Abstract
Background
Immediate recurrence of atrial fibrillation (AF) after radiofrequency (RF) catheter ablation is commonly observed within 3 d after the procedure. The mechanism and pharmacological management of immediate AF recurrence remain unclear.
Methods
A total of 50 consecutive patients with paroxysmal AF were randomized to receive either low-dose landiolol (landiolol group) or a placebo (placebo group). In the landiolol group, intravenous landiolol (0.5 μg kg−1 min−1) was administered for 3 d after AF ablation.
Results
No serious adverse event associated with RF catheter ablation or landiolol administration was observed. The prevalence of immediate AF recurrence (≤3 d after RF catheter ablation) was significantly lower in the landiolol group than in the placebo group (16% vs. 48%, p=0.015). Although the postprocedural change in heart rate was significantly lower in the landiolol group compared to that in the placebo group, the changes in blood pressure and body temperature were not different between the two groups. Multiple logistic regression analysis revealed that landiolol treatment was the only independent predictor of immediate AF recurrence after ablation (odds ratio: 0.180; 95% confidence interval: 0.044–0.729; p=0.016).
Conclusions
Prophylactic administration of low-dose landiolol after AF ablation may be effective and safe for preventing immediate AF recurrence within 3 d after AF ablation.
Keywords: Atrial fibrillation, Landiolol, Catheter ablation, Immediate recurrence
1. Introduction
Radiofrequency (RF) catheter ablation is becoming an effective therapy for drug-resistant atrial fibrillation (AF) [1]. However, the rate of AF recurrence after successful RF catheter ablation remains relatively high [2], and recurrences are common within 3 d after the procedure [3,4]. Immediate AF recurrence interferes with postprocedural management, prolongs hospital stays, and increases healthcare costs. However, immediate pharmacological management after AF ablation is often difficult because of a lack of drugs with both good efficacy and dose adjustability. Therefore, a new treatment strategy is needed for preventing immediate AF recurrence after ablation.
Although there is considerable evidence for a mechanistic link between cardiac sympathetic nervous dysfunction and the development of AF [5,6], it is not clear whether sympathetic nerve activity is related to immediate AF recurrence after catheter ablation. As left atrial (LA) ganglionated plexi is present in the vicinity of the pulmonary vein (PV), RF energy applications around the PV affect sympathetic nervous activation [7] and may be associated with immediate AF recurrence after catheter ablation. Several recent studies have described the efficacy of landiolol hydrochloride, an ultra-short-acting beta adrenoceptor antagonist, for the prevention of AF after open-heart surgery [8–11]. It has mainly been used to treat AF after cardiovascular surgery. Because of its extremely short half-life (4 min) and high β1 selectivity, landiolol may also be useful for controlling AF after RF catheter ablation without major side effects. At low doses, landiolol exerts a clinically relevant negative chronotropic effect without negative inotropic effects [11–14]. Accordingly, the purpose of the present study was to investigate the prophylactic effect of continuous low-dose landiolol administration against immediate AF recurrence after catheter ablation.
2. Methods
2.1. Patients
This study included 50 consecutive patients with symptomatic, drug-resistant, non-valvular paroxysmal AF who underwent RF catheter ablation at Yamagata University Hospital (Table 1). All patients had symptomatic, paroxysmal AF, which was defined as AF episodes that spontaneously terminated and lasted for >30 s and <7 d during treatment with antiarrhythmic drugs (AADs). All AADs were discontinued five half-lives before AF ablation with the exception of amiodarone, which was discontinued at least 6 weeks before the RF procedure. Patients who were treated with oral β-blockers, angiotensin-converting enzyme (ACE) inhibitors, angiotensin receptor blockers (ARBs), and/or statins at study enrollment continued to take these drugs with no change in dose until the end of AF ablation. Ethical approval was obtained from the institutional review committee (approval date, February 15, 2010; approval number, 148), and all patients gave their informed, written consent before participation.
Table 1.
