The significance of C-reactive protein for the prediction of net-adverse clinical outcome in patients with acute pulmonary embolism

© 2020 Inst. Sci. inf., Univ. Defence in Belgrade. All rights reserved. Background/Aim. Acute pulmonary embolism (APE) may have different clinical manifestations. Also, its outcome can range from complete recovery to early death. Major bleeding (MB) as a due of the therapy also contributes to the overall adverse outcome. So far, it is unknown what the best predictors are for short-term mortality and MB among the several commonly used biomarkers. The aim of this study was to evaluate the significance of C-reactive protein (CRP) and other biomarkers for the prediction of adverse clinical outcomes. Methods. This clinical, observational, retrospective-prospective study included 219 consecutive adult patients treated for APE. Results. Among 219 patients, 22 (10%) died within the first month after diagnosis. Twenty seven patients (12.3%) had at least one episode of MB. Composite end-point [net-adverse clinical outcome (NACO)] was estimated in 47 (21.5%) of patients. The average values of all biomarkers were higher in the group of patient who died, and differences were statistically significant. Similar results were obtained for composite end-point. In terms of MB, none of biomarkers did not have significance, but CRP had a slight tendency toward significance. Results from univariate logistic regression model showed that troponin was statistically significant predictor of 30-day mortality. However, after adjusting for other variables, in multivariate logistic regression model troponin failed to be significant independent predictor of 30-day mortality. Unlike troponin, CRP and brain natriuretic peptide (BNP) were significant in all models – uni and multivariate (they were independent predictors of 30-day mortality). Conclusion. CRP has a good predictive value for 30-day mortality and NACO, and potential for MB in patients treated for APE

P6459Comparison of the new BLLADS score with other scores for the prediction of major bleeding in patients with acute pulmonary embolism

Abstract Background Hemorrhagic complications are a major obstacle for aggressive antithrombotic therapy in patients with acute pulmonary embolism (PE). Objectives We aimed to develop a simple risk score for predicting major bleeding (MB) in patients with acute PE using medical history and laboratory data at admission, including the potential influence of thrombolytic therapy, and to compare its predictive power to bleeding risk scores previously developed for patients with atrial fibrillation or venous thromboembolism. Methods A total of 630 consecutive patients treated for PE in six Serbian University hospitals were followed up for the occurrence of MB over a 90-day period after admission. A 6-component bleeding risk score was developed after Cox regression analysis of possible variables presented at admission. The use of thrombolytic therapy was also tested as a risk factor for bleeding and was integrated into the score. The ATRIA, HAS BLED, RIETE and VTE-BLEED scores were calculated for each patient at baseline and the predictive performances were compared with new score using c-statistics. Results MB occurred in 61 (9.7%) patients during the 90-day follow-up, with no increased risk of all-cause mortality (p=0.108). Six independent factors associated with MB were included in the final model (previous bleeding, leukocyte count ≥14x109/L, receipt of thrombolytic therapy, anemia, drugs associated with bleeding, and recent surgery; BLLADS). For the six- and five-variable models (without points for thrombolysis), C-indices were 0.774 (95% confidence interval [CI], 0.713–0.835, p&lt;0.001) and 0.713 (95% CI, 0.639–0.788, p&lt;0.001), respectively. The predictive power of the BLLADS score was found to be superior in comparison with other four scores: c-index 0.779 (95% CI 0.716–0.841, p&lt;0.001), 0,614 (95% CI 0.535–0.692, p=0.005), 0.591 (95% CI 0.518–0.664, p=0.025), 0.589 (95% CI 0.518–0.659, p=0.029), 0.586 (95% CI 0.508–0.664, p=0.035), for continuous BLLADS, RIETE, VTE-BLEED, ATRIA and HAS BLED scores, respectively. Conclusion A simple six-variable score including the use of thrombolysis was developed with sufficient discriminative capacity comparing to current available scores for the prediction of 90-day MB for non-selected PE patients. </jats:sec

P6465Are we calculated enough? Glomerular filtration rate as a predictor of intra-hospital prognosis in patients with pulmonary embolism

