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Background/Aim. Percutaneous coronary interventions (PCI) in bifurcation lesions having more than 50% stenosis of both the main branch (MB) and the side branch (SB) remain challenging. Measurements of the vessel diameters and angles using quantitative coronary angiography (QCA) software have been used in evaluating PCI outcomes. We investigated potential effects of provisional stenting of the MB on SB coronary blood flow by determining quantitative vessel parameters in “true” non-left main coronary bifurcation lesions using conventional two-dimensional QCA. Methods. The study was prospective and conducted in a highvolume university PCI center. Study included patients with “true” native coronary artery bifurcations (Medina 1.0.1; 0.1.1; 1.1.1) treated with “provisional” stenting of the MB. Patients were excluded from the study if having left ventricular ejection fraction of less than 30%, having renal failure with creatinine clearance below 30 mL/kg/m2 or bifurcation lesions within the culprit artery causing myocardial infarction, grafted surgically or previously treated by PCI. QCA analysis included measurements of reference vessel diameters (RVD), diameter stenosis (DS) and bifurcation angles. Results. The study included 70 patients with 72 “true” non-left main bifurcations. Most of the bifurcations were located in the left anterior descending (LAD) – diagonal (Dg) territory. Compromise of the SB ostium defined as thrombolysis in myocardial infarction (TIMI) < 3 coronary flow occurred in 17/72 (23.6%) bifurcations. It was treated by either balloon angioplasty only of the SB ostium (9/17, 52.9%) or stent implantation [8/17 (47.1%)]. In a logistic regression analysis, including previously recognized predictors of SB compromise (bifurcation’s angles, RVD, DS and ratio of MB RVD to stent diameter ratio), only MB RVD to stent diameter ratio after PCI remained independent predictor of SB coronary flow compromise after stent implantation in the MB [OR 2.758 (95% CI 1.298–5.862); p = 0.008]. Conclusions. It appears that SB decreased coronary blood flow after “provisional” stenting in “true” non-left main bifurcations is associated with greater MB to stent diameter ratio.

Introduction/Objective. Chronic obstructive pulmonary disease (COPD) exacerbation is mostly triggered by infectious agents and seriously compromises the patient’s quality of life and predicts a poor outcome of the disease as well. If the signs of the probable bacterial cause of COPD exacerbation are presented in an intubated patient, initial antimicrobial management must be launched. Depending on the results of the respiratory system sample cultures, the initial antimicrobials can be changed or continued. The objective of this study is to present in-hospital suggestions regarding the use of the initial antimicrobial management of urgently intubated COPD adults with the probable bacterial cause of exacerbations, considering the source of bacterial acquisition (i.e. facility- or community-acquired bacteria). Methods. The cross-sectional study covered 51 patients urgently intubated on admission to the medical Intensive Care Unit of the Zemun Clinical Hospital Center during 2015/2016. The patients were divided into two groups: community-acquired (n = 26) and facility-acquired infection group (n = 25). The respiratory system samples were processed in the Microbiology Laboratory. Results. Acinetobacter and Pseudomonas spp. were the most frequently isolated bacteria in both groups, followed by Staphylococcus aureus and Klebsiella spp. as the third most frequent bacteria in the community- and facility-acquired group, respectively. The parallel use of tigecycline and aminoglycosides proved to cover a sensitive microbial spectrum in 52% of examinees of the community-acquired and 32% of examinees of the facility-acquired group. Conclusion. The present study suggests the initial management of intubated adults with probable bacterial infection-induced COPD exacerbation by the parallel use of tigecycline and aminoglycosides. [Project of the Serbian Ministry of Education, Science and Technological Development, Grant no. 173033]

Introduction. Since clinical and electrocardiographic features of various cardiac disorders may overlap, the differential diagnosis of left ventricular (LV) dysfunction may be difficult even for the most experienced physicians. Recent advances in cardiac imaging may help clinicians to establish an accurate diagnosis and initiate adequate treatment. The aim of this case report is to raise awareness of a very short-lasting LV dysfunction during respiratory infections and to underline the importance of multimodality imaging in this clinical setting. Case outline. A previously healthy 37-year-old male presented with atypical chest pain and ST-segment elevation in the inferolateral leads during severe mental stress and acute respiratory infection. Acute myocardial infarction, myocarditis, coronary vasospasm and stress cardiomyopathy were all considered as a differential diagnosis. A rapid onset of severe LV dysfunction and a complete recovery within 4 days was detected by echocardiography and further evaluated by multimodality imaging, including multislice computed tomography and cardiac magnetic resonance imaging. Conclusion. Severe, but very short-lasting LV dysfunction may be triggered by various causes, including upper respiratory tract infections. Since the symptoms of respiratory infections may obscure those of LV dysfunction, myocardial dysfunction in these patients may go undetected with possible serious consequences.

