Diagnostic Value of 18F-Fluorodeoxyglucose Positron Emission Tomography Computed Tomography in Prosthetic Pulmonary Valve Infective Endocarditis

ObjectivesThe aim of this study was to assess the diagnostic performances of ¹⁸F-fluorodeoxyglucose (¹⁸F-FDG) positron emission tomography (PET)/computed tomography (CT) in congenital heart disease (CHD) patients with pulmonary prosthetic valve or conduit endocarditis (PPVE) suspicion.BackgroundPPVE is a major issue in the growing CHD population. Diagnosis is challenging, and usual imaging tools are not always efficient or validated in this specific population. Particularly, the diagnostic yield of ¹⁸F-FDG PET/CT remains poorly studied in PPVE.MethodsA retrospective multicenter study was conducted in 8 French tertiary centers. Children and adult CHD patients who underwent ¹⁸F-FDG PET/CT in the setting of PPVE suspicion between January 2010 and May 2020 were included. The cases were initially classified as definite, possible, or rejected PPVE regarding the modified Duke criteria and finally by the Endocarditis Team consensus. The result of ¹⁸F-FDG PET/CT had been compared with final diagnosis consensus used as gold-standard in our study.ResultsA total of 66 cases of PPVE suspicion involving 59 patients (median age 23 years, 73% men) were included. Sensitivity, specificity, positive predictive value, and negative predictive value of ¹⁸F-FDG PET/CT in PPVE suspicion were respectively: 79.1% (95% CI: 68.4%-91.4%), 72.7% (95% CI: 60.4%-85.0%), 91.9% (95% CI: 79.6%-100.0%), and 47.1% (95% CI: 34.8%-59.4%). ¹⁸F-FDG PET/CT findings would help to correctly reclassify 57% (4 of 7) of possible PPVE to definite PPVE.ConclusionsUsing ¹⁸F-FDG PET/CT improves the diagnostic accuracy of the Duke criteria in CHD patients with suspected PPVE. Its high positive predictive value could be helpful in routine to shorten diagnosis and treatment delays and improve clinical outcomes.     

Hybrid Cardiac Magnetic Resonance/Fluorodeoxyglucose Positron Emission Tomography to Differentiate Active From Chronic Cardiac Sarcoidosis

ObjectivesThe purpose of this study was to investigate the diagnostic value of simultaneous hybrid cardiac magnetic resonance (CMR) and ¹⁸F-fluorodeoxyglucose positron emission tomography (FDG-PET) for detection and differentiation of active (aCS) from chronic (cCS) cardiac sarcoidosis.BackgroundLate gadolinium enhancement (LGE) CMR and FDG-PET are both established imaging techniques for the detection of CS. However, there are limited data regarding the value of a comprehensive simultaneous hybrid CMR/FDG-PET imaging approach that includes CMR mapping techniques.MethodsForty-three patients with biopsy-proven extracardiac sarcoidosis (median age: 48 years, interquartile range: 37-57 years, 65% male) were prospectively enrolled for evaluation of suspected CS. After dietary preparation for suppression of myocardial glucose metabolism, patients were evaluated on a 3-T hybrid PET/MR scanner. The CMR protocol included T1 and T2 mapping, myocardial function, and LGE imaging. We assumed aCS if PET and CMR (ie, LGE or T1/T2 mapping) were both positive (PET+/CMR+), cCS if PET was negative but CMR was positive (PET?/CMR+), and no CS if patients were CMR negative regardless of PET findings.ResultsAmong the 43 patients, myocardial glucose uptake was suppressed successfully in 36 (84%). Hybrid CMR/FDG-PET revealed aCS in 13 patients (36%), cCS in 5 (14%), and no CS in 18 (50%). LGE was present in 14 patients (39%); T1 mapping was abnormal in 10 (27%) and T2 mapping abnormal in 2 (6%). CS was diagnosed based on abnormal T1 mapping in 4 out of 18 CS patients (22%) who were LGE negative. PET FDG uptake was present in 17 (47%) patients.ConclusionsComprehensive simultaneous hybrid CMR/FDG-PET imaging is useful for the detection of CS and provides additional value for identifying active disease. Our results may have implications for enhanced diagnosis as well as improved identification of patients with aCS in whom anti-inflammatory therapy may be most beneficial.     

