Abstract
Background
Our previous study reported a modified endoscopic procedure for nonvalvular atrial fibrillation (AF) that requires only 3 ports in the left chest wall.
Hypothesis
Certain preoperative variables might be predictive risk factors for AF recurrence among patients who underwent this procedure.
Methods
From October 2010 to April 2014, 114 patients with either paroxysmal AF (PAF) or nonparoxysmal AF (non‐PAF) underwent the procedure and completed postoperative cardiac‐rhythm measurement via electrocardiography and Holter monitoring. Univariate and multivariate analyses of the possible AF‐related risk factors were conducted.
Results
During 2‐year follow‐up, 99 of 114 patients (86.8%) were free from atrial tachyarrhythmia. Results from univariate analyses showed that AF duration, left atrial diameter (LAD), left atrial minimum volume, left atrial empty fraction, left atrial expansion index, and left atrial active empty fraction (LAAEF) were significantly associated with postoperative AF recurrence. Results from multivariate analyses showed that AF duration (odds ratio [OR]: 1.194, 95% CI: 1.063‐1.340, P = 0.003), LAD (OR: 1.101, 95% CI: 1.005‐1.205, P = 0.039), and LAAEF (OR: 0.490, 95% CI: 0.277‐0.865, P = 0.014) were independent risk factors. There was no difference in AF recurrence between patients with PAF and non‐PAF (P = 0.250).
Conclusions
Our 2‐year follow‐up study suggested that low LAAEF, long AF duration, and large LAD might be potential predictive risk factors for AF recurrence. Patients with PAF and non‐PAF had a similar AF recurrence rate after modified endoscopic ablation.
Keywords: Atrial Fibrillation, Modified Endoscopic Ablation, Recurrence, Risk Factors
1. INTRODUCTION
For >2 decades, the cut‐and‐sew Cox‐Maze III procedure was considered the gold standard for surgical treatment of atrial fibrillation (AF). However, it has not been widely accepted because of its complexity. In 2005, Wolf and colleagues1 reported the first series of video‐assisted pulmonary vein isolation (PVI) for nonvalvular AF, and the results showed that 91% of patients were free from AF at 3‐month follow‐up. Since then, various techniques of minimally invasive surgical PVI have been reported, and the success rate ranged from 55.1% to 71%.2, 3, 4, 5, 6, 7 However, all of these techniques require bilateral video‐assisted thoracoscopy. We previously introduced a modified endoscopic procedure that requires only 3 ports in the left chest wall, and the early result showed 89.1% of the patients were in sinus rhythm after the procedure.8 This article retrospectively analyzed the data from patients who had undergone this procedure at our center to evaluate the risk factors of AF recurrence. We focused on the role of preoperative left atrial (LA) function measured by echocardiography.
2. METHODS
2.1. Patient selection
From October 2010 to April 2014, 114 patients underwent modified endoscopic ablation at our center. Indications for surgery were symptomatic drug‐refractory nonvalvular AF, failed catheter ablation, or history of stroke or embolism. Contraindications included LA size >70 mm, left ventricular (LV) ejection fraction <30%, previous cardiac surgery, and severe pleural adhesions. We follow the terminology recommended in the 2012 Heart Rhythm Society/European Heart Rhythm Association/European Cardiac Arrhythmia Society Expert Consensus Statement on Catheter and Surgical Ablation of Atrial Fibrillation.9 To identify the role of preoperative LA function in predicting AF recurrence, all of these patients underwent preoperative echocardiography. During the study, we classified all the patients as having either PAF or non‐PAF. Non‐PAF included persistent AF and long‐standing AF. The study was approved by the institutional review board and individual consents were obtained.
