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Since diastolic dysfunction is an early sign of the heart disease, detecting diastolic disturbances is predicted to be the way for early recognizing underlying heart disease in athletes. So-called chamber stiffness index (E/e′)/LVDd was predicted to be useful in distinguishing physiological from pathological left ventricular hypertrophy, because it was shown to be reduced in athletes. It remains unknown whether it is reduced in all athletic population. Standard and tissue Doppler were used to assess cardiac parameters at rest in 16 elite male wrestlers, 21 water polo player, and 20 sedentary subjects of similar age. In addition to (E/e′)/LVDd index, a novel (E/e′)/LVV, (E/e′)/RVe′lat indices were determined. Progressive continuous maximal test on treadmill was used to assess the functional capacity. VO2 max was the highest in water polo players, and higher in wrestlers than in controls. LVDd, LVV, LVM/BH2.7 were higher in athletes. Left ventricular early diastolic filling velocity, deceleration and isovolumetric relaxation time did not differ. End-systolic wall stress was significantly higher in water polo players. RV e′ was lower in water polo athletes. Right atrial pressure (RVE/e′) was the highest in water polo athletes. (E/e′lat)/LVDd was not reduced in athletes comparing to controls (water polo players 0.83 ± 0.39, wrestlers 0.73 ± 0.29, controls 0.70 ± 0.28; P = 0.52), but (E/e′s)/RVe′lat better distinguished examined groups (water polo players 0.48 ± 0.37, wrestlers 0.28 ± 0.15, controls 0.25 ± 0.16, P = 0.015) and it was the only index which predicted VO2 max. In conclusion, intensive training does not necessarily reduce (E/e′lat)/LVDd index. A novel index (E/e′s)/RVe′lat should be investigated furthermore in detecting diastolic adaptive changes. (Echocardiography 2011;28:276-287)

In patients with previous myocardial infarction (MI), assessment of myocardial viability and physiological significance of coronary artery stenoses are essential for appropriate guidance of revascularization. The aim of the study was to evaluate the relation between fractional flow reserve (FFR) and myocardial viability as assessed by gated SPECT MIBI perfusion scintigraphy in patients with previous MI undergoing elective PCI. The study population consisted of 26 patients (mean age 55 ± 7 years; 21 male) with a previous MI and a significant coronary stenosis in a single infarct-related coronary vessel for which PCI was being performed. In all patients, FFR was evaluated before and immediately after PCI. SPECT imaging was done before and 3 ± 1 months after PCI. A region representing the MI was considered viable if MIBI uptake was ≥55% of the normal region. Improvement in perfusion after revascularization was considered achieved if perfusion abnormalities decreased by 5% or more and there was a decrease in segmental score of ≥1 in three segments in PCI-related vascular territory. Extent of perfusion abnormalities decreased from 32 ± 16% to 27 ± 19% after PCI (P

Cardiac involvement by non-Hodgkin's lymphoma is not uncommon, however rarely diagnosed during life due to nonspecific clinical presentation. We report a case of secondary cardiac lymphoma in patient who presented with new-onset atrial fibrillation. Cardiac lymphoma was in a form of bulky right atrial mass, infiltrating the atrial septum and cavo-atrial junction with concomitant mild pericardial effusion. In the present case, we illustrate complementary role of transthoracic, transesophageal echocardiography and multislice CT scan with three-dimensional reconstruction, in detection and evaluation of secondary cardiac tumor. Usefulness of echocardiography to follow up the effects of chemotherapy is also shown. (Echocardiography 2010;27:332-336)

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.

We appreciate the interest of Dr. Mielewczik and colleagues in the C-CURE (Cardiopoietic stem Cell therapy in heart failURE) trial. As outlined in our paper [(1)][1], feasibility and safety were the primary endpoints in this first-in-man study that assessed cardiogenically-oriented, autologous bone

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.

Optimal treatment for chronic total occlusion (CTO) in the infarct-related coronary artery is not clear. Our aim was to assess myocardial perfusion, left ventricular ejection fraction (EF), and left ventricular size using gated single-photon emission computed tomography (SPECT) myocardial perfusion imaging with 99mTc-methoxy-isobutyl-isonitrile in patients with CTO before and 1 year after recanalization.Thirty patients with earlier myocardial infarction and at least one CTO underwent percutaneous coronary intervention (PCI) as well as nitrate-enhanced gated SPECT myocardial perfusion and dobutamine stress echocardiography before and 11 +/- 1 months after recanalization. They were divided into three groups based on the outcome of the follow-up angiography: (i) successful recanalization with no evidence of in-stent restenosis (n=13); (ii) successful recanalization with in-stent restenosis (n=7) and (iii) unsuccessful recanalization (n=10).Overall success of recanalization for CTO was 74%. In group 1, myocardial viability was preserved in 11 of 13 (85%) patients at baseline. Gated SPECT at 1 year showed a significant decrease in perfusion abnormalities (29 +/- 12 to 23 +/- 14%, P0.05) and left ventricular end-diastolic volume (EDV) (168 +/- 47 to 151 +/- 47 ml, P0.05). Improvement in EF (51 +/- 11 to 54 +/- 13%, P0.05) and reduction in left ventricular end-systolic volume (ESV) (84 +/- 37 to 77 +/- 40 ml, P0.05) did not reach the level of significance. Myocardial viability was preserved in only two of seven patients (28%) in group 2. Neither mean perfusion abnormalities (37 +/- 24 to 35 +/- 22%, P0.05) nor global left ventricular parameters (EF 41 +/- 15 vs. 42 +/- 19%, EDV 298 +/- 33 vs. 299 +/- 57 mL, ESV 197 +/- 12 vs. 195 +/- 32 ml; P0.05) changed at the follow-up. In group 3, myocardial viability was preserved in seven of 10 patients (70%) at baseline, but no significant changes in perfusion (40 +/- 18 vs. 41 +/- 19%, P0.05) and left ventricular function (EF 42 +/- 17 vs. 44 +/- 14%, EDV 228 +/- 101 vs. 227 +/- 81 ml, ESV 143 +/- 87 vs. 146 +/- 8 ml; P0.05) were seen at the follow-up.Myocardial perfusion and EDV may significantly improve 1 year after PCI provided recanalization of CTO was successful. Our preliminary findings suggest that successful recanalization of CTO may have favorable outcome on left ventricular perfusion and function, particularly in patients with viable myocardium before PCI. The gated SPECT myocardial perfusion imaging with 99mTc-methoxy-isobutyl-isonitrile may be useful for monitoring long-term functional outcome of PCI in patients with CTO.