Ultrasound is becoming increasingly available and incorporated into emergency medicine. Focused echocardiographic evaluation in resuscitation (FEER) is a training program available to emergency doctors in order to ensure adequate application of echocardiography in the cardiac arrest setting. The FEER protocol provides an algorithm, whereby a “quick view” can be provided in 10 seconds during minimal interruptions in chest compressions. Performing ultrasound in the cardiac arrest setting is challenging for emergency doctors. The International Liaison Committee on Resuscitation recommend the ‘quick look’ echocardiography view can be obtained during the 10-second pulse check, minimizing the disruption to cardiopulmonary resuscitation.

Introduction. Data on effects of thrombus aspiration on left ventricular diastolic function in ST-elevation myocardial infarction (STEMI) population are scarce. Objective. We sought to compare echocardiographic indices of the diastolic function and outcomes in STEMI patients treated with and without manual thrombus aspiration, in an academic, high-volume percutaneous coronary intervention (PCI) center. Methods. A total of 433 consecutive patients who underwent primary PCI in 2011-2012 were enrolled in the study. Patients were not eligible for the study if they already suffered a myocardial infarction, had been previously revascularized, received thrombolytics, presented with cardiogenic shock, had significant valvular disease, atrial fibrillation or had previously implanted pacemaker. Comprehensive echocardiogram was performed within 48 hours. During follow-up patients’ status was assessed by an office visit or telephone interview. Results. Patients treated with thrombus aspiration (TA+, n=216) had similar baseline characteristics as those without thrombus aspiration (TA-, n=217). Groups had similar total ischemic time (319 ± 276 vs. 333±372 min; p=0.665), but TA+ group had higher maximum values of troponin I (39.5 ± 30.5 vs. 27.6 ± 26.9 ng/ml; p15, as a marker of severe diastolic dysfunction (TA+ 23.1% vs. TA- 15.2%; p=0.050). During average follow-up of 14Ѓ}5 months, major adverse cardiac/ cerebral events occurred at the similar rate (log rank p=0.867). Conclusion. Thrombus aspiration is associated with a greater incidence of severe diastolic dysfunction in unselected STEMI patients treated with primary PCI, but it doesn’t influence the incidence of major adverse cardiovascular events. [Projekat Ministarstva nauke Republike Srbije, br. 175099]

Introduction. Adherence to proposed lifestyle changes and prescribed medication in patients with stable coronary artery disease (SCAD) is poor. Objective. We sought to investigate the influence of adjusting guideline proposed medications on relief of angina in a large group of patients with SCAD in Serbia. Methods. The study included a total of 3,490 patients from 15 cardiology clinics with symptoms of stable angina and at least one of the following criteria: abnormal electrocardiogram (ECG), history of myocardial infarction (MI), positive stress test, significant coronary artery disease on coronary angiogram or previous revascularization. All the patients underwent comprehensive evaluation at initial visit and after two months. The relief of angina was study end-point defined as any reduction in Canadian Cardiology Society (CCS) class, number of angina attacks per week and/or number of tablets of short-acting nitrates per week. Results. Most patients were included based on abnormal ECG (48.4%). At Visit 1, the average number of prescribed classes of medications to a single patient increased from 4.16 ± 1.29 to 4.63 ± 1.57 (p < 0.001). At the follow-up, the patients had significantly lower blood pressure (141 ± 19 / 85 ± 11 vs. 130 ± 12 / 80 ± 8 mmHg; p < 0.001) and most of them reported CCS class I (63.3%). The average weekly number of angina attacks was reduced from 2.82 ± 2.50 at Visit 1 to 1.72 0 ± 1.66 at Visit 2, as well as average weekly use of short-acting nitrates to treat these attacks (2.69 ± 2.53 to 1.74 ± 1.47 tablets; p < 0.001 for all). Conclusion. Adjustment of prescribed medications to guideline recommendations in a large Serbian patient population with prevalent risk factors led to significant relief of angina.