2.2. Echocardiographic assessment
The echocardiographic results were collected 1 week before the procedure. All images were obtained with a Philips iE33 ultrasound machine (Philips Medical Systems, Andover, MA). Two‐dimensional (2D) tissue‐harmonic images were obtained in the parasternal plane and apical 4‐chamber views (for LA diameter [LAD] measurement). The left atrial maximum volume (LAVmax) and the left atrial minimum volume (LAVmin) were calculated from these apical 4‐chamber zoomed views of the LA with the use of the biplane method of discs with a frame rate of 80 frames/s. LA emptying fraction (LAEF) was calculated as follows: (LAVmax – LAVmin) / LAVmax. LA expansion index (LAEI) was derived as follows: (LAVmax – LAVmin) / LAVmin. To evaluate LA mechanical function, LA volume (LAVp) was obtained immediately before atrial systole (before the electrocardiographic [ECG] P wave in SR or just before mitral valve opening in AF). LA passive emptying fraction (LAPEF) was calculated as follows: (LAVmax – LAVp) / LAVmax. LA active emptying fraction (LAAEF) was derived as follows: (LAVP – LAVmin) / LAVP. LV ejection fraction was calculated by the Simpson method. The measurements were acquired from 3 consecutive beats and subsequently averaged. Measurements were performed by 2 observers who were blinded to the patients at the time of echocardiographic assessment.
2.3. Surgical technique
We used the surgical technique we have previously reported.8 Three ports close to the subscapular angle line of the left chest wall were created. Bilateral PVI was performed using AtriCure Isolator Synergy ablation clamp (AtriCure, Inc., Mason, OH). A circumferential left atrial ablation (CLAA) was made using the clamp from the left inferior pulmonary vein to the right superior pulmonary vein. Other linear lesions, including from left pulmonary vein to incision of LAA and from left inferior pulmonary vein to the mitral valve annulus, were made using the AtriCure Synergy ablation pen (AtriCure). The ablation of ganglionic plexi on the posterior left atrium was also performed with the pen. The LAA was excluded using the EZ 45 stapler (Ethicon Endo‐Surgery, Cincinnati, OH) or Endo GIA (Covidien/Medtronic, Minneapolis, MN). The ligament of Marshall was divided under direct vision. Electrical isolation of all pulmonary veins was tested using the pen. Subsequently, if sinus rhythm failed to be restored, cardioversion was performed immediately.
2.4. Postoperative management
Amiodarone was administered to patients at 200 mg/d for a blanking period of 3 months and was stopped in the presence of a stable sinus rhythm. For those who were intolerant to amiodarone, we recommended betaloc. Warfarin was maintained in the first 3 months after the procedure and then withdrawn if there was no recurrence of AF. International normalized ratio was targeted at 2.0 to 3.0. During the blanking period, electrical cardioversion was performed if a patient had symptomatic AF <48 hours or was adequately anticoagulated. For those who failed to restore sinus rhythm after cardioversion, we prescribed antiarrhythmic medication (amiodarone, mexiletine, or betaloc), as well as warfarin for those who had CHA2DS2‐VASC score ≥ 2. These patients were closely followed.
2.5. Follow‐up
All patients completed at least a 2‐year follow‐up. Follow‐up protocol included physical examination, 12‐lead ECG examinations, and 24‐hour Holter monitoring at 3, 6, 12, and 24 months. Besides the periodic follow‐up time points, patients who visited the hospital after the procedure due to clinical symptoms (eg, palpitation) all underwent ECG and 24‐hour Holter monitoring, and these results were also used to define whether the patients had AF recurrence. Success was defined as no episodes of any atrial tachyarrhythmia (ATA; including AF, atrial tachycardia, or atrial flutter) lasting ≥30 seconds off antiarrhythmic drugs in any ECG or Holter measurements after the blanking period (3 months), which were measured either in our center or in local hospitals.
2.6. Statistical analysis
Continuous variables were expressed as mean ± SD unless otherwise specified, and categorical data were expressed as counts and proportions. Differences between PAF and non‐PAF patients were examined by using the t test for normally distributed variables and by using nonparametric tests for abnormally distributed variables. The χ2 test was used for categorical variables. Logistic regression analysis was used to study the effects of baseline characteristics on procedure success. Univariate logistic regression models were fitted for each of the potential predictors. A P value of <0.1 was used to select covariates included in the multivariate logistic regression. Odds ratio (OR) and 95% confidence interval (CI) were calculated. The Kaplan–Meier method combined with log‐rank tests was used for comparing the difference of AF recurrence between PAF and non‐PAF patients. Statistical analyses were performed by using SPSS version 18.0 (SPSS, Chicago, IL). A P value <0.05 for 2‐tailed tests was statistically significant.