Baseline patient characteristics.
| All patients (n=50) | Placebo group (n=25) | Landiolol group (n=25) | p-Value | |
|---|---|---|---|---|
| Age, years | 58±9 | 59±10 | 57±8 | 0.193 |
| Male gender, n (%) | 39 (78) | 21 (84) | 18 (72) | 0.306 |
| Systolic blood pressure, mmHg | 118±14 | 119±12 | 117±16 | 0.593 |
| Diastolic blood pressure, mmHg | 72±10 | 72±9 | 72±11 | 0.855 |
| Heart rate, bpm | 64±9 | 62±11 | 66±8 | 0.148 |
| Duration of AF history, months (IQR) | 38 (19–88) | 35 (10–69) | 39 (23–101) | 0.218 |
| CHADS2 score, 0/1/2 | 25/21/4 | 16/8/1 | 9/13/3 | 0.126 |
| Structural heart disease | 8 (16) | 3 (12) | 5 (20) | 0.700 |
| Hypertension, n (%) | 22 (44) | 11 (44) | 11 (44) | 1.000 |
| Diabetes mellitus, n (%) | 4 (8) | 1 (4) | 3 (12) | 0.602 |
| TIA/stroke, n (%) | 0 (0) | 0 (0) | 0 (0) | – |
| Dyslipidemia, n (%) | 22 (44) | 13 (52) | 9 (36) | 0.255 |
| Medications | ||||
| ACE inhibitors or ARBs, n (%) | 14 (28) | 6 (24) | 8 (32) | 0.529 |
| Oral β-blocker, n (%) | 22 (44) | 10 (40) | 12 (48) | 0.569 |
| Statin, n (%) | 10 (20) | 4 (16) | 6 (24) | 0.724 |
| Ineffective AADs | ||||
| Number of ineffective AADs (IQR) | 3 (1–3) | 2 (1–3) | 3 (2–3) | 0.337 |
| Class I, n (%) | 45 (90) | 24 (96) | 21 (84) | 0.346 |
| Amiodarone, n, (%) | 8 (16) | 1 (4) | 7 (28) | 0.054 |
| Bepridil, n (%) | 13 (26) | 6 (24) | 7 (28) | 0.747 |
| Laboratory data | ||||
| eGFR, mL/min·1.73 cm2 | 78±16 | 80±14 | 77±17 | 0.492 |
| hsCRP, mg/dL (IQR) | 0.041 (0.027–0.077) | 0.034 (0.024–0.055) | 0.056 (0.029–0.090) | 0.140 |
| BNP, pg/mL (IQR) | 34 (15–50) | 25 (14–48) | 37 (22–66) | 0.048 |
| Echocardiographic parameters | ||||
| LA diameter, mm | 39±6 | 39±6 | 39±6 | 1.000 |
| LV end-diastolic dimension, mm | 50±5 | 49±4 | 50±5 | 0.749 |
| LV ejection fraction, % | 64±7 | 64±6 | 64±9 | 0.969 |
| RF catheter ablation | ||||
| Fluoroscopy time, min | 87±28 | 80±21 | 96±32 | 0.054 |
| Procedure time, min | 233±48 | 241±50 | 224±46 | 0.221 |
| CTI blockline, n (%) | 14 (28) | 8 (32) | 6 (24) | 0.529 |
| CFAE ablation, n (%) | 13 (26) | 8 (32) | 5 (20) | 0.333 |
Data are presented as mean±standard deviation. AAD, antiarrhythmic drug; ACE, angiotensin converting enzyme; AF, atrial fibrillation; ARB, angiotensin receptor blocker; BNP, B-type natriuretic peptide; CHADS2, congestive heart failure; hypertension; age ≥75; diabetes mellitus; prior stroke, transient ischemic attack, or thromboembolism; CFAE, complex fractionated atrial electrogram; CTI, cavotricuspid isthmus; eGFR, estimated glomerular filtration rate; hsCRP, high-sensitivity C-reactive protein; IQR, interquartile range; LA, left atrium; LV, left ventricle; RF, radiofrequency; TIA, transient ischemic attack.
