New-Onset Paroxysmal Atrial Fibrillation in the Setting of Acute Pulmonary Embolism Is Associated with All-Cause Hospital Mortality in Women but Not in Men.

BACKGROUND: Patients with acute pulmonary embolism (PE) may have various types of atrial fibrillation (AF). The role of AF in hemodynamic states and outcomes may differ between men and women. METHODS: In total, 1600 patients (743 males and 857 females) with acute PE were enrolled in this study. The severity of PE was assessed using the European Society of Cardiology (ESC) mortality risk model. Patients were allocated into three groups according to their electrocardiography recordings taken during hospitalization: sinus rhythm, new-onset paroxysmal AF, and persistent/permanent AF. The association between the types of AF and all-cause hospital mortality was tested using regression models and net reclassification index (NRI) and integrated discrimination index (IDI) statistics with respect to sex. RESULTS: There were no differences between the frequencies of the types of AF between men and women: 8.1% vs. 9.1% and 7.5% vs. 7.5% (p = 0.766) for paroxysmal and persistent/permanent AF, respectively. We found that the rates of paroxysmal AF significantly increased across the mortality risk strata in both sexes. Among the types of AF, the presence of paroxysmal AF had a predictive value for all-cause hospital mortality independent of mortality risk and age in women only (adjusted HR, 2.072; 95% CI, 1.274-3.371; p = 0.003). Adding paroxysmal AF to the ESC risk model did not improve the reclassification of patient risk for the prediction of all-cause mortality, but instead enhanced the discriminative power of the existing model in women only (NRI, not significant; IDI, 0.022 (95% CI, 0.004-0.063); p = 0.013). CONCLUSION: The occurrence of paroxysmal AF in female patients with acute PE has predictive value for all-cause hospital mortality independent of age and mortality risk.

Prognostic significance of symptomatic deep vein thrombosis in patients with acute symptomatic pulmonary embolism regarding the European Society of Cardiology mortality risk model.

BACKGROUND: Deep vein thrombosis (DVT) can be symptomatic or asymptomatic in patients with acute pulmonary embolism (PE). The prognostic value of the symptomatic DVT at the presentation regarding the prognosis of PE is unknown. METHODS: Data were extracted from the REgional Pulmonary Embolism Registry (REPER) which enrolled 1604 hospitalized patients after multidetector computed tomography (MDCT) diagnosed symptomatic acute PE. According to the ESC risk model, patients were classified into four subgroups. Patients who had leg edema with or without pain, and patients with leg pain and DVT confirmed by compression ultrasound were considered to have symptomatic DVT. This study aimed to compare all-cause hospital mortality between patients with symptomatic DVT and patients without symptoms or signs of DVT across the PE risk stratums. RESULTS: All-cause mortality in patients with symptomatic DVT compared to those who had no symptoms or signs of DVT were 2/196 (1.0%) vs. 11/316 (3.5%), P=0.145, 4/129 (3.1%) vs. 17/228 (7.5%), P=0.106, 14/196 (7.1%) vs. 54/290 (18.6%), P<0.001 and 16/55 (29.1%) vs. 51/139 (36.7%), P=0.402 in patients with low, intermediate-low, intermediate-high and high-risk PE, respectively. In multivariate analysis symptomatic DVT was associated with decreased in-hospital mortality only in patients with intermediate-high PE (OR 0.320, 95%CI 0.164-0.627; P=0.001). Intermediate-high risk PE patients with symptomatic DVT who were treated with thrombolysis had significantly lower hospital mortality than patients without symptoms or signs of DVT (2.2% vs. 11.4%, P=0.003). CONCLUSIONS: Intermediate-high risk PE patients with symptomatic DVT at presentation may benefit from thrombolysis and have lower hospital all-cause mortality in such circumstances.

Pulmonary embolism bleeding score index (PEBSI): A new tool for the detection of patients with low risk for major bleeding on thrombolytic therapy.

