Optimisation of detecting chronic thromboembolic pulmonary hypertension in acute pulmonary embolism survivors: the InShape IV study.

INTRODUCTION: Chronic thromboembolic pulmonary hypertension (CTEPH) is often diagnosed late in acute pulmonary embolism (PE) survivors: more efficient testing to expedite diagnosis may considerably improve patient outcomes. The InShape II algorithm safely rules out CTEPH (failure rate 0.29%) while requiring echocardiography in only 19% of patients but may be improved by adding detailed reading of the computed tomography pulmonary angiography (CTPA) diagnosing the index PE. METHODS: Twelve new algorithms, incorporating the CTEPH prediction score, ECG reading, NT-proBNP levels and dedicated CTPA reading were evaluated in the international InShape II (n=341) and part of the German FOCUS cohort (n=171). Evaluation criteria included failure rate, defined as the incidence of confirmed CTEPH in PE patients in whom echocardiography was deemed unnecessary by the algorithm, and the overall net reclassification index (NRI) compared to the InShape II algorithm. RESULTS: The algorithm starting with CTPA reading of the index PE for 6 signs of CTEPH, followed by the ECG/NTproBNP assessment and echocardiography resulted in the most beneficial change compared to InShape II with a need for echocardiography in 20% (+5%), a failure rate of 0%, and an NRI of +3.5, reflecting improved performance over the InShape II algorithm. In the FOCUS cohort, this approach lowered echocardiography need to 24% (-6%) and missed no CTEPH cases, with an NRI of +6.0. CONCLUSION: Dedicated CTPA reading of the index PE improved the performance of the InShape II algorithm and may improve the selection of PE survivors who require echocardiography to rule out CTEPH.

Magnetic resonance imaging for diagnosis of recurrent ipsilateral deep vein thrombosis.

The diagnosis of recurrent ipsilateral deep vein thrombosis (DVT) is challenging, because persistent intravascular abnormalities after previous DVT often hinder a diagnosis by compression ultrasonography. Magnetic resonance direct thrombus imaging (MRDTI), a technique without intravenous contrast and with a 10-minute acquisition time, has been shown to accurately distinguish acute recurrent DVT from chronic thrombotic remains. We have evaluated the safety of MRDTI as the sole test for excluding recurrent ipsilateral DVT. The Theia Study was a prospective, international, multicenter, diagnostic management study involving patients with clinically suspected acute recurrent ipsilateral DVT. Treatment of the patients was managed according to the result of the MRDTI, performed within 24 hours of study inclusion. The primary outcome was the 3-month incidence of venous thromboembolism (VTE) after a MRDTI negative for DVT. The secondary outcome was the interobserver agreement on the MRDTI readings. An independent committee adjudicated all end points. Three hundred five patients were included. The baseline prevalence of recurrent DVT was 38%; superficial thrombophlebitis was diagnosed in 4.6%. The primary outcome occurred in 2 of 119 (1.7%; 95% confidence interval [CI], 0.20-5.9) patients with MRDTI negative for DVT and thrombophlebitis, who were not treated with any anticoagulant during follow-up; neither of these recurrences was fatal. The incidence of recurrent VTE in all patients with MRDTI negative for DVT was 1.1% (95% CI, 0.13%-3.8%). The agreement between initial local and post hoc central reading of the MRDTI images was excellent (κ statistic, 0.91). The incidence of VTE recurrence after negative MRDTI was low, and MRDTI proved to be a feasible and reproducible diagnostic test. This trial was registered at www.clinicaltrials.gov as #NCT02262052.

Prediction of chronic thromboembolic pulmonary hypertension with standardised evaluation of initial computed tomography pulmonary angiography performed for suspected acute pulmonary embolism.