2.2. Study protocol
This study was designed as a prospective, randomized, single blind study. All patients were equally randomized for treatment with landiolol (landiolol group) or a placebo (placebo group) on the first day of their hospitalization. In the landiolol group, 1 mg/mL of landiolol hydrochloride (Onoact, Ono Pharmaceutical Co., Osaka, Japan) in a 0.9% sodium chloride solution was administrated intravenously (0.5 μg kg−1 min−1) for 3 d immediately after catheter ablation [15]. A placebo solution (0.9% sodium chloride) was intravenously administered to patients in the placebo group. All patients remained hospitalized under continuous rhythm monitoring from admission to discharge. Immediate AF recurrence was defined as AF or atrial tachycardia (AT) lasting >5 min [10]. The primary end points of the study were the proportion of patients who were free of recurrent AF/AT in the 3 d immediately after catheter ablation and any serious complications caused by catheter ablation or landiolol treatment.
2.3. RF catheter ablation
Extensive PV isolation was performed with 3-dimensional mapping (CARTO®, Biosense Webster Inc., USA). After transseptal catheterization, a 7-Fr 10-polar ring catheter (Lasso, Biosense Webster, Inc., Diamond Bar, CA, USA) and a 7-Fr quadripolar ablation catheter with a 3.5-mm distal electrode and deflectable tip (ThermoCool, Biosense Webster) were positioned in the LA. Intravenous heparin was given to maintain an activated clotting time of 300–350 s during the entire procedure. After selective PV angiography, a single Lasso catheter was then positioned inside the PV within 5 mm of the ostium to map PV potentials. RF energy was delivered using the temperature control mode with a target temperature of 42 °C and a maximum power output of 25–35 W. The endpoint of extensive PV isolation was the creation of an extensive ipsilateral bidirectional conduction block, which was confirmed from the atrium to the PV and vice versa. In addition, the bidirectional conduction block was reconfirmed at least 60 min after successful PV isolation [6]. After PV isolation, if AF was sustained or induced with coronary sinus (CS) burst pacing at a cycle length up to 200 ms and lasted >3 min [6,16], RF catheter ablation targeting for complex fractionated atrial electrogram (CFAE) was added. If AF did not terminate or was inducible after these procedures, sinus rhythm was restored by transthoracic cardioversion. A cavotricuspid isthmus (CTI) block line was created in patients with coexistence of an atrial flutter with a confirmed bidirectional block.
2.4. Heart rate, blood pressure, body temperature and C-reactive protein
The patients׳ heart rates, blood pressures, and body temperatures were measured every 8 h during the four consecutive days before and after RF catheter ablation. The changes in heart rate, blood pressure, and body temperature were defined as the difference in values between baseline and during the 3 d after ablation. The change in C-reactive protein (CRP) level was also measured as the difference in CRP 1 d before and 1 d after AF ablation.
2.5. Mid-term follow-up
Patients remained hospitalized under continuous rhythm monitoring for at least 3 d after the procedure, and were followed for at least 12 months after AF ablation. After discharge, all patients were seen in our hospital, at the outpatient arrhythmia clinic, or by their referring physician at 2 weeks and 1 month, and then every 3 months thereafter. At each hospital visit, the patients underwent 12-lead electrocardiography and intensive questioning regarding any arrhythmia-related symptoms. Holter electrocardiography and portable electrocardiographic monitoring (HCG-901, OMRON, Kyoto, Japan) were performed for any patient reporting symptoms suggesting recurrent arrhythmia. Telephone interviews were also carried out for all patients at the end of follow-up. If the electrocardiogram showed any AF episodes during follow-up, patients received a diagnosis of clinical recurrence of AF, irrespective of the presence of symptoms. Repeat ablation was not performed in any of the patients during the study period.
2.6. Statistical analysis
Continuous variables were expressed as means±standard deviation. Skewed variables were presented as medians with interquartile ranges. We employed Student׳s t-test and the chi-square test to compare continuous and categorical variables, respectively. When the data were not normally distributed, the Mann–Whitney U test was used. Univariate analysis with logistic regression analysis was used to identify significant predictors of immediate AF recurrence within 3 d of RF catheter ablation. All parameters with p<0.10 in the univariate analysis were entered into the multivariable analysis. AF-free curves were constructed based on the Kaplan–Meier method and compared using log-rank tests. A p-value <0.05 was considered statistically significant.