3. RESULTS
3.1. Baseline characteristics and perioperative results
Baseline characteristics between PAF and non‐PAF were compared (Table 1). Patients with non‐PAF had a longer AF duration (12.7 ± 8.4 vs 6.8 ± 5.3 y; P = 0.002) and larger LAD (45.3 ± 9.3 vs 42.6 ± 7.1 mm; P = 0.015). Moreover, these patients had more prior stroke (24.5% vs 8.2%; P = 0.017).
Table 1.
Baseline characteristics of patients
| Variables | Overall, N = 114 | PAF, n = 61 | Non‐PAF, n = 53 | P Value |
|---|---|---|---|---|
| Male sex | 73 (64.0) | 38 (62.3) | 35 (66.0) | 0.678 |
| Age, y | 61.1 ± 11.0 | 59.2 ± 11.4 | 63.4 ± 10.2 | 0.472 |
| AF duration, y | 9.6 ± 7.5 | 6.8 ± 5.3 | 12.7 ± 8.4 | 0.002 |
| LVEF, % | 57.6 ± 7.1 | 56.7 ± 7.5 | 58.6 ± 6.5 | 0.486 |
| NYHA class I–II | 92 (80.7) | 51 (83.6) | 41 (77.4) | 0.399 |
| HTN | 70 (59.8) | 34 (55.7) | 36 (67.9) | 0.182 |
| DM | 35 (30.7) | 18 (29.5) | 17 (32.1) | 0.767 |
| Hyperthyroidism | 14 (12.3) | 6 (9.8) | 8 (15.1) | 0.394 |
| Prior cardiac surgery | 0 (0) | 0 (0) | 0 (0) | |
| Prior stroke | 18 (15.8) | 5 (8.2) | 13 (24.5) | 0.017 |
| Prior CA | 17 (14.9) | 11 (18.0) | 6 (11.3) | 0.316 |
| Prior anticoagulation | 81 (71.1) | 40 (65.6) | 41 (77.4) | 0.166 |
| Prior AAD use | ||||
| Amiodarone | 82 (71.9) | 43 (70.5) | 39 (73.6) | 0.714 |
| Betaloc | 58 (50.9) | 28 (45.9) | 30 (56.6) | 0.254 |
| Mexiletine | 13 (11.4) | 8 (13.1) | 5 (9.4) | 0.537 |
| Digoxin | 32 (28.1) | 14 (23.0) | 18 (44.0) | 0.192 |
| CHA2DS2‐VASc score ≥ 2 | 71 (62.3) | 34 (55.7) | 37 (69.8) | 0.122 |
| LA size and function | ||||
| LAD, mm | 43.9 ± 8.3 | 42.6 ± 7.1 | 45.3 ± 9.3 | 0.015 |
| LAVmin, mL | 46.8 ± 7.9 | 44.8 ± 7.4 | 49.1 ± 7.8 | 0.614 |
| LAVmax, mL | 63.5 ± 9.0 | 62.9 ± 9.3 | 64.3 ± 8.6 | 0.085 |
| LAVp, mL | 55.2 ± 8.4 | 56.0 ± 9.4 | 54.5 ± 7.5 | 0.954 |
| LAEF, % | 25.6 ± 11.4 | 28.1 ± 10.3 | 22.8 ± 11.9 | 0.272 |
| LAEI, % | 38.1 ± 24.2 | 42.3 ± 23.1 | 33.3 ± 24.7 | 0.847 |
| LAPEF, % | 12.3 ± 5.7 | 13.2 ± 5.2 | 11.3 ± 6.1 | 0.269 |
| LAAEF, % | 16.0 ± 8.1 | 17.7 ± 7.6 | 14.0 ± 8.2 | 0.436 |
Abbreviations: AAD, antiarrhythmic drug; AF, atrial fibrillation; CA, catheter ablation; CHA2DS2‐VASc, CHF, HTN, age ≥ 75 y, DM, stroke/TIA, vascular disease, age 65–74 y, sex category (female); CHF, congestive heart failure; DM, diabetes mellitus; HTN, hypertension; LAAEF, left atrial active emptying fraction; LAD, left atrial diameter; LAEF, left atrial emptying fraction; LAEI, left atrial expansion index; LAPEF, left atrial passive emptying fraction; LAVmax, left atrial maximum volume; LAVmin, left atrial minimum volume; LAVp, left atrial volume immediately before systole; LVEF, left ventricular ejection fraction; non‐PAF, nonparoxysmal atrial fibrillation; NYHA, New York Heart Association; PAF, paroxysmal atrial fibrillation; SD, standard deviation; TIA, transient ischemic attack.