OBJECTIVES: Closer reading of computed tomography pulmonary angiography (CTPA) scans of patients presenting with acute pulmonary embolism (PE) may identify those at high risk of developing chronic thromboembolic pulmonary hypertension (CTEPH). We aimed to validate the predictive value of six radiological predictors that were previously proposed. METHODS: Three hundred forty-one patients with acute PE were prospectively followed for development of CTEPH in six European hospitals. Index CTPAs were analysed post hoc by expert chest radiologists blinded to the final diagnosis. The accuracy of the predictors using a predefined threshold for 'high risk' (≥ 3 predictors) and the expert overall judgment on the presence of CTEPH were assessed. RESULTS: CTEPH was confirmed in nine patients (2.6%) during 2-year follow-up. Any sign of chronic thrombi was already present in 74/341 patients (22%) on the index CTPA, which was associated with CTEPH (OR 7.8, 95%CI 1.9-32); 37 patients (11%) had ≥ 3 of 6 radiological predictors, of whom 4 (11%) were diagnosed with CTEPH (sensitivity 44%, 95%CI 14-79; specificity 90%, 95%CI 86-93). Expert judgment raised suspicion of CTEPH in 27 patients, which was confirmed in 8 (30%; sensitivity 89%, 95%CI 52-100; specificity 94%, 95%CI 91-97). CONCLUSIONS: The presence of ≥ 3 of 6 predefined radiological predictors was highly specific for a future CTEPH diagnosis, comparable to overall expert judgment, while the latter was associated with higher sensitivity. Dedicated CTPA reading for signs of CTEPH may therefore help in early detection of CTEPH after PE, although in our cohort this strategy would not have detected all cases. KEY POINTS: • Three expert chest radiologists re-assessed CTPA scans performed at the moment of acute pulmonary embolism diagnosis and observed a high prevalence of chronic thrombi and signs of pulmonary hypertension. • On these index scans, the presence of ≥ 3 of 6 predefined radiological predictors was highly specific for a future diagnosis of chronic thromboembolic pulmonary hypertension (CTEPH), comparable to overall expert judgment. • Dedicated CTPA reading for signs of CTEPH may help in early detection of CTEPH after acute pulmonary embolism.

4D flow cardiovascular magnetic resonance derived energetics in the Fontan circulation correlate with exercise capacity and CMR-derived liver fibrosis/congestion.

AIM: This study explores the relationship between in vivo 4D flow cardiovascular magnetic resonance (CMR) derived blood flow energetics in the total cavopulmonary connection (TCPC), exercise capacity and CMR-derived liver fibrosis/congestion. BACKGROUND: The Fontan circulation, in which both caval veins are directly connected with the pulmonary arteries (i.e. the TCPC) is the palliative approach for single ventricle patients. Blood flow efficiency in the TCPC has been associated with exercise capacity and liver fibrosis using computational fluid dynamic modelling. 4D flow CMR allows for assessment of in vivo blood flow energetics, including kinetic energy (KE) and viscous energy loss rate (EL). METHODS: Fontan patients were prospectively evaluated between 2018 and 2021 using a comprehensive cardiovascular and liver CMR protocol, including 4D flow imaging of the TCPC. Peak oxygen consumption (VO2) was determined using cardiopulmonary exercise testing (CPET). Iron-corrected whole liver T1 (cT1) mapping was performed as a marker of liver fibrosis/congestion. KE and EL in the TCPC were computed from 4D flow CMR and normalized for inflow. Furthermore, blood flow energetics were compared between standardized segments of the TCPC. RESULTS: Sixty-two Fontan patients were included (53% male, 17.3 ± 5.1 years). Maximal effort CPET was obtained in 50 patients (peak VO2 27.1 ± 6.2 ml/kg/min, 56 ± 12% of predicted). Both KE and EL in the entire TCPC (n = 28) were significantly correlated with cT1 (r = 0.50, p = 0.006 and r = 0.39, p = 0.04, respectively), peak VO2 (r = - 0.61, p = 0.003 and r = - 0.54, p = 0.009, respectively) and % predicted peak VO2 (r = - 0.44, p = 0.04 and r = - 0.46, p = 0.03, respectively). Segmental analysis indicated that the most adverse flow energetics were found in the Fontan tunnel and left pulmonary artery. CONCLUSIONS: Adverse 4D flow CMR derived KE and EL in the TCPC correlate with decreased exercise capacity and increased levels of liver fibrosis/congestion. 4D flow CMR is promising as a non-invasive screening tool for identification of patients with adverse TCPC flow efficiency.

Hemodynamic interplay of vorticity, viscous energy loss, and kinetic energy from 4D Flow MRI and link to cardiac function in healthy subjects and Fontan patients.

