Cost-Effectiveness of Performing Reference Ultrasonography in Patients with Deep Vein Thrombosis.

BACKGROUND: The diagnosis of recurrent ipsilateral deep vein thrombosis (DVT) with compression ultrasonography (CUS) may be hindered by residual intravascular obstruction after previous DVT. A reference CUS, an additional ultrasound performed at anticoagulant discontinuation, may improve the diagnostic work-up of suspected recurrent ipsilateral DVT by providing baseline images for future comparison. OBJECTIVES: To evaluate the cost-effectiveness of routinely performing reference CUS in DVT patients. METHODS: Patient-level data (n = 96) from a prospective management study (Theia study; NCT02262052) and claims data were used in a decision analytic model to compare 12 scenarios for diagnostic management of suspected recurrent ipsilateral DVT. Estimated health care costs and mortality due to misdiagnosis, recurrent venous thromboembolism, and bleeding during the first year of follow-up after presentation with suspected recurrence were compared. RESULTS: All six scenarios including reference CUS had higher estimated 1-year costs (€1,763-€1,913) than the six without reference CUS (€1,192-€1,474). Costs were higher because reference CUS results often remained unused, as 20% of patients (according to claims data) would return with suspected recurrent DVT. Estimated mortality was comparable in scenarios with (14.8-17.9 per 10,000 patients) and without reference CUS (14.0-18.5 per 10,000). None of the four potentially most desirable scenarios included reference CUS. CONCLUSION: One-year health care costs of diagnostic strategies for suspected recurrent ipsilateral DVT including reference CUS are higher compared to strategies without reference CUS, without mortality benefit. These results can inform policy-makers regarding use of health care resources during follow-up after DVT. From a cost-effectiveness perspective, the findings do not support the routine application of reference CUS.

Automated quantification of the pulmonary vasculature in pulmonary embolism and chronic thromboembolic pulmonary hypertension.

The shape and distribution of vascular lesions in pulmonary embolism (PE) and chronic thromboembolic pulmonary hypertension (CTEPH) are different. We investigated whether automated quantification of pulmonary vascular morphology and densitometry in arteries and veins imaged by computed tomographic pulmonary angiography (CTPA) could distinguish PE from CTEPH. We analyzed CTPA images from a cohort of 16 PE patients, 6 CTEPH patients, and 15 controls. Pulmonary vessels were extracted with a graph-cut method, and separated into arteries and veins using deep-learning classification. Vascular morphology was quantified by the slope (α) and intercept (ß) of the vessel radii distribution. To quantify lung perfusion defects, the median pulmonary vascular density was calculated. By combining these measurements with densities measured in parenchymal areas, pulmonary trunk, and descending aorta, a static perfusion curve was constructed. All separate quantifications were compared between the three groups. No vascular morphology differences were detected in contrast to vascular density values. The median vascular density (interquartile range) was -567 (113), -452 (95), and -470 (323) HU, for the control, PE, and CTEPH group. The static perfusion curves showed different patterns between groups, with a statistically significant difference in aorta-pulmonary trunk gradient between the PE and CTEPH groups (p = 0.008). In this proof of concept study, not vasculature morphology but densities differentiated between patients of three groups. Further technical improvements are needed to allow for accurate differentiation between PE and CTEPH, which in this study was only possible statistically by measuring the density gradient between aorta and pulmonary trunk.

Haemodynamic performance of 16-20-mm extracardiac Goretex conduits in adolescent Fontan patients at rest and during simulated exercise.

OBJECTIVES: To date, it is not known if 16-20-mm extracardiac conduits are outgrown during somatic growth from childhood to adolescence. This study aims to determine total cavopulmonary connection (TCPC) haemodynamics in adolescent Fontan patients at rest and during simulated exercise and to assess the relationship between conduit size and haemodynamics. METHODS: Patient-specific, magnetic resonance imaging-based computational fluid dynamic models of the TCPC were performed in 51 extracardiac Fontan patients with 16-20-mm conduits. Power loss, pressure gradient and normalized resistance were quantified in rest and during simulated exercise. The cross-sectional area (CSA) (mean and minimum) of the vessels of the TCPC was determined and normalized for flow rate (mm2/l/min). Peak (predicted) oxygen uptake was assessed. RESULTS: The median age was 16.2 years (Q1-Q3 14.0-18.2). The normalized mean conduit CSA was 35-73% smaller compared to the inferior and superior vena cava, hepatic veins and left/right pulmonary artery (all P < 0.001). The median TCPC pressure gradient was 0.7 mmHg (Q1-Q3 0.5-0.8) and 2.0 (Q1-Q3 1.4-2.6) during rest and simulated exercise, respectively. A moderate-strong inverse non-linear relationship was present between normalized mean conduit CSA and TCPC haemodynamics in rest and exercise. TCPC pressure gradients of ≥1.0 at rest and ≥3.0 mmHg during simulated exercise were observed in patients with a conduit CSA ≤ 45 mm2/l/min and favourable haemodynamics (<1 mmHg during both rest and exercise) in conduits ≥125 mm2/l/min. Normalized TCPC resistance correlated with (predicted) peak oxygen uptake. CONCLUSIONS: Extracardiac conduits of 16-20 mm have become relatively undersized in most adolescent Fontan patients leading to suboptimal haemodynamics.

