Predictors of arrhythmia recurrence in patients with non-valvular atrial fibrillation after sinus rhytmh restoring: the role of the rs10465885 polymrphism in connexin-40 gene
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Abstract
The aim – to determine the predictors of arrhythmia recurrence in patients with non-valvular atrial fibrillation (AF) after the sinus rhythm (SR) restoring, and to establish the role of the rs10465885 polymorphism in connexin-40 (Cx40) gene.
Material and methods. We enrolled 104 patients (pts) with non-sustained non-valvular AF (average age (53±10) years, 80 (76.9 %) men). The distribution of rs10465885 polymorphic variants in Cx40 gene (n=73) was as follows:
TT – 17 (23.3 %) pts, CT – 33 (45.2 %), СС – 23 (31.5 %). We analyzed 122 cases of SR restoring: 32 (26.2 %) – pharmacological cardioversion (29 pts); 63 (51.6 %) – electrical cardioversion (ECV) (53 pts); 27 (22.2 %) – radiofrequency catheter ablation (RFA) (22 pts). The follow-up median was 23 months. According to the phenotypic parameters, associated with rs10465885, the sample of 104 pts (122 SR restoring cases) was stratified into 4 phenotypic clusters (PC): PC1 – 43 pts (57 SR restoring cases), PC2 – 24 (26); PC3 – 18 (20); and PC4 – 19 (19). According to PC and rs10465885 status (carriage or relatively high probability of non-CC or CC variant), the sample of 104 pts (122 SR restoring cases) was stratified into 4 integral clusters (IC): IC1 (PC1 + non-СС) – 26 pts (32 SR restoring cases); IC2 (PC1 + СС) – 17 (25); IC3 (combined group [РC234] + non-СС) – 49 (50); IC4 (РC234 + СС) – 12 (15).
Results. The risk of AF recurrence after ECV was 1,429 times higher than that of RFA. In addition, the risk of AF recurrence after restoration of SR in patients with the CHA2DS2-VASc scale score 1 was 1,550 times lower than in patients with 0 and ≥ 2 score. PC1, in comparison with PC234, was associated with a higher frequency of rs10465885 СС variant (taking into account the pts with a relatively high probability of СС carriage). PC1 was presented mainly by men under 40 years of age, with no pronounced structural and functional changes of the left ventricle. Additionally, PC1 was characterized by an earlier AF onset, the higher prevalence of subclinical AF, and a lower risk of stroke by the CHA2DS2-VASc scale. IC2 (vs IC4) was most significantly associated factor with the AF recurrence at 90 and 180 days after SR restoring.
Conclusions. The variant of SR restoring and the CHA2DS2-VASc score were the predictors of AF-free survival. The carriage (or relatively high probability of carriage) of the polymorphic variant rs10465885 СС in Cx40 gene additionally increases the risk of arrhythmia recurrence at the 3- and 6-month follow-up after SR restoration in patients with non-valvular AF and the PC1 features (as compared to PC234).
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