- Academic Editor
†These authors contributed equally.
Background: The combination of left atrial appendage closure (LAAC) and
catheter ablation (CA) in a single procedure is a safe and effective form of
treatment for atrial fibrillation (AF). However, several findings have argued
that LAAC might increase the risk of AF recurring. Therefore, this study
investigated the impact of insufficient ablation on AF recurrence after the
hybrid procedures of CA and LAAC. Methods: We reviewed 107 consecutive
patients with AF who received the CA and LAAC hybrid procedures (combined group).
In the case–control study, another 107 patients who underwent only CA (ablation
group) were successfully matched using propensity score matching. After
correcting the insufficient ablation, 107 consecutive patients were enrolled
prospectively. During the follow-up period, postprocedural 24-hour monitor
recordings and a portable electrocardiogram (ECG) monitoring device were used to detect AF
recurrence. Transesophageal echocardiography was used to evaluate LAAC.
Results: The combined group showed an increase in the risk of AF
recurrence after 539.2
Atrial fibrillation (AF) is responsible for an increased risk of thromboembolic stroke and impaired quality of life [1]. Catheter ablation (CA), including radiofrequency ablation and cryoballoon ablation, has become a standard procedure to attenuate the symptoms and improve the quality of life of patients with AF, by reducing the AF burden [2]. However, previous studies have failed to find significant reductions in the risk of stroke after AF ablation [3, 4]. Consequently, clinical guidelines recommend antithrombotic therapy in AF patients to reduce the risk of stroke even after catheter ablation [5]. Additionally, the issue of bleeding risk in patients with continuous anticoagulation after AF ablation has received considerable critical attention [6].
In an effort to reduce both the risk of embolism and bleeding, left atrial
appendage closure (LAAC) has been widely used in patients with a high
CHA
Between January 2017 and December 2018, there were 107 symptomatic nonvalvular
AF patients (combined group) included in this single-center study, who underwent
CA combined with LAAC at Changhai Hospital.
The inclusion criteria were a HAS-BLED score
Radiofrequency ablation procedure was performed with an uninterrupted direct oral anticoagulant. Activated clotting time (ACT) was targeted between 300 and 350 seconds throughout the procedure. A coronary sinus catheter was positioned in the coronary sinus (CS) through the left femoral vein and through a right ventricle catheter in the right ventricle. Following transseptal puncture, point-by-point ablation was performed using a Tacticath Quartz catheter (Abbott Inc, St. Paul, MN, USA) and power-control mode with a power of 30–40 W within the LA. All patients underwent pulmonary vein isolation (PVI). According to the discretion of the operator, patients underwent different additional ablation strategies, including roof, mitral linear ablation, etc.
Following transseptal puncture, a 28 mm cryoballoon (Arctic Front Advance,
Medtronic, MN, USA) was inserted into the left atrium. After insertion, the
cryoballoon was inflated and wedged into the ostia of the pulmonary veins, and
contrast medium was injected to confirm perfect pulmonary vein (PV) occlusion. A
180-second freeze was delivered when the time to PVI was
Following the ablation procedure, the Watchman device (Boston Scientific, Marlborough, MA, USA) was implanted. The previously used FlexCath sheath or Agilis NxT sheath was replaced by a 14F sheath. Under the protection of the pigtail catheter, the sheath for the Watchman device was delivered to the ostium of the left atrial appendage (LAA). Angiography of the LAA was performed from multiple angles and based on that the proper Watchman device was selected and released into the correct position. Before releasing the device, angiography was performed again to ensure that the position of the device was correct and that no- or minimal residual blood flow was observed.
Based on the results of the case–control study, we speculated that insufficient ablation is a correctable risk factor that is associated with AF recurrence. A standard wide circumferential pulmonary vein antral isolation approach and suitable additional ablation were used to correct the insufficiency ablation in both the radiofrequency ablation and cryoballoon ablation, as shown in Fig. 1. Successively, we prospectively enrolled 107 patients undergoing AF ablation combined with LAAC on a corrected strategy (corrected group). The pulmonary vein antrum was ablated sufficiently, and a suitable additional ablation strategy was used intentionally. The AF-free survival rate of the corrected group was compared to the other two groups. The study flowchart is shown in the graphical abstract.
Comparison of insufficient ablation and corrected ablation. (A) Insufficient ablation of radiofrequency ablation for pulmonary vein antrum. (B) Corrected ablation of radiofrequency ablation for pulmonary vein antrum. (C) Insufficient ablation of cryoballoon ablation for pulmonary vein antrum. (D) Corrected ablation of cryoballoon ablation for pulmonary vein antrum.
After radiofrequency ablation or cryoballoon ablation procedure, patients in the ablation group received anticoagulation for at least three months. Data were obtained by 24-hour monitoring at the 3-, 6-, and 12-month follow-up procedures to evaluate the outcome of the AF ablation. A recurrent AF is defined as an AF or atrial tachycardia that lasts longer than 30 seconds without antiarrhythmic drugs.