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.

Percutaneous recanalization of coronary artery chronic total occlusion remains a technical challenge for the interventional cardiologist, with a lower success rate than most other lesions. Operator experience and specific tips and tricks with novel dedicated technical devices are needed to obtain procedural success in the majority of situations. The authors report a case of successful revascularization of a chronically occluded left anterior descending coronary artery using a novel penetration device (Tornus, Asahi) to facilitate balloon and stent deployment.

ObjectivesThe aim of our study was to compare coronary vasomotion after implantation of a second-generation biolimus A9-eluting stent (BES) and of a sirolimus-eluting stent (SES).BackgroundDrug-eluting stents (DES) have been associated with impaired local coronary vasomotion, delayed endothelialization, and increased late thrombotic risk. New DES with different drugs, pharmacokinetics, and polymers have been developed.MethodsNineteen patients with a BES and 15 patients with a SES were studied 9 months after stent implantation. Endothelium-dependent and -independent coronary vasomotion were tested proximally and distally to the stent as well as at a reference segment during right atrial pacing at increasing heart rates. Quantitative coronary angiographic measurements were performed offline.ResultsOf the patients with BES, 2 showed vasoconstriction with increased heart rate and 17 showed vasodilatation. Of the patients with a SES, 9 showed vasoconstriction while 6 showed vasodilatation. The SES showed significant vasoconstriction at both the proximal (−2.3 ± 10% vs. 7.9 ± 10%) and the distal (−5.4 ± 9% vs. 6.1 ± 8%) segments to the stent compared with the BES (p = 0.003 for proximal, p < 0.001 for distal segment). Endothelium-independent vasomotion after intracoronary nitrates did not differ significantly between the 2 groups (p = NS for proximal and distal segment).ConclusionsUnlike the case with the SES, endothelium-dependent vasomotion at adjacent stent segments seems to be preserved after BES implantation. This result may be explained by the different drug release kinetics, DES design, or characteristics of polymer used in the stent system.

Aims The aim of the study was to evaluate the relation between fractional flow reserve (FFR) and simultaneously evaluated coronary flow reserve by thermodilution (CFRthermo), with the improvement of left ventricular (LV) function in patients with previous myocardial infarction (MI) undergoing percutaneous coronary intervention (PCI). Methods and results Study population consisted of 46 patients (mean age 53 ± 7 years; 36 male) with previous MI and significant coronary stenosis undergoing PCI of infarct-related coronary artery. In all patients, we evaluated FFR and CFRthermo by single pressure/thermo wire during maximal hyperaemia before and immediately after PCI. We performed echocardiographic assessment of LV ejection fraction before and 6 months after PCI. Dobutamine stress echocardiography test was also performed before PCI. LV functional improvement was observed in 33/46 (72%) of patients. In patients with LV functional recovery in comparison with patients with no recovery, there was a significant difference in FFR before PCI (0.56 ± 0.14 vs. 0.70 ± 0.07, P < 0.001), improvement of FFR (0.35 ± 0.14 vs. 0.21 ± 0.07, P < 0.001), improvement of CFRthermo (1.3 ± 0.6 vs. 0.5 ± 0.3, P < 0.001), and CFRthermo after PCI (2.6 ± 0.7 vs. 2.0 ± 0.4, P < 0.001). When only parameters evaluated before PCI were taken into account, FFR before angioplasty ( P = 0.001) and dobutamine-assessed viability ( P = 0.006) were the most significant multivariate predictors of myocardial recovery. When all significant univariate parameters were evaluated, the most significant independent predictors for improvement in myocardial function were the improvement of CFRthermo during angioplasty ( P < 0.001) and FFR before angioplasty ( P = 0.002). Conclusion Simultaneous evaluation of FFR and CFRthermo provide significant complementary data on the improvement in myocardial function in patients with previous MI. However, the evaluation of FFR before angioplasty identifies viable myocardium that may recover following revascularization and may be used as an alternative to non-invasive testing.

INTRODUCTION. Mortality in ST elevation myocardial infarction (STEMI) ranges from 4-24% and is dependent on the variety of patients? clinical characteristics (CC) that are present prior to and within the first hours of the onset of MI, affecting reliability of the diagnosis. The higher mortality rate of patients with STEMI should be associated with a higher rate of applied reperfusion therapy according to guidelines and randomized study results, which is in opposition to everyday hospital practice. OBJECTIVE. The aim of this study was to analyze the mortality of STEMI patients in relationship to their clinical characteristics at presentation, their age, sex, risk factors, prior coronary disease, and time interval from symptom onset to hospital presentation, complications and administered therapy. METHOD. The analysis involved patients treated in five coronary care units, four Belgrade Hospital Centres and the Belgrade Emergency Centre of the Clinical Centre of Serbia. Evaluated data was obtained from the Serbian National Registry for Acute Coronary Syndrome (REAKSS) and databases of local coronary care units (CCU). RESULTS. During 2005 and 2006, a total of 2739 patients with STEMI, of average age 63.3?11.7, with 64.9% males aged 61.3?11.7 and 35.1% females aged 67.0?10.7 (p0.05). Regarding risk factors, hypertension was present in 61.8% of patients, more often among women (69.1% vs.57.9%) (p0.05), and was significantly higher among females 23.5% vs. 20.1% in males (p

Serum cholesterol is positively associated with the risk of developing coronary heart disease. The aim of this study was to determine the relation between response of coronary arteries to ergonovine provocation and lipid profile in patients with nonsignificant coronary artery disease. 105 patients (46 male, 59 female, mean age 52 ± 8 years) with chest pain syndrome and nonsignificant coronary artery stenosis (< 50% diameter stenosis) were analyzed. Ergonovine test was performed at the end of diagnostic catheterization. Coronary spasm was defined as total or near total obstruction of the coronary artery. By quantitative coronary arteriography, changes of minimal luminal diameter (MLD) during ergonovine provocation were evaluated. Total cholesterol, LDL and HDL cholesterol, and triglycerides were measured. There was a significant negative correlation between resting MLD and LDL cholesterol (r = –0.215; p = 0.034), and a significant positive correlation between MLD decrease provoked by ergonovine and total cholesterol (r = 0.275; p = 0.006), as well as LDL cholesterol (r = 0.284; p = 0.004), but not for HDL cholesterol and triglycerides (p = NS [not significant]). In patients with nonsignificant coronary artery stenosis evaluated by ergonovine provocation, there was not only a significant negative correlation between MLD and LDL cholesterol, but also a positive correlation between coronary vasoconstriction induced by ergonovine provocation and both total and LDL cholesterol.

