Vascular Positron Emission Tomography and Restenosis in Symptomatic Peripheral Arterial Disease: A Prospective Clinical Study

ObjectivesThis study determined whether in vivo positron emission tomography (PET) of arterial inflammation (¹⁸F-fluorodeoxyglucose [¹⁸F-FDG]) or microcalcification (¹⁸F-sodium fluoride [¹⁸F-NaF]) could predict restenosis following PTA.BackgroundRestenosis following lower limb percutaneous transluminal angioplasty (PTA) is common, unpredictable, and challenging to treat. Currently, it is impossible to predict which patient will suffer from restenosis following angioplasty.MethodsIn this prospective observational cohort study, 50 patients with symptomatic peripheral arterial disease underwent ¹⁸F-FDG and ¹⁸F-NaF PET/computed tomography (CT) imaging of the superficial femoral artery before and 6 weeks after angioplasty. The primary outcome was arterial restenosis at 12 months.ResultsForty subjects completed the study protocol with 14 patients (35%) reaching the primary outcome of restenosis. The baseline activities of femoral arterial inflammation (¹⁸F-FDG tissue-to-background ratio [TBR] 2.43 [interquartile range (IQR): 2.29 to 2.61] vs. 1.63 [IQR: 1.52 to 1.78]; p < 0.001) and microcalcification (¹⁸F-NaF TBR 2.61 [IQR: 2.50 to 2.77] vs. 1.69 [IQR: 1.54 to 1.77]; p < 0.001) were higher in patients who developed restenosis. The predictive value of both ¹⁸F-FDG (cut-off TBR_max value of 1.98) and ¹⁸F-NaF (cut-off TBR_max value of 2.11) uptake demonstrated excellent discrimination in predicting 1-year restenosis (Kaplan Meier estimator, log-rank p < 0.001).ConclusionsBaseline and persistent femoral arterial inflammation and micro-calcification are associated with restenosis following lower limb PTA. For the first time, we describe a method of identifying complex metabolically active plaques and patients at risk of restenosis that has the potential to select patients for intervention and to serve as a biomarker to test novel interventions to prevent restenosis.     

Peri-Coronary Adipose Tissue Density Is Associated With 18F-Sodium Fluoride Coronary Uptake in Stable Patients With High-Risk Plaques

ObjectivesThis study aimed to assess the association between increased lesion peri-coronary adipose tissue (PCAT) density and coronary ¹⁸F-sodium fluoride (¹⁸F-NaF) uptake on positron emission tomography (PET) in stable patients with high-risk coronary plaques (HRPs) shown on coronary computed tomography angiography (CTA).BackgroundCoronary ¹⁸F-NaF uptake reflects the rate of calcification of coronary atherosclerotic plaque. Increased PCAT density is associated with vascular inflammation. Currently, the relationship between increased PCAT density and ¹⁸F-NaF uptake in stable patients with HRPs on coronary CTA has not been characterized.MethodsPatients who underwent coronary CTA were screened for HRP, which was defined by 3 concurrent plaque features: positive remodeling; low attenuation plaque (LAP) (<30 Hounsfield units [HU]) and spotty calcification; and obstructive coronary stenosis ≥50% (plaque volume >100 mm³). Patients with HRPs were recruited to undergo ¹⁸F-NaF PET/CT. In lesions with stenosis ≥25%, quantitative plaque analysis, mean PCAT density, maximal coronary motion−corrected ¹⁸F-NaF standard uptake values (SUVmax), and target-to-background ratios (TBR) were measured.ResultsForty-one patients (age 65 ± 6 years; 68% men) were recruited. Fifty-one lesions in 23 patients (56%) showed increased coronary ¹⁸F-NaF activity. Lesions with ¹⁸F-NaF uptake had higher surrounding PCAT density than those without ¹⁸F-NaF uptake (−73 HU; interquartile range −79 to −68 HU vs. −86 HU; interquartile range −94 to −80 HU; p < 0.001). ¹⁸F-NaF TBR and SUVmax were correlated with PCAT density (r = 0.63 and r = 0.68, respectively; all p < 0.001). On adjusted multiple regression analysis, increased lesion PCAT density and LAP volume were associated with ¹⁸F-NaF TBR (β = 0.25; 95% confidence interval: 0.17 to 0.34; p < 0.001 for PCAT, and β = 0.07; 95% confidence interval: 0.03 to 0.11; p = 0.002 for LAP).ConclusionsIn patients with HRP features on coronary CTA, increased density of PCAT was associated with focal ¹⁸F-NaF PET uptake. Simultaneous assessment of these imaging biomarkers by ¹⁸F-NaF PET and CTA might refine cardiovascular risk prediction in stable patients with HRP features.     

