Study population
From March 2017 to August 2017, AF patients in the AF ablation waiting list of Beijing Anzhen Hospital were enrolled for primary cognitive screening. Patients over 60 years of age with normal cognitive functions were included and further randomly divided into ablated AF patients (study group) and AF patients who are awaiting ablation (practice group). Exclusion criteria included pre-existing neurological or clinically evident neurovascular disease, significant pre-morbid depression and/or anxiety, anticipated difficulty with neurocognitive assessment (e.g., deafness, language difficulties), and with history of cardiopulmonary bypass surgery.
In the study group, cognitive assessment was administered at 24 h prior to ablation and 48 h after the ablation procedure respectively. The practice group was set up to determine the practice effect of cognitive tests resulted from repeated testing, two consecutive cognitive assessment were administered to them with a 72-h interval before the ablation. All patients provided a written informed consent for both the baseline and post-procedural cognitive assessments.
In patients of the study group consenting to accept an extra 6-month cognitive assessment at enrollment, practice effect was not considered in 6-month cognitive assessment, for previous study have reported similar test results between the baseline and 3-month assessment in non-ablated AF patients [10].
Neuropsychological testing
A trained interviewer administered neuropsychological testing to all included patients. A well-established formal testing battery consisting of nine tests were used, which is based on the Canadian Study of Health and Aging [11,12,13,14,15] (Appendix Table 4).
The interviewer recorded both the number of correct answers and the time taken to complete the tests. To reduce the potential influence by other factors, parallel neuropsychological testing was conducted in the same room, by the same interviewer, and at the same time of the day for each recruited patient.
Visual analog scales were also utilized to assess the presence of mood disorder levels which may influence the scores on neuropsychological tests. Patients were asked to estimate their current levels of depression and anxiety by marking a line standardized to 10 cm in length [13].
Definition of POCD at 48 h after ablation
The reliable change index (RCI) was used to analyze the neuropsychological testing scores and to identify POCD [15, 16].The details of the RCI calculation are listed as follows:
For all the patients in both the study group and the practice group, the initial testing raw score (X1) was subtracted from the final testing raw score (X2) to produce a ΔX for each task except the timed tasks. We subtracted the final testing raw score (X2) from the initial testing raw score (X1) to calculate a ΔX for the timed tasks (Trail Making Task, Parts A and B, and Grooved Pegboard Test, Dominant and Non-dominant Hands).
To eliminate any learning and practice effects, we subtracted the mean difference [Mean(ΔXp)] of the practice group from the change in study group patient's testing scores (ΔX) and then divided it by the SD of the change in test results of the practice group [SD(ΔXp)], controlling for the expected variability, to obtain the final z-score for every test.
A combined test score (∑Zcombined) was created by using the sum of z-scores for each test (∑Z 1,2,3…9) divided by the SD of this summation in the practice group (SD [∑Zpractice 1,2,3…9]).
$$\sum Z_{{{\text{combined}}}} = \sum Z{\text{ }}1,2,3 \ldots 9/SD{\text{ }}(\sum Z_{{{\text{practice}}}} 1,2,3 \ldots 9)$$
We defined the presence of POCD when the z-score < − 1.96 on ≥ 2 tests, or the combined z-score < − 1.96 [15, 16].
Cognitive assessment in 6-month follow-up
Comparisons of neuropsychological outcomes were made among pre-operation, and 48 h and 6 months post-operation. The mean difference between cognitive assessments in the practice group was defined as practice effect and was subtracted from raw scores of 48 h postoperative tests in the study group. All test results were transformed to z scores. A global cognitive score was created by averaging the z scores of each subtest and standardizing them [17]. Absolute test scores were reversed for timed tasks, hence higher z scores always represent better test performance.
Perioperative anticoagulation management
Transesophageal echocardiography (TEE) was performed in every patient to rule out the left atrium or atrial appendage thrombus before the AF ablation procedure.
During admission, for patients on warfarin, a nonstop strategy was used (i.e., no low-molecular-weight heparin LMWH bridging) if the international normalized ratio (INR) value was between 2.0 and 3.0. If the patient's INR value was below 2.0, bridging with LMWH while titrating warfarin was conducted until a therapeutic INR was obtained. If the INR value was above 3.0, we titrated the warfarin dose by stopping or reducing the warfarin dose under close monitoring. For patients on new oral anticoagulants (NOAC), we stopped using NOAC after admission and bridged with full-dose LMWH and reinitiated NOAC at six hours after the ablation procedure. For those not on warfarin or NOAC at admission, full-dose LMWH was administered, and post-procedure oral anticoagulation use was a shared decision between doctors and patients. All patients were treated with anticoagulants for at least 3 months postoperatively, and then at 3 months, patients with a CHA2DS2-VAS score > = 2 were encouraged to continue using oral anticoagulation.
During the procedure, ACT was measured every 30 min to maintain an ACT level above 300 s.
AF ablation procedure
After overnight fasting, the patients received AF ablation procedures under conscious sedation with fentanyl. Circumferential pulmonary vein isolation was applied for the patients with paroxysmal atrial fibrillation (PAF) [18, 19] while a fixed '2C3L' approach for patients with non-paroxysmal AF [20] were applied, guided by a three-dimensional electroanatomic mapping system (CARTO, Biosense-Webster, Inc.). The '2C3L' strategy is a fixed approach for ablation of persistent AF, which consists of bilateral circumferential pulmonary vein antrum isolation ('2C') and three linear ablation sets ('3L').Linear ablation is empirically applied across the mitral isthmus, the left atrial roof, and the cavo-tricuspid isthmus. Ablation energy was delivered with a maximum power of 30 to 35 W with continuous heparinized saline flow at a rate of 17 mL/min.
Statistical analysis
The data were reported as the mean ± standard deviation (SD) for continuous variables and frequency (%) for categorical variables, while the Student’s t-test and chi-squared test were deployed to assess the differences between the groups. Univariate logistic regression analysis was performed to assess the association of each variable with POCD. The variables with a P value < 0.05 in the univariate analysis and of clinical importance were then included in the multivariate logistic regression analysis, including the CHA2DS2-VASc score (< 2 for males, < 3 for females), the minimum intraoperative ACT (< 300 s), and non-administration of oral anticoagulants within the one month prior to the ablation. Probability values less than 0.05 were considered as significant difference. All analyses were conducted using SPSS version 22.0 for Windows.