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.

Circulating miRNAs and Vascular Injury Markers Associate with Cardiovascular Function in Older Patients Reaching End-Stage Kidney Disease.

The prevalence of end-stage kidney disease (ESKD) is rapidly increasing and mostly occurring in patients aged 65 years or older. The main cause of death in these patients is cardiovascular disease (CVD). Novel markers of vascular integrity may thus be of clinical value for identifying patients at high risk for CVD. Here we associated the levels of selected circulating angiogenic miRNAs, angiopoietin-2 (Ang-2) and asymmetric dimethylarginine (ADMA) with cardiovascular structure and function (as determined by cardiovascular MRI) in 67 older patients reaching ESKD that were included from 'The Cognitive decline in Older Patients with End stage renal disease' (COPE) prospective, multicentered cohort study. We first determined the association between the vascular injury markers and specific heart conditions and observed that ESKD patients with coronary heart disease have significantly higher levels of circulating ADMA and miR-27a. Moreover, circulating levels of miR-27a were higher in patients with atrial fibrillation. In addition, the circulating levels of the vascular injury markers were associated with measures of cardiovascular structure and function obtained from cardiovascular MRI: pulse wave velocity (PWV), ejection fraction (EF) and cardiac index (CI). We found Ang-2 and miR-27a to be strongly correlated to the PWV, while Ang-2 also associated with ejection fraction. Finally, we observed that in contrast to miR-27a, Ang-2 was not associated with a vascular cause of the primary kidney disease, suggesting Ang-2 may be an ESKD-specific marker of vascular injury. Taken together, among older patients with ESKD, aberrant levels of vascular injury markers (miR-27a, Ang-2 and ADMA) associated with impaired cardiovascular function. These markers may serve to identify individuals at higher risk of CVD, as well as give insight into the underlying (vascular) pathophysiology.

Evolution of Systemic Sclerosis-Associated Interstitial Lung Disease One Year After Hematopoietic Stem Cell Transplantation or Cyclophosphamide.

OBJECTIVE: Hematopoietic stem cell transplantation (HSCT) and cyclophosphamide (CYC) are treatment options for progressive systemic sclerosis associated with interstitial lung disease (SSc-ILD). The aims of our retrospective observational study were to evaluate: 1) the evolution of SSc-ILD in SSc patients treated with HSCT (assessed by high-resolution computed tomography [HRCT]; a group of patients treated with CYC was included as frame of reference); 2) how results of pulmonary function tests (PFTs) are associated with HRCT findings; and 3) which factors predict ILD reduction. METHODS: We semiquantitatively scored total ILD extent, reticulations, and ground-glass opacities (GGO) scores at baseline and at the 1-year HRCTs of SSc patients treated with HSCT or CYC. Linear association between changes in HRCT scores and PFT results and predictors of ILD improvement were studied. RESULTS: We included 51 patients (those treated with HSCT [n = 20] and those treated with CYC [n = 31]). The mean change in total ILD score was -5.1% (95% confidence interval [95% CI] -10.2, 0.0) in the HSCT treatment group (P = 0.050), and -1.0% (95% CI -4.3, 2.3) in the CYC treatment group (P = 0.535). For all patients, the evolution of HRCT scores was weakly associated with relative changes in PFT results. In univariate logistic regression, higher ground-glass opacities, higher total ILD, and lower single-breath diffusing capacity for carbon monoxide scores at baseline predicted improvement of ILD extent after treatment, but a multivariable model could not be built to assess independency of predictors. CONCLUSION: One year after treatment with HSCT, a nonsignificant but clear reduction of SSc-ILD extent was observed. Changes in PFT results were associated with changes in HRCT scores but the correlation was weak and cannot be considered conclusive.

