Abstract The ODYSSEY OUTCOMES trial, comprising over 47 000 patient-years of placebo-controlled observation, demonstrated important reductions in the risk of recurrent ischaemic cardiovascular events with the monoclonal antibody to proprotein convertase subtilisin/kexin type 9 alirocumab, as well as lower all-cause death. These benefits were observed in the context of substantial and persistent lowering of low-density lipoprotein cholesterol with alirocumab compared with that achieved with placebo. The safety profile of alirocumab was indistinguishable from matching placebo except for a ∼1.7% absolute increase in local injection site reactions. Further, the safety of alirocumab compared with placebo was evident in vulnerable groups identified before randomization, such as the elderly and those with diabetes mellitus, previous ischaemic stroke, or chronic kidney disease. The frequency of adverse events and laboratory-based abnormalities was generally similar to that in placebo-treated patients. Thus, alirocumab appears to be a safe and effective lipid-modifying treatment over a duration of at least 5 years.

Abstract Aims Long-term, placebo-controlled cholesterol-lowering trials have demonstrated legacy effects (clinical benefits that persist or emerge after trial end). It is unknown whether legacy effects follow a short period of very low low-density lipoprotein cholesterol (LDL-C) levels achieved with statin plus proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor. Methods and results In 18 924 patients with recent acute coronary syndrome, the ODYSSEY OUTCOMES trial compared the PCSK9 inhibitor alirocumab with placebo, each added to high-intensity or maximum-tolerated statin therapy. Patients with two consecutive LDL-C levels <0.39 mmol/L (15 mg/dL) on alirocumab had blinded placebo substitution for the remainder of the trial with continued statin treatment. In post hoc analyses, major adverse cardiovascular events (MACE) in these patients were compared to MACE in propensity score–matched patients from the placebo group with similar baseline characteristics and study medication adherence. In the alirocumab group, 730 patients had blinded placebo substitution at a median of 8.3 months from randomization, after a median of 6.0 months with LDL-C <0.39 mmol/L. They were matched to 1460 placebo patients. Both groups had lower baseline LDL-C and lipoprotein(a) and better study medication adherence than those of the overall cohort. Over a median follow-up of 2.8 years, MACE occurred in 47 (6.4%) alirocumab patients with limited-duration, very low achieved LDL-C vs. 122 (8.4%) matched placebo patients (treatment hazard ratio 0.72; 95% confidence interval 0.51, 0.997; P = 0.047). Conclusion A short period of LDL-C levels <0.39 mmol/L achieved with statin and alirocumab, followed by statin monotherapy, was associated with a lower risk of MACE than statin monotherapy throughout the observation period. Clinical benefit persisted for several years. Trial registration ClinicalTrials.gov NCT01663402

Background: The prevalence of chronic heart failure (CHF) is up to 1-2% of the adult population in developed countries, rising to >10% after the age of 70. Heart failure with reduced ejection fraction (HFrEF) remains a prevalent clinical syndrome associated with significant morbidity and mortality. Objective: The aim of this study was to evaluate the clinical efficacy of sacubitril/valsartan in a group of ambulatory patients with heart failure with reduced ejection fraction (HFrEF) and its effect on the hemodynamic, metabolic, renal, and cardiac remodeling parameters. Methods: From January 2018 to May 2021, 106 patients with chronic heart failure with reduced ejection fraction (HFrEF) were prospectively enrolled. Patients treated with sacubitril/valsartan (ARNI) were compared with an arm of the same size (n = 53) and matched by age and gender who were taking a standard optimal medical therapy for HFrEF. Results: The 106 patients completing the study were characterized by age: 69.5 ± 8.0, 64% are male gender. The mean duration of follow-up in the 2 treatment arms was 12 months. In the ARNI arm, we evaluate the hemodynamic, metabolic, renal, and cardiac remodeling parameters upon the initial evaluation and at the end of the follow-up after 12 months treatment with sacubitril/valsartan. The LVEF values increased significantly (p < 0.001) in the ARNI arm compared to the OMT arm, 42.1 % vs. 30.1%. The LVMI decreased from a baseline value of 153.1 g/m2 to 147.8 g/m2 with significant improvement only in the arm treated with ARNI. The eGFR values increased significantly (p < 0.001) in the ARNI arm compared to the OMT arm 70.1 vs. 64.9 mL/min/1.73 m2. Initiation and titration of sacubitril-valsartan was associated with a reduction in NT-pro-BNP concentration, the values of NT-pro-BNP improved significantly only in the arm treated with ARNI 3107.1 vs. 5678.2. Mortality and re-hospitalization due to HF were lower in the arm treated with ARNI compared to the control (20.3 vs. 32.4 % and 25.3 vs. 46.6 %, respectively; p < 0.05). Conclusion: Sacubitril/valsartan is an important advancement in the treatment of HFrEF. Sacubitril/valsartan induce “hemodynamic recovery”. This study provides real-world data demonstrating incremental improvements in functional and echocardiographic outcomes in optimally treated patients with HFrEF switched to sacubitril/valsartan in ambulatory setting.

