Episode Of Acute Pulmonary Embolism Research Articles

SCUBE1 promotes pulmonary artery smooth muscle cell proliferation and migration in acute pulmonary embolism by modulating BMP7.

After an episode of acute pulmonary embolism (APE), activated platelets have the ability to release various bioactive factors that can stimulate both proliferation and migration of pulmonary artery smooth muscle cells (PASMCs). SCUBE1 has been previously reported to engage in platelet-platelet interactions, potentially contributing to the activation of platelets in early onset thrombi. The purpose of this study was to examine the alterations in SCUBE1 expression in PASMCs after APE, as well as understand the mechanism behind these changes. The platelet-rich plasma samples of both APE patients and healthy individuals were collected. A hyperproliferative model of PASMCs was established by using platelet-derived growth factor (PDGF) as a stimulator and various assays were used to investigate how SCUBE1-mediated BMP7 can regulate PDGF-induced PASMC proliferation and migration. Elevated level of SCUBE1 were observed in platelet-rich plasma from patients with APE and in PASMCs induced by PDGF. SCUBE1 interference ameliorated PDGF-driven cell proliferation and migration, and also downregulated PCNA expression. Additionally, mechanistic studies demonstrated that SCUBE1 could directly bind to bone morphogenetic protein 7 (BMP7) and enhance BMP7 expression, which completely abolished the impact of SCUBE1 silencing on proliferation and migration ability of PASMCs after PDGF treatment. In the PDGF-induced proliferation of PASMCs, the expression of SCUBE1 and BMP7 was upregulated. Silencing of SCUBE1 impeded PDGF-induced proliferation and migration of PASMCs by restraining BMP7.

Acute Pulmonary Embolism and Immunity in Animal Models.

Venous thromboembolism, encompassing acute pulmonary embolism (APE) and deep vein thrombosis (DVT), is a potentially fatal disease with complex pathophysiology. Traditionally, the Virchow triad provided a framework for understanding the pathogenic contributors to thrombus formation, which include endothelial dysfunction, alterations in blood flow and blood hypercoagulability. In the last years, it has become apparent that immunity plays a central role in thrombosis, interacting with classical prothrombotic mechanisms, oxidative stress and vascular factors. Thrombosis amplifies inflammation, and exaggerated inflammatory processes can trigger thrombosis mainly due to the activation of leukocytes, platelets, and endothelial cells. APE-related endothelium injury is a major trigger for immune system activation. Endothelium is also a key component mediating inflammatory reaction and it is relevant to maintain vascular permeability. Exaggerated right ventricular wall stress and overload, with coexisting systemic hypotension and hypoxemia, result in myocardial injury and necrosis. Hypoxia, tissue factor activation and cytokine storm are engaged in the thrombo-inflammatory processes. Thrombus development is characterized by inflammatory state vascular wall caused mainly by an early extravasation of leukocytes and intense selectins and cytokines production. Nevertheless, immunity of DVT is well described, little is known about potential chemokine and cellular differences between thrombus that develops in the vein and thrombus that detaches and lodges in the pulmonary circulation being a cause of APE. There is a paucity of data considering inflammatory state in the pulmonary artery wall during an acute episode of pulmonary embolism. The main aim of this review is to summarize the knowledge of immunity in acute phase of pulmonary embolism in experimental models.

5-year outcomes of pulmonary embolism patients according to symptoms at 6-month: the QOLAPE study

Abstract Funding Acknowledgements Type of funding sources: Public hospital(s). Main funding source(s): CHU Toulouse Rangueil Background Venous thromboembolic disease is a common cardiovascular disease, but long-term data on patient survival according to mid-term symptoms are scarce. Objective To describe outcomes (mortality and functional status) of pulmonary embolism (PE) 5 years after a first inaugural symptomatic episode of acute PE according to symptoms persistence at 6-months. Methods 137 patients with acute symptomatic PE were consecutively recruited at a French University Hospital from 2015 to 2017. Clinical characteristics were compared at 5-years between patients with persistent respiratory symptoms and asymptomatic patients at 6-month. Telephone collection of vital status, recurrence of VTE, NYHA score, current treatment, bleeding events as well as follow-up provided by a specialist were carried out in March 2022 on 105 patients (11% were lost of follow up). Results Patients were predominantly male (n=63, 57.5%) 60.2 yo. PE was initially classified at low, intermediate low, intermediate high and high risk respectively in 42.8, 25.7, 30.5 and 1%. 60 patients (57%) were symptomatics at 6 months. At 5 years, survival was 87.1% with a 17.7% recurrence rate regardless of initial PE presentation and severity, and 50% of patients remain symptomatic. Age, hypertension, diabetes, renal failure, obesity and the existence of a psychiatric pathology are associated with a higher mortality at 5 years. The survival and recurrence of MTVE at 5 years are similar between symptomatic or asymptomatic status at 6 months but symptomatic patients at 6 months are twice as many symptomatic at 5 years than asymptomatic patients at 6 months. Conclusion After an inaugural acute symptomatic PE is 5-year survival was 87%. Age, obesity, diabetes, renal failure, hypertension and the existence of an underlying psychiatric pathology are associated with a poorer prognosis at 5 years. The persistence of symptoms at 6 months of PE was not correlated with survival or recurrence of VTE at 5 years but at the persistence of symptoms at 5 years.

