Background: Expert reading often reveals radiological signs of chronic thromboembolic pulmonary hypertension (CTEPH) or chronic PE on computed tomography pulmonary angiography (CTPA) performed at... Show moreBackground: 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 (kstatistics 0.46; 0.61) at slightly lower sensitivities. The CTEPH-non-expert readers had moderate agreement on the presence of CTEPH (Kappa-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. Show less
Background: The Post-Pulmonary Embolism Syndrome (PPES) comprises heterogeneous entities, including chronic thromboembolic disease with/without pulmonary hypertension (CTEPH/CTEPD), and... Show moreBackground: 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. Show less
Boon, G.J.A.M.; Hout, W.B. van den; Barco, S.; Bogaard, H.J.; Delcroix, M.; Huisman, M.V.; ... ; Klok, F.A. 2021
Background Diagnostic delay of chronic thromboembolic pulmonary hypertension (CTEPH) exceeds 1 year, contributing to higher mortality. Health economic consequences of late CTEPH diagnosis are... Show moreBackground Diagnostic delay of chronic thromboembolic pulmonary hypertension (CTEPH) exceeds 1 year, contributing to higher mortality. Health economic consequences of late CTEPH diagnosis are unknown. We aimed to develop a model for quantifying the impact of diagnosing CTEPH earlier on survival, quality-adjusted life-years (QALYs) and healthcare costs.Material and methods A Markov model was developed to estimate lifelong outcomes, depending on the degree of delay. Data on survival and quality of life were obtained from published literature. Hospital costs were assessed from patient records (n=498) at the Amsterdam UMC - VUmc, which is a Dutch CTEPH referral center. Medication costs were based on a mix of standard medication regimens.Results For 63-year-old CTEPH patients with a 14-month diagnostic delay of CTEPH (median age and delay of patients in the European CTEPH Registry), lifelong healthcare costs were estimated at EUR 117100 for a mix of treatment options. In a hypothetical scenario of maximal reduction of current delay, improved survival was estimated at a gain of 3.01 life-years and 2.04 QALYs. The associated cost increase was EUR 44654, of which 87% was due to prolonged medication use. This accounts for an incremental cost-utility ratio of EUR 21900/QALY.Conclusion Our constructed model based on the Dutch healthcare setting demonstrates a substantial health gain when CTEPH is diagnosed earlier. According to Dutch health economic standards, additional costs remain below the deemed acceptable limit of EUR 50000/QALY for the particular disease burden. This model can be used for evaluating cost-effectiveness of diagnostic strategies aimed at reducing the diagnostic delay. Show less
Residual pulmonary hypertension is an important sequela after pulmonary endarterectomy for chronic thromboembolic pulmonary hypertension. Recurrent thrombosis or embolism could be a contributor to... Show moreResidual pulmonary hypertension is an important sequela after pulmonary endarterectomy for chronic thromboembolic pulmonary hypertension. Recurrent thrombosis or embolism could be a contributor to this residual pulmonary hypertension but the potential extent of its role is unknown in part because data on incidence are lacking. We aimed to analyze the incidence of new intravascular abnormalities after pulmonary endarterectomy and determine hemodynamic and functional implications. A total of 33 chronic thromboembolic pulmonary hypertension patients underwent routine CT pulmonary angiography before and six months after pulmonary endarterectomy, together with right heart catheterization and exercise testing. New vascular lesions were defined as (1) a normal pulmonary artery before pulmonary endarterectomy and containing a thrombus, web, or early tapering six months after pulmonary endarterectomy or (2) a pulmonary artery already containing thrombus, web, or early tapering at baseline, but increasing six months after pulmonary endarterectomy. Nine of 33 (27%) chronic thromboembolic pulmonary hypertension patients showed new vascular lesions on CT pulmonary angiography six months after pulmonary endarterectomy. In a subgroup of patients undergoing CT pulmonary angiography 18 months after pulmonary endarterectomy, no further changes in lesions were noted. Hemodynamic and functional outcomes were not different between patients with and without new vascular lesions. New vascular lesions are common after pulmonary endarterectomy for chronic thromboembolic pulmonary hypertension; currently their origin, dynamics, and long-term consequences remain unknown. Show less