Thoracic Aortic 18F-Sodium Fluoride Activity and Ischemic Stroke in Patients With Established Cardiovascular Disease

BackgroundAortic atherosclerosis represents an important contributor to ischemic stroke risk. Identifying patients with high-risk aortic atheroma could improve preventative treatment strategies for future ischemic stroke.ObjectivesThe purpose of this study was to investigate whether thoracic ¹⁸F-sodium fluoride positron emission tomography (PET) could improve the identification of patients at the highest risk of ischemic stroke.MethodsIn a post hoc observational cohort study, we quantified thoracic aortic and coronary ¹⁸F-sodium fluoride activity in 461 patients with stable cardiovascular disease undergoing PET combined with computed tomography (CT). Progression of atherosclerosis was assessed by change in aortic and coronary CT calcium volume. Clinical outcomes were determined by the occurrence of ischemic stroke and myocardial infarction. We compared the prognostic utility of ¹⁸F-sodium fluoride activity for predicting stroke to clinical risk scores and CT calcium quantification using survival analysis and multivariable Cox regression.ResultsAfter 12.7 ± 2.7 months, progression of thoracic aortic calcium volume correlated with baseline thoracic aortic ¹⁸F-sodium fluoride activity (n = 140; r = 0.31; P = 0.00016). In 461 patients, 23 (5%) patients experienced an ischemic stroke and 32 (7%) a myocardial infarction after 6.1 ± 2.3 years of follow-up. High thoracic aortic ¹⁸F-sodium fluoride activity was strongly associated with ischemic stroke (HR: 10.3 [95% CI: 3.1-34.8]; P = 0.00017), but not myocardial infarction (P = 0.40). Conversely, high coronary ¹⁸F-sodium fluoride activity was associated with myocardial infarction (HR: 4.8 [95% CI: 1.9-12.2]; P = 0.00095) but not ischemic stroke (P = 0.39). In a multivariable Cox regression model including imaging and clinical risk factors, thoracic aortic ¹⁸F-sodium fluoride activity was the only variable associated with ischemic stroke (HR: 8.19 [95% CI: 2.33-28.7], P = 0.0010).ConclusionsIn patients with established cardiovascular disease, thoracic aortic ¹⁸F-sodium fluoride activity is associated with the progression of atherosclerosis and future ischemic stroke. Arterial ¹⁸F-sodium fluoride activity identifies localized areas of atherosclerotic disease activity that are directly linked to disease progression and downstream regional clinical atherothrombotic events. (DIAMOND–Dual Antiplatelet Therapy to Reduce Myocardial Injury [DIAMOND], NCT02110303; Study Investigating the Effect of Drugs Used to Treat Osteoporosis on the Progression of Calcific Aortic Stenosis [SALTIRE II], NCT02132026; Novel Imaging Approaches To Identify Unstable Coronary Plaques, NCT01749254; and Role of Active Valvular Calcification and Inflammation in Patients With Aortic Stenosis, NCT01358513)     

18F-GP1 Positron Emission Tomography and Bioprosthetic Aortic Valve Thrombus

BackgroundBioprosthetic valve thrombosis may have implications for valve function and durability.ObjectivesUsing a novel glycoprotein IIb/IIIa receptor radiotracer 18F-GP1, we investigated whether positron emission tomography (PET)-computed tomography (CT) could detect thrombus formation on bioprosthetic aortic valves.MethodsEx vivo experiments were performed on human platelets and explanted bioprosthetic aortic valves. In a prospective cross-sectional study, patients with either bioprosthetic or normal native aortic valves underwent echocardiography, CT angiography, and 18F-GP1 PET-CT.ResultsFlow cytometric analysis, histology, immunohistochemistry, and autoradiography demonstrated selective binding of 18F-GP1 to activated platelet glycoprotein IIb/IIIa receptors and thrombus adherent to prosthetic valves. In total, 75 participants were recruited: 53 with bioprosthetic valves (median time from implantation 37 months [IQR: 12-80 months]) and 22 with normal native aortic valves. Three participants had obstructive valve thrombosis, and a further 3 participants had asymptomatic hypoattenuated leaflet thickening on CT angiography. All bioprosthetic valves, but none of the native aortic valves, demonstrated focal 18F-GP1 uptake on the valve leaflets: median maximum target-to-background ratio 2.81 (IQR: 2.29-3.48) vs 1.43 (IQR: 1.28-1.53) (P < 0.001). Higher 18F-GP1 uptake was independently associated with duration of valve implantation and hypoattenuated leaflet thickening. All 3 participants with obstructive valve thrombosis were anticoagulated for 3 months, leading to resolution of their symptoms, improvement in mean valve gradients, and a reduction in 18F-GP1 uptake.ConclusionsAdherence of activated platelets is a common and sustained finding on bioprosthetic aortic valves. 18F-GP1 uptake is higher in the presence of thrombus, regresses with anticoagulation, and has potential use as an adjunctive clinical tool. (18F-GP1 PET-CT to Detect Bioprosthetic Aortic Valve Thrombosis; NCT04073875)     

Feasibility of 68Ga-Labeled Fibroblast Activation Protein Inhibitor PET/CT in Light-Chain Cardiac Amyloidosis