Keep minds opening for chronic thromboembolic pulmonary hypertension: More data, less clarity

Chronic thromboembolic pulmonary hypertension (CTEPH) is a rare sequelae of pulmonary embolism (PE), resulting from persistent obstruction of pulmonary arteries with non‐resolving thromboemboli and consecutive pulmonary small‐vessel remodeling.1,2 From the landmark research by Pengo et al.3 reporting that the cumulative incidence of CTEPH after acute episode of PE was 3.8% (95% confidence interval [CI] 1.1–6.5) at 2 years, subsequent studies reported a notable wide range of incidences, ranging from 0.1% to 11.8%,4,5 which keep the rationale of routine screening for CTEPH after an episode of PE in intense debate.

Decreased Haemoglobin Level Measured at Admission Predicts Long Term Mortality after the First Episode of Acute Pulmonary Embolism.

Background: Decreased hemoglobin concentration was reported to predict long term prognosis in patients various cardiovascular diseases including congestive heart failure and coronary artery disease. We hypothesized that hemoglobin levels may be useful for post discharge prognostication after the first episode of acute pulmonary embolism. Therefore, the aim of the current study was to evaluate a potential prognostic value of a decreased hemoglobin levels measured at admission due to the first episode of acute PE for post discharge all cause mortality during at least 2 years follow up. Methods: This was a prospective, single-center, follow-up, observational, cohort study of consecutive survivors of the first PE episode. Patients were managed according to ESC current guidelines. After the discharge, all PE survivors were followed for at least 24 months in our outpatient clinic. Results: During 2 years follow-up from the group of 402 consecutive PE survivors 29 (7.2%) patients died. Non-survivors were older than survivors 81 years (40−93) vs. 63 years (18−97) p < 0.001 presented higher sPESI 2 (0−4) vs. 1 (0−5), p < 0.001 driven by a higher frequency of neoplasms (37.9% vs. 16.6%, p < 0.001); and had lower hemoglobin (Hb) level at admission 11.7 g/dL (6−14.8) vs. 13.1 g/dL (3.1−19.3), p < 0.001. Multivariable analysis showed that only Hb and age significantly predicted all cause post-discharge mortality. ROC analysis for all cause mortality showed AUC for hemoglobin 0.688 (95% CI 0.782−0.594), p < 0.001; and for age 0.735 (95% CI 0.651−0.819) p < 0.001. A group of 59 subjects with hemoglobin < 10.5 g/dL showed mortality rate of 16.9% (OR for mortality 4.19 (95% CI 1.82−9.65), p-value < 0.00, while among 79 patients with Hb > 14.3 g/dL only one death was detected. Interestingly, patients in age > 64 years hemoglobin levels < 13.2 g/dL compared to patients in the same age but with >13.2 g/dL showed OR 3.6 with 95% CI 1.3−10.1 p = 0.012 for death after the discharge. Conclusions: Lower haemoglobin measured in the acute phase especially in patients in age above 64 years showed significant impact on the prognosis and clinical outcomes in PE survivors.

Predictors of 90-Day Mortality in Patients with Acute Pulmonary Embolism- a 5-Year Retrospective Cohort Study of Patients in One Canadian Health Region