BackgroundThe pathophysiology of chronic thromboembolic pulmonary hypertension (CTEPH) is not fully understood. Poor-quality anticoagulation may contribute to a higher risk of CTEPH after acute... Show moreBackgroundThe pathophysiology of chronic thromboembolic pulmonary hypertension (CTEPH) is not fully understood. Poor-quality anticoagulation may contribute to a higher risk of CTEPH after acute pulmonary embolism (PE), partly explaining the transition from acute PE to CTEPH. We assessed the association between the time in therapeutic range (TTR) of vitamin-K antagonist (VKA) treatment and incidence of CTEPH after a PE diagnosis.MethodsCase-control study in which the time spent in, under and above therapeutic range was calculated in 44 PE patients who were subsequently diagnosed with CTEPH (cases). Controls comprised 150 consecutive PE patients in whom echocardiograms two years later did not show pulmonary hypertension. All patients were treated with VKA for at least 6 months after the PE diagnosis. Time in (TTR), under and above range were calculated. Mean differences between cases and controls were estimated by linear regression.ResultsMean TTR during the initial 6-month treatment period was 72% in cases versus 78% in controls (mean difference -6%, 95%CI -12 to -0.1), mainly explained by more time above the therapeutic range in the cases. Mean difference of time under range was 0% (95%CI -6 to 7) and 2% (95CI% -3 to 7) during the first 3 and 6 months, respectively. In a multivariable model, adjusted odds ratios (ORs) for CTEPH were around unity considering different thresholds for 'poor anticoagulation', i.e. TTR <50%, <60% and <70%.ConclusionSubtherapeutic initial anticoagulation was not more prevalent among PE patients diagnosed with CTEPH than in those who did not develop CTEPH. Show less
BACKGROUND: Between 16% and 51% of patients with chronic thromboembolic pulmonary hypertension will have residual pulmonary hypertension (PH) after pulmonary endarterectomy (PEA). Whether residual... Show moreBACKGROUND: Between 16% and 51% of patients with chronic thromboembolic pulmonary hypertension will have residual pulmonary hypertension (PH) after pulmonary endarterectomy (PEA). Whether residual PH is related to remaining (sub-)segmental macrovascular lesions or to microvascular disease is unknown. New imaging techniques can provide detailed information about (sub-)segmental pulmonary arteries and parenchymal perfusion. The aim of this study was to describe the prevalence after PEA of remaining (sub-)segmental vascular lesions on electrocardiogram-gated computed tomography pulmonary angiography (CTPA) and parenchymal hypoperfusion on magnetic resonance imaging (MRI) and to relate these imaging abnormalities to the presence or absence of residual PH after PEA.METHODS: In a prospective cohort of patients with operable chronic thromboembolic pulmonary hypertension, hemodynamics, CTPA, and lung perfusion MRI were performed before and 6 months after PEA. The percentage of (sub-)segmental vascular lesions was calculated on CTPA and parenchymal hypoperfusion on lung perfusion MRI.RESULTS: PEA led to significant improvements in hemodynamics and a reduction of imaging abnormalities. Residual PH was present in 45% of patients after PEA, whereas remaining (sub-)segmental vascular lesions and parenchymal hypoperfusion were present in 20% and 21% of the pulmonary vasculature, respectively. Patients with and without residual PH after PEA had similar percentages of remaining (sub-)segmental vascular lesions (25% +/- 14% vs 17% +/- 15%; p = 0.16) and similar degrees of parenchymal hypoperfusion (20% +/- 7% vs 19% +/- 6%; p = 0.63).CONCLUSIONS: After successful PEA, advanced imaging shows that around 20% of the pulmonary vasculature remains abnormal, independent of the presence of residual PH. This may suggest that microvascular disease, rather than residual macrovascular lesions, plays a prominent role in residual PH after PEA. (C) 2019 International Society for Heart and Lung Transplantation. All rights reserved. Show less
Rijken, J.A.; Vos, B. de; Leemans, C.R.; Zwezerijnen, G.J.C. ben; Graaf, P. de; Hensen, E.F.; ... ; Symersky, P. 2020