Objective: The aim of this study was to evaluate corelation of serum level of NGAL to severity of hypertension and diastolic disfunction in patients with ST- segment elevation myocardial infarction treated with fibrinolytic therapy. Design and method: We included 54 consecutive ST-segment elevation myocardial infarction patients treated with fibrinolytic therapy (alteplase). The median follow-up time was 6 days (interquartile range, 5 to 7 days). Blood samples were drawn immediately after admission prior to fibrinolytic administration. The endpoints were mean systolic and diastolic pressure (continuously monitored) and mean E/A ratio as a measure of diastolic function. Results: Patients with high NGAL (above 134,05 &mgr;g/l; 75th percentile) had significantly higher mean systolic and mean diastolic blood pressure compared to patients with low NGAL (under 134,05 &mgr;g/l; 75th percentile), p = 0,001 and p = 0,003; respectively. Patients with high NGAL (above 134,05 &mgr;g/l; 75th percentile) had significantly lower E/A ratio compared to patients with low NGAL (under 134,05 &mgr;g/l; 75th percentile), p = 0,004. Conclusions: High NGAL significantly corelates with severity of hypertension and diastolic dysfunction in patients with acute STEMI.

Introduction: Atrial fibrillation (AF) is the most common form of cardiac arrhythmia in clinical practice and its prevalence increases with age. Patients who develop AF also have cardiovascular risk factors, structural heart disease, and comorbidities, all of which can increase mortality. AF causes a significant economic burden with the increasing trend in AF prevalence and hospitalizations. Research Objectives: The objective of our study is to evaluate the impact of the most common known risk factors on the incidence of atrial fibrillation as an important precursor of cardiac and cerebrovascular morbidity and mortality among our patients in Bosnia and Herzegovina during median follow up period (September 2006 - September 2016). The other objective is to estimate the CHA2DS2-VASc score among our patients based on clinical parameters. Patients and methods: This study includes 2352 ambulant and hospitalized patients with atrial fibrillation. All patients underwent clinical evaluation which includes thorough assessment for potential risk factors and concomitant conditions in order to determine which of them represent the most common among examinees with atrial fibrillation. Results: The results show that male gender has slightly more incidence of AF. Obesity and overweight with BMI ≥ 27, cigarettes smoking and sedentary life style are almost present in patients with AF. Arterial hypertension, coronary artery disease, diabetes mellitus, chronic obstructive pulmonary disease, chronic renal dysfunction, structural and valvular heart disease and peripheral vascular disease are the most common comorbidities among our patients. The mean CHA2DS2-VASc score was 3.2±1.4 and the mean HAS-BLED score was 2.1±1.2. Conclusion: Atrial fibrillation is the most common sustained cardiac rhythm disorder. The study shows that obesity, alcohol consumption, smoking cigarettes and dyslipidemia can be considered as triggers and predisposing factors for appearance of AF. Arterial hypertension, coronary artery disease, chronic obstructive pulmonary disease, diabetes mellitus, Peripheral vascular disease and chronic kidney disease are playing important role in developing of AF.

