Long-Term Prognosis after ST-Elevation Myocardial Infarction in Patients with Premature Coronary Artery Disease.

BACKGROUND: A significant percentage of younger patients with myocardial infarction have premature coronary artery disease (CAD). The aims of this study were to analyze all-cause mortality and major adverse cardiovascular events (MACEs cardiovascular death, non-fatal reinfarction, stroke, target vessel revascularization) during eight-year follow-up in patients with ST-elevation myocardial infarction (STEMI) and premature CAD. METHOD: We analyzed 2560 STEMI patients without previous CAD and without cardiogenic shock at admission who were treated with primary PCI. CAD was classified as premature in men aged <50 years and women <55 years. RESULTS: Premature CAD was found in 630 (24.6%) patients. Patients with premature CAD have fewer comorbidities and better initial angiographic findings compared to patients without premature CAD. The incidence of non-fatal adverse ischemic events was similar to the incidence in older patients. Premature CAD was an independent predictor for lower mortality (HR 0.50 95%CI 0.28-0.91) and MACEs (HR 0.27 95%CI 0.15-0.47). In patients with premature CAD, EF < 40% was the only independent predictor of mortality (HR 5.59 95%CI 2.18-8.52) and MACEs (HR 4.18, 95%CI 1.98-8.13). CONCLUSIONS: Premature CAD was an independent predictor for lower mortality and MACEs. In patients with premature CAD, EF < 40% was an independent predictor of eight-year mortality and MACEs.

The Influence of Hyperthyroidism on the Coagulation and on the Risk of Thrombosis.

Introduction: Apart from the well-known fact that hyperthyroidism induces multiple prothrombotic disorders, there is no consensus in clinical practice as to the impact of hyperthyroidism on the risk of thrombosis. The aim of this study was to examine the various hemostatic and immunologic parameters in patients with hyperthyroidism. Methods: Our study consists of a total of 200 patients comprised of 64 hyperthyroid patients, 68 hypothyroid patients, and 68 euthyroid controls. Patient thyroid status was determined with standard tests. Detailed hemostatic parameters and cardiolipin antibodies of each patient were determined. Results: The values of factor VIII (FVIII), the Von Willebrand factor (vWF), fibrinogen, plasminogen activator inhibitor-1 (PAI-1), and anticardiolipin antibodies of the IgM class were significantly higher in the hyperthyroid patients than in the hypothyroid patients and euthyroid controls. The rate of thromboembolic manifestations was much higher in hyperthyroid patients (6.25%) than in hypo-thyroid patients (2.9%) and euthyroid controls (1.4%). Among hyperthyroid patients with an FVIII value of ≥1.50 U/mL, thrombosis was recorded in 8.3%, while in hyperthyroid patients with FVIII value ≤ 1.50 U/mL the occurrence of thrombosis was not recorded. The incidence of atrial fibrillation (AF) was significantly higher (8.3%) in the hyperthyroid patients compared to the hypothyroid patients (1.5%) and euthyroid controls (0%). Conclusions: High levels of FVIII, vWF, fibrinogen, PAI-1, and anticardiolipin antibodies along with other hemostatic factors contribute to the presence of a hypercoaguable state in patients with hyperthyroidism. The risk of occurrence of thrombotic complications is especially pronounced in patients with a level of FVIII exceeding 150% and positive anticardiolipin antibodies of the IgM class. Patients with AF are at particularly high risk of thrombotic complications due to a hyperthyroid prothrombotic milieu.

Information, Coding, and Biological Function: The Dynamics of Life.

In the mid-20th century, two new scientific disciplines emerged forcefully: molecular biology and information-communication theory. At the beginning, cross-fertilization was so deep that the term genetic code was universally accepted for describing the meaning of triplets of mRNA (codons) as amino acids. However, today, such synergy has not taken advantage of the vertiginous advances in the two disciplines and presents more challenges than answers. These challenges not only are of great theoretical relevance but also represent unavoidable milestones for next-generation biology: from personalized genetic therapy and diagnosis to Artificial Life to the production of biologically active proteins. Moreover, the matter is intimately connected to a paradigm shift needed in theoretical biology, pioneered a long time ago, that requires combined contributions from disciplines well beyond the biological realm. The use of information as a conceptual metaphor needs to be turned into quantitative and predictive models that can be tested empirically and integrated in a unified view. Successfully achieving these tasks requires a wide multidisciplinary approach, including Artificial Life researchers, to address such an endeavour.