3. Results
3.1. Baseline characteristics
The baseline characteristics of the study group are summarized in Table 1. The mean patient age was 58±9 years, and the majority was male (78%). Overall, 22 (44%), four (8%), and 22 (44%) patients had hypertension, diabetes mellitus, and dyslipidemia, respectively, and these rates did not differ between the two groups. Baseline blood pressure, heart rate, and duration of AF history were not different between the two groups. CHADS2 (congestive heart failure; hypertension; age≥75; diabetes mellitus; prior stroke, transient ischemic attack, or thromboembolism) scores were also not significantly different between the two groups. Neither prior stroke nor transient ischemic attack was observed in the present study. Although no differences were found for medications or the number of ineffective AADs, patients in the landiolol group tended to receive amiodarone more frequently (p=0.054). The plasma level of brain natriuretic peptide was slightly higher in the landiolol group than in the placebo group (p=0.048). LA diameter, left ventricular end-diastolic dimension, and left ventricular ejection fraction were not different between the two groups.
3.2. RF catheter ablation
Extensive PV isolation was achieved in all patients. The creation of a bidirectional block line at the CTI and RF catheter ablation targeting for CFAE were performed in 14 (28%) and 13 (26%) patients, respectively. The mean fluoroscopy and procedure times were 87±28 min and 233±48 min, respectively.
3.3. Immediate AF recurrence within 3 d after ablation
The patients remained hospitalized under continuous rhythm monitoring for at least 3 d after the procedure. No patients experienced adverse events attributable to landiolol administration such as bradycardia, hypotension, or liver dysfunction. During the 3 d after ablation, AF recurrences were less frequently observed in the landiolol group than in the placebo group (16% [4/25] vs. 48% [12/25], p=0.015; Fig. 1A). Among patients who did not receive oral β-blockers, AF recurrences were also less frequently observed in the landiolol group than in the placebo group (8% [1/13] vs. 47% [7/15], p=0.023; Fig. 1B). Although AF recurrences tended to be less frequently observed in the patients in the landiolol group who took oral β-blockers compared to the patients in the placebo group on oral β-blockers, this difference was statistically insignificant (25% [3/12] vs. 50% [5/10], p=0.225; Fig. 1C).
Fig. 1.
Prevalence of atrial fibrillation (AF) recurrence within 3 d of catheter ablation. Recurrence was defined as AF or atrial tachycardia lasting longer than 5 min. (A) All patients. (B) Patients not taking oral β-blockers. (C) Patients taking oral β-blockers.
3.4. Change in heart rate, blood pressure, body temperature, and CRP levels
Although heart rate elevation after RF catheter ablation was significantly lower in the landiolol group than in the placebo group (Fig. 2), the changes in blood pressure and body temperature before and after AF ablation were not significantly different between the two groups (Figs. 3 and 4). The change in CRP level was also not different between the landiolol group and the placebo group (Fig. 5).
Fig. 2.
(A) Mean heart rate during the study period. (B) Change in heart rate between baseline and the initial 3 d after catheter ablation.
Fig. 3.
(A) Mean blood pressure during study period. (B) Change in blood pressure between baseline and the initial 3 d after catheter ablation.
Fig. 4.
(A) Mean body temperature during the study period. (B) Change in body temperature between baseline and the initial 3 d after catheter ablation.
Fig. 5.
Change of C-reactive protein level between baseline and 1 d after catheter ablation.
3.5. Predictors of immediate AF recurrence after ablation
Univariate logistic regression analysis revealed that landiolol treatment was the only predictor of immediate AF recurrence after ablation (odds ratio [OR]: 0.206, 95% confidence interval [CI]: 0.055–0.777, p=0.020). Multivariate logistic regression analysis, including factors with significance <0.10 by univariate analysis, revealed that landiolol treatment was the only independent factor affecting the prevention of immediate AF recurrence after ablation (OR: 0.180, 95% CI: 0.044–0.729, p=0.016; Table 2).
Table 2.