Values are presented as n (%) or mean ± SD.
No patient died in the perioperative period and there was no conversion to sternotomy. No patient required pacemaker insertion. Three (2.6%) patients experienced postoperative left pleural effusion requiring left thoracocentesis. One (0.9%) patient had pericardial effusion 1 month after discharge and received pericardial drainage at our center. One (0.9%) patient had slow wound healing. The mean procedure time was 113.7 ± 18.8 minutes and the mean follow‐up was 30.6 ± 6.5 months.
3.2. Rhythm results
Complete rhythm documentation was available for the 114 patients with ECG and Holter monitoring. At discharge, 105 of the 114 patients (92.1%) were free from ATA. At the 2‐year interval, 99 (86.8%) patients were free from ATA and all were asymptomatic and off antiarrhythmic drugs. Fifteen (13.2%) patients (6 with PAF and 9 with non‐PAF) failed to maintain sinus rhythm off antiarrhythmic drugs after the procedure. No patients experienced postoperative stroke.
3.3. Recurrence of ATAs
We classified all the patients into 2 groups: (1) freedom from ATA and (2) recurrence. The possible risk factors for AF recurrence in the 2 groups were compared (Table 2). Univariate analysis showed that 6 variables had P values <0.10, including AF duration, LAD, LAVmin, LAEF, LAEI, and LAAEF. AF type (PAF and non‐PAF) was not statistically significant. Then we included these 6 variables in the multivariate analysis. The results showed that AF duration (OR: 1.194, 95% CI: 1.063‐1.340, P = 0.003), LAD (OR: 1.101, 95% CI: 1.005‐1.205, P = 0.039), and LAAEF (OR: 0.490, 95% CI: 0.277‐0.865, P = 0.014) were identified as independent risk factors on multivariate analysis (Table 2). Kaplan–Meier analysis (Figure 1) showed no difference between the PAF group and non‐PAF group (P = 0.250).
Table 2.
Comparison of AF recurrence‐related risk factors
| Univariate Analysis | Multivariate Analysis | |||||
|---|---|---|---|---|---|---|
| Variables | Freedom From ATA, n = 99 | Recurrence, n = 15 | OR (95% CI) | P Value | OR (95% CI) | P Value |
| Male sex | 64 (64.6) | 9 (60.0) | 0.820 (0.270‐2.494) | 0.727 | ||
| Age, y | 60.8 ± 11.2 | 63.1 ± 10.1 | 1.020 (0.968‐1.075) | 0.449 | ||
| Non‐PAF | 44 (44.4) | 9 (60.0) | 1.875 (0.620‐5.669) | 0.265 | ||
| AF duration[1] | 9.0 ± 7.1 | 13.6 ± 9.2 | 1.076 (1.018‐1.137) | 0.010 | 1.194 (1.063‐1.340) | 0.003 |
| LVEF, % | 57.8 ± 7.3 | 56.3 ± 5.1 | 0.971 (0.902‐1.045) | 0.432 | ||
| HTN | 60 (60.1) | 10 (66.7) | 1.300 (0.413‐4.092) | 0.654 | ||
| DM | 28 (28.3) | 7 (46.7) | 2.219 (0.735‐6.697) | 0.157 | ||
| Prior CA | 14 (14.1) | 3 (20.0) | 1.518 (0.380‐6.068) | 0.555 | ||
| ECV during hospitalization | 3 (3.0) | 2 (13.3) | ||||
| Sinus rhythm on discharge | 92 (92.9) | 13 (86.7) | ||||
| LA size and function | ||||||
| LAD, mm | 43.2 ± 8.2 | 48.1 ± 7.8 | 1.064 (1.004‐1.127) | 0.037 | 1.101 (1.005‐1.205) | 0.039 |
| LAVmin, mL | 46.1 ± 7.8 | 51.5 ± 7.0 | 1.098 (1.016‐1.187) | 0.019 | ||
| LAVmax, mL | 63.9 ± 9.1 | 61.1 ± 7.7 | 0.965 (0.909‐1.026) | 0.254 | ||
| LAVp, mL | 55.6 ± 7.3 | 52.3 ± 13.7 | 0.963 (0.908‐1.020) | 0.201 | ||
| LAEF, % | 27.2 ± 11.3 | 15.7 ± 4.7 | 0.872 (0.805‐0.945) | 0.001 | ||
| LAEI, % | 41.0 ± 24.6 | 19.0 ± 6.5 | 0.910 (0.858‐0.964) | 0.001 | ||
| LAPAF, % | 12.6 ± 5.9 | 10.3 ± 4.0 | 0.922 (0.824‐1.030) | 0.151 | ||
