Background/Objectives: This study aims to investigate the potential etiopathogenesis of HFpEF development and identify possible different phenotypes of HFpEF in patients with chronic obstructive pulmonary disease (COPD) and systemic sclerosis-associated interstitial lung diseases (SS-ILDs). It could help clinicians improve early HFpEF personalized detection and management. Methods: This study included 150 patients with chronic lung diseases (CLDs), such as COPD and SS-ILD, who were outside of exacerbation, had no history of chronic heart failure (CHF), and had a left ventricular ejection fraction (LV EF) of ≥50%. The functional status of the lungs, heart, endothelial dysfunction, and acid–base balance was assessed. The results obtained were compared in groups of patients with CLD depending on the presence or absence of HF with preserved ejection fraction (HFpEF). The diagnosis of HFpEF was established based on the HFA-PEFF Score classification. Nonparametric statistical methods were used. Results: In patients with CLD, indicators such as age, longitudinal size of the right atrium, mid-regional pro-atrial natriuretic peptide (MR-proANP), and highly sensitive cardiac troponin T (hsTnT) were higher than in the group of patients without HFpEF. In patients with COPD and HFpEF, statistically significant changes were found in the volume of the left atrium. In patients with SS-ILD and HFpEF, statistically significant differenceswere found in SBP before and after the 6 min walk test (6MWT), the Borg scale before 6MWT, MR-proANP, and the longitudinal dimension of the right atrium. Conclusions: The results of our study allow us to identify two different mechanisms of HFpEF development: In patients with COPD, the predominant factor in the development of HFpEF was hypoxia, while in patients with SS-ILD, myocardial dysfunction with remodeling developed against the background of secondary pulmonary hypertension, highlighting the importance of phenotype-specific evaluation. These findings suggest potential approaches for personalized risk stratification and the development of targeted management strategies for patients with HFpEF.

Atrial fibrillation (AF) is the most common persistent heart rhythm disorder, the prevalence of which increases with age. The progressive prevalence of AF is becoming a serious threat to public health throughout the world, as it is associated with high mortality rates. In the review, we analyzed the literature data on the state of knowledge of the genetic nature of AF. To achieve this goal, a systematic search and subsequent analysis of publications and online resources was carried out. All publications are indexed in PubMed, Medline, e-library, Coogle Scholar. To date, at least 30 loci associated with AF have been identified. At the same time, the research results depend on such factors as ethnicity, concomitant cardiac and extracardiac diseases, inheritance mechanisms, and intergenic interactions. The complexity of etiopathogenesis, the heterogeneity of AF poses the task of researchers to further search for factors that play a leading role in the development of the disease. Significant progress in understanding the genetic basis of AF was achieved with the advent of large-scale genomic GWAS studies, which include genotyping up to a million common variants or single nucleotide polymorphisms. The currently available data on the association of candidate genes with AF in case-control studies are controversial and necessitate more detailed studies on various ethnic groups.

The article presents the results of the DAPA-HF study - evaluating the efficacy of dapagliflozin, used at a dose of 10 mg once a day, in addition to the standard treatment for patients with chronic heart failure with reduced left ventricular ejection fraction, compared to placebo. An analysis of current clinical recommendations related to this issue was carried out, the results of recent clinical studies and metaanalyses conducted were highlighted. Based on the results of the study, the need is postulated to optimize drug therapy of this category to patients with persistent symptoms of heart failure, despite standard therapy, with the addition of dapagliflozin to reduce the risk of cardiovascular death and hospitalizations for heart failure, improve the course of the disease. Keywords: chronic heart failure, dapagliflozin, low ejection fraction, effects of type 2 sodium-glucose co transporter inhibitors, diabetes mellitus.

Atrial fibrillation (AF) is the most common persistent heart rhythm disorder. The prevalence of AF increases with age. According to the GeneCards.org database, the PRRX1 gene encodes the homeodomain transcription factor that is highly expressed in the developing heart, especially in connective tissue. This suggested that the expression of the PRRX1 gene may be associated with the processes of remodeling of the left atrium, which occurs at AF. 198 persons were included in the case-control molecular genetic study. The main group included patients with AF (n=75), the control group consisted of 2 subgroups: subgroup 1 (control group 1) included conditionally healthy patients (n=73), subgroup 2 (control group 2) consisted of patients with arterial hypertension (AH) and coronary heart disease (CHD) without diagnosed AF at the time of inclusion in the study (n=50). The scientific study was approved by the Ethics Committee of Karaganda Medical University NC JSC (Protocol No. 14 dated 14.04.2020). All participants were included in the study after the informed consent signing. The study included patients with AF at the age from 26 to 84 years. The average age of patients in the main group was 66.76±9.13 (CI 64.66-68.86). 57.3% participants of the main group were male and 42.7% – female. DNA isolation was carried out in Shared Laboratory the Scientific Research Center of Karaganda Medical University NC JSC. The sampling was carried out in accordance with the standards of operational procedures (SOP) in the treatment rooms of medical organizations. 5-6 ml of whole blood was taken from the ulnar vein into vacuum tubes containing EDTA. The analysis of the rs 3903239 polymorphism of the PRRX1 gene was carried out by genotyping method based on polymerase chain reaction using CFX 96 DNA amplifier (Bio-Rad, USA), detecting in real time. In order to find the association of genes polymorphism with AF in the Kazakh population, we choose the rs 3903239 polymorphism, identified on the 1q24 chromosome of the PRRX gene. The analysis of the results was carried out using the Bio-Rad CFX Manager 2 software. The frequency of the rs 3903239 polymorphism genotypes of the PRRX1 gene in the main group and in the control groups was in the Hardy – Weinberg equilibrium. The frequency of the minor G allele occurrence in the Kazakh population corresponded to the frequency of the allele in the general population in accordance with the base 1000genome G=0.3393 (1699/5008, 1000G). The predominant clinical and anamnestic predictors in the risk of AF development in the Kazakh population were chronic heart failure (49.3% relative to 18%; OR 4.436), age ≥ 60 years (78.6% relative to 66%; OR 1,900), coronary heart disease, in particular, myocardial infarction (26.7% relative to 20%; OR 1,455). The rs 3903239 polymorphism of the PRRX1 gene in the dominant inheritance model is associated with the risk of AF development: the frequency of occurrence of genotypes with the rare G (AG+GG) allele prevailed among patients with AF compared with the group of practically healthy patients (66.7% versus 54.8%; OR 1,650).

Background/Objectives. Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia and represents a major public health problem. Genetic factors contribute to AF susceptibility, including variants associated with atrial remodeling. Methods. This case–control study investigated the rs3903239 polymorphism of the PRRX1 gene in a Kazakh population. The main group included patients with AF (n = 75), the control group consisted of 2 subgroups: subgroup 1 (control group 1) included conditionally healthy patients (n = 73), subgroup 2 (control group 2) consisted of patients with arterial hypertension (AH) and coronary heart disease (CHD) without diagnosed AF at the time of inclusion in the study (n = 50). Genotype and allele frequencies were compared between patients with AF and two control groups. The frequency of the rs3903239 polymorphism genotypes of the PRRX1 gene in the main group and in the control groups was in the Hardy–Weinberg equilibrium. Results. The frequency of the rare G allele (AG + GG genotypes) was higher in patients with AF compared with conditionally healthy controls; however, this difference did not reach statistical significance (OR 1.357; 95% CI 0.845–2.178). Conclusions. The observed differences represent a non-significant trend and do not demonstrate a statistically confirmed association between the rs3903239 polymorphism of the PRRX1 gene and AF in the Kazakh population.