Univariate and multivariate analyses of immediate AF recurrence after catheter ablation.
| Odds ratio | 95% Confidence interval | p-Value | |
|---|---|---|---|
| Univariate analysis | |||
| Age, per 1 year increase | 1.013 | 0.946–1.086 | 0.705 |
| Male | 0.778 | 0.191–3.167 | 0.726 |
| Duration of AF history, per 1 month increase | 1.003 | 0.992–1.014 | 0.594 |
| CHADS2 score, per 1 point increase | 0.436 | 0.151–1.261 | 0.126 |
| Presence of | |||
| Structural heart disease | 0.257 | 0.029–2.294 | 0.224 |
| Hypertension | 0.296 | 0.079–1.106 | 0.070 |
| Diabetes mellitus | 0.689 | 0.066–7.192 | 0.756 |
| Dyslipidemia | 1.429 | 0.433–4.717 | 0.558 |
| Use of | |||
| ACE inhibitors or ARBs | 0.262 | 0.051–1.350 | 0.109 |
| Oral β-blocker | 1.429 | 0.433–4.718 | 0.558 |
| Statin | 0.890 | 0.197–4.012 | 0.880 |
| AADs, per 1 drug increase | 1.401 | 0.905–2.168 | 0.131 |
| Amiodarone | 0.257 | 0.029–2.294 | 0.224 |
| Bepridil | 2.314 | 0.625–8.575 | 0.209 |
| Laboratory data | |||
| eGFR, per SD (15.6 mL/min 1.73 cm2) increase | 1.013 | 0.693–2.305 | 0.431 |
| CRP before ablation, per SD (0.14 mg/dL) increase | 0.711 | 0.290–1.749 | 0.457 |
| CRP after ablation, per SD (0.59 mg/dL) increase | 0.632 | 0.282–1.419 | 0.267 |
| BNP, per SD (46.2 pg/mL) increase | 0.562 | 0.227–1.393 | 0.212 |
| Echocardiographic parameters | |||
| LA diameter, per SD (5.9 mm) increase | 1.027 | 0.563–1.871 | 0.932 |
| LV end-diastolic dimension, per SD (4.8 mm) increase | 0.729 | 0.388–1.368 | 0.325 |
| LV ejection fraction, per SD (7.2%) increase | 0.597 | 0.318–1.121 | 0.109 |
| RF catheter ablation | |||
| Procedure time, per 1 min increase | 1.002 | 0.990–1.015 | 0.748 |
| CFAE ablation | 1.477 | 0.394–5.536 | 0.563 |
| Others | |||
| Landiolol treatment | 0.206 | 0.055–0.777 | 0.020 |
| Change of systolic BP, per 1 mmHg increase | 0.966 | 0.905–1.030 | 0.289 |
| Change of diastolic BP, per 1 mmHg increase | 0.991 | 0.926–1.062 | 0.807 |
| Change of heart rate, per 1 bpm increase | 0.988 | 0.933–1.046 | 0.674 |
| Change of CRP, 1 mg/dL increase | 0.644 | 0.201–2.059 | 0.458 |
| Multivariate analysis | |||
| Hypertension | 0.249 | 0.060–1.032 | 0.055 |
| Landiolol treatment | 0.180 | 0.044–0.729 | 0.016 |
AAD, antiarrhythmic drug; ACE, angiotensin-converting enzyme; AF, atrial fibrillation; ARB, angiotensin receptor blocker; BNP, B-type natriuretic peptide; BP, blood pressure; CHADS2, congestive heart failure; hypertension; age ≥75; diabetes mellitus; prior stroke, transient ischemic attack, or thromboembolism; CFAE, complex fractionated atrial electrogram; CRP, C-reactive protein; CTI, cavotricuspid isthmus; eGFR, estimated glomerular filtration rate; LA, left atrium; LV, left ventricle; RF, radiofrequency; TIA, transient ischemic attack.
3.6. Mid-term follow-up after ablation
After a 3-month blanking period, β-blockers and AADs were discontinued in all patients. During a median 15-month follow-up after RF catheter ablation (range, 12–50.8 months), AF recurrences were confirmed in 13 patients (52%) in the placebo group and nine patients (36%) in the landiolol group. The AF-free rate post-ablation tended to be greater in the landiolol group than in the placebo group (p=0.126). No AT or serious complication was noted for any of the patients.
4. Discussion
The results of this study demonstrate that (1) low-dose landiolol (0.5 μg kg−1 min−1) prevent heart rate elevation after AF ablation; (2) prophylactic administration of low-dose landiolol successfully prevented immediate AF recurrence within 3 d after AF ablation without any adverse effects.
