Model for predicting the recurrence of atrial fibrillation after monopolar or bipolar radiofrequency ablation in patients with AF and mitral valve disease

Currently, surgical radiofrequency ablation (MAZE) is one of the most effective treatments for patients with non-isolated atrial fibrillation [1, 2]. The results of long-term follow-up after surgery showed that the proportion of patients maintaining sinus rhythm was 60–85%, and the rest of the follow-up patients had a recurrence of atrial fibrillation or atrial flutter [3, 4].

Relevant studies have pointed out that the recurrence of atrial fibrillation after ablation may be related to age, left atrial diameter, type of atrial fibrillation, postoperative atrial tachycardia, and higher preoperative euroscore. Patients with a left atrial diameter > 70 mm, persistent or permanent atrial fibrillation, or Euro score > 6 points had a higher risk of postoperative recurrence of atrial fibrillation [5,6,7]. A Chinese multicentre study reported that the recurrence of atrial fibrillation after radiofrequency ablation was associated with right atrial diameter, hypertension, diabetes, and smoking [8]. A new large meta-analysis including more than 50,000 patients from 20 centres examined the association between obesity and the recurrence of atrial fibrillation after catheter ablation. Obese patients (body mass index [BMI] > 28 kg/m2) had a higher probability of atrial fibrillation relapse after catheter ablation (OR = 1.30) [9]. The treatment method mentioned in the study was catheter ablation, which was different from the surgical radiofrequency ablation in our study; however, the results could be instructive and inspirational.

In a Japanese multicentre study, 450 patients with non-isolated atrial fibrillation who underwent atrial fibrillation cryoablation maze between 2001 and 2019 were examined. After logistic regression analysis, atrial fibrillation f-wave voltage < 0.2 mV, history of atrial fibrillation > 5 years, and left atrial volume > 100 ml/m2 were associated with postoperative atrial fibrillation recurrence. Therefore, a new risk assessment model was established using these three influencing factors, with a maximum score of 10 points. The postoperative recurrence rate of atrial fibrillation was higher in patients with > 7 points [10].

A related paper compared the efficacy of two different surgical methods (modified minimally invasive MAZE using monopolar radiofrequency ablation vs. open surgery MAZE using bipolar radiofrequency ablation) in patients with non-isolated atrial fibrillation [4]. Based on these results, we will further explore the factors related to the recurrence of atrial fibrillation and the maintenance of sinus rhythm after radiofrequency ablation, aiming to quickly and effectively filter patients with higher postoperative atrial fibrillation recurrence risk and select appropriate patients for clinical atrial fibrillation. The treatment plan provides new ideas, and the factors affecting the recurrence of postoperative atrial fibrillation provide valuable references for preventing the recurrence of postoperative atrial fibrillation.

Patients

This retrospective study included a total of 275 AF patients from two inpatient wards in the First Affiliated Hospital, School of Medicine, Zhejiang University. We divided these patients into two groups——the minimally invasive MAZE group(mi-MAZE group, who underwent modified minimally invasive MAZE with monopolar radiofrequency ablation and mitral valve surgery from January 1, 2014 to November 30, 2020) and the open surgery MAZE group (os-MAZE group, who underwent traditional bipolar radiofrequency ablation and mitral valve surgery from January 1, 2014 to November 30, 2020). Patients with a history of atrial fibrillation less than 2 years and a left atrial diameter < 60 mm with mitral valve disease were selected. 29 patients were excluded because they did not meet the above criteria. 12 patients were excluded due to lack of preoperative echocardiography or laboratory examination. 7 were excluded due to lack of follow-up after surgery, and 1 were excluded due to severe postoperative complications. Eventually 224 AF patients(79 patients in mi-MAZE group and 145 patients in os-MAZE group) were included.

In fact, 107 of the 224 patients had been studied in a previously published article, and we found that there was no statistically significant difference in the postoperative atrial fibrillation recurrence rate (sinus rhythm rate) between mi-MAZE group and os-MAZE group [4]. Therefore, on this basis, we added newly 117 patients from November 2019 to November 2020, and the original conclusion still holds (see Supplementary Materials) that postoperative recurrence of atrial fibrillation in patients with non-isolated atrial fibrillation was not significantly associated with the ablation method received. Therefore, these patients were included in this study. Non-isolated atrial fibrillation patients (224 patients) who underwent radiofrequency ablation of atrial fibrillation from 2014 to 2020 in the Department of Cardiac and Great Vascular Surgery, Affiliated Hospital of Zhejiang University School of Medicine were included in this study.

Preoperative baseline data and intraoperative and postoperative monitoring indicators are summarized in the supplementary materials.

Surgical technique

The mi-MAZE group: Our hospital used an original surgery technique for the mi-MAZE group—— After general anesthesia, incision was made in the fourth intercostal space of the right chest. After heparinization, peripheral extracorporeal circulation was established through the femoral artery and vein. Blunt dissection and monopolar ablation of the right superior and inferior pulmonary veins were done during extracorporeal circulation. The left upper and lower pulmonary veins are bluntly separated after heart arrest. The Medtronic Cardioblate flushing radiofrequency system which is connected to the monopolar ablation pen was used for ablation. Left atrial ablation path includes: left and right pulmonary vein ring, the line which connects right superior pulmonary vein and left superior pulmonary vein, the line which connects right lower pulmonary vein and left lower pulmonary vein, the line which connects the incision on interatrial groove and mitral annulus, the line which connects left lower pulmonary vein and mitral annulus, and the line which connects left atrial appendage and left superior pulmonary vein. After the ablation is completed, the valve is replaced or repaired and the left atrial appendage is ligated. The epicardial temporary pacing leads are placed routinely.

