Epicardial adipose tissue (EAT) contains ganglionated plexuses and adipocytes that can affect the pathogenesis of atrial fibrillation (AF). The aim of this study was to quantify the EAT surrounding the left atrium (LA) and correlate it with occurrence of AF and outcome after catheter ablation. EAT was evaluated using 64-slice multidetector computed tomography in 68 patients with AF and 34 controls. EAT volume was acquired by semiautomatically tracing axial images from the pulmonary artery to the coronary sinus. Topographic distribution of EAT was assessed by dividing the periatrial space into 8 equal regions. EAT volume significantly increased in patients with AF than in controls (29.9 ± 12.1 vs 20.2 ± 6.5 cm 3 , p <0.001). Most EAT was located in regions (1) within the superior vena cava, right pulmonary artery, and right-sided roof of the LA (29.8%), (2) within the aortic root, pulmonary trunk, and left atrial appendage (26.5%), and (3) between the left inferior pulmonary vein and left atrioventricular groove (18.1%). Baseline variables were analyzed in patients with (n = 24) and without (n = 44) AF recurrence after ablation. The recurrent group showed significantly increased EAT (35.2 ± 12.5 vs 26.8 ± 11.1 cm 3 , p = 0.007). Multivariate analysis revealed that EAT was an independent predictor of AF recurrence after ablation (p = 0.038). In conclusion, EAT of LA was increased in patients with AF. Large clusters of EAT were observed adjacent to the anterior roof, left atrial appendage, and lateral mitral isthmus. Abundance of EAT was independently related to AF recurrence after ablation.
Several studies have shown that epicardial adipose tissue (EAT) is not an anatomic depot of fat but may secrete proinflammatory hormones and cytokines related to coronary artery disease (CAD) and arrhythmias. Furthermore, the clinical significance of EAT in patients with metabolic syndrome, diabetes mellitus, and CAD has been well established. Recently, 2 reports have described that pericardial fat volume of the entire heart is significantly increased in patients with atrial fibrillation (AF) using multidetector computed tomography. However, information focusing on topographic distribution of EAT surrounding the left atrium (LA) and influence of catheter ablation on outcome is still limited. Therefore, the aim of this study was to delineate EAT adjacent to the LA and evaluate its impact on clinical outcome in patients undergoing catheter ablation of AF.
Methods
Sixty-eight consecutive patients with AF (43 with paroxysmal AF and 25 with persistent AF) who underwent radiofrequency ablation of the LA and in whom 64-slice multidetector computed tomography was performed before ablation were included. This group was compared to 34 age- and gender-matched controls who underwent multidetector computed tomography for screening of CAD and had no history of AF. This study was approved by the clinical ethics committee.
Details of the computed tomographic protocols have been described previously. Briefly, the LA and pulmonary veins (PVs) were evaluated with an electrocardiographically gated, 64-slice multidetector computed tomographic scanner (Aquilion 64 CFX, Toshiba Medical System, Tokyo, Japan). All participants underwent contrast-enhanced computed tomographic scanning during sinus rhythm. Patients were instructed to hold their breath to acquire the images, which covered an area from the superior margin of the pulmonary hilum to the cardiac apex (collimation 64 × 0.5 mm, gantry rotation time 350 ms, table speed 6.3 mm/rotation, tube voltage 120 kV, effective tube current 545 mA). Acquisition time was 8 to 12 seconds depending on heart rate.
All computed tomographic images were analyzed offline with software developed by the Department of Biomedical Engineering, Chung Yuan Christian University (Chung-Li, Taiwan). Volume of EAT was obtained using a semiautomated method and fat was recognized using threshold attenuation values of −50 to −200 HU. Axial images at atrial end-diastole were used to trace EAT from the pulmonary artery to the coronary sinus. Total number of slices traced manually was 60 to 112 depending on atrial size. All slices were verified for accuracy by 2 investigators. To understand the topographic distribution of EAT the periatrial space was equally divided into 8 regions. That is, the periatrial space was divided equally into halves in the x, y, and z planes ( Figure 1 ). Region 1 indicates the space of the right anterior-superior LA, region 2 the space of the left anterior-superior LA, region 3 the space of the right anterior-inferior LA, region 4 the space of the left anterior-inferior LA, region 5 the space of the right posterior-superior LA, region 6 the space of the left posterior-superior LA, region 7 the space of the right posterior-inferior LA, and region 8 the space of the left posterior-inferior LA.