The purpose of this study was to directly assess (patho)physiology of intraventricular hemodynamic interplay between four-dimensional flow cardiovascular magnetic resonance imaging (4D Flow MRI)-derived vorticity with kinetic energy (KE) and viscous energy loss (EL) over the cardiac cycle and their association to ejection fraction (EF) and stroke volume (SV). Fifteen healthy subjects and thirty Fontan patients underwent whole heart 4D Flow MRI. Ventricular vorticity, KE, and EL were computed over systole (vorticity_volavg systole, KEavg systole, and ELavg systole) and diastole (vorticity_volavg diastole, KEavg diastole, and ELavg diastole). The association between vorticity_vol and KE and EL was tested by Spearman correlation. Fontan patients were grouped to normal and impaired EF groups. A significant correlation was found between SV and vorticity in healthy subjects (systolic: ρ = 0.84, P < 0.001; diastolic: ρ = 0.81, P < 0.001) and in Fontan patients (systolic: ρ = 0.61, P < 0.001; diastolic: ρ = 0.54, P = 0.002). Healthy subjects showed positive correlation between vorticity_vol versus KE (systole: ρ = 0.96, P < 0.001; diastole: ρ = 0.90, P < 0.001) and EL (systole: ρ = 0.85, P < 0.001; diastole: ρ = 0.84, P < 0.001). Fontan patients showed significantly elevated vorticity_vol compared with healthy subjects (vorticity_volavg systole: 3.1 [2.3-3.9] vs. 1.7 [1.3-2.4] L/s, P < 0.001; vorticity_volavg diastole: 3.1 [2.0-3.7] vs. 2.1 [1.6-2.8] L/s, P = 0.002). This elevated vorticity in Fontan patients showed strong association with KE (systole: ρ = 0.91, P < 0.001; diastole: ρ = 0.85, P < 0.001) and EL (systole: ρ = 0.82, P < 0.001; diastole: ρ = 0.89, P < 0.001). Fontan patients with normal EF showed significantly higher vorticity_volavg systole and ELavg systole, but significantly decreased KE avg diastole, in the presence of normal SV, compared with healthy subjects. Healthy subjects show strong physiological hemodynamic interplay between vorticity with KE and EL. Fontan patients demonstrate a pathophysiological hemodynamic interplay characterized by correlation of elevated vorticity with KE and EL in the presence of maintained normal stroke volume. Altered vorticity and energetic hemodynamics are found in the presence of normal EF in Fontan patients.NEW & NOTEWORTHY Physiologic intraventricular hemodynamic interplay/coupling is present in the healthy left ventricle between vorticity versus viscous energy loss and kinetic energy from four-dimensional flow cardiovascular magnetic resonance imaging (4D Flow MRI). Conversely, Fontan patients present compensatory pathophysiologic hemodynamic coupling by an increase in intraventricular vorticity that positively correlates to viscous energy loss and kinetic energy levels in the presence of maintained normal stroke volume. Altered vorticity and energetics are found in the presence of normal ejection fraction in Fontan patients.

Evolution of CT findings after anticoagulant treatment for acute pulmonary embolism in patients with and without an ultimate diagnosis of chronic thromboembolic pulmonary hypertension.

INTRODUCTION: The pulmonary arterial morphology of patients with pulmonary embolism (PE) is diverse and it is unclear how the different vascular lesions evolve after initiation of anticoagulant treatment. A better understanding of the evolution of computed tomography pulmonary angiography (CTPA) findings after the start of anticoagulant treatment may help to better identify those PE patients prone to develop chronic thromboembolic pulmonary hypertension (CTEPH). We aimed to assess the evolution of various thromboembolic lesions on CTPA over time after the initiation of adequate anticoagulant treatment in individual acute PE patients with and without an ultimate diagnosis of CTEPH. METHODS: We analysed CTPA at diagnosis of acute PE (baseline) and at follow-up in 41 patients with CTEPH and 124 patients without an ultimate diagnosis of CTEPH, all receiving anticoagulant treatment. Central and segmental pulmonary arteries were scored by expert chest radiologists as normal or affected. Lesions were further subclassified as 1) central thrombus, 2) total thrombotic occlusion, 3) mural thrombus, 4) web or 5) tapered pulmonary artery. RESULTS: Central thrombi resolved after anticoagulant treatment, while mural thrombi and total thrombotic occlusions either resolved or evolved into webs or tapered pulmonary arteries. Only patients with an ultimate diagnosis of CTEPH exhibited webs and tapered pulmonary arteries on the baseline scan. Moreover, such lesions always persisted after follow-up. CONCLUSIONS: Webs and tapered pulmonary arteries at the time of PE diagnosis strongly indicate a state of chronic PE and should raise awareness for possible CTEPH, particularly in patients with persistent dyspnoea after anticoagulant treatment for acute PE.