BACKGROUND Acute pulmonary embolism (PE) can be fatal if not treated. PE is linked to major co-morbidities such as cancer and ischemic heart disease. Recurrence of PE may occur and is linked to high morbidity and death. Although acute PE is a common diagnosis, the incidence is still unknown in our health region. Published studies from other countries indicate an annual incidence between 0.2 and 0.8 /1000 persons, where the variation may be related to different inclusion criteria. Our knowledge about the association between concomitant diseases and PE and its outcomes is mostly based on data from clinical trials, and these patients may not fully represent real-life PE patients. This potentially limits our understanding of concomitant disorders that are associated to PE. We sought to determine 90-day survival and predictors of mortality for patients with acute PE in a real world setting. METHODS We retrospectively analyzed a cohort of adult outpatients aged ≥18 years with objectively confirmed acute PE between 2014 and 2019. PE was identified by positive diagnostic imaging from radiology reports obtained via search of the Picture Archiving and Communication System (PACS) database in the Eastern Health Region of Newfoundland and Labrador, Canada. We defined the clinical end-point as all-cause death within 90 days of PE diagnosis at a health facility in the health region. Cox-regression analysis was used to study the impact of patient characteristics and comorbidities on 90-day survival after the episode of acute PE. RESULTS A total of 1184 patients were identified as having acute PE between 2014 and 2019 within the Eastern Health Region. The annual incidence of PE among adults was estimated at 0.95/1000 persons. Of the total, 785 patients were diagnosed with acute PE as outpatients and were included in our study. Mean age was [SD] 63.4 ± 15.9 years, weight [SD] 92.0 ± 30.4 kilograms, and 42.3% were men. Patients were followed for 67274 person-days and 61 (7.8%) of outpatients died. Surgery ≤ 2 weeks prior to acute PE (44.6%), cancer (44.2%) and previous venous thromboembolism (15.2%) were most prevalent comorbid conditions among the patients [Table 1]. Male patients had a multivariate-adjusted hazard ratio (HR) of 5.63 (95% CI: 1.49 - 21.32); p = 0.011; 3.24 (95%CI: 1.47 - 7.14); p=0.004 and 2.48 (95% CI: 1.39-4.42); p=0.002 for 7, 30 and 90-day mortality respectively compared to females. Patients who had surgery ≤ 2 weeks prior to acute PE were associated with HR: 6.29 (95%CI: 1.31 - 30.29) p=0.0218; HR: 4.34 (95%CI: 1.79 - 10.48) p=0.001 and HR: 2.00 (95%CI: 1.18 - 3.52); p=0.010 higher risk of 7, 30 and 90 day-mortality, respectively. Having cancer was associated with increased risk of 30-day (HR: 6.13[95%CI: 1.81 - 20.72]; p=0.004) and 90-day (HR; 4.27 [95%CI: 1.87 - 9.72]; p<0.001) mortality. An increase in weight is associated with lower risk of 30 (HR; 0.95 [95%CI: 0.94 - 0.99]; p=0.007) and 90-day mortality (HR: 0.97[95%CI: 0.95 - 0.99]; p<0.001) respectively [Figure 1]. CONCLUSIONS Male sex, surgery ≤ 2 weeks prior to PE, cancer and weight are factors that predicted 90-mortality among patients with acute PE. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Acute on Chronic Thromboembolic Pulmonary Hypertension: Case Series and Review of Management.

Chronic thromboembolic pulmonary hypertension (CTEPH) is a distinct form of precapillary pulmonary hypertension classified as group 4 by the World Symposium on Pulmonary Hypertension (WSPH) and should be excluded during an episode of acute pulmonary embolism (PE). Patients presenting to emergency departments with sudden onset of signs and symptoms of acute PE may already have a pre-existing CTEPH condition decompensated by the new PE episode. Identifying an underlying and undiagnosed CTEPH during acute PE, while challenging, is an important consideration as it will alter the patients’ acute and long-term management. Differential diagnosis and evaluation require an interdisciplinary expert team. Analysis of the clinical condition, the CT angiogram, and the hemodynamic situation are important considerations; patients with CTEPH usually have significantly higher sPAP at the time of index PE, which is unusual and unattainable in the context of acute PE and a naïve right ventricle. The imaging may reveal signs of chronic disease such as right ventricle hypertrophy bronchial collaterals and atypical morphology of the thrombus. There is no standard for the management of acute on chronic CTEPH. Herein, we provide a diagnostic and management algorithm informed by several case descriptions and a review of the literature.

Mass-spectrometric identification of oxidative modifications in plasma-purified plasminogen: Association with hypofibrinolysis in patients with acute pulmonary embolism

