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In patients with pulmonary embolism (PE), the D-dimer assay is commonly utilized as part of the diagnostic workup, but data on D-dimer for early risk stratification and short-term mortality prediction are limited. The purpose of this study was to determine D-dimer levels as a predictive biomarker of PE outcomes in younger (<50 years of age) compared to older patients. We conducted retrospective analysis for 930 patients diagnosed with PE between 2015 and 2019 as part of the Serbian University Multicenter Pulmonary Embolism Registry (SUPER).All patients had D-dimer levels measured within 24 hours of hospital admission. The primary outcome was mortality at 30 days or during hospitalization. Patients were categorized into two groups based on age (≤ 50 and >50 years of age). Younger patients constituted 20.5% of the study cohort. Regarding all-cause mortality, 5.2% (10/191)of patients died in group under the 50 years of age; the short-term all-causemortality was 12.4% (92/739) in older group.We have found that there was significant difference in plasma D-dimer level between patients ≤ 50 years of age and older group (>50), p= 0.006.D-dimer plasma level had good predictive value for the primary outcome in younger patients (c-statistics 0.710; 95% CI, 0.640-0.773; p<0.031). The optimal cutoff level for D-dimer to predict PE-cause death in patients aged > 50 years was found to be 8.8 mg/l FEU(c-statistics 0,580; 95% CI 0.544-0.616; p=0.049). In younger PE patients, D-dimer levels have good prognostic performance for 30-day all-cause mortalityand concentrations above 6.3 mg/l FEU are associated with increased risk of death. D-dimer in patients aged over 50 years does not have predictive ability for all-caused short-term mortality. The relationship between D-dimer and age in patients with PE may need further evaluation.

ABSTRACTObjectives: To examine a relationship between protein C (PC) and antithrombin III (AT III) activities with ejection fraction of left ventricle (EFLV), in the early phase of acute ST-elevation myocardial infarction (STEMI) treated with primary percutaneous coronary intervention (pPCI), and to investigate whether PC and AT III are associated with major adverse cardiovascular events (MACE) within 6 months following from pPCI.Patients and methods: The research had a prospective character and included 357 patients who had, following the diagnosis of the STEMI, undergone pPCI at the Clinic of Cardiology and Emergency Internal Medicine, Military Medical Academy, Belgrade, Serbia, from January 2010 until April 2019.Results: The EFLV positively correlated with PC values (rho = 0.229). There was a statistically significant increase in the PC values between patients with MACE compared with those without MACE at 6 months’ follow-up evaluation (p < 0.0001). Also, significant difference in PC values between patients who died in hospital and those who were alive at 6 months’ follow-up (p < 0.01) was observed. PC values were different across different EFLV groups (p < 0.001), increasing from the 1stto the 4thEFLV quartiles: the median and the interquartile values for the 1st, 2nd, 3rdand 4thquartiles were 1.0400IU/l ± 0.15, 1.1400IU/l ± 0.15, 1.1350IU/l ± 0.16 and 1.2200IU/l ± 0.14, respectively.Conclusion: Increased PC activity in the early phase of STEMI is associated with higher EFLV 5 days after the pPCI as well as with MACE at 6 months after the pPCI.

AbstractBackground:Systemic thrombolytic therapy is not recommended for patients with intermediate-risk pulmonary embolism (PE) because of major bleeding and intracranial bleeding overcomes the benefit of reperfusion.Patients and methods:A total of 342 PE patients with intermediate-risk PE from the multicenter Serbian PE registry were involved in the study. Of this group, 227 were not treated with reperfusion therapy (anticoagulation only), 91 were treated with conventional thrombolysis protocols at the discretion of their physicians and 24 patients were treated with ultrasound assisted catheter thrombolysis (USACT) with the EKOS® system. All patients treated with USACT had at least one factor which is associated with an increased risk of bleeding. Other patient characteristics were similar across the treatment groups. All-cause and PE-related mortality at 30 days and rate of major bleeding at 7 days were the main efficacy and safety outcomes of the study.Results:The 30-day all-cause mortality were 11.5% versus 17.6% versus 0.0% for no reperfusion, conventional thrombolysis protocols and USACT groups (p = 0.056), respectively. The difference between the rate of 30-day PE-related mortality was in a favour of EKOS and no reperfusion compare to conventional protocols (0.0% vs. 3.5% vs. 11.0%, p = 0.013, respectively). Major bleeding at 7 days, was presented in 1.8% versus 7.7% versus 8.0% (p = 0.021) in no reperfusion, conventional thrombolysis and USACT groups with no intracranial bleeding.Conclusion:In the patients with intermediate-risk PE and at least one bleeding factor, USACT could be an alternative treatment to anticoagulant therapy only and conventional thrombolytic protocols.

