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Introduction: The concept of post Pulmonary Embolism syndrome includes various combinations of functional, haemodynamic or imaging abnormalities in patients after pulmonary embolism (PE). Although residual obstruction of pulmonary vascular bed is suggested to be a major cause of post Pulmonary Embolism syndrome (post-PE syndrome) other cardiopulmonary abnormalities can be responsible for functional impairment. Therefore, we analyzed the frequency of post-PE syndrome and its potential causes., Material and Methods: We report data of consecutive 845 PE survivors (468 F, aged 62 ± 18 yrs) who were anticoagulated, and followed for at least 6 months. All symptomatic subjects at follow up underwent diagnostic workup., Results: 35% (290/845) of PE survivors recovered functionally, while 65% patients reported a decreased exercise tolerance compatible with post-PE syndrome. One hundred and five symptomatic cases were lost to follow up. After diagnostic workup, chronic thromboembolic pulmonary hypertension (CTEPH) was diagnosed in 38 of 450 (8.4%) symptomatic subjects and chronic thromboembolic pulmonary disease (CTED) was diagnosed in 15/450 (3.3%) of them. Chronic heart failure with reduced ejection fraction (EF) was found in 6.9% (31/450) of patients and 154 patients (34.2%) had leftsided diastolic dysfunction. Valve heart disease was detected in 6.2% (28/450), atrial fibrillation in 31/450 (6.9%), Other causes of reduced exercise tolerance include coronary artery disease in 31/450 (6.9%), pulmonary disease 42/450 (9.3%), morbid obesity 15/450 (3.3%), neoplasms 15/450 (3.3%), psychiatric disorders 1%, rheumatoid disease 1%, anemia 1%., Conclusions: Approximately 65% of PE survivors report functional impairment, despite at least 6 months of anticoagulation. Persistent pulmonary artery thromboemboli resulting in CTEPH or CTED were detected in 7.2% of PE survivors and 11.8% of symptomatic patients. Leftsided diastolic dysfunction was the most prevalent echocardiographic abnormality, and remained the most common cause of functional limitation affected 34.2% of symptomatic cases., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Background: Risk factors for atherosclerosis and venous thromboembolism (VTE) overlap and are mostly associated with endothelial dysfunction (ED). We hypothesized that ED is present in patients after the first episode of acute pulmonary embolism (APE) and predicts the risk of VTE recurrence., Design and Methods: Patients, at least 6months after the first episode of symptomatic, confirmed APE were included in this case-control study. The exclusion criteria were risk factors for cardiovascular diseases and other conditions associated with endothelial dysfunction. Eighty two patients (aged 38±11years; 44 M; 38 F) were enrolled in the study, 39 after provoked APE, 43 after unprovoked APE, and 30 controls (C) (aged 38±12years; 15 M, 15 F). In order to evaluate the endothelial function in patients with a history of APE flow-mediated dilation (FMD) of the brachial artery and biomarkers of endothelial dysfunction (sVCAM-1, sICAM-1, ADMA, E-selectin) were measured. Subsequently all patients were followed up in an outpatient clinic for VTE recurrence., Results: FMD was more often impaired in APE patients than in controls (5.3% (0.8-20.3) vs. 13.8% (4.1-24.3); p<0.0001). Biomarker levels differed between APE and C groups: sVCAM-1 (631ng/ml (105-2382) vs. 495ng/ml (348-934); p=0.04) and sICAM-1 (679ng/ml (279-1006) vs. 600ng/ml (394-766); p=0.002). There were 19 recurrences of VTE during the at least 12-month follow-up (15 with history of unprovoked-APE and 4 after provoked-APE). E-selectin ≥39ng/ml and sICAM-1≤655ng/ml indicated