RF energy applications to the LA evoke an inflammatory response, which can cause subsequent AF recurrence shortly after AF ablation. Oral et al. performed PV isolation in 110 consecutive AF patients, and found that early AF recurrence occurred in 35% of patients at a mean of 3.7±3.5 d after the procedure. The recurrence of AF was most frequently observed within 3 d of the procedure in approximately 70% of cases [3]. The transient use of small amounts of corticosteroids, such as intravenous hydrocortisone the day of the procedure and oral prednisolone for 3 d afterward, was reported to prevent immediate AF recurrences [16]. Recently, anti-inflammatory treatment by colchicine to reduce early recurrences after AF ablation was reported by Deftereos et al. [17]. These effects seem to be associated with decreased levels of inflammatory mediators, including body temperature, CRP, and interleukin-6 levels. Earlier reports demonstrated that relatively high-dose landiolol (2–5 μg kg−1 min−1) exerted an anti-inflammatory effect and could prevent AF after cardiac surgery [8,9]. Even though low-dose landiolol (0.5 μg kg−1 min−1) did not suppress CRP levels after AF ablation, AF recurrence was less frequent in the landiolol group. Landiolol may be superior to corticosteroids and colchicine for the prevention of immediate AF recurrence. Corticosteroids cause several side effects such as infections, rise in blood glucose level, and gastric ulcer. In particular, upper gastrointestinal side effects are a common risk in patients after AF ablation [18]. In addition, compared with oral anti-inflammatory drugs, landiolol is safer when side effects occur. Intravenously administered landiolol has an extremely short half-life (4 min) compared with oral drugs.
Cardiac sympathetic nerve over-activity is also associated with AF occurrence after cardiac surgery [19]. Sympathetic nerve disintegrity enhances automaticity or triggered activity, stimulating the fibrillation process, and shortens atrial refractoriness in a non-uniform fashion that favors AF perpetuation [19]. High washout rate of iodine-123-metaiodobenzylguanidine imaging and enhanced cardiac sympathetic tone were independently associated with AF recurrence after catheter ablation [6]. Landiolol suppresses the postprocedural heart rate and AF onset without lowering CRP levels, which suggests that controlling excessive sympathetic activity might be the most plausible reason for the effectiveness of landiolol in the present study. We administered a low-dose infusion of landiolol (0.5 μg kg−1 min−1) [15] at a rate lower than those described in other studies to minimize the incidence of side effects. Fujiwara et al. reported that infusion of landiolol (1.5–2.5 μg kg−1 min−1) for 2 d after coronary artery bypass grafting had a preventive effect on the appearance of AF without suppressing cardiac function [10]. In a study published by Sezai et al., administration of landiolol at 2 μg kg−1 min−1 from the time of central anastomosis during coronary artery bypass grafting and for 2 subsequent days was associated with a lower incidence of AF [8]. Because RF catheter ablation is a relatively non-invasive procedure, low-dose landiolol may have been effective for preventing immediate AF recurrence. Interestingly, our subgroup analysis revealed that landiolol was more effective among patients not taking oral β-blockers compared to those taking oral β-blockers. Prophylactic low-dose landiolol therapy may be more suitable for patients not taking oral β-blockers. In addition, none of the patients developed hypotension or bradycardia, indicating the safety of low-dose landiolol administration after AF ablation.
A previous study reported that patients with early AF recurrences were significantly less likely to have long-term freedom from recurrent AF than patients without early recurrences [3]. In the present study, landiolol administration tended to improve the mid-term prognosis compared to placebo. In a previous study, corticosteroid administration shortly after AF ablation effectively prevented AF recurrences immediately after ablation and during a 14-month follow-up period [16]. Electrical remodeling (shortening of atrial refractoriness) proceeds within a few days of AF and contributes to increased AF stability, whereas reverse remodeling after the restoration of sinus rhythm occurs much more slowly [20]. A longer AF-free period after AF ablation might have enabled the atria to inhibit electrical, contractile, and structural remodeling and facilitated reverse remodeling, resulting in a greater AF-free rate during the mid-term follow-up period