Abstract
Background and Objectives: Recurrence of atrial fibrillation (AF) within six months after sinus rhythm restoration with direct current cardioversion (DCC) is a significant treatment challenge. Currently, the factors influencing outcome are mostly unknown. Studies have found a link between genetics and the risk of AF and efficacy of rhythm control. The aim of this study was to examine the association between eight single-nucleotide variants (SNVs) and the risk of AF development and recurrence after DCC. Materials and Methods: Regarding the occurrence of AF, 259 AF cases and 108 controls were studied. Genotypes for the eight SNVs located in the genes CAV1, MYH7, SOX5, KCNN3, ZFHX3, KCNJ5 and PITX2 were determined using high-resolution melting analysis and confirmed with Sanger sequencing. Six months after DCC, a telephone interview was conducted to determine whether AF had recurred. A polygenic risk score (PRS) was calculated as the unweighted sum of risk alleles. Multivariate regression analyses were performed to assess SNV and PRS association with AF occurrence and recurrence after DCC. Results: The risk allele of rs2200733 (PITX2) was significantly associated with the development of AF (p = 0.012, OR = 2.31, 95% CI = 1.206–4.423). AF recurred in 60% of patients and the allele generally associated with a decreased risk of AF of rs11047543 (SOX5) was associated with a greater risk of AF recurrence (p = 0.014, OR = 0.223, 95% CI = 0.067–0.738). A PRS of greater than 7 was significantly associated (p = 0.008) with a higher likelihood of developing AF after DCC (OR = 4.174, 95% CI = 1.454–11.980). Conclusions: A higher PRS is associated with increased odds of AF recurrence after treatment with DCC. PITX2 (rs2200733) is significantly associated with an increased risk of AF. The protective allele of rs11047543 (SOX5) is associated with a greater risk of AF recurrence. Further studies are needed to predict the success of rhythm control and guide patient selection towards the most efficacious treatment.
Highlights
A polygenic risk score (PRS) of >7 was significantly associated (p = 0.008) with a higher likelihood of the recurrence of atrial fibrillation (AF) after direct current cardioversion (DCC) (OR = 4.174, 95% confidence interval (CI) = 1.454–11.980), as was the duration of AF (p = 0.026, oddsThe ratioodds (OR) = 1.014, 95% CI = 1.002–1.026) (Figure 3, Table S4)
We found that as the number of cases included in the multiple regression analysis decreased, the odds ratio and confidence interval increased from OR = 4.174 for the 97 patients treated with DCC for whom follow-up data were available to OR = 38.766 for the 50 patients for whom transthoracic echocardiography data were available
We conclude that a higher PRS of single-nucleotide variants (SNVs) rs3807989 (CAV1), rs11047543 (SOX5), rs28631169 (MYH7), rs2106261 (ZFHX3), rs13376333 (KCNN3), rs75190942 (KCNJ5), rs2200733 (PITX2) and rs6838973 (PITX2) is likely associated with increased odds of AF recurrence after successful sinus rhythm restoration with DCC
Summary
Genetic studies have identified common single-nucleotide variants (SNVs) that are associated with AF [3,4,5,6,7,8,9,10]. Effort has been directed towards developing polygenic risk scores (PRS) for certain therapies, with the aim of predicting the potential efficacy based on the genotypes of patients [11,12,13]. Recurrence of atrial fibrillation (AF) within six months after sinus rhythm restoration with direct current cardioversion (DCC) is a significant treatment challenge. The aim of this study was to examine the association between eight single-nucleotide variants (SNVs) and the risk of AF development and recurrence after DCC. Multivariate regression analyses were performed to assess SNV and PRS association with AF occurrence and recurrence after DCC.
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