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BackgroundCoronary chronic total occlusion (CTO) is characterized by the presence of collateral blood vessels which can provide additional blood supply to CTO-artery dependent myocardium. Successful CTO recanalization is followed by significant decrease in collateral donor artery blood flow and collateral derecruitment, but data on coronary hemodynamic changes in relation to myocardial function are limited. We assessed changes in coronary flow velocity reserve (CFVR) by echocardiography in collateral donor and recanalized artery following successful opening of coronary CTO.MethodsOur study enrolled 31 patients (60 ± 9 years; 22 male) with CTO and viable myocardium by SPECT scheduled for percutaneous coronary intervention (PCI). Non-invasive CFVR was measured in collateral donor artery before PCI, 24 h and 6 months post-PCI, and 24 h and 6 months in recanalized artery following successful PCI of CTO.ResultsCollateral donor artery showed significant increase in CFVR 24 h after CTO recanalization compared to pre-PCI values (2.30 ± 0.49 vs. 2.71 ± 0.45,p = 0.005), which remained unchanged after 6-months (2.68 ± 0.24). Baseline blood flow velocity of the collateral donor artery significantly decreased 24 h post-PCI compared to pre-PCI (0.28 ± 0.06 vs. 0.24 ± 0.04 m/s), and remained similar after 6 months, with no significant difference in maximum hyperemic blood flow velocity pre-PCI, 24 h and 6 months post-PCI. CFVR of the recanalized coronary artery 24 h post-PCI was 2.55 ± 0.35, and remained similar 6 months later (2.62 ± 0.26, p = NS).ConclusionsIn patients with viable myocardium, prompt and significant CFVR increase in both recanalized and collateral donor artery, was observed within 24 h after successful recanalization of CTO artery, which maintained constant during the 6 months.Trial registrationClinicalTrials.gov (NumberNCT04060615).

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) &lt, 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 &lt, 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.

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 In ST‐segment–elevation myocardial infarction, angiography‐based complete revascularization is superior to culprit‐lesion‐only percutaneous coronary intervention. Quantitative flow ratio (QFR) is a novel, noninvasive, vasodilator‐free method used to assess the hemodynamic significance of coronary stenoses. We aimed to investigate the incremental value of QFR over angiography in nonculprit lesions in patients with ST‐segment–elevation myocardial infarction undergoing angiography‐guided complete revascularization. Methods and Results This was a retrospective post hoc QFR analysis of untreated nontarget vessels (any degree of diameter stenosis [DS]) from the randomized multicenter COMFORTABLE AMI (Comparison of Biolimus Eluted From an Erodible Stent Coating With Bare Metal Stents in Acute ST‐Elevation Myocardial Infarction) trial by assessors blinded for clinical outcomes. The primary end point was cardiac death, spontaneous nontarget vessel myocardial infarction, and clinically indicated nontarget vessel revascularization (ie, ≥70% DS by 2‐dimensional quantitative coronary angiography or ≥50% DS and ischemia) at 5 years. Of 1161 patients with ST‐segment–elevation myocardial infarction, 946 vessels in 617 patients were analyzable by QFR. At 5 years, the rate of the primary end point was significantly higher in patients with QFR ≤0.80 (n=35 patients, n=36 vessels) versus QFR >0.80 (n=582 patients, n=910 vessels) (62.9% versus 12.5%, respectively; hazard ratio [HR], 7.33 [95% CI, 4.54–11.83], P P =0.008) and nontarget vessel revascularization (58.6% versus 7.7%, respectively; HR, 10.99 [95% CI, 6.39–18.91], P 30% DS by 3‐dimensional quantitative coronary angiography. Conclusions Our study suggests incremental value of QFR over angiography‐guided percutaneous coronary intervention for nonculprit lesions among patients with ST‐segment–elevation myocardial infarction undergoing primary percutaneous coronary intervention.

The aim of this randomized prospective study was to evaluate the quality of life (QoL) using the “Seattle Angina Questionnaire” (SAQ) in patients with chronic total occlusion (CTO) in coronary arteries treated with either percutaneous coronary intervention (PCI) or optimal medical therapy (OMT), or only with OMT. The potential benefits of recanalization of CTO by PCI have been controversial because of the scarcity of randomized controlled trials. A total of 100 patients with CTO were randomized (1:1) prospectively into the PCI CTO or the OMT group (50 patients in each group). There were no baseline differences in the SAQ scores between the groups, except for physical limitation scores (P = 0.03). During the mean follow-up (FUP) of 275 ± 88 days, patients in the PCI group reported less physical activity limitations (72.7 ± 21.3 versus 60.5 ± 27, P = 0.014), less frequent angina episodes (89.8 ± 17.6 versus 76.8 ± 27.1, P = 0.006), better QoL (79.9 ± 22.7 versus 62.5 ± 25.5, P = 0.001), greater treatment satisfaction (91.2 ± 13.6 versus 81.4 ± 18.4, P = 0.003), and borderline differences in angina stability (61.2 ± 26.5 versus 51.0 ± 23.7, P = 0.046) compared to patients in the OMT group. There were no significant differences in SAQ scores in the OMT group at baseline and during the FUP. There was a statistically significant increase in all five domains in the PCI group. Symptoms and QoL measured by the SAQ were significantly improved after CTO PCI compared to OMT alone.