Prognostic Implications of the Timing of ST-Elevation Myocardial Infarction Development in Relation to COVID-19 Infection.

Background: Patients with ST-segment elevation myocardial infarction (STEMI) and COVID-19 infection have a worse clinical course and prognosis. The prognostic significance of the timing of STEMI in relation to COVID-19 infection was not investigated. Objectives: To assess whether the time of STEMI development in relation to COVID-19 infection (concurrent or following the infection) influenced the short-term prognosis. Methods: This was an observational study of consecutive COVID-19 patients with STEMI admitted to the COVID-hospital Batajnica (February 2021-March 2022). The patients were divided into the "STEMI first" group: patients with STEMI and a positive polymerase chain reaction test for COVID-19, and the "COVID-19 first" group: patients who developed STEMI during COVID-19 treatment. All patients underwent coronary angiography. The primary endpoint was in-hospital all-cause mortality. Results: The study included 87 patients with STEMI and COVID-19 (Mage, 66.7 years, 66% male). The "STEMI first" group comprised 54 (62.1%) patients, and the "COVID-19 first" group included 33 (37.9%) patients. Both groups shared a comparatively high burden of comorbidities, similar angiographic and procedural characteristics, and high percentages of performed percutaneous coronary interventions with stent implantation (90.7% vs. 87.9%). In-hospital mortality was significantly higher in the "COVID-19 first" group compared to the "STEMI first" group (51.5% vs. 27.8%). Following adjustment, the "COVID-19 first" group had a hazard ratio of 3.22 (95% confidence interval, 1.18-8.75, p = .022) for in-hospital all-cause death, compared with the "STEMI first" group (reference). Conclusion: Clinical presentation with COVID-19 infection, followed by STEMI ("COVID-19 first"), was associated with greater short-term mortality compared to patients presenting with STEMI and testing positive for COVID-19 ("STEMI first").

Late presentation of traumatic tricuspid valve chordal rupture and pericardial rupture with cardiac herniation: a case report.

BACKGROUND: Although chest trauma happens very often, accompanying tricuspid valve injuries occur rarely and may be manifested by scarce symptoms and signs. Pericardial rupture with cardiac herniation is even a bigger rarity. Transthoracic echocardiography plays a key role in the diagnosis of valve injuries but is of limited value in cardiac herniation. CASE PRESENTATION: We present the case of 58-year-old man who experienced severe chest trauma in a car accident. Symptoms of right heart failure occurred 10 years after the injury, due to the loss of tricuspid leaflet support caused by the rupture of tendinous chords with significant tricuspid regurgitation. Intraoperatively, old posttraumatic pericardial rupture into left pleura was also found, with partial cardiac herniation and pressure of the edge of pericardium on all left-sided coronary arteries simultaneously. The patient was successfully operated and is free of symptoms 4 years later. CONCLUSIONS: This case emphasizes the importance of timely diagnosis and underlines a mechanism that leads to delayed rupture of the tricuspid valve apparatus. Repeated echocardiography in all patients who experienced chest trauma could be of great importance. Also, given the limited value of echocardiography in posttraumatic pericardial rupture and cardiac herniation, cardiac computed tomography should be performed.

Depression, anxiety, and quality of life as predictors of rehospitalization in patients with chronic heart failure.

BACKGROUND: Chronic heart failure (CHF) is a severe condition, often co-occurring with depression and anxiety, that strongly affects the quality of life (QoL) in some patients. Conversely, depressive and anxiety symptoms are associated with a 2-3 fold increase in mortality risk and were shown to act independently of typical risk factors in CHF progression. The aim of this study was to examine the impact of depression, anxiety, and QoL on the occurrence of rehospitalization within one year after discharge in CHF patients. METHODS: 148 CHF patients were enrolled in a 10-center, prospective, observational study. All patients completed two questionnaires, the Hospital Anxiety and Depression Scale (HADS) and the Questionnaire Short Form Health Survey 36 (SF-36) at discharge timepoint. RESULTS: It was found that demographic and clinical characteristics are not associated with rehospitalization. Still, the levels of depression correlated with gender (p ≤ 0.027) and marital status (p ≤ 0.001), while the anxiety values ​​were dependent on the occurrence of chronic obstructive pulmonary disease (COPD). However, levels of depression (HADS-Depression) and anxiety (HADS-Anxiety) did not correlate with the risk of rehospitalization. Univariate logistic regression analysis results showed that rehospitalized patients had significantly lower levels of Bodily pain (BP, p = 0.014), Vitality (VT, p = 0.005), Social Functioning (SF, p = 0.007), and General Health (GH, p = 0.002). In the multivariate model, poor GH (OR 0.966, p = 0.005) remained a significant risk factor for rehospitalization, and poor General Health is singled out as the most reliable prognostic parameter for rehospitalization (AUC = 0.665, P = 0.002). CONCLUSION: Taken together, our results suggest that QoL assessment complements clinical prognostic markers to identify CHF patients at high risk for adverse events. CLINICAL TRIAL REGISTRATION: The study is registered under http://clinicaltrials.gov (NCT01501981, first posted on 30/12/2011), sponsored by Charité - Universitätsmedizin Berlin.