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.

Extracardiac conduit adequacy along the respiratory cycle in adolescent Fontan patients.

OBJECTIVES: Adequacy of 16-20mm extracardiac conduits for adolescent Fontan patients remains unknown. This study aims to evaluate conduit adequacy using the inferior vena cava (IVC)-conduit velocity mismatch factor along the respiratory cycle. METHODS: Real-time 2D flow MRI was prospectively acquired in 50 extracardiac (16-20mm conduits) Fontan patients (mean age 16.9 ± 4.5 years) at the subhepatic IVC, conduit and superior vena cava. Hepatic venous flow was determined by subtracting IVC flow from conduit flow. The cross-sectional area (CSA) was reported for each vessel. Mean flow and velocity was calculated during the average respiratory cycle, inspiration and expiration. The IVC-conduit velocity mismatch factor was determined as follows: Vconduit/VIVC, where V is the mean velocity. RESULTS: Median conduit CSA and IVC CSA were 221 mm2 (Q1-Q3 201-255) and 244 mm2 (Q1-Q3 203-265), respectively. From the IVC towards the conduit, flow rates increased significantly due to the entry of hepatic venous flow (IVC 1.9, Q1-Q3 1.5-2.2) versus conduit (3.3, Q1-Q3 2.5-4.0 l/min, P < 0.001). Consequently, mean velocity significantly increased (IVC 12 (Q1-Q3 11-14 cm/s) versus conduit 25 (Q1-Q3 17-31 cm/s), P < 0.001), resulting in a median IVC-conduit velocity mismatch of 1.8 (Q1-Q3 1.5-2.4), further augmenting during inspiration (median 2.3, Q1-Q3 1.8-3.0). IVC-conduit mismatch was inversely related to measured conduit size and positively correlated with conduit flow. The normalized IVC-conduit velocity mismatch factor during expiration and the entire respiratory cycle correlated with peak VO2 (r = -0.37, P = 0.014 and r = -0.31, P = 0.04, respectively). CONCLUSIONS: Important blood flow accelerations are observed from the IVC towards the conduit in adolescent Fontan patients, which is related to peak VO2. This study, therefore, raises concerns that implanted 16-20mm conduits have become undersized for older Fontan patients and future studies should clarify its effect on long-term outcome.

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.

Ruling out Pulmonary Embolism in Patients with (Suspected) COVID-19-A Prospective Cohort Study.

Background Diagnostic strategies for suspected pulmonary embolism (PE) have not been prospectively evaluated in COVID-19 patients. Methods Prospective, multicenter, outcome study in 707 patients with both (suspected) COVID-19 and suspected PE in 14 hospitals. Patients on chronic anticoagulant therapy were excluded. Informed consent was obtained by opt-out approach. Patients were managed by validated diagnostic strategies for suspected PE. We evaluated the safety (3-month failure rate) and efficiency (number of computed tomography pulmonary angiographies [CTPAs] avoided) of the applied strategies. Results Overall PE prevalence was 28%. YEARS was applied in 36%, Wells rule in 4.2%, and "CTPA only" in 52%; 7.4% was not tested because of hemodynamic or respiratory instability. Within YEARS, PE was considered excluded without CTPA in 29%, of which one patient developed nonfatal PE during follow-up (failure rate 1.4%, 95% CI 0.04-7.8). One-hundred seventeen patients (46%) managed according to YEARS had a negative CTPA, of whom 10 were diagnosed with nonfatal venous thromboembolism (VTE) during follow-up (failure rate 8.8%, 95% CI 4.3-16). In patients managed by CTPA only, 66% had an initial negative CTPA, of whom eight patients were diagnosed with a nonfatal VTE during follow-up (failure rate 3.6%, 95% CI 1.6-7.0). Conclusion Our results underline the applicability of YEARS in (suspected) COVID-19 patients with suspected PE. CTPA could be avoided in 29% of patients managed by YEARS, with a low failure rate. The failure rate after a negative CTPA, used as a sole test or within YEARS, was non-negligible and reflects the high thrombotic risk in these patients, warranting ongoing vigilance.

Efficacy and safety of a 12-week outpatient pulmonary rehabilitation program in Post-PE Syndrome.