Furthermore, 2 phases of multidetector computed tomographic images were obtained for functional assessment of the LA and PVs. Phase 1 was end-systole of the atrium and indicated minimal volume of LA. Phase 2 was end-diastole of the atrium and indicated maximal volume of LA. Maximal and minimal volumes of the LA and left atrial appendage were acquired for analysis. Ejection fractions of the LA and left atrial appendage were defined as (maximal volume minus minimal volume)/maximal volume.
Each patient underwent an electrophysiologic study and catheter ablation in a fasting nonsedated state. Details have been described previously. In brief, the PV ostia were identified by fluoroscopy and marked on a 3-dimensional map of the LA. Continuous circumferential lesions were created encircling the right and left PV ostia guided by the NavX system using a 4-mm-tip ablation catheter (EP Technologies, Boston Scientific, Inc., Natick, Massachusetts). Radiofrequency energy was applied continuously while repositioning the catheter tip every 40 seconds with a target temperature of 50°C to 55°C and maximum power of 50 W in the temperature-control mode with the 4-mm-tip catheter. Radiofrequency ablation was performed on the venous side of the left atrial appendage ridge while encircling the left PV ostia. After completion of the circumferential lesion set, ipsilateral superior and inferior PVs were mapped carefully by a circular catheter recording (Spiral SC, AF Division, St. Jude Medical, Inc., Minnetonka, Minnesota) during sinus rhythm or coronary sinus pacing. Supplementary ablations were applied along circumferential lines close to the earliest ipsilateral PV spikes. After successful isolation of all 4 PVs, which was confirmed by PV circumferential mapping, high current (3 to 5 times pacing threshold) and wide (8 ms) pulse duration stimulation from the proximal and distal coronary sinus was performed (in 10-ms decrements from 250 to 150 ms with 5- to 10-second duration of each pacing cycle length) and repeated 3 to 5 times. If an induced AF was sustained for >1 minute, an additional linear ablation was performed at the anterior roof followed by the mitral isthmus if AF persisted. In nonparoxysmal AF, PV isolation plus linear ablation was performed as the first and second steps. If AF did not stop, an additional ablation of complex fractionated atrial electrographic sites was performed sequentially based on results of complex fractionated atrial electrographic maps after PV isolation. The end point of ablation of complex fractionated atrial electrographic sites was to obtain prolongation of cycle length (fibrillation interval >120 ms), eliminate complex fractionated atrial electrographic sites, or abolish local fractionated potentials (bipolar voltage <0.05 mV). If the AF still did not stop after additional ablation of complex fractionated atrial electrographic sites, sinus rhythm was restored by electric cardioversion.
After discharge patients underwent follow-up (2 weeks after catheter ablation and every 1 month to 3 months thereafter) at our cardiology clinic or with referring physicians where routine electrocardiograms were obtained during each follow-up visit, and antiarrhythmic drugs were prescribed for 8 weeks to prevent any early recurrence of AF. During each follow-up visit after ablation 24-hour Holter monitoring and/or cardiac event recording with a recording duration of 1 week were performed to define the cause of clinical symptoms. Recurrence of atrial arrhythmia was defined as an episode lasting >1 minute and that was confirmed by electrocardiograms 3 months after ablation (blanking period). The end point for follow-up was a clinically documented recurrence of atrial arrhythmias or repeat ablation procedures.
All quantitative data were expressed as mean ± SD or percentage. Chi-square test with Yates correction or Fisher’s exact test was used for categorical data. Student’s t test or Mann–Whitney U test was used for continuous data if appropriate. Variables chosen to be tested in multivariate analysis were those with a p value <0.1 in univariate analysis. A p value <0.05 was considered statistically significant.
