Aims: To systematically assess late outcomes of acute pulmonary embolism (PE) and to investigate the clinical implications of post-PE impairment (PPEI) fulfilling prospectively defined criteria.... Show moreAims: To systematically assess late outcomes of acute pulmonary embolism (PE) and to investigate the clinical implications of post-PE impairment (PPEI) fulfilling prospectively defined criteria. Methods and results: A prospective multicentre observational cohort study was conducted in 17 large-volume centres across Germany. Adult consecutive patients with confirmed acute symptomatic PE were followed with a standardized assessment plan and pre-defined visits at 3, 12, and 24 months. The co-primary outcomes were (i) diagnosis of chronic thromboembolic pulmonary hypertension (CTEPH), and (ii) PPEI, a combination of persistent or worsening clinical, functional, biochemical, and imaging parameters during follow-up. A total of 1017 patients (45% women, median age 64 years) were included in the primary analysis. They were followed for a median duration of 732 days after PE diagnosis. The CTEPH was diagnosed in 16 (1.6%) patients, after a median of 129 days; the estimated 2-year cumulative incidence was 2.3% (1.2-4.4%). Overall, 880 patients were evaluable for PPEI; the 2-year cumulative incidence was 16.0% (95% confidence interval 12.8-20.8%). The PPEI helped to identify 15 of the 16 patients diagnosed with CTEPH during follow-up (hazard ratio for CTEPH vs. no CTEPH 393; 95% confidence interval 73-2119). Patients with PPEI had a higher risk of re-hospitalization and death as well as worse quality of life compared with those without PPEI. Conclusion: In this prospective study, the cumulative 2-year incidence of CTEPH was 2.3%, but PPEI diagnosed by standardized criteria was frequent. Our findings support systematic follow-up of patients after acute PE and may help to optimize guideline recommendations and algorithms for post-PE care. Show less
Introduction: We recently proposed a scale for assessment of patient-relevant functional limitations following an episode of venous thromboembolism (VTE). Further development of this post-VTE... Show moreIntroduction: We recently proposed a scale for assessment of patient-relevant functional limitations following an episode of venous thromboembolism (VTE). Further development of this post-VTE functional status (PVFS) scale is still needed.Methods: Guided by the input of VTE experts and patients, we refined the PVFS scale and its accompanying manual, and attempted to acquire broad consensus on its use.Results: A Delphi analysis was performed involving 53 international VTE experts with diverse scientific and clinical backgrounds. In this process, the number of scale grades of the originally proposed PVFS scale was reduced and descriptions of the grades were improved. After these changes, a consensus was reached on the number/definitions of the grades, and method/timing of the scale assessment. The relevance and potential impact of the scale was confirmed in three focus groups totaling 18 VTE patients, who suggested additional changes to the manual, but not to the scale itself. Using the improved manual, the.-statistics between PVFS scale self-reporting and its assessment via the structured interview was 0.75 (95%CI 0.58-1.0), and 1.0 (95%CI 0.83-1.0) between independent raters of the recorded interview of 16 focus groups members.Conclusion: We improved the PVFS scale and demonstrated broad consensus on its relevance, optimal grades, and methods of assessing among international VTE experts and patients. The interobserver agreement of scale grade assignment was shown to be good-to-excellent. The PVFS scale may become an important outcome measure of functional impairment for quality of patient care and in future VTE trials. Show less
Haemodynamic instability and right ventricular dysfunction are the key determinants of short-term prognosis in patients with acute pulmonary embolism (PE). Residual thrombi and persistent right... Show moreHaemodynamic instability and right ventricular dysfunction are the key determinants of short-term prognosis in patients with acute pulmonary embolism (PE). Residual thrombi and persistent right ventricular dysfunction may contribute to post-PE functional impairment, and influence the risk of developing chronic thromboembolic pulmonary hypertension. Patients with haemodynamic instability at presentation (high-risk PE) require immediate primary reperfusion to relieve the obstruction in the pulmonary circulation and increase the chances of survival. Surgical removal of the thrombi or catheter-directed reperfusion strategies is alternatives in patients with contraindications to systemic thrombolysis. For haemodynamically stable patients with signs of right ventricular overload or dysfunction (intermediate-risk PE), systemic standard-dose thrombolysis is currently not recommended, because the risk of major bleeding associated with the treatment outweighs its benefits. In such cases, thrombolysis should be considered only as a rescue intervention if haemodynamic decompensation develops. Catheter-directed pharmaco-logical and pharmaco-mechanical techniques ensure swift recovery of echocardiographic and haemodynamic parameters and may be characterized by better safety profile than systemic thrombolysis. For survivors of acute PE, little is known on the effects of reperfusion therapies on the risk of chronic functional and haemodynamic impairment. In intermediate-risk PE patients, available data suggest that systemic thrombolysis may have little impact on long-term symptoms and functional limitation, echocardiographic parameters, and occurrence of chronic thromboembolic pulmonary hypertension. Ongoing and future interventional studies will clarify whether 'safer' reperfusion strategies may improve early clinical outcomes without increasing the risk of bleeding and contribute to reducing the burden of long-term complications after intermediate-risk PE. Show less
IntroductionSymptoms and functional limitation are frequently reported by survivors of acute pulmonary embolism (PE). However, current guidelines provide no specific recommendations on which... Show moreIntroductionSymptoms and functional limitation are frequently reported by survivors of acute pulmonary embolism (PE). However, current guidelines provide no specific recommendations on which patients should be followed after acute PE, when follow-up should be performed, and which tests it should include. Definition and classification of late PE sequelae are evolving, and their predictors remain to be determined.MethodsIn a post hoc analysis of the Pulmonary Embolism Thrombolysis (PEITHO) trial, we focused on 219 survivors of acute intermediate-risk PE with clinical and echocardiographic follow-up 6 months after randomisation as well as over the long term (median, 3years after acute PE). The primary outcome was a composite of (1) confirmed chronic thromboembolic pulmonary hypertension (CTEPH) or (2) post-PE impairment' (PPEI), defined by echocardiographic findings indicating an intermediate or high probability of pulmonary hypertension along with New York Heart Association functional class II-IV.ResultsConfirmed CTEPH or PPEI occurred in 29 (13.2%) patients, (6 with CTEPH and 23 with PPEI). A history of chronic heart failure at baseline and incomplete or absent recovery of echocardiographic parameters at 6 months predicted CTEPH or PPEI at long-term follow-up.ConclusionsCTEPH or PPEI occurs in almost one out of seven patients after acute intermediate-risk PE. Six-month echocardiographic follow-up may be useful for timely detection of late sequelae. Show less
This thesis describes the diagnostic management, short term prognosis and long term complications of pulmonary embolism. We have validated a newly derived clinical decision rule, the revised Geneva... Show moreThis thesis describes the diagnostic management, short term prognosis and long term complications of pulmonary embolism. We have validated a newly derived clinical decision rule, the revised Geneva score, for predicting the pre-test probability of having acute pulmonary embolism. This rule can be used in clinical practice to managge patients with suspected pulmonary embolism. We further found that NT-pro-BNp levels are the best predictors of benign clinical course, when compared to troponin and D-dimer levels, and CT derived maesurements of the right ventricular volume and function. Finally, we demonstrate that although the incidence of chronic thromboembolic pulmonary hypertension after acute pulmonary embolism is very low, the long term clinical course after pulmonary embolism is complicated frequently by mortalitity, recurrent venous thombosis, newly diagnosed maligancies and arterial cardiovascular events. Show less
