Objectives This study sought to determine whether arterial inflammation measured by18 F-fluorodeoxyglucose positron emission tomography (18 F-FDG-PET) improves prediction of cardiovascular disease ...(CVD) beyond traditional risk factors. Background It is unknown whether arterial18 F-FDG uptake measured with routine PET imaging provides incremental value for predicting CVD events beyond Framingham risk score (FRS). Methods We consecutively identified 513 individuals from 6,088 patients who underwent18 F-FDG-PET and computed tomography (CT) imaging at Massachusetts General Hospital between 2005 and 2008 and who met additional inclusion criteria: ≥30 years of age, no prior CVD, and free of cancer. CVD events were independently adjudicated, while blinded to clinical data, using medical records to determine incident stroke, transient ischemic attack, acute coronary syndrome, revascularization, new-onset angina, peripheral arterial disease, heart failure, or CVD death. FDG uptake was measured in the ascending aorta (as target-to-background-ratio TBR), while blinded to clinical data. Results During follow-up (median 4.2 years), 44 participants developed CVD (2 per 100 person-years at risk). TBR strongly predicted subsequent CVD independent of traditional risk factors (hazard ratio: 4.71; 95% confidence interval CI: 1.98 to 11.2; p < 0.001) and (hazard ratio: 4.13; 95% CI: 1.59 to 10.76; p = 0.004) after further adjustment for coronary calcium score. Addition of arterial PET measurement to FRS scores improved the C-statistic (mean ± standard error 0.62 ± 0.03 vs. 0.66 ± 0.03). Further, incorporation of TBR into a model with FRS variables resulted in an integrated discrimination of 5% (95% CI: 0.36 to 9.87). Net reclassification improvements were 27.48% (95% CI: 16.27 to 39.92) and 22.3% (95% CI: 11.54 to 35.42) for the 10% and 6% intermediate-risk cut points, respectively. Moreover, TBR was inversely associated with the timing of CVD (beta −0.096; p < 0.0001). Conclusions Arterial FDG uptake, measured from routinely obtained PET/CT images, substantially improved incident CVD prediction beyond FRS among individuals undergoing cancer surveillance and provided information on the potential timing of such events.
Abstract Objectives : Recent data shows a relationship between aortic valve (AV) inflammation and calcification. However, direct evidence linking early valve inflammation (prior to hemodynamic ...compromise) to subsequent calcium (Ca) deposition is lacking in humans. We sought to test the hypothesis whether local AV inflammation predisposes to subsequent AV Ca deposition. Methods : We identified 111 individuals (age 6049, 68, 50.5% male) without active cancer or aortic stenosis who underwent 2 PET/CT studies 1–5 years apart for cancer surveillance. AV inflammation was determined by measuring FDG uptake (maximum standardized uptake value, SUVmax) within the AV on baseline PET/CT. Subsequent deposition of AV Ca was determined by comparing baseline and follow-up CT scans, determined as an increase in AV Ca volume score (CaVS). Patients were classified as “non-progressors” or “progressors” based on Square Root difference in CaVS (using a pre-determined cut-off value of 2.5). CT and PET measurements were conducted by 2 mutually blinded laboratories. Results : During follow-up, AV Ca increased in 23 patients (20.2%) classified as “progressors”, of whom 9 (9.2%) demonstrated subsequent ‘incident’ AV Ca. The AV SUVmax (mean ± SD) was higher in progressors vs. non-progressors (2.03 ± 0.52 vs.1.74 ± 0.36, p = 0.02) and especially in patients with-vs. without-incident AV Ca (2.28 ± 0.42 vs. 1.73 ± 0.36, p < 0.001). Moreover, AV inflammation (AV SUVmax) independently predicted subsequent calcification after adjusting for cardiovascular risk factors OR (95%CI): 4.99 (1.30–19.15), p = 0.02. Conclusion : The findings suggest that early AV inflammation may predispose to AV sclerosis. The evaluation of valvular metabolic activity may prove useful for developing a better understanding of calcific valve disease.
