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

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.

The aim of this paper is to present the preliminary results of the monitoring study of the frequency of congenital heart disease in newborns in Tuzla Canton (Bosnia and Herzegovina), and their distribution by sex of the newborn and maternal age. The study used the data from the book of protocols and case records of the Clinic for Gynecology and Obstetrics, the University Clinical Center in Tuzla. The analysis of 8,521 newborns between 1 January 2007 and 31 December 2008 has resulted in the frequency of 1.76%, i.e. 1.31% for the mature newborns and 0.45% for the premature newborns respectively. Of the total number of registered anomalies, 10% was associated with congenital anomalies of other systems. No statistically significant differences were found in the subsamples of both mature and premature newborns when it comes to the distribution of congenital heart disease by sex of newborns and maternal age. The frequency registered in the analyzed period suggests the necessity of screening and monitoring congenital heart disease in the observed population.