18F-Sodium Fluoride Positron Emission Tomography and Computed Tomography in Acute Aortic Syndrome

BackgroundAcute aortic syndrome is associated with aortic medial degeneration. ¹⁸F-sodium fluoride (¹⁸F-NaF) positron emission tomography (PET) detects microscopic tissue calcification as a marker of disease activity.ObjectivesIn a proof-of-concept study, this investigation aimed to establish whether ¹⁸F-NaF PET combined with computed tomography (CT) angiography could identify aortic medial disease activity in patients with acute aortic syndrome.MethodsPatients with aortic dissection or intramural hematomas and control subjects underwent ¹⁸F-NaF PET/CT angiography of the aorta. Aortic ¹⁸F-NaF uptake was measured at the most diseased segment, and the maximum value was corrected for background blood pool activity (maximum tissue-to-background ratio [TBR_max]). Radiotracer uptake was compared with change in aortic size and major adverse aortic events (aortic rupture, aorta-related death, or aortic repair) over 45 ± 13 months.ResultsAortic ¹⁸F-NaF uptake co-localized with histologically defined regions of microcalcification and elastin disruption. Compared with control subjects, patients with acute aortic syndrome had increased ¹⁸F-NaF uptake (TBR_max: 1.36 ± 0.39 [n = 20] vs 2.02 ± 0.42 [n = 47] respectively; P < 0.001) with enhanced uptake at the site of intimal disruption (+27.5%; P < 0.001). ¹⁸F-NaF uptake in the false lumen was associated with aortic growth (+7.1 mm/year; P = 0.011), and uptake in the outer aortic wall was associated with major adverse aortic events (HR: 8.5 [95% CI: 1.4-50.4]; P = 0.019).ConclusionsIn patients with acute aortic syndrome, ¹⁸F-NaF uptake was enhanced at sites of disease activity and was associated with aortic growth and clinical events. ¹⁸F-NaF PET/CT holds promise as a noninvasive marker of disease severity and future risk in patients with acute aortic syndrome. (¹⁸F Sodium Fluoride PET/CT in Acute Aortic Syndrome [FAASt]; NCT03647566)     

Diagnostic Accuracy of [11C]PIB Positron Emission Tomography for Detection of Cardiac Amyloidosis

ObjectivesThis dual-site study evaluated the diagnostic accuracy of the method.BackgroundPittsburgh compound ([¹¹C]PIB) positron emission tomography (PIB-PET) has shown promise as a specific and noninvasive method for the diagnosis of cardiac amyloidosis (CA).MethodsThe study had 2 parts. In the initial study, 51 subjects were included, 36 patients with known CA and increased wall thickness (15 immunoglobulin light chain [AL] and 21 transthyretin [ATTR] amyloidosis) and 15 control patients (7 were nonamyloid hypertrophic and 8 healthy volunteers). Subjects underwent PIB-PET and echocardiography. Sensitivity and specificity of PIB-PET were established for 2 simple semiquantitative approaches, standardized uptake value ratio (SUVR) and retention index (RI). The second part of the study included 11 amyloidosis patients (5 AL and 6 hereditary ATTR) without increased wall thickness to which the optimal cutoff values of SUVR (>1.09) and RI (>0.037 min^-1) were applied prospectively.ResultsThe diagnostic accuracy of visual inspection of [¹¹C]PIB uptake was 100% in discriminating CA patients with increased wall thickness from controls. Semiquantitative [¹¹C]PIB uptake discriminated CA from controls with a 94% (95% confidence interval [CI]: 80% to 99%) sensitivity for both SUVR and RI and specificity of 93% (95% CI: 66% to 100%) for SUVR and 100% (95% CI: 75% to 100%) for RI. [¹¹C]PIB uptake was significantly higher in AL-CA than in ATTR-CA patients (p < 0.001) and discriminated AL-CA from controls with 100% (95% CI: 88% to 100%) accuracy for both the semiquantitative measures. In the prospective group without increased wall thickness, RI was elevated compared to controls (p = 0.001) and 5 of 11 subjects were evaluated as [¹¹C]PIB PET positive.ConclusionsIn a dual-center setting, [¹¹C]PIB PET was highly accurate in detecting cardiac involvement in the main amyloid subtypes, with 100% accuracy in AL amyloidosis. A proportion of amyloidosis patients without known cardiac involvement were [¹¹C]PIB PET positive, indicating that the method may detect early stages of CA.     