the group without recurrence of VTE. In a group of 43 unprovoked APE patients both E-selectin<39ng/ml and sICAM-1>655ng/ml were found in 17 subjects. Eleven of them (65%) were diagnosed with recurrent VTE., Conclusions: Endothelial function is significantly impaired in patients after an episode of APE as indicated by FMD assessment and biomarker levels. Low concentrations of E-selectin and high levels of sICAM-1 are associated with a high risk of recurrent thromboembolism., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Background: Patent foramen ovale (PFO) is an established risk factor for ischemic stroke. Since acute right ventricular dysfunction (RVD) observed in patients with PE can lead to right-to-left inter-atrial shunt via PFO, we hypothesized that PFO is a risk factor for ischemic stroke in PE with significant right ventricular dysfunction., Methods: 55 patients (31 F, 24M), median age 49 years (range 19-83 years) with confirmed PE underwent echocardiography for RVD and PFO assessment. High risk acute PE was diagnosed in 3 (5.5%) patients, while 16 (29%) hemodynamically stable with RVD patients formed a group with intermediate-risk PE. PFO was diagnosed in 19 patients (34.5%). Diffusion-weighted MRI of the brain for acute ischemic stroke (AIS) was performed in all patients 4.91 ± 4.1 days after admission., Results: AIS was detected by MRI in 4 patients (7.3%). Only one stroke was clinically overt and resulted in hemiplegia. All 4 AIS occurred in the PFO positive group (4 of 19 patients), and none in subjects without PFO (21.0% vs 0%, p=0.02). Moreover, all AIS occurred in patients with RVD and PFO, and none in patients with PFO without RVD (50% vs 0%, p=0.038)., Conclusion: Our data suggest that acute pulmonary embolism resulting in right ventricular dysfunction may lead to acute ischemic stroke in patients with patent foramen ovale. However, the clinical significance of such lesions remains to be determined., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Introduction: According to current ESC guidelines not only hemodynamic parameters, but also indices of right ventricular dysfunction such as NT-proBNP have a significant prognostic value in acute pulmonary embolism (PE). MR-proADM is a significant predictor of short-term mortality in acute heart failure and adds prognostic value to NT-proBNP. We hypothesized that plasma MR-proADM is elevated in acute PE, correlates with the severity of PE and has prognostic value. We also compared prognostic values of MR-proADM and NT-proBNP for the prediction of early mortality in acute PE., Material & Methods: We studied 98 patients (51F/47M, 59.6 ± 18.4 yr) with acute PE. On admission blood samples were collected for MR-proADM and NT-proBNP., Results: MR-proADM reflected the severity of acute PE: 0.734 nmol/L in low-risk acute PE (0.384-1.342), 0.995 nmol/L in intermediate-risk acute PE (0.394-7.499) and 2.062 nmol/L in high-risk acute PE (0.447-3.098), p<0.001. MR-proADM was higher in non-survivors than in survivors 2.123 nmol/L (1.543-4.220), vs. 0.910 nmol/L (0.384-7.449), p=0.0003. The AUC of MR-proADM and NT-proBNP ROC curves for predicting all-cause mortality were 0.935 (95% CI 0.861-0.977) and 0.844 (95% CI 0.749-0. 913), respectively. In univariable analysis NT-proBNP and MR-proADM were significant predictors of all-cause mortality HR 1.00 (95% CI 1.000-1.0002, p=0.029) and 1.65 (95% CI 1.214 - 2.249, p=0.015). However, in multivariate analysis, MR-proADM but not NT-proBNP was a significant predictor of all-cause mortality., Conclusion: NT-proBNP and MR-proADM are of similar predictive value in the assessment of outcome in acute PE, however MR-proADM seems to be superior in predicting all-cause mortality., (© 2013.)