Introduction. The athletic heart syndrome is characterized by morphological, functional and electrophysiological alterations as an adaptive response to vigorous physical activity. Athletes heart is predominantly associated with a programmed, intensive training. But as there are different kinds of physical activities, the degree of these changes is highly variable. Electrophysiological characteristics of the athlete's heart. The response of the body to vigorous physical activity is a multiorgan system phenomenon. The integrated functioning of each of these organ systems is very important, but the cardiovascular system plays a critical role in mediating the activity. Because of that, most changes in the neurohumoral regulation pre- dominantly affect the cardiovascular system. These changes include: depression of sympathetic activity and stimulation of parasympathetic activity, so electrophysiological characteristics of the athlete's heart must differ from the sedentary. Although these facts, are well known, the athlete's heart is not a precisely defined concept. It is a gray zone between physiology and pathology. Conclusion. Considering the number of sudden cardiac deaths in athletes, it is needless to say how important it is to distinguish physiological changes of the heart due to physical activity, and pathological changes due to some cardiac diseases.

Background Nicorandil, as a selective potassium channel opener, has dual action including coronary and peripheral vasodilatation and cardioprotective effect through ischemic preconditioning. Considering those characteristics, nicorandil was suggested to reduce the degree of microvascular dysfunction. Methods Thirty-two patients with ST-elevation myocardial infarction undergoing primary percutaneous coronary intervention (pPCI) were included in the study. Index of microvascular resistance (IMR) was measured in all patients immediatelly after pPCI before the after administration of Nicorandil. ST segment resolution was monitored before intervention and 60 min after terminating the procedure. Echocardiographic evaluation of myocardial function and transthoracic Doppler derived Coronary flow reserve (CFR) of infarct related artery (IRA) was performed during hospitalization and 3 months later. Results IMR was significantly lower after administration of Nicorandil (9.9 ± 3.7 vs. 14.1 ± 5.1, p

Mitral valve aneurysm (MVA) is a rare valve disease. The case is reported of pathologically proven MVA in a 61-year-old diabetic male with chronic alcoholic liver disease who presented with dyspnea and new-onset atrial fibrillation, without clinical elements of current or recent infection. Transthoracic echocardiography revealed a 'cystic' formation of the anterior mitral leaflet (AML) with mild mitral regurgitation (MR) and aortic regurgitation (AR) hitting the AML. Transesophageal echocardiography (TEE) showed clearly that the formation on the AML was a valve aneurysm, and depicted the site of aneurysm rupture with an additional jet of MR through the rupture. Following mitral valve replacement, pathology of the excised valve showed chronic bacterial endocarditis with calcified bacterial colonies, myxomatous changes with fibrinoid dissection of lamina fibrosa, and neovascularization of the leaflet. The mechanisms of MVA formation are discussed, together with its potential complications, diagnostic modalities and therapeutic strategies. The present case emphasizes that MVA is often a remnant of endocarditis, even when the latter is clinically silent and undiagnosed. The importance of chronic AR directed towards the AML as a predisposing condition for MVA formation is also underlined in this case. The superiority of TEE in providing a full exploration of the mitral valve morphology is verified.

Background Although new-onset atrial fibrillation (AF) frequently recurs following the acute myocardial infarction, the significance of AF recurrences is unknown. Objective The objective of the present study was to evaluate the incidence, clinical predictors and prognostic significance of AF recurrences following the acute myocardial infarction. Methods and results A total of 320 consecutive patients with AF following the acute myocardial infarction were evaluated and the patients with AF recurrences were compared to those with single episodes of AF in whom AF did not recur after restoration of sinus rhythm. The incidence of AF recurrences was 22.5%. AF recurrences were highly associated with congestive heart failure and worse Killip class was identified as the most important predictor of AF recurrences. Patients with AF recurrences had poorer outcome, including higher in-hospital (36.1% versus 12.9%) and 7-year (68.2% versus 48.6%) mortality. After multivariate adjustment, AF recurrence remained an independent predictor of in-hospital [odds ratio (OR)=3.08, 95% confidence interval (CI), 1.45–6.53, p =0.001], and 7-year [relative risk (RR)=1.52, 95% CI, 1.00–2.31, p =0.026] mortality. Conclusion New-onset AF frequently recurs following the acute myocardial infarction and our analysis demonstrated that recurrences of AF independently predicted in-hospital and long-term mortality.

To investigate whether biphasic response during dipyridamole echocardiography test (DET), which represents viable but potentially ischemic myocardium in the infarcted region, affects prognosis of patients after uncomplicated acute myocardial infarction, we performed high-dose DET in 80 consecutive patients younger than 65 years with first acute myocardial infarction and preserved left ventricular function. Patients were followed up for 27 +/- 12 months for new coronary events. According to DET results all patients were classified into 4 groups: group 1 consisted of 20 patients with biphasic response; group 2 included 14 patients with sustained improvement in regional contractility; group 3 consisted of 24 patients showing no change in contractility; and group 4 included 22 patients with worsening response. Cumulative survival free of total coronary events was significantly lower in group 1 patients compared with all other groups (P.05). By multivariate Cox analysis biphasic response was the strongest independent predictor of stable angina pectoris (odds ratio = 12.1, P = .0002), followed by hyperlipoproteinemia (odds ratio = 5.9, P = .006). On the other hand, development of acute coronary syndromes could not have been predicted by actual clinical or DET parameters.

