Edited by: Tong Liu, Tianjin Medical University, China
Reviewed by: Deyong Long, Capital Medical University, China; Ohad Ziv, Case Western Reserve University, United States
This article was submitted to Cardiac Rhythmology, a section of the journal Frontiers in Cardiovascular Medicine
†These authors have contributed equally to this work
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Tachycardia-bradycardia syndrome (TBS) is a common clinical arrhythmia used to describe a special subtype of sick sinus syndrome (SSS), with a long pause (RR intervals > 3 s) on termination of atrial fibrillation (AF) (
Previous studies only compared the feasibility and safety between ablation and pacing strategy in TBS patients. Studies showed that >85% of the patients may avoid the pacemaker when ablation for atrial fibrillation was performed. However, the long outcome of ablation for atrial fibrillation superior to pacing is not clear. In our study, we conducted a large-scale retrospective analysis involving 306 patients with TBS with an average follow-up time of 6 years, to evaluate whether catheter ablation improved the long-term outcome of the patients with TBS compared with cardiac pacing.
This single-center retrospective study was approved by the Ethics Committee of the First Affiliated Hospital of Dalian Medical University, Liaoning Province, China. We retrospectively analyzed 1,371 patients undergoing pacemaker implantation and 795 patients underwent catheter ablation due to atrial fibrillation from 2012 to 2017. A total of 306 patients with TBS were ultimately selected, including 165 patients with pacemaker implantation (Pacing group) and 141 patients with catheter ablation (Ablation group).
In this study, TBS diagnosis was in accordance with the diagnostic criteria of BM Kaplan (
Study population and flow chart.
We provided two treatment options and listed the pros and cons to the patient prior to procedure. And then the patient chose one strategy. In the ablation group, the TBS patients were all diagnosed with paroxysmal atrial fibrillation and received pulmonary vein isolation (PVI) only without addition lesion sets as the ablation strategy. The ablation procedures for this group are as described in a previous study (
The primary endpoint of this study was a composite endpoint, consisting of all cause mortality cardiovascular rehospitalization and thromboembolic events. Cardiovascular rehospitalization was defined as patients who were re-hospitalized for cardiovascular diseases, including tachycardia, bradycardia, coronary atherosclerotic heart disease (i.e., angina pectoris and/or myocardial infarction), and heart failure. The definition of thrombotic events referred to the occurrence of stroke and/or peripheral thrombotic events (i.e., pulmonary embolism, mesenteric artery embolism, and lower extremity arterial embolism). The definition of the progression of heart failure, we are mainly concerned with NYHA cardiac function grade and left ventricular enlargement or ejection fraction decrease.
Patients in the ablation group and the pacing group underwent follow-up for an average of 73.2 ± 17.0 months and 77.6 ± 21.3 months, respectively. The follow-ups were completed by a designated follow-up clinic. Patients in the ablation group had follow-ups in the postoperative months 3, 6, and 12, followed by once every 12 months after the operation via telephone and outpatient visit. Patients in the pacing group were followed up by retrospectively reviewing patient pacemaker programmed records, as well as through telephone and outpatient visits. Twenty-four-hour holter or ECG in the ablation group and pacing group were performed to detect the recurrence of AF at 3, 6, and 12 months visit and annually visit during follow up period. Patient data such as symptoms, recurrence of atrial fibrillation, repeated pacing or catheter ablation, usage of medication, rehospitalization occurrence, and the reasons for cardiovascular rehospitalization or thromboembolic events were collected during follow-ups.
The continuous variables are presented as mean ± standard deviation and compared using an independent sample
The clinical characteristics of the patients with TBS are shown in
Characteristics of the study subjects.