BackgroundSystemic amyloid light chain (AL) amyloidosis is the most common type of amyloidosis, leading to cardiomyocyte necrosis and interstitial fibrosis. Gallium-68-labeled fibroblast activation protein inhibitor 04 (⁶⁸Ga-FAPI-04) has recently been introduced for imaging fibroblast activation in cardiac diseases. To date, cardiac fibroblast and cardiac amyloidosis (CA) phenotype activities have not been mapped.ObjectivesThe aim of this study was to evaluate the feasibility of ⁶⁸Ga-FAPI-04 positron emission tomography (PET)/computed tomography (CT) in assessing AL CA.MethodsThirty consecutive patients (mean age: 59.1 ± 7.7 years; 20 men, 10 women) with biopsy-proven AL amyloidosis were enrolled prospectively (including 27 with AL CA and 3 without AL CA). All patients underwent ⁶⁸Ga-FAPI-04 PET/CT (107.4 ± 26.5 MBq). Global standardized uptake values and left ventricular (LV) molecular volume were calculated in correlation to echocardiography (n = 30), cardiac magnetic resonance (n = 18), and clinical biomarkers. Subsequently, the patients were categorized as having patchy (PET-patchy), extensive (PET-extensive), and negative (PET-negative) patterns.ResultsOf all patients, 80% (24 of 30) showed increased LV uptake (PET-patchy [n = 4] vs PET-extensive [n = 20]), whereas 6 patients did not show visible myocardial uptake. Standardized uptake value ratio and LV molecular volume were significantly higher in the PET-extensive than the PET-patchy group (2.79 mL ± 1.22 mL vs 1.53 mL ± 0.66 mL [P = 0.045] and 198.3 mL ± 59.97 mL vs 127.8 mL ± 25.82 [P = 0.005], respectively). Additionally, ⁶⁸Ga-FAPI-04 uptake was significantly correlated with clinical biomarkers (Mayo stage and N-terminal pro–brain natriuretic peptide), interventricular septal thickness, left ventricular ejection fraction (LVEF), LV end-systolic volume, extracellular volume, and LV global strain (P < 0.05).Conclusions⁶⁸Ga-FAPI-04 PET/CT is feasible in detecting myocardial fibroblast activation in patients with AL CA in correlation with myocardial remodeling. It might provide complementary information on cardiac molecular characterization and staging of disease.     

Coronary 18F-Sodium Fluoride Uptake Predicts Outcomes in Patients With Coronary Artery Disease

BackgroundReliable methods for predicting myocardial infarction in patients with established coronary artery disease are lacking. Coronary ¹⁸F-sodium fluoride (¹⁸F-NaF) positron emission tomography (PET) provides an assessment of atherosclerosis activity.ObjectivesThis study assessed whether ¹⁸F-NaF PET predicts myocardial infarction and provides additional prognostic information to current methods of risk stratification.MethodsPatients with known coronary artery disease underwent ¹⁸F-NaF PET computed tomography and were followed up for fatal or nonfatal myocardial infarction over 42 months (interquartile range: 31 to 49 months). Total coronary ¹⁸F-NaF uptake was determined by the coronary microcalcification activity (CMA).ResultsIn a post hoc analysis of data collected for prospective observational studies, the authors studied 293 study participants (age: 65 ± 9 years; 84% men), of whom 203 (69%) showed increased coronary ¹⁸F-NaF activity (CMA >0). Fatal or nonfatal myocardial infarction occurred only in patients with increased coronary ¹⁸F-NaF activity (20 of 203 with a CMA >0 vs. 0 of 90 with a CMA of 0; p < 0.001). On receiver operator curve analysis, fatal or nonfatal myocardial infarction prediction was highest for ¹⁸F-NaF CMA, outperforming coronary calcium scoring, modified Duke coronary artery disease index and Reduction of Atherothrombosis for Continued Health (REACH) and Secondary Manifestations of Arterial Disease (SMART) risk scores (area under the curve: 0.76 vs. 0.54, 0.62, 0.52, and 0.54, respectively; p < 0.001 for all). Patients with CMA >1.56 had a >7-fold increase in fatal or nonfatal myocardial infarction (hazard ratio: 7.1; 95% confidence interval: 2.2 to 25.1; p = 0.003) independent of age, sex, risk factors, segment involvement and coronary calcium scores, presence of coronary stents, coronary stenosis, REACH and SMART scores, the Duke coronary artery disease index, and recent myocardial infarction.ConclusionsIn patients with established coronary artery disease, ¹⁸F-NaF PET provides powerful independent prediction of fatal or nonfatal myocardial infarction.     

Parametric Imaging of Biologic Activity of Atherosclerosis Using Dynamic Whole-Body Positron Emission Tomography

BackgroundFor molecular imaging of atherosclerotic vessel wall activity, tracer kinetic analysis may yield improved contrast versus blood, more robust quantitative parameters, and more reliable characterization of systems biology.ObjectivesThe authors introduce a novel dynamic whole-body positron emission tomography (PET) protocol that is enabled by rapid continuous camera table motion, followed by reconstruction of parametric data sets using voxel-based Patlak graphical analysis.MethodsTwenty-five subjects were prospectively enrolled and underwent dynamic PET up to 90 minutes after injection of 2-[¹⁸F]fluoro-2-deoxy-D-glucose (FDG). Two sets of images were generated: 1) the established standard of static standardized uptake value (SUV) images; and 2) parametric images of the metabolic rate of FDG (MR_FDG) using the Patlak plot–derived influx rate. Arterial wall signal was measured and compared using the volume-of-interest technique, and its association with hematopoietic and lymphoid organ signal and atherosclerotic risk factors was explored.ResultsParametric MR_FDG images provided excellent arterial wall visualization, with elimination of blood-pool activity, and enhanced focus detectability and reader confidence. Target-to-background ratio (TBR) from MR_FDG images was significantly higher compared with SUV images (2.6 ± 0.8 vs 1.4 ± 0.2; P < 0.0001), confirming improved arterial wall contrast. On MR_FDG images, arterial wall signal showed improved correlation with hematopoietic and lymphoid organ activity (spleen P = 0.0009; lymph nodes P = 0.0055; and bone marrow P = 0.0202) and increased with the number of atherosclerotic risk factors (r = 0.49; P = 0.0138), where signal from SUV images (SUV_max P = 0.9754; TBR_max P = 0.8760) did not.ConclusionsAbsolute quantification of MR_FDG is feasible for arterial wall using dynamic whole-body PET imaging. Parametric images provide superior arterial wall contrast, and they might be better suited to explore the relationship between arterial wall activity, systemic organ networks, and cardiovascular risk. This novel methodology may serve as a platform for future diagnostic and therapeutic clinical studies targeting the biology of arterial wall disease.     