Successful Caesarean Section on Ticagrelor Treatment One Day after Primary Percutaneous Coronary Intervention.

Caesarean section is a challenging intervention in patients treated with dual antiplatelet therapy. We present a case of a 32-year-old pregnant woman experiencing large acute myocardial infarction (MI) of the anterolateral wall, complicated by cardiogenic shock in the 38th week of pregnancy, and treated with drug-eluting stent implantation and dual antiplatelet therapy (DAPT) consisting of aspirin and ticagrelor. Less than 24 h after the MI delivery started, an urgent Caesarean section was indicated. As multiplate aggregometry testing showed a relatively insufficient level of ticagrelor platelet inhibition and a moderate level of aspirin platelet inhibition, a Caesarean section was performed without discontinuation of ticagrelor, which was decided due to the need for emergency surgery. Local hemostatic measures including administration of tranexamic acid were applied. The patient did not experience excessive bleeding. A healthy male baby was born. To the best of our knowledge, this is the first reported case of surgery in pregnant women treated with DAPT without ticagrelor discontinuation.

Morphometric and volumetric analysis of lacrimal glands in patients with thyroid eye disease.

Assessment of morphometric and volumetric changes in lacrimal glands in thyroid eye disease, its clinical manifestations in relation of disease progression. Retrospective volumetric analysis included both genders and was performed on total of 183 patients - 91 patients with diagnosed Grave's disease and thyroid eye disease and 92 patients without Grave's disease and thyroid eye disease who underwent multidetector computed tomography (MDCT) examination in routine daily work according to other medical indications. In the group of females, there was statistical significance between patients with thyroid eye disease and controls who were smoking and had body weight gain. We found statistical significance in volumetric enlargements for both orbits in both genders for the patients group when compared to controls. There was also statistical significance in morphometric characteristics for the lacrimal gland diameters measured. Determination planimetric morphometric parameters of importance were coronary height of lacrimal gland of the right eye, coronary height of lacrimal gland of the left eye and coronary width of lacrimal gland of the left eye for the group of males. In a group of females the established determination parameters of importance were the coronary height of lacrimal gland of the left eye, the axial width of lacrimal gland of the left eye, volume of lacrimal gland of the right eye and the volume of lacrimal gland of the left eye. When we compared the displaced lacrimal gland coming forward (proptosis) in time progressing disease between group of patients and controls, we also found statistical significant connection. Evaluation of lacrimal gland volumetric and morphometric data may increase validity of defining this anatomical substrate and its morphology disruption as liable tool for thyroid eye disease progression follow up and treatment planning and outcome.

Prognostic Impact of Non-Cardiac Comorbidities on Long-Term Prognosis in Patients with Reduced and Preserved Ejection Fraction following Acute Myocardial Infarction.

BACKGROUND: We aimed to analyze the prevalence and long-term prognostic impact of non-cardiac comorbidities in patients with reduced and preserved left-ventricular ejection fraction (EF) following ST-elevation myocardial infarction (STEMI). METHOD: A total of 3033 STEMI patients undergoing primary percutaneous coronary intervention (pPCI) were divided in two groups: reduced EF < 50% and preserved EF ≥ 50%. The follow-up period was 8 years. RESULTS: Preserved EF was present in 1726 (55.4%) patients and reduced EF was present in 1389 (44.5%) patients. Non-cardiac comorbidities were more frequent in patients with reduced EF compared with patients with preserved EF (38.9% vs. 27.4%, respectively, p < 0.001). Lethal outcome was registered in 240 (17.2%) patients with reduced EF and in 40 (2.3%) patients with preserved EF, p < 0.001. Diabetes and chronic kidney disease (CKD) were independent predictors for 8-year mortality in patients with preserved EF. In patients with reduced EF, CKD was independently associated with 8-year mortality. CONCLUSION: In patients who had reduced EF, the prevalence of non-cardiac comorbidities was higher than in patients who had preserved EF after STEMI. Only diabetes mellitus and CKD were independently associated with 8-year mortality in analyzed patients.