Introduction. Echocardiography is a highly operator-dependant technique which requires adequate training and skills that are frequently not present, considering the widespread use of cardiovascular ultrasound. This could particularly be true for hand-held echo devices which made echocardiography more accessible but are frequently used by non-cardiologists and non-experts. Outline of Cases. We present a 45-year-old female and a 37-year-old male with heart murmurs due to atrial and ventricular septal defect, respectively. Congenital septal defects were undiagnosed in both patients during several outpatient examinations due to challenging image acquisition. Careful re-evaluation revealed that, depending on the scanning technique, it was possible to detect or overlook the real cause of the murmur using either hand-held or high-end echo device. Conclusion. Our report underlines the need of adequate knowledge and training of medical professionals performing pocket-size hand-held echocardiography, since potential misdiagnoses may not be related to limited imaging capabilities of pocket-sized echo devices only, but also to inability of insufficiently trained users to obtain good quality images and interpret them adequately. [Projekat Ministarstva nauke Republike Srbije, br. 175099]

Background/Aim. Long-term intensive training is associated with distinctive cardiac adaptations which are known as athlete’s heart. The aim of this study was to determine whether the use of anabolic androgenic steroids (AAS) could affect echocardiographic parameters of left ventricular (LV) morphology and function in elite strength and endurance athletes. Methods. A total of 20 elite strength athletes (10 AAS users and 10 non-users) were compared to 12 steroid-free endurance athletes. All the subjects underwent comprehensive standard echocardiography and tissue Doppler imaging. Results. After being indexed for body surface area, both left atrium (LA) and LV end-diastolic diameter (LVEDD) were significantly higher in the endurance than strength athletes, regardless of AAS use (p < 0.05, for both). A significant correlation was found between LA diameter and LVEDD in the steroid-free endurance athletes, showing that 75% of LA size variability depends on variability of LVEDD (p < 0.001). No significant differences in ejection fraction and cardiac output were observed among the groups, although mildly reduced LV ejection fraction was seen only in the AAS users. The AAS-using strength athletes had higher A-peak velocity when compared to steroidfree athletes, regardless of training type (p < 0.05 for both). Both AAS-using and AAS-free strength athletes had lower e’ peak velocity and higher E/e’ ratio than endurance athletes (p < 0.05, for all). Conclusions. There is no evidence that LV ejection fraction in elite athletes is altered by either type of training or AAS misuse. Long-term endurance training is associated with preferable effects on LV diastolic function compared to strength training, particularly when the latter is combined with AAS abuse.

Introduction. Spontaneous coronary artery dissection (SCAD) is a rare cause of the acute coronary syndrome. It occurs mostly in patients without atherosclerotic coronary artery disease, carrying fairly high early mortality rate. The treatment of choice (interventional, surgical, or medical) for this serious condition is not well-defined. Case report. A 41-year old woman was admitted to our hospital after the initial, unsuccessful thrombolytic treatment for anterior myocardial infarction administered in a local hospital without cardiac catheterization laboratory. Immediate coronary angiography showed spontaneous coronary dissection of the left main and left anterior descending coronary artery. Follow-up coronary angiography performed 5 days after, showed extension of the dissection into the circumflex artery. Because of preserved coronary blood flow (thrombolysis in myocardial infarction - TIMI II-III), and the absence of angina and heart failure symptoms, the patient was treated medicaly with dual antiplatelet therapy, a low molecular weight heparin, a beta-blocker, an angiotensinconverting enzyme (ACE) inhibitor and a statin. The patient was discharged after 12 days. On follow-up visits after 6 months and 2 years, the patient was asymptomatic, and coronary angiography showed the persistence of dissection with preserved coronary blood flow. Conclusion. Immediate coronary angiography is necessary to assess the coronary anatomy and extent of SCAD. In patients free of angina or heart failure symptoms, with preserved coronary artery blood flow, medical therapy is a viable option. Further evidence is needed to clarify optimal treatment strategy for this rare cause of acute coronary syndrome.