Management of functional intrathoracic sympathetic paragangliomas in succinate dehydrogenase subunit D (SDHD) mutation carriers is challenging, and there is no uniform guideline for treatment to... Show moreManagement of functional intrathoracic sympathetic paragangliomas in succinate dehydrogenase subunit D (SDHD) mutation carriers is challenging, and there is no uniform guideline for treatment to date. The risks of potential malignant behavior and long-term cardiovascular morbidity have to be weighed against the risks of treatment complications. We report the multidisciplinary and shared decision-making approach that resulted in successful surgical removal of 3 paragangliomas in a SDHD mutation carrier. (C) 2020 by The Society of Thoracic Surgeons Show less
Objective Little is known about the prevalence and degree of deformation of surgically implanted aortic biological valve prostheses (bio-sAVRs). We assessed bio-sAVR deformation using multidetector... Show moreObjective Little is known about the prevalence and degree of deformation of surgically implanted aortic biological valve prostheses (bio-sAVRs). We assessed bio-sAVR deformation using multidetector-row computed tomography (MDCT). Methods Three imaging databases were searched for patients with MDCT performed after bio-sAVR implantation. Minimal and maximal valve ring diameters were obtained in systole and/or diastole, depending on the acquired cardiac phase(s). The eccentricity index (EI) was calculated as a measure of deformation as (1 - (minimal diameter/maximal diameter)) x 100%. EI of < 5% was considered none or trivial deformation, 5-10% mild deformation, and > 10% non-circular. Indications for MDCT and implanted valve type were retrieved. Results One hundred fifty-two scans of bio-sAVRs were included. One hundred seventeen measurements were performed in systole and 35 in diastole. None or trivial deformation (EI < 5%) was seen in 67/152 (44%) of patients. Mild deformation (EI 5-10%) was seen in 59/152 (39%) and non-circularity was found in 26/152 (17%) of cases. Overall, median EI was 5.5% (IQR 3.4-7.8). In 77 patients, both systolic and diastolic measurements were performed from the same scan. For these scans, the median EI was 6.5% (IQR 3.4-10.2) in systole and 5.1% (IQR3.1-7.6) in diastole, with a significant difference between both groups (p = 0.006). Conclusions Surgically implanted aortic biological valve prostheses show mild deformation in 39% of cases and were considered non-circular in 17% of studied valves. Show less
BACKGROUND: Chronic thromboembolic pulmonary hypertension (CTEPH) is often diagnosed after a long delay, even though signs may already be present on the computed tomography pulmonary angiogram ... Show moreBACKGROUND: Chronic thromboembolic pulmonary hypertension (CTEPH) is often diagnosed after a long delay, even though signs may already be present on the computed tomography pulmonary angiogram (CTPA) used to diagnose a preceding acute pulmonary embolism (PE). In this setting of suspected acute PE, we evaluated the diagnostic accuracy of dedicated CTPA reading for the diagnosis of already existing CTEPH.METHODS: Three blinded expert radiologists scored radiologic signs of CTEPH on initial CTPA scans with confirmed acute PE in 50 patients who were subsequently diagnosed with CTEPH during follow-up (cases), and in 50 patients in whom sequential echocardiograms performed >2 years after the acute PE diagnosis did not show any signs of pulmonary hypertension (controls). All 50 control index CTPA scans had signs of right ventricular (RV) overload. Sensitivity and specificity of expert CTPA reading was calculated, and best-predicting radiologic parameters were identified.RESULTS: The overall expert reading yielded a sensitivity of 72% (95% confidence interval [CI] 58%-84%) and a specificity of 94% (95% CI 83%-99%) for CTEPH diagnosis. Multivariate analysis identified 6 radiologic parameters as independent predictors: intravascular webs; pulmonary artery retraction or dilatation; bronchial artery dilatation; right ventricular (RV) hypertrophy; and interventricular septum flattening. The presence of 3 or more these parameters was associated with a sensitivity of 70% (95% CI 55%-82%), a specificity of 96% (95% CI 86%-100%), and a c-statistic of 0.92.CONCLUSIONS: Standardized reading of CTPA scans performed for acute PE can be useful for the diagnosis of CTEPH when structured identification of 6 characteristics is employed during interpretation. The use of this strategy may help reduce diagnostic delay of CTEPH. (C) 2019 International Society for Heart and Lung Transplantation. All rights reserved. Show less