Age- and Gender-Related Differences in the Hemodynamic Status of Patients with Mild or Moderate Hypertension.

Purpose: The aim of this study was to use non-invasive impedance cardiography (ICG) to determine the hemodynamic status of patients with grade 1 and grade 2 hypertension in relation to gender and age. Patients and Methods: We analyse prospectively collected data of 158 patients with grade 1 or grade 2 arterial hypertension. Patients were grouped according to age: 1) <50 years and 2) ≥50 years. Hemodynamic status of patients was assessed by using non-invasive ICG. For the purpose of this study two hemodynamic parameters were used: a) systemic vascular resistance index (SVRI) and b) left cardiac work index (LCWI). The primary endpoint was the hemodynamic status of patients. The secondary endpoint was hypertension-mediated organ damage. Results: Increased SVRI was assessed in 80% of patients, more common in the ≥50 years group than in the <50 years group (88.5% vs 64.8%; p < 0.01). The occurrence of increased systemic vascular resistance correlates hierarchically with increasing age. Elevated LCWI (hypervolemia and/or hyperinotropy) was present in 63% of patients, more often in males than females (70.3% vs 57.1%; p < 0.05) as well in those <50 years than in older patients (70.4% vs 59.6%; p < 0.05). Patients with diabetes were less likely to have hypervolemia/hyperinotropy than those without diabetes (46.7% vs 67.2%; p < 0.01). Hypervolemia/hyperinotropy (46.7%) and hypovolemia/hypoinotropy (43.3%) were present in a similar percentage of diabetic patients. Left ventricular hypertrophy was found in 30 patients (19%). Patients with left ventricular hypertrophy were more commonly male (66.7% vs 42.2%; p = 0.016) and had increased systemic vascular resistance (96.7% vs 77.3%; p = 0.015) compared to the patients without left ventricular hypertrophy. Hypertensive retinopathy grade III was found in 14 patients (8.9%). Elevated daytime systolic pressure, diabetes and increased age are independent predictors of grade III hypertensive retinopathy. Patients with reduced renal function had higher mean systolic blood pressure (p < 0.05), were more commonly male (p < 0.01) and older (p < 0.01) than those without reduced renal function. Conclusion: Although there are certain correlations between hemodynamic disorders and age and gender, specific hemodynamic status of an individual patient with hypertension cannot reliably be predicted on the basis of age and gender. The measurement of hemodynamic parameters by ICG can guide the clinician to select appropriate antihypertensive therapy to the patients' hemodynamic pathophysiologic condition.

Use of Anticoagulant Therapy in Patients with Acute Myocardial Infarction and Atrial Fibrillation.

The incidence of atrial fibrillation (AF) in acute coronary syndrome (ACS) ranges from 2.3-23%. This difference in the incidence of AF is explained by the different ages of the patients in different studies and the different times of application of both reperfusion and drug therapies in acute myocardial infarction (AMI). About 6-8% of patients who underwent percutaneous intervention within AMI have an indication for oral anticoagulant therapy with vitamin K antagonists or new oral anticoagulants (NOAC).The use of oral anticoagulant therapy should be consistent with individual risk of bleeding as well as ischemic risk. Both HAS-BLED and CHA2DS2VASc scores are most commonly used for risk assessment. Except in patients with mechanical valves and antiphospholipid syndrome, NOACs have an advantage over vitamin K antagonists (VKAs). One of the advantages of NOACs is the use of fixed doses, where there is no need for successive INR controls, which increases the patient's compliance in taking these drugs. The use of triple therapy in ACS is indicated in the case of patients with AF, mechanical valves as well as venous thromboembolism. The results of the studies showed that when choosing a P2Y12 receptor blocker, less potent P2Y12 blockers such as Clopidogrel should be chosen, due to the lower risk of bleeding. It has been proven that the presence of AF within AMI is associated with a higher degree of reinfarction, more frequent stroke, high incidence of heart failure, and there is a correlation with an increased risk of sudden cardiac death. With the appearance of AF in ACS, its rapid conversion into sinus rhythm is necessary, and in the last resort, good control of heart rate in order to avoid the occurrence of adverse clinical events.