Introduction. Previous animal and human studies provided the evidence that testosterone may affect ventricular repolarization by shortening of the QT interval. Synthetic derivatives of testosterone, modified to enhance its anabolic properties, are occasionally abused by some competitive athletes. Objective. We assessed whether the QT interval duration could discriminate androgenic anabolic steroids (AAS)-using strength athletes (SA) from drug-free endurance athletes (EA), by comparing 25 formulas for QT interval correction. Methods. We recruited 22 elite male athletes involved in long-term strength or endurance training and 20 sedentary controls. All elite

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Introduction. Pacemaker syndrome consists of the symptoms and signs present in the single chamber (VVI) pacemaker patient with electrode placed in the right ventricular apex. It is caused by inadequate timing of atrial and ventricular contractions. Pacemaker syndrome without a pacemaker (or pseudopacemaker syndrome) refers to occurrence of symptoms in the presence of marked first-degree atrioventricular (AV) block, when P wave is too close to the preceding QRS complex producing the same haemodynamic disturbance as artificial pacemaker cardiac stimulation with retrograde VA conduction. Case Outline. We present the patient with acute inferior myocardial infarction due to late bare metal stent thrombosis, treated with primary pectutaneous coronary intervention. Hospital course was complicated by complete heart block which was treated with temporary pacing. During the stand-by mode of temporary pacing, sinus rhythm with marked first-degree AV block (PQ interval 480 ms) was observed while the patients re-experienced the symptoms that were present prior to pacemaker implantation. Temporary pacing was continued for the next 24 hours when spontaneous shorteninig of PQ interval (250-270 ms) was noticed; since the patient was asymptomatic during the stand-by mode, the pacemaker electrodes were removed and the patient discharged 11 days after admission. Conclusion. Conduction disturbances, such as the varying degrees of AV blocks, are relatively common in acute inferior myocardial infarction. The first degree AV blok is usually asymptomatic and does not require treatment, unless when it is associated with pseudopacemaker syndrome. In that case, temporary pacing provides haemodynamic stability until conduction system recovers.

Introduction Data regarding patients with acute coronary syndrome (ACS) did not exist in Serbia until 2002. By establishing the National Registry for Acute Coronary Syndrome (NRACS), the data collection based on the filled-in "coronary questionnaire" for each patient hospitalized and diagnosed with acute infarction of the myocardium (AIM) and unstable angina pectoris (UAP) was initiated in Serbia. Objective The aim of the study was to analyze clinical characteristics, complications, applied reperfusion-thrombolytic treatment and standard therapy, and mortality rate of patients treated in coronary or intensive care units during the 2002, 2003, 2004 and 2005. Method We chose a "coronary protocol" with minimal set of the patient’s data that was filled-in by the attending physician. The collection of the data was initiated in July 2002. Results During four months of 2002, 4202 patients were treated for ACS; in 2003 12739 patents, in 2004 12351 patients and 12598 patients in 2005. AIM with ST elevation (STAIM), as related to AIM without ST elevation (NSTAIM), was more often encountered in Serbian population in comparison to other European countries: in 2002, it was registered among 52.3% of patients, in 2003 among 52.7%, in 2004 among 51.8%, and in 2005 among 50.7% of patients. The patients suffering from the ACS in Serbia were of younger age, with a significant prevalence of females, as compared to the data from the European countries. Thrombolytic therapy in STAIM was applied in only 24.5% of patients in 2002, which then rose by each year, to reach 36.4% of patients in 2005. At the same time, as expected, hospital mortality rate decreased: from 14.8% in 2002 to 8.2% in 2005. STAIM patients untreated by thrombolytic therapy had a considerably higher mortality rate: in 2002 it was 20.3%, in 2003 15.3%, in 2004 14.3%, and in 2005 13.8%. Total mortality rate in patients with STAIM gradually decreased from 19% in 2002 to 11.7% in 2005. Conclusion From 2002-2005, the patients treated for ACS in Serbia were younger, with higher prevalence of females, and with a higher incidence of STAIM in relation to NSTAIM. The administration of reperfusion therapy in STAIM patients has been increasing significantly, from 24.5% in 2002 to 36.4% in 2005, and was followed by a decrease in hospital mortality rate of 14.8% in 2002 to 8.2% in 2005. Overall mortality of STAIM patients treated with or without thrombolytic therapy gradually decreased from19% in 2002 to 11.7% in 2005.