Detection and Characterization of Thrombosis in Humans Using Fibrin-Targeted Positron Emission Tomography and Magnetic Resonance

ObjectivesThe authors present a novel technique to detect and characterize LAA thrombus in humans using combined positron emission tomography (PET)/cardiac magnetic resonance (CMR) of a fibrin-binding radiotracer, [⁶⁴Cu]FBP8.BackgroundThe detection of thrombus in the left atrial appendage (LAA) is vital in the prevention of stroke and is currently performed using transesophageal echocardiography (TEE).MethodsThe metabolism and pharmacokinetics of [⁶⁴Cu]FBP8 were studied in 8 healthy volunteers. Patients with atrial fibrillation and recent TEEs of the LAA (positive n = 12, negative n = 12) were injected with [⁶⁴Cu]FBP8 and imaged with PET/CMR, including mapping the longitudinal magnetic relaxation time (T₁) in the LAA.Results[⁶⁴Cu]FBP8 was stable to metabolism and was rapidly eliminated. The maximum standardized uptake value (SUV_Max) in the LAA was significantly higher in the TEE-positive than TEE-negative subjects (median of 4.0 [interquartile range (IQR): 3.0-6.0] vs 2.3 [IQR: 2.1-2.5]; P < 0.001), with an area under the receiver-operating characteristic curve of 0.97. An SUV_Max threshold of 2.6 provided a sensitivity of 100% and specificity of 84%. The minimum T₁ (T_1Min) in the LAA was 970 ms (IQR: 780-1,080 ms) vs 1,380 ms (IQR: 1,120-1,620 ms) (TEE positive vs TEE negative; P < 0.05), with some overlap between the groups. Logistic regression using SUV_Max and T_1Min allowed all TEE-positive and TEE-negative subjects to be classified with 100% accuracy.ConclusionsPET/CMR of [⁶⁴Cu]FBP8 is able to detect acute as well as older platelet-poor thrombi with excellent accuracy. Furthermore, the integrated PET/CMR approach provides useful information on the biological properties of thrombus such as fibrin and methemoglobin content. (Imaging of LAA Thrombosis; NCT03830320)     

Somatostatin Receptor PET/MR Imaging of Inflammation in Patients With Large Vessel Vasculitis and Atherosclerosis

BackgroundAssessing inflammatory disease activity in large vessel vasculitis (LVV) can be challenging by conventional measures.ObjectivesWe aimed to investigate somatostatin receptor 2 (SST₂) as a novel inflammation-specific molecular imaging target in LVV.MethodsIn a prospective, observational cohort study, in vivo arterial SST₂ expression was assessed by positron emission tomography/magnetic resonance imaging (PET/MRI) using ⁶⁸Ga-DOTATATE and ¹⁸F-FET-βAG-TOCA. Ex vivo mapping of the imaging target was performed using immunofluorescence microscopy; imaging mass cytometry; and bulk, single-cell, and single-nucleus RNA sequencing.ResultsSixty-one participants (LVV: n = 27; recent atherosclerotic myocardial infarction of ≤2 weeks: n = 25; control subjects with an oncologic indication for imaging: n = 9) were included. Index vessel SST₂ maximum tissue-to-blood ratio was 61.8% (P < 0.0001) higher in active/grumbling LVV than inactive LVV and 34.6% (P = 0.0002) higher than myocardial infarction, with good diagnostic accuracy (area under the curve: ≥0.86; P < 0.001 for both). Arterial SST₂ signal was not elevated in any of the control subjects. SST₂ PET/MRI was generally consistent with ¹⁸F-fluorodeoxyglucose PET/computed tomography imaging in LVV patients with contemporaneous clinical scans but with very low background signal in the brain and heart, allowing for unimpeded assessment of nearby coronary, myocardial, and intracranial artery involvement. Clinically effective treatment for LVV was associated with a 0.49 ± 0.24 (standard error of the mean [SEM]) (P = 0.04; 22.3%) reduction in the SST₂ maximum tissue-to-blood ratio after 9.3 ± 3.2 months. SST₂ expression was localized to macrophages, pericytes, and perivascular adipocytes in vasculitis specimens, with specific receptor binding confirmed by autoradiography. SSTR2-expressing macrophages coexpressed proinflammatory markers.ConclusionsSST₂ PET/MRI holds major promise for diagnosis and therapeutic monitoring in LVV. (PET Imaging of Giant Cell and Takayasu Arteritis [PITA], NCT04071691; Residual Inflammation and Plaque Progression Long-Term Evaluation [RIPPLE], NCT04073810)     

