Alcohol drinks, especially wine, have been described since 6,000 B.C. For many years in modern medicine, wine in moderation has been considered healthy for cardiovascular prevention, i.e., recommended by nutrition committees. Some regional guidelines still recommend one to two standard drinks per day. By the very recent (January 2023), World Health Organization and Canadian Guidance on alcohol emphasize that any alcoholic drink is hazardous to the health and the safe amount is zero. The risk starts with every single drop. It was also nicely summarized in the manuscript “Alcohol-dose question and the weakest link in a chemical interplay” (Explor Cardiol. 2023;1:15–25. doi: 10.37349/ec.2023.00003) especially from the standpoint of a researcher in the cardiovascular arena. The newest recommendations are based on observational studies and their meta-analysis, therefore establishing associations, pointing out that alcohol may somewhat prevent cardiovascular diseases and diabetes type 2, but with a significant increase in non-cardiovascular morbidity and mortality, especially cancers. Previous recommendations, therefore, may be obsolete as they were based on studies where abstainers from alcoholic beverages had inherent higher risks. The current controversy with conflicting guidelines for alcoholic beverage consumption in the era of precision medicine may stimulate more fundamental investigations up to genetic ones and find the cause-effect relations. In the era of precision medicine, it may come closer to discovering the causes of cancers and many other diseases, enabling predictions of reactions to alcoholic beverages by each person, not just in the population.

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.

INTRODUCTION Sodium-glucose cotransporter-2 (SGLT2) inhibitors are integral in treating patients with heart failure, regardless of the existence of diabetes mellitus. In light of their benefits on the heart muscle, the question of their effect on acute coronary syndrome is raised, and a hypothesis as to whether they can be implemented in its treatment is proposed. The aim of the article was to indicate the potential of using SGLT2 inhibitors in the treatment of myocardial infarction (MI). EVIDENCE ACQUISITION A PubMed search for articles published between October 2017 and May 2022 was conducted using the following keywords: "SGLT2 inhibitors," "Acute Coronary Syndrome," "Treatment," "Prognosis." Reference lists of identified articles were searched for further articles. EVIDENCE SYNTHESIS Reports from clinical trials and animal studies thus far investigating mechanistic pathways of SGLT2 inhibitors' effect in relation to acute myocardial infarction were interplayed to extract relevant findings and analyze the safety of this therapy in acute coronary syndrome (ACS) patients. CONCLUSIONS SGLT2 inhibitors indicate beneficial effects in acute cardiovascular incident by various mechanisms, and early initiation of therapy may improve outcomes for AMI survivors.

Background The incidence of the signs and symptoms of acute pulmonary embolism (PE) according to mortality risk, age and sex has been partly explored. Patients and methods A total of 1242 patients diagnosed with acute PE and included in the Regional Pulmonary Embolism Registry were enrolled in the study. Patients were classified as low risk, intermediate risk or high risk according to the European Society of Cardiology mortality risk model. The incidence of the signs and symptoms of acute PE at presentation with respect to sex, age, and PE severity was investigated. Results The incidence of haemoptysis was higher in younger men with intermediate-risk (11.7% vs 7.5% vs 5.9% vs 2.3%; p=0.01) and high-risk PE (13.8% vs 2.5% vs 0.0% vs 3.1%; p=0.031) than in older men and women. The frequency of symptomatic deep vein thrombosis was not significantly different between subgroups. Older women with low-risk PE presented with chest pain less commonly (35.8% vs 55.8% vs 48.8% vs 51.9%, respectively; p=0.023) than men and younger women. However, younger women had a higher incidence of chest pain in the lower-risk PE group than in the intermediate-risk and high-risk PE subgroups (51.9%, 31.4% and 27.8%, respectively; p=0.001). The incidence of dyspnoea (except in older men), syncope and tachycardia increased with the risk of PE in all subgroups (p<0.01). In the low-risk PE group, syncope was present more often in older men and women than in younger patients (15.5% vs 11.3% vs 4.5% vs 4.5%; p=0.009). The incidence of pneumonia was higher in younger men with low-risk PE (31.8% vs<16% in the other subgroups, p<0.001). Conclusion Haemoptysis and pneumonia are prominent features of acute PE in younger men, whereas older patients more frequently have syncope with low-risk PE. Dyspnoea, syncope and tachycardia are symptoms of high-risk PE irrespective of sex and age.

In modern cardiology, sodium‐glucose cotransporter 2 (SGLT2) inhibitors are critical components of heart failure (HF) treatment algorithms and exert their effects primarily by preventing glucose reabsorption and facilitating its urinary excretion. The objective was to systematically review randomized controlled trials (RCTs) assessing the effects of SGLT2 inhibitors, particularly canagliflozin, empagliflozin, dapagliflozin, ertugliflozin, sotagliflozin (dual SGLT inhibitor), and their use in HF. Systematic searches of PubMed/Medline, The Cochrane Central Register of Controlled Trials (CENTRAL), and ClinicalTrials.gov databases were performed. There were no restrictions imposed on the date and status of publication; however, there were restrictions on language for the searched studies. A total of 1139 records were identified in the bibliographic searches from both databases and the register of choice for this systematic review. Following duplicate removal, screening for titles and abstracts, and thorough assessment of full‐text articles, 12 RCTs met the inclusion criteria. Altogether, 83 878 patients were included in this review. Among the included studies, two RCTs, with six respective reports, investigated canagliflozin, four RCTs with 13 derived reports investigated dapagliflozin, three RCTs with 12 separate reports studied the effects of empagliflozin, one RCT and its three respective reports assessed ertugliflozin's effects, and two RCTs with one added report investigated the dual inhibitor sotagliflozin. Pooled meta‐analytic effects of SGLT2 inhibitors were as follows: on atrial fibrillation odds ratio (OR) = 0.83, 95% confidence interval (CI): 0.68–1.01, prediction interval (PI): 0.57–1.19; on HF hospitalization OR = 0.69, 95% CI: 0.60–0.78, PI: 0.60–0.78; on cardiovascular death OR = 0.82, 95% CI: 0.58–1.15, PI: 0.42–1.60; and on major adverse cardiovascular events OR = 0.90, 95% CI: 0.77–1.06, PI: 0.71–1.15. SGLT2 inhibitors significantly improve the quality of life in HF patients. Their beneficial effects on HF, especially in left ventricular dysfunction, have made their use possible irrespective of diabetes mellitus or atrial fibrillation status.

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.