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Background: Heart failure remains one of the most prevalent clinical syndromes associated with significant morbidity and mortality. According to current guidelines, the prescription of a MRA is recommended to reduce the risk of HF hospitalization and death in all patients with symptomatic heart failure and no contraindications for this therapy. Objective: The aim of our study was to determine the efficacy of eplerenone vs. spironolactone on left ventricular systolic function by measuring left ventricle ejection fraction (LVEF) in patients with chronic heart failure, especially their effect on preventing hospitalization, reducing mortality, and improving clinical status among patients with chronic HF. Methods: From June 2021 to June 2022, the study was a randomized, prospective clinical trial single blind study. A total of 142 patients of chronic heart failure with reduced ejection fraction were selected by random sampling. Each patient was randomly allocated into either of the two groups and was continued receiving treatment with either spironolactone (Spiron-HF group) or eplerenone (Epler-HF group). Patients in Epler-HF group were compared with an arm of the same size and matched by age and gender patients in Spiron-HF group for management of chronic HFrEF. Each patient was evaluated clinically, biochemically, and echocardiographically at the beginning of treatment (baseline) after 6 months and at the end of 12th month. Echocardiography was performed to find out change in left ventricular systolic function. Results: After 12 months of treatment, significant improvement of left ventricular ejection fraction was observed in eplerenone treated arm (37.9 ± 3.8 ± 4.6 in Spiron-HF group versus 40.1 ± 5.7 in Epler-HF group; P < 0.05). A significant reduction in left ventricular end-systolic volume (6.3 ± 2.5ml in Spiron-HF versus 17.8± 4.4ml in Epler-HF group; P < 0.05) and left ventricular systolic diameter volume (2.7 ± 0.5ml in Spiron-HF versus 6.7 ± 0.2ml in Epler-HF group; P < 0.05), occurred after 12 months of treatment. Left ventricular global longitudinal strain (LV GLS) was significantly improved in Epler-HF group compared with Spiron-HF group (0.6 ± 0.4 versus 3.4 ± 0.9; P < 0.05). There were no significant differences observed in reduction of left ventricular end-diastolic volume (2.2 ± 0.5 ml versus 4.7 ± 1.1ml; P =0.103) and left ventricular diastolic diameter (1.2 ± 0.6 versus 1.7 ± 0.3; P=0.082) in both arms. The effects of both MRA agents spironolactone and eplerenone on the primary composite outcome, each of the individual mortality and hospital admission outcomes are shown in Figure 1 and 2. Patients of the Epler-HF group showed statistically significant lower cardiovascular mortality (HR 0.53; 95% CI 0.34–0.82; p= 0.007) and all-cause mortality (HR 0.64; 95% CI 0.44–0.93; p= 0.022) than patients of the Spiron-HF group. The statistical analysis did not show a statistically significant difference between Epler -HF and Spiron-HF study groups regarding the risk of the primary composite outcome; cardiovascular death or hospitalization due to HF (Hazard Ratio (HR) eplerenone vs. spironolactone = 0.95; 95% Confidence Interval (CI) 0.73– 1.27; p= 0.675). Conclusion: Our study has demonstrated favorable effects of eplerenone on cardiac remodeling parameters and reduction of cardiovascular mortality and all-cause mortality compared with spironolactone in the treatment of HFrEF. The ability of eplerenone to effectively block the mineralocorticoid receptor while minimizing side effects and a significant reduction in the risk of hospitalization and cardiovascular death confirms its key role in the treatment of patients with chronic HFrEF.

G. Schwartz, M. Szarek, Deepak L. Bhatt, V. Bittner, M. Bujas‐Bobanovic, R. Díaz, S. Fazio, Z. Fras et al.

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

M. Halilčević, E. Begić, Amela Džubur, A. Džubur, B. Aziri, A. Durak-Nalbantić, A. Begić, Ammar Brkić et al.

Aim To examine a relation of thyroid function, neutrophil-lymphocyte ratio (NLR) with left ventricular function measured through the left ventricular ejection fraction (LVEF) in patients with acute myocardial infarction treated with percutaneous coronary intervention (PCI). Methods This prospective research involved 160 consecutive patients with acute myocardial infarction. Patients were divided into those with normal thyroid hormone status (n=80) and those with hypothyroidism (newly diagnosed) (n=80). Inflammatory parameters and parameters of hormonal status were taken for analysis: thyroid-stimulating hormone (TSH), thyroxine (T4), triiodothyronine (T3), free thyroxine (FT4), and free triiodothyronine (FT3). All patients underwent transthoracic echocardiographic examination (TTE) five days upon admission, and left ventricular ejection fraction (LVEF) was analysed. Results Significant difference between the two groups was verified in values of T3, T4, erythrocytes, haemoglobin, haematocrit, neutrophil, lymphocytes, NLR, C-reactive protein (CRP) and sedimentation rate. Patients with euthyroidism had a higher frequency of coronary single-vessel disease (p=0.035) and a significantly lower frequency of triple vessel disease (p=0.046), as well as a higher median value of LVEF (p=0.003). There was a significant correlation between LVEF with haemoglobin values (p=0.002), NLR (p=0.001), and CRP (p=001). Conclusion The altered status of the thyroid gland in acute myocardial infarction is associated with the severity of the coronary blood vessel lesion, LVEF and correlates with inflammatory response.

