The early detection of coronary artery disease in patients with type 2 diabetes mellitus remains uncertain. The aim of the study was to explore the correlation of circulating biomarkers for inflammation Interleukin-6 (IL-6), high-sensitivity C-reactive protein (hs-CRP) as well as N-terminal pro-

Introduction: Components of the metabolic syndrome (MetSy) have gone through myriad of changes ever since the initial cluster was defined. The Seven Countries Study taught us the basics of classical risk factors for atherosclerotic artery disease and their influence on both cardiovascular and cerebrovascular morbidity and mortality. Material and Methods: In a 3-continent, 7-country (USA, Japan, Greece, the Netherlands, Finland, Italy, and former Yugoslavia then, now Croatia and Serbia) sample of 12,763 participants -- all healthy men over 40 at entry -- systematic, quinquennial checkups were conducted over 4 decades and MetSy was defined using the IDF definition. ResultS: A total of 9,09% of participants were identified to have MetSy, while the detailed description of risk factors' combination is shown in Table 1 and Figure 1, below. Conclusion: The leading combination was hypertension (HTA), diabetes (DM) and dyslipidemia (HLP), while hypertension was the hallmark risk factor irrelevant of presence or absence of MetSy. The results of this study call for a contemporary comprehensive research involving both sexes that could elucidate better real life risk factors' relationships in aforementioned countries.

BACKGROUND Diabetes mellitus is an independent risk factor for stroke and atrial fibrillation. Therefore, the risk/benefit profile of the oral factor Xa inhibitor edoxaban stratified by diabetes is of clinical interest. METHODS 21,105 patients enrolled in ENGAGE AF-TIMI 48 were stratified into 2 pre-specified groups: without (N = 13,481) and with diabetes (N = 7,624). RESULTS On average, patients with diabetes were younger, and had a higher body mass index, CHA2DS2-VASc score and baseline endogenous Factor Xa activity. After multivariate adjustments, patients with diabetes had a similar rate of stroke and systemic embolism compared to those without diabetes (adjusted hazard ratio (HRadj) 1.08; 95% confidence interval (CI) 0.94-1.24; p = 0.28). However, the risk of major bleeding was significantly higher in patients with diabetes (HRadj 1.28; 95% CI 1.14-1.44; p < 0.001). The treatment effect of edoxaban (vs warfarin) was not modified by diabetes (all p-interactions > 0.05), a finding supported by the preserved edoxaban concentrations and inhibition of Factor Xa regardless of diabetes. The HRs of stroke and systemic embolism in patients receiving the higher-dose edoxaban regimen vs warfarin were 0.93 and 0.84 (p-interaction = 0.54) in those with and without diabetes respectively. The higher-dose edoxaban regimen reduced major bleeding (by 19-21%) and cardiovascular death (by 7-17%) regardless of diabetes (p-interactions = 0.81 and 0.33 respectively). CONCLUSION Patients with diabetes in ENGAGE AF-TIMI 48 had higher bleeding risk, but after adjustment similar stroke risk, compared to those without diabetes. The higher-dose edoxaban regimen had similar efficacy compared to warfarin, while reducing bleeding and cardiovascular mortality, irrespective of diabetes.

Heart failure is a major cause of morbidity, mortality and re-hospitalizations and is highly prevalent in myocardial infarction survivors. Cardiac rehabilitation based on exercise training and heart failure self-care counseling have each been shown to improve clinical status and clinical outcomes. We designed our study with aim to evaluate the usefulness of exercise based in house cardiac rehabilitation/ secondary prevention program in patients with heart failure with mid-range ejection fraction (HFmrEF) after myocardial infarction. Out of 2753 patients who were admitted to our three weeks in- hospital secondary prevention program – exercised based cardiac rehabilitation, we analyze a total of 219 patients who were admitted early after coronary revascularization (percutaneus coronary interventions or coronary bypass surgery) with HFmrEF. The majority of patients were males (68%). Risk factors and co morbidities were noted. Patients were selected for exercise training after six minute walking test or exercise stress test (cardiopulmonary dominantly to evaluate unexpected exertional dyspnea). After 3 weeks in house cardiac rehabilitation the patients were re-tested. The major comorbidities in our patient population were as follows: hypertension, diabetes and dyslipidemia. Six minutes walking test was performed and the total distance walked ranged from 120 to 480 meters and the beginning of the program. Patient had 7 -days a week training program. After the 3 weeks in hospital exercise rehabilitation the improvement in the test was ∼32%. Cardiopulmonary test showed also improvement of functional capacity.We noted several rhythm disturbance complications by telemetry (VES, SVES). None had acutisation of heart failure (with peripheral edema and congestion). All patients fulfilled cardiac rehabilitation program. Supervised multidisciplinary cardiac rehabilitation program, including an individualized exercise component is effective and can improve functional status and exercise tolerance in patient with HFmrEF after myocardial infarction.