Results
Age, gender, and body mass index were similar in patients with AF and controls. Incidences of diabetes mellitus, CAD, and hypertension, and levels of total cholesterol and triglyceride were also similar between the 2 groups. However, EAT and left atrial volumes were significantly increased in patients with AF compared to controls ( Table 1 ). In multivariate analysis, only EAT was significantly increased (p = 0.03) in the AF group. Amount of EAT varied from 10.3 to 69.9 cm 3 in patients with AF and was not significantly different between patients with paroxysmal and those with persistent AF (27.1 ± 9.6 vs 34.8 ± 15.3 cm 3 , p = 0.067). EAT was distributed unevenly around the LA. Most EAT was located in the region surrounded by (1) the superior vena cava, right pulmonary artery, and right-sided roof of the LA (region 1, ∼29.8% of total EAT amount; Figure 2 ), (2) the aortic root, pulmonary trunk, and left atrial appendage (region 2, ∼26.5% of total EAT amount; Figure 2 ), and (3) between the left inferior PV and left atrioventricular groove (region 8, ∼18.1% of total EAT amount; Figure 2 ). Other minor distributions were in areas between the right superior and inferior PV (region 5, ∼6.5% of total EAT amount), between the left atrial appendage and left superior PV (region 6, ∼8.3% of total EAT amount), and adjacent to the proximal coronary sinus (region 7, ∼7.1% of total EAT amount). Regional analysis between the AF and control groups showed that EAT in regions 1, 2, 4, 5, and 8 were significantly increased in patients with AF ( Table 1 ). In multivariate analysis adjusted for left atrial volume, EAT in regions 1 (p = 0.005) and 5 (p = 0.002) were significantly increased in patients with AF.
| Variable | AF | Normal | p Value |
|---|---|---|---|
| (n = 68) | (n = 34) | ||
| Age (years) | 54.7 ± 8.5 | 54.1 ± 9.0 | 0.74 |
| Men | 52 (76%) | 21 (62%) | 0.35 |
| Body mass index (kg/m 2 ) | 25.6 ± 3.3 | 26.0 ± 2.7 | 0.73 |
| Diabetes | 7 (10%) | 4 (12%) | 0.98 |
| Coronary artery disease | 5 (7%) | 4 (12%) | 0.94 |
| Hypertension | 10 (15%) | 9 (26%) | 0.76 |
| Total cholesterol (mg/dl) | 193.3 ± 32.6 | 196.6 ± 21.9 | 0.20 |
| Triglyceride (mg/dl) | 158.7 ± 53.7 | 162.1 ± 67.3 | 0.97 |
| Left atrial volume (cm 3 ) | 126.7 ± 45.0 | 97.4 ± 19.7 | 0.001 |
| Epicardial adipose tissue (cm 3 ) | |||
| Total | 29.9 ± 12.1 | 20.2 ± 6.5 | <0.001 |
| Region | |||
| 1 | 8.92 ± 3.58 | 5.35 ± 2.15 | <0.001 |
| 2 | 7.93 ± 4.42 | 5.77 ± 2.97 | 0.011 |
| 3 | 0.58 ± 0.67 | 0.42 ± 0.55 | 0.29 |
| 4 | 0.51 ± 0.76 | 0.19 ± 0.47 | 0.027 |
| 5 | 1.94 ± 1.79 | 0.74 ± 0.60 | <0.001 |
| 6 | 2.48 ± 1.93 | 2.33 ± 1.66 | 0.85 |
| 7 | 2.12 ± 1.10 | 2.05 ± 1.09 | 0.64 |
| 8 | 5.41 ± 3.16 | 3.34 ± 1.79 | 0.001 |
After evaluating global distribution of EAT near the LA, we found that EAT volume was significantly increased around the anterior 1/2 of the LA than around the posterior 1/2 of the LA (17.9 ± 7.3 vs 11.7 ± 4.2 cm 3 , p <0.001). In addition, EAT volume was significantly larger around the superior 1/2 of the LA than around the inferior 1/2 of the LA (21.3 ± 8.9 vs 14.2 ± 5.0 cm 3 , p <0.001; Figure 3 ).
Twenty-two patients had AF recurrence during a mean follow-up period of 228 ± 79 days. Clinical and anatomical parameters including age, gender, body mass index, volume and ejection fraction of the LA and left atrial appendage were compared between patients with and without AF recurrence after catheter ablation ( Table 2 ). In univariate analysis total volume of EAT (p = 0.007) was related to recurrence of AF. Multivariate analysis showed that only EAT amount (p = 0.038) was an independent predictor of AF recurrence after catheter ablation.