Introduction. Rapidly vanishing lung pseudotumor (phantom tumor) refers to the transient well-demarcated accumulation of pleural fluid in the interlobar pulmonary fissures. Most frequently their appearance is associated with congestive heart failure, but also other disorders like hypoalbuminemia, renal insufficiency or pleuritis. Its rapid disappearance in response to the treatment of the underlying disorder is a classical feature of this clinical entity. Case report. A 47-yearold woman, chronic smoker with symptoms of shortness of breath, orthopnea, chills, cough, weakness and the temperature of 39.2°C was admitted to our hospital. A posteroanterior chest X-ray revealed cardiomegaly with the cardiothoracic ratio of > 0.5, blunting of both costophrenic angles and an adjacent 6 x 5 cm well-defined, rounded opacity in the right interlobar fissure. Transthoracic 2-dimensional echocardiography demonstrated left ventricular hyperthrophy with a systolic ejection fraction of 25% and moderate mitral regurgitation. The patient’s symptoms resolved rapidly after diuresis, and repeated chest X-ray four days later showed that the right lung opacity and pleural effusions had vanished. Conclusion. The presented case underlines the importance of the possibility of vanishing lung tumor in patients with left ventricular failure and a sharp oval lung mass on the chest X-ray. This is the way to avoid incorrect interpretation of this finding causing additional, unnecessary, costly or invasive imaging, interventions and drugs.

Introduction: Previous animal and human studies provided the evidence that testosterone may affect ventricular repolarization by shortening of the QT interval. Synthetic derivatives of testosterone, modified to enhance its anabolic properties, are occasionally abused by some competitive athletes., Objective: We assessed whether the QT interval duration could discriminate androgenic anabolic steroids (AAS)-using strength athletes (SA) from drug-free endurance athletes (EA), by comparing 25 formulas for QT interval correction., Methods: We recruited 22 elite male athletes involved in long-term strength or endurance training and 20 sedentary controls. All elite SA reported AAS abuse, whereas EA and controls were AAS-free., Results: AAS-using SA had markedly shorter QT-interval than AAS-free EA (348 +/- 42.3 vs. 400 +/- 34.2 ms; p < 0.001). Also, drug-free EA had a significantly longer QT-interval than sedentary persons (400 +/- 34.2 vs. 358 +/- 18.9 ms; p < 0.01). In contrast, no significant difference in the QT-interval duration was observed between AAS users and control group (348 +/- 42.3 vs. 358 +/- 18.9 ms; p = 0.394). After the QT interval was adjusted for heart rate (HR) according to 25 different formulas, only the Ashman equation yielded considerable differences among the groups that were in line with those observed before correction., Conclusion: Inconsistent results obtained by different correction formulas along with inability to discriminate QT (QTc) interval duration between AAS-misusing athletes and control group do not support the use of QT (QTc) interval for anti-doping purposes.

Introduction: Pacemaker syndrome consists of the symptoms and signs present in the single chamber (VVI) pacemaker patient with electrode placed in the right ventricular apex. It is caused by inadequate timing of atrial and ventricular contractions. Pacemaker syndrome without a pacemaker (or pseudopacemaker syndrome) refers to occurrence of symptoms in the presence of marked first-degree atrioventricular (AV) block, when P wave is too close to the preceding QRS complex producing the same haemodynamic disturbance as artificial pacemaker cardiac stimulation with retrograde VA conduction., Case Outline: We present the patient with acute inferior myocardial infarction due to late bare metal stent thrombosis, treated with primary pectutaneous coronary intervention. Hospital course was complicated by complete heart block which was treated with temporary pacing. During the stand-by mode of temporary pacing, sinus rythm with marked first-degree AV block (PQ interval 480 ms) was observed while the patients re-experienced the symptoms that were present prior to pacemaker implantation. Temporary pacing was continued for the next 24 hours when spontaneous shorteninig of PQ interval (250-270 ms) was noticed; since the patient was asymptomatic during the stand-by mode, the pacemaker electrodes were removed and the patient discharged 11 days after admission., Conclusion: Conduction disturbances, such as the varying degrees of AV blocks, are relatively common in acute inferior myocardial infarction. The first degree AV blok is usually asymptomatic and does not require treatment, unless when it is associated with pseudopacemaker syndrome. In that case, temporary pacing provides haemodynamic stability until conduction system recovers.