ObjectivesMechanisms behind disturbed fibrinolysis in pulmonary embolism (PE) are poorly understood. We hypothesized that oxidative stress-induced changes in plasminogen contribute to impaired fibrinolysis in patients with acute PE. MethodsOxidative and other modifications were investigated using mass-spectrometry in plasminogen purified from pooled plasma of 5 acute PE patients on admission and after 3 months of anticoagulant treatment, along with plasma clot lysis time, a measure of global efficiency of fibrinolysis, and a stable oxidative stress marker, plasma 8-isoprostane. ResultsTwenty sites of oxidation, 3 sites of carbonylation and 4 sites of S-nitrosylation were identified in plasminogen. The intensity of peptides oxidized at cysteine residues with respect to unmodified peptides decreased after 3 months of anticoagulation (p = 0.018). This was not observed for oxidized methionine residues (p = 0.9). Oxidized tryptophan (n = 4) and proline (n = 2), as well as carbonylation at 3 threonine residues were selectively identified in acute PE episode, not after 3 months. This was accompanied by 12.8% decrease in clot lysis time (p = 0.043). Deamidation occurred at the arginine, previously identified to undergo the cleavage by plasminogen activator. Methylated were two lysine-binding sites important for an interaction of plasminogen with fibrin. Other identified modifications involved: glycation, acetylation, phosphorylation, homocysteinylation, carbamylation and dichlorination (88 modifications at 162 sites). ConclusionsData suggest that oxidative stress-induced changes in plasminogen molecules may contribute to less effective global fibrinolysis in patients with acute PE. The comprehensive library of posttranslational modifications in plasminogen molecules was provided, including modifications of sites reported to be involved in important biological functions.

P281 A CASE OF ACUTE PULMONARY EMBOLISM IN A PATIENT WITH CHRONIC THROMBOEMBOLIC PULMONARY HYPERTENSION MISSED: PROFITABLE COLLABORATION BETWEEN A SPOKE CENTER AND A HUB

Abstract The case of one patient is described: 78–year–old, obese, suffering from type II diabetes mellitus and arterial hypertension who complained of mild exertional dyspnea for one year. On ECG sinus rhythm 80 bpm, negative T wave from V1 to V4, right bundle branch block. He was sent to the emergency unit for further investigations. Here the blood chemistry results: D–dimer 1761 (normal &amp;lt;250 ng / ml), NT pro–BNP 9312 (normal &amp;lt;93 ng / l), troponin 21 (normal &amp;lt;14 ng / ml); pulmonary CT angiography demonstrated filling defects referable to bilateral lobar, segmental and subsegmental bilateral thromboembolism. The estimated PASP was 90 mmHg with AcT 55 msec and the presence of a mid–systolic notch on the pulmonary flow profile. A diagnosis of intermediate–high risk PE was made and, according to the local PDTA, written informed consent was obtained, the patient underwent treatment with percutaneous thrombectomy with loco–regional ultrasound–assisted thrombolysis (USAT–rtPA 24 mg in 12 hours). The RV / LV ratio was slightly reduced (1.1) and so was the estimated PASP (60 mmHg). He performed a lung perfusion scan with the detection of areas of diffuse pulmonary hypoperfusion. He was discharged on February 28, 2021, on therapy with Dabigatran 150 mg BID. 3 months later he carried out a cardiological check–up: he was in NYHA II class; the echocardiogram showed RV hypokinesia, TAPSE 15 mm, PASP 76 mmHg. In the suspicion of chronic thromboembolic pulmonary hypertension (CTEPH), he was sent to a HUB centre (Pavia) for a clinical assessment. Several tests were carried out to confirm the diagnosis of CTEPH and on 29 September 2021, the patient underwent bilateral pulmonary endarterectomy. Conclusion The case describes a patient with an episode of acute pulmonary embolism on a pre–existing unrecognized thromboembolic pulmonary hypertension, which partially benefited from percutaneous thrombectomy. Cases of CTEPH are infrequent; however, they must be recognized and sent, for a thorough evaluation, to an expert centre, to start the appropriate diagnostic therapeutic path, as in the case reported.

P210 VENTRICULAR FIBRILLATION IN AN ELDERLY WOMAN WITH APPARENTLY UNREMARKABLE PAST CARDIOLOGICAL HISTORY: AN UNEXPECTED CULPRIT

