BACKGROUND: Heat-not-burn (HNB) technology by the U.S. Food and Drug Administration has been classified as a modified risk tobacco product, which can be a better option for those populations who cannot give up the habit of smoking. The outlook on the effects of these products is quite controversial in the scientific world. OBJECTIVE: To present the effect of HNB tobacco products on the cardiovascular system, with reference to the existence of possible benefits of the technology. METHODS: The literature search was conducted in PubMed/Medline, the Cochrane Central Register of Controlled Trials (CENTRAL), and ClinicalTrials.gov databases, with reliance on a well-defined guiding research statement. Quality appraisal was performed using the CASP checklist for randomized controlled trials. RESULTS: The search of three databases identified 167 records, and after selection process, 25 randomized controlled trials were eligible for our study’s criteria. Twenty studies investigated the effects of HNB products on biomarkers of clinical relevance. Five studies evaluated other functional heart parameters rather than biomarkers. CONCLUSION: With HNB tobacco products, significant reductions were found in biomarkers of exposure and biological effect related to pathways involved in cardiovascular disease, including inflammation, oxidative stress, lipid metabolism, platelet function, and endothelial dysfunction.

The management of patients with acute pulmonary embolism (aPE) depend on the risk stratification at hospital admission. It is unknown when normotensive aPE patients with some other risk factors deteriorate. Patients with objectively established acute PE diagnosis enrolled in the regional PE registry from January 2015 to December 2021, were studied in this investigation. According to European Society od Cardiology criteria patients were stratified during admission to hospital in four risk stratums. The timing for death and the main reason for death were recorded. PE-related death was defined if patient has died because of cardiac arrest or obstructive shock if there is no another possible reason for that. In the REPER registry. Among 1541 patients (514 low risk, 366 intermediate-low risk, 472 intermediate-high risk and 189 high risk) with aPE, 101 (6.6%) have died primary from aPE and 64 (4.2%) have died from other reasons during the 30-day follow-up. PE-related death across the mortality risk groups were 0.8%, 1.1%, 8.5% and 28.5% in low-risk, intermediate-low, intermediate-high and high risk PE, respectively. Median time from hospital admission to PE related death was significantly longer in intermediate-high than in high risk patients 4.5 (2.0–9.0) vs 1.0 (1.0–4.5) days, p=0.001. In the high risk group 50.9% of patients died during the first 24 hours, 9.0% in the next 24 hours and 83.0% of patients died during the first 5 days from admission. In the intermediate-high risk group 17.5% died in the first 24 hours, 12.5% died in the next 24 hours and next 25% died till the fifth day. There was no difference in timing of non PE-related death between intermediate-high and high risk patients 9.5 (6.0–18.5) vs 7.0 (3.0–23.5) days, p=0.631. There is significant delay in timing of death in intermediate-high compare to high risk PE patients, however, almost 50% of patients who died in the intermediate-high risk PE patients have died inside the first 5 days from hospital admission. Type of funding sources: None.

Introduction In one third of all patients with epilepsy, seizure freedom is not achieved through anti-seizure medication (ASM). These patients have an increased risk of earlier death, poorer cognitive development, and reduced quality of life. Cenobamate (CNB) has recently been approved as a promising novel ASM drug for the treatment of adults with focal-onset epilepsy. However, there is little experience for its application in pediatric patients. Methods In a multicenter study we evaluated retrospectively the outcome of 16 pediatric patients treated “off label” with CNB. Results In 16 patients with a mean age of 15.38 years, CNB was started at an age of 15.05 years due to DRE. Prior to initiation of therapy, an average of 10.56 (range 3–20) ASM were prescribed. At initiation, patients were taking 2.63 (range 1–4) ASM. CNB was increased by 0.47 ± 0.27mg/kg/d every 2 weeks with a mean maximum dosage of 3.1 mg/kg/d (range 0.89–7) and total daily dose of 182.81 mg (range 50–400 mg). Seizure freedom was achieved in 31.3% and a significant seizure reduction of >50% in 37.5%. Adverse events occurred in 10 patients with fatigue/somnolence as the most common. CNB is taken with high adherence in all but three patients with a median follow-up of 168.5 days Conclusion Cenobamate is an effective ASM for pediatric patients suffering from drug-resistant epilepsy. In addition to excellent seizure reduction or freedom, it is well-tolerated. Cenobamate should be considered as a novel treatment for DRE in pediatric patients.

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 aims 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 signs or symptoms 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 inhospital 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 signs or symptoms 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.