Coronary collateral circulation exerts protective effects on myocardial ischemia due to coronary artery disease (CAD) and can be promoted by exercise (E) with heparin (H) co-administration. Whether this arteriogenetic effects is accompanied by functional improvement of left ventricle (LV) during stress remains unknown. To establish the stress-induced functional effects on LV regional and global function of 2-week cycle of H+E in patients with “no-option” CAD. In a prospective, single-center, double-blind, randomized, parallel-group study we recruited 32 “no-option” patients (27 males; mean age of 61±8 years), with stable angina and CTO, refractory to OMT, not suitable for revascularization and with E-induced ischemia. All underwent 2-week cycle of E (2 E test per day, 5 days a week) and were pre-treated with i.v. 0.9% saline or unfractionated H (100 IU/kg up to maximum of 5.000IU, 10 min prior to E). Canadian Class Score (CCS) and 12-lead E-ECG for time-to-1 mm ST-segment depression were assessed at entry and after treatment. LV function was evaluated during treadmill exercise with conventional and advanced imaging indices: Wall Motion Score Index (WMSI); Ejection Fraction (EF); Force (systolic blood pressure/end-systolic volume); Global Longitudinal Strain (GLS). Post-treatment exercise-time and CCS improved in both groups. In H+E patients exercise-time improved from 369.8±107.8 sec to 475.3±114.6 sec (p=0.001) while in E patients improved from 384±152.7 sec to 464.8±134.1 sec (p=0.019). CCS score changed in H+E from 2.6±0.7 to 1.9±0.7 (p=0.000), and in E group from 2.4±0.7 to 2.1±0.9 (p=0.046). At peak exercise, H+E was different from E group for EF and GLS (see Table). Effects of H+E on SE parameters H+E p P+E p *H+E vs P+E STRESS Time 0 vs Time 1 Time 0 vs Time 1 Time 0 Time 1 WMSI 1.377 vs 1.279 0.005 1.404 vs 1.376 0.290 0.626 0.255 EF (%) 60.9 vs 64.8 0.016 61.2 vs 57.8 0.284 0.943 0.016 Force (mmHg/mL) 6.36 vs 6.5 0.158 5.82 vs 4.68 0.209 0.760 0.098 GLS (%) −16.96 vs −18.50 0.001 −15.79 vs −15.60 0.380 0.325 0.027 SE = stress echocardiography; H+E = heparin+exercise; P+E = placebo+exercise; Time 0 = before randomization; Time 1 = after 2-week therapy cycle. *p values. A 2-week, H+E cycle is associated with improvement in regional and global LV function during exercise, concordantly shown by conventional (WMSI, EF) and advanced (GLS) echocardiographic indices of LV function. This integrates and supplements the classical objective index based on ST-segment depression, unable to localize and quantify the functional consequences of therapy on myocardial ischemia.

