Pulmonary Artery 18F-Fluorodeoxyglucose Uptake by PET/CMR as a Marker of Pulmonary Hypertension in Sarcoidosis

ObjectivesThis study investigated whether pulmonary artery (PA) ¹⁸F-FDG uptake is associated with hypertension, and if it correlates to elevated pulmonary pressures.Background¹⁸F-fluorodeoxyglucose (FDG) positron emission tomography (PET) combined with computed tomography or cardiac magnetic resonance (CMR) has been used to assess inflammation mostly in large arteries of the systemic circulation. Much less is known about inflammation of the vasculature of the pulmonary system and its relationship to pulmonary hypertension (PH).MethodsIn a single-center cohort of 175 patients with suspected cardiac sarcoidosis, who underwent hybrid thoracic PET/CMR, ¹⁸F-FDG uptake in the PA was quantified according to maximum standardized uptake value (SUVmax) and target-to-background ratio (TBR) and compared with available results from right heart catheterization (RHC) or transthoracic echocardiography (TTE).ResultsThirty-three subjects demonstrated clear ¹⁸F-FDG uptake in the PA wall. In the subgroup of patients who underwent RHC (n = 10), the mean PA pressure was significantly higher in the group with PA ¹⁸F-FDG uptake compared with the group without uptake (34.4 ± 7.2 mm Hg vs 25.6 ± 9.3 mm Hg; P = 0.003), and 9 (90%) patients with PA ¹⁸F-FDG uptake had PH when a mean PA pressure cutoff of 25 mm Hg was used compared with 18 (45%) in the nonuptake group (P < 0.05). In the subgroup that underwent TTE, signs of PH were present in a significantly higher number of patients with PA ¹⁸F-FDG uptake (14 [51.9%] vs 37 [29.8%]; P < 0.05). Qualitative assessment of ¹⁸F-FDG uptake in the PA wall showed a sensitivity of 33% and specificity of 96% for separating patients with PH based on RHC-derived PA pressures. SUVmax and TBR in the PA wall correlated with PA pressure derived from RHC and/or TTE.ConclusionsWe demonstrate that ¹⁸F-FDG uptake by PET/CMR in the PA is associated with PH and that its intensity correlates with PA pressure.     

Chemotherapy versus best supportive care in advanced lung cancer and idiopathic interstitial pneumonias: A retrospective multi-centre cohort study

BackgroundThe clinical questions of whether chemotherapy as initial treatment, compared with best supportive care (BSC), improves overall survival (OS) and whether it increases the occurrence risk of acute exacerbation of idiopathic interstitial pneumonia (IIP) in patients with advanced-stage lung cancer and IIP remain inconclusive. This study addresses these issues, given that chemotherapy-related acute exacerbation of IIP may be a direct cause of mortality in these patients.MethodsWe enrolled 1003 patients from 110 Japanese institutions and collected clinical profiles from 707 and 296 patients in the chemotherapy (men: women, 645:62; mean age, 70.4 ± 6.9 years) and BSC (men: women, 261:35; mean age, 75.2 ± 7.8) groups, respectively. We used propensity score matching to create 222 matched pairs from both groups using patient demographic data (age, sex, smoking status, performance status, history of acute exacerbation of IIP, desaturation on exertion, clinical diagnosis of IIP, high-resolution computed tomography findings, serum fibrotic markers, pulmonary function status, and lung cancer histopathology). Logistic or Cox regression analyses were performed using matched data to assess the effects of chemotherapy on the risk of acute exacerbation of IIP or OS, respectively.ResultsIn the well-matched cohort, chemotherapy improved OS (hazard ratio: 0.629, 95% confidence interval [CI]: 0.506–0.783, p < 0.0001); however, it involved significant acute exacerbation of IIP (odds ratio: 1.787, 95% CI: 1.026–3.113) compared to BSC.ConclusionsCompared with BSC, chemotherapy can improve OS in patients with advanced-stage lung cancer and IIP; however, it increases the risk of acute exacerbation of IIP.     

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.     

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.     