Background Stroke volume response during stress is a major determinant of functional status in heart failure and can be measured by two-dimensional (2-D) volumetric stress echocardiography (SE). The present study hypothesis is that SE may identify mechanisms underlying the change in stroke volume by measuring preload reserve through end-diastolic volume (EDV) and left ventricular contractile reserve (LVCR) with systolic blood pressure and end-systolic volume (ESV). Methods We enrolled 4,735 patients (age 63.6 ± 11.3 yrs, 2800 male) referred to SE for known or suspected coronary artery disease (CAD) and/or heart failure (HF) in 21 SE laboratories in 8 countries. In addition to regional wall motion abnormalities (RWMA), force was measured at rest and peak stress as the ratio of systolic blood pressure by cuff sphygmomanometer/ESV by 2D with Simpson's or linear method. Abnormal values of LVCR (peak/rest) based on force were ≤1.10 for dipyridamole (n=1,992 patients) and adenosine (n=18); ≤2.0 for exercise (n=2,087) or dobutamine (n=638). Results Force-based LVCR was obtained in all 4,735 pts. Lack of stroke volume increase during stress was due to either abnormal LVCR and/or blunted preload reserve, and 57 % of patients with abnormal LVCR nevertheless showed increase in stroke volume. Conclusions Volumetric SE is highly feasible with all stresses, and more frequently impaired in presence of ischemic RWMA, absence of viability and reduced coronary flow velocity reserve. It identifies an altered stroke volume response due to reduced preload and/or contractile reserve.

Objectives The purpose of this study was to assess the functional and prognostic correlates of B-lines during stress echocardiography (SE). Background B-profile detected by lung ultrasound (LUS) is a sign of pulmonary congestion during SE. Methods The authors prospectively performed transthoracic echocardiography (TTE) and LUS in 2,145 patients referred for exercise (n = 1,012), vasodilator (n = 1,054), or dobutamine (n = 79) SE in 11 certified centers. B-lines were evaluated in a 4-site simplified scan (each site scored from 0: A-lines to 10: white lung for coalescing B-lines). During stress the following were also analyzed: stress-induced new regional wall motion abnormalities in 2 contiguous segments; reduced left ventricular contractile reserve (peak/rest based on force, ≤2.0 for exercise and dobutamine, ≤1.1 for vasodilators); and abnormal coronary flow velocity reserve ≤2.0, assessed by pulsed-wave Doppler sampling in left anterior descending coronary artery and abnormal heart rate reserve (peak/rest heart rate) ≤1.80 for exercise and dobutamine (≤1.22 for vasodilators). All patients completed follow-up. Results According to B-lines at peak stress patients were divided into 4 different groups: group I, absence of stress B-lines (score: 0 to 1; n = 1,389; 64.7%); group II, mild B-lines (score: 2 to 4; n = 428; 20%); group III, moderate B-lines (score: 5 to 9; n = 209; 9.7%) and group IV, severe B-lines (score: ≥10; n = 119; 5.4%). During median follow-up of 15.2 months (interquartile range: 12 to 20 months) there were 38 deaths and 28 nonfatal myocardial infarctions in 64 patients. At multivariable analysis, severe stress B-lines (hazard ratio [HR]: 3.544; 95% confidence interval [CI]: 1.466 to 8.687; p = 0.006), abnormal heart rate reserve (HR: 2.276; 95% CI: 1.215 to 4.262; p = 0.010), abnormal coronary flow velocity reserve (HR: 2.178; 95% CI: 1.059 to 4.479; p = 0.034), and age (HR: 1.031; 95% CI: 1.002 to 1.062; p = 0.037) were independent predictors of death and nonfatal myocardial infarction. Conclusions Severe stress B-lines predict death and nonfatal myocardial infarction. (Stress Echo 2020 - The International Stress Echo Study [SE2020]; NCT03049995)

Introduction: The use of clopidogrel is associated with a large variability in the response to this drug, wherein the results of the numerous studies indicate that even one out of three patients can be placed in the category of non responder. Corresponding section headings: Among the many causes of modified pharmacodynamic effects of clopidogrel, special attention is addressed to the possible clopidogrel-statin interaction. Numerous studies have focused on this problem, but it still seems to be missing the right answer. Conclusion: This paper reviews some of the most important facts regarding concomitant use of clopidogrel and statins, and specific issues to be addressed for safe treatment of patients.

Background/Aim. Impaired endothelial function has been previously documented in patients with atrial fibrillation (AF) and underlying comorbidities or older patients with idiopathic AF. The aim of this study was to evaluate systemic endothelial function in younger AF patients (less than < 60 years old) with lone AF (that is, without associated cardiopulmonary comorbidities, including arterial hypertension), by comparing brachial artery flow-mediated dilation (FMD) in lone AF patients with FMD of healthy subjects in sinus rhythm. Methods. Two groups of participants were prospectively enrolled. The first group comprised of 38 AF patients (the mean age 45 ? 11 years, 68% male) with persistent (> 7 days) lone AF. The second group comprised of 28 healthy controls in sinus rhythm (the mean age 43 ? 13, 53% male), matched by age, gender and atherosclerotic risk factors. All the participants underwent physical examination, laboratory analysis [including determination of C-reactive protein (CRP)], standard echocardiography and exercise-stress testing. Brachial artery FMD and endothelium independent dilation (NMD) were assessed with a high-resolution ultrasound probe and arterial diameters taken from 5 consecutive cardiac cycles were averaged for each measurement to accommodate to beat-to-beat flow variations in AF. Results. There were no differences between the 2 groups regarding age, gender and most clinical, laboratory and echocardiographic characteristics (all p > 0.05), apart from the increased heart rate (p = 0.018), body mass index (p = 0.027), CRP levels (p = 0.007) and left atrial anteroposterior dimension (p < 0.001) in AF patients. FMD of AF patients [median value 5.0%, interquartile range (IQR) 2.87%-7.50%] was significantly lower (p < 0.001) than FMD of healthy controls (median value 8.85%, IQR 5.80%- 12.50%), whereas there were no differences in median NMD values (p > 0.05). In the multivariate analysis, the independent FMD determinants in our study population were the presence of AF, smoking and total cholesterol levels (all p < 0.001). In patients with AF, the strongest independent FMD determinant was arrhythmia duration (p < 0.001), followed by smoking (p = 0.013) and total cholesterol levels (p = 0.045). Conclusions. Our findings confirm that sustained AF is associated with systemic endothelial dysfunction even in relatively young patients with no cardiovascular disorders or risk factors. AF is an independent contributor to lower FMD and a prolonged arrhythmia duration may confer the risk for more profound endothelial damage.