Objective: Various clinical and biochemical parameters predict the prognosis of patients with acute pulmonary embolism(APE). Treatment of APE can improve a patient's hemodynamic status, restoring adequate peripheral organ perfusion. Therefore, we hypothesized that improvement of renal function can predict short term prognosis of APE patients., Material & Method: We evaluated 232 consecutive patients (94 men,aged 67 ± 18 years) with APE proven by spiral computer tomography. Blood samples were collected for creatinine assays on admission and 72 hours later, the glomerular filtration rate(eGFR) was estimated using the MDRD formula., Results: During the first 72 hours, 6 subjects died, while during the first 30 days 24(10%) subjects died (APE mortality 8%). On admission eGFR<60 ml/min was present in 113 patients(49%) and after 72 hours in 85 patients(38%). In 26 patients(11%) eGFR on admission was <60 ml/min and renal function did not improve during subsequent 72 hours. In this group the 30-day all-cause and APE-related mortality rates were 27% and 23%, respectively, while serious adverse events occurred in 38% of them. 206 patients with eGFR>60 ml/min showed a more favorable prognosis (8% 30-day all-cause mortality) than subjects with eGFR<60 ml/min and a stable eGFR during the first 72 hours (27% mortality rate, p<0.003). Persistent renal dysfunction predicted all-cause and PE-related 30-day mortality (hazard risk 2.53(CI 95%:0.96-6.68),p=0.06 and 3.04(CI 95%:1.28-7.26),p=0.01, respectively)., Conclusion: Approximately 50% of patients with APE have at least a moderately impaired renal function on admission. Renal function improves within 72 hours in patients with a good prognosis, while "persistent" renal dysfunction indicates an increased mortality., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

Introduction: In acute pulmonary embolism (APE) the increase of pulmonary vascular resistance depends on the thromboli load and potentially on the pulmonary bed contraction caused by neurohormonal reaction. Plasma levels of endothelin were reported to be elevated in pulmonary arterial hypertension. However, there are only a few studies assessing endothelin in patients with APE., Materials & Methods: Therefore in our study we evaluated endothelin concentration in 55 patients (29M, 26F, age 57+/-19 yrs) with confirmed APE for potential value in risk stratification. Patients were compared with 24 healthy volunteers at similar age. On admission blood samples were collected for plasma endothelin concentration. The quantitative assessment of right ventricular (RV) function was performed by echocardiography., Results: Endothelin concentrations were similar in APE patients and in control group (1.41(0.22-9.68)pg/mL vs. 1.62(0.27-8.92)pg/mL; p = NS). There was no differences in endothelin levels between APE patients with and without RV dysfunction (1.46(0.38-4.54)pg/mL vs. 1.41(0.22-9.68)pg/mL; p = NS). Endothelin concentration did not differ between patients with serious adverse events and APE group with event-free clinical course (3.19(0.38-4.27)pg/mL vs. 1.38(0.22-9.68)pg/mL; p = NS). There was no significant correlation between endothelin levels and blood saturation, time from the first symptoms, heart rate, blood pressure, tricuspid valve regurgitation pressure gradient and other echocardiographic parameters., Conclusions: We concluded that plasma endothelin concentrations assessed on admission are not elevated in patients with APE and it does not play as important role in acute phase of increase of pressure in pulmonary arteries as in chronic pulmonary hypertension.

Background: Despite long-term anticoagulation in some patients after acute pulmonary embolism (APE) pulmonary thrombi are not completely resolved. We hypothesized that elevated D-dimer concentration reflecting increased endogenous fibrinolysis may indicate incomplete pulmonary thrombi resolution after the first episode of PE., Methods: 55 patients aged 54.7+/-18.6 years were anticoagulated for 6 months with acenocumarol (74.5% patients) or low molecular weight heparin (25.5% patients) when control spiral computed tomography (sCT), lung perfusion scintigraphy and D-dimer assessment were performed., Results: Incomplete recanalization of pulmonary circulation was found in 39 (70.9%) patients - thrombi at sCT and/or > or =1 wedge-shaped perfusion defect at scintigraphy. Age, sex, rate of unprovoked APE, malignancies, thrombolysis in the acute phase and type of long-term anticoagulation were similar in patients without and with complete recanalization. D-dimer at follow-up but not on admission was higher in patients with then without incomplete recanalization (median 340 (80-2280) vs 160 (60-390) ng/mL, p=0.02). All 11 (20%) patients with D-dimer level >500 ng/mL at follow-up did not resolve thromboemboli completely. ROC analysis showed that D-dimer at follow-up identified patients with incomplete recanalization (AUC 0.709, 95% CI (0.560-0.831), p=0.007). Multivariable analysis confirmed that D-dimer >350 ng/mL at follow-up and right ventricle dysfunction at the diagnosis were independent predictors of incomplete recanalization (OR 18.58 (95% CI 1.97-175.19) and 7.03 (95% CI 1.43-34.6), respectively, p=0.0006)., Conclusion: Elevated D-dimer after 6 months anticoagulation and right ventricular dysfunction at the diagnosis predict incomplete recanalization of pulmonary circulation after first episode of APE.