OBJECTIVE: To assess whether the difference in risk of cardiovascular mortality between urban and rural areas of Serbia could be explained by differences in the use of cardiovascular medication. METHODS: The Serbian cohorts of the Seven Countries Study, Velika Krsna (VK), Zrenjanin (ZR) and Belgrade (BG), were enrolled in 1962-1964 and were followed up for 25 years. The survivors of these cohorts were re-examined in 1987, 1988 and 1989, respectively. This second examination of elderly men aged 65 to 84 years included a questionnaire about current use of cardiovascular medication, risk factors and diseases and a physical examination. All subjects were followed until death or the predefined censor date (10 years after baseline). The Cox proportional hazards model was used to calculate the risk of cardiovascular mortality in the rural cohorts compared to the urban cohort and to adjust for confounding. MAIN OUTCOME MEASURE: Cardiovascular death. RESULTS: A total of 227 men from VK, 184 men from ZR and 287 men from BG were followed for a mean duration of 7.4 years and was complete for all subjects. After exclusion of 13 subjects with missing medication data, the incidences of cardiovascular mortality in VK, ZR, and BG were 60, 74, and 26 per 1,000 person-years, respectively. The prevalence of cardiovascular medication use was 38% in VK, 52% in ZR, and 59% in BG. The greatest difference in use of specific medication was observed for betablockers (0% in VK and ZR, 13% in BG). After adjustment for cardiovascular risk factors, diseases and age, the relative risks (RRs) of cardiovascular mortality were 2.12 [95% CI: 1.44-3.12], and 2.27 [95% CI: 1.56-3.30] in VK, and ZR compared to BG. Additional adjustment for the use of cardiovascular medication increased these RRs to 2.40 [95% CI: 1.61-3.60] and 2.55 [95% CI: 1.72-3.78], respectively. CONCLUSION: The variation in cardiovascular medication use could not explain the excess risk of mortality in the rural Serbian cohorts compared to urban Belgrade.

Background— The clinical significance of pericardial biopsy is controversial. The aim of this study was to assess the feasibility and diagnostic value of 3 approaches to pericardial biopsy: fluoroscopic control and standard sampling, pericardioscopy guidance with standard sampling, and pericardioscopy guidance with extensive sampling. Methods and Results— Forty-nine subsequent patients with a large pericardial effusion underwent parietal pericardial biopsy. In group 1 (12 patients, 66.7% males, age 46.7±12.2 years), pericardial biopsy was guided by fluoroscopy (3 to 6 samples per patient). Group 2 included 22 patients (50% males, age 50.8±10.4 years) undergoing 4 to 6 pericardial biopsies per patient guided by pericardioscopy (16F flexible endoscope). In group 3, extensive pericardial sampling was performed, guided by pericardioscopy (15 patients, 53.3% males, age 53.7±12.8 years, 18 to 20 samples per patient). Sampling efficiency was better with pericardioscopy (group 2, 84.9%; group 3, 84.2%) compared with fluoroscopic guidance (group 1, 43.7%; P P P P P Conclusions— Pericardioscopic guidance enhanced pericardial sampling efficiency. The diagnostic value of pericardial biopsy was significantly improved by extensive sampling made possible by pericardioscopy.

The prognostic meaning of myocardial viability is most important in patients with severe left ventricular dysfunction and ischaemic heart disease, but its prognostic significance in patients with previous myocardial infarction and mild-to-moderate myocardial dysfunction is uncertain. The aim of this study was to assess the prognostic value of a 201 Tl single photon emission computed tomography (SPECT) rest-redistribution study in patients with previous myocardial infarction, ischaemic heart disease and mild-to-moderate myocardial dysfunction. Myocardial viability was assessed in 55 patients (50 male; mean age 58±9 years) by 201 Tl SPECT rest-redistribution (after 4 h) scintigraphy. All patients had previous myocardial infarction (>3 months) and angiographically documented coronary artery disease, with the mean ejection fraction of 43±10%. Out of 55 patients, 20 were medically treated and 35 were revascularized. The follow-up period for adverse cardiac events, including death and non-fatal myocardial infarction, was 12 months. 201 Tl SPECT study was positive for myocardial viability in 36 patients (65%) and negative in 19 patients (35%). Sensitivity, specificity, positive and negative predictive values for functibnal improvement in the follow-up period were 85%, 75%, 92% and 60%. Out of seven (13%) cardiac events in the follow-up period (four cardiac deaths and three reinfarctions), five occurred in 20 medically treated patients and two in 35 revascularized patients (25% vs 6%, P < 0.05). Absence of myocardial viability was the only variable associated with adverse cardiac events (P = 0.02). Survival at 12 months, as determined by using Kaplan-Meier analysis, was 56% for medically treated and non-viable patients, 80% for revascularized and non-viable patients, 91% for medically treated and viable patients, and 100% for revascularized and viable patients (P=0.0034). These findings suggest that in patients with previous myocardial infarction and mild-to-moderate myocardial dysfunction, the absence of myocardial viability as determined by the 201 Tl SPECT study was the only variable associated with adverse cardiac events. The best 12 month survival was observed in revascularized viable patients, whereas the worse prognosis was found in non-viable, medically treated patients.

In a STEMI setting, stent implantation for a myocardial bridge (MB) with significant systolic compression in the mid LAD, is a challenging issue.The risk of coronary rupture during stent implantation arises from: (i) a thin intima of the bridged artery; (ii) a thin myocardial layer toward the right ventricle; (iii) a smaller LAD diameter in the MB; (iv) high inflation pressure in the balloon. Perforation with a coronary fistula resolving spontaneously within several months is one of the possible scenarios. We report a case of a coronary fistula between mid LAD and right ventricle after MB stenting in a patient with STEMI, with spontaneous angiographic deterioration after several days. Stent graft implantation in case of a coronary fistula with increasing flow is an effective therapeutic concept.