In the combined group and corrected group, a direct oral anticoagulant was
recommended for three months after procedures. Dual antiplatelet drugs were
prescribed in the next 3 months followed by
lifelong aspirin use, if a satisfactory
transesophageal echocardiography (TEE) or computerized tomography (CT) result was
confirmed at the 3-month follow-up. The definition of a successful LAAC included
the desired positioning of the Watchman device, complete coverage of the LAA
ostium, and a peri-device flow of
A t-test was used to compare continuous variables and
In total, 214 patients were included in the case–control study, 107 patients were in the combined group and 107 matched controls were in the ablation group. There was no significant difference in the demographic characteristics between the two groups. Interestingly, the procedure time was not significantly increased, while the fluoroscopy time was prolonged in the combined group compared with the ablation group. There is a greater number of ablating attempts and a longer duration of ablation in the ablation group for both the radiofrequency and cryoballoon ablations. The characteristics and ablation parameters for the two groups are shown in Table 1. These results suggested that insufficient ablation may contribute to a higher recurrence of AF and atrial tachycardia in the combined group.
Variables | Combined group |
Ablation group |
Corrected group |
vs. | vs. | |
(N = 107) | (N = 107) | (N = 107) | p value | p value | ||
Age | 67.0 |
66.3 |
65.2 |
0.599 | 0.206 | |
Male | 56 (52.3%) | 60 (56.1%) | 58 (54.2%) | 0.583 | 0.784 | |
Paroxysmal AF (%) | 77 (72.0%) | 72 (67.3%) | 75 (70.1%) | 0.457 | 0.763 | |
BMI (kg/m |
24.3 |
24.7 |
25.0 |
0.682 | 0.060 | |
CHA |
3.3 |
3.2 |
3.0 |
0.654 | 0.145 | |
HAS-BLED | 2.8 |
2.8 |
2.7 |
0.292 | 0.229 | |
Scr (µmol /L) | 75.5 |
78.1 |
76.5 |
0.763 | 0.693 | |
GFR (mL/min) | 87.9 |
88.0 |
89.7 |
0.611 | 0.390 | |
ALT (U/L) | 32.2 |
34.8 |
33.9 |
0.208 | 0.374 | |
AST (U/L) | 20.2 |
21.0 |
19.8 |
0.719 | 0.667 | |
Serum kalium (mmol/L) | 3.9 |
3.9 |
3.9 |
0.295 | 0.975 | |
LAD (mm) | 4.1 |
4.1 |
4.0 |
0.641 | 0.733 | |
LAD-after (mm) | 4.0 |
4.1 |
4.0 |
0.216 | 0.992 | |
EF (%) | 61.4 |
61.0 |
60.0 |
0.497 | 0.090 | |
LVDD (mm) | 4.4 |
4.6 |
4.5 |
0.821 | 0.773 | |
IVS (mm) | 1.0 |
1.1 |
1.0 |
0.596 | 0.161 | |
BNP (pg/mL) | 163.1 |
171.0 |
169.9 |
0.779 | 0.810 | |
MR (mL) | 2.6 |
2.5 |
2.3 |
0.458 | 0.181 | |
TR (mL) | 2.7 |
3.1 |
2.7 |
0.642 | 0.937 | |
AR (mL) | 0.4 |
0.3 |
0.5 |
0.545 | 0.103 | |
Cryoballoon ablation (%) | 54 (50.5%) | 60 (56.1%) | 56 (52.3%) | 0.411 | 0.784 | |
Radiofrequency ablation | N = 53 | N = 47 | N = 51 | |||
Number of ablating attempts | 47.2 |
58.8 |
75.5 |
|||
Duration of ablation (s) | 1695.2 |
2099.1 |
2396.5 |
|||
Procedure time (min) | 128.3 |
126.1 |
142.9 |
0.720 | 0.024 | |
Fluoroscopy time (min) | 8.6 |
4.1 |
10.9 |
|||
Additional ablation (%) | 7 (13.2%) | 17 (36.2%) | 19 (37.3%) | 0.007 | ||
Cryoballoon ablation | N = 54 | N = 60 | N = 56 | |||
Number of ablating attempts | 4.8 |
6.1 |
6.5 |
|||
Duration of ablation | 811.1 |
996.0 |
1179.8 |
|||
Procedure time (min) | 93.4 |
95.4 |
132.5 |
0.648 | 0.001 | |
Fluoroscopy time (min) | 10.1 |
6.0 |
13.0 |
|||
Additional ablation (%) | 0 (0%) | 5 (8.3%) | 6 (10.7%) | 0.030 |
After 599.0
The Kaplan–Meier survival curve for the primary endpoint. AF, atrial fibrillation.
Variable | Univariable analysis | Multivariable analysis | ||
β-coefficient (95% CI) | p | β-coefficient (95% CI) | p | |
Groups | 0.518 (0.288 to 0.934) | 0.029 | 0.473 (0.262 to 0.852) | 0.013 |
AF type | 2.819 (1.609 to 4.939) | 2.551 (1.415 to 4.598) | 0.002 | |
LAD | 1.014 (1.004 to 1.023) | 0.004 | 1.010 (1.001 to 1.019) | 0.029 |
LAD, left atrial diameter; AF, atrial fibrillaiton.