Background: Electrocardiography (ECG) signs, typical or acute pulmonary embolism, and their changes can be used for the prediction of clinical and haemodynamic outcomes.Purpose: To study the predictive value of the resolution of admission ECG signs in higher risk pulmonary embolism patients for 30-day survival and for the decrease in right ventricular systolic pressure.Methods: We analysed the 12-lead ECGs at admission and daily for the first 5 days after hospitalisation in 110 intermediate-high and high-risk pulmonary embolism patients admitted to the intensive care unit of a single tertiary centre. The predictive value of the resolution of four ECG signs were analysed for 30-day survival and for the changes in right ventricular systolic pressure during hospitalisation: S-wave in the first standard lead, right bundle branch block pattern, S-wave in the aVL lead and negative T-waves in precordial leads.Results: ECG recordings showed the existence of S-wave in the I lead in 71 (64.5%), S-wave in the aVL in 77 (70%), right bundle branch block pattern in 30 (27.3%) and negative T-waves in 66 (60%) patients. All-cause 30-day in-hospital mortality was 13.6%. Among the ECG signs, only the presence of right bundle branch block at admission was significantly associated with 30-day all-cause mortality (hazard ratio (HR) adjusted for age, gender and right ventricular systolic pressure at admission was 7.7, 95% confidence interval (CI) 2.1–27.9; P=0.002). The resolution of three ECG signs during the first 5 days of hospitalisation, S-wave in the I lead (HR 26.4, 95% CI 3.1–226.6; P=0.003), S-wave in the aVL (HR 21.5, 95% CI 2.6–175.3; P=0.004) and right bundle branch block configuration (HR 5.2, 95% CI 1.3–20.8; P=0.020) were associated with 30-day survival. The intermediate-high and high-risk pulmonary embolism patients with S-wave resolution in lead aVL had 0.0% and 7.1% 30-day all-cause mortality, respectively. The patients with resolution of the S-wave in the first lead and in aVL as well as right bundle branch block had more pronounced changes in right ventricular systolic pressure at discharge (27±13 vs. 13±15 mmHg; P=0.011 for S-wave in I lead resolution, 27±12 vs. 15±17 mmHg; P=0.004 for S-wave in aVL resolution and 23±14 vs. 9±14 mmHg; P=0.040 for right bundle branch block resolution) than patients without resolution.Conclusion: Resolution of S-waves and right bundle branch block in ECG correlates with lower all-cause 30-day mortality in intermediate-high and high-risk pulmonary embolism patients. Resolution of S-waves in the first lead and in aVL and right bundle branch block correlates with a decrease of right ventricular systolic pressure.

AbstractBackground:Activity of protein C has important role in the development of early necrosis and no-reflow phenomenon in patients with ST-segment elevation myocardial infarction (STEMI) after successful primary percutaneous coronary intervention (pPCI).Methods:We examined association between plasma activity of protein C, antithrombin, coagulation factors II, VII, VIII and fibrinogen to early formation of new Q-waves (myocardial necrosis) before pPCI and early ST-segment resolution (microcirculatory reperfusion) after pPCI in patients with acute STEMI. According to ischaemic time, patients were considered as early or late presenters. 12-lead ECG was analysed for the presence of new Q-wave at admission and for significant ST-segment resolution 60 minutes after primary PCI.Results:In early presenters’ group, protein C activity was significantly lower in patients who did not achieve significant ST-segment resolution after pPCI compared to patients who did (1.11 IU/L vs. 0.99 IU/L, p = .006) and in patients who had new Q-waves compared to group who had not (1.04 UI/l vs. 1.11 IU/L, p = .038). There was significant negative correlation between protein C activity and maximal CK-MB levels (R2 = 0.06, p = .009) and BNP levels (R2 = 0.109, p = .003) and significant positive correlation between protein C activity with LVEF (R2 = 0.065, constant = 33.940, b = 11.968, p = .007) in early STEMI presenters. There were no differences between the activity of other examined haemostasis factors.Conclusion:Therefore we concluded that STEMI patients with early myocardial necrosis and no-reflow phenomenon after pPCI have lower activity of plasma protein C levels.

ObjectiveThe objective of the study was to determine whether women signifi cantly have more frequently right ventricular infarction than men.MethodsThe study population consisted of consecutive patients with ST-segment elevation myocardial infarction (STEMI) who underwent primary percutaneous intervention. The following criteria were used for the diagnosis of right ventricular infarction: ST-segment elevation in one of the right precordial leads V4R-V6R for equal or more than 1 mm together with ST-segment elevation in at least two contiguous inferior leads. The odds ratio for the diagnosis was calculated according to gender. Searching PubMed, nine more relevant studies that used the same criteria for the diagnosis of right ventricular infarction were identifi ed and a meta-analysis was conducted.ResultsIn our group of 517 consecutive patients with STEMI, 32 (23.5%) of 136 women and 42 (11.0%) of 381 men had RVI (odds ratio (OR) = 2.48, 95% confi dence interval (CI): 1.49-4.13; P= 0.001). Two hundred and seventy-fi ve patients had inferior STEMI and among them 32 (42.7%) of 75 women and 42 (23.1%) of 182 men, had a right ventricular infarction (OR = 2.48, 95%CI: 1.40-4.40; P= 0.002). In a meta-analysis, a total number of 4,326 patients with inferior STEMI were included. Four hundred and thirty-seven (41.4%) out of 1,056 women and 1,221 (37.3%) out of 3,270 men, had been diagnosed with RVI (OR = 1.27, 95%CI: 1.09 - 1.48; P= 0.021).ConclusionRight ventricular infarctions occur more frequently in women than in men.