Cardiomyopathies are diseases of the heart muscle, and present a heterogeneous group of myocardial diseases with mechanical or electrical dysfunction, characterized by ventricular hypertrophy or dilatation. They can be strictly related to the heart muscle (primary), or as part of a systemic disease (secondary), and represent a factor that leads to a reduced quality of life, the occurrence of heart failure and mortality. The primary ones are those that are genetic conditioning, the mixed ones include dilated and restrictive cardiomyopathy, and the acquired ones are caused by myocarditis, stress-induced, peripartum, tachycardia-induced and those caused by endocrine pathology (primarily in newborns of mothers with a diagnosis of diabetes mellitus). Etiologically, they can arise as a result of a genetic mutation, an inflammatory process, and they are also divided into metabolic, toxic and those caused by some other cause. The aim of the article was to present the characteristics of cardiomyopathies themselves in relation to the etiological factor, with review of the diagnostic and therapeutic modality.

Aim The aim of this study was to link the values of D-dimer and C-reactive protein (CRP), with the occurrence of pericardial effusion in patients who had coronavirus disease 2019 (COVID-19) and have preserved systolic function of the left ventricle (LV). Methods This was a prospective study and included 146 patients who underwent echocardiographic examination 30 days after the acute phase of COVID-19. Patients who were placed on mechanical ventilation, patients who had pulmonary thromboembolism or acute coronary syndrome during the acute period of the disease, patients who had an ejection fraction of the LV <50%, patients who were diagnosed with pericarditis during acute illness or clinical signs of heart failure (or had elevated N-terminal-pro hormone B-type natriuretic peptide value), with verified renal or hepatic dysfunction were excluded from the study, including patients with diabetes mellitus Type 1, patients with cancer, connective tissue disease, or pregnant women. The existence of cardiovascular risk factors (hypertension, diabetes mellitus Type 2, and hyperlipidemia), the presence of previous ischemic heart disease, maximum values of D-dimer, and CRP (during the first 15 days of the disease) was taken into the analysis. Results Effusion was verified around the right atrium (RA) in 104 patients (3.85 ± 1.75 mm), in 135 patients next to the free wall of the right ventricle (RV) (5.24 ± 2.29 mm), in front of the apex of the LV in 27 patients (2.44 ± 0.97 mm), next to the lateral wall of LV in 35 patients (4.43 ± 3.21 mm), and behind the posterior wall of LV in 30 patients (2.83 ± 1.62 mm). Mean CRP values during the acute phase of the disease were 43.0 mg/L (8.6–76.2 mg/L), whereas D-dimer mean value was 880.00 μg/L (467.00 –2000.00 μg/L). CRP values correlated with effusion next to the free wall of RV (rho = 0.202; P = 0.018). The D dimer correlated with effusion around RA (rho = 0.308; P = 0.0001). Conclusion The clinical picture of the post-COVID patients could be explained by the appearance of pericardial effusion. D-dimer value correlates with the occurrence of effusion around RA, whereas CRP value correlates with effusion next to the free wall of RV.

E. Begić, Ada Djozic, Emina Karavelic, Nadira Zatric, Adela Sinancevic, A. Džubur, A. Durak-Nalbantić, A. Begić et al.

Background: Familial hypercholesterolemia (FH) is an inherited disorder characterized by significantly elevated levels of low-density lipoprotein (LDL) cholesterol and is usually diagnosed after the occurrence of major adverse cardiovascular event. Aim: The aim of this study was to evaluate FH existence, increase awareness of this disorder, and highlight the importance of early treatment which leads to a reduction of premature cardiovascular events and death. Methods: The research had a cross-sectional, descriptive, and analytical character, and included 6881 (n = 6881) patients who were hospitalized in the Clinic for Heart, Blood Vessel and Rheumatic Diseases, Clinical Center University of Sarajevo, Sarajevo, Bosnia and Herzegovina, in the period from January 2019 to January 2021. LDL values were analyzed, and all patients with LDL ≥4 mmol/L were included in the study. The Dutch Lipid Score was calculated for all patients, and the findings of invasive coronary angiography were taken into account in those patients for whom it was performed. Results: From 6881 patients, 74 patients had LDL ≥4 mmol/L. Possible FH (score: 3–5) was found in 25 patients, probable FH (score: 6–8) in 2 patients, while the diagnosis of definite FH was not made in any patient. A ST-elevation myocardial infarction was an indication for hospitalization in 44.60% (n = 33), hypertension in 14.87% (n = 11), and angina pectoris in 14.87% (n = 11) of patients. Patients under the age of 65 had higher Dutch Lipid Score compared to the patients above the age of 65, regardless of male or female. Correlational analysis indicated a significant positive relationship between Dutch Lipid Score and level of cholesterol (r =0.385; P < 0.01) and LDL (r = 0.401; P < 0.001). Statistically significant predictors in the explanation of FH were age (β = −0.45; P < 0.001) and LDL (β = 0.52; P < 0.001). Conclusion: LDL values and age are the main determinants of the FH existence, and the effect on LDL values should be imperative in clinical practice.