Results of currently available randomized trials have shown divergent outcomes in diabetic patients undergoing percutaneous coronary intervention (PCI) or coronary artery bypass grafting (CABG). The 2018 ESC/EACTS guidelines on myocardial revascularization do not recommend PCI in patients with diabetes and SYNTAX score ≥23. We aimed to compare the all-cause 4-year mortality after revascularization for complex coronary artery disease (CAD) in diabetics. The study group comprised consecutive diabetics with angiographically proven three-vessel CAD (≥50% diameter stenosis) and/or unprotected left main CAD (≥50% diameter stenosis) without major hemodynamic instability, who were treated in two institutions with PCI or referred for CABG between 2008 and 2010. All-cause mortality was ascertained by telephone contacts and/or from Mortality Registries. Using the hospital data system, 5145 patients were screened and 4803 elected not to follow the inclusion criteria. Out of 342 included patients, 177 patients underwent PCI and 165 patients were referred for CABG. Patients with whom CABG was performed were significantly older (64.69±8.8 vs. 62.6±9.4, p=0.03), more often on insulin treatment (91/165=55.2% vs. 26/177=14.7%, p<0.01), had more complex anatomical characteristics i.e. higher SYNTAX scores (32.5 IQR (15) vs. 18.0 IQR (15), p<0.01) and with left main stenosis (70/165=42.4% vs. 7/177=4.0%, p<0.01), compared to patients treated with PCI. The cumulative incidence rates of all-cause death were significantly different between PCI and CABG at 4 years (16/177=9.0% vs. 26/165=15.7%, respectively, log-rank p=0.03). There was a higher incidence of all-cause mortality in PCI patients with intermediate (23–32) and high (≥33) SYNTAX scores compared with those with low (0–22) SYNTAX scores (6/32=18.8% vs. 6/124=4.8%, log-rank p=0.01; 4/21=19.1% vs. 6/124=4.8%, log-rank p=0.02, respectively). On the contrary, patients who underwent CABG displayed similar morality rates irrespective of the SYNTAX scores (SYNTAX 0–22: 5/34=14.7%; SYNTAX 23–32: 9/54=16.7%; SYNTAX ≥33: 12/77=15.6%; log-rank p=0.9). Finally, when compared with CABG, more deaths were observed following PCI with intermediate and high SYNTAX scores (intermediate SYNTAX (23–32) PCI: 6/32=18.8% vs. CABG: 26/165=15.8%, log-rank p=0.94; high SYNTAX (≥33) PCI: 4/21=19.1% vs. CABG 26/165=15.8%, log-rank p=0.87). During a 4-year follow-up, CABG in comparison with PCI was associated with a higher rate of all-cause death, which can be accounted for by older age and comorbidities. In diabetics, our analysis is suggestive that PCI probably should be avoided in patients with SYNTAX ≥23, which is in concordance with the most recent guidelines. Individualized risk assessment as well as quantification of CAD by SYNTAX score remains essential in choosing appropriate revascularization method in patients with diabetes and complex CAD. None

AIMS The long-term outcomes of biolimus-eluting stents (BESs) with biodegradable polymer as compared with bare-metal stent (BMS) in patients with ST-segment elevation myocardial infarction (STEMI) remain unknown. METHODS AND RESULTS We performed a 5-year clinical follow-up of 1157 patients (BES: N = 575 and BMS: N = 582) included in the randomized COMFORTABLE AMI trial. Serial intracoronary imaging of stented segments using both intravascular ultrasound (IVUS) and optical coherence tomography performed at baseline and 13 months follow-up were analysed in 103 patients. At 5 years, BES reduced the risk of major adverse cardiac events [MACE; hazard ratio (HR) 0.56, 95% confidence interval (CI): 0.39-0.79, P = 0.001], driven by lower risks for target vessel-related reinfarction (HR 0.44, 95% CI: 0.22-0.87, P = 0.02) and ischaemia-driven target lesion revascularization (HR 0.41, 95% CI: 0.25-0.66, P < 0.001). Definite stent thrombosis (ST) was recorded in 2.2% and 3.9% (HR 0.57, 95% CI: 0.28-1.16, P = 0.12) with no differences in rates of very late definite ST (1.3% vs. 1.6%, P = 0.77). Optical coherence tomography showed no difference in the frequency of malapposed stent struts at follow-up (BES 0.08% vs. BMS 0.02%, P = 0.10). Uncovered stent struts were rarely observed but more frequent in BES (2.1% vs. 0.15%, P < 0.001). In the IVUS analysis, there was no positive remodelling in either group (external elastic membrane area change BES: -0.63 mm2, 95% CI: -1.44 to 0.39 vs. BMS -1.11 mm2, 95% CI: -2.27 to 0.04, P = 0.07). CONCLUSION Compared with BMS, the implantation of biodegradable polymer-coated BES resulted in a lower 5-year rate of MACE in patients with STEMI undergoing primary percutaneous coronary intervention. At 13 months, vascular healing in treated culprit lesions was almost complete irrespective of stent type. CLINICAL TRIAL REGISTRATION http://www.clinicaltrials.gov. Unique identifier: NCT00962416.