A three-phase method for identifying functionally related protein groups in weighted PPI networks.

Identifying significant protein groups is of great importance for further understanding protein functions. This paper introduces a novel three-phase heuristic method for identifying such groups in weighted PPI networks. In the first phase a variable neighborhood search (VNS) algorithm is applied on a weighted PPI network, in order to support protein complexes by adding a minimum number of new PPIs. In the second phase proteins from different complexes are merged into larger protein groups. In the third phase these groups are expanded by a number of 2-level neighbor proteins, favoring proteins that have higher average gene co-expression with the base group proteins. Experimental results show that: (i) the proposed VNS algorithm outperforms the existing approach described in literature and (ii) the above-mentioned three-phase method identifies protein groups with very high statistical significance.

Variable Neighborhood Search for Partitioning Sparse Biological Networks into the Maximum Edge-Weighted k-Plexes.

In a network, a k-plex represents a subset of n vertices where the degree of each vertex in the subnetwork induced by this subset is at least n-k. The maximum edge-weight k-plex partitioning problem is to find the k-plex partitioning in edge-weighted network, such that the sum of edge weights is maximal. The Max-EkPP has an important role in discovering new information in large biological networks. We propose a variable neighborhood search (VNS) algorithm for solving Max-EkPP. The VNS implements a local search based on the 1-swap first improvement strategy and the objective function that takes into account the degree of every vertex in each partition. The objective function favors feasible solutions and enables a gradual increase of the function's value, when moving from slightly infeasible to barely feasible solutions. Experimental computation is performed on real metabolic networks and other benchmark instances from the literature. Comparing to the previously proposed integer linear programming (ILP), VNS succeeds to find all known optimal solutions. For all other instances, the VNS either reaches previous best known solution or improves it. The proposed VNS is also tested on a large-scale dataset not considered up to now.

Impact on long-term mortality of access and non-access site bleeding after primary percutaneous coronary intervention.

OBJECTIVES: The influence of the bleeding site on long-term survival after the primary percutaneous coronary intervention (PCI) is poorly understood. This study sought to investigate the relationship between in-hospital access site versus non-access site bleeding and very late mortality in unselected patients treated with primary PCI. METHODS: Data of the 2715 consecutive patients with ST-segment elevation myocardial infarction treated with primary PCI, enrolled in a prospective registry of a high volume tertiary centre, were analysed. Bleeding events were assessed according to the Bleeding Academic Research Consortium (BARC) criteria. The primary outcome was 4-year mortality. RESULTS: The BARC type ≥2 bleeding occurred in 171 patients (6.3%). Access site bleeding occurred in 3.8%, and non-access site bleeding in 2.5% of patients. Four-year mortality was significantly higher for patients with bleeding (BARC type ≥2) than in patients without bleeding (BARC type 0+1), (36.3% vs 16.2%, p<0.001). Patients with non-access site bleeding had higher 4 year mortality (50.7% vs 26.5%, p=0.001). After multivariable adjustment, BARC type ≥2 bleeding was the independent predictor of 4 year mortality (HR 2.01; 95% CI 1.49 to 2.71, p<0.001). Patients with a non-access site bleeding were at 2-fold higher risk of very late mortality than patients with an access site bleeding (HR 2.62; 1.78 to 3.86, p<0.001 vs HR 1.57; 1.03 to 2.38, p=0.034). CONCLUSIONS: Both access and non-access site BARC type ≥2 bleeding is independently associated with a high risk of 4-year mortality after primary PCI. Patients with non-access site bleeding were at higher risk of late mortality than patients with access site bleeding.

Oxidative stress markers predict early left ventricular systolic dysfunction after acute myocardial infarction treated with primary percutaneous coronary intervention.