In the paper by Obradovic et al., the first name and surname of the authors have been interchanged. The correct names of the author are listed below: Slobodan Obradovic, Boris Dzudovic, Bojana Subotic, Jovan Matijasevic, Zorica Mladenovic, Aleksandar Bokan, Jadranka Trobok, Sandra Pekovic, Sonja Salinger-Martinovic, Ljiljana Jovanovic, Ljiljana Kos, Tamara Kovacevic-Preradovic, Maja Nikolic, Vladimir Miloradovic, Ana Kovacevic-Kuzmanovic, Zec Nenad, Natasa Markovic-Nikolic, Ilija Srdanovic, Zoran Gluvic, Srdjan Kafedzic, Sasa Pancevacki, Aleksandar Neskovic and Stavros Konstantinides.

Introduction: Over the past 15 years, direct oral anticoagulant (DOAC) drugs have replaced vitamin K antagonists in a number of indications requiring oral anticoagulant therapy. Review work: The article written is an overview of the most important information related to the use of DOAC drugs in the secondary prevention of venous thromboembolism (VTE). The first randomized studies with dabigatran, rivaroxaban and apixaban are presented, which introduced these drugs into clinical practice in the first step, and then enabled the prolonged safe use of these drugs in the secondary prevention of VTE. Studies have also been described as current attitudes for the use of DOAC in patients with VTE associated with malignancy and antiphospholipid syndrome. An assessment of the risk of bleeding in patients with DOAC is also presented. Finally, we briefly presented the results of the use of DOAC in the treatment of pulmonary embolism in a group of patients from the regional PE registry.

Abstract Aims Women’s participation is steadily growing in medical schools, but they are still not sufficiently represented in cardiology, particularly in cardiology leadership positions. We present the contemporary distribution of women leaders in cardiology departments in the World Health Organization European region. Methods and results Between August and December 2020, we applied purposive sampling to collect data and analyse gender distribution of heads of cardiology department in university/third level hospitals in 23 countries: Austria, Azerbaijan, Belgium, Bosnia-Herzegovina, Croatia, France, Germany, Greece, Italy, North Macedonia, Morocco, Poland, Portugal, Russia, Serbia, Slovakia, Slovenia, Spain, Switzerland, Tunisia, Turkey, Ukraine, and the UK. Age, cardiology subspecialty, and number of scientific publications were recorded for a subgroup of cardiology leaders for whom data were available. A total of 849 cardiology departments were analysed. Women leaders were only 30% (254/849) and were younger than their men counterpart (♀ 52.2 ± 7.7 years old vs. ♂ 58.1 ± 7.6 years old, P = 0.00001). Most women leaders were non-interventional experts (♀ 82% vs. ♂ 46%, P < 0.00001) and had significantly fewer scientific publications than men {♀ 16 [interquartile range (IQR) 2–41] publications vs. ♂ 44 (IQR 9–175) publications, P < 0.00001}. Conclusion Across the World Health Organization European region, there is a significant gender disparity in cardiology leadership positions. Fostering a diverse and inclusive workplace is a priority to achieve the full potential and leverage the full talents of both women and men.

Background: Two-dimensional volumetric exercise stress echocardiography (ESE) provides an integrated view of left ventricular (LV) preload reserve through end-diastolic volume (EDV) and LV contractile reserve (LVCR) through end-systolic volume (ESV) changes. Purpose: To assess the dependence of cardiac reserve upon LVCR, EDV, and heart rate (HR) during ESE. Methods: We prospectively performed semi-supine bicycle or treadmill ESE in 1344 patients (age 59.8 ± 11.4 years; ejection fraction = 63 ± 8%) referred for known or suspected coronary artery disease. All patients had negative ESE by wall motion criteria. EDV and ESV were measured by biplane Simpson rule with 2-dimensional echocardiography. Cardiac index reserve was identified by peak-rest value. LVCR was the stress-rest ratio of force (systolic blood pressure by cuff sphygmomanometer/ESV, abnormal values ≤2.0). Preload reserve was defined by an increase in EDV. Cardiac index was calculated as stroke volume index * HR (by EKG). HR reserve (stress/rest ratio) <1.85 identified chronotropic incompetence. Results: Of the 1344 patients, 448 were in the lowest tertile of cardiac index reserve with stress. Of them, 303 (67.6%) achieved HR reserve <1.85; 252 (56.3%) had an abnormal LVCR and 341 (76.1%) a reduction of preload reserve, with 446 patients (99.6%) showing ≥1 abnormality. At binary logistic regression analysis, reduced preload reserve (odds ratio [OR]: 5.610; 95% confidence intervals [CI]: 4.025 to 7.821), chronotropic incompetence (OR: 3.923, 95% CI: 2.915 to 5.279), and abnormal LVCR (OR: 1.579; 95% CI: 1.105 to 2.259) were independently associated with lowest tertile of cardiac index reserve at peak stress. Conclusions: Heart rate assessment and volumetric echocardiography during ESE identify the heterogeneity of hemodynamic phenotypes of impaired chronotropic, preload or LVCR underlying a reduced cardiac reserve.