Abstract An 85–year–old woman experienced cardiac arrest while she was at the supermarket. Cardiopulmonary resuscitation was promptly performed with ROSC after DC shock on ventricular fibrillation and immediate hemodynamic and neurological recovery. The first ECG performed by the rescuers did not show acute ischemic changes and the patient was admitted to the Cardiological Intensive Care Unit. Past medical history revealed only a previous episode of acute pulmonary embolism for which she was on oral anticoagulant therapy for a limited period of time. She had not family history of sudden cardiac death or cardiomyopathies. Before admission she was completely asymptomatic and she never complained of angina pectoris, palpitation or dyspnoea. The echocardiogram at admission showed moderate left atrial enlargement and hypokinesia of left ventricle apex and mid–apical lateral wall with global EF of 50%. Pulmonary and aortic CT angiography showed no pathological findings. In order to rule out an ACS, the patient underwent a coronary angiography which documented the absence of critical coronary stenosis. Finally, a cardiac MRI with gadolinium was performed, revealing the presence of two small areas of transmural LGE affecting inferior basal and lateral mid–apical segments with no edema, consistent with ischaemic myocardial scars. In light of this findings and to rule out paradoxical coronary artery embolism we decided to perform a transcranial echocolordoppler that showed the absence of a patent foramen ovale. Furthermore, continuous ECG monitoring during the hospital stay did not document arrhythmic recurrences. In consideration of the high probability of ischemic heart disease, therapy with antiplatelet agent, beta–blocker, ace–inhibitor and statin was introduced and the patient was discharged after ICD implantation. Three months later, during her first follow–up visit, we documented short episodes of atrial fibrillation at ICD interrogation. This was in line with the hypothesis of a ventricular fibrillation and cardiac arrest in the contest of an ischemic heart disease with myocardial scars probably due to undatale coronary artery embolism. Oral anticoagulant therapy was started in addition to previous therapy.

Incidence and predictors of chronic thromboembolic pulmonary hypertension following acute pulmonary embolism: An echocardiography guided approach

There is significant variability in the worldwide epidemiology of chronic thromboembolic pulmonary hypertension (CTEPH). We thereby aim to determine the incidence and predictors of CTEPH, following an episode of acute pulmonary embolism (PE), using non-invasive modalities. Patients with acute PE were prospectively followed-up and after receiving at least 3 months of effective anticoagulation, persistently symptomatic patients with echocardiographic evidence of persistent pulmonary hypertension, were investigated further for CTEPH. Incidence of CTEPH was 8.19%. Delayed presentation, higher pulmonary artery pressures at presentation and discharge, and greater thrombotic burden were significant predictors for the development of CTEPH following acute PE.

Особливості клінічного перебігу та чинники, пов’язані з короткотерміновим прогнозом у хворих з тромбоемболією легеневої артерії

The aim – to study the clinical, anamnestic and instrumental parameters associated with short-term prognosis in patients with pulmonary embolism (PE). Materials and methods. This study was conducted from September 1, 2019 to December 31, 2020 on the basis of the city clinical hospital. The preliminary analysis included 187 patients with acute pulmonary embolism. The study found that 25 (13.3 %) patients died within 30 days (group I): 19 (76.0 %) patients belonged to a high risk of predicted early death and 6 (24.0 %) – to intermediate-high risk. For further analysis, a comparison group (group II) was formed and included 106 (56.7 %) patients who survived within 30 days of the onset of an acute episode of PE: 54 (50.9 %) patients belonged to high risk, 52 (49.1 %) – to intermediate high risk. All patients with pulmonary embolism received anticoagulant therapy according to the current ESC guidelines. Results. The average age of patients in group I was 69.08 ± 14.15 years and was significantly higher than in group II: 65.25 ± 13.29 (p = 0.0169). The proportion of high-risk patients was significantly greater in the І group, the proportion of patients of intermediate-high risk was significantly greater in group II (p = 0.0409). The incidence of classes IV and V according to the PESI index, assessed in patients of intermediate-high risk, was the same in both groups, while patients with the PESI index class III prevailed in group II (p = 0.0380). The risk factors for venous thromboembolism occurred more frequently in patients of group I, i.e. congestive heart failure (p = 0.0065) and obesity (p = 0.0482). Conclusions. There is a high mortality rate within 30 days (13.3 %) in hospitalized patients with acute PE, including 26 % of high-risk patients and 10.3 % of intermediate-high risk. Age over 65 years, the presence of congestive heart failure and obesity are independent factors that, according to uni- and multivariate logistic regression analysis, are associated with poor short-term prognosis in patients with PE. Key words: pulmonary embolism, venous thromboembolism, short-term prognosis, anticoagulant therapy.

Determinants and Management of the Post-Pulmonary Embolism Syndrome.

Acute pulmonary embolism (PE) is not only a serious and potentially life-threatening disease in the acute phase, in recent years it has become evident that it may also have a major impact on a patient's daily life in the long run. Persistent dyspnea and impaired functional status are common, occurring in up to 50% of PE survivors, and have been termed the post-PE syndrome (PPES). Chronic thromboembolic pulmonary hypertension is the most feared cause of post-PE dyspnea. When pulmonary hypertension is ruled out, cardiopulmonary exercise testing can play a central role in investigating the potential causes of persistent symptoms, including chronic thromboembolic pulmonary disease or other cardiopulmonary conditions. Alternatively, it is important to realize that post-PE cardiac impairment or post-PE functional limitations, including deconditioning, are present in a large proportion of patients. Health-related quality of life is strongly influenced by PPES, which emphasizes the importance of persistent limitations after an episode of acute PE. In this review, physiological determinants and the diagnostic management of persistent dyspnea after acute PE are elucidated.