Abstract Background Pulmonary embolism (PE) can lead to multi-organ damage including an acute renal dysfunction which is associated with adverse events and high long-term mortality rate. Purpose The aim of our study was to investigate the predictive role of renal dysfunction on intrahospital mortality risk in patients hospitalized due to PE. The study was performed in intensive care units of six university hospitals. Methods The prospective cohort study comprised 665 consecutive patients with acute PE which was confirmed using MDCT. All patients underwent echocardiography examination on admission and blood samples were collected for troponin I (TnI), B-type natriuretic peptide (BNP) and routine laboratory analyses. Results Based on estimated glomerular filtration rate (GFR), patients were divided into three groups: first with the GFR &lt;30ml/min, second with GFR 30–60 ml/min, and third with GFR &gt;60 ml/min. During hospitalization in the first group the overall incidence of death was recorded in 28 (45.9%), in the second in 42 (18.9%), and in the third in 30 (7.9%) patients (p&lt;0.0001). Pulmonary embolism as a cause of death was recorded in the first group in 18 (29.5%) patients, in the second in 25 (11.3%) and in the third in 17 (4.5%) patients (p&lt;0.0001). Fatal bleeding was recorded in the first group in 1 (1.6%), in the second in 1 (0.5%) and in the third group in 3 (0.8%) patients (p&lt;0.05). There were no significant differences regarding major bleeding frequency among the groups. Multivariate analysis showed that age, comorbidities, hemodynamic status, TnI, and GFR were strongly associated with an overall mortality rate and with death due to PE, while the use of anticoagulation therapy influenced the fatal bleeding rate. After controlling for age, we found that GFR on admission had a significant effect on in-hospital survival. Compared with patients in the third group, those from the second group had more than 2 fold increased mortality risk [OR 2.17 (CI 1.301–3.625), p=0.001], and patients in the first group had 6 fold higher risk of mortality [OR 6.006 (CI 3.487–6.006)]. In the ROC analysis GFR showed significant predictive value for intra-hospital mortality risk in PE patients [AUC= 0.725, 95% CI (0.68–0.78), p&lt;0.001]. The highest sensitivity (64%) and specificity (70%) had GFR “cutoff” value of 59.12/min. Conclusion Renal dysfunction, on admission, in patients with acute PE is strongly associated with high intrahospital mortality risk and fatal bleeding. The estimation of GFR in these patients is important not only for prediction of the outcome but also for the prevention of bleeding complications, regarding the optimal dosage of anticoagulants. Even though it seems that GFR calculation is not still the clinical routine in PE. </jats:sec

P5591Efficacy and safety of lower dose slow infusion of t-PA for intermediate-risk pulmonary embolism patients with risk for bleeding

Abstract Background Current guidelines do not recommend thrombolytic therapy for the treatment of intermediate-risk pulmonary embolism (PE) because of the tight balance between the benefit and safety with classic protocols. Aim The aim of this study was to compare the new thrombolytic protocol with lower-dose slow-infusion (LDSI) of tissue plasminogen activator (tPA) to classic 2-hours tPA infusion protocol or no-reperfusion in patients with intermediate-high risk PE with higher bleeding risk regarding 30-day efficacy and safety. Methods Among 849 patients with PE from the Serbian multicenter registry, 469 patients who fulfilled criteria for intermediate-risk PE were involved in the study. After propensity score matching 425 patients [263 (61.9%), 99 (23.3%) and 63 (14.8%) were treated with no-reperfusion, classic tPA protocol (100 mg for 2 hours) and LDSI of tPA (2–5 mg/hour either vie local catheter or systemic venous infusion with dose range of 25–50 mg)]. The basic characteristics of patients were well balanced between groups except that patients treated with LDSI of tPA had significantly higher usage of drugs which can be associated to bleeding and more previous bleeding events. Thirty day all-cause and PE-caused mortality and 7-day major bleeding were the main efficacy and safety end-points, respectively. Results All-cause and PE-cause 30-day mortality were 8.7% vs 16.2% vs 1.6% (Log rank p=0.007) and 4.5% vs 11.0% vs 0.0% (Log rank p=0.008) in patients with no-reperfusion, classic tPA protocol and LDSI of tPA protocol, respectively. Major bleeding at 7 days were 2.7% vs 8.1% vs 14.3% (Log rank p=0.001) in patients with no-reperfusion, classic tPA protocol and LDSI of tPA protocol, respectively. There was one fatal intracranial bleeding during catheter infusion of tPA. Conclusion Lower-dose slow-infusion of tPA protocol decreased significantly all-cause and PE-cause mortality at 30-day at the cost of excess of non-fatal major bleeding at 7-day in patients with intermediate-risk PE and higher risk for bleeding. Acknowledgement/Funding None </jats:sec

Different predictive value for short-term all-cause mortality with commonly used biomarkers regarding the cause of pulmonary embolism