BACKGROUND: The Post-Pulmonary Embolism Syndrome (PPES) comprises heterogeneous entities, including chronic thromboembolic disease with/without pulmonary hypertension (CTEPH/CTEPD), and deconditioning. OBJECTIVES: To assess underlying physiological determinants of PPES, and efficacy and safety of rehabilitation training in these patients. METHODS: 56 consecutive PE patients with persistent dyspnea and/or functional limitations despite ≥3 months of anticoagulation underwent standardized diagnostic work-up including exercise testing as part of routine practice. All diagnostic (imaging and cardiopulmonary function) tests were interpreted by a core group of experienced clinicians. A subgroup of patients without CTEPH or other treatable conditions was referred for a 12-week personalized rehabilitation program, studying changes in physical condition and patient-reported outcome measures. RESULTS: Persistent vascular occlusions were observed in 21/56 patients (38%) and CTEPH was confirmed in ten (18%). Regarding those without CTEPH, impaired cardiopulmonary responses were evident in 18/39 patients with available CPET data (46%), unrelated to chronic thrombi. Rehabilitation was completed by 27 patients after excluding 29 (patients with CTEPH or treatable comorbidities, refusal, ineligibility, or training elsewhere). Training intensity, PE-specific quality of life (PEmb-QoL) and fatigue (CIS) improved with a median difference of 20 W (p = 0.001), 3.9 points (p < 0.001) and 16 points (p = 0.003), respectively. Functional status (Post-VTE Functional Status Scale) improved ≥1 grade in 18 (67%) patients, and declined in one (3.7%). CONCLUSIONS: Our findings suggest that abnormal cardiopulmonary responses to exercise are common in patients with PPES and are not limited to those with chronic thrombi. Offering pulmonary rehabilitation to patients not treated otherwise seems safe and promising.

Identification of chronic thromboembolic pulmonary hypertension on CTPAs performed for diagnosing acute pulmonary embolism depending on level of expertise.

BACKGROUND: Expert reading often reveals radiological signs of chronic thromboembolic pulmonary hypertension (CTEPH) or chronic PE on computed tomography pulmonary angiography (CTPA) performed at the time of acute pulmonary embolism (PE) presentation preceding CTEPH. Little is known about the accuracy and reproducibility of CTPA reading by radiologists in training in this setting. OBJECTIVES: To evaluate 1) whether signs of CTEPH or chronic PE are routinely reported on CTPA for suspected PE; and 2) whether CTEPH-non-expert readers achieve comparable predictive accuracy to CTEPH-expert radiologists after dedicated instruction. METHODS: Original reports of CTPAs demonstrating acute PE in 50 patients whom ultimately developed CTEPH, and those of 50 PE who did not, were screened for documented signs of CTEPH. All scans were re-assessed by three CTEPH-expert readers and two CTEPH-non-expert readers (blinded and independently) for predefined signs and overall presence of CTEPH. RESULTS: Signs of chronic PE were mentioned in the original reports of 14/50 cases (28%), while CTEPH-expert radiologists had recognized 44/50 (88%). Using a standardized definition (≥3 predefined radiological signs), moderate-to-good agreement was reached between CTEPH-non-expert readers and the experts' consensus (k-statistics 0.46; 0.61) at slightly lower sensitivities. The CTEPH-non-expert readers had moderate agreement on the presence of CTEPH (κ-statistic 0.38), but both correctly identified most cases (80% and 88%, respectively). CONCLUSIONS: Concomitant signs of CTEPH were poorly documented in daily practice, while most CTEPH patients were identified by CTEPH-non-expert readers after dedicated instruction. These findings underline the feasibility of achieving earlier CTEPH diagnosis by assessing CTPAs more attentively.

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.

Detection of upper extremity deep vein thrombosis by magnetic resonance non-contrast thrombus imaging.

BACKGROUND: Compression ultrasonography (CUS) is the first-line imaging test for diagnosing upper extremity deep vein thrombosis (UEDVT), but often yields inconclusive test results. Contrast venography is still considered the diagnostic standard but is an invasive technique. OBJECTIVES: We aimed to determine the diagnostic accuracy of magnetic resonance noncontrast thrombus imaging (MR-NCTI) for the diagnosis of UEDVT. METHODS: In this international multicenter diagnostic study, we prospectively included patients with clinically suspected UEDVT who were managed according to a diagnostic algorithm that included a clinical decision rule (CDR), D-dimer test, and diagnostic imaging. UEDVT was confirmed by CUS or (computed tomography [CT]) venography. UEDVT was excluded by (1) an unlikely CDR and normal D-dimer, (2) a normal serial CUS or (3) a normal (CT) venography. Within 48 h after the final diagnosis was established, patients underwent MR-NCTI. MR-NCTI images were assessed post hoc by two independent radiologists unaware of the presence or absence of UEDVT. The sensitivity, specificity, and interobserver agreement of MR-NCTI for UEDVT were determined. RESULTS: Magnetic resonance noncontrast thrombus imaging demonstrated UEDVT in 28 of 30 patients with UEDVT and was normal in all 30 patients where UEDVT was ruled out, yielding a sensitivity of 93% (95% CI 78-99) and specificity of 100% (95% CI 88-100). The interobserver agreement of MR-NCTI had a kappa value of 0.83 (95% CI 0.69-0.97). CONCLUSIONS: Magnetic resonance noncontrast thrombus imaging is an accurate and reproducible method for diagnosing UEDVT. Clinical outcome studies should determine whether MR-NCTI can replace venography as the second-line imaging test in case of inconclusive CUS.