Biomarkers of Thrombo-Inflammatory Responses in Pulmonary Embolism Patients With Pre-Existing Versus New-Onset Atrial Fibrillation.

Pulmonary embolism (PE) patients have an increased prevalence and incidence of atrial fibrillation (AF). Because comorbid AF increases risk of morbidity and mortality, we sought to investigate the role of thrombo-inflammatory biomarkers in risk stratifying patients who experience an acute PE episode. Study participants were enrolled from a Pulmonary Embolism Response Team (PERT) registry between March 2016 and March 2019 at Loyola University Medical Center and Gottlieb Memorial Hospital. This cohort was divided into 3 groups: PE patients with a prior diagnosis of AF (n = 8), PE patients with a subsequent diagnosis of AF (n = 11), and PE patients who do not develop AF (n = 71). D-dimer, CRP, PAI-1, TAFIa, FXIIIa, A2A, MP, and TFPI were profiled using the ELISA method. All biomarkers were significantly different between controls and PE patients (P < 0.05). Furthermore, TFPI was significantly elevated in PE patients who subsequently developed AF compared to PE patients who did not develop AF (157.7 ± 19.0 ng/mL vs. 129.0 ± 9.3 ng/mL, P = 0.0386). This study suggests that thrombo-inflammatory biomarkers may be helpful in indicating an acute PE episode. Also, elevated TFPI levels may be associated with an increased risk of developing AF after a PE.

Incidence and predictors of chronic thromboembolic pulmonary hypertension following first episode of acute pulmonary embolism.

Late obstructive pulmonary artery remodeling presented as CTEPH portends adverse sequelae and therapeutic challenges. Although progressive dyspnea on exertion beyond three-month period of treatment with anticoagulants is a diagnostic cornerstone, uncertainty still surrounds early identification and risk factors. We have conducted a prospective study among survivors of acute pulmonary embolism (PE) who were treated by anticoagulants for at least 3 months. Patients with preexisting pulmonary hypertension (PH), severe chronic obstructive pulmonary disease (COPD), and low ejection fraction (EF) in baseline echocardiography (EF < 30%) were excluded. Complete follow-up for 290 subjects were performed. According to a predetermined stepwise diagnostic protocol, patients with exertional Dyspnea and PH probable features in echocardiography underwent lung perfusion scan. Cumulative two-year incidence of CTEPH was 8.6% (n = 25). There was no patient with normal baseline right ventricular (RV) function in CTEPH group. In the same way, none of these patients had only segmental involvement in baseline CT angiography (CTA) in CTEPH group. Greater proportion of CTEPH group received fibrinolytic therapy, however the difference was not significant (2.6% vs 8 %, P = 0.16). Multivariate logistic regression demonstrated significant association of RV diameter, and PAP in baseline echocardiography as well as RV strain in CTA with development of CTEPH. Corresponding odds ratios were 1.147 (1.063-1.584) P < 0.0001) , 1.062 (1.019-1.106, P = 0.004), and 2.537 (1.041-6.674), P = 0.027), respectively. We found that incidence of CTEPH was relatively high in the present investigation. RV diameter, baseline PAP and RV dysfunction were independent predictors of CTEPH.

Differential effect of anticoagulant treatment on vascular morphology in patients with acute pulmonary embolism