Background/Aim. The evaluation of blood levels of cardiac troponin I (cTnI), D-dimer, B-type natriuretic peptide (BNP), and C-reactive protein (CRP) on admission and during the treatment of pulmonary embolism (PE) are the part of routine diagnostic process and estimation of mortality risk. The aim of this study was to evaluate the predictive value of these biomarkers on admission for all-cause 30-day mortality in consecutive PE patients regarding whether they classified as spontaneous, transiently provoked, or permanently provoked PE. Methods. This retrospective analysis was gained from the data of 590 PE patients from the Serbian University Multicenter Pulmonary Embolism Registry (SUPER). Patients had at least one of these biomarkers (BNP, CRP, cTnI, and D-dimer) measured during the first 24 hours upon admission. Results. Receiver operating characteristic (ROC) curve analyses demonstrated that BNP had the highest prognostic accuracy for 30-day mortality in patients (n = 219) who had data for all examined biomarkers. BNP provided an AUC of 0.785 (p < 0.001). Separately, BNP had the highest c-statistic for all three groups of patients. CRP had a modest predictive value for the 30-day all-cause mortality in the group with transient provoked PE. Troponin I had a very modest predictive value for the 30-day all-cause mortality only in patients with spontaneous PE, and D-dimer was a very weak predictor of this end-point only in patients with persistent provoked PE. Conclusion. Patients with spontaneous, transient provoked, and persistent provoked PE have a significantly different profile of blood biomarkers level with different prognostic significance for early all-cause mortality

Platelet aggregability and anticoagulant proteins activity during dobutamine stress echocardiography in asymptomatic patients four months after percutaneous coronary intervention

© 2019 Inst. Sci. inf., Univ. Defence in Belgrade. All rights reserved. Background/Aim. Platelets aggregability (PA) and the activation of hemostasis during myocardial ischemia within physical or mental stress, can be one of many factors that influence the process of stent thrombosis after the percutaneous coronary intervention (PCI). The aim of the study is to investigate the relationship between the PA and activity of anticoagulant proteins with myocardial ischemia during the dobutamine stress echocardiography (DSE) in the asymptomatic patients 4 months after the PCI. Methods. The study population included 74 asymptomatic patients who had a successful PCI 4 months before a high-dose DSE. PA on epinephrine (EPI) and adenosine diphosphate (ADP) were determined by the Light Transmission Aggregometry (LTA), together with plasma activity of protein C and antithrombin before the DSE and at the peak stage of the stress test. The patients were divided into several groups on the basis of whether they have baseline or induced disturbance of segmental myocardial kinetics or not. All patients were on the clopidogrel and aspirin therapy at the time of DSE. Results. There were no statistically significant difference in the PA ADP (47.50% vs 50.20%; p = 0.970) as well as on EPI (59.30% vs 60.30%, p = 0.600) before and at the peak of DSE. A statistically significant difference was found in the anticoagulant activity of the antithrombin (84.85% vs 74.75%, p = 0.001) and protein C (77.75% vs 67.60%, p < 0.001). A significance of differences in antithrombin and the protein C, refered to the result before and at the peak levels of the test. There was no significant difference in the PA and plasma activity of anticoagulant proteins in the patients with or without induced myocardial ischemia at the peak of DSE. The patients who had an increased wall motion score index at the peak of DSE, had a higher EPI induced PA than the patients with normal myocardial contractility (68.60% vs 54.70%, respectively; p = 0.017). Conclusion. There are no changes in the PA before and after DSE, however, plasma activity of anticoagulant proteins decreased at the peak level of the test. The PA on EPI significantly increases at the peak of DSE in the patients with segmental myocardial hypocontractility

Predictive value of admission glycemia in diabetics with pulmonary embolism compared to non-diabetic patients

Aims: To examine the relationship between admission glucose (AG) level and short-term in-hospital mortality and to investigate the association between hyperglycemia and major bleeding in PE patients with and without DMT2. Methods: We evaluated 1165 patients with diagnosed acute PE with multi-detector computed tomography pulmonary angiography (MDCT-PA) enrolled in the Regional multicenter PE registry (REPER). The study population was classified to patients with diabetes mellitus type 2 (DMT2) and those without diabetes. According to quartiles of AG patients, both groups separately were categorized into four subgroups (DMT2 I: 15.7 mmol/L and (non-DMT2 I: 7.9 mmol/L). Results: All-cause mortality was higher in the DMT2 group (9.5% vs. 18.2%, p < 0.001), and PE-cause mortality was 6% for the patients without DMT2 and 12.4% for DMT2 patients (p = 0.02). The patients in the fourth AG quartiles in both groups, without DMT2 and with DMT2, had significantly higher all-cause and PE-cause in-hospital mortality compared with the first quartile. Rates of major bleeding were similar between the groups. On the multivariable analysis, after adjusting for age, gender and mortality risk, the adherence in the fourth AG quartile had an independent predictive value for all-cause death (HR 2.476, 95% CI 1.017–6.027) only in DM patients. Conclusion: In our cohort of patients with acute PE, diabetes was associated with increased rates for all-cause and PE-cause mortality