Aims: To determine prognostic significance of global left ventricular (LV) contractile reserve, defined by dobutamine-induced changes of Tei index (Delta Tei), in patients with dilated cardiomyopathy (DCM)., Methods and Results: Thirty-eight patients with idiopathic DCM underwent high-dose (up to 40 microg/kg/min) dobutamine stress echocardiography. Prognostic value of different indices of LV contractile reserve, including Delta Tei, as well as changes of ejection fraction (Delta EF) and wall motion score index (Delta WMSi), was analysed. Patients were followed up for 5 years for cardiac mortality. Patients with preserved contractile reserve, defined by Delta Tei > -0.35, had significantly lower cardiac mortality when compared with those without it (38 vs. 77%, P = 0.02). Also, the Kaplan-Meier survival analysis revealed that patients with contractile reserve had better 5-year survival when compared with those without contractile reserve (log-rank = 6.01, P = 0.014). However, of all examined indices of contractile reserve, Cox's regression analysis identified Delta WMSi as the only independent predictor of 5-year mortality., Conclusion: Our data indicate that the presence of contractile reserve assessed by Delta Tei may identify patients with favourable long-term prognosis. Prognostic value of Delta Tei appears to be similar to Delta EF, but less powerful than Delta WMSi.

Introduction: Takotsubo cardiomyopathy is a relatively novel cardiac syndrome that is characterized by transient left ventricular asynergy involving apical and mid-ventricular segments., Epidemiology and Pathophysiology: It occurs predominantly in elderly women in the absence of obstructive coronary artery disease and is usually associated with severe emotional or physical stress. This syndrome is manifested with chest pain, electrocardiographic changes that mimic acute myocardial infarction, and minimal myocardial enzymatic release. Several different mechanisms have been proposed: coronary artery spasm, dynamic left ventricular outflow/ intracavitary obstruction, coronary microvascular dysfunction and direct catecholamine-mediated cardiomyocite injury., Therapy and Prognosis: Complete recovery usually occurs after dramatic presentation, frequently complicated with acute heart failure. Therapy is empiric and directed towards supportive measures against cardiogenic shock, acute heart failure, dysrhythmias. In-hospital mortality rate is less than 1%, but long-term prognosis is still unknown. In addition to the review of the literature on takotsubo cardiomyopathy, we present the first series of patients with this syndrome detected in Clinical Hospital Center Zemun.

Background: Gestational hypertension (GH) is associated with hemodynamic changes, and alterations of systolic and diastolic left ventricular (LV) function. However, the magnitude and pattern of changes of different parameters of LV function and contractility in this patient population have not been fully clarified., Methods: Thirty-five pregnant women with GH underwent three echocardiographic examinations, in second and third trimester of pregnancy, and 1 month after delivery. Twelve normotensive pregnant women served as gestational age-matched controls. Hemodynamic parameters and standard indexes of LV systolic and diastolic function were analyzed. Additionally, we have measured peak systolic velocity of mitral annulus (S'), end-systolic elastance (Ees), and early transmitral to early lengthening velocity of mitral annulus ratio (E/E') as parameters of longitudinal function, contractility, and filling, respectively., Results: Women with GH had initially higher body weight, blood pressure, and heart rate (P < 0.005, P < 0.0001, and P = 0.011, respectively). Temporal analysis of different echocardiographic parameters revealed increase in wall thickness from baseline to second measurement, with consequential increase in LV mass in women with GH (P = 0.014 for septum, P = 0.010 for posterior wall, and P = 0.09 for LV mass). No significant changes of LV volumes, ejection fraction (EF), transmitral flow parameters, S', Ees, and E/E' were observed throughout the follow-up in both groups (P = nonsignificant for all). Importantly, pattern of changes was similar in both groups for all examined parameters (P = nonsignificant between groups, for all)., Conclusions: It appears that changes of LV longitudinal function, filling, and contractility during pregnancy are not significant and not influenced by GH.