[Diagnosis of recurrent venous thromboembolism]. / Diagnostiek van een recidief veneuze trombo-embolie.

A correct diagnosis of recurrent venous thromboembolism (VTE) is essential as patients diagnosed with a recurrence are mostly treated with lifelong anticoagulant treatment. However, the diagnosis of recurrent VTE is complex as routine diagnostic tests for suspected VTE are less accurate in patients without a prior VTE. Clinical decision rules (CDR) and D-dimer tests have a lower specificity in suspected recurrent VTE, leading to an increase in required diagnostic imaging tests. In contrast to suspected recurrent pulmonary embolism (PE), the safety of a CDR and D-dimer test in excluding recurrent deep vein thrombosis (DVT) is debated. A CDR in combination with D-dimer testing followed by computed tomography pulmonary angiography is the preferred diagnostic management for suspected recurrent PE. In suspected recurrent DVT, compression ultrasonography is the imaging technique of choice and in case of a suspected recurrent ipsilateral DVT and an inconclusive ultrasonography, magnetic resonance direct thrombus imaging is decisive.

Reduced scan time and superior image quality with 3D flow MRI compared to 4D flow MRI for hemodynamic evaluation of the Fontan pathway.

Long scan times prohibit a widespread clinical applicability of 4D flow MRI in Fontan patients. As pulsatility in the Fontan pathway is minimal during the cardiac cycle, acquiring non-ECG gated 3D flow MRI may result in a reduction of scan time while accurately obtaining time-averaged clinical parameters in comparison with 2D and 4D flow MRI. Thirty-two Fontan patients prospectively underwent 2D (reference), 3D and 4D flow MRI of the Fontan pathway. Multiple clinical parameters were assessed from time-averaged flow rates, including the right-to-left pulmonary flow distribution (main endpoint) and systemic-to-pulmonary collateral flow (SPCF). A ten-fold reduction in scan time was achieved [4D flow 15.9 min (SD 2.7 min) and 3D flow 1.6 min (SD 7.8 s), p < 0.001] with a superior signal-to-noise ratio [mean ratio of SNRs 1.7 (0.8), p < 0.001] and vessel sharpness [mean ratio 1.2 (0.4), p = 0.01] with 3D flow. Compared to 2D flow, good-excellent agreement was shown for mean flow rates (ICC 0.82-0.96) and right-to-left pulmonary flow distribution (ICC 0.97). SPCF derived from 3D flow showed good agreement with that from 4D flow (ICC 0.86). 3D flow MRI allows for obtaining time-averaged flow rates and derived clinical parameters in the Fontan pathway with good-excellent agreement with 2D and 4D flow, but with a tenfold reduction in scan time and significantly improved image quality compared to 4D flow.

Dobutamine stress testing for the evaluation of atrial and diastolic ventricular function in Fontan patients.

