (P < 0.001). There was no correlation between PCAT attenuation and hyperemic MBF (r = - 0.11), and PCAT attenuation was not associated with impaired hyperemic MBF in univariable or multivariable analysis of all vessels (P > 0.1). CONCLUSION: In patients with stable CAD, LAP burden was independently associated with impaired hyperemic MBF and a stronger predictor of impaired hyperemic MBF than NCP burden. There was no association between PCAT attenuation and hyperemic MBF.

Native Aortic Valve Disease Progression and Bioprosthetic Valve Degeneration in Patients With Transcatheter Aortic Valve Implantation.

BACKGROUND: Major uncertainties remain regarding disease activity within the retained native aortic valve, and regarding bioprosthetic valve durability, after transcatheter aortic valve implantation (TAVI). We aimed to assess native aortic valve disease activity and bioprosthetic valve durability in patients with TAVI in comparison with subjects with bioprosthetic surgical aortic valve replacement (SAVR). METHODS: In a multicenter cross-sectional observational cohort study, patients with TAVI or bioprosthetic SAVR underwent baseline echocardiography, computed tomography angiography, and 18F-sodium fluoride (18F-NaF) positron emission tomography. Participants (n=47) were imaged once with 18F-NaF positron emission tomography/computed tomography either at 1 month (n=9, 19%), 2 years (n=22, 47%), or 5 years (16, 34%) after valve implantation. Patients subsequently underwent serial echocardiography to assess for changes in valve hemodynamic performance (change in peak aortic velocity) and evidence of structural valve dysfunction. Comparisons were made with matched patients with bioprosthetic SAVR (n=51) who had undergone the same imaging protocol. RESULTS: In patients with TAVI, native aortic valves demonstrated 18F-NaF uptake around the outside of the bioprostheses that showed a modest correlation with the time from TAVI (r=0.36, P=0.023). 18F-NaF uptake in the bioprosthetic leaflets was comparable between the SAVR and TAVI groups (target-to-background ratio, 1.3 [1.2-1.7] versus 1.3 [1.2-1.5], respectively; P=0.27). The frequencies of imaging evidence of bioprosthetic valve degeneration at baseline were similar on echocardiography (6% versus 8%, respectively; P=0.78), computed tomography (15% versus 14%, respectively; P=0.87), and positron emission tomography (15% versus 29%, respectively; P=0.09). Baseline 18F-NaF uptake was associated with a subsequent change in peak aortic velocity for both TAVI (r=0.7, P<0.001) and SAVR (r=0.7, P<0.001). On multivariable analysis, 18F-NaF uptake was the only predictor of peak velocity progression (P<0.001). CONCLUSIONS: In patients with TAVI, native aortic valves demonstrate evidence of ongoing active disease. Across imaging modalities, TAVI degeneration is of similar magnitude to bioprosthetic SAVR, suggesting comparable midterm durability. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02304276.

Respiration-averaged CT versus standard CT attenuation map for correction of 18F-sodium fluoride uptake in coronary atherosclerotic lesions on hybrid PET/CT.

BACKGROUND: To evaluate the impact of respiratory-averaged computed tomography attenuation correction (RACTAC) compared to standard single-phase computed tomography attenuation correction (CTAC) map, on the quantitative measures of coronary atherosclerotic lesions of 18F-sodium fluoride (18F-NaF) uptake in hybrid positron emission tomography and computed tomography (PET/CT). METHODS: This study comprised 23 patients who underwent 18F-NaF coronary PET in a hybrid PET/CT system. All patients had a standard single-phase CTAC obtained during free-breathing and a 4D cine-CT scan. From the cine-CT acquisition, RACTAC maps were obtained by averaging all images acquired over 5 seconds. PET reconstructions using either CTAC or RACTAC were compared. The quantitative impact of employing RACTAC was assessed using maximum target-to-background (TBRMAX) and coronary microcalcification activity (CMA). Statistical differences were analyzed using reproducibility coefficients and Bland-Altman plots. RESULTS: In 23 patients, we evaluated 34 coronary lesions using CTAC and RACTAC reconstructions. There was good agreement between CTAC and RACTAC for TBRMAX (median [Interquartile range]): CTAC = 1.65 [1.23 to 2.38], RACTAC = 1.63 [1.23 to 2.33], p = 0.55), with coefficient of reproducibility of 0.18, and CMA: CTAC = 0.10 [0 to 1.0], RACTAC = 0.15 [0 to 1.03], p = 0.55 with coefficient of reproducibility of 0.17 CONCLUSION: Respiratory-averaged and standard single-phase attenuation correction maps provide similar and reproducible methods of quantifying coronary 18F-NaF uptake on PET/CT.

Observer repeatability and interscan reproducibility of 18F-sodium fluoride coronary microcalcification activity.