Abstract Introduction Chronic thromboembolic pulmonary hypertension (CTEPH) is described as one of the most severe consequence of acute pulmonary embolism (APE). When signs of chronic PE are present on the CT pulmonary angiogram (CTPA) used to diagnose APE, the question arises whether there is underlying CTEPH. The relevance of chronic lesions, as well as the effect of anticoagulant treatment on their development is currently unknown. Purpose To investigate the effect of anticoagulant treatment on CTPA derived vascular morphological abnormalities in patients with APE. Methods We performed a case-cohort study. As cases, we selected CTEPH patients who had a prior history of a first APE episode. As cohort, we selected patients who had a follow-up CTPA performed 6 months after first episode APE in the context of a clinical trial (den Exter 2015). A baseline (i.e. at moment of APE diagnosis) CTPA and a follow-up CTPA was available for all patients. Experienced chest radiologists morphologically assessed 20 segmental pulmonary arteries per patient as “normal” or “affected” (as defined by a total occlusion by thrombus, central thrombus, mural thrombus, web or tapered pulmonary artery). Pulmonary segmental vessels of the entire cohort were merged for the analysis. All patients were treated adequately with anticoagulant treatment (vitamin K antagonists, direct oral anticoagulation or low molecular weight heparin) in the period between baseline and follow-up CTPA according to current guidelines. Results A total of 30 cases and 116 controls were included. Mean time between baseline and follow-up CTPA was 193 (62) days. At baseline CTPA, 1647 (56%) of the 2920 pulmonary segmental vessels were scored as affected. Almost all central thrombi resolved after oral anticoagulant treatment (1103/1191=93%). Webs (n=85) and tapered pulmonary arteries (n=57) did not change in morphology at follow-up (Figure 1). Most vessels containing a total occlusion by a thrombus at baseline resolved completely (156/280=56%), changed to a tapered pulmonary artery (26%) or became a web (7%). Mural thrombi either remained unchanged (16/34=47%), resolved completely (29%) or became a web (24%). Conclusion After anticoagulant treatment for APE almost all central thrombi completely resolved, whereas mural thrombi or total occlusions by thrombi either resolved or transformed to a web or tapered pulmonary artery. Interestingly, none of the webs and tapered pulmonary arteries resolved after anticoagulant treatment. Therefore, webs and tapered pulmonary arteries at the moment of APE diagnosis indicate a chronic PE state. Figure 1. Web at baseline and follow-up Funding Acknowledgement Type of funding source: Private company. Main funding source(s): Research grant from Actelion Pharmaceuticals

Evaluation of the Incidence of Chronic Thromboembolic Pulmonary Hypertension 1Year After First Episode of Acute Pulmonary Embolism: A Cohort Study.

Chronic thromboembolic pulmonary hypertension (CTEPH) is an important complication after acute pulmonary embolism (PE) with considerable morbidity and mortality. The aim of this study was to estimate the CTEPH incidence in a cohort after the first occurrence of PE. We conducted a 1-year follow-up cohort study between 2015 and 2018 to assess the incidence of CTEPH in 474 patients with their first acute episode of PE. For the diagnosis of CTEPH, patients with unexplained persistent dyspnea during follow-up underwent transthoracic echocardiography, right heart catheterization, ventilation-perfusion lung scanning, and CT pulmonary angiography. Overall, 317 patients were included in the study. The mean age of the patients was 56.5 ± 16years. One hundred and three patients (32%) had exertional dyspnea at the 1-year follow-up. Patients with evidence of pulmonary hypertension (PH) on echocardiography underwent right heart catheterization. Eleven patients (18%) had no PH (mPAP < 25mmHg); 47 patients (81%) had mPAP > 25mmHg. Fifteen patients had PAWP > 15mmHg, including those with underlying left heart problems or valvular diseases. There were 32 patients with PAH (mPAP > 25mmHg and PVR > 3 WU) undergoing CTEPH studies; 22 patients (6.9%) had multiple segmental defects suggesting CTEPH on a perfusion scan. The incidence of CTEPH observed in this study 1year after the first episode of acute PE was approximately 6.9%. This incidence seems to be high in our population, and diagnostic and therapeutic strategies for the early identification of CTEPH are needed.

Quality of life and functional limitations after pulmonary embolism and its prognostic relevance

BackgroundWhile the importance of patients’ quality of life (QoL) in chronic cardiac or pulmonary disease is uncontroversial, the burden of an acute pulmonary embolism (PE) on QoL has received little attention thus far. ObjectivesWe aimed to validate the German PEmb‐QoL questionnaire, identify associations between QoL and clinical/functional parameters, and investigate the prognostic relevance of QoL for long‐term survival in survivors of an acute PE episode. Patients/MethodsPatients were invited for a clinical follow‐up visit including assessment of QoL using the German PEmb‐QoL questionnaire 6 months after an objectively confirmed PE at a single center. Internal consistency reliability, construct‐related validity, and regressions between PEmb‐QoL and clinical patient‐characteristics were assessed using standard scale construction techniques. ResultsOverall, 101 patients [median age, 69 ([interquartile range] IQR 57‐75) years; women, 48.5%] were examined 208 (IQR 185‐242) days after PE. Internal consistency reliability and construct‐related validity of the PEmb‐QoL questionnaire were acceptable. As many as 47.0% of patients reported dyspnea, 27.5% had right ventricular (RV) dysfunction on transthoracic echocardiography (TTE), and 25.3% were diagnosed with post‐PE impairment (PPEI) at 6‐month follow‐up. Furthermore, 15.9% of patients were diagnosed with depression 6 months after an acute PE. The QoL was affected by dyspnea, preexisting pulmonary disease, and PPEI, and a reduced QoL was associated with an increased risk for long‐term mortality after an observation period of 3.6 years. ConclusionsThe German PEmb‐QoL questionnaire is a reliable instrument for assessing QoL 6 months after PE. The QoL was affected by dyspnea, preexisting pulmonary disease, and PPEI and was associated with long‐term mortality.