Predictors of acute exacerbation in biopsy-proven idiopathic pulmonary fibrosis

BackgroundAcute exacerbation (AE) is a major cause of death in patients with idiopathic pulmonary fibrosis (IPF). Current evidence on AE-IPF has been largely based on clinical, rather than pathological, analyses.MethodsWe investigated AE incidence and its predictors using clinical, radiological, and pathological data of patients diagnosed with IPF by multi-disciplinary discussion.This study, a secondary analysis of previous research, included 155 patients with IPF who underwent surgical lung biopsy (SLB). Cumulative AE incidence was evaluated by the Kaplan–Meier method. Predictors of AE-IPF were analyzed with a Fine-Gray sub-distribution hazard model. Sub-analysis was performed using propensity score-matching analysis.ResultsIn this cohort, the median age of the patients was 66 years and the median percent-predicted forced vital capacity was 82.8%. The cumulative AE incidence rates at 30 days and one year post SLB were 1.9% and 7.6%, respectively. On multivariable analysis, a lower percent-predicted diffusing capacity of the lung for carbon monoxide (%DL_CO) (hazard ratio 0.98 per 1% increase, P = 0.02) and fibroblastic foci (FF)-present (vs. absent; hazard ratio 3.01, P = 0.04) were independently associated with a higher incidence of AE. The propensity score-matching analysis with adjustment for age, gender, and %DL_CO revealed that the cumulative AE incidence rate was significantly higher in the FF-present subgroup than in the FF-absent subgroup (1-year incidence rate, 10.5% vs. 0%, respectively; P = 0.04 by Gray's test).ConclusionsFF and %DL_CO were independent predictors of AE in patients with biopsy-proven IPF. FF may be associated with the pathogenesis of AE-IPF.     

Vessel invasion as a predictive factor for recurrence after surgery in stage I lung adenocarcinoma

BackgroundPatients with early-stage lung cancer who underwent R0 resection often encounter disease recurrence, especially during the early phase; thus, it is deemed vital to determine the predictive factors for recurrence after surgery. In this study, we aimed to identify the independent variables associated with recurrence after complete surgical resection of pathological stage I lung adenocarcinoma.MethodsWe retrospectively reviewed the medical records of 169 patients who underwent pulmonary resection for primary lung adenocarcinoma pathological stage I with curative intent lung cancer surgery from 2015 to December 2018 at our institution for information on the recurrence of the disease.ResultsPer the multivariate analysis, the presence of micropapillary pattern and vessel invasion were found to be independent predictors of disease recurrence after surgery (odds ratio [OR]: 9.36, 95% confidence interval [CI]: 2.42–36.2, P = 0.0012; and OR: 4.50, 95% CI: 1.52–13.4, P = 0.0068, respectively). Vessel invasion was also found to be an independent predictor of disease recurrence after surgery within a year (OR 11.4, 95% CI 3.08–42.5, P = 0.0003).ConclusionsThe presence of vessel invasion may help in distinguishing patients with the highest risk of early-phase disease recurrence after surgery. Patients with stage I adenocarcinoma with vessel invasion should undergo intensive surveillance after surgery.     

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.     

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.     

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.     

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)     

Platythorax progresses with lung involvement in pleuroparenchymal fibroelastosis

BackgroundPatients diagnosed with pleuroparenchymal fibroelastosis (PPFE) exhibit unique clinical features, including upper lobe-dominant lung involvement and platythorax (or flattened thoracic cage). Although platythorax have been shown to be a sign of disease progression, the temporal relationship between the progression of platythorax and the extent of lung involvement has not been closely investigated.MethodsWe retrospectively investigated patients diagnosed with PPFE, who did not exhibit fibrotic lesions other than PPFE in the lower lobes. We estimated the fibrosis score, which is a visual score indicating the percentage of lung parenchyma occupied by the disease on computed tomography images selected every 2 cm from the lung apex to the lung base, and the flat chest index (the ratio of the anteroposterior diameter of the thoracic cage to the transverse diameter of the thoracic cage). Additionally, we investigated serial changes in the flat chest index and fibrosis score.ResultsA total of 29 patients were included in this study. The fibrosis score was found to be weakly and inversely correlated with forced vital capacity %predicted at the diagnosis (r = ?0.40, p = 0.038). Furthermore, the annual changes in the flat chest index and fibrosis score was found to be moderately and inversely correlated (r = ?0.663, p = 0.0037).ConclusionsThese results indicate that there is a causal relationship between the progression of fibroelastosis and that of platythorax in patients with PPFE.     

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.     