Pulmonary ductal coarctation: An entity associated with congenital heart defects involving the right ventricle outflow tract.

We present a case of a prematurely born 2-month-old girl with a double outlet right ventricle with pulmonary atresia and a left pulmonary artery coarctation arising after ductal closure. The case highlights the importance of knowledge and identification of such an anomaly in patients with congenital heart malformations with severe pulmonary stenosis to atresia.

Altered Ascending Aorta Hemodynamics in Patients After Arterial Switch Operation for Transposition of the Great Arteries.

BACKGROUND: Patients with transposition of the great arteries (TGA) have an altered aortic geometry after an arterial switch operation (ASO), with neo-aortic root dilatation as an important complication. Geometry-related aortic hemodynamics have been assumed to contribute to pathology of the ascending aorta (AAo). PURPOSE: To evaluate aortic flow displacement (FD) and regional wall shear stress (WSS) in relation to ascending neo-aortic geometry in children after ASO. STUDY TYPE: Prospective. POPULATION: Twenty-eight TGA patients after ASO and 10 healthy volunteers. FIELD STRENGTH/SEQUENCE: 3.0T/4D flow (segmented fast-spoiled echo pulse), noncontrast-enhanced MR angiography (Dixon), and anatomic images (SSFP). ASSESSMENT: Aortic diameters and body surface area-indexed aortic dimensions (Z-scores), normalized FD and planar ascending aortic WSS. STATISTICAL TESTS: Mann-Whitney and chi-square tests for differences in FD magnitude, WSS, and FD directionality between groups, respectively. Spearman rank correlation to assess the degree of association between aortic geometry, FD and WSS parameters. Shapiro-Wilk test to evaluate distribution normality on the absolute differences in octant location between FD and WSS. RESULTS: TGA patients showed a significantly dilated proximal AAo and relatively small mid-AAo dimensions at the level of the pulmonary arteries (Z-scores neo-aortic root: 4.38 ± 1.96 vs. 1.52 ± 0.70, P < 0.001; sinotubular junction: 3.48 ± 2.67 vs. 1.38 ± 1.30, P = 0.010; mid-AAo: 0.32 ± 3.06 vs. 1.69 ± 1.24, P = 0.001). FD magnitude was higher in TGA patients (neo-aortic root: 0.048 ± 0.027 vs. 0.021 ± 0.006, P < 0.001; sinotubular junction: 0.054 ± 0.037 vs. 0.029 ± 0.013, P < 0.05) and was related to the neo-aortic Z-score. Clear areas of higher WSS at the right and anterior aortic wall regions along the distal AAo were detected in TGA patients, most pronounced in those with relatively smaller mid-AAo diameters. DATA CONCLUSION: TGA-specific geometry related to the ASO, evidenced by neo-aortic root dilatation and a sudden change in vessel diameter at mid-AAo level, leads to more aortic flow asymmetry in the proximal AAo and WSS distribution with higher WSS at the right and anterior aortic wall regions along the distal AAo. LEVEL OF EVIDENCE: 1 Technical Efficacy Stage: 3 J. Magn. Reson. Imaging 2020;51:1105-1116.

Trends in diagnostic methods and treatment of latent tuberculosis infection in a tertiary care center from 2000 to 2017.