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)     

Worldwide Diagnostic Reference Levels for Single-Photon Emission Computed Tomography Myocardial Perfusion Imaging: Findings From INCAPS

ObjectivesThis study sought to establish worldwide and regional diagnostic reference levels (DRLs) and achievable administered activities (AAAs) for single-photon emission computed tomography (SPECT) myocardial perfusion imaging (MPI).BackgroundReference levels serve as radiation dose benchmarks to compare individual laboratories against aggregated data, helping to identify sites in greatest need of dose reduction interventions. DRLs for SPECT MPI have previously been derived from national or regional registries. To date there have been no multiregional reports of DRLs for SPECT MPI from a single standardized dataset.MethodsData were submitted voluntarily to the INCAPS (International Atomic Energy Agency Nuclear Cardiology Protocols Study), a cross-sectional, multinational registry of MPI protocols. A total of 7,103 studies were included. DRLs and AAAs were calculated by protocol for each world region and for aggregated worldwide data.ResultsThe aggregated worldwide DRLs for rest-stress or stress-rest studies employing technetium Tc 99m–labeled radiopharmaceuticals were 11.2 mCi (first dose) and 32.0 mCi (second dose) for 1-day protocols, and 23.0 mCi (first dose) and 24.0 mCi (second dose) for multiday protocols. Corresponding AAAs were 10.1 mCi (first dose) and 28.0 mCi (second dose) for 1-day protocols, and 17.8 mCi (first dose) and 18.7 mCi (second dose) for multiday protocols. For stress-only technetium Tc 99m studies, the worldwide DRL and AAA were 18.0 mCi and 12.5 mCi, respectively. Stress-first imaging was used in 26% to 92% of regional studies except in North America where it was used in just 7% of cases. Significant differences in DRLs and AAAs were observed between regions.ConclusionsThis study reports reference levels for SPECT MPI for each major world region from one of the largest international registries of clinical MPI studies. Regional DRLs may be useful in establishing or revising guidelines or simply comparing individual laboratory protocols to regional trends. Organizations should continue to focus on establishing standardized reporting methods to improve the validity and comparability of regional DRLs.     

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)     

Dynamic Stress Computed Tomography Perfusion With a Whole-Heart Coverage Scanner in Addition to Coronary Computed Tomography Angiography and Fractional Flow Reserve Computed Tomography Derived

ObjectivesThe aims of the study were to test the diagnostic accuracy of integrated evaluation of dynamic myocardial computed tomography perfusion (CTP) on top of coronary computed tomography angiography (cCTA) plus fractional flow reserve computed tomography derived (FFR_CT) by using a whole-heart coverage computed tomography (CT) scanner as compared with clinically indicated invasive coronary angiography (ICA) and invasive fractional flow reserve (FFR).BackgroundRecently, new techniques such as dynamic stress computed tomography perfusion (stress-CTP) emerged as potential strategies to combine anatomical and functional evaluation in a one-shot scan. However, previous experiences with this technique were associated with high radiation exposure.MethodsEighty-five consecutive symptomatic patients scheduled for ICA were prospectively enrolled. All patients underwent rest cCTA followed by stress dynamic CTP with a whole-heart coverage CT scanner (Revolution CT, GE Healthcare, Milwaukee, Wisconsin). FFR_CT was also measured by using the rest cCTA dataset. The diagnostic accuracy to detect functionally significant coronary artery disease (CAD) in a vessel-based model of cCTA alone, cCTA+FFR_CT, cCTA+CTP, or cCTA+FFR_CT+CTP were assessed and compared by using ICA and invasive FFR as reference. The overall effective dose of dynamic CTP was also measured.ResultsThe prevalence of obstructive CAD and functionally significant CAD was 77% and 57%, respectively. The sensitivity and specificity of cCTA alone, cCTA+FFR_CT, and cCTA+CTP were 83% and 66%, 86% and 75%, and 73% and 86%, respectively. Both the addition of FFR_CT and CTP improves the area under the curve (AUC: 0.876 and 0.878, respectively) as compared with cCTA alone (0.826; p < 0.05). The sequential strategy of cCTA+FFR_CT+CTP showed the highest AUC (0.919; p < 0.05) as compared with all other strategies. The mean effective radiation dose (ED) for cCTA and stress CTP was 2.8 ± 1.2 mSv and 5.3 ± 0.7 mSv, respectively.ConclusionsThe addition of dynamic stress CTP on top of cCTA and FFR_CT provides additional diagnostic accuracy with acceptable radiation exposure.     