| LAAEF, % | 17.1 ± 8.0 | 8.6 ± 3.5 | 0.788 (0.688‐0.903) | 0.001 | 0.490 (0.277‐0.865) | 0.014 |
Abbreviations: AF, atrial fibrillation; ATA, atrial tachyarrhythmia; CA, catheter ablation; CI, confidence interval; DM, diabetes mellitus; ECV, electrical cardioversion; HTN, hypertension; LAAEF, left atrial active emptying fraction; LAD, left atrial diameter; LAEF, left atrial emptying fraction; LAEI, left atrial expansion index; LAPEF, left atrial passive emptying fraction; LAVmax, left atrial maximum volume; LAVmin, left atrial minimum volume; LAVp, left atrial volume immediately before systole; LVEF, left ventricular ejection fraction; non‐PAF, nonparoxysmal atrial fibrillation; OR, odds ratio; SD, standard deviation.
Data are presented as n (%) or mean ± SD unless indicated otherwise.
Figure 1.
Kaplan–Meier analysis of postoperative AF recurrence between patients with PAF and non‐PAF (P = 0.250). Abbreviations: ATA, atrial tachyarrhythmia; non‐PAF, non paroxysmal atrial fibrillation; PAF, paroxysmal atrial fibrillation
4. DISCUSSION
Since Wolf and colleagues1 reported the first series of video‐assisted PVI in 2005, the following decade has witnessed important changes in the management of symptomatic AF with various modified endoscopic ablation.10 Several single‐center studies reported overall 1‐year freedom from AF between 62% and 80%.7,11, 12, 13 The longest follow‐up was reported by Hu and colleagues.6 Their single‐center study enrolled 78 patients who had undergone 5‐year follow‐up; freedom from AF was 69.2% in patients with PAF and 44.1% in those with non‐PAF.
Our general 2‐year success rate for our modified endoscopic procedure was 86.8% (99 of 114). There was no difference in AF recurrence rate between PAF patients and non‐PAF patients (P = 0.250). It might be partially explained by the complete transmurality and continuity of our technique. Previous studies have shown that continuous, transmural ablation lines are essential to reliably block electrical propagation.14, 15 Residual gaps caused by incomplete lesions, even as small as 1.1 mm, are still able to allow for effective conduction both of normal paced rhythm or AF.14 This may result in the postoperative AF recurrence. During our procedure, we routinely performed ≥10× overlapping ablation at the antrum of the right and left pulmonary veins. In addition, we also routinely performed a CLAA ring using a bipolar radiofrequency clamp, which connects the left inferior pulmonary vein to the right superior pulmonary vein across the left atrial roof, anterior and posterior wall (Figure 2). By adding the CLAA ring, LA roof ablation can be achieved.
Figure 2.
CLAA ring made by bipolar radiofrequency clamp, connecting left inferior pulmonary vein, right superior pulmonary vein, and left atrial roof. Abbreviations: CLAA, circumferential left atrial ablation
The effectiveness of adding an ablation line at the LA roof has been proven in several studies before.16, 17 Hocini and colleagues17 reported that ablation along the LA roof resulted in a slowing of the AF process and termination of AF in 47% of patients who were diagnosed with PAF. In our study, in which complete transmurality and continuity were guaranteed by overlapping ablation and the addition of a CLAA ring, the modified endoscopic procedure had a similar success rate in PAF and non‐PAF patients.
