Background Chronic thromboembolic pulmonary hypertension (CTEPH) is the most severe long-term complication of acute pulmonary embolism (PE). We aimed to evaluate the impact of a symptom screening... Show moreBackground Chronic thromboembolic pulmonary hypertension (CTEPH) is the most severe long-term complication of acute pulmonary embolism (PE). We aimed to evaluate the impact of a symptom screening programme to detect CTEPH in PE survivors.Methods This was a multicentre cohort study of patients diagnosed with acute symptomatic PE between January 2017 and December 2018 in 16 centres in Spain. Patients were contacted by phone 2 years after the index PE diagnosis. Those with dyspnoea corresponding to a New York Heart Association (NYHA)/WHO scale≥II, visited the outpatient clinic for echocardiography and further diagnostic tests including right heart catheterisation (RHC). The primary outcome was the new diagnosis of CTEPH confirmed by RHC.Results Out of 1077 patients with acute PE, 646 were included in the symptom screening. At 2 years, 21.8% (n=141) reported dyspnoea NYHA/WHO scale≥II. Before symptom screening protocol, five patients were diagnosed with CTEPH following routine care. In patients with NYHA/WHO scale≥II, after symptom screening protocol, the echocardiographic probability of pulmonary hypertension (PH) was low, intermediate and high in 76.6% (n=95), 21.8% (n=27) and 1.6% (n=2), respectively. After performing additional diagnostic test in the latter 2 groups, 12 additional CTEPH cases were confirmed.Conclusions The implementation of this simple strategy based on symptom evaluation by phone diagnosed more than doubled the number of CTEPH cases. Dedicated follow-up algorithms for PE survivors help diagnosing CTEPH earlier. Show less
Gleditsch, J.; Jervan, O.; Tavoly, M.; Geier, O.; Holst, R.; Klok, F.A.; ... ; Hopp, E. 2022
Background: Persistent dyspnea is a common symptom after pulmonary embolism (PE). However, the pathophysiology of persistent dyspnea is not fully clarified. This study aimed to explore possible... Show moreBackground: Persistent dyspnea is a common symptom after pulmonary embolism (PE). However, the pathophysiology of persistent dyspnea is not fully clarified. This study aimed to explore possible associations between diffuse myocardial fibrosis, as assessed by cardiac magnetic resonance (CMR) T1 mapping, and persistent dyspnea in patients with a history of PE.Methods: CMR with T1 mapping and extracellular volume fraction (ECV) calculations were performed after PE in 51 patients with persistent dyspnea and in 50 non-dyspneic patients. Patients with known pulmonary disease, heart disease and CTEPH were excluded.Results: Native T1 was higher in the interventricular septum in dyspneic patients compared to non-dyspneic patients; difference 13 ms (95% CI: 2-23 ms). ECV was also significantly higher in patients with dyspnea; difference 0.9 percent points (95% CI: 0.04-1.8 pp). There was no difference in native T1 or ECV in the left ventricular lateral wall. Native T1 in the interventricular septum had an adjusted Odds Ratio of 1.18 per 10 ms increase (95% CI: 0.99-1.42) in predicting dyspnea, and an adjusted Odds Ratio of 1.47 per 10 ms increase (95% CI: 1.10-1.96) in predicting Incremental Shuttle Walk Test (ISWT) score < 1020 m.Conclusion: Septal native T1 and ECV values were higher in patients with dyspnea after PE compared with those who were fully recovered suggesting a possible pathological role of myocardial fibrosis in the development of dyspnea after PE. Further studies are needed to validate our findings and to explore their pathophysiological role and clinical significance. Show less
Boon, G.J.A.M.; Ende-Verhaar, Y.M.; Bavalia, R.; Bouazzaoui, L.H. el; Delcroix, M.; Dzikowska-Diduch, O.; ... ; InShape II Study Grp 2021
Background The current diagnostic delay of chronic thromboembolic pulmonary hypertension (CTEPH) after pulmonary embolism (PE) is unacceptably long, causing loss of quality-adjusted life years and... Show moreBackground The current diagnostic delay of chronic thromboembolic pulmonary hypertension (CTEPH) after pulmonary embolism (PE) is unacceptably long, causing loss of quality-adjusted life years and excess mortality. Validated screening strategies for early CTEPH diagnosis are lacking. Echocardiographic screening among all PE survivors is associated with overdiagnosis and cost-ineffectiveness. We aimed to validate a simple screening strategy for excluding CTEPH early after acute PE, limiting the number of performed echocardiograms. Methods In this prospective, international, multicentre management study, consecutive patients were managed according to a screening algorithm starting 3 months after acute PE to determine whether echocardiographic evaluation of pulmonary hypertension (PH) was indicated. If the 'CTEPH prediction score' indicated high pretest probability or matching symptoms were present, the 'CTEPH rule-out criteria' were applied, consisting of ECG reading and N-terminalpro-brain natriuretic peptide. Only if these results could not rule out possible PH, the patients were referred for echocardiography. Results 424 patients were included. Based on the algorithm, CTEPH was considered absent in 343 (81%) patients, leaving 81 patients (19%) referred for echocardiography. During 2-year follow-up, one patient in whom echocardiography was deemed unnecessary by the algorithm was diagnosed with CTEPH, reflecting an algorithm failure rate of 0.29% (95% CI 0% to 1.6%). Overall CTEPH incidence was 3.1% (13/424), of whom 10 patients were diagnosed within 4 months after the PE presentation. Conclusions The InShape II algorithm accurately excluded CTEPH, without the need for echocardiography in the overall majority of patients. CTEPH was identified early after acute PE, resulting in a substantially shorter diagnostic delay than in current practice. Show less