Aim: The aim of this study was to examine whether the termination of long-term clopidogrel therapy results in a proinflammatory state and whether lipid parameters influence the inflammatory response after stopping the drug.Methods: A prospective, multicenter study was conducted among 200 patients with implanted coronary stents who received dual antiplatelet therapy for one year, without ischemic or bleeding events. According to the guidelines, clopidogrel was discontinued after one year. In all patients, the high-sensitivity C-reactive protein (hsCRP), soluble CD40 ligand (sCD40L) and lipid [total cholesterol, triglycerides, high-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol (LDL-C)] levels were measured twice: on the day of cessation of clopidogrel and 45 days after the termination of clopidogrel treatment.Results: In men (n=151), the sCD40L serum levels were significantly higher 45 days after the discontinuation of clopidogrel (p=0.007), while the hsCRP levels were not significantly different (p=0.407). Furthermore, when analyzed across the HDL-C quartiles, the hsCRP and sCD40L values were found to be associated with the levels of HDL-C after the discontinuation of clopidogrel in men. In addition, the men in the first HDL-C quartile exhibited the most pronounced increase in the sCD40L levels (p=0.001) and had significantly higher hsCRP levels (p=0.001) compared to the subjects in the other quartiles. Other lipid parameters did not show any associations with the sCD40L or hsCRP levels.Conclusions: The discontinuation of clopidogrel is associated with higher increments in the sCD40L level, and a pronounced proinflammatory response is associated with a lower HDL-C concentration.

Within modern medicine at the beginning of 21st century, we are witnessing a revolutionary development of the invasive diagnostics and therapy of cardiovascular system diseases. With the discovery of X-rays at the end of 19th century by Wilhelm Roentgen, it is appropriate to reflect on the gifted individuals whose efforts drastically altered radiology and cardiology. The early techniques used in peripheral percutaneous transluminal angioplasty form the basis for subsequent percutaneous intervention both in the peripheral and coronary arteries and are largely the contribution of Charles Dotter. The main goal of his work was the use of catheters for diagnosis and treatment in an attempt to replace the scalpel. He was 20 years ahead of his time, especially with percutaneous transluminal angioplasty. The first percutaneous transluminal angioplasty marked a new era in the treatment of peripheral atherosclerotic lesions. This practical genius dedicated his considerable energy to the belief that there is always a better way to treat disease. His personal contributions to clinical medicine, research, and teaching have saved millions of limbs and lives all over the world. European physicians, who were more open to unproven techniques, almost immediately embraced percutaneous transluminal angioplasty. Without the contribution and help of his colleagues, Forssmann, Sones and Gruntzig, all of them pioneers, nothing would be done. They were all ahead of there time and opened completely new chapter in medicine.

Routine thrombus aspiration is proposed to be superior to conventional primary percutaneous coronary intervention (PCI) in terms of improved myocardial perfusion, in patients with ST-segment elevation acute myocardial infarction (STEMI). However, myocardial perfusion after thrombus aspiration has not been evaluated by a quantitative, invasive method. We intend to determine whether manual thrombus aspiration in the infarct-related coronary artery increases myocardial perfusion assessed by index of microcirculatory resistance (IMR) compared with conventional primary PCI.PATA STEMI is a single-center, prospective, randomized trial with a planned inclusion of 128 patients with the first STEMI. Prior to coronary angiography, patients are randomly assigned to thrombus aspiration using the Eliminate aspiration catheter (Terumo Medical Supply, Japan) or to conventional primary PCI. After completion of primary PCI, IMR is determined both in infarct-related artery and in noninfarct-related arteries without critical stenoses. The primary end-point is a group mean value of IMR after thrombus aspiration compared with conventional primary PCI. Secondary end-points are myocardial perfusion grade, resolution of ST-segment elevation, enzymatic estimation of infarct size, left ventricular remodeling assessed by echocardiographic indices, and major adverse cardiac events rate at 1, 6, and 12 months.If manual thrombus aspiration significantly reduces microcirculatory resistance, thereby improving myocardial perfusion, it may become the routine strategy in primary PCI.

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

Objectives This study sought to study the efficacy and safety of newer-generation drug-eluting stents (DES) compared with bare-metal stents (BMS) in an appropriately powered population of patients with ST-segment elevation myocardial infarction (STEMI). Background Among patients with STEMI, early generation DES improved efficacy but not safety compared with BMS. Newer-generation DES, everolimus-eluting stents, and biolimus A9-eluting stents, have been shown to improve clinical outcomes compared with early generation DES. Methods Individual patient data for 2,665 STEMI patients enrolled in 2 large-scale randomized clinical trials comparing newer-generation DES with BMS were pooled: 1,326 patients received a newer-generation DES (everolimus-eluting stent or biolimus A9-eluting stent), whereas the remaining 1,329 patients received a BMS. Random-effects models were used to assess differences between the 2 groups for the device-oriented composite endpoint of cardiac death, target-vessel reinfarction, and target-lesion revascularization and the patient-oriented composite endpoint of all-cause death, any infarction, and any revascularization at 1 year. Results Newer-generation DES substantially reduce the risk of the device-oriented composite endpoint compared with BMS at 1 year (relative risk [RR]: 0.58; 95% confidence interval [CI]: 0.43 to 0.79; p=0.0004). Similarly, the risk of the patient-oriented composite endpoint was lower with newer-generation DES than BMS (RR: 0.78; 95% CI: 0.63 to 0.96; p=0.02). Differences in favor of newer-generation DES were driven by both a lower risk of repeat revascularization of the target lesion (RR: 0.33; 95% CI: 0.20 to 0.52; p < 0.0001) and a lower risk of target-vessel infarction (RR: 0.36; 95% CI: 0.14 to 0.92; p=0.03). Newer-generation DES also reduced the risk of definite stent thrombosis (RR: 0.35; 95% CI: 0.16 to 0.75; p=0.006) compared with BMS. Conclusions Among patients with STEMI, newer-generation DES improve safety and efficacy compared with BMS throughout 1 year. It remains to be determined whether the differences in favor of newer-generation DES are sustained during long-term follow-up. (J Am Coll Cardiol Intv 2014;7:55-63) (C) 2014 by the American College of Cardiology Foundation

The diagnostic accuracy of the physical and pharmacological stress echocardiography tests is higher than routine exercise electrocardiography. They have an acceptable safety profile and have been rarely associated with severe adverse effects.We present a case of acute anterior myocardial reinfarction immediately after exercise and pharmacological (dipyridamole-atropine) stress echocardiography testing 1 month after successful stent implantation in LAD. Our patient was a 43-year-old man with a history of heavy smoking and hypertension. Remarkably, the stress echocardiogram was non-diagnostic few hours before the infarction occurred. Angiography performed 4 months after the reinfarction revealed neither a culprit lesion nor stent thrombosis.Aggressive "last generation" pharmacological stress testing may provide optimal diagnostic accuracy, but as in our case, complications may occur, even after negative stress testing. To our knowledge, this is the first reported case of an acute myocardial infarction as a severe complication of stress testing, which developed in a patient after stent implantation.