OBJECTIVE: To assess the atrial and ventricular diastolic function response to dobutamine stress in Fontan patients, and to relate these measurements to exercise capacity and events during the follow-up. METHODS: We performed a secondary analysis of a cross-sectional multicentre study of Fontan patients with intra-atrial lateral tunnel (ILT) or extracardiac conduit (ECC) modification. Subjects underwent cardiac MRI during rest and low-dose dobutamine stress, and cardiopulmonary exercise testing. Atrial and diastolic ventricular function parameters were derived from volume-time curves.Medical records were abstracted for a composite end-point of death, listing for transplant, arrhythmia and reintervention. Spearman's r correlation tests and Cox proportional hazards models were used to assess the relation between the dobutamine response for atrial and diastolic ventricular function and outcomes, including exercise capacity. RESULTS: We included 57 patients (26 ECC; 31 ILT) aged 12.8 (IQR (10.3-15.5)) years. During dobutamine stress atrial cyclic volume change increased (3.0 (0.4-5.9) mL/m2, p<0.001), as did early (1.9 (-1.6 to 3.6) mL/m2, p=0.001) and late emptying volume (2.2 (0.2-4.4) mL/m2, p<0.001).Ventricular early filling decreased (-1.6 (-5.7 to 0.7) mL/m2,p=0.046) and ventricular late filling increased (1.0 (-0.4 to 3.4) mL/m2,p<0.001) while stroke volume remained similar.Only for patients with the ECC modification, atrial early emptying volume increase correlated with peak oxygen uptake (ρ=0.66,p=0.002). No other parameter related to exercise capacity.During a median 7.1-year follow-up, 22 patients reached the composite endpoint. No parameter predicted events during the follow-up. CONCLUSIONS: Dobutamine stress augmented atrial reservoir and pump function for Fontan patients. Atrial early emptying reserve related to exercise capacity in ECC patients. No other atrial or diastolic ventricular function parameter related to outcomes.

Cost-effectiveness of magnetic resonance imaging for diagnosing recurrent ipsilateral deep vein thrombosis.

The diagnostic workup of recurrent ipsilateral deep vein thrombosis (DVT) using compression ultrasonography (CUS) can be complicated by persistent intravascular abnormalities after a previous DVT. We showed that magnetic resonance direct thrombus imaging (MRDTI) can exclude recurrent ipsilateral DVT. However, it is unknown whether the application of MRDTI in daily clinical practice is cost effective. The aim of this study was to evaluate the cost effectiveness of MRDTI-based diagnosis for suspected recurrent ipsilateral DVT during first year of treatment and follow-up in the Dutch health care setting. Patient-level data of the Theia study (NCT02262052) were analyzed in 10 diagnostic scenarios, including a clinical decision rule and D-dimer test and imaging with CUS and/or MRDTI. The total costs of diagnostic tests and treatment during 1-year follow-up, including costs of false-positive and false-negative diagnoses, were compared and related to the associated mortality. The 1-year health care costs with MRDTI (range, €1219-1296) were generally lower than strategies without MRDTI (range, €1278-1529). This was because of superior specificity, despite higher initial diagnostic costs. Diagnostic strategies including CUS alone and CUS followed by MRDTI in case of an inconclusive CUS were potential optimal cost-effective strategies, with estimated average costs of €1529 and €1263 per patient and predicted mortality of 1 per 737 patients and 1 per 609 patients, respectively. Our model shows that diagnostic strategies with MRDTI for suspected recurrent ipsilateral DVT have generally lower 1-year health care costs than strategies without MRDTI. Therefore, compared with CUS alone, applying MRDTI did not increase health care costs.

Computed Tomography Pulmonary Perfusion for Prediction of Short-Term Clinical Outcome in Acute Pulmonary Embolism.

Background Computed tomography pulmonary angiography (CTPA) is the imaging modality of choice for the diagnosis of acute pulmonary embolism (PE). With computed tomography pulmonary perfusion (CTPP) additional information on lung perfusion can be assessed, but its value in PE risk stratification is unknown. We aimed to evaluate the correlation between CTPP-assessed perfusion defect score (PDS) and clinical presentation and its predictive value for adverse short-term outcome of acute PE. Patients and Methods This was an exploratory, observational study in 100 hemodynamically stable patients with CTPA-confirmed acute PE in whom CTPP was performed as part of routine clinical practice. We calculated the difference between the mean PDS in patients with versus without chest pain, dyspnea, and hemoptysis and 7-day adverse outcome. Multivariable logistic regression analysis and likelihood-ratio test were used to assess the added predictive value of PDS to CTPA parameters of right ventricle dysfunction and total thrombus load, for intensive care unit admission, reperfusion therapy and PE-related death. Results We found no correlation between PDS and clinical symptoms. PDS was correlated to reperfusion therapy ( n = 4 with 16% higher PDS, 95% confidence interval [CI]: 3.5-28%) and PE-related mortality ( n = 2 with 22% higher PDS, 95% CI: 4.9-38). Moreover, PDS had an added predictive value to CTPA assessment for PE-related mortality (from Chi-square 14 to 19, p = 0.02). Conclusion CTPP-assessed PDS was not correlated to clinical presentation of acute PE. However, PDS was correlated to reperfusion therapy and PE-related mortality and had an added predictive value to CTPA-reading for PE-related mortality; this added value needs to be demonstrated in larger studies.