BACKGROUND: Estimation of bleeding risk is an unmet need for individualized therapy in acute pulmonary embolism (PE) patients with increased mortality risk. METHODS: We analyzed the association between various patients' characteristics and occurrence of major bleeding (MB) according to the modified International Society of Thrombosis and Hemostasis (ISTH) criteria ("overt" bleeding is the only modification from the original criteria) at 7 days from admission to the hospital and thrombolytic therapy with a tissue-plasminogen activator (tPA). Pulmonary embolism bleeding score index (PEBSI) was created using multivariate regression analyses, and finely, dichotomous index was used for the discrimination of patients with low risk for MB from those with high risk. RESULTS: During the 6-year period (2015-2021) 367 PE patients were treated with tPA and included in the Regional PE registry. Among them, 29 (7.9%) fulfilled the criteria for MB. Five factors were identified as significantly associated with MB and were used to build the PEBSI score: previous bleeding, recent surgery, diabetes, the use of drugs that could be associated with bleeding, and anemia. PEBSI score showed c-index for 7-day MB 0.794 (95CI% 0.698-0.889). Patients with PEBSI scores of 0 or 1 had a low risk for MB (2.8%) and those with scores>1 had a high risk for MB (18.6%) (p < 0.001). Internal validation of PEBSI score using a randomly, equally split method confirmed the discriminative value of the PEBSI score. CONCLUSION: Novel PEBSI score has significant power to discriminate patients with low risk for MB on thrombolytic therapy from those with high risk.

The influence of smoking habits on cadmium and lead blood levels in the Serbian adult people.

According to the World Health Organization, in 2015, the Serbian population ranked among the highest ones in Europe in terms of smoking habit: 44.3% males and 36.2% females aged 18-64 smoked tobacco. In the last 7 years, 25% of total mortality in men and 9% in women from Serbia were associated with smoking. Tobacco smoking is one of the most important sources of exposure to many toxic substances in general population. Our study confirmed higher blood levels of two toxic metals, cadmium and lead, in the blood of smokers (3.5 and 1.5 times higher than in non-smokers, respectively). Furthermore, smoking habits, such as number of smoked cigarettes per day, smoking period and cigarette type, along with age, were shown to influence these metals' blood concentration. Higher blood levels of Cd and Pb were found in smokers consuming more than 10 cigarettes per day for more than 10 years. The present study also highlighted the importance of the controlled tobacco production, since it was shown that consumption of illicit tobacco could manifold the exposure to toxic metals that can subsequently increase the frequency of related diseases as well.

Differences between activities of coagulation factors after one month of therapy with different direct oral anticoagulant in pulmonary embolism patients.

WHAT IS KNOWN AND OBJECTIVE: Direct oral anticoagulants (DOACs) are frequently used for the treatment of pulmonary embolism (PE), but both clinical and laboratory data comparing their efficacy and safety are conflicting. This study investigated and compared the impact of three DOACs (apixaban, rivaroxaban and dabigatran) on coagulation cascade in acute PE patients. METHODS: After the initial treatment, acute PE patients were randomly allocated to one of three groups, and treatment continued using one of the three DOACs. Following 1 month of treatment, the activity of factors II, VII and VIII, as well as protein C, antithrombin, D-dimer and fibrinogen, were measured, and the values were compared between the groups. RESULTS AND DISCUSSION: One hundred consecutive PE patients were included. The mean values for the activity of factors II and VII and protein C were higher in patients on apixaban than in patients on rivaroxaban (1.45 ± 1.12 (IU/mL) vs 1.13 ± 0.92 (IU/mL), P < 0.001; 1.24 ± 1.10 (IU/mL) vs 1.05 ± 0.98 (IU/mL), P = 0.024 and 1.15 ± 0.62 vs 1.02 ± 0.68 (IU/mL), P = 0.019, respectively). The mean of factor II activity and the median of factor VIII activity were also significantly higher in patients on apixaban than in patients on dabigatran (1.45 ± 1.12 vs 1.20 ± 0.96 (IU/mL), P = 0.003 and 2.9 (2.0-4.0) vs 2.1 (1.5-2.7) (IU/mL), P = 0.001, respectively). No difference was noticed in D-dimer concentrations, or in the activity of the other factors measured. Additionally, no difference was noticed between the rivaroxaban and dabigatran groups. WHAT IS NEW AND CONCLUSION: Apixaban had a significantly higher thrombin activity, above the laboratory determined normal range, compared to patients on rivaroxaban and dabigatran. This higher thrombin activity in patients on apixaban may contribute to a better haemostatic response during the therapy or increased prothrombotic state after therapy interruption.