Mechanical ventilation for acute exacerbation of fibrosing interstitial lung diseases

BackgroundAcute exacerbation of fibrosing interstitial lung diseases, including idiopathic pulmonary fibrosis, is associated with poor prognosis. Accordingly, tracheal intubation and invasive mechanical ventilation are generally avoided in such patients. However, the efficacy of invasive mechanical ventilation for acute exacerbation of fibrosing interstitial lung diseases remains unclear. Therefore, we aimed to investigate the clinical course of patients with acute exacerbation of fibrosing interstitial lung diseases who were treated with invasive mechanical ventilation.MethodsWe retrospectively analyzed 28 patients with acute exacerbation of fibrosing interstitial lung diseases who underwent invasive mechanical ventilation at our hospital.ResultsOf the 28 included patients (20 men, 8 women; mean age, 70.6 years), 13 (46.4%) were discharged alive and 15 died. Ten patients (35.7%) had idiopathic pulmonary fibrosis. Univariate analysis revealed that longer survival was significantly associated with lower partial pressure of arterial carbon dioxide (hazard ratio [HR] 1.04 [1.01–1.07]; p = 0.002) and higher pH (HR 0.0002 [0–0.02] levels; p = 0.0003) and less severe general status according to the Acute Physiology and Chronic Health Evaluation II score (HR 1.13 [1.03–1.22]; p = 0.006) at the time of mechanical ventilation initiation. In addition, the univariate analysis indicated that patients without long-term oxygen therapy use had significantly longer survival (HR 4.35 [1.51–12.52]; p = 0.006).ConclusionsInvasive mechanical ventilation may effectively treat acute exacerbation of fibrosing interstitial lung diseases if good ventilation and general conditions can be maintained.     

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.     

Extent of pulmonary fibrosis on high-resolution computed tomography is a prognostic factor in patients with pleuroparenchymal fibroelastosis

BackgroundSeveral prognostic factors for pleuroparenchymal fibroelastosis (PPFE) have recently been reported. However, detailed high-resolution computed tomography (HRCT) findings have not yet been evaluated as prognostic factors. This study retrospectively investigated whether HRCT findings are prognostic factors in patients with PPFE compared to those with idiopathic pulmonary fibrosis (IPF).MethodsPatients with PPFE and IPF diagnosed at our hospital between January 2008 and December 2016 were enrolled. Clinical and HRCT characteristics were obtained. In addition to our patients, we also analyzed data of PPFE patients whose cause of death had been identified in previous studies.ResultsWe enrolled 15 patients with PPFE and 75 patients with IPF. Consolidation and maximum pleural thickening were significantly higher in patients with PPFE than in those with IPF (both P < .001). Fibrosis score, honeycomb area, and traction bronchiectasis were not significantly different between these patient groups but were significant prognostic factors in patients with PPFE in univariate analysis (P = .021, P = .017, and P = .014, respectively). The proportions of deaths by acute exacerbation or lung cancer were significantly lower in patients with PPFE than in those with IPF (P < .001 and P = .001, respectively), whereas death by respiratory failure was significantly more frequent in PPFE patients (P < .001).ConclusionsHRCT findings, such as fibrosis score, honeycomb area, and traction bronchiectasis, were independent prognostic factors in patients with PPFE. Respiratory failure, but not acute exacerbation and lung cancer, was the main cause of death in patients with PPFE.     

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.     

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)     

Human epididymis protein 4 is a new biomarker to predict the prognosis of progressive fibrosing interstitial lung disease

BackgroundThe clinical course and prognosis of progressive fibrosing interstitial lung diseases (PF-ILDs) vary between individuals. Notably, predictive serum biomarkers for disease management are needed. Serum human epididymis protein 4 (HE4) is reportedly elevated in patients with idiopathic pulmonary ?brosis (IPF); however, its clinical utility remains unknown. We evaluated the potential of serum HE4 as a biomarker for patients with PF-ILD.MethodsSerum HE4 was measured in a retrospective study consisting of 34 patients with PF-ILD and 40 healthy volunteers. The relationship between serum HE4 levels and clinical parameters or prognosis was investigated. To validate the significance of results obtained, a prospective observational study was performed in 37 patients presenting PF-ILD and 40 control patients without PF-ILD.ResultsSerum HE4 levels were higher in patients with PF-ILD than in healthy volunteers (P < 0.01). Moreover, serum HE4 levels correlated with the extent of honeycombing on chest high-resolution computed tomography (r = 0.41, P = 0.015). In multivariate analysis using the Cox proportional hazard model, higher HE4 levels (>238 pmol/L) were associated with an elevated mortality risk; hazard ratio (HR) 7.27, 95% CI 1.56–34.0, P = 0.01 in the derivation cohort; HR 44.3, 95% CI 4.19–468, P < 0.01 in validation cohort.ConclusionsSerum HE4 levels may serve as a new diagnostic and prognostic biomarker for patients with PF-ILD.     