Accuracy of Cardiac Magnetic Resonance Imaging in Diagnosing Pediatric Cardiac Masses: A Multicenter Study

BackgroundAfter diagnosis of a cardiac mass, clinicians must weigh the benefits and risks of ascertaining a tissue diagnosis. Limited data are available on the accuracy of previously developed noninvasive pediatric cardiac magnetic resonance (CMR)-based diagnostic criteria.ObjectivesThe goals of this study were to: 1) evaluate the CMR characteristics of pediatric cardiac masses from a large international cohort; 2) test the accuracy of previously developed CMR-based diagnostic criteria; and 3) expand diagnostic criteria using new information.MethodsCMR studies (children 0-18 years of age) with confirmatory histological and/or genetic diagnosis were analyzed by 2 reviewers, without knowledge of prior diagnosis. Diagnostic accuracy was graded as: 1) single correct diagnosis; 2) correct diagnosis among a differential; or 3) incorrect diagnosis.ResultsOf 213 cases, 174 (82%) had diagnoses that were represented in the previously published diagnostic criteria. In 70% of 174 cases, both reviewers achieved a single correct diagnosis (94% of fibromas, 71% of rhabdomyomas, and 50% of myxomas). When ≤2 differential diagnoses were included, both reviewers reached a correct diagnosis in 86% of cases. Of 29 malignant tumors, both reviewers indicated malignancy as a single diagnosis in 52% of cases. Including ≤2 differential diagnoses, both reviewers indicated malignancy in 83% of cases. Of 6 CMR sequences examined, acquisition of first-pass perfusion and late gadolinium enhancement were independently associated with a higher likelihood of a single correct diagnosis.ConclusionsCMR of cardiac masses in children leads to an accurate diagnosis in most cases. A comprehensive imaging protocol is associated with higher diagnostic accuracy.     

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.     

Prognostic Value of Stress Dynamic Computed Tomography Perfusion With Computed Tomography Delayed Enhancement

ObjectivesThis study sought to evaluate the prognostic value of stress dynamic computed tomography (CT) perfusion (CTP) with CT delayed enhancement (CTDE) in patients with suspected or known coronary artery disease (CAD) and in subgroups of patients with stent, heavy calcification, or stenosis.BackgroundThe prognostic value of stress dynamic CTP with CTDE is unknown.MethodsParticipants were 540 patients with suspected or known CAD. Major adverse cardiac event(s) (MACE) consisted of cardiac death, nonfatal myocardial infarction, unstable angina, or hospitalization for congestive heart failure. Ischemic score was calculated by scoring the reduction of normalized myocardial blood flow in 16 segments excluding areas of myocardial scarring. Ischemic perfusion defect (IPD) was defined as Ischemic score ≥4. Scar score was also calculated by scoring the transmural extent of scarring in each segment on CTDE.ResultsDuring a median follow-up of 2.9 years, 43 MACEs occurred. By adding IPD to obstructive CAD (≥50% stenosis) on coronary CT angiography, the concordance index for predicting MACEs increased from 0.73 to 0.82 in patients with suspected CAD (p = 0.028) and from 0.61 to 0.73 in patients with known CAD (p = 0.004). IPD and scar score of ≥4 were independent predictors when adjusted for each other in patients with suspected (adjusted hazard ratios: 7.5 [p < 0.001] and 3.0 [p = 0.034], respectively) or known CAD (adjusted hazard ratios: 4.4 [p = 0.001] and 3.2 [p = 0.024], respectively). Patients with IPD had a higher annualized event rate than those without IPD in subgroups of those with stent (11.5% vs. 2.6%; p < 0.001), heavy calcification (13.3% vs. 3.1%; p < 0.001), 50% to 69% stenosis (8.8% vs. 1.0%; p < 0.001), or ≥70% stenosis (12.4% vs. 3.6%; p < 0.001).ConclusionsStress dynamic CTP with CTDE had incremental prognostic value over CT angiography in each group with suspected or known CAD and was prognostically useful in subgroups of patients with stent, heavy calcification, or obstructive CAD. IPD and myocardial scarring may play complementary roles in prognostic stratification.     

