Surgical ablation should be recommended in patients with symptomatic AF during valve surgery. LAA excision is suggested to reduce the incidence of AF induced thrombotic events [1]. Surgical techniques improvements were achieved to decrease the postoperative AF recurrence, however, the outcome of surgical ablation is still not satisfactory in AF patients with VHD, especially those with rheumatic valvular diseases [15]. Limited number of studies have reported that AF duration, left atrial size and the severity of mitral regurgitation were independent risk factors for AF recurrence in valvular AF patients [16, 17].
CircRNA is a kind of non-coding RNA and is derived from the process of alternative splicing of pre-mRNAs [18, 19]. The 5’ends and 3’ends of the spliced RNA act as the upstream splice acceptor and the downstream splice donor and are finally covalently linked to each other which is known as back-splicing. Researchers have demonstrated that circRNAs can act as a microRNA sponge to regulate miRNA function [20], bind with proteins to regulate the interaction between proteins [21] and form peptide to participate different biological process [22]. Recent years, circRNAs as clinical biomarkers have been proved in the central nervous disease [11] and cancers [12], however, the function of circRNAs in AF remain poorly understood. In our former study, we have described the expression profile of circRNAs in AF patients with VHD and validated ten differentially expressed circRNAs in patients LAA tissue [13]. To our knowledge, this was the first study to evaluated the relationship between LAA circRNAs and AF recurrence after surgical ablation.
According to our previous study [13], the five most differentially expressed circRNAs were selected in this study. We found the recurrence rate of valvular persistent AF patients was 40.4% in our center. The recurrence rate was higher than other studies because of the larger preoperative left atrial diameter of patients enrolled in this study (the average left atrial diameter was 5.2cm) and the large amount of rheumatic valvular disease patients (52.9%). We found that increased age (P = 0.002) and longer AF duration (P < 0.001) were common in AF recurrence group. The expression of the circRNAs showed that there were four circRNAs (circ 81906-RYR2, circ 44782-LAMA2, circ 418-KCNN2 and circ 35880-ANO5) increased significantly in AF recurrence patients. Furthermore, multivariate analysis showed that increased expression of circ 81906-RYR2 was an independent risk factor for AF recurrence besides advanced age and longer AF duration which were reported in previous study [16, 23]. Nomogram was used to visualize the predictive model and the total score of each patient was calculated by the formula of the predictive model. The results of ROC curve showed that the expression of circ-81906 RYR2 alone was not accuratly enough to predict AF recurrence. It was more effective to make the prediction of AF recurrence by the predictive model. The Kaplan-Meier plot also proved that patients with total score over 70 points was high risk to experience AF recurrence during follow-up, in the other hand, patients under 70 points could be considered as low risk of AF recurrence after surgery.
Themistoclakis el al. reported that recurrence of atrial tachycardias after 2 months were associated with AF recurrence after the blanking period [8]. In this study, 64 patients were found AF recurrence in 3 months after surgery, and 43 patients (67.2%) among them remain AF till one year after surgery. We also found that 21 patients in AFR1 group restored sinus rhythm and 12 patients in SRM1 group relapsed into AF one-year after surgery. After calculated the predicted points of the AFR1 patients, there were 28 patients under 70 points, and in those patients, who restored sinus rhythm in one year, there were 16 patients under 70 points. In a word, for those low risk patients (total score less than 70 points) who experienced AF 3 months after surgery, early interventions, such as cardioversion and antiarrhythmic drugs therapy, were effective to help restore sinus rhythm in one year.
Several limitations of this study should be mentioned. First, the patient amount and the follow-up length of this study is limited, more AF patients with VHD and longer length of follow-up are needed to make the validation of the predictive model. Second, LAA tissue is necessary for the detection of circ 81906-RYR2, therefore, such kind of detection is restricted to surgical ablation. For those patients received catheter ablation, extra LAA section is needed to get the LAA tissue. Third, AF recurrence is always asymptomatic and undetectable, long term heart rhythm monitor is recommended.