Vascular smooth muscle cells (VSMC) respond to arterial wall injury by intimal proliferation and play a key role in atherogenesis by proliferating and migrating excessively in response to repeated injury, such as hypertension and atherosclerosis. In contrast, fully differentiated, quiescent VSMC allow arterial vasodilatation and vasoconstriction. Exaggerated and uncontrolled VSMC proliferation appears therefore to be a common feature of both atherosclerosis and hypertension. Signal transduction pathways in eukaryotic cells integrate diverse extracellular signals, and regulate complex biological responses such as growth, differentiation and death. One group of proline-directed Ser/Thr protein kinases, the mitogen-activated protein kinases (MAPKs), plays a central role in these signalling pathways. Much attention has focused in recent years on subfamilies of MAPKs, the extracellular signal regulated kinases (ERKs). Here we overview the work on ERKs 1 to 2, emphasising when possible their biological activities in VSMC proliferation. It is clear from numerous studies including our own, that ERK1/ERK2 pathway has an important role in VSMC proliferation induced by insulin (INS) and thrombin. Despite the physiological and pathophysiological importance of INS and thrombin, possible signal transduction pathways involved in INS and thrombin regulation of VSMC's proliferation remains poorly understood. Thus, this review examines recent findings in signaling mechanisms involved in INS and thrombin- triggered VSMC's proliferation with particular emphasis on ERK1/2 signaling pathways. Future investigations should now focus on the mechanisms of MAPK activation which might therefore represent a new mechanism involved in the antiproliferative effect revealed in this review.

Background: Chronic heart failure (CHF) is a widespread disease with severe quality of life impairment and a poor prognosis. Beta-blockers are the mainstay of CHF therapy; yet they are under-prescribed and under-dosed in clinical practice. This is particularly evident in elderly patients, which may be due to a fear of side-effects or intolerance. Beta-blockers have further not been adequately tested in patients with diastolic CHF, which is particularly common in elderly patients. Finally, comparative data on the use of different beta-blockers in patients with CHF is scarce., Aim: To compare the tolerance of bisoprolol and carvedilol in elderly patients with CHF., Methods: CIBIS-ELD is an investigator-initiated, multi-centre, 1:1 randomised, double-blind, phase III trial comparing bisoprolol and carvedilol in patients >or=65 years with systolic or diastolic CHF. Recruitment started in April 2005 and is anticipated to be completed by April 2008 with at least 800 patients enrolled., Perspective: This is the first large scale head to head beta-blockers trial in an elderly population with CHF. Besides determining which of two standard beta-blockers is best tolerated in elderly patients with systolic or diastolic CHF, we expect to gain further insight into the treatment of the particular population of patients with diastolic CHF.

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 (p < 0.01) who underwent treatment. Most of the patients (80.5%) were distributed within the elderly groups of 60, 70 and 80 years of age, with the highest percent of mortality rate (45.9%) noted at age 80 years. Anterior localization of myocardial infarction was observed in 40.2% of patients, with lethal outcome in 21.4% patients, while 59.8% of patients suffered inferiorly localized MI with much lower mortality rate (12.2%, p < 0.01). In 2005, STEMI was registered in 48.7%, while in 2006 in 44.7% of patients. Prior angina pectoris was present in 19.9% of patients, more frequently among women (p < 0.05), prior MI in 14.5% of patients, more often among males (p < 0.05), while aortocoronary revascularization was found in 3.9% of patients. Hospital mortality rate due to STEMI was higher in the group of patients with a history of prior MI (19.1% vs. 15.7%; p > 0.05). Regarding risk factors, hypertension was present in 61.8% of patients, more often among women (69.1% vs.57.9%) (p < 0.01), carrying a higher mortality rate of 18.9% vs. 9.9% among males (p < 0.01). Hyperlipidemia was found in 31.9% of patients; more frequently among women 34.8% vs. 30.4% males (p < 0.05), as well as diabetes mellitus observed in 25.1% of patients; 22.4% males and 30.1% females (p < 0.01). 39.6% of patients were smokers; 46.9% males and 28.0% females (p < 0.01). Heart failure had 33.4% of patients; mortality rate was registered in 28.2% of patients, and was significantly higher than in the non heart failure group (7.9%, p < 0.01). Heart rhythm disorders were registered in 21.3% of patients, more frequently involving posterior MI 55.3% vs 44.7% of anterior MI (p > 0.05), and was significantly higher among females 23.5% vs. 20.1% in males (p < 0.05). In 2005 in Belgrade hospitals, reperfusion therapy (RT) was performed in 34.6% of patients, mostly as thrombolytic therapy (TT) (in 99.0% of patients), and as percutaneous coronary intervention (PCI) in 1.0% of patients. STEMI mortality rate was 12.8%. In 2006, in the CCU of the In the Emergency Center RT was applied in 48.0% of patients, TT in 13.8% and PCI in 34.2%, while classical therapy without RT was applied in 52.0% of patients., Conclusion: Clinical characteristics significantly influence mortality in STEMI; a significantly higher mortality is among women, patients in their 80's and 90's, anterior MI localization and prior coronary disease. RT significantly lowers mortality in STEMI compared to the use of classical therapeutic approach and therefore STEMI patients with a higher mortality determined by their prehospital charactheristics, i.e. higher risk, are those who have higher benefit of RT, which should be taken into consideration when making decision about the therapy of choice.