Screening for latent tuberculosis infection (LTBI) is indicated before immunosuppressive therapies but is complicated by lack of a gold standard and limited by, e.g., immunosuppression. This study aimed to investigate a series of patients diagnosed with LTBI during screening before immunosuppressive therapy, describing how the use of diagnostic tests and treatment evolved over time. This retrospective cohort study included all individuals diagnosed with LTBI during screening before intended immunosuppressive therapy in a tertiary care hospital between January 2000 and December 2017. Evidence for LTBI, including history, tuberculin skin test (TST), QuantiFERON (QFT) result and suggestive lesions on chest radiography (CXR), and CT scan if available, was analyzed. The study included 295 individuals with LTBI, with median follow-up of 3.8 years (IQR 1.7-7.4 years). During screening, TST, QFT, and CXR were positive in 80.8%, 53.4%, and 22.7%, respectively. Chest CT revealed lesions associated with past tuberculosis infection in around 70%, significantly more frequent than CXR. In patients diagnosed with LTBI, we observed that the use of TST declined over time whereas the use of QFT increased, and that isoniazid was replaced with rifampicin as preferential treatment. Preventive treatment was started in 82.3%, of whom 88.6% completed treatment. During follow-up, no individuals developed active tuberculosis. The diagnosis of LTBI was based on history, TST, QFT, and/or CXR in nearly every possible combination, but mostly on TST and QFT. The most striking trends were the decreased use of TST, increased use of QFT, and the replacement of isoniazid with rifampicin for treatment.

CT-Based Biomarkers for Prediction of Chronic Thromboembolic Pulmonary Hypertension After an Acute Pulmonary Embolic Event.

OBJECTIVE. The purpose of this study is to assess CT-based markers predictive of the development of chronic thromboembolic pulmonary hypertension (CTEPH) after acute pulmonary embolism. MATERIALS AND METHODS. Identified from a search of local registries, 48 patients who had CTEPH develop were included in the study group, and 113 patients who had complete resolution of acute pulmonary embolism were included in the control group. Baseline CT scans obtained at the time of the initial pulmonary embolism event were evaluated for the degree of clot-induced vessel obstruction, the quantitative Walsh score, the ratio of the right ventricle diameter to the left ventricle diameter, the right atrium diameter, the pulmonary artery diameter, right heart thrombus, pericardial effusion, lung infarction, and mosaic attenuation. Classification and regression tree analysis was used to create a decision tree. The decision tree was externally validated on an anonymized cohort of 50 control subjects and 50 patients with CTEPH. RESULTS. During univariable analysis, an increase in the degree occlusive clot on initial imaging, a decrease in the Walsh score, absence of pericardial effusion, presence of lung infarction, and the presence of mosaic attenuation were associated with an increased probability of CTEPH development. In the final decision tree, the occlusive nature of the clot remained. Two patients in the cohort used for external validation had nondiagnostic findings and were excluded. The decision process correctly classified 33% (16/48) of patients who had CTEPH develop and 86% (43/50) of patients who did not have CTEPH develop, for an odds ratio of 3.1 (95% CI, 1.1-8.3). CONCLUSION. The presence of an occlusive clot on initial imaging is associated with an increased probability of CTEPH development. Presence of mosaic attenuation and lung infarction may also predict CTEPH development, although additional studies are needed.

Automated Cardiac Valve Tracking for Flow Quantification with Four-dimensional Flow MRI.

Purpose To compare four-dimensional flow MRI with automated valve tracking to manual valve tracking in patients with acquired or congenital heart disease and healthy volunteers. Materials and Methods In this retrospective study, data were collected from 114 patients and 46 volunteers who underwent four-dimensional flow MRI at 1.5 T or 3.0 T from 2006 through 2017. Among the 114 patients, 33 had acquired and 81 had congenital heart disease (median age, 17 years; interquartile range [IQR], 13-49 years), 51 (45%) were women, and 63 (55%) were men. Among the 46 volunteers (median age, 28 years; IQR, 22-36 years), there were 19 (41%) women and 27 (59%) men. Two orthogonal cine views of each valve were used for valve tracking. Wilcoxon signed-rank test was used to compare analysis times, net forward volumes (NFVs), and regurgitant fractions. Intra- and interobserver variability was tested by using intraclass correlation coefficients (ICCs). Results Analysis time was shorter for automated versus manual tracking (all patients, 14 minutes [IQR, 12-15 minutes] vs 25 minutes [IQR, 20-25 minutes]; P < .001). Although overall differences in NFV and regurgitant fraction were comparable between both methods, NFV variation over four valves was smaller for automated versus manual tracking (all patients, 4.9% [IQR, 3.3%-6.7%] vs 9.8% [IQR, 5.1%-14.7%], respectively; P < .001). Regurgitation severity was discordant for seven pulmonary valves, 22 mitral valves, and 21 tricuspid valves. Intra- and interobserver agreement for automated tracking was excellent for NFV assessment (intra- and interobserver, ICC ≥ 0.99) and strong to excellent for regurgitant fraction assessment (intraobserver, ICC ≥ 0.94; interobserver, ICC ≥ 0.89). Conclusion Automated valve tracking reduces analysis time and improves reliability of valvular flow quantification with four-dimensional flow MRI in patients with acquired or congenital heart disease and in healthy volunteers. © RSNA, 2018 Online supplemental material is available for this article. See also the editorial by François in this issue.