Patients with lower leg cast immobilization or who had knee arthroscopy have an increased risk of venous thrombosis. Because of this increased risk, thromboprophylaxis was given to the majority of... Show morePatients with lower leg cast immobilization or who had knee arthroscopy have an increased risk of venous thrombosis. Because of this increased risk, thromboprophylaxis was given to the majority of these patients in the Netherlands, despite insufficient evidence for its effect. In this thesis, two large randomized controlled trials (including 1500 patients each, in which half of patients were randomized to prophylaxis with Low Molecular Weight Heparin (LMWH) and half of patients to no treatment) are described. Despite having an increased VTE risk, routine thromboprophylaxis with low dose LMWH did not decrease VTE risk in these patients. Therefore, we recommend no routine thromboprophylaxis with anticoagulants to these patients. Identification of high-risk patients and selective treatment of patients can be beneficial. Therefore, prediction models for the development of VTE in these patients were developed. The prediction models had good predictive value and were validated in two other studies. Hence, identification of high-risk patient can help to optimize prophylactic treatment: providing a higher dose or longer duration of anticoagulant treatment to patients with an additionally increased risk, whilst patients with a low risk will not be needlessly exposed to the burden and risk of anticoagulants. Show less
The objectives of this thesis are to simplify, to validate and compare diagnostic strategies in patients with clinical suspicion of acute pulmonary embolism (PE). The revised Geneva score was... Show moreThe objectives of this thesis are to simplify, to validate and compare diagnostic strategies in patients with clinical suspicion of acute pulmonary embolism (PE). The revised Geneva score was simplified and validated. Furthermore, four widely used clinical decision rules (CDRs) were directly compared in excluding PE. It was concluded that the four CDRs in combination with a D-dimer test performed similarly in the exclusion of acute PE. And we confirmed that a normal CT-scan alone can safely exclude PE in patients in whom CTPA is required to rule out VTE in these patients. We showed that the algorithm consisting of a CRD, D-dimer test and CT-scan is also effective in the management of patients with clinically suspected recurrent acute PE. In addition, the role of NT-pro-BNP has been evaluated for the risk assessment for adverse clinical outcome for patients with proven acute PE and we showed the ability to distinguish an increased risk with elevated NT-pro-BNP values for complications during the hospital stay and 30-day mortality. Finally, it is concluded that home treatment with anticoagulant seems effective and safe in patients with acute PE, when selected according to pre defined criteria. Show less
In the first part of this thesis we described two new diagnostic algorithms for patients with clinically suspected deep venous thrombosis and pulmonary embolism. These management strategies include... Show moreIn the first part of this thesis we described two new diagnostic algorithms for patients with clinically suspected deep venous thrombosis and pulmonary embolism. These management strategies include both pretest clinical probability and D-dimer assay, and reduce the need for non-invasive imaging tests. These novel strategies are safe in excluding deep venous thrombosis and pulmonary embolism. The results of the first part of this thesis led to a different, more simple diagnostic strategy in patients with venous thromboembolism. In the second part of this thesis we described two follow-up studies which led to the identification of new risk factors and early predictors for PTS. At present, the results of these studies enable us to provide individualized information to patients with a first deep venous thrombosis about their risk for the development of PTS. Future research should focus on validating and standardizing diagnostic criteria for PTS. A standardized diagnosis is necessary to improve the uniformity of the diagnosis and to enhance the ability to compare results of different studies. Moreover, objective diagnosis of PTS will allow physicians to monitor the development and course of PTS in their own patients. Show less