Female ( |
162 (52.9%) |
Age (mean ± SD, y) | 62.6 ± 8.6 |
Diabetes ( |
75 (24.5%) |
Hypertension ( |
137 (44.7%) |
Coronary heart disease ( |
61 (19.9%) |
Stroke ( |
5 (1.6%) |
AF duration (Mean ± SD, y) | 4.6 ± 3.4 |
Total heart rate (mean ± SD, beats/24 h) | 91,486 ± 13,341 |
Mean heart rate (mean ± SD, beats/min) | 64.9 ± 8.4 |
Longest pause (mean ± SD, s) | 5.6 ± 2.3 |
Amaurosis ( |
111 (36.2%) |
Syncope ( |
97 (31.7%) |
LAD (mean ± SD, mm) | 38.4 ± 4.18 |
LVD (mean ± SD, mm) | 45.42 ± 4.16 |
LVEF (mean ± SD, %) | 57.7 ± 2.38 |
CHA2DS2-VASc score ( |
1.7 ± 1.1 |
NYHA classification (mean ± SD) | 1.4 ± 0.5 |
Ablation therapy ( |
141(46%) |
Pacing therapy ( |
165(54%) |
Cardiovascular related hospitalization ( |
104 (34.0%) |
Stroke ( |
18 (5.9%) |
Peripheral thrombosis ( |
6 (2.0%) |
Characteristics of the two groups.
Female ( |
75 (53.2%) | 87 (52.7%) | 0.935 |
Age (mean, y) | 62.7 ± 8.8 | 62.4 ± 8.4 | 0.790 |
Diabetes ( |
30 (21.3%) | 45 (27.3%) | 0.224 |
Hypertension ( |
60 (42.6%) | 77 (46.7%) | 0.471 |
Coronary heart disease ( |
24 (17.0%) | 37 (20.6%) | 0.238 |
Stroke ( |
2 (1.4%) | 3 (1.8%) | 0.783 |
Total heart rate (mean ± SD, beats/24 h) | 97,179 ± 16,888 | 89,311 ± 19,422 | 0.030 |
Mean heart rate (mean ± SD, beats/min) | 65 ± 7 | 64 ± 8 | 0.283 |
AF duration (mean ± SD, y) | 4.3 ± 2.96 | 5.0 ± 3.78 | 0.065 |
Longest pause (mean ± SD, s) | 5.2 ± 2.2 | 6.0 ± 2.3 | 0.081 |
Amaurosis ( |
47 (33.3%) | 64 (38.8%) | 0.323 |
Syncope ( |
43 (30.5%) | 54 (32.7%) | 0.676 |
CHA2DS2-VASc score (mean ± SD) | 1.65 ± 1.0 | 1.75 ± 1.2 | 0.469 |
NYHA classification (mean ± SD) | 1.37 ± 0.48 | 1.45 ± 0.49 | 0.130 |
LAD (mean ± SD, mm) | 37.96 ± 3.91 | 38.78 ± 4.37 | 0.086 |
LVD (mean ± SD, mm) | 45.18 ± 3.86 | 45.45 ± 4.05 | 0.553 |
LVEF (mean ± SD, %) | 57.95 ± 2.58 | 57.52 ± 2.17 | 0.116 |
After an average follow-up of 75.5 ± 19.1 months, 116 patients (82.3%) in the ablation group maintained sinus rhythm. In addition, 16 patients (11.4%) in the ablation group had pacemaker implantation due to recurrence of atrial fibrillation with long pauses, and another 6 patients (4.3%) in the ablation group had recurring atrial fibrillation, but no long pauses and without pacemaker implantation. In the pacing group, only 31 patients (18.8%) maintained sinus rhythm, and 8 patients (4.8%) received ablation. Compared with the ablation group, more patients in the pacing group progressed to persistent atrial fibrillation [39 (23.6%) vs. 3 (2.1%),
Comparison of therapeutic results between ablation group and pacing group.
Amaurosis ( |
9 (6.3%) | 0 | NS |
Syncope ( |
7 (4.9%) | 0 | NS |
Freedom from AF ( |
116 (82.3%) | 31 (18.8%) | <0.001 |
AF progression ( |
3 (2.1%) | 39 (23.6%) | <0.001 |
Heart failure progression ( |
4 (2.8%) | 18 (10.9%) | 0.006 |
NYHA class (mean ± SD) | 1.50 ± 0.74 | 2.11 ± 0.83 | <0.001 |
AADs use ( |
10 (7.1%) | 68 (41.2%) | <0.001 |
Anticoagulation ( |
3 (2.1%) | 27 (16.4%) | <0.001 |
Crossover therapy | 16 | 8 | 0.035 |
Pacemaker implement ( |
16 (11.3%) | – | NS |
Cather ablation ( |
– | 8 (4.8%) | NS |
Operation complications ( |
2 (1.4%) | 4 (2.4%) | 0.527 |
Compared with the ablation group, the pacing group had a higher incidence of the primary study endpoint (59.4 vs.14.2%, OR 6.05, 95% CI: 3.73–9.80,
Comparison of the primary end point between ablation group and pacing group.