Computed tomography pulmonary angiography versus ventilation-perfusion lung scanning for diagnosing pulmonary embolism during pregnancy: a systematic review and meta-analysis.

Differences between computed tomography pulmonary angiography and ventilation-perfusion lung scanning in pregnant patients with suspected acute pulmonary embolism are not well-known, leading to ongoing debate on which test to choose. We searched in PubMed, EMBASE, Web of Science and the Cochrane Library databases and identified all relevant articles and abstracts published up to October 1, 2017. We assessed diagnostic efficiency, frequency of non-diagnostic results and maternal and fetal exposure to radiation exposure. We included 13 studies for the diagnostic efficiency analysis, 30 for the analysis of non-diagnostic results and 22 for the radiation exposure analysis. The pooled rate of false negative test results was 0% for both imaging strategies with overlapping confidence intervals. The pooled rates of non-diagnostic results with computed tomography pulmonary angiography and ventilation-perfusion lung scans were 12% (95% confidence interval: 8-17) and 14% (95% confidence interval: 10-18), respectively. Reported maternal and fetal radiation exposure doses were well below the safety threshold, but could not be compared between the two diagnostic methods given the lack of high quality data. Both imaging tests seem equally safe to rule out pulmonary embolism in pregnancy. We found no significant differences in efficiency and radiation exposures between computed tomography pulmonary angiography and ventilation-perfusion lung scanning although direct comparisons were not possible.

Stress increases intracardiac 4D flow cardiovascular magnetic resonance -derived energetics and vorticity and relates to VO2max in Fontan patients.

BACKGROUND: We hypothesize that dobutamine-induced stress impacts intracardiac hemodynamic parameters and that this may be linked to decreased exercise capacity in Fontan patients. Therefore, the purpose of this study was to assess the effect of pharmacologic stress on intraventricular kinetic energy (KE), viscous energy loss (EL) and vorticity from four-dimensional (4D) Flow cardiovascular magnetic resonance (CMR) imaging in Fontan patients and to study the association between stress response and exercise capacity. METHODS: Ten Fontan patients underwent whole-heart 4D flow CMR before and during 7.5 µg/kg/min dobutamine infusion and cardiopulmonary exercise testing (CPET) on the same day. Average ventricular KE, EL and vorticity were computed over systole, diastole and the total cardiac cycle (vorticity_volavg cycle, KEavg cycle, ELavg cycle). The relation to maximum oxygen uptake (VO2 max) from CPET was tested by Pearson's correlation or Spearman's rank correlation in case of non-normality of the data. RESULTS: Dobutamine stress caused a significant 88 ± 52% increase in KE (KEavg cycle: 1.8 ± 0.5 vs 3.3 ± 0.9 mJ, P < 0.001), a significant 108 ± 49% increase in EL (ELavg cycle: 0.9 ± 0.4 vs 1.9 ± 0.9 mW, P < 0.001) and a significant 27 ± 19% increase in vorticity (vorticity_volavg cycle: 3441 ± 899 vs 4394 ± 1322 mL/s, P = 0.002). All rest-stress differences (%) were negatively correlated to VO2 max (KEavg cycle: r = - 0.83, P = 0.003; ELavg cycle: r = - 0.80, P = 0.006; vorticity_volavg cycle: r = - 0.64, P = 0.047). CONCLUSIONS: 4D flow CMR-derived intraventricular kinetic energy, viscous energy loss and vorticity in Fontan patients increase during pharmacologic stress and show a negative correlation with exercise capacity measured by VO2 max.

Lower prevalence of subsegmental pulmonary embolism after application of the YEARS diagnostic algorithm.