BACKGROUND: We aimed to establish the observer repeatability and interscan reproducibility of coronary 18F-sodium-fluoride positron emission tomography (PET) uptake using a novel semi-automated approach, coronary microcalcification activity (CMA). METHODS: Patients with multivessel coronary artery disease underwent repeated hybrid PET and computed tomography angiography (CTA) imaging (PET/CTA). CMA was defined as the integrated standardized uptake values (SUV) in the entire coronary tree exceeding 2 standard deviations above the background SUV. Coefficients of repeatability between the same observer (intraobserver repeatability), between 2 observers (interobserver repeatability) and coefficient of reproducibility between 2 scans (interscan reproducibility), were determined at vessel and patient level. RESULTS: In 19 patients, CMA was assessed twice in 43 coronary vessels on two PET/CT scans performed 12 ± 5 days apart. There was excellent intraclass correlation for intraobserver and interobserver repeatability as well as interscan reproducibility (all ≥ 0.991). There was 100% intraobserver, interobserver and interscan agreement for the presence (CMA > 0) or absence (CMA = 0) of coronary18F-NaF uptake. Mean CMA was 3.12 ± 0.62 with coefficients of repeatability of ≤ 10% for all measures: intraobserver 0.24 and 0.22, interobserver 0.30 and 0.29 and interscan 0.33 and 0.32 at a per-vessel and per-patient level, respectively. CONCLUSIONS: CMA is a repeatable and reproducible global measure of coronary atherosclerotic activity.

Quantifying microcalcification activity in the thoracic aorta.

BACKGROUND: Standard methods for quantifying positron emission tomography (PET) uptake in the aorta are time consuming and may not reflect overall vessel activity. We describe aortic microcalcification activity (AMA), a novel method for quantifying 18F-sodium fluoride (18F-NaF) uptake in the thoracic aorta. METHODS: Twenty patients underwent two hybrid 18F-NaF PET and computed tomography (CT) scans of the thoracic aorta less than three weeks apart. AMA, as well as maximum (TBRmax) and mean (TBRmean) tissue to background ratios, were calculated by two trained operators. Intra-observer repeatability, inter-observer repeatability and scan-rescan reproducibility were assessed. Each 18F-NaF quantification method was compared to validated cardiovascular risk scores. RESULTS: Aortic microcalcification activity demonstrated excellent intra-observer (intraclass correlation coefficient 0.98) and inter-observer (intraclass correlation coefficient 0.97) repeatability with very good scan-rescan reproducibility (intraclass correlation coefficient 0.86) which were similar to previously described TBRmean and TBRmax methods. AMA analysis was much quicker to perform than standard TBR assessment (3.4min versus 15.1min, P<0.0001). AMA was correlated with Framingham stroke risk scores and Framingham risk score for hard cononary heart disease. CONCLUSIONS: AMA is a simple, rapid and reproducible method of quantifying global 18F-NaF uptake across the ascending aorta and aortic arch that correlates with cardiovascular risk scores.

Comparison of diabetes to other prognostic predictors among patients referred for cardiac stress testing: A contemporary analysis from the REFINE SPECT Registry.

BACKGROUND: Diabetes mellitus (DM) is increasingly prevalent among contemporary populations referred for cardiac stress testing, but its potency as a predictor for major adverse cardiovascular events (MACE) vs other clinical variables is not well delineated. METHODS AND RESULTS: From 19,658 patients who underwent SPECT-MPI, we identified 3122 patients with DM without known coronary artery disease (CAD) (DM+/CAD-) and 3564 without DM with known CAD (DM-/CAD+). Propensity score matching was used to control for the differences in characteristics between DM+/CAD- and DM-/CAD+ groups. There was comparable MACE in the matched DM+/CAD- and DM-/CAD+ groups (HR 1.15, 95% CI 0.97-1.37). By Chi-square analysis, type of stress (exercise or pharmacologic), total perfusion deficit (TPD), and left ventricular function were the most potent predictors of MACE, followed by CAD and DM status. The combined consideration of mode of stress, TPD, and DM provided synergistic stratification, an 8.87-fold (HR 8.87, 95% CI 7.27-10.82) increase in MACE among pharmacologically stressed patients with DM and TPD > 10% (vs non-ischemic, exercised stressed patients without DM). CONCLUSIONS: Propensity-matched patients with DM and no known CAD have similar MACE risk compared to patients with known CAD and no DM. DM is synergistic with mode of stress testing and TPD in predicting the risk of cardiac stress test patients.

18F-Sodium Fluoride (18F-NaF) for Imaging Microcalcification Activity in the Cardiovascular System.