Introduction: Atrial fibrillation represents the most common cardiac arrhythmia in clinical practice. By year 2030, 14–17 million AF patients are anticipated in the European Union. Atrial fibrillation remains one of the major causes of stroke, heart failure, sudden death all over the world. Research Objectives: The objective of our study is to determine the cardiac and cerebrovascular events (myocardial infarction, heart failure, stroke, sudden cardiac death) and their cumulative incidence during 11 years follow up period. Patients and methods: This study includes 2352 ambulant and hospitalized patients with atrial fibrillation (AF) who were enrolled during the follow up period. All patients underwent clinical evaluation in order to determine cardiac and cerebrovascular events (myocardial infarction, heart failure, stroke, sudden cardiac death) and their cumulative incidence. Results: The results of cumulative incidence for sudden cardiac death was 1.71%, for stroke 2.56%, for myocardial infarction 1.20% and for heart failure was 5.73%. In our study the age-adjusted incidence and prevalence of AF are slightly lower in women. The study shows that the risk of death is higher in females than in males with AF. Conclusion: Despite good progress in the management of patients with atrial fibrillation (AF), this arrhythmia remains one of the major causes of stroke, heart failure, sudden death. Effective treatment of patients with atrial fibrillation includes not only rate control, rhythm control, and prevention of stroke, but also management of cardiovascular risk factors and concomitant diseases.

Introduction: The term masked hypertension (MH) should be used for untreated individuals who have normal office blood pressure but elevated ambulatory blood pressure. For treated patients, this condition should be termed masked uncontrolled hypertension (MUCH). Research Objectives: Masked uncontrolled hypertension (MUCH) has gone unrecognized because few studies have used 24-h ABPM to determine the prevalence of suboptimal BP control in seemingly well-treated patients, and there are few such studies in large cohorts of treated patients attending usual clinical practice. This is important because masked hypertension is associated with a high risk of cardiovascular events. This study was conducted to obtain more information about the association between hypertension and other CV risk factors, about office and ambulatory blood pressure (BP) control as well as on cardiovascular (CV) risk profile in treated hypertensive patients, also to define the prevalence and characteristics of masked uncontrolled hypertension (MUCH) among treated hypertensive patients in routine clinical practice. Patients and methods: In this study 2514 male and female patients were included during a period of 5 years follow up. All patients have ambulatory blood pressure monitoring (ABPM) for at least 24h. We identified patients with treated and controlled BP according to current international guidelines (clinic BP, 140/90mmHg). Cardiovascular risk assessment was based on personal history, clinic BP values, as well as target organ damage evaluation. Masked uncontrolled hypertension (MUCH) was diagnosed in these patients if despite controlled clinic BP, the mean 24-h ABPM average remained elevated (24-h systolic BP ≥130mmHg and/or 24-h diastolic BP ≥80mmHg). Results: Patients had a mean age of 60.2+10 years, and the majority of them (94.6%) were followed by specialist physicians. Average clinic BP was 150.4+16/89.9+12 mmHg. About 70% of patients displayed a very high-risk profile. Ambulatory blood pressure monitoring (ABPM) was performed in all recruited patients for at least 24h. Despite the combined medical treatment (78% of the patients), clinic control (<140/90 mmHg) was achieved in only 26.2% of patients, the corresponding control rate for ambulatory BP (<130/80 mmHg) being 32.7%. From 2514 patients with treated BP, we identified 803 with treated and controlled office BP control (<140/90 mmHg), of whom 258 patients (32.1%) had MUCH according to 24-h ABPM criteria (mean age 57.2 years, 54.7% men). The prevalence of MUCH was slightly higher in males, patients with borderline clinic and office BP (130–139/80–89 mmHg), and patients at high cardiovascular risk (smokers, diabetes, obesity). Masked uncontrolled hypertension (MUCH) was most often due to poor control of nocturnal BP, with the proportion of patients in whom MUCH was solely attributable to an elevated nocturnal BP almost double that solely attributable to daytime BP elevation (22.3 vs. 10.1%, P 0.001). Conclusion: The prevalence of masked suboptimal BP control in patients with treated and well-controlled clinic BP is high. The characteristics of patients with MUCH (male, longer duration of hypertension, obesity, smoking history, and diabetes) indicate that this is a higher-risk group with most to gain from improved BP.