Background: Right ventricular dysfunction (RVD) is a well-known predictor of early death in patients with acute pulmonary embolism and thus early identification of RVD is critical in the risk stratification or management of acute pulmonary embolism (PE). Aim of this study was to investigate a useful role of cardiac biomarker NTproBNP for predicting echocardiographic right ventricular dysfunction in patients with acute pulmonary embolism. Methods: A retrospective analysis was performed in 195 consecutive adult patients with pulmonary embolism from the Serbian University Pulmonary Embolism Registry (SUPER 2015-2019) created by six university clinics: Military Medical Academy (Belgrade), Institute of Pulmonary Diseases (Sremska Kamenica), Clinical Center (Nis), University Clinic Zvezdara, Clinical Center (Kragujevac) and University Clinical Centre of Republic of Srpska (Banja Luka). All patients were divided into RVD group and non-RVD group according to whether there was increase in systolic pressure in right ventricle (>40mmHg) on echocardiography. Odds ratios (OR) and 95% confidence intervals (CI) assessing the risk factors for RVD were assessed by multivariate logistic regression. The ability of the NT proBNP in predicting the RVD was described by the Receiving Operating Curves analysis. Results: The mean age is a strong predictor of echocardiographic RVD in patients with PE. The simple measurements of this cardiac biomarker could be helpful in clinical decision-making or risk stratification in patients with PE.

BACKGROUND This study examined the accuracy of cardiopulmonary exercise testing (CPET) on a treadmill (TM) and recumbent ergometry (RE) in the predicting coronary artery disease (CAD) severity and prognosis. METHODS Forty Caucasian subjects, mean age 63.5 ± 7.6, with significant coronary artery lesions (≥50%) were included. Within two months of coronary angiography, TM and RE CPET were performed on two visits 2-4 days apart and subsequently followed up to 32 ± 10 months. RESULTS Mean left ventricular ejection fraction was 56.7 ± 9.6%. TM CPET exhibited a higher occurrence of ST segment depression ≥ 1 mm (71.05% vs 28.95%, p = 0.04). Subjects with 1-2 stenotic coronary arteries (SCA) demonstrated a better CPET response compared to those with 3-SCA. ROC analysis revealed a high predictive value for the ventilation/carbon dioxide production (VE/VCO2) slope obtained on TM (area 0.84, p = 0.003, Sn 88.9%, Sp 72%) in distinguishing between 1 and 2-SCA and 3-SCA. Among all CPET parameters, work efficiency (∆VO2/∆WR) during RE predicted cumulative cardiac events (p < 0.01). CONCLUSIONS CPET parameters hold predictive value for CAD severity and prognosis. CPET on a TM appears to be more reliable in the quantification of CAD compared to RE.

Introduction: Postoperative Atrial Fibrillation (POAF) is associated with a higher rate of postoperative complications and mortality, as well as with longer hospitalization and increased treatment costs. We have designed and performed a randomized, trial of pharmacological prophylaxis in which the event of interest is POAF. Aim: The aim of this study is to reduce the risk of postoperative, complications associated with this arrhythmia. Methods: We included 240 stable patients with a coronary heart disease, who were referred to elective surgical revascularization of the myocardium. The patients were assigned into three groups of 80 patients each: group A (BB, beta blocker, comparator), group B (BB+ Amiodarone) and group C (BB + Rosuvastatin). The goal was to establish whether intervention by combination therapy was more useful than a comparator. Results: An event of interest (POAF) has occurred in 66 of the total 240 patients. Number of new POAF cases is the lowest in Group B, 14 (17.5%) compared to 25 (31.25%) new cases in the comparator group, and 27 new cases (33.75%) in group C. Absolute risk reduction was 13.75%, ≈14% less POAF in group B compared to comparator. Relative risk reduction was 56% (RR 0.56, p = 0.04). Number Needed to Treat was 7.27. In group C, 33.75% of patients developed POAF. Absolute risk was insignificantly higher in group C (2.5%, NS) compared to the comparator .The number needed to harm was high, 40. Conclusion: The results of our research show that prophylaxis of POAF with combined therapy BB + Amiodarone was the most efficient one.