Background: It has been shown that transient increase in left ventricular stiffness, assessed by Doppler-derived early filling deceleration time, occurs during the first 24 to 48 hours after myocardial infarction but returns to normal within several days. It has been reported that hyperbaric oxygen treatment has a favorable effect on left ventricular systolic function in patients with acute myocardial infarction treated with thrombolysis. However, there are no data on the effects of hyperbaric oxygen on diastolic function after myocardial infarction., Methods: To assess acute and short-term effects of hyperbaric oxygen on left ventricular chamber stiffness, we studied 74 consecutive patients with first acute myocardial infarction who were randomly assigned to treatment with hyperbaric oxygen combined with streptokinase or streptokinase alone. After thrombolysis, patients in the hyperbaric oxygen group received 100% oxygen at 2 atm for 60 minutes in a hyperbaric chamber. All patients underwent 2-dimensional and Doppler echocardiography 1 (after thrombolysis), 2, 3, 7, 21, and 42 days after myocardial infarction., Results: Patient characteristics, including age, sex, risk factors, adjunctive postinfarction therapy, infarct location, and baseline left ventricular volumes and ejection fraction, were similar between groups (P >.05 for all). For both groups, deceleration time decreased nonsignificantly from day 1 to day 3 and increased on day 7 (P <.001, for both groups), increasing nonsignificantly subsequently. The E/A ratio increased in the entire study group throughout the time of study (P <.001, for both groups). The pattern of changes of deceleration time was similar in both groups (P >.05 by analysis of variance), as was in subgroups determined by early reperfusion success., Conclusions: These data in a small clinical trial do not support a benefit of hyperbaric oxygen on left ventricular diastolic filling in patients with acute myocardial infarction treated with thrombolysis.

Background: It has been shown that preinfarction angina may have beneficial effects on infarct size and mortality. However, there are no studies that have serially assessed the impact of preinfarction angina on left ventricular (LV) function in a large series of patients., Hypothesis: The study was undertaken to determine whether preinfarction angina (within 7 days before infarction) influences LV remodeling., Methods: In all, 119 consecutive patients with acute myocardial infarction were serially evaluated by 2-dimensional echocardiography (on Days 1, 2, 3, and 7; at 3 and 6 weeks; and at 3, 6, and 12 months following infarction). Left ventricular volumes were determined using Simpson's biplane formula and normalized for body surface area. Wall motion score index and sphericity index were calculated for each study. Coronary angiography was performed before discharge., Results: Preinfarction angina was detected in 39 of 119 patients. Initial echocardiographic and clinical data as well as the incidence of patent infarct-related artery and collaterals were similar for patients with and without preinfarction angina. In the subset of thrombolysed patients, patients with preinfarction angina showed decrease of LV end-diastolic and end-systolic volumes during the follow-up period (p = 0.033 and p = 0.001, respectively), and improvement of wall motion score index (p < 0.001) and ejection fraction occurred (p = 0.001), without changing of LV shape (p > 0.05); in addition, patients with preinfarction angina had smaller LV volumes and higher ejection fraction than did those without angina, from 3 weeks onward. These favorable effects were not detected in patients not treated with thrombolysis., Conclusions: These data indicate that preinfarction angina has an inhibiting effect on long-term LV remodeling in patients who underwent thrombolysis for first acute myocardial infarction. It appears that preinfarction angina has no impact on infarct size and early postinfarction LV function.