Prognostic Value of Quantitative Metrics From Positron Emission Tomography in Ischemic Heart Failure

ObjectivesThe aim of this study was to investigate the prognostic and clinical value of quantitative positron emission tomographic (PET) metrics in patients with ischemic heart failure.BackgroundAlthough myocardial flow reserve (MFR) is a strong predictor of cardiac risk in patients without heart failure, it is unknown whether quantitative PET metrics improve risk stratification in patients with ischemic heart failure.MethodsThe study included 254 patients referred for stress and rest myocardial perfusion imaging and viability testing using PET. Major adverse cardiac event(s) (MACE) consisted of death, resuscitated sudden cardiac death, heart transplantation, acute coronary syndrome, hospitalization for heart failure, and late revascularization.ResultsMACE occurred in 170 patients (67%) during a median follow-up of 3.3 years. In a multivariate Cox proportional hazards model including multiple quantitative PET metrics, only MFR predicted MACE significantly (p = 0.013). Beyond age, symptom severity, diabetes mellitus, previous myocardial infarction or revascularization, 3-vessel disease, renal insufficiency, ejection fraction, as well as presence and burden of ischemia, scar, and hibernating myocardium, MFR was strongly associated with MACE (adjusted hazard ratio per increase in MFR by 1: 0.63; 95% confidence interval: 0.45 to 0.91). Incorporation of MFR into a risk assessment model incrementally improved the prediction of MACE (likelihood ratio chi-square test [16] = 48.61 vs. chi-square test [15] = 39.20; p = 0.002).ConclusionsIn this retrospective analysis of a single-center cohort, quantitative PET metrics of myocardial blood flow all improved risk stratification in patients with ischemic heart failure. However, in a hypothesis-generating analysis, MFR appears modestly superior to the other metrics as a prognostic index.     

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.     

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.     

Peridevice Leak Following Amplatzer Left Atrial Appendage Occlusion: Cardiac Computed Tomography Classification and Clinical Outcomes

ObjectivesThis study aimed to investigate cardiac computed tomography (CT) and transesophageal echocardiography (TEE) peridevice leak (PDL) assessments, and the clinical relevance of PDL.BackgroundPDL assessment is integral during follow-up after left atrial appendage (LAA) occlusion. Comparative studies of TEE and cardiac CT are sparse, and the clinical relevance of PDL is uncertain.MethodsThis was a single-center observational study of consecutive patients undergoing LAA occlusion with Amplatzer devices (Amplatzer Cardiac Plug/Amulet) between 2010 and 2018 (N = 415). Patients with both 8-week CT and TEE were included for analysis (n = 346). Images were analyzed by blinded investigators (K.K. and A.S.). PDL on cardiac CT was classified from grade 1 to 3, based on PDL at the device disc, device lobe, and LAA contrast patency. Primary clinical outcome was a composite of ischemic stroke, transient ischemic attack, systemic embolism, or all-cause death.ResultsPDL was present in 110 patients (32%) by TEE, with 29 (8%) >3 mm. By cardiac CT, 210 patients (61%) had PDL at the disc, with contrast patency in 204 patients (59%). A grade 3 PDL (gap at disc, lobe, and LAA contrast patency) was present in 63 patients (18%). Bland-Altman analysis showed poor agreement between CT and TEE for leak sizing. CT and TEE detected PDL was not significantly associated with worse outcome, hazard ratio: 1.82 (95 % confidence interval: 0.95 to 3.50); p = 0.07 and hazard ratio: 1.43 (95% confidence interval: 0.74 to 2.76); p = 0.28, respectively.ConclusionsPDL occurrence is substantially higher with CT compared with TEE, with a large discrepancy between modalities in leak quantification. A novel CT-based classification is proposed, yet PDL was not associated with worse clinical outcome.     

Extracellular Volume Fraction by Computed Tomography Predicts Long-Term Prognosis Among Patients With Cardiac Amyloidosis