Aims The aim of this study was to assess the prognostic value of myocardial viability recognized as a contractile response to vasodilator stimulation in patients with left ventricular dysfunction in a large scale, prospective, multicentre, observational study. Methods and Results Three hundred and seven patients (mean age 60±10 years) with angiographically proven coronary artery disease, previous (>3 months) myocardial infarction and severe left ventricular dysfunction (ejection fraction

It is still controversial whether the arrhythmias in acute pericarditis are of myocardial or pericardial origin. The aim of the present study was to investigate the occurrence of arrhythmias and conduction disorders in patients with acute pericarditis with no endomyocardial biopsy evidence of myocarditis (group 1:40 patients, 65% males, mean age 45.6 ± 15.7 years, mean heart rate [HR] 98.7 ± 22.2 beats per minute) in comparison to endomyocardial biopsy proven acute myocarditis/perimyocarditis (group 2:10 patients, 3/10 with perimyocarditis, 70% males, mean age 46.1 ± 15.8 years, mean heart rate 76.7 ± 33.1 beats per minute). At the initial assessment all patients underwent comprehensive clinical work-up including echocardiography, cardiac catheterization, and endomyocardial biopsy. In all patients biventricular endomyocardial biopsy was performed using standard femoral approach and Schikumed 7 F for 8 F bioptomes. Tissue samples were stained by H & E, v. Gieson and independently reviewed by two cardiac pathologists. In addition immunohistochemistry and immunocytochemistry were performed, and only patients fulfilling Dallas and World Heart Federation criteria were selected for group 2. Comparative analysis of electrocardiograms and 24-hour Holter recordings at initial presentation revealed in group 1 vs group 2 significantly less frequent paroxysmal supraventricular tachyarrhythmias (5% vs 40%), and ventricular fibrillation (0 vs 20%), in contrast to atrial fibrillation that occurred more often (20% vs 0) (all p < 0.05). Furthermore, in the group 2 one patient died due to VF and two patients underwent ICD implantation. Low voltage (40% vs 30%) and ST/T wave changes (47.5% vs 30%), as well as the incidence of the II° AV block (5% vs 0) and complete AV block (2.5% vs 10%) were not significantly different between the groups. In conclusion, patients with pericarditis and no endomyocardial biopsy indications of myocarditis had significantly less often life threatening rhythm disorders in contrast to patients with endomyocardial biopsy proven acute myocarditis/perimyocarditis. On the contrary, incidence of transitory atrial fibrillation was higher in acute pericarditis, than in myocarditis.

Aim The aim of this study was to evaluate simultaneously echocardiographic, haemodynamic and angiographic changes that occur during adenosine and dipyridamole infusion, in patients with one-vessel coronary artery stenosis. This would assess whether deterioration in left ventricular haemodynamics during vasodilator agent infusion is influenced by vasodilation per se, or the development of myocardial ischaemia. Methods and results We performed adenosine (140 μg.kg−1.min−1 over 4 min) and dipyridamole (up to 0·84 mg.kg−1 over 10 min) stress echocardiography tests, together with angiographic and haemodynamic assessment, in 26 patients undergoing elective coronary angioplasty. In 12 of 26 patients, adenosine and dipyridamole tests were repeated 24 h after angioplasty. The criterion for echocardiography test positivity was the appearance of a new transient regional wall motion abnormality. Coronary angiograms were analysed with quantitative coronary arteriography. Adenosine and dipyridamole induced regional dysfunction in 18/26 (69%) and 14/26 (54%) patients before angioplasty, respectively ( P =ns). In the echocardiography-positive patients, the percent diameter stenosis was significantly (P

Dipyridamole stress is the forerunner and prototype of pharmacological stress echo tests in the diagnosis of coronary artery disease. Among the various stress echo tests, it is probably the least technically demanding to perform and the easiest to interpret. Its accuracy is similar to dobutamine stress echocardiography but its feasibility is higher. The prognostic impact of dipyridamole stress echo has also been proven for presentation of hard end-points such as cardiac death. The safety and prognostic value of this test has been conclusively demonstrated as a result of extensive experience in large scale multicentre projects. Dipyridamole stress is many different tests in one: dipyridamole atropine is best for diagnosis; dipyridamole dobutamine or dipyridamole-exercise is highly sensitive for the detection of minor forms of coronary artery disease; low and high dose dipyridamole is best suited for prognostic stratification; infra-low dipyridamole with low dose dobutamine administration is probably best suited for selective myocardial viability identification. Each patient should have their own test, tailored on the basis of the clinical picture and the diagnostic issue.

This study sought to study the efficacy and safety of newer-generation drug-eluting stents (DES) compared with bare-metal stents (BMS) in an appropriately powered population of patients with ST-segment elevation myocardial infarction (STEMI).Among patients with STEMI, early generation DES improved efficacy but not safety compared with BMS. Newer-generation DES, everolimus-eluting stents, and biolimus A9-eluting stents, have been shown to improve clinical outcomes compared with early generation DES.Individual patient data for 2,665 STEMI patients enrolled in 2 large-scale randomized clinical trials comparing newer-generation DES with BMS were pooled: 1,326 patients received a newer-generation DES (everolimus-eluting stent or biolimus A9-eluting stent), whereas the remaining 1,329 patients received a BMS. Random-effects models were used to assess differences between the 2 groups for the device-oriented composite endpoint of cardiac death, target-vessel reinfarction, and target-lesion revascularization and the patient-oriented composite endpoint of all-cause death, any infarction, and any revascularization at 1 year.Newer-generation DES substantially reduce the risk of the device-oriented composite endpoint compared with BMS at 1 year (relative risk [RR]: 0.58; 95% confidence interval [CI]: 0.43 to 0.79; p = 0.0004). Similarly, the risk of the patient-oriented composite endpoint was lower with newer-generation DES than BMS (RR: 0.78; 95% CI: 0.63 to 0.96; p = 0.02). Differences in favor of newer-generation DES were driven by both a lower risk of repeat revascularization of the target lesion (RR: 0.33; 95% CI: 0.20 to 0.52; p0.0001) and a lower risk of target-vessel infarction (RR: 0.36; 95% CI: 0.14 to 0.92; p = 0.03). Newer-generation DES also reduced the risk of definite stent thrombosis (RR: 0.35; 95% CI: 0.16 to 0.75; p = 0.006) compared with BMS.Among patients with STEMI, newer-generation DES improve safety and efficacy compared with BMS throughout 1 year. It remains to be determined whether the differences in favor of newer-generation DES are sustained during long-term follow-up.