Quantification of BIM mRNA in circulating tumor cells of osimertinib-treated patients with EGFR mutation-positive lung cancer

BackgroundThe response rate for osimertinib is high among patients with untreated epidermal growth factor receptor (EGFR) mutation-positive non-small cell lung cancer (NSCLC). However, there exist no biomarkers to predict the efficacy of the same. This study investigated whether BIM-γ mRNA expression in circulating tumor cells (CTCs) predicts poor outcomes for osimertinib treatment in patients with EGFR mutation-positive NSCLC.MethodsPatients with advanced EGFR-tyrosine kinase inhibitor-untreated NSCLC or post-operative recurrence with EGFR-sensitive mutations (exon 19 deletion or L858R mutation) were included. Informed consent was obtained from all participants. The candidate biomarker BIM-γ was measured in CTCs after blood collection (10 mL of whole blood) at baseline. CTCs were collected with the ClearCell FX system, and quantitative real-time PCR was performed. Relative expression of BIM-γ mRNA from CTCs, as normalized to the reference gene (GAPDH mRNA), was calculated using the KCL22 cell line for calibration.ResultsWe enrolled 30 EGFR mutation-positive NSCLC patients treated with osimertinib during the period from April 2018 through December 2019. All the patients had an EGFR mutation at the primary site: exon 19 deletion in 15 cases and L858R in 15 cases. Median CTC count at baseline was 12 (range 3–127)/7.5 mL, and median BIM-γ mRNA expression was 0.073 (range 0–1.37). Furthermore, the response rate to osimertinib was worse in patients with high than in those with low BIM-γ mRNA expression (n = 15 each) (26.6% vs. 73.3%, respectively; p = 0.011). Progression-free survival did not significantly differ between groups (p = 0.13).ConclusionsBIM-γ mRNA overexpression in CTCs from EGFR mutation-positive NSCLC patients is a potential a biomarker for poor response to osimertinib.Clinical trial registration numberUMIN:00032055.     

Incidence and Predictors of Atrial Fibrillation in Cardiac Sarcoidosis: A Multimodality Imaging Study

BackgroundIn cardiac sarcoidosis (CS), the risk and predictors of new-onset atrial fibrillation (AF) are poorly known.ObjectivesThe authors evaluated the incidence and characteristics of AF in newly diagnosed CS.MethodsThe authors studied 118 patients (78 women, mean age 50 years) with AF-naive CS having undergone cardiac ¹⁸F-fluorodexoyglucose positron emission tomography (¹⁸F-FDG PET) at the time of diagnosis. Details of patient characteristics and medical or device therapy were collected from hospital charts. The PET scans were re-analyzed for presence of atrial and ventricular inflammation, and coincident cardiac magnetic resonance (CMR) studies and single-photon emission computed tomography (SPECT) perfusions were analyzed for cardiac structure and function, including the presence and extent of myocardial scarring. Detection of AF was based on interrogation of intracardiac devices and on ambulatory or 12-lead electrocardiograms.ResultsAltogether 34 patients (29%) suffered paroxysms of AF during follow-up (median, 3 years) with persistent AF developing in 7 patients and permanent AF in 4. The estimated 5-year incidence of AF was 55% (95% CI: 34%-72%) in the 39 patients with atrial ¹⁸F-FDG uptake at the time of diagnosis vs 18% (95% CI: 10%-28%) in the 79 patients without atrial uptake (P < 0.001). In cause-specific Cox regression analysis, atrial uptake was an independent predictor of AF (P < 0.001) with HR of 6.01 (95% CI: 2.64-13.66). Other independent predictors were an increased left atrial maximum volume (P < 0.01) and history of sleep apnea (P < 0.01). Ventricular involvement by PET, SPECT, or CMR was nonpredictive. Symptoms of AF prompted electrical cardioversion in 12 patients (35%). Three of the 34 patients (9%) experiencing AF suffered a stroke versus none of those remaining free of AF.ConclusionsIn newly diagnosed CS, future AF is relatively common and associated with atrial inflammation and enlargement on multimodality cardiac imaging.