Background/Aim. Early detection of left ventricle (LV) systolic dysfunction could be a clue for surgical treatment in patients with significant aortic stenosis (AS). Therefore, we evaluated LV peak of global longitudinal strain (PGLS) using speckle tracking imaging at rest and during low-dose dobutamine infusion in asymptomatic patients with moderate and severe AS and preserved LV ejection fraction (EF). Methods. All the patients underwent coronary angiography and had no obstructive coronary disease (defined as having no stenosis greater than 50% in diameter). The patients were divided into two groups: above and below median of 0.785 cm2 aortic valve area (AVA). PGLS was measured from acquired apical 4-chamber and 2-chamber cine loops using a EchoPac PC-workstation at rest and during 5 μg/kg/min, 10 μg/kg/min, and 20 μg/kg/min dobutamine infusion, respectively. The global strain was the average of segment strains from the apical views. Results: A total of 62 patients with moderate and severe AS (AVA < = 1.5 cm2), the mean age 66.12 ± 9.91, (57.14% males), were enrolled in this prospective study. At rest, mean gradient was 43.57 ± 0.29 mmHg and mean EF was 72.24 ± 0.45%. When divided according to median AVA, both groups had decreased average PGLS at rest (-9.33 ± 4.46% vs -8.95 ± 3.08%; p = ns). During dobutamine both groups increased their average PGLS, but only the group with AVA > median reached the statistical significance (- 8.71 ± 2.68% vs -11.93 ± 3.74%, p = 0.002). In addition, PGLS increase was also significant in 4-chamber view in the patients with AVA above median, but only when comparing baseline to peak 20 μg/kg/min (-10.72 ± 3.07% vs -13.14 ± 4.79%; p = 0.034). Conversely, in both groups the increase of PGLS in 2-chamber view did not reach significance. Conclusion. Two-dimensional strain speckle tracking analysis of myocardial deformation with measurement of peak systolic strain during dobutamine infusion is a feasible and accurate method to determine myocardial longitudinal systolic function and contractile reserve and may contribute to clinical decision making in patients with significant AS.

Background/Aim. Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia in general population. The aim of the study was to compare all-cause mortality and cardiovascular mortality in patients with lone and idiopathic AF to correspondent mortality in general population of Serbia. Methods. A longitudinal observational study included the patients with nonvalvular AF as the main indication for inhospital and/or outpatient treatment in the Clinical Center of Serbia, during a period 1992-2007, if the latest date of first diagnosed AF was early January 2003; in that way, the total follow- up could last at least 5 years (minimum 1 year prospectively), or until death. Principles of oral anticoagulation, heart rhythm and frequency control during the study period were conducted according to the latest international guidelines for diagnosis and treatment of AF in the study period. Lone and idiopathic AF were defined as AF in patients without any underlying disease, younger than 60 years (lone AF) or older (idiopathic AF). To compare mortality of the study population with mortality of general population we used the standardized mortality ratio (SMR) and chi-square test with p < 0.05 as a level of statistical significance. Results. Out of 442 patients with AF and no underlying disease, aged 47 ? 12.6 years, with mean follow-up of 11.5 ? 7.2 years, 12 patients (2.7%) died: 7 patients of non-cardiovascular causes and 5 patients (1.1%) of cardiovascular death. When compared to the general population of Serbia, all-cause mortality and cardiovascular mortality in the patients with lone and idiopathic AF were not higher than in general population (p < 0.05). Conclusion. All-cause mortality and cardiovascular mortality of patients with lone and idiopathic AF are similar to all-cause mortality and cardiovascular mortality in general population of Serbia.