Bypass Grafting and Native Coronary Artery Disease Activity

ObjectivesThe aim of this study was to describe the potential of ¹⁸F-sodium fluoride (¹⁸F-NaF) positron emission tomography (PET) to identify graft vasculopathy and to investigate the influence of coronary artery bypass graft (CABG) surgery on native coronary artery disease activity and progression.BackgroundAs well as developing graft vasculopathy, CABGs have been proposed to accelerate native coronary atherosclerosis.MethodsPatients with established coronary artery disease underwent baseline ¹⁸F-NaF PET, coronary artery calcium scoring, coronary computed tomographic angiography, and 1-year repeat coronary artery calcium scoring. Whole-vessel coronary microcalcification activity (CMA) on ¹⁸F-NaF PET and change in calcium scores were quantified in patients with and without CABG surgery.ResultsAmong 293 participants (mean age 65 ± 9 years, 84% men), 48 (16%) underwent CABG surgery 2.7 years [IQR: 1.4-10.4 years] previously. Although all arterial and the majority (120 of 128 [94%]) of vein grafts showed no ¹⁸F-NaF uptake, 8 saphenous vein grafts in 7 subjects had detectable CMA. Bypassed native coronary arteries had 3 times higher CMA values (2.1 [IQR: 0.4-7.5] vs 0.6 [IQR: 0-2.7]; P < 0.001) and greater progression of 1-year calcium scores (118 Agatston unit [IQR: 48-194 Agatston unit] vs 69 [IQR: 21-142 Agatston unit]; P = 0.01) compared with patients who had not undergone CABG, an effect confined largely to native coronary plaques proximal to the graft anastomosis. In sensitivity analysis, bypassed native coronary arteries had higher CMA (2.0 [IQR: 0.4-7.5] vs 0.8 [IQR: 0.3-3.2]; P < 0.001) and faster disease progression (24% [IQR: 16%-43%] vs 8% [IQR: 0%-24%]; P = 0.002) than matched patients (n = 48) with comparable burdens of coronary artery disease and cardiovascular comorbidities in the absence of bypass grafting.ConclusionsNative coronary arteries that have been bypassed demonstrate increased disease activity and more rapid disease progression than nonbypassed arteries, an observation that appears independent of baseline atherosclerotic plaque burden. Microcalcification activity is not a dominant feature of graft vasculopathy.     

Comparison Between ESC and Duke Criteria for the Diagnosis of Prosthetic Valve Infective Endocarditis

ObjectivesThe primary objective was to assess the value of the European Society of Cardiology (ESC) criteria, including ¹⁸F-fluorodeoxyglucose positron emission tomography/computed tomography (¹⁸F-FDG-PET/CT) in prosthetic valve infective endocarditis (PVE). Secondary objectives were: 1) to assess the reproducibility of ¹⁸F-FDG-PET/CT; 2) to compare its diagnostic value with that of echocardiography; and 3) to assess the diagnostic value of the presence of a diffuse splenic uptakeBackground¹⁸F-FDG PET/CT has been added as a major criterion in the ESC 2015 infective endocarditis (IE) guidelines, but the benefit of the ESC criteria has not been prospectively compared with the conventional Duke criteria.MethodsBetween 2014 and 2017, 175 patients with suspected PVE were prospectively included in 3 French centers. After exclusion of patients with uninterpretable ¹⁸F-FDG PET/CT, 115 patients were evaluated, including 91 definite and 24 rejected IE, as defined by an expert consensus.ResultsCardiac uptake by ¹⁸F-FDG PET/CT was observed in 67 of 91 patients with definite PVE and 6 with rejected IE (sensitivity 73.6% [95% confidence interval (CI): 63.3% to 82.3%], specificity 75% [95% CI: 53.3% to 90.2%]). The ESC 2015 classification increased the sensitivity of Duke criteria from 57.1% (95% CI: 46.3% to 67.5%) to 83.5% (95% CI: 74.3% to 90.5%) (p < 0.001), but decreased its specificity from 95.8% (95% CI: 78.9% to 99.9%) to 70.8% (95% CI: 48.9% to 87.4%). Intraobserver reproducibility of ¹⁸F-FDG PET/CT was good (kappa = 0.84) but interobserver reproducibility was less satisfactory (kappa = 0.63). A diffuse splenic uptake was observed in 24 (20.3%) patients, including 23 (25.3%) of definite PVE, and only 1 (4.2%) rejected PVE (p = 0.024).Conclusions¹⁸F-FDG PET/CT is a useful diagnostic tool in suspected PVE, and explains the greater sensitivity of ESC criteria than Duke criteria. However, ¹⁸F-FDG PET/CT also presents with important limitations concerning its feasibility, specificity, and reproducibility. Our study describes for the first time a new endocarditis criterion, that is, the presence of a diffuse splenic uptake on ¹⁸F-FDG PET/CT.     