The os-MAZE group: After general anesthesia, traditional sternotomy was made in the midline. After heparinization, extracorporeal circulation was established through ascending aorta and right atrium. Blunt dissection and bipolar ablation of the right superior and inferior pulmonary veins were done during extracorporeal circulation and the Marshall ligament was cut off. The left upper and lower pulmonary veins are bluntly separated after heart arrest. The Medtronic Cardioblate flushing radiofrequency system which is connected to the bipolar and the mono- polar ablation pen was used for ablation. Left atrial ablation lines were the same as in mi-MAZE group. The right atrium ablation lines include: the line which connects superior vena cava and inferior vena cava, the line which connects right atrial anterior wall incision, coronary sinus and tricuspid posterolateral annulus, the line which connects right atrial anterior wall incision and atrial septal fossa, the line which connects the tricuspid anterior leaflet and the right atrial appendage, and the line which connects the tricuspid posterior valve annulus and the incision on right atrial anterior wall. After the ablation is completed, the valve is replaced or repaired and the left atrial appendage is ligated. The epicardial temporary pacing leads were placed routinely.

The patients’ surgical approaches were determined by the surgeon.

Follow up

The primary endpoints during the postoperative follow-up were recurrence of atrial fibrillation (or atrial flutter) and death. The main follow-up items were as follows: 3 months after surgery, 6 months after surgery, 1 year after surgery, and at least once a year after the electrocardiography and echocardiography results: electrocardiography to determine whether sinus rhythm was maintained and echocardiography to determine the left atrium anterior and posterior diameter, left atrium upper and lower diameter, left atrium left and right diameter, mitral valve transvalvular pressure difference, left ventricular end-systolic diameter, left ventricular end-diastolic diameter, and left ventricular ejection fraction. Moreover, the medical outcome study (MOS) item short form health survey (SF-36) scores at 3 months, 6 months, and 1 year after surgery, were determined. The follow-up was performed until 15 January 2021.

Since postoperative recurrence of atrial fibrillation in patients with non-isolated atrial fibrillation was not significantly associated with the ablation method received(see Supplementary Materials), we included 224 patients as a whole group to find the reason of postoperative recurrence of non-isolated atrial fibrillation. A total of 224 patients were randomly divided into two groups: the training and validation sets according to the ratio 3:1. Relevant studies have indicated that the ratio of the training and validation sets can vary from 2:1 to 4:1 [1, 2, 11]. The training set data were used for the construction and internal validation of the prediction model, and the validation set data were used for the external validation of the prediction model .

Statistical analysis

Data were analysed using the SPSS 21.0 software (IBM SPSS Statistics, IBM Corp., Armonk, NY, USA) and Graph Pad Prism(GraphPad Software, San Diego, California, USA). The measurement data that conformed to the normal distribution are represented by the mean and standard deviation, those that did not conform are represented by the median and quartile, and the discrete variables are represented by the frequency and percentage. Measurement data that conformed to the normal distribution were compared using the standard t-test, and those that did not conform were compared using the two-sample Kolmogorov–Smirnov test or the Mann–Whitney test. The difference between the groups of discrete variables was determined using the chi-square test. If the total sample size was ≥40 and the expected frequency in all cells was ≥5, the Pearson chi-square test was used. If the total sample size was ≥40 and there was at least one expected frequency ≤ 5 in the cell, a continuously corrected chi-square test was used. If the total sample size was < 40 or minimum expected frequency < 1, Fisher’s exact test was used. The results were evaluated using a 95% confidence interval and a significance level of P < 0.05. Taking the recurrence of atrial fibrillation as the outcome event, the survival curve was drawn using the Kaplan–Meier method, cumulative maintenance sinus rate was evaluated, and difference between groups was tested using the log-rank test.

The continuous variable threshold (cut-off value) associated with the analysis of postoperative atrial fibrillation recurrence was determined by the minimum P-value method using X-tile software(Yale university, New Haven, Connecticut, USA) [12]. Univariate and multivariate Cox regression analyses using SPSS software, were used to screen out the statistical factors that were significantly associated with postoperative atrial fibrillation recurrence. Hazard ratios (HR), 95% confidence intervals (CI), and P values ​​were evaluated using Cox regression analysis. A prediction model of atrial fibrillation recurrence after radiofrequency ablation was constructed through the screening of relevant factors, and the Cox regression model of relevant factors was established using R language (R studio). The Harrell’s concordance index (C-index) was used to evaluate the prediction model and consistency of the actual situation. The receiver operating characteristic (ROC) analysis and its area under the curve (AUC) were used to evaluate the performance of the model [13]. Internal validation was used to verify the model and judge the degree of bias between the predictive effect of the model and the actual situation. The repeat sampling method was used with a sampling frequency of 1000 [14, 15] to draw a nomogram to obtain the weight of each related factor. The SPSS software was used for survival analysis and the Kaplan–Meier method was used to draw the survival curve with postoperative atrial fibrillation recurrence as the outcome event, compare the differences between the subgroups, and establish a simplified atrial fibrillation recurrence prediction scale. Cox univariate regression was used to analyse the differences between groups of the scale, and external validation was used to verify the scale model through the validation set. The repeated sampling method was also used with a sampling frequency of 1000. The C-index was used to evaluate the consistency of the predicted situation with the actual situation.

The SPSS software was used for statistical analysis, X-tile 3.6.1 software to determine continuous variable threshold, and R 4.0.3 and R studio software(RStudio Inc., JJ Allaire, Boston, Massachusetts, USA) for R language programming. The R language software package uses rms, Hmisc, Survival, open, openxlsx, lattice, Formula, and ggplot2 for package implementation. Statistical significance was set at P < 0.05.

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