Brown adipose tissue (BAT) consumes glucose when it is activated by cold exposure, allowing its detection in humans by (18)F-fluorodeoxyglucose (FDG) positron emission tomography (PET) with computed ...tomography (CT). The investigators recently described a novel noninvasive and nonionizing imaging method to assess BAT in mice using contrast-enhanced ultrasound (CEUS). Here, they report the application of this method in healthy humans.
Thirteen healthy volunteers were recruited. CEUS was performed before and after cold exposure in all subjects using a continuous intravenous infusion of perflutren gas-filled lipid microbubbles and triggered imaging of the supraclavicular space. The first five subjects received microbubbles at a lower infusion rate than the subsequent eight subjects and were analyzed as a separate group. Blood flow was estimated as the product of the plateau (A) and the slope (β) of microbubble replenishment curves. All underwent (18)F-FDG PET/CT after cold exposure.
An increase in the acoustic signal was noted in the supraclavicular adipose tissue area with increasing triggering intervals in all subjects, demonstrating the presence of blood flow. The area imaged by CEUS colocalized with BAT, as detected by ¹⁸F-FDG PET/CT. In a cohort of eight subjects with an optimized CEUS protocol, CEUS-derived BAT blood flow increased with cold exposure compared with basal BAT blood flow in warm conditions (median Aβ = 3.3 AU/s interquartile range, 0.5-5.7 AU/s vs 1.25 AU/s interquartile range, 0.5-2.6 AU/s; P = .02). Of these eight subjects, five had greater than twofold increases in blood flow after cold exposure; these responders had higher BAT activity measured by (18)F-FDG PET/CT (median maximal standardized uptake value, 2.25 interquartile range, 1.53-4.57 vs 0.51 interquartile range, 0.47-0.73; P = .02).
The present study demonstrates the feasibility of using CEUS as a noninvasive, nonionizing imaging modality in estimating BAT blood flow in young, healthy humans. CEUS may be a useful and scalable tool in the assessment of BAT and BAT-targeted therapies.
Coronary vascular events are most often caused by rupture of atherosclerotic plaques. Prior to their rupture, such plaques are likely to have at least one of several high-risk structural or ...biological processes known to associate with increased risk of atherothrombosis. Thus, efforts have long been directed to identify these high risk features non-invasively. While current imaging modalities are adept at measuring high-risk structural features, such as luminal stenosis and vessel wall morphology, they cannot directly report on the important high-risk biological features. On the other hand, molecular imaging techniques, such as positron emission tomography (PET) coupled with sensitive probes provide a unique opportunity to assess atherosclerotic plaque biology, and have the potential to complement structural information and thus, improve risk stratification and enable enhanced monitoring of therapeutic interventions.
Background
Current guidelines recommend early P2Y12 inhibitor administration in non‐ST‐elevation myocardial infarction, but it is unclear if precatheterization use is associated with longer delays to ...coronary artery bypass grafting (CABG) or higher risk of post‐CABG bleeding and transfusion. This study examines the patterns and outcomes of precatheterization P2Y12 inhibitor use in non‐ST‐elevation myocardial infarction patients who undergo CABG.
Methods and Results
Retrospective analysis was done of 20 304 non‐ST‐elevation myocardial infarction patients in the ACTION (Acute Coronary Treatment and Intervention Outcomes Network) Registry (2009–2014) who underwent catheterization within 24 hours of admission and CABG during the index hospitalization. Using inverse probability‐weighted propensity adjustment, we compared time from catheterization to CABG, post‐CABG bleeding, and transfusion rates between patients who did and did not receive precatheterization P2Y12 inhibitors. Among study patients, 32.9% received a precatheterization P2Y12 inhibitor (of these, 2.2% were given ticagrelor and 3.7% prasugrel). Time from catheterization to CABG was longer among patients who received precatheterization P2Y12 inhibitor (median 69.9 hours 25th, 75th percentiles 28.2, 115.8 versus 43.5 hours 21.0, 71.8, P<0.0001), longer for patients treated with prasugrel (median 114.4 hours 66.5, 155.5) or ticagrelor (90.4 hours 48.7, 124.5) compared with clopidogrel (69.3 27.5, 114.6, P<0.0001). Precatheterization P2Y12 inhibitor use was associated with a higher risk of post‐CABG major bleeding (75.7% versus 73.4%, adjusted odds ratio 1.33, 95% confidence interval 1.22‐1.45, P<0.0001) and transfusion (47.6% versus 35.7%, adjusted odds ratio 1.51, 95% confidence interval 1.41‐1.62, P<0001); these relationships did not differ among patients treated with clopidogrel, prasugrel, or ticagrelor.