Diagnostic Accuracy of Cardiac Computed Tomography and 18-F Fluorodeoxyglucose Positron Emission Tomography in Cardiac Masses

ObjectivesThis study sought to assess the diagnostic accuracy of cardiac computed tomography (CT) and ¹⁸F-fluorodeoxyglucose (¹⁸F-FDG) with positron emission tomography/computed tomography (PET/CT) in defining the nature of cardiac masses.BackgroundThe diagnostic accuracy of cardiac CT and ¹⁸F-FDG PET/CT in identifying the nature of cardiac masses has been analyzed to date only in small samples.MethodsOf 223 patients with echocardiographically diagnosed cardiac masses, a cohort of 60 cases who underwent cardiac CT and ¹⁸F-FDG PET/CT was selected. All masses had histological confirmation, except for a minority of thrombotic formations. For each mass, 8 morphological CT signs, standardized uptake value (SUV_max, SUV_mean), metabolic tumor volume, and total lesion glycolysis in ¹⁸F-FDG PET were used as diagnostic markers.ResultsIrregular tumor margins, pericardial effusion, invasion, solid nature, mass diameter, CT contrast uptake, and pre-contrast characteristics were strongly associated with the malignant nature of masses. The coexistence of at least 5 CT signs perfectly identified malignant masses, whereas the detection of 3 or 4 CT signs did not accurately discriminate the masses’ nature. The mean SUV_max, SUV_mean, metabolic tumor volume, and total lesion glycolysis values were significantly higher in malignant than in benign masses. The diagnostic accuracy of SUV, metabolic tumor volume, and total lesion glycolysis ¹⁸F-FDG PET/CT parameters was excellent in detecting malignant masses. Among patients with 3 or 4 pathological CT signs, the presence of at least 1 abnormal ¹⁸F-FDG PET/CT parameter significantly increased the identification of malignancies.ConclusionsCardiac CT is a powerful tool to diagnose cardiac masses as the number of abnormal signs was found to correlate with the lesions’ nature. Similarly, ¹⁸F-FDG PET/CT accurately identified malignant masses and contributed with additional valuable information in diagnostic uncertainties after cardiac CT. These imaging tools should be performed in specific clinical settings such as involvement of great vessels or for disease-staging purposes.     

Center Valve Preference and Outcomes of Transcatheter Aortic Valve Replacement: Insights From the AMTRAC Registry

BackgroundData on outcomes of transcatheter aortic valve replacement (TAVR) using balloon-expandable valves (BEVs) or self-expandable valves (SEVs) as well as the impact of center valve preference on these outcomes are limited.ObjectivesThe aim of this study was to compare outcomes of TAVR procedures using third-generation BEVs and SEVs stratified by center valve preference.MethodsIn a multicenter registry (n = 17), 13 centers exhibited valve preference (66.6%-90% of volume) and were included. Outcomes were compared between BEVs and SEVs stratified by center valve preference.ResultsIn total, 7,528 TAVR procedures (3,854 with SEVs and 3,674 with BEVs) were included. The mean age was 81 years, and the mean Society of Thoracic Surgeons score was 5.2. Baseline characteristics were similar between BEVs and SEVs. Need for pacemaker implantation was higher with SEVs at BEV- and SEV-dominant centers (17.8% vs 9.3% [P < 0.001] and 12.7% vs 10.0% [P = 0.036], respectively; HR: 1.51; P for interaction = 0.021), risk for cerebrovascular accident was higher with SEVs at BEV-dominant but not SEV-dominant centers (3.6% vs 1.1% [P < 0.001] and 2.2% vs 1.4% [P = 0.162]; HR: 2.08; P for interaction < 0.01). Aortic regurgitation greater than mild was more frequent with SEVs at BEV-dominant centers and similar with BEVs regardless of center dominance (5.2% vs 2.8% [P < 0.001] and 3.4% vs 3.7% [P = 0.504], respectively). Two-year mortality was higher with SEVs at BEV-dominant centers but not at SEV-dominant centers (21.9% vs 16.9% [P = 0.021] and 16.8% vs 16.5% [P = 0.642], respectively; HR: 1.20; P for interaction = 0.032).ConclusionsPeriprocedural outcomes, aortic regurgitation greater than mild, and 2-year mortality are worse when TAVR is performed using SEVs at BEV-dominant centers. Outcomes are similar regardless of valve type at SEV-dominant centers. The present results stress the need to account for this factor when comparing BEV and SEV outcomes. (The Aortic+Mitral Transcatheter [AMTRAC] Valve Registry; NCT04031274)     

Pittsburgh B Compound Positron Emission Tomography in Patients With AL Cardiac Amyloidosis