Based on the above results, we hypothesized that insufficient ablation may be
associated with a higher AF recurrence when AF ablation was combined with LAAC.
In the prospective study, there was no statistical difference in demographic data
between patients in the combined group and the corrected group. After correcting
the insufficient ablation, the corrected group showed an increase in additional
ablations, number of ablating attempts, duration of ablation, procedure time, and
fluoroscopy time. After a follow-up period of 420.4
Peri-device leaks of
The main finding of our study was to demonstrate that insufficient ablation is associated with AF recurrence after hybrid procedures of ablation and LAAC. Insufficient ablation is common in CA combined with LAAC procedures that may lead to AF recurrence in a case–control study. In this prospective study, we found that AF recurrence was reduced by correcting the insufficient ablation.
Accumulating evidence has demonstrated that stroke risk in AF patients with a
high CHA
Pioneering research demonstrated that the combination of radiofrequency ablation and LAAC can be implemented safely [7]. Subsequent research expanded the sample size, extended the follow-up duration, and further confirmed the safety and feasibility of this hybrid regimen [14, 15, 16, 17, 18, 19, 20]. Recent studies have demonstrated the safety and efficacy of concomitant cryoballoon ablation and LAAC [21, 22]. The expert consensus statement by the EHRA/EAPCI [23] suggested that the hybrid procedures of CA and LAAC are an effective and practical approach due to the common aspects (e.g., transseptal puncture and anticoagulation). In contrast to the studies above, there are also some other studies that argue that the combination may lead to a higher risk of AF recurrence. Luani et al. [10] found that the left atrial volume increased significantly after interventional LAAC. Additional research also found significant increases in the left atrial size and decreases in the left atrial function, which may result in AF recurrence [11]. In the present study, we compared the left atrial diameters before and after the procedures in the different groups and found no significant difference in the left atrial size. Therefore, it seems likely that other factors beyond the remodeling of the left atrial could be influencing the increased recurrence of AF post-LAAC. These factors might include the specific effects of the AF ablation and LAAC procedures.
In the case–control study, we demonstrated a significant reduction in the AF-free survival rate in the combined group. Interestingly, the procedure time was not significantly prolonged when LAAC was added following CA in the combined group. Additional analysis found a reduction in the number of additional ablations and ablating attempts in addition to the duration of ablation in the combined group. It implies that insufficient ablation is common following the hybrid procedures of CA and LAAC owing to the intention of reducing the procedural time, which may lead to a recurrence of AF. There might be two reasons for insufficient ablation. One is that we aimed to avoid tissue edema of the ridge, which might contribute to the occurrence of the new peri-device leak associated with the combination strategy [17]. However, it remains controversial as to whether a residual leakage can cause adverse cardiac events. The other reason is to reduce the fluoroscopy time and the use of contrast agents. In this prospective study, we corrected the insufficient ablating strategy and improved the clinical outcome. This rescue study confirmed the adverse effects of insufficient ablation in the hybrid procedure. It is worth mentioning that insufficient ablation was unintentional and should be corrected intentionally.
We found that insufficient ablation is common in hybrid procedures of CA and LAAC and may lead to the recurrence of atrial fibrillation. It should be corrected intentionally by sufficient ablation of pulmonary vein antrum and additional ablation.
Several limitations existed in this study. First, this study was a single-center clinical trial for Chinese patients, which may introduce selection bias. Second, the prospective study was not a randomized controlled trial. Therefore, the exact impact of insufficient ablation on AF recurrence may be difficult to assess. Third, the symptoms and quality of life of the patients were not assessed in this study, meaning the clinical effect of insufficient ablation was not evaluated comprehensively. Finally, the present study did not include a functional assessment of left atrial reservoir strain by speckle tracking echocardiography. Literature data suggest that an impaired left atrial reservoir strain has been associated with early AF recurrence after electrical cardioversion [24] and after catheter ablation [25, 26].
The datasets generated and analyzed during this study are not publicly available but are available from the corresponding author on reasonable request. Requests to access the datasets should be directed to Songqun Huang huangsongqun@hotmail.com.
XYD, ZFG and SQH designed the research study. XMH and SQH performed the research. JC and AHQ provided help and advice. YZ collected data. YZ and SHD analyzed the data. All authors contributed to editorial changes in the manuscript. All authors read and approved the final manuscript. All authors have participated sufficiently in the work and agreed to be accountable for all aspects of the work.
The study was conducted in accordance with the Declaration of Helsinki. The study was approved by the institutional review board of Shanghai Changhai Hospital, Second Military Medical University. The ethics approval number is CHEC2020-147. Informed consent was obtained from all subjects involved in the study.
Not applicable.
This study was supported by a grant from the Natural Science Foundation of Shanghai (No.20ZR1456700), the Health Commission of Zhejiang Province (Project No.2022KY508) and National Natural Science Foundation of China (82000283).
The authors declare no conflict of interest.
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