Background/Aim. Brachial artery flow-mediated dilation (FMD) is extensively used for non-invasive assessment of endothelial function. Traditionally, FMD is calculated as a percent change of arterial diameter from the baseline value at an arbitrary time point after cuff deflation (usually 60 seconds). Considerable individual differences in brachial artery temporal response to hyperemic stimulus have been observed, potentially influenced by the presence of atherosclerotic risk factors (RF). The importance of such differences for the evaluation of endothelial function has not been well established. The aim of the stady was to determine the time course of maximal brachial artery endothelium- dependent dilation in healthy adults with and without RF, to explore the correlation of RF with brachial artery temporal response and to evaluate the importance of individual differences in temporal response for the assessment of endothelial function. Methods. A total of 115 healthy volunteers were included in the study. Out of them, 58 had no RF (26 men, mean age 44 ? 14 years) and 57 had at least one RF (29 men, mean age 45 ? 14 years). High-resolution color Doppler vascular ultrasound was used for brachial artery imaging. To determine maximal arterial diameter after cuff deflation and the time-point of maximal vasodilation off-line sequential measurements were performed every 10 seconds from 0 to 240 seconds after cuff release. True maximal FMD value was calculated as a percent change of the true maximal diameter from the baseline, and compared with FMD value calculated assuming that every participant reached maximal dilation at 60 seconds post cuff deflation (FMD60). Correlation of different RF with brachial artery temporal response was assessed. Results. A maximal brachial artery endothelium-dependent vasodilation occurred from 30-120 seconds after cuff release, and the mean time of endothelium-dependent dilation was 68 ? 20 seconds. Individuals without RF had faster endothelium-dependent dilation (mean time 62 ? 17 seconds), and a shorter timespan (30 to 100 seconds), than participants with RF (mean time 75 ? 21 seconds, time-span 40 to 120 seconds) (p < 0.001). Time when the maximal endotheliumdependent dilation occurred was independently associated with age, serum lipid fractions (total cholesterol, LDL and HDL cholesterol), smoking, physical activity and C-reactive protein. True maximal FMD value in the whole group (6.7 ? 3.0%) was significantly higher (p < 0.001) than FMD60 (5.2 ? 3.5%). The same results were demonstrated for individuals with RF (4.9 ? 1.7% vs 3.1 ? 2.3%, p < 0.001) and without RF (8.4 ? 2.9% vs 7.2 ? 3.2%, p < 0.05). Conclusion. The temporal response of endothelium- dependent dilation is influenced by the presence of coronary FR and individually heterogeneous. When calculated according to the commonly used approach, i.e. 60 seconds after cuff deflation, FMD is significantly lower than the true maximal FMD. The routinely used measurement time-points for FMD assessment may not be adequate for the detection of true peak vasodilation in individual persons. More precise evaluation of endothelial function can be achieved with sequential measurement of arterial diameter after hyperemic stimulus.

Background/Aim. Atrial fibrillation (AF) increases the risk for ischemic stroke and other thromboembolic (TE) events. Aim of the study was to examine the relationship between clinical types of atrial fibrillation (AF) and (TE) events. Methods. This longitudinal, observational study included patients with nonvalvular AF as main indication for in-hospital and/or outpatient treatment in the Cardiology Clinic, Clinical Center of Serbia during a period 1992-2007. The treatment of AF was based on the International Guidelines for diagnosis and treatment of AF, correspondent to given study period. Clinical types of AF were defined according to the latest ACC/AHA/ESC Guidelines for AF, from 2006. Diagnosis of central and systemic TE events during a follow-up was made exclusively by the neurologist and vascular surgeon. Results. During a follow-up of 9.9 ? 6 years, TE events were documented in 88/1 100 patients (8%). In the time of TE event 46/88 patients (52.3%) had permanent AF. The patients with permanent AF were at baseline significantly older and more frequently had underlying heart disease and diabetes mellitus. Cumulative TE risk during follow-up was similar for patients with paroxysmal and permanent AF, and significantly higher as compared to TE risk in patients with persistent AF. However, multivariate Cox proportional hazard regression analysis with independent variables clinical types of AF at baseline and in the time of TE event, clinical and echocardiographic characteristics and therapy for prevention of TE complications at baseline and at the time of TE event, did not reveal independent predictive value of clinical type of AF for the occurrence of TE events during a follow-up. Conclusion. TE risk in patients with AF does not depend on clinical type of AF. Treatment for prevention of TE events should be based on the presence of well recognized risk factors, and not on the clinical type of AF.

Background— This study sought to determine whether the 1-year differences in major adverse cardiac event between a stent eluting biolimus from a biodegradable polymer and bare-metal stents (BMSs) in the COMFORTABLE trial (Comparison of Biolimus Eluted From an Erodible Stent Coating With Bare Metal Stents in Acute ST-Elevation Myocardial Infarction) were sustained during long-term follow-up. Methods and Results— A total of 1161 patients were randomly assigned to biolimus-eluting stent (BES) and BMS at 11 centers, and follow-up rates at 2 years were 96.3%. A subgroup of 103 patients underwent angiography at 13 months. At 2 years, differences in the primary end point of cardiac death, target-vessel myocardial infarction, and target lesion revascularization continued to diverge in favor of BES-treated patients (5.8%) compared with BMS-treated patients (11.9%; hazard ratio=0.48; 95% confidence interval, 0.31–0.72; P P =0.049). Differences in the primary end point were driven by a reduction in target lesion revascularization (3.1% versus 8.2%; P P =0.023). The composite of death, any reinfarction and revascularization (14.5% versus 19.3%; P =0.03), and cardiac death or target-vessel myocardial infarction (4.2% versus 7.2%; P =0.036) were less frequent among BES-treated patients compared with BMS-treated patients. The 13-month angiographic in-stent percent diameter stenosis amounted to 12.0±7.2 in BES- and 39.6±25.2 in BMS-treated lesions ( P Conclusions— Among patients with ST-segment–elevation myocardial infarction undergoing primary percutaneous coronary intervention, BES continued to improve cardiovascular events compared with BMS beyond 1 year. Clinical Trial Registration— URL: http://www.clinicaltrials.gov . Unique identifier: NTC00962416.