BackgroundIt remains unknown whether the noninvasive evaluation of the degree of amyloid deposition in the myocardium can predict the prognosis of patients with light chain (AL) cardiac amyloidosis.ObjectivesThe purpose of this study was to demonstrate that ¹¹C-Pittsburgh B compound positron emission tomography (¹¹C-PiB PET) is useful for prognostication of AL cardiac amyloidosis by noninvasively imaging the myocardial AL amyloid deposition.MethodsThis study consecutively enrolled 41 chemotherapy-naïve AL cardiac amyloidosis patients. The amyloid deposit was quantitatively assessed with amyloid P immunohistochemistry in endomyocardial biopsy specimens and was compared with the degree of myocardial ¹¹C-PiB uptake on PET. The primary endpoint was a composite of all-cause death, heart transplantation, and acute decompensated heart failure.ResultsThe degree of myocardial ¹¹C-PiB PET uptake was significantly higher in the cardiac amyloidosis patients compared with normal subjects and correlated well with the degree of amyloid deposit on histology (R² = 0.343, p < 0.001). During follow-up (median: 423 days, interquartile range: 93 to 1,222 days), 24 patients experienced the primary endpoint. When the cardiac amyloidosis patients were divided into tertiles by the degree of myocardial ¹¹C-PiB PET uptake, patients with the highest PiB uptake experienced the worst clinical event-free survival (log-rank p = 0.014). The degree of myocardial PiB PET uptake was a significant predictor of clinical outcome on multivariate Cox regression analysis (adjusted hazard ratio: 1.185; 95% confidence interval: 1.054 to 1.332; p = 0.005).ConclusionsThese proof-of-concept results show that noninvasive evaluation of myocardial amyloid load by ¹¹C-PiB PET reflects the degree of amyloid deposit and is an independent predictor of clinical outcome in AL cardiac amyloidosis patients.     

Correlation between preoperative 18F-FDG PET/CT findings and postoperative short-term prognosis in lung cancer patients with idiopathic interstitial pneumonia after lung resection

BackgroundThe present study aimed to investigate the correlation between preoperative 2-deoxy-2-[¹⁸F]fluoro-d-glucose (¹⁸F-FDG) PET/CT findings and short-term survival in lung cancer patients with idiopathic interstitial pneumonia (IIP).MethodsWe retrospectively reviewed the data of 425 patients who underwent lung resection for non-small cell lung cancer without preoperative radiation therapy between November 2012 and October 2017. The maximum SUV (SUVmax) in the IIP area except the lung cancer site was measured in each patient.ResultsThirty-one of the 425 patients (7.3%) showed findings of IIP in chest CT. Five of the 31 patients (16.1%) developed acute exacerbation (AE) after lung resection (AE+ group). Twenty-six of the 31 patients (83.9%) did not develop AE (AE– group). In the AE+ group, ¹⁸F-FDG SUVmax in the IIP area was significantly higher (1.9 ± 0.6 vs. 2.7 ± 0.7, p = 0.02) compared with that in the AE? group. The receiver operating characteristic analysis identified an SUVmax threshold score of 2.55 (p = 0.02) for AE. There was no 90-day mortality in the patients with SUVmax < 2.55 (n = 25). On the other hand, the 90-day mortality rate in patients with SUVmax ≥ 2.55 (n = 6) was 33.3% (2 patients).Conclusions¹⁸F-FDG PET/CT may predict AE after lung resection and could be related to short-term survival in lung cancer patients with IIP. Further investigations are needed to improve the prognosis in patients with high SUVmax in the IIP area.     

Subclinical Leaflet Thrombosis in Transcatheter and Surgical Bioprosthetic Valves: PARTNER 3 Cardiac Computed Tomography Substudy

BackgroundSubclinical leaflet thrombosis, characterized by hypoattenuated leaflet thickening (HALT) and reduced leaflet motion observed on 4-dimensional computed tomography (CT), may represent a form of bioprosthetic valve dysfunction.ObjectivesThe U.S. Food and Drug Administration mandated CT studies to understand the natural history of this finding, differences between transcatheter and surgical valves, and its association with valve hemodynamics and clinical outcomes.MethodsThe PARTNER 3 (The Safety and Effectiveness of the SAPIEN 3 Transcatheter Heart Valve in Low-Risk Patients With Aortic Stenosis) CT substudy randomized 435 patients with low–surgical-risk aortic stenosis to undergo transcatheter aortic valve replacement (n = 221) or surgery (n = 214). Serial 4-dimensional CTs were performed at 30 days and 1 year and were analyzed independently by a core laboratory.ResultsThe incidence of HALT increased from 10% at 30 days to 24% at 1 year. Spontaneous resolution of 30-day HALT occurred in 54% of patients at 1 year, whereas new HALT appeared in 21% of patients at 1 year. HALT was more frequent in transcatheter versus surgical valves at 30 days (13% vs. 5%; p = 0.03), but not at 1 year (28% vs. 20%; p = 0.19). The presence of HALT did not significantly affect aortic valve mean gradients at 30 days or 1 year. Patients with HALT at both 30 days and 1 year, compared with those with no HALT at 30 days and 1 year, had significantly increased aortic valve gradients at 1 year (17.8 ± 2.2 mm Hg vs. 12.7. ± 0.3 mm Hg; p = 0.04).ConclusionsSubclinical leaflet thrombosis was more frequent in transcatheter compared with surgical valves at 30 days, but not at 1 year. The impact of HALT on thromboembolic complications and structural valve degeneration needs further assessment.     