BACKGROUND: Despite successful primary percutaneous coronary intervention (PCI) after ST-segment elevation myocardial infarction (STEMI), some patients develop left ventricular systolic dysfunction (LVSD) and acute heart failure (HF). Identifying patients with an increased risk of developing LVSD by means of biomarkers may help select patients requiring more aggressive therapy. OBJECTIVES: The aim of this study was to evaluate the relationship between the levels of oxidative stress markers and development of LVSD and acute HF early after STEMI. MATERIAL AND METHODS: The study enrolled 148 patients with the first STEMI, who were treated by primary PCI < 12 h from the onset of symptoms. We assessed the impact of different biomarkers for developing LVSD and acute HF (Killip ≥ 2) including: markers of necrosis - peak creatine kinase (CK), markers of myocardial stretch - B-type natriuretic peptide (BNP), inflammatory markers - C-reactive protein (CRP), leucocyte and neutrophil count, as well as oxidative stress markers - total thiol groups, catalase, superoxide dismutase (SOD) and glutathione reductase (GR). RESULTS: In multivariate analysis, thiol groups, peak CK, anterior wall infarction, and age were predictors of LVEF ≤ 40%. Out of 16 variables significantly associated with the Killip ≥ 2 in univariate logistic regression analysis, 5 appeared to be independently associated with acute HF in multivariate analysis: catalase, BNP, leucocytes, neutrophil count, and size of left atrium. CONCLUSIONS: In this study, we have shown for the first time that thiol groups and catalase are independent predictors of STEMI complication - LVSD and acute HF, respectively. Beside routine used biomarkers of necrosis and myocardial stretch, thiol groups and catalase may provide additional information regarding the risk stratification.

Prognostic performance of serial in-hospital measurements of copeptin and multiple novel biomarkers among patients with worsening heart failure: results from the MOLITOR study.

AIMS: In heart failure, various biomarkers are established for diagnosis and risk stratification; however, little is known about the relevance of serial measurements during an episode worsening heart failure (WHF). This study sought to investigate the trajectory of natriuretic peptides and multiple novel biomarkers during hospitalization for WHF and to determine the best time point to predict outcome. METHODS AND RESULTS: MOLITOR (Impact of Therapy Optimisation on the Level of Biomarkers in Patients with Acute and Decompensated Chronic Heart Failure) was an eight-centre prospective study of 164 patients hospitalized with a primary diagnosis of WHF. C-terminal fragment of pre-pro-vasopressin (copeptin), N-terminal pro-B-type natriuretic peptide (NT-proBNP), mid-regional pro-atrial natriuretic peptide (MR-proANP), mid-regional pro-adrenomedullin (MR-proADM), and C-terminal pro-endothelin-1 (CT-proET1) were measured on admission, after 24, 48, and 72 h, and every 72 h thereafter, at discharge and follow-up visits. Their performance to predict all-cause mortality and rehospitalization at 90 days was compared. All biomarkers decreased during recompensation (P < 0.05) except MR-proADM. Copeptin at admission was the best predictor of 90 day mortality or rehospitalization (χ2  = 16.63, C-index = 0.724, P < 0.001), followed by NT-proBNP (χ2  = 10.53, C-index = 0.646, P = 0.001), MR-proADM (χ2  = 9.29, C-index = 0.686, P = 0.002), MR-proANP (χ2  = 8.75, C-index = 0.631, P = 0.003), and CT-proET1 (χ2  = 6.60, C-index = 0.64, P = 0.010). Re-measurement of copeptin at 72 h and of NT-proBNP at 48 h increased prognostic value (χ2  = 23.48, C-index = 0.718, P = 0.00001; χ2  = 14.23, C-index = 0.650, P = 0.00081, respectively). CONCLUSIONS: This largest sample of serial measurements of multiple biomarkers in WHF found copeptin at admission with re-measurement at 72 h to be the best predictor of 90 day mortality and rehospitalization.

Correction to: Analysis of the CYP2C19 genotype associated with bleeding in Serbian STEMI patients who have undergone primary PCI and treatment with clopidogrel.

The correct Author names are shown in this paper.

Predictive value of metabolic syndrome definitions in patients with myocardial infarction with ST segment elevation - are they all the same?