Primary end point | 20 (14.2%) | 98 (59.4%) | 6.05 (3.73–9.80) | <0.001 | <0.001 |
All-cause mortality | 0 (0%) | 1 (0.6%) | NS | NS | NS |
Cardiovascular related hospitalization | 20 (14.2%) | 84 (50.9%) | 4.87 (2.99–7.95) | <0.001 | <0.001 |
Thrombosis events | 3 (2.1%) | 21 (12.7%) | 6.06 (1.81–20.35) | 0.001 | 0.009 |
Stroke | 3 (2.1%) | 15 (9.1%) | 4.60 (1.30–16.23) | 0.010 | – |
Peripheral thrombosis | 0 (0.0%) | 6 (3.6%) | NS | 0.022 | – |
Kaplan–Meier curves comparing probability of the primary end point. Month 0 is the time of the baseline visit. The panel shows the probability of composite end events (cardiovascular related hospitalization or thrombosis events).
Kaplan–Meier curves comparing probability of cardiovascular related hospitalization. Month 0 is the time of the baseline visit.
Kaplan–Meier curves comparing probability of thrombosis events. Month 0 is the time of the baseline visit.
This large-scale retrospective study involved 306 patients with TBS, including 141 patients in the ablation group and 165 patients in the pacing group, with an average follow-up of nearly 6 years. The use of ablation for atrial fibrillation in TBS patients was associated with a significantly lower rate of a composite of cardiovascular hospitalization and thrombosis than pacing therapy. Furthermore, catheter ablation reduced the progression of atrial fibrillation and heart failure. To our knowledge, this study was the first to compare the effects of catheter ablation and cardiac pacing on the long-term prognosis in TBS patients, TBS patients may be benefit from ablation therapy vs. pacing therapy.
Kaplan and Langendorf were the first to describe TBS in 1973 (
Numerous studies have confirmed that catheter ablation is an effective and safe method for treating paroxysmal atrial fibrillation, with a success rate of >82% in >5 years (
Cardiovascular related hospitalization, thromboembolic events, and heart failure progression are essential endpoints for evaluating the prognosis of TBS patients. However, few studies have evaluated the hard endpoints of catheter ablation vs. pacing in patients with TBS. Chen et al. (
This was a retrospective study, so the clinical evidence level is low, and a prospective randomized controlled study is needed to verify our findings. TBS patients in the pacing group had a higher proportion of anticoagulation but inadequate, suggesting that an increase in anticoagulation rate may effectively reduce the incidence of thromboembolic events in the pacing group. Lower use of anticoagulation in the entire group may limit the applicability of the data. Adequate use of anticoagulation in TBS patients may reduce the difference of the prognosis between the two therapy strategies. In our series these patients had relatively normal left atrial size. This data may not be applicable to patients with moderate or severely dilated left atria. Additionally, there may have been a selection bias during the selection of treatment strategies in this retrospective study.
The original contributions presented in the study are included in the article/supplementary material, further inquiries can be directed to the corresponding author/s.
The studies involving human participants were reviewed and approved by the ethics committee of First Affiliated Hospital of Dalian Medical University. Written informed consent for participation was not required for this study in accordance with the national legislation and the institutional requirements.
YX, LG, and XYi contributed to conception and design of the study. YW, ZW, and MY organized the database. XYu and XX performed the statistical analysis. YW wrote the first draft of the manuscript. RZ wrote sections of the manuscript. All authors contributed to manuscript revision, read, and approved the submitted version.
The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The handling editor declared a past co-authorship with one of the authors YX.
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Area-under-the-curve
Confidential interval
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New oral anticoagulants
New York Heart Association
Tachycardia-bradycardia syndrome
vitamin K.