M. Banach, Peter E. Penson, M. Vrablík, M. Bunc, K. Dyrbuś, J. Fedacko, D. Gaita, M. Gierlotka et al.

Atherosclerotic cardiovascular disease (ASCVD) and consequent acute coronary syndromes (ACS) are substantial contributors to morbidity and mortality across Europe. Much of these diseases burden is modifiable, in particular by lipid-lowering therapy (LLT). Current guidelines are based on the sound premise that with respect to low density lipoprotein cholesterol (LDL-C), "lower is better for longer", and the recent data have strongly emphasized the need of also "the earlier the better". In addition to statins, which have been available for several decades, the availability of ezetimibe and inhibitors of proprotein convertase subtilisin/kexin type 9 (PCSK9) are additional very effective approach to LLT, especially for those at very high and extremely high cardiovascular risk. LLT is initiated as a response to an individual's calculated risk of future ASCVD and is intensified over time in order to meet treatment goals. However, in real-life clinical practice goals are not met in a substantial proportion of patients. This Position Paper complements existing guidelines on the management of lipids in patients following ACS. Bearing in mind the very high risk of further events in ACS, we propose practical solutions focusing on immediate combination therapy in strict clinical scenarios, to improve access and adherence to LLT in these patients. We also define an 'Extremely High Risk' group of individuals following ACS, completing the attempt made in the recent European guidelines, and suggest mechanisms to urgently address lipid-medicated cardiovascular risk in these patients.

Patients and Methods: Patients were hospitalized under a diagnosis of pulmonary embolism, which was confirmed on the basis of the following criteria: clinical picture, changes in the electrocardiogram (ECG), serum D-dimer values and computed tomography (CT) angiography with contrast. The PAOI score was determined according to CT findings. On admission, systolic, diastolic and pulse pressure were measured.

F. Zvizdić, E. Begić, A. Mujaković, E. Hodžić, B. Prnjavorac, Omer Bedak, F. Čustović, Haris Bradaric et al.

Introduction: The most appropriate choice of pharmacological treatment of heart rhythm disorders occurring in patients with chronic obstructive pulmonary disease (COPD) and cardiovascular comorbidity is often a topic of debate between pulmonologists and cardiologists in clinical practice, although numerous studies and clinical trials have demonstrated evidence to support the use of selective beta-blockers (BBs) in these patients. Aim: To examine the difference in the number of exacerbations in patients treated with a combination of verapamil and digoxin or BB alone in patients with different COPD stages. Patients and methods: The study included 68 patients (n = 68) diagnosed with COPD who were followed-up during a 12-month period, and the number of exacerbations were analyzed. The patients were divided into two groups according to the stage of COPD: GOLD II (moderate), and GOLD III (severe), and in each group a subdivision was established in relation to the use of either a combination of verapamil and digoxin or the use of BBs alone in pharmacological treatment. The inclusion criteria for patients were defined as following: a) established diagnosis of COPD according to present or deteriorated relevant clinical symptoms and signs, b) the ejection fraction (EF) of a left ventricle (LV) >35%, and c) spirometric cut-points classified as GOLD II (FEV1 / FVC <0.7, FEV1 predicted 50-80%), or GOLD III (FEV1/FVC <0.7, FEV1 predicted 30-50%) stage of the COPD. The exclusion criteria were EF of LV <35% and a lethal outcome during a follow-up period (2 patients were encountered). Exacerbation was defined as functional deterioration of the COPD symptoms verified by spirometric functional testing, frequency of hospitalizations according to GOLD stage assignment or verified clinical symptoms deterioration. Results: Regardless the pharmacological treatment, there is a statistically significant increase in the number of COPD exacerbations, in a 12-month period follow-up, in the GOLD III group (severe) compared to the GOLD II group (moderate). In the group of patients taking verapamil and digoxin, a two-tailed t-test was used to analyze the results between the GOLD II and GOLD III stage groups, p = 0.01, and 2. In the group of patients taking BBs, a two-tailed t-test was also used to analyze the results between the GOLD II and GOLD III stage groups, p = 0.003). Within the COPD GOLD II stage group, there appears to be no statistically significant difference in the number of exacerbations between the patients taking verapamil and digoxin (n = 24) and the patients taking BBs alone (n = 15), although, in patients taking BBs alone, there appears to be a trend towards a decrease in the exacerbations compared to the number of exacerbations in patients taking verapamil and digoxin (p = 0.007). Within the COPD GOLD III stage group, there is no difference in the number of exacerbations between the patients taking verapamil and digoxin (n = 20), and the patients taking BBs alone (n = 9), as analyzed by a two-tailed t-test, p = 0.577. Conclusion: Use of selective BBs in the treatment of cardiovascular comorbidity in patients with COPD represents a far better choice of pharmacological approach in the treatment of patients diagnosed with COPD GOLD II (moderate) stage.

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