Introduction: The commonest mitral regurgitation etiologies are degenerative (60%), rheumatic post-inflammatory, 12%) and functional (25%). Due to the large number of patients with acute MI, the incidence of ischaemic MR is also high. Ischaemic mitral regurgitation is a complex multifactorial disease that involves left ventricular geometry, the mitral annulus, and the valvular/subvalvular apparatus. Ischaemic mitral regurgitation is an important consequence of LV remodeling after myocardial infarction. Research Objectives: The objective of this study is to determine the role of echocardiography in detecting and assessment of mitral regurgitation mechanism, severity, impact on treatment strategy and long term outcome in patients with myocardial infarction during the follow up period of 5 years. Also one of objectives to determine if the absence or presence of ischaemic MR is associated with increased morbidity and mortality in patients with myocardial infarction. Patients and methods: The study covered 138 adult patients. All patients were subjected to echocardiography evaluation after acute myocardial infarction during the period of follow up for 5 years. The patients were examined on an ultrasound machine Philips iE 33 xMatrix, Philips HD 11 XE, and GE Vivid 7 equipped with all cardiologic probes for adults and multi-plan TEE probes. We evaluated mechanisms and severity of mitral regurgitation which includes the regurgitant volume (RV), effective regurgitant orifice area (EROA), the regurgitant fraction (RF), Jet/LA area, also we measured the of vena contracta width (VC width cm) for assessment of IMR severity, papillary muscles anatomy and displacement, LV systolic function ± dilation, LV regional wall motion abnormality WMA, LV WMI, Left ventricle LV remodeling, impact on treatment strategy and long term mortality. Results: We analyzed and follow up 138 patients with previous (>16 days) Q-wave myocardial infarction by ECG who underwent TTE and TEE echocardiography for detection and assessment of ischaemic mitral regurgitation (IMR) with baseline age (62 ± 9), ejection fraction (EF 41±12%), the regurgitant volume (RV) were 42±21 mL/beat, and effective regurgitant orifice area (EROA) 20±16 mm2, the regurgitant fraction (RF) were 48±10%, Jet/LA area 47±12%. Also we measured the of vena contracta width (VC width cm) 0,4±0,6 for assessment of IMR severity. During 5 years follow up, total mortality for patients with moderate/severe IMR–grade II-IV (54.2±1.8%) were higher than for those with mild IMR–grade I (30.4±2.9%) (P<0.05), the total mortality for patients with EROA ≥20 mm2(54±1.9%) were higher than for those with EROA <20 mm2(27.2±2.7%) (P<0.05), and the total mortality for patients with RVol ≥30 mL (56.8±1.7%) were higher than for those with RVol<30ml (29.4±2.9%) (P<0.05). After assessment of IMR and during follow up period 64 patients (46%) underwent CABG alone or combined CABG with mitral valve repair or replacement. In this study, the procedure of concomitant down-sized ring annuloplasty at the time if CABG surgery has a failure rate around 24% in terms of high late recurrence rate of IMR during the follow period especially after 18–42 months. Conclusion: The presence of ischaemic MR is associated with increased morbidity and mortality. Chronic IMR, an independent predictor of mortality with a reported survival of 40–60% at 5 years. Ischaemic mitral regurgitation has important prognosis implications in patients with coronary heart disease. Recognizing the mechanism of valve incompetence is an essential point for the surgical planning and for a good result of the mitral repair. It is important that echocardiographers understand the complex nature of the condition. Despite remarkable progress in reparative surgery, further investigation is still necessary to find the best approach to treat ischaemic mitral regurgitation.

No abstract available.

AIM To assess serum levels and correlation between uric acid (UA) and C-reactive protein (CRP) in acute coronary syndrome (ACS) and apparently healthy individuals. METHODS The cross-sectional study included 116 examinees of age 44 to 83 years, distributed in two groups: 80 ACS patients including 40 with acute myocardial infarction (AMI), and 40 with unstable angina pectoris (UAP), and 36 apparently healthy (control group) individuals. Patients with ACS were hospitalized at the Cardiology Clinic, Clinical Centre Sarajevo in the period October- December 2012. Laboratory analyses were conducted by standard methods. The accepted statistical significance level was p<0.05. RESULTS Serum levels of CRP and UA were higher in patients with ACS as compared to control group (p<0.01). The median serum UA was insignificantly lower, and CRP was significantly higher in patients with AMI compared to UAP (p=0.118 and p=0.001, respectively). CRP and UA correlated positively in both ACS and control groups (rho=0.246; p=0.028 and rho=0.374; p=0.027). A positive correlation between serum CRP and UA was noted in patients with AMI, but negative in patients with UAP (p>0.05). CONCLUSION The correlation between CRP and UA in the patients with ACS indicates the association of oxidative stress and inflammation intensity in damaged cardiomyocytes. Correlation between UA and CRP in apparently healthy individuals indicates a possible role of UA as a marker of low-grade inflammation and its potential in risk assessment in cardiovascular diseases.