Background: The potential of angiography to evaluate the hemodynamic severity of a left main coronary artery (LM) stenosis is limited. Noninvasive transthoracic Doppler echocardiographic coronary flow velocity reserve (CFVR) evaluation of intermediate coronary stenosis has demonstrated remarkably high negative prognostic value. The aim of this study was to assess clinical outcomes in patients with angiographically intermediate LM stenosis and preserved CFVR (>2.0) as evaluated by transthoracic Doppler echocardiographic CFVR. Methods: The initial study population included 102 patients with intermediate coronary stenosis of the LM referred for transthoracic Doppler echocardiographic CFVR assessment. Peak diastolic CFVR measurements were performed in the distal segment of the left anterior descending coronary artery after intravenous adenosine (140 &mgr;g/kg/min), and CFVR was calculated as the ratio between maximal hyperemic and baseline coronary flow velocity. Nineteen patients had impaired CFVR (≤2.0) and were excluded from further analysis, as well as two patients with poor acoustic windows. The final group consisted of 81 patients (mean age, 60 ± 9 years; 76 men) evaluated for adverse cardiac events including death, myocardial infarction, and revascularization. Results: Mean follow‐up duration was 62 ± 26 months. Mean CFVR was 2.4 ± 0.4. Total event‐free survival was 75 of 81 (92.6%), as six patients were referred for revascularization (five patients with coronary artery bypass grafting, one patient with percutaneous coronary intervention). There were no documented myocardial infarctions or cardiovascular deaths in the follow‐up period. Conclusions: In patients with angiographically intermediate and equivocal LM stenosis and preserved CFVR values of >2.0, revascularization can be safely deferred. HIGHLIGHTSWe performed TDE CFVR of the intermediate coronary stenosis of LM.TDE CFVR>2 is associated with good long‐term clinical outcomes.TDE CFVR might be used as a valuable diagnostic tool in assessing LM stenosis.

Background/Aim. Decision-making by the Heart Team is an established way of making appropriate decisions regarding the management of patients with coronary artery dis-ease. In clinical practice, it is not infrequent to see changes in decisions made by different Heart Teams. However, clinical implications regarding changes in the Heart Team decisions are not clear. The aim of this study was to determine clinical implications of change in the Heart Team decision in patients in whom surgical myocardial revascularization was advised first but consequently changed to percutaneous coronary intervention (PCI). Methods. We retrospectively analyzed data for 1,501 patients admitted to a single tertiary care high-volume center for coronary artery bypass grafting (CABG). In all patients, decisions were made by the Heart Team prior to admission. Upon admission, decisions were reevaluated by another Heart Team. The decision regarding the mode of revascularization was changed in 73 (4.86%) of patients. Propensity matching was made with patients from the same population who underwent CABG. Patients in both groups were followed for major adverse cardiac events (MACE) and total mortality for 12 months. Results. PCI and CABG groups were balanced with respect to demo-graphic and clinical characteristics. All patients had two- and three vessel disease, with similar incidence of left main stenosis (26% in the PCI group and 30.10% in the CABG group). EuroSCORE II was similar between the groups (2.48 ? 2.38 vs. 2.36 ? 2.92). During the follow-up period, a total of 5 (6.80%) MACE in the PCI group and 12 (5.80%) MACE in the CABG group were observed (log rank 0.096, p = 0.757). A total of 6 (8.20%) patients died in the PCI group, and 15 (7.30%) patients died in the CABG group (log rank 0.067, p = 0.796). Conclusion. Our data indicate that patients in whom CABG was advised first but consequently changed to PCI have a prognosis similar to CABG patients over 12 months after the index procedure.