Conclusions
Precatheterization P2Y12 inhibitor use occurs commonly among non‐ST‐elevation myocardial infarction patients who undergo early catheterization and in‐hospital CABG. Despite longer delays to surgery, the majority of pretreated patients proceed to CABG <3 days postcatheterization. Precatheterization P2Y12 inhibitor use is associated with higher risks of postoperative bleeding and transfusion.
For decades, the identification of significant luminal narrowing has been the hallmark to characterize the presence and extent of coronary artery disease. However, it is now known that ...characterizations of systemic atherosclerosis burden and inflammation, as well as the local quality of plaque composition and morphology, allow better characterization of coronary artery disease and thus may allow improved prediction of adverse cardiovascular events. Plaque characterized histologically as a thin-cap fibroatheroma (ie, an atheroma with a thin fibrous cap, an underlying lipid-rich necrotic core, and inflammatory activity) has been recognized as representing vulnerable or high-risk plaque. Positron emission tomography (PET) and cardiac computed tomography (CT) are noninvasive modalities that provide metabolic (PET) and morphologic (CT) information about atherosclerotic plaque. PET allows the quantification of the uptake of fluorine 18 fluorodeoxyglucose (FDG) within the arterial wall, which provides a measure of macrophage activity within atheromatous plaque. Coronary CT allows the depiction of plaque morphology and composition. Thus, integrated imaging with PET and CT (PET/CT) permits coregistration of FDG activity with the presence and morphology of plaque and may lead to improved characterization of vulnerable plaque or vulnerable patients, or both. This review details the methods and principles of cardiac FDG PET and coronary CT and provides an overview of the research, with an emphasis on the identification and characterization of vulnerable plaque.
Objectives The study sought to test whether high-dose statin treatment would result in greater reductions in plaque inflammation than low-dose statins, using fluorodeoxyglucose-positron emission ...tomography/computed tomographic imaging (FDG-PET/CT). Background Intensification of statin therapy reduces major cardiovascular events. Methods Adults with risk factors or with established atherosclerosis, who were not taking high-dose statins (n = 83), were randomized to atorvastatin 10 versus 80 mg in a double-blind, multicenter trial. FDG-PET/CT imaging of the ascending thoracic aorta and carotid arteries was performed at baseline, 4, and 12 weeks after randomization and target-to-background ratio (TBR) of FDG uptake within the artery wall was assessed while blinded to time points and treatment. Results Sixty-seven subjects completed the study, providing imaging data for analysis. At 12 weeks, inflammation (TBR) in the index vessel was significantly reduced from baseline with atorvastatin 80 mg (% reduction 95% confidence interval: 14.42% 8.7% to 19.8%; p < 0.001), but not atorvastatin 10 mg (% reduction: 4.2% –2.3% to 10.4%; p > 0.1). Atorvastatin 80 mg resulted in significant additional relative reductions in TBR versus atorvastatin 10 mg (10.6% 2.2% to 18.3%; p = 0.01) at week 12. Reductions from baseline in TBR were seen as early as 4 weeks after randomization with atorvastatin 10 mg (6.4% reduction, p < 0.05) and 80 mg (12.5% reduction, p < 0.001). Changes in TBR did not correlate with lipid profile changes. Conclusions Statin therapy produced significant rapid dose-dependent reductions in FDG uptake that may represent changes in atherosclerotic plaque inflammation. FDG-PET imaging may be useful in detecting early treatment effects in patients at risk or with established atherosclerosis. (Evaluate the Utility of 18FDG-PET as a Tool to Quantify Atherosclerotic Plaque; NCT00703261 )
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