The rate of identified isolated subsegmental pulmonary embolism (ssPE) has doubled with advances in computed tomography pulmonary angiography (CTPA) technology, but its clinical relevance is debated. The YEARS diagnostic algorithm was shown to safely reduce the number of required CTPAs in the diagnostic management of PE. We hypothesized that the higher threshold for performing CTPA in YEARS was associated with a lower prevalence of ssPE compared to the conventional diagnostic algorithm. We compared 2291 consecutive patients with suspected PE managed according to YEARS to 3306 consecutive control patients managed according to the Wells score for the prevalence of isolated ssPE. In the YEARS cohort, 52% were managed without CTPA, 12% had pulmonary embolism (PE) of which 10% were isolated ssPE, and the 3-month diagnostic failure rate was 0·35%. In the control cohort, 32% were managed without CTPA, 20% had PE of which 16% were isolated ssPE, and the 3-month failure rate was 0·73%. The isolated ssPE prevalence was significantly lower in YEARS (absolute difference 6·2% (95% confidence interval [CI] 1·4-10), Odds Ratio 0·58 (95% CI 0·37-0·90). In conclusion, YEARS is associated with a lower prevalence of isolated ssPE, due to reduction in CTPAs by the higher D-dimer threshold. This was however not associated with a higher risk of recurrent VTE during follow-up.

Predicting cardiopulmonary involvement in patients with systemic sclerosis: complementary value of nailfold videocapillaroscopy patterns and disease-specific autoantibodies.

Objective: To evaluate the prevalence of anti-extractable nuclear antigen (anti-ENA) antibodies in Dutch SSc patients and the predictive power of the combination of specific anti-ENA antibodies and nailfold videocapillaroscopy (NVC) patterns to improve identification of patients with high risk for cardiopulmonary involvement. Methods: A total of 287 patients (79%) from the Leiden SSc-Cohort had data available on NVC-pattern (no SSc-specific, early, active, late) and anti-ENA antibodies. Associations between anti-ENA/NVC combinations with cardiopulmonary parameters were explored using logistic regression. Results: Prevalence of ACA was 37%, anti-Scl-70 24%, anti-RNP 9%, anti-RNAPIII 5%, anti-fibrillarin 4%, anti-Pm/Scl 3%, anti-Th/To 0.3% and anti-Ku 1.4%. NVC showed a SSc-specific pattern in 88%: 10% early, 42% active and 36% late. The prevalence of different NVC patterns was equally distributed among specific anti-ENA antibodies, except for the absence of early pattern in anti-RNP positive patients. Fifty-one percent had interstitial lung disease (ILD), 59% had decreased diffusion capacity for carbon monoxide and 16% systolic pulmonary artery pressure >35 mmHg (sPAP↑). Regardless of ENA-subtype, NVC-pattern showed a stable association with presence of ILD or sPAP↑. For ILD, the odds ratios (ORs) were 1.3-1.4 ( P < 0.05 for analyses with anti-RNAPIII, anti-RNP). For diffusion capacity for carbon monoxide, the OR was 1.5 ( P < 0.05 for analyses with ACA, anti-Scl-70, anti-RNAPIII, anti-RNP). For sPAP↑, the ORs were 2.2-2.4 ( P < 0.05 for analyses with anti-RNAPIII, anti-RNP). Conclusion: In Dutch SSc patients, all SSc-specific auto-antibodies were found, with ACA and anti-Scl-70 being the most prevalent. Strikingly, the association between NVC-pattern and heart/lung involvement was independent of specific anti-ENA antibodies, which might indicate microangiopathy is an important cause of organ involvement.

Liver Fat Assessed With CT Relates to MRI Markers of Incipient Brain Injury in Middle-Aged to Elderly Overweight Persons.

OBJECTIVE: Obesity has been related to structural brain abnormalities. Increasing evidence suggests that accumulation of fat in the liver is an important determinant of cardiometabolic complications of obesity. The purpose of this study was to investigate the association between CT-assessed liver-to-spleen attenuation ratio as a measure of liver steatosis and MRI-assessed brain tissue integrity in middle-aged to elderly persons. SUBJECTS AND METHODS: CT and MRI were performed on 213 participants (114 women, 99 men; mean age, 65 ± 7 years). Brain tissue integrity was assessed by magnetization transfer imaging. Linear regression analysis was adjusted for age, sex, vascular risk factors, and total body fat estimated from bioelectrical impedance analysis. RESULTS: Seventy-nine participants had normal weight (body mass index [BMI], 18.5-24.9), and 134 were overweight (BMI ≥ 25). Significant interaction was found between liver-to-spleen ratio and BMI (p = 0.001). In the overweight group, liver fat was associated with reduced brain tissue integrity in both gray matter (standardized ß = 0.22; 95% CI, 0.07-0.36) and white matter (standardized ß = 0.31; 95% CI, 0.15-0.45). These associations were not found in the normal weight group (gray matter standardized ß = -0.08; 95% CI, -0.33 to 0.16; white matter standardized ß = -0.09; 95% CI, -0.36-0.14). CONCLUSION: The results indicate that liver fat assessed with CT relates to MRI markers of incipient brain injury in middle-aged to elderly overweight persons.