First-generation drug-eluting stents (DES) have been associated with impaired localized coronary vasomotion and delayed endothelialization. We aimed to compare coronary vasomotion after implantation of a newer-generation everolimus-eluting stent (EES), with a first-generation paclitaxel-eluting stent (PES). Coronary vasomotion was studied in 19 patients with EES and 13 with PES. Vasomotor response was measured proximally and distally to the stent and in a remote vessel (reference segment). Quantitative coronary angiography was performed offline. Endothelium independent vasomotion did not differ significantly between the two groups. EES showed significant vasodilatation while PES showed vasoconstriction at both proximal (+4.5 ± 3.6 vs −4.2 ± 6.9, p

Background: Treatment of STEMI has considerably evolved over the past 2 decades. However, predictors of adverse events after STEMI are mostly based on early studies without consistent use of reperfusion therapy, P2Y12 inhibitors, and drug-eluting stent implantation. We aimed to identify predictors of adverse events among patients with ST-elevation myocardial infarction (STEMI) undergoing contemporary primary percutaneous coronary intervention (PCI). Methods: Individual data of 2655 patients from 2 primary PCI trials (EXAMINATION, N=1504; COMFORTABLE-AMI, N=1161) with identical endpoint definition and event adjudication were pooled. Predictors of patient-oriented (death or reinfarction) and device-oriented (definite stent thrombosis [ST] and target-lesion revascularization [TLR]) outcomes at 1 year were identified by multivariable Cox regressions analysis. Results: Killip class III/IV was the strongest predictor of death or reinfarction (OR5.11, 95%CI2.48-10.52), ST (OR7.74, 95%CI2.87-20.93), and any TLR (OR2.88, 95%CI1.17-7.06). Impaired LVEF (OR4.77, 95%CI2.10-10.82), final TIMI flow 0-2 (OR1.93, 95%CI1.05-3.54), hypertension (OR1.69, 95%CI1.11-2.59), age (OR1.68, 95%CI1.41-2.01), and peak CK (OR1.25, 95%CI1.02-1.54) were independent predictors of death or reinfarction. Allocation to treatment with DES was an independent predictor of a lower risk of ST (OR0.35, 95%CI0.16-0.74) and any TLR (OR0.34, 95%CI0.21-0.54). Conclusions: Killip class remains the strongest predictor of death or reinfarction among STEMI patients undergoing primary PCI. Noteworthy, DES use independently predicts a lower risk of TLR and definite ST.

International audience; AIMS: Primary percutaneous coronary intervention (PPCI) is the recommended treatment for patients with acute ST-segment elevation myocardial infarction (STEMI). Despite substantial evidence of its effectiveness, a 2007 study reported that only 40-45% of European STEMI patients were treated with PPCI, with large variations in treatment availability between countries. In 2008, the Stent for Life (SFL) initiative was launched by the European Association of Percutaneous Cardiovascular Interventions and EuroPCR in partnership with the European Society of Cardiology (ESC) Working Group on Acute Cardiac Care and country-specific national cardiac societies. The aim is to promote the prioritisation of percutaneous coronary intervention treatment towards those who will benefit most, namely STEMI patients. The following countries are currently participating: Bulgaria, Egypt, France, Greece, Italy, Portugal, Romania, Serbia, Spain and Turkey. METHODS AND RESULTS: Since SFL was launched, several activities have been initiated in the participating countries. Preliminary reports suggest that major increases have been seen in the numbers of PPCI performed, with some countries reporting very significant increases in PPCI use from 2008-2010. Improvements in STEMI mortality rates have also been observed. CONCLUSIONS: This report summarises the progress of the SFL initiative in the 10 target countries.

Item does not contain fulltext BACKGROUND: The effect of intensified platelet inhibition for patients with unstable angina or myocardial infarction without ST-segment elevation who do not undergo revascularization has not been delineated. METHODS: In this double-blind, randomized trial, in a primary analysis involving 7243 patients under the age of 75 years receiving aspirin, we evaluated up to 30 months of treatment with prasugrel (10 mg daily) versus clopidogrel (75 mg daily). In a secondary analysis involving 2083 patients 75 years of age or older, we evaluated 5 mg of prasugrel versus 75 mg of clopidogrel. RESULTS: At a median follow-up of 17 months, the primary end point of death from cardiovascular causes, myocardial infarction, or stroke among patients under the age of 75 years occurred in 13.9% of the prasugrel group and 16.0% of the clopidogrel group (hazard ratio in the prasugrel group, 0.91; 95% confidence interval [CI], 0.79 to 1.05; P=0.21). Similar results were observed in the overall population. The prespecified analysis of multiple recurrent ischemic events (all components of the primary end point) suggested a lower risk for prasugrel among patients under the age of 75 years (hazard ratio, 0.85; 95% CI, 0.72 to 1.00; P=0.04). Rates of severe and intracranial bleeding were similar in the two groups in all age groups. There was no significant between-group difference in the frequency of nonhemorrhagic serious adverse events, except for a higher frequency of heart failure in the clopidogrel group. CONCLUSIONS: Among patients with unstable angina or myocardial infarction without ST-segment elevation, prasugrel did not significantly reduce the frequency of the primary end point, as compared with clopidogrel, and similar risks of bleeding were observed. (Funded by Eli Lilly and Daiichi Sankyo; TRILOGY ACS ClinicalTrials.gov number, NCT00699998.).

undergoing primary percutaneous coronary intervention for ST-segment elevation myocardial infarction: an analysis of the ARMYDA-6 MI (Antiplatelet therapy for Reduction of MYocardial Damage during Angioplasty-Myocardial Infarction) Study Fabio Mangiacapra ⁎, Giuseppe Patti , Emanuele Barbato , Dejan Orlic , Aaron J. Peace , Andrea D'Ambrosio , Miodrag Ostojic , William Wijns , Germano Di Sciascio a,⁎,1 a Department of Cardiovascular Sciences, Campus Bio-Medico University, Rome, Italy b Cardiovascular Center Aalst, OLV Hospital, Aalst, Belgium c Department of Diagnostics and Catheterization Laboratories, Division of Cardiology, Clinical Center of Serbia, Medical School of Belgrade, Belgrade, Serbia