BackgroundLight chain (AL) and transthyretin (ATTR) amyloid fibrils are deposited in the extracellular space of the myocardium, resulting in heart failure and premature mortality. Extracellular expansion can be quantified by computed tomography, offering a rapid, cheaper, and more practical alternative to cardiac magnetic resonance, especially among patients with cardiac devices or on renal dialysis.ObjectivesThis study sought to investigate the association of extracellular volume fraction by computed tomography (ECV_CT), myocardial remodeling, and mortality in patients with systemic amyloidosis.MethodsPatients with confirmed systemic amyloidosis and varying degrees of cardiac involvement underwent electrocardiography-gated cardiac computed tomography. Whole heart and septal ECV_CT was analyzed. All patients also underwent clinical assessment, electrocardiography, echocardiography, serum amyloid protein component, and/or technetium-99m (^99mTc) 3,3-diphosphono-1,2-propanodicarboxylic acid scintigraphy. ECV_CT was compared across different extents of cardiac infiltration (ATTR Perugini grade/AL Mayo stage) and evaluated for its association with myocardial remodeling and all-cause mortality.ResultsA total of 72 patients were studied (AL: n = 35, ATTR: n = 37; median age: 67 [IQR: 59-76] years, 70.8% male). Mean septal ECV_CT was 42.7% ± 13.1% and 55.8% ± 10.9% in AL and ATTR amyloidosis, respectively, and correlated with indexed left ventricular mass (r = 0.426; P < 0.001), left ventricular ejection fraction (r = 0.460; P < 0.001), N-terminal pro–B-type natriuretic peptide (r = 0.563; P < 0.001), and high-sensitivity troponin T (r = 0.546; P < 0.001). ECV_CT increased with cardiac amyloid involvement in both AL and ATTR amyloid. Over a mean follow-up of 5.3 ± 2.4 years, 40 deaths occurred (AL: n = 14 [35.0%]; ATTR: n = 26 [65.0%]). Septal ECV_CT was independently associated with all-cause mortality in ATTR (not AL) amyloid after adjustment for age and septal wall thickness (HR: 1.046; 95% CI: 1.003-1.090; P = 0.037).ConclusionsCardiac amyloid burden quantified by ECV_CT is associated with adverse cardiac remodeling as well as all-cause mortality among ATTR amyloid patients. ECV_CT may address the need for better identification and risk stratification of amyloid patients, using a widely accessible imaging modality.     

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.     

Implementing Coronary Computed Tomography Angiography in the Catheterization Laboratory

Coronary computed tomography angiography (CCTA) is now an established tool in the diagnostic work-up of patients suspected to have coronary artery disease. Yet, its usefulness beyond this phase has not been fully explored. The current review focuses on the implementation of CCTA as a tool to plan and guide coronary interventions in the catheterization laboratory. Specifically, we explore the potential of CCTA to improve patient selection for percutaneous revascularization, provide the rationale for better resource use, and present a novel approach to incorporate 3-dimensional CT guidance for percutaneous coronary interventions.     

Sex-Specific Computed Tomography Coronary Plaque Characterization and Risk of Myocardial Infarction

ObjectivesThis study was designed to investigate whether coronary computed tomography angiography assessments of coronary plaque might explain differences in the prognosis of men and women presenting with chest pain.BackgroundImportant sex differences exist in coronary artery disease. Women presenting with chest pain have different risk factors, symptoms, prevalence of coronary artery disease and prognosis compared to men.MethodsWithin a multicenter randomized controlled trial, we explored sex differences in stenosis, adverse plaque characteristics (positive remodeling, low-attenuation plaque, spotty calcification, or napkin ring sign) and quantitative assessment of total, calcified, noncalcified and low-attenuation plaque burden.ResultsOf the 1,769 participants who underwent coronary computed tomography angiography, 772 (43%) were female. Women were more likely to have normal coronary arteries and less likely to have adverse plaque characteristics (p < 0.001 for all). They had lower total, calcified, noncalcified, and low-attenuation plaque burdens (p < 0.001 for all) and were less likely to have a low-attenuation plaque burden >4% (41% vs. 59%; p < 0.001). Over a median follow-up of 4.7 years, myocardial infarction (MI) occurred in 11 women (1.4%) and 30 men (3%). In those who had MI, women had similar total, noncalcified, and low-attenuation plaque burdens as men, but men had higher calcified plaque burden. Low-attenuation plaque burden predicted MI (hazard ratio: 1.60; 95% confidence interval: 1.10 to 2.34; p = 0.015), independent of calcium score, obstructive disease, cardiovascular risk score, and sex.ConclusionsWomen presenting with stable chest pain have less atherosclerotic plaque of all subtypes compared to men and a lower risk of subsequent MI. However, quantitative low-attenuation plaque is as strong a predictor of subsequent MI in women as in men. (Scottish Computed Tomography of the HEART Trial [SCOT-HEART]; NCT01149590)