Accumulating preclinical and clinical evidence suggests that calcification is one of the body's primary responses to injury and a key pathological feature of cardiovascular disease. Calcification activity can now be imaged using 18F-sodium fluoride (18F-NaF) positron emission tomography (PET) in combination with either computed tomography or magnetic resonance. These techniques allow visualization of calcification activity and, therefore, provide different information to the established macroscopic calcium imaged with computed tomography. Indeed, 18F-NaF PET has been used to investigate a wide range of valvular conditions, including aortic stenosis, mitral annular calcification, and bioprosthetic valve disease, as well as vascular conditions, including abdominal aortic aneurysm disease, coronary, and carotid atherosclerosis, peripheral vascular disease, and erectile dysfunction. In this brief review, we will focus on how 18F-NaF PET has improved our pathophysiological understanding of cardiovascular calcification and how it can be used as a marker of vascular calcification, providing a useful tool that can be utilized in clinical trials investigating the prediction of both disease progression and clinical events. Finally, we will discuss how 18F-NaF might be employed clinically to improve patient assessment and to guide decision-making.

Short-term repeatability of myocardial blood flow using 82Rb PET/CT: The effect of arterial input function position and motion correction.

BACKGROUND: We tested the repeatability of myocardial blood flow (MBF) quantified using 82Rb with and without motion correction (MC) and with arterial input functions estimated from left ventricle (LV) and atrium (LA). METHODS: Twenty-one patients referred for clinical 82Rb PET/CT underwent repeated rest scans in a single imaging session. Global MBF was quantified using three different assessments by two operators: (1) automatic processing without MC and LV arterial input function (AIF), (2) with MC and LV-AIF, and (3) with MC and LA-AIF. Inter-scan and inter-operator repeatability were tested using coefficient of variation (CV). RESULTS: MC with LV-AIF did not change MBF (no MC: 1.01 ± 0.30 mL/min/g vs MC with LV-AIF: 1.01 ± 0.29, P = 0.70), whereas MC with LA-AIF showed significantly lower MBF assessments (0.95 ± 0.28 mL/min/g, P = 0.0006). We report significant improvement for test-retest reproducibility for global MBF following MC (CV; No MC: 16.0, MC (LV-AIF): 9.2, MC (LA-AIF): 8.8). Good inter-operator repeatability was observed for LV-AIF (CV = 4.7) and LA-AIF (CV = 5.6) for global MBF assessments. CONCLUSIONS: MC significantly improved the test-retest repeatability between operators and between scans. MBF obtained after MC with LV-AIF were comparable, whereas MBFs after MC and LA-AIF were significantly reduced.

Aortic valve perivascular adipose tissue computed tomography attenuation in patients with aortic stenosis.

OBJECTIVE: Aortic stenosis (AS) shares pathophysiological similarities with atherosclerosis including active inflammation. CT attenuation of perivascular adipose tissue provides a measure of vascular inflammation that is linked to prognosis and has the potential to be applied to the aortic valve. We investigated perivascular adipose tissue attenuation around the aortic valve in patients with AS. METHODS: CT attenuation was measured in the perivascular adipose tissue extending 3 mm radially and 10 mm longitudinally around the aortic valve in patients with and without AS. Associations between perivascular adipose tissue attenuation and AS disease severity, activity and progression were investigated. RESULTS: Perivascular adipose tissue attenuation around the aortic valve demonstrated good intraobserver and interobserver repeatability (interobserver: intraclass correlation coefficient 0.977 (95% CI: 0.94, 0.99)) but was similar between patients with AS (n=120) and control subjects (n=80) (-62.4 (-68.7, -56.5) Hounsfield units (HU) vs -61.2 (-65.3, -55.6) HU, p=0.099). There were no differences between perivascular adipose tissue attenuation in patients with mild (-60.2 (-66.9, -55.1) HU), moderate (-62.8 (-69.6, -56.80) HU) or severe (-62.3 (-69.3, -55.4) HU) AS (all p>0.05), and perivascular adipose tissue attenuation did not demonstrate an association with AS severity as assessed by echocardiography or CT calcium scoring, nor with disease activity assessed by 18F-sodium fluoride positron emission tomography. Moreover, there was no association between baseline aortic valve perivascular adipose tissue attenuation and subsequent AS progression (annualised change in peak velocity: r=0.072, p=0.458). Similar results were found using five other image analysis methods. CONCLUSIONS: CT-derived aortic valve perivascular adipose tissue attenuation is not associated with AS disease severity, activity or progression suggesting that it has no value in the investigation and management of patients with AS.

CT Attenuation of Periaortic Adipose Tissue in Abdominal Aortic Aneurysms.