Characterization and improved quantification of left ventricular inflow using streamline visualization with 4DFlow MRI in healthy controls and patients after atrioventricular septal defect correction.

PURPOSE: To evaluate trans-left atrioventricular valve (LAVV) blood flow and optimize left ventricular inflow quantification in healthy controls and patients after atrioventricular septal defect (AVSD) correction. MATERIALS AND METHODS: Twenty-five patients after AVSD correction and 25 controls underwent 4DFlow MRI. Using streamline visualization in four- and two-chamber views, inflow direction at early and late filling was defined at the annulus level and at the peak inflow velocity (PIV) level. Trans-LAVV flow volume and velocity were assessed from a static 2D-multiplanar-reformat (MPR), a 4D-MPR tracking LAVV annulus and a 4D-MPR tracking the PIV-level, angulated perpendicular to the inflow. RESULTS: In patients, on average 9° more laterally directed inflow was found at the PIV-level compared to controls. In controls, 4DFlow velocity mapping with LAVV annulus tracking resulted in lower absolute error with aortic flow (3 (1-8) mL) than with static 2D-MPR (7 (4-16) mL, P = 0.001). In patients, 4D-MPR tracking the PIV-level, resulted in lower absolute error with aortic flow (2 (1-4) mL) than with 4D-MPR LAVV annulus tracking (6 (2-10) mL, P = 0.003). CONCLUSION: Streamline visualization of 4DFlow MRI data revealed dynamic trans-LAVV inflow and more lateral flow after AVSD correction. Streamline visualization improved trans-LAVV flow quantification as the positioning and angulation of the measurement plane was optimized, allowing an accurate assessment of left ventricular inflow.

Characterization and quantification of dynamic eccentric regurgitation of the left atrioventricular valve after atrioventricular septal defect correction with 4D Flow cardiovascular magnetic resonance and retrospective valve tracking.

BACKGROUND: To characterize and directly quantify regurgitant jets of left atrioventricular valve (LAVV) in patients with corrected atrioventricular septal defect (AVSD) by four-dimensional (4D)Flow Cardiovascular Magnetic Resonance (CMR), streamline visualization and retrospective valve tracking. METHODS: Medical ethical committee approval and informed consent from all patients or their parents were obtained. In 32 corrected AVSD patients (age 26 ± 12 years), echocardiography and whole-heart 4DFlow CMR were performed. Using streamline visualization on 2- and 4-chamber views, the angle between regurgitation and annulus was followed throughout systole. On through-plane velocity-encoded images reformatted perpendicular to the regurgitation jet the cross-sectional jet circularity index was assessed and regurgitant volume and fraction were calculated. Correlation and agreement between different techniques was performed with Pearson's r and Spearman's rho correlation and Bland-Altman analysis. RESULTS: In 8 patients, multiple regurgitant jets over the LAVV were identified. Median variation in regurgitant jet angle within patients was 36°(IQR 18-64°) on the 2-chamber and 30°(IQR 20-40°) on the 4-chamber. Regurgitant jets had a circularity index of 0.61 ± 0.16. Quantification of the regurgitation volume was feasible with 4DFlow CMR with excellent correlation between LAVV effective forward flow and aortic flow (r = 0.97, p < 0.001) for internal validation and moderate correlation with planimetry derived regurgitant volume (r = 0.65, p < 0.001) and echocardiographic grading (rho = 0.51, p = 0.003). CONCLUSIONS: 4DFlow CMR with streamline visualization revealed multiple, dynamic and eccentric regurgitant jets with non-circular cross-sectional shape in patients after AVSD correction. 4DFlow with retrospective valve tracking allows direct and accurate quantification of the regurgitation of these complex jets.