Propensity-Matched 1-Year Outcomes Following Transcatheter Aortic Valve Replacement in Low-Risk Bicuspid and Tricuspid Patients

ObjectivesThe aim of this study was to compare 1-year outcomes after transcatheter aortic valve replacement (TAVR) in low surgical risk patients with bicuspid aortic stenosis to patients with tricuspid aortic stenosis.BackgroundThe pivotal TAVR trials excluded patients with bicuspid aortic valves. The Low Risk Bicuspid Study 30-day primary endpoint of death or disabling stroke was 1.3%.MethodsThe Low Risk Bicuspid Study is a prospective, single-arm, TAVR trial that enrolled patients from 25 U.S. sites. A screening committee confirmed bicuspid anatomy and valve classification on computed tomography using the Sievers classification. Valve sizing was by annular measurements. An independent clinical events committee adjudicated all serious adverse events, and an independent core laboratory assessed all echocardiograms. The 150 patients from the Low Risk Bicuspid Study were propensity matched to the TAVR patients in the randomized Evolut Low Risk Trial using the 1:1 5- to-1-digit greedy method, resulting in 145 pairs.ResultsAll-cause mortality or disabling stroke at 1 year was 1.4% in the bicuspid and 2.8% in the tricuspid group (P = 0.413). A pacemaker was implanted in 16.6% of bicuspid and 17.9% of tricuspid patients (P = 0.741). The effective orifice area was similar between groups at 1 year (2.2 ± 0.7 cm² vs 2.3 ± 0.6 cm², P = 0.677) as was the mean gradient (8.7 ± 3.9 mm Hg vs 8.5 ± 3.1 mm Hg, P = 0.754). Fewer patients in the bicuspid group had mild or worse paravalvular leak (21.3% vs 42.6%, P < 0.001).ConclusionsThere were no significant differences in clinical or forward flow hemodynamic outcomes between the propensity-matched groups at 1 year.     

18F-FDG-Based Radiomics and Machine Learning: Useful Help for Aortic Prosthetic Valve Infective Endocarditis Diagnosis?

BackgroundFluorine-18 fluorodeoxyglucose (¹⁸F-FDG)-positron emission tomography (PET)/computed tomography (CT) results in better sensitivity for prosthetic valve endocarditis (PVE) diagnosis, but visual image analysis results in relatively weak specificity and significant interobserver variability.ObjectivesThe primary objective of this study was to evaluate the performance of a radiomics and machine learning–based analysis of ¹⁸F-FDG PET/CT (PET-ML) as a major criterion for the European Society of Cardiology score using machine learning as a major imaging criterion (ESC-ML) in PVE diagnosis. The secondary objective was to assess performance of PET-ML as a standalone examination.MethodsAll ¹⁸F-FDG-PET/CT scans performed for suspected aortic PVE at a single center from 2015 to 2021 were retrospectively included. The gold standard was expert consensus after at least 3 months’ follow-up. The machine learning (ML) method consisted of manually segmenting each prosthetic valve, extracting 31 radiomics features from the segmented region, and training a ridge logistic regressor to predict PVE. Training and hyperparameter tuning were done with a cross-validation approach, followed by an evaluation on an independent test database.ResultsA total of 108 patients were included, regardless of myocardial uptake, and were divided into training (n = 68) and test (n = 40) cohorts. Considering the latter, PET-ML findings were positive for 13 of 22 definite PVE cases and 3 of 18 rejected PVE cases (59% sensitivity, 83% specificity), thus leading to an ESC-ML sensitivity of 72% and a specificity of 83%.ConclusionsThe use of ML for analyzing ¹⁸F-FDG-PET/CT images in PVE diagnosis was feasible and beneficial, particularly when ML was included in the ESC 2015 criteria. Despite some limitations and the need for future developments, this approach seems promising to optimize the role of ¹⁸F-FDG PET/CT in PVE diagnosis.     

Applicability of lung ultrasound in the assessment of COVID-19 pneumonia: Diagnostic accuracy and clinical correlations

BackgroundThe purpose of this study was to assess the diagnostic accuracy of lung ultrasound (LUS) in determining the severity of coronavirus disease 2019 (COVID-19) pneumonia compared with thoracic computed tomography (CT) and establish the correlations between LUS score, inflammatory markers, and percutaneous oxygen saturation (SpO₂).MethodsThis prospective observational study, conducted at Târgu-Mureș Pulmonology Clinic included 78 patients with confirmed severe acute respiratory syndrome coronavirus-2 infection via nasopharyngeal real-time-polymerase chain reaction (RT-PCR) (30 were excluded). Enrolled patients underwent CT, LUS, and blood tests on admission. Lung involvement was evaluated in 16 thoracic areas, using AB₁ B₂ C (letters represent LUS pattern) scores ranging 0–48.ResultsLUS revealed bilateral B-lines (97.8%), pleural irregularities with thickening/discontinuity (75%), and subpleural consolidations (70.8%). Uncommon sonographic patterns were alveolar consolidations with bronchogram (33%) and pleural effusion (2%). LUS score cutoff values of ≤14 and > 22 predicted mild COVID-19 (sensitivity [Se] = 84.6%; area under the curve [AUC] = 0.72; P = 0.002) and severe COVID-19 (Se = 50%, specificity (Sp) = 91.2%, AUC = 0.69; P = 0.02), respectively, and values > 29 predicted the patients’ transfer to the intensive care unit (Se = 80%, Sp = 97.7%). LUS score positively correlated with CT score (r = 0.41; P = 0.003) and increased with the decrease of SpO₂ (r = −0.49; P = 0.003), with lymphocytes decline (r = −0.52; P = 0.0001). Patients with consolidation patterns had higher ferritin and C-reactive protein than those with B-line patterns (P = 0.01; P = 0.03).ConclusionsLUS is a useful, non-invasive and effective tool for diagnosis, monitoring evolution, and prognostic stratification of COVID-19 patients.