CONTEXT The efficacy and safety of drug eluting stents compared with bare metal stents remains controversial in patients with ST segment elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PCI). OBJECTIVE To compare stents eluting biolimus from a biodegradable polymer with bare metal stents in primary PCI. DESIGN SETTING AND PATIENTS A prospective randomized single blinded controlled trial of 1161 patients presenting with STEMI at 11 sites in Europe and Israel between September 19 2009 and January 25 2011. Clinical follow up was performed at 1 and 12 months. INTERVENTION Patients were randomized 1:1 to receive the biolimus eluting stent (n = 575) or the bare metal stent (n = 582). MAIN OUTCOME MEASURES Primary end point was the rate of major adverse cardiac events a composite of cardiac death target vessel related reinfarction and ischemia driven target lesion revascularization at 1 year. RESULTS Major adverse cardiac events at 1 year occurred in 24 patients (4.3) receiving biolimus eluting stents with biodegradable polymer and 49 patients (8.7) receiving bare metal stents (hazard ratio [HR] 0.49; 95 CI 0.30 0.80; P = .004). The difference was driven by a lower risk of target vessel related reinfarction (3 [0.5] vs 15 [2.7]; HR 0.20; 95 CI 0.06 0.69; P = .01) and ischemia driven target lesion revascularization (9 [1.6] vs 32 [5.7]; HR 0.28; 95 CI 0.13 0.59; P < .001) in patients receiving biolimus eluting stents compared with those receiving bare metal stents. Rates of cardiac death were not significantly different (16 [2.9] vs 20 [3.5] P = .53). Definite stent thrombosis occurred in 5 patients (0.9) treated with biolimus eluting stents and 12 patients (2.1; HR 0.42; 95 CI 0.15 1.19; P = .10) treated with bare metal stents. CONCLUSION Compared with a bare metal stent the use of biolimus eluting stents with a biodegradable polymer resulted in a lower rate of the composite of major adverse cardiac events at 1 year among patients with STEMI undergoing primary PCI. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00962416.

Background: The idea to enter the normal pericardial sac safely was unrealistic until recently. The development of a novel instrument (PerDUCER® pericardial access device) for percutaneous access to the pericardium could potentially have a significant impact, not only on patients with pericardial diseases but even more, or primarily, on diagnosis and treatment of myocardial and coronary disease and arrhythmias. Hypothesis: The overall objective of the present study was to evaluate the feasibility and safety of the percutaneous pericardial access with PerDUCER in patients with pericardial disease, and to analyze our initial experience with this new technique, with particular emphasis on sequential procedural steps. Methods: The device was studied in five patients with pericardial disease (two men, mean age 50.4 years, range 30–68, four with normal body mass index). The procedure consists of two distinct techniques: (1) access to the mediastinal space, and (2) pericardial capture, puncture, and insertion of the guidewire. Access to the mediastinal space includes the introduction of a blunt cannula, a 0.038 guidewire, a dilator-introducer sheath set, and insertion of the PerDUCER device. Key points of the PerDUCER procedure are as follows: introduction of the blunt cannula without resistance, placement of the dilator-introducer sheath at the upper third of the heart, systolic movements of the PerDUCER device, successful vacuum and capture of pericardium, puncture and introduction of the intrapericardial guidewire. Results: Access to the mediastinal space was accomplished in four of five patients, as were pericardial capture and probably puncture. However, despite numerous successful captures and probably punctures of pericardium, we were not able to confirm introduction of the intrapericardial guidewire into the pericardial cavity in any of our patients (0/5). The procedure was very well tolerated in all patients (5/5). No major complications developed during the procedure, bearing in mind that the intrapericardial placement of the guidewire was not achieved. Minor complications included pain at the dilator-introducer sheath entry site (5/5) and mild transient fever (2/5). Conclusions: According to the present experience, we believe that, with minor modifications, the PerDUCER device could be successfully implemented for pericardial entry in patients with pericardial disease. Further studies are needed to evaluate the feasibility and safety of this new instrument in patients with a normal pericardium. This could open a most exciting spectrum of possible implementations of the device in the future.

Background Dipyridamole and dobutamine stress echocardiography testing are most widely utilized, but their sensitivity remained suboptimal in comparison to routine exercise stress echocardiography. The aim of our study is to compare, head-to-head, exercise, dobutamine and dipyridamole stress echocardiography tests, performed with state-of-the-art protocols in a large scale prospective group of patients. Methods Dipyridamole-atropine (Dipatro: 0.84 mg/kg over 10 min i.v. dipyridamole with addition of up to 1 mg of atropine), dobutamine-atropine (Dobatro: up to 40 mcg/kg/min i.v. dobutamine with addition of up to 1 mg of atropine) and exercise (Ex, Bruce) were performed in 166 pts. Of them, 117 pts without resting wall motion abnormalities were enrolled in study (91 male; mean age 54 ± 10 years; previous non-transmural myocardial infarction in 32 pts, angina pectoris in 69 pts and atypical chest pain in 16 pts). Tests were performed in random sequence, in 3 different days, within 5 day period under identical therapy. All patients underwent coronary angiography. Results Significant coronary artery disease (CAD; ≥50% diameter stenosis) was present in 69 pts (57 pts 1-vessel CAD, 12 multivessel CAD) and absent in 48 pts. Sensitivity (Sn) was 96%, 93% and 90%, whereas specificity (Sp) was 92%, 92% and 87% for Dobatro, Dipatro and Ex, respectively (p = ns). Concomitant beta blocker therapy did not influence peak rate-pressure product and Sn of Dobatro and Dipatro (p = ns). Conclusion When state-of-the-art protocols are used, dipyridamole and dobutamine stress echocardiography have comparable and high diagnostic accuracy, similar to maximal post-exercise treadmill stress echocardiography.