Several studies have demonstrated that an enlarged LA predicts the recurrence of AF after catheter ablation or surgical ablation.18, 19 Our study also found that LAD was a predictor of AF recurrence after modified endoscopic procedure. Compared with LA size, the evaluation of LA function has attracted less attention. However, LA function should not be ignored because it is useful in predicting the success of restoring sinus rhythm in patients with AF after ablation.20 LA function has been described in 3 phases within the cardiac cycle: reservoir, conduit, and booster pump.21 During ventricular systole, the LA serves as a reservoir and undergoes passive expansion that is driven by the apical descent of the mitral annulus. As the mitral valve opens following completion of ventricular ejection, the LA serves as a conduit to let blood flow directly from the pulmonary veins into the left ventricle. The booster pump refers to the active contraction of the LA, often known as the “atrial kick,” which increases ventricular end‐diastolic volume. LAEF reflects global LA function, whereas LAEI, LAPEF, and LAAEF reflect reservoir, conduit, and booster pump function, respectively.20
It has been recognized that impaired LA function independently contributes to adverse cardiac outcomes.22, 23 Haffajee and colleagues24 reported that LAEF is an independent predictor of postoperative AF and may help to identify patients who are most likely to benefit from prophylaxis for postoperative AF. Dodson and colleagues25 studied 346 patients with AF refereed for cardiac magnetic resonance pulmonary vein mapping before PVI and found a strong association between LAPEF and recurrent AF after PVI that persisted. Our results were not in accordance with these studies, but showed that LAAEF strongly predicted late AF recurrence. It might be explained by the role of LA booster pump in AF. It has been hypothesized that diastolic LV pressure was increased in patients with nonvalvular AF.26 LV relaxation abnormalities led to a reduction in passive LA emptying, with the development of higher atrial pressure and larger LA volume. During this course, LA active contraction was enhanced as a compensatory response to the increased LV pressure and reduced passive LA emptying.27 Over time, this balance might be broken and the LA and pulmonary veins dilate, resulting in vulnerability to AF.27, 28 Although Dodson and colleagues25 concluded that LAPEF may be used as a potential marker for risk stratification in patients undergoing PVI, our study suggested that LAAEF as a compensatory effect should not be ignored and played an important role in predicting AF recurrence among patients undergoing the modified endoscopic procedure. Long AF duration also accelerates the diminishing LA booster pump function and increases AF recurrence.
4.1. Study limitations
Our study has several limitations. First, the events of AF recurrence after the procedure (n = 15) might not be sufficient enough to find robust risk factors from multivariate analyses. Further studies with a larger sample size and longer follow‐up should be performed to confirm our findings. Second, AF recurrence is not a perfect time varying outcome as good as death or reoperation because continuous monitoring of patients all the time after the surgery is not feasible in the real world. The current monitoring methods (ECG and 24‐hour Holter) will overestimate the success rate. However, even this is not a perfect choice; AF recurrence might be the most appropriate one. Many previous studies used AF recurrence as a primary outcome.6,11, 12, 13,25 Finally, we used 2D echocardiography to assess LA function. Other types of measurements, such as 3D echocardiography, computed tomographic scanning, and cardiac magnetic resonance imaging, might be more accurate. However, the 2D echocardiogram is much easier to obtain in our daily clinical practice and it is not practical to screen every AF patient by using 3D echocardiography, computed tomographic scanning, or cardiac magnetic resonance imaging before arranging the procedure.
5. CONCLUSION
In our 2‐year follow‐up, we found that low LAAEF, long AF duration, and large LAD might be predictive risk factors for AF recurrence. Patients with PAF and non‐PAF patients had a similar AF recurrence rate after modified endoscopic ablation.
Acknowledgments
The authors thank the Clinical Research Unit of Shanghai Xinhua Hospital for its contribution in the statistical analysis. The authors also thank Saie Shen, MD, Yuan Sun, MD, Yin Cai, MD, Ms Huihua Chen, and Ms Yu Su for their excellent support in experiment and clinic.
Conflicts of interest
The authors declare no potential conflicts of interest.
An K, Zhu J, Ma N, Tang M, Mei J. Predictive risk factors for recurrent atrial fibrillation after modified endoscopic ablation: A 2‐year follow‐up. Clin Cardiol. 2018;41:372–377. 10.1002/clc.22878
Funding information This work was supported by the Science and Technology Commission of Shanghai Municipality (grants 13XD1403200 and 11441900200) and the Xinhua Hospital (grant 13YJ29).
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