The thesis deals with an improvement of management of patients (pts) with non-valvular atrial fibrillation (AF) based on the study the associations of single nucleotide polymorphism (SNP) rs10465885 in connexin-40 (Cx40) gene with phenotypic (clinical) data, and the determination of rs10465885 role in prediction of AF clinical course.We consecutively enrolled 186 Caucasians with AF under the age of 65 (on average (52 ± 10) years, 123 (66,1 %) males), representing the different regions of Ukraine. One hundred forty pts (75,3 %) presented with hypertension; coronary artery disease - 122 (65,6 %); myocardial fibrosis - 53 (28,5 %); metabolic cardiomyopathy - 11 (5,9 %); heart failure (HF) - 149 (80,1 %). Paroxysmal AF was diagnosed in 86 (46,2 %) pts, persistent - 72 (38,7 %), and stable - 28 (15,1 %). AF was first diagnosed (FD-AF) in 48 (25,8 %) pts. The median of AF onset age was 49 ([quartiles] 42-55) years. The discrimination of rs10465885 variants was studied by means of real-time polymerase chain reaction in 112 (60,2 %) pts. The reference ("wild-type") allele was represented by thymidine nucleotide (T), the minor - cytidylic one (C). We also enrolled a control group of practically healthy Caucasians (60 (77 %) males; middle age (51 ± 11) years), without a history of AF.We retrospectively analyzed 122 cases of sinus rhythm restoration (SRR) in 104 pts, in particular: 32 (26,2 %) cases - pharmacological cardioversion (PCV), 63 (51,6 %) - direct-current cardioversion (DC-CV), 27 (22,2 %) - radiofrequency catheter ablation (RFA). The average follow-up duration was 23 (15-29) months. At the 3-months follow-up ("90 days"), AF recurrence after SRR (AF90) was detected in 43,4 % of cases (53/122); 6-months ("180 days") (AF180) - 50,0 % (61/122); 1 year ("360 days") (AF360) - 65,5 % (76/116). Transition to stable AF occurred in 20,9 % of cases (32 out of 153 pts with available data).The distribution of rs10465885 genotypes and alleles among AF pts was as follows: TT genotype - 29 (25.9 %) pts, CT - 55 (49,1 %), CC - 28 (25,0 %); T allele - 50,5 %, C - 49,5 %. The corresponding distribution among controls was as follows: TT genotype - 22 (28,2 %) persons, CT - 32 (41,0 %), CC - 24 (30,8 %); T allele - 48,7 %, C - 51,3 % (consistent with Hardy-Weinberg equilibrium). Thus, the distribution of rs10465885 genotypes and alleles among AF pts and controls was comparable (p = 0,520 and p = 0,755, respectively).It was determined, that rs10465885 CC group, as opposed to the merged TT/CT group, was associated with a lower frequency of HF patients, the higher frequency of FD-AF cases with unknown precise duration of the first diagnosed AF episode (FD-AF [UPD]), better left ventricular (LV) mid-wall fractional shortening (MWFS), as well as the lower frequency of patients with LV hypertrophy.Considering the genotype-phenotypic associations, we indentified the phenotypic cluster (group) of AF pts, which was associated with more frequent detection of rs10465885 CC genotype carriers, and was presented, to a greater extent, by males with the earliest AF onset, without significant comorbidities and myocardial structural and functional changes. In addition, the revealed cluster was characterized by the higher prevalence of asymptomatic AF cases, the lower CHA2DS2-VASc score, as well as the additional increase of AF90 and AF180 risk in case of rs10465885 CC genotype carriage.We built two nonlinear Artificial Neural Networks models (multilayer perceptrones) for AF90 and AF360 risk prediction. In case of rs10465885 CC genotype carriage, we determined the additional increase of AF90 risk after PCV in pts with CHA2DS2-VASc score "0" and normal or mildly decreased LV MWFS, and in the case of its moderate decrease - both after PCV and DC-CV. Together with AF90 risk groups, in case of rs10465885 CC genotype carriage, we determined the additional increase of AF360 risk either after PCV (because of FD-AF of known precise duration) or DC-CV (because of FD-AF [UPD]) in patients without HF and mildly increased left atrial dimension (LAD). In case of rs10465885 CC genotype carriage, we determined the additional increase of AF360 risk after RFA in patients without HF and normal/mildly increased LAD, as well as in patients with HF I-IIA stage and moderately increased LAD.