Purpose To assess periaortic adipose tissue attenuation at CT angiography in different abdominal aortic aneurysm disease states. Materials and Methods In a retrospective observational study from January 2018 to December 2022, periaortic adipose tissue attenuation was assessed at CT angiography in patients with asymptomatic or symptomatic (including rupture) abdominal aortic aneurysms and controls without aneurysms. Adipose tissue attenuation was measured using semiautomated software in periaortic aneurysmal and nonaneurysmal segments of the abdominal aorta and in subcutaneous and visceral adipose tissue. Periaortic adipose tissue attenuation values between the three groups were assessed using Student t tests and Wilcoxon rank sum tests followed by a multiregression model. Results Eighty-eight individuals (median age, 70 years [IQR, 65-78]; 78 male and 10 female patients) were included: 70 patients with abdominal aortic aneurysms (40 asymptomatic and 30 symptomatic, including 24 with rupture) and 18 controls. There was no evidence of differences in the periaortic adipose tissue attenuation in the aneurysmal segment in asymptomatic patients versus controls (-81.44 HU ± 7 [SD] vs -83.27 HU ± 9; P = .43) and attenuation in nonaneurysmal segments between asymptomatic patients versus controls (-75.43 HU ± 8 vs -78.81 HU ± 6; P = .08). However, symptomatic patients demonstrated higher periaortic adipose tissue attenuation in both aneurysmal (-57.85 HU ± 7; P < .0001) and nonaneurysmal segments (-58.16 HU ± 8; P < .0001) when compared with the other two groups. Conclusion Periaortic adipose tissue CT attenuation was not increased in stable abdominal aortic aneurysm disease. There was a generalized increase in attenuation in patients with symptomatic disease, likely reflecting the systemic consequences of acute rupture. Keywords: Abdominal Aortic Aneurysm, Periaortic Adipose Tissue Attenuation, CT Angiography ClinicalTrials.gov registration no. NCT02229006 © RSNA, 2024.

First-in-human controlled inhalation of thin graphene oxide nanosheets to study acute cardiorespiratory responses.

Graphene oxide nanomaterials are being developed for wide-ranging applications but are associated with potential safety concerns for human health. We conducted a double-blind randomized controlled study to determine how the inhalation of graphene oxide nanosheets affects acute pulmonary and cardiovascular function. Small and ultrasmall graphene oxide nanosheets at a concentration of 200 µg m-3 or filtered air were inhaled for 2 h by 14 young healthy volunteers in repeated visits. Overall, graphene oxide nanosheet exposure was well tolerated with no adverse effects. Heart rate, blood pressure, lung function and inflammatory markers were unaffected irrespective of graphene oxide particle size. Highly enriched blood proteomics analysis revealed very few differential plasma proteins and thrombus formation was mildly increased in an ex vivo model of arterial injury. Overall, acute inhalation of highly purified and thin nanometre-sized graphene oxide nanosheets was not associated with overt detrimental effects in healthy humans. These findings demonstrate the feasibility of carefully controlled human exposures at a clinical setting for risk assessment of graphene oxide, and lay the foundations for investigating the effects of other two-dimensional nanomaterials in humans. Clinicaltrials.gov ref: NCT03659864.

EPidemiology Of Cardiogenic sHock in Scotland (EPOCHS): A multicentre, prospective observational study of the prevalence, management and outcomes of cardiogenic shock in Scotland.

Background: Despite high rates of cardiovascular disease in Scotland, the prevalence and outcomes of patients with cardiogenic shock are unknown. Methods: We undertook a prospective observational cohort study of consecutive patients with cardiogenic shock admitted to the intensive care unit (ICU) or coronary care unit at 13 hospitals in Scotland for a 6-month period. Denominator data from the Scottish Intensive Care Society Audit Group were used to estimate ICU prevalence; data for coronary care units were unavailable. We undertook multivariable logistic regression to identify factors associated with in-hospital mortality. Results: In total, 247 patients with cardiogenic shock were included. After exclusion of coronary care unit admissions, this comprised 3.0% of all ICU admissions during the study period (95% confidence interval [CI] 2.6%-3.5%). Aetiology was acute myocardial infarction (AMI) in 48%. The commonest vasoactive treatment was noradrenaline (56%) followed by adrenaline (46%) and dobutamine (40%). Mechanical circulatory support was used in 30%. Overall in-hospital mortality was 55%. After multivariable logistic regression, age (odds ratio [OR] 1.04, 95% CI 1.02-1.06), admission lactate (OR 1.10, 95% CI 1.05-1.19), Society for Cardiovascular Angiographic Intervention stage D or E at presentation (OR 2.16, 95% CI 1.10-4.29) and use of adrenaline (OR 2.73, 95% CI 1.40-5.40) were associated with mortality. Conclusions: In Scotland the prevalence of cardiogenic shock was 3% of all ICU admissions; more than half died prior to discharge. There was significant variation in treatment approaches, particularly with respect to vasoactive support strategy.