Carbamazepine exhibits significant inter-individual variability in its efficacy and safety, which leads to unpredictable therapy outcomes for the majority of patients. Although its complex biotransformation depends on CYP3A5 activity, evidence of association between carbamazepine treatment outcomes and CYP3A5 functional variations remains inconclusive. The aim of the present study was to investigate the distribution of two of the functionally important CYP3A5 variants *2 and *3 as well as their effects on carbamazepine dose requirements, plasma concentrations and clearance in a Serbian population. The study involved 40 paediatric epileptic patients on steady-state carbamazepine treatment. Genotyping was conducted using the PCR-RFLP method, and carbamazepine plasma concentrations were determined using the HPLC method. CYP3A5*2 and *3 polymorphisms were found at frequencies of 0.0% and 97.5%, respectively, which corresponds well to previously published data for Caucasians. No differences in CYP3A5*3 allele frequencies were detected among epileptic patients in comparison to healthy volunteers within similar ethnic populations (p>0.08), indicating that CYP3A5 polymorphism does not represent a risk factor for epilepsy development. There was an observed tendency towards lower dosage requirements (mean±SD: 15.06±4.45 mg/kg vs. 18.74±5.55 mg/kg; p=0.26), higher plasma concentrations (mean±SD: 0.45±0.13 mg/kg vs. 0.38±0.03 mg/kg; p=0.47) and lower clearance (mean±SD: 0.14±0.05 mg/kg vs. 0.15±0.01 mg/kg; p=0.79) of carbamazepine in homozygous carriers of CYP3A5*3/*3 compared to heterozygous CYP3A5*1A/*3 Serbians. Because these genotype groups did not differ significantly in terms of their carbamazepine pharmacokinetics parameters, the proposed effects of CYP3A5*3 on carbamazepine metabolism could not be confirmed.

ObjectivePatients with moderate and severe aortic stenosis (AS) and without obstructive epicardial coronary disease have been shown to have an impairment of coronary fl ow velocity reserve (CFVR). Recently, it has been shown that CFVR is an independent predictor for future cardiovascular events in AS patients. We investigated parameters representing left ventricular (LV) mass and wall thickness, diastolic dysfunction, LV workload and haemodynamic indexes of AS severity to determine which contributes the most to impaired CFVR in patients with AS and a nonobstructed coronary angiogram.Method and resultsA total of 77 patients with moderate or severe AS, mean age 65.66 ± 11.02 y (57.14% males), were enrolled in this prospective study. All patients had standard Doppler-echo study, coronary angiography and adenosine-stress transthoracic Doppler-echo for CFVR measurement. We took 2.5 as a cut-off value for impaired CFVR. Univariate analysis showed that aortic valve area (AVA), maximal velocity (Vmax), mean pressure gradient (Pmean), energy loss index (ELI), aortic valve resistance (AVR) and stroke work loss (SWL) were associated (P =0.05) with impaired CFVR. Multivariate analysis showed that AVR was the best predictor of impaired CFVR (RR 0.900, CI: 0.983-0.997, P =0.007). Using ROC analysis, the AVR value of 211.22 dynes∙s∙cm− 5 had the highest accuracy in predicting the impaired CFVR (AUC-0.681, P =0.007, sensitivity 72%, specifi city 52%, CI: 0.561-0.800).ConclusionHaemodynamic indices of AS severity, together with LV workload parameters, are the main determinants of CFVR. Among all parameters, AVR is the strongest predictor of CFVR in patients with moderate or severe AS and a nonobstructed coronary angiogram.

ObjectiveThis study on responsiveness to clopidogrel and aspirin evaluates its interaction with: (i) patient characteristics; (ii) procedure characteristics; (iii) antiplatelet dose.Methods and resultsAfter elective PCI, 60 patients receiving aspirin 100 mg daily, and clopidogrel 75mg daily were monitored with the PFA 100 test and VASP assay.Non-responsiveness to aspirin and clopidogrel was found in 23 (38%) and 18 (30%) of 60 patients, respectively. Seven (12%) patients were dual nonresponders. Non-responders to both aspirin and clopidogrel were more often smokers. Non-responders to clopidogrel, in addition had elevated infl ammatory markers (P< 0.05). Dual non-responders had (i) a higher platelet count, LDL, and CRP; (ii) a lower HDL (P< 0.05). Clopidogrel non-responders were receiving 150 mg clopidogrel, with a positive response in 72%.Eighty % of non-responders to 150 mg clopidogrel were also non-responders to aspirin.ConclusionBaseline patient characteristics and clopidogrel dose modify the antiplatelet response. Also, patients resistant to both aspirin and clopidogrel do no benefi t from an increased clopidogrel dose.

The aim of this study is to analyze prognostic capability of pulse pressure (PP) in acute myocardial infarction (AMI).