OBJECTIVES: We sought to determine the predictive power of metabolic syndrome (MS) definitions on the prognosis in patients with myocardial infarction with ST-segment elevation (STEMI). METHODS: We prospectively included 507 patients with STEMI who were admitted for primary percutaneous coronary intervention and could be identified for MS using the AHA-NHLBI, NCEP-ATP III and IDF definitions. After applying these criteria, we divided the group in patients with MS and without MS; we compared baseline characteristics, clinical findings and outcomes among these patients. RESULTS: The prevalence of MS was lowest with the NCEP-ATP III definition (37.87%), followed by the AHA-NHLBI definition (42.80%) and highest when using the IDF definition (44.38%). During follow-up, the occurrence of new myocardial infarction and new revascularization was significantly higher in patients with MS. Only in a group of patients with MS according to the NCEP-ATP III definition, a higher number of strokes were recorded. Multivariate analysis shows that MS according to the NCEP-ATP III definition was an independent predictor for MACE (OR 1.830, 95% CI 1.238-2.704, p = .002) but not for mortality. CONCLUSION: Metabolic syndrome according to the NCEP-ATP III definition was associated with increased risk of the development of new cardiovascular events among the patients with STEMI.

Analysis of the CYP2C19 genotype associated with bleeding in Serbian STEMI patients who have undergone primary PCI and treatment with clopidogrel.

PURPOSE: Bleeding is one of the possible adverse events during clopidogrel therapy. The CYP2C19 gene is the most significant genetic factor which influences response to clopidogrel treatment. We aimed to examine the contribution of the CYP2C19 gene to bleeding occurrence during clopidogrel therapy in Serbian patients with ST segment elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PCI). METHODS: This case-control study included 53 patients who experienced bleeding and 55 patients without bleeding. Bleeding events were defined and classified using the Bleeding Academic Research Consortium (BARC) criteria. All patients were prescribed daily doses of clopidogrel during the 1-year follow-up after PCI. The CYP2C19*17 (c.-806C>T, rs12248560), rs11568732 (c.-889T>G, CYP2C19*20), CYP2C19*2 (c.681G>A; rs4244285) and CYP2C19*3 (c.636G>A; rs4986893) variants were analysed in all 108 patients. Additionally, sequencing of all nine exons, 5'UTR and 3'UTR in the rs11568732 carriers was performed. RESULTS: Association between bleeding (BARC type ≥ 2) and the CYP2C19*17 variant was not observed [odds ratio (OR), 0.53; 95% confidence interval (CI), 0.2-1.1; p = 0.107). The rs11568732 variant showed significant association with bleeding (OR, 3.7; 95% CI, 1.12-12.44; p = 0.025). Also, we found that the rs11568732 variant appears independently of haplotype CYP2C19*3B, which is contrary to the previous findings. CONCLUSIONS: Our results indicate the absence of CYP2C19*17 influence and turn the attention to the potential significance of the rs11568732 variant in terms of adverse effects of clopidogrel. However, it is necessary to conduct an independent conformation study in order to verify this finding. Also, an analysis of the functional implication of the rs11568732 variant is necessary in order to confirm the significance of this variant, both in relation to its influence on gene expression and in relation to its medical significance.

Dabigatran - Metabolism, Pharmacologic Properties and Drug Interactions.

BACKGROUND: The superiority of dabigatran has been well proven in the standard dosing regimen in prevention of stroke and systemic embolism in patients with non-valvular atrial fibrillation (NVAF) and extended venous thromboembolism (VTE) treatment. Dabigatran, an anticoagulant with a good safety profile, reduces intracranial bleeding in patients with atrial fibrillation and decreases major and clinically relevant non-major bleeding in acute VTE treatment. However, several important clinical issues are not fully covered by currently available directions with regard to dabigatran administration. The prominent one is reflected in the fact that dynamic impairment in renal function due to dehydratation may lead to haemorragic complications on the one hand, while on the other hand glomerular hyperfiltration may be a possible cause of dabigatran subdosing, hence reducing the drug's efficacy. Furthermore, limitations of the Cockcroft-Gault formula, considered a standard equation for assessing the renal function, may imply that other calculations are likely to obtain more accurate estimates of the kidney function in specific patient populations. Method and Conclusions: Although not routinely recommended, a possibility of monitoring dabigatran in special clinical settings adds to optimization of its dosage regimens, timely perioperative care and administration of urgently demanded thrombolytic therapy, therefore significantly improving this drug's safety profile. Despite the fact that dabigatran has fewer reported interactions with drugs, food constituents, and dietary supplements, certain interactions still remain, requiring considerable caution, notably in elderly, high bleeding risk patients, patients with decreased renal function and those on complex drug regimens. Additionally, upon approval of idarucizumab, an antidote to dabigatran solution, hitherto being a major safety concern, has been finally reached, which plays a vital role in life-threatening bleeding and emergency interventions and surgery.