Introduction. Congenital anomalies of the aortic arch, although numerous and heterogeneous, occur in less than 1% of individuals at autopsies. Left aortic arch with an aberrant right subclavian artery, also called arteria lusoria dextra, is the most common anomaly of the aortic arch, occurring in 0.5-2.5% of individuals. Case Outline. We report the case of a 48-year-old man suffering from acute inferoposterior-wall ST elevation myocardial infarction successfully treated by primary percutaneous coronary intervention. Ten years ago, the patient had undergone coronary artery bypass graft surgery with the implantation of two arterial grafts - left and right internal mammary arteries on both left anterior descending and right coronary artery. After several attempts to canulate truncus brachiocephalicus, angiogram revealed the left aortic arch with the aberrant right subclavian artery. To our knowledge, this is the first described case of primary percutaneous coronary intervention via the aberrant right subclavian artery and right internal mammary artery graft with stent implantation in the infarct related lesion of the distal segment of right coronary artery. Subsequent 64-multidetector computed tomography confirmed the angiographic findings. Conclusion. Early recognition of congenital anomalies of the aortic arch and its great vessels, even before coronary artery bypass graft surgery, could be crucial for the urgent and successful treatment of patients with life-threatening conditions, such as ST segment elevation myocardial infarction.

Summary What is known and objective Premature discontinuation of clopidogrel in patients undergoing percutaneous coronary intervention is a significant risk factor for thrombotic adverse outcomes. However, recent studies indicate that even discontinuation of long-term use of clopidogrel may be associated with multiple adverse outcomes, that is, rebound phenomenon whose mechanism is not definitely clear. The aim of the study was to examine the effect of clopidogrel withdrawal in those on combined aspirin and clopidogrel therapy. Methods This prospective, multicenter study enrolled 200 patients who underwent coronary stent implantation and were on dual antiplatelet therapy (100 mg aspirin + 75 mg clopidogrel) 1 year after the stent placement. In all patients, we measured the platelet aggregation, by multiplate electrode aggregometry, using two agonists [adenosine diphosphate with PGE1 (ADPHS) and arachidonic acid (ASPI)] two times: on the day of cessation of clopidogrel and 90 days after clopidogrel was stopped. Results and discussion Following clopidogrel discontinuation, we registered an increase in ASPI values (P

Background: Lipoprotein-associated phospholipase A(2) (Lp-PLA(2)) has been suggested as an inflammatory marker of cardiovascular risk. The predictive value of Lp-PLA(2) in ST-segment elevation myocardial infarction (STEMI) treated by primary percutaneous coronary intervention (PCI) has not been established. The aim of this study was to determine whether plasma Lp-PLA(2) is a predictor of a major adverse cardiac event (MACE) in patients with the first anterior STEMI treated by primary PCI. Methods: This study consisted of 100 consecutive patients with first anterior STEMI who underwent primary PCI within 6 hours of the symptom onset. Plasma Lp-PLA(2) level was measured on admission using a turbidimetric immunoassay (diaDexus, Inc., USA). The Receiver Operating Characteristic analysis was performed to identify the most useful Lp-PLA(2) cut-off level for the prediction of MACE. The patients were divided into two groups according to the cut-off Lp-PLA(2) level: high Lp-PLA(2) group (>= 463 ng/mL, n = 33) and low Lp-PLA(2) group ( lt 463 ng/mL, n = 67). MACE was defined as cardiac death, non-fatal reinfarction, and target vessel revascularization. Results: Patients in the high Lp-PLA(2) group had significantly higher total-, LDL-cholesterol, apolipoprotein B levels, and significantly lower estimated glomerular filtration rates compared with the low Lp-PLA(2) group. The incidence of 30-day mortality was 18.2% (6/33) in high Lp-PLA(2) group, while in the low Lp-PLA(2) group no patient died (p lt 0.001). The 30-day MACE occurred in 24.2% of the high Lp-PLA(2) group and 3% of the low Lp-PLA(2) group (p = 0.001). Multiple logistic regression analysis identified the plasma Lp-PLA(2) level as an independent predictor of MACE (OR 1.011, 95%CI 1.001 - 1.013, p = 0.037). Conclusions: In patients with first anterior STEMI treated by primary PCI, the plasma Lp-PLA(2) level is an independent predictor of 30-day MACE. (Clin. Lab. 2012;58:1135-1144. DOI: 10.7754/Clin.Lab.2012.111102)