Abstract 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.

Introduction: Since December 2019, the humanity is constantly under affection of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Despite global dissemination, neither the treatment or the specific predictive factors have been found or strictly defined yet. Aim: Aim of this study was to assess the long-term (1 year) predictive value of high-sensitive Troponin T (hsTnT) in COVID-19 affected, hospitalised patients. Methods: Between 5 March 2020 and 31 March 2020, 87 consecutive patients hospitalised at University Clinical Centre of the Republic of Srpska due to SARS-CoV2caused pneumonia, in whom hsTnT was measured, were included. The Kaplan-Meier analysis was used to assess differences in all-cause mortality between the groups. Independent predictors of all-cause mortality were identified through univariateand multivariate Cox regression analysis. Results: Compared with patients who had normal hsTnT levels, patients with raised hsTnT were significantly older (70.7 ± 13.23 vs 49 ± 15.29; p < 0.001). Glucose values were significantly increased in patients with raised hsTnT (9.29 ± 5.14 vs 6.76 ± 2.46 [4.1-5.9] mmol/L; p = 0.005), as well as serum creatinine (179.07 ± 225.58 vs 87.53 ± 18.16 μmol/L; p = 0.01), hsTnT (187.43 ± 387.29 vs 7.58 ± 3.40 pg/mL; p = 0.003), D-dimer (5.94 ± 13.78 vs 1.04 ± 1.26 [0-0.50] mg/L; p = 0.024), C-reactive protein (125.92 ± 116.82 vs 69.97 ± 73.09) [< 5.0] mg/L; p = 0.009) and calcium (1.32 ± 0.46 vs 1.03 ± 0.173 [2.20-2.65] mmol/L; p = 0.001). Kaplan-Meier analysis revealed that the number of all-cause deaths at 1 year was 19 of whom 18 were presented with elevated hsTnT (log-rank p < 0.001). When univariate Cox regression was applied, multiple predictors of all-cause mortality have been identified ie age, haemoglobin, haematocrit, urea, CK-MB as well as hsTnT. In a multiple regression model, hsTnT remained an independent predictor of poor outcome. Conclusion: Results from this study showed that the value of hsTnT during hospitalisation is possibly associated with long-term poor outcome of COVID-19 patients. Therefore, hsTnT may appear as a surrogate factor to differentiate between patients at high risk who need more intensive follow-ups.

Background In the past 3 decades, the arterial switch procedure has replaced the atrial switch procedure as treatment of choice for transposition of the great arteries. Although survival is superior after the arterial switch procedure, data on pregnancy outcomes are scarce and transposition of the great arteries after arterial switch is not yet included in the modified World Health Organization classification of maternal cardiovascular risk. Methods and Results The ROPAC (Registry of Pregnancy and Cardiac disease) is an international prospective registry of pregnant women with cardiac disease, part of the European Society of Cardiology EURObservational Research Programme. Pregnancy outcomes in all women after an arterial switch procedure for transposition of the great arteries are described. The primary end point was a major adverse cardiovascular event, defined as combined end point of maternal death, supraventricular or ventricular arrhythmias requiring treatment, heart failure, aortic dissection, endocarditis, ischemic coronary events, and thromboembolic events. Altogether, 41 pregnant women (mean age, 26.7±3.9 years) were included, and there was no maternal mortality. A major adverse cardiovascular event occurred in 2 women (4.9%): heart failure in one (2.4%) and ventricular tachycardia in another (2.4%). One woman experienced fetal loss, whereas no neonatal mortality was observed. Conclusions Women after an arterial switch procedure for transposition of the great arteries tolerate pregnancy well, with a favorable maternal and fetal outcome. During counseling, most women should be reassured that the risk of pregnancy is low. Classification as modified World Health Organization risk class II seems appropriate.