P2771A novel doppler index for the diagnosis of post pulmonary embolism impairment syndrome

Abstract Introduction Follow-up studies demonstrated that after an episode of acute pulmonary embolism (PE), half of patients report functional limitation. Chronic thromboembolic pulmonary hypertension (CTEPH) is diagnosed in approximately 4%, while others are supposed to have heart failure with preserved ejection fraction (HFpEF) or chronic thromboembolic disease (CTED). Echo can not only assess tricuspidal regurgitation pressure gradient (TRPG) indicating pulmonary hypertension but also with tissue Doppler, E/e' ratio can diagnose left ventricular diastolic dysfunction. We tried to asses if a novel echo index: TRPG to E/e' could be useful in differentiation between CTEPH, CTED and HFpEF. Material and methods We analyzed data of consecutive 535 PE survivors (313 F, aged 61±17 yrs). 342/535 (64%) reported significant functional impairment after at least 6 months anticoagulation. All symptomatic subjects underwent detailed diagnostic workup which included standardized echocardiography, lung scintigraphy, pulmonary functional tests, and chest CT, RHC and coronary angiography when appropriate. Results Eventually, out of 342 symptomatic PE survivors (220 F, aged 65±15 yrs) CTEPH was diagnosed In 17 cases, CTED in 8 pts and HFpEF in 174 pts and in the remaining other causes were found (i.e. coronary artery disease, anemia, pulmonary disease). Doppler echocardiography showed that TRPG/E/e' was significantly increased in CTEPH and CTED patients when compared to subjects with HFpEF (Table 1). Echocardiographic doppler assessment HFpEF p CTEPH p CTED p n=174 HFpEF vs CTEPH n=17 CTEPH vs CTED n=8 HFpEF vs CTED TRPG (mmHg) 26.7±8.9 &lt;0.01 59.5±32.0 0.013 34.4±15.1 ns E/e' 11.1±2.9 ns 10.1±32.0 ns 8.9±2.0 ns TRPG / E/e' 2.5±1.0 &lt;0.001 6.0±2.4 &lt;0.01 3.8±1.1 0.013 TRPG, Tricuspidal regurgitation pressure gradient; CTEPH, Chronic thromboembolic pulmonary hypertension; CTED, Chronic thromboembolic disease; HFpEF, Heart failure with preserved ejection fraction. Conclusion Our data indicate that echocardiographic index TRPG/(E/e') may be helpful in the differentiation of functional limitation in patients after pulmonary embolism.

Atrial Fibrillation in Patients with Acute Pulmonary Embolism: Clinical Significance and Impact on Prognosis.

Pulmonary embolism (PE) is one of the most common causes of cardiovascular death. The most often PE etiology is a deep vein thrombosis (DVT) of the lower extremities, but embolic material can arise in pelvic or upper extremity veins as well as in right heart chambers. There is growing number of evidences of atrial fibrillation (AF) involvement in PE. The presence of AF in patients with PE may be both the cause and the consequence of PE. The PE association with AF should be considered in patients without confirmed DVT and with history of AF, which itself is associated with prothrombotic state. The valuable diagnostic method is echocardiography that may bring the insight into source of embolic material. Another possible AF and PE association is the AF as a consequence of an abrupt increase in pulmonary vascular resistance due to the occlusion of the pulmonary vessels. Large-scale population-based studies have provided a considerable body of evidence on the involvement of PE in the onset of subsequent AF. Another important issue is the influence of AF on prognosis in patients with PE. Most investigators demonstrated a negative impact of AF on mortality. The main problem to resolve is whether AF is an independent mortality risk factor or whether it occurs as a result of comorbidities or the severity of a PE episode. Although the pathophysiological basis of this bidirectional relationship exists, many questions are still unresolved and require further studies, including the significance of paroxysmal AF accompanying an acute PE episode, the usefulness of PE risk scales in patients with concomitant AF, and the effect of anticoagulant treatment on PE and AF occurrence. Regardless of the type of AF, clinicians should be alert to the possibility of PE in patients with previous history of AF or presenting with new-onset AF.