This study sought to evaluate the feasibility and safety of autologous bone marrow-derived and cardiogenically oriented mesenchymal stem cell therapy and to probe for signs of efficacy in patients with chronic heart failure.In pre-clinical heart failure models, cardiopoietic stem cell therapy improves left ventricular function and blunts pathological remodeling.The C-CURE (Cardiopoietic stem Cell therapy in heart failURE) trial, a prospective, multicenter, randomized trial, was conducted in patients with heart failure of ischemic origin who received standard of care or standard of care plus lineage-specified stem cells. In the cell therapy arm, bone marrow was harvested and isolated mesenchymal stem cells were exposed to a cardiogenic cocktail. Derived cardiopoietic stem cells, meeting release criteria under Good Manufacturing Practice, were delivered by endomyocardial injections guided by left ventricular electromechanical mapping. Data acquisition and analysis were performed in blinded fashion. The primary endpoint was feasibility/safety at 2-year follow-up. Secondary endpoints included cardiac structure/function and measures of global clinical performance 6 months post-therapy.Mesenchymal stem cell cocktail-based priming was achieved for each patient with the dose attained in 75% and delivery without complications in 100% of cases. There was no evidence of increased cardiac or systemic toxicity induced by cardiopoietic cell therapy. Left ventricular ejection fraction was improved by cell therapy (from 27.5 ± 1.0% to 34.5 ± 1.1%) versus standard of care alone (from 27.8 ± 2.0% to 28.0 ± 1.8%, p 0.0001) and was associated with a reduction in left ventricular end-systolic volume (-24.8 ± 3.0 ml vs. -8.8 ± 3.9 ml, p 0.001). Cell therapy also improved the 6-min walk distance (+62 ± 18 m vs. -15 ± 20 m, p 0.01) and provided a superior composite clinical score encompassing cardiac parameters in tandem with New York Heart Association functional class, quality of life, physical performance, hospitalization, and event-free survival.The C-CURE trial implements the paradigm of lineage guidance in cell therapy. Cardiopoietic stem cell therapy was found feasible and safe with signs of benefit in chronic heart failure, meriting definitive clinical evaluation. (C-Cure Clinical Trial; NCT00810238).

Brain natriuretic peptide (NT-pro-BNP) was implicated in the regulation of hypothalamic-pituitary-adrenocortical (HPA) responses to psychological stressors. However, HPA axis activation in different physical stress models and its interface with NT-pro-BNP in the prediction of cardiopulmonary performance is unclear. Cardiopulmonary test on a treadmill was used to assess cardiopulmonary parameters in 16 elite male wrestlers (W), 21 water polo player (WP) and 20 sedentary age-matched subjects (C). Plasma levels of NT-pro-BNP, cortisol and adrenocorticotropic hormone (ACTH) were measured using immunoassay sandwich technique, radioimmunoassay and radioimmunometric techniques, respectively, 10min before test (1), at beginning (2), at maximal effort (3), at 3rdmin of recovery (4). In all groups, NT-pro-BNP decreased between 1 and 2; increased from 2 to 3; and remained unchanged until 4. ACTH increased from 1 to 4, whereas cortisol increased from 1 to 3 and stayed elevated at 4. In all groups together, ΔNT-pro-BNP2/1 predicted peak oxygen consumption (B=37.40, r=0.38, p=0.007); cortisol at 3 predicted heart rate increase between 2 and 3 (r=-0.38,B=-0.06, p=0.005); cortisol at 2 predicted peak carbon-dioxide output (B=2.27, r=0.35, 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.

Background: Glycogen phosphorylase BB (GPBB) is released from cardiac cells during myocyte damage. Previous studies have shown contradictory results regarding the relation of enzyme release and reversible myocardial ischemia. The aim of this study was to determine the plasma kinetics of GPBB as a response to the exercise stress echocardiographic test (ESET), and to define the relationship between myocardial ischemia and enzyme plasma concentrations. Methods: We studied 46 consecutive patients undergoing ESET, with recent coronary angiography. In all patients, a submaximal stress echo test according to Bruce protocol was performed. Concentration of GPBB was measured in peripheral blood that was sampled 5 min before and 10, 30 and 60 min after ESET. Results: There was significant increase of GPBB concentration after the test (p=0.021). Significant increase was detected 30 min (34.9% increase, p=0.021) and 60 min (34.5% increase, p=0.016) after ESET. There was no significant effect of myocardial ischemia on GPBB concentrations (p=0.126), and no significant interaction between sampling intervals and myocardial ischemia, suggesting a similar release profile of GPBB in ischemic and non-ischemic conditions (p=0.558). Patients in whom ESET was terminated later (stages 4 or 5 of standard Bruce protocol; n=13) had higher GPBB concentrations than patients who terminated ESET earlier (stages 1, 2 or 3; n=33) (p=0.049). Baseline GPBB concentration was not correlated to any of the patients’ demographic, clinical and hemodynamic characteristics. Conclusions: GPBB plasma concentration increases after ESET, and it is not related to inducible myocardial ischemia. However, it seems that GPBB release during ESET might be related to exercise load/duration.

A 47-year-old male patient was admitted to our Emergency Hospital’s coronary unit with an acute myocardial infarction, localized inferolaterally. He had been hospitalized 2 months before this occurrence because of persistent chest pain accompanied by elevation of the ST segment in precordial and inferior leads, for which he received thrombolytic therapy. Selective cardiac catheterization was then also effected, and showed diffuse ectasia of coronary arteries with no significant stenoses. Since streptokinase had been applied recently, the patient was given standard therapy as well as electroshocks because of chamber fibrillation. Two hours after admission, the infarct pain ceased and rapid ECG improvement occurred. Repeated coronarography showed a situation identical to the previous one. The patient was sent home to proceed with drug therapy.

The associations between serum total and HDL cholesterol and three lifestyle factors—consumption of Turkish coffee, consumption of alcohol, and cigarette smoking—were examined in two Serbian cohorts of the Seven Countries Study. In 1988 and 1989, 319 men from Zrenjanin and Belgrade, 65 to 84 years old and free of myocardial infarction, participated. The men from Zrenjanin were originally working in a large cooperative, and the men from Belgrade were faculty members of the university. HDL cholesterol, alcohol consumption, and cigarette smoking were significantly higher in Zrenjanin than in Belgrade. Serum total cholesterol levels and coffee consumption were not different. ANCOVA showed that serum total cholesterol levels were 8.2% higher (P in men consuming two small cups of coffee per day compared with abstainers, and this was also seen after adjustment for cigarette smoking, age, body mass index, cohort, and alcohol consumption. In men consuming one or more alcoholic drinks per day (more than 10 g/d alcohol), HDL cholesterol levels were increased by 0.19 mmol/L (15.4%) compared with men consuming no alcohol (P . This association was stronger in the Zrenjanin cohort than in the Belgrade cohort (P . Smoking was not associated with total cholesterol or with HDL cholesterol levels. In Serbian men, boiled Turkish coffee and alcohol consumption are independently associated with serum total and HDL cholesterol levels, respectively. (Arterioscler Thromb Vase Biol. 1995;15:1793-1797.)