Objective The aim of this study was to evaluate the diagnostic potential of low-dose adenosine stress echocardiography in detection of myocardial viability. Background Vasodilation through low dose dipyridamole infusion may recruit contractile reserve by increasing coronary flow or by increasing levels of endogenous adenosine. Methods Forty-three patients with resting dyssynergy, due to previous myocardial infarction, underwent low-dose adenosine (80, 100, 110 mcg/kg/min in 3 minutes intervals) echocardiography test. Gold standard for myocardial viability was improvement in systolic thickening of dyssinergic segments of ≥ 1 grade at follow-up. Coronary angiography was done in 41 pts. Twenty-seven patients were revascularized and 16 were medically treated. Echocardiographic follow up data (12 ± 2 months) were available in 24 revascularized patients. Results Wall motion score index improved from rest 1.55 ± 0.30 to 1.33 ± 0.26 at low-dose adenosine (p < 0.001). Of the 257 segments with baseline dyssynergy, adenosine echocardiography identified 122 segments as positive for viability, and 135 as necrotic since no improvement of systolic thickening was observed. Follow-up wall motion score index was 1.31 ± 0.30 (p < 0.001 vs. rest). The sensitivity of adenosine echo test for identification of viable segments was 87%, while specificity was 95%, and diagnostic accuracy 90%. Positive and negative predictive values were 97% and 80%, respectively. Conclusion Low-dose adenosine stress echocardiography test has high diagnostic potential for detection of myocardial viability in the group of patients with left ventricle dysfunction due to previous myocardial infarction. Low dose adenosine stress echocardiography may be adequate alternative to low-dose dobutamine test for evaluation of myocardial viability.

Background Insulin resistance (IR) assessed by the Homeostatic Model Assessment (HOMA) index in the acute phase of myocardial infarction in non-diabetic patients was recently established as an independent predictor of intrahospital mortality. In this study we postulated that acute IR is a dynamic phenomenon associated with the development of myocardial and microvascular injury and larger final infarct size in patients with ST-segment elevation myocardial infarction (STEMI) treated by primary percutaneous coronary intervention (pPCI). Methods In 104 consecutive patients with the first anterior STEMI without diabetes, the HOMA index was determined on the 2nd and 7th day after pPCI. Worst-lead residual ST-segment elevation (ST-E) on postprocedural ECG, coronary flow reserve (CFR) determined by transthoracic Doppler echocardiography on the 2nd day after pPCI and fixed perfusion defect on single-photon emission computed tomography myocardial perfusion imaging (SPECT-MPI) determined six weeks after pPCI were analyzed according to HOMA indices. Results IR was present in 55 % and 58 % of patients on day 2 and day 7, respectively. Incomplete post-procedural ST-E resolution was more frequent in patients with IR compared to patients without IR, both on day 2 (p = 0.001) and day 7 (p 20% (OR 11.37, 95% CI 1.34-96.21, p = 0.026). Conclusion IR assessed by the HOMA index during the acute phase of the first anterior STEMI in patients without diabetes treated by pPCI is independently associated with poorer myocardial reperfusion, impaired coronary microcirculatory function and potentially with larger final infarct size.

Clinical data on 10,451 high-dose (up to 0.84 mg/kg over 10 minutes) dipyridamole-echocardiography tests (DET) performed in 9,122 patients were prospectively collected from 33 echocardiographic laboratories, each contributing greater than 100 tests. All patients were studied for documented or suspected coronary artery disease (1,117 early [less than 18 days] after acute myocardial infarction and 293 had unstable angina). Significant side effects including major adverse reactions and minor but limiting side effects occurred in 113 patients (1.2%). Major adverse reactions occurred in 7 cases (0.07%). In 6 of these cases, adverse reactions were associated with echocardiographically assessed ischemia and included 1 prolonged cardiac asystole (complicated by acute myocardial infarction and coma, with death after 23 days), 1 short-lasting cardiac asystole, 2 myocardial infarctions, 1 pulmonary edema and 1 sustained ventricular tachycardia. In all 6 cases, the cardiologist-echocardiographer performing the study had a limited experience (less than 100 tests) with DET, and at off-line reading in 5 cases, the obvious echo-positivity preceded the onset of complications by 1 to 5 minutes. The only ischemia-independent major side effect was a short-lasting cardiac asystole that was reversed by aminophylline and atropine. Significant side effects associated with echocardiographically assessed ischemia occurred in 89 additional cases (21 with and 68 without concomitant echocardiographically assessed myocardial ischemia). The most frequent of these side effects was hypotension or bradycardia, or both, which occurred in 40 patients with negative and 6 with positive DET. In all cases, side effects promptly subsided after aminophylline. In 1,857 cases, the high dose was not given for echo-positivity before the eighth minute.(ABSTRACT TRUNCATED AT 250 WORDS)

Objectives. This study was designed to assess the clinical, hemodynamic and diagnostic effects of the addition of dobutamine to dipyridamole echocardiography. Background. Pharmacologic stress echocardiography with either dipyridamole or dobutamine has gained acceptance because of its safety, feasibility, diagnostic accuracy and prognostic power. The main limitation of the two tests is a less than ideal sensitivity in some patient subsets, such as those with limited coronary artery disease. We hypothesized that two pharmacologic stresses might act synergistically in the induction of ischemia by combining the mechanisms of inappropriate coronary vasodilation (with dipyridamole) and an increase in myocardial oxygen consumption (with dobutamine). Methods. One hundred fifty patients (mean [±SD] age 51 ± 11 years) referred for stress echocardiography were initially studied by dipyridamole-dobutamine echocardiography. The test was stopped during the dipyridamole step in 95 patients for achievement of a predetermined end point (obvious dyssynergy induced by lower or higher dipyridamole dose), and dipyridamoledobutamine tests were performed in 55 patients (negative dipyridamole echocardiographic test). In the same 150 patients the dobutamine echocardiographic test (up to 40 μg/kg body weight per min) was performed on a separate day. Results. Significant coronary artery disease (>50% diameter stenosis of at least one major coronary vessel by quantitative coronary arteriography) was present in 131 patients (one vessel in 115; two vessels in 10, three vessels in 6), with normal coronary arteriography in 19. The feasibility of the dipyridamoledobutamine test was 96%. Self-limiting side effects occurred in 5% of patients. The peak rate-pressure product was lowest during the dipyridamole test (132 ± 30) and was comparable during the dobutamine (186 ± 59) and dipyridamole-dobutamine tests (179 ± 45, p = NS vs. dobutamine; p < 0.01 vs. dipyridamole). Sensitivity was 71% for dipyridamole, 75% for dobutamine and 92% for dipyridamole-dobutamine echocardiography (dipyridamole vs. dipyridamole-dobutamine, p < 0.01; dobutamine vs. dipyridamole-dobutamine, p < 0.01; dipyridamole vs. dobutamine, p = NS), whereas specificity was 89% for dipyridamole, 79% for dobutamine and 89% for dipyridamole-dobutamine echocardiography (p = NS for all). Conclusions. Routine dobutamine addition to dipyridamole stress testing is clinically useful and well tolerated. It expands the spectrum of the disease detectable by pharmacologic stress echocardiography and allows documentation of milder forms of coronary artery disease that can be missed by conventional dipyridamole or dobutamine stress echocardiography.

Objectives. We sought to evaluate the effects of combined administration of infra-low dose dipyridamole and low dose dobutamine on assessment of myocardial viability. Background. Low dose pharmacologic stress echocardiography with either dobutamine or dipyridamolc infusion has been proposed for the recognition of myocardial viability. Methods. Thirty-four patients with rest wall motion dyssynergy by two-dimensional echocardiography and with angiographically proved coronary artery disease underwent in combination with two-dimensional echocardiographic monitoring: 1) low dose (5 to 10 μg/kg per min over 3 min) dobutamine infusion; 2) infra-low dose (0.28 mg/kg over 4 min) dipyridamole infusion; 3) combination of infra-low dose dipyridamole infusion immediately followed by low dose dobutamine infusion (combined dipyridamole-dobutamine). Results. Follow-up rest echocardiography was available in 30 patients. After revascularization, 82 segments showed a contractile improvement of ≥1 grade, whereas 63 segments remained unchanged. The sensitivity of dobutamine, dipyridamole and combined dipyridamole-dobutamine for predicting recovery was 72% (95% confidence interval [CI] 60.9% to 81.3%), 67% (CI 55.8% to 77%) and 94% (CI 86.3% to 97.9%), respectively. The specificity of dipyridamole, dobutamine and combined dipyridamole-dobutamine was 95% (CI 86.7% to 99%), 92% (CI 82.4% to 97.3%) and 89% (CI 78.4% to 95.4%), respectively. The accuracy of the dobutamine, dipyridamole and combined dipyridamole-dobutamine test was 80%, 79% and 92%, respectively (combined dipyridamole-dobutamine vs. dobutamine, p < 0.05; combined dipyridamole-dobutamine vs. dipyridamole, p < 0.01). Conclusions. Infra-low dose dipyridamole added to low dose dobutamine recruits an inotropic reserve in asynergic segments that were nonresponders after either dobutamine or dipyridamole alone and destined to recover after revascularization.

Background The risk stratification of patients with diabetes mellitus (DM) is a major objective for the clinicians, and it can be achieved by coronary flow velocity reserve (CFVR) or with coronary artery calcium score (CS). CS evaluates underlying coronary atherosclerotic plaque burden and CFVR estimates both presence of coronary artery stenosis and microvascular function. Consequently, CFVR may provide unique risk information beyond the extent of coronary atherosclerosis. Aim Our aim is to assess joint prognostic value of CFVR and CS in asymptomatic DM patients. Materials and methods We prospectively included 200 asymptomatic patients (45,5 % male, mean age 57,35 ± 11,25), out of which, there were 101 asymptomatic patients with DM and 99 asymptomatic patients without DM, but with one or more conventionally risk factors for coronary artery disease. We analyzed clinical, biochemical, metabolic, inflammatory parameters, CS by Agatston method, transthoracic Doppler echocardiography CFVR of left anterior descending artery and echocardiographic parameters. Results Total CS and CS LAD were significantly higher, while mean CFVR was lower in diabetics compared to the nondiabetics. During 1 year follow-up, 24 patients experienced cardio-vascular events (one cardiovascular death, two strokes, three myocardial infarctions, nine new onsets of unstable angina and nine myocardial revascularizations): 19 patients with DM and five non DM patients, (p = 0,003). Overall event free survival was significantly higher in non DM group, compared to the DM group (94,9 % vs. 81,2 %, p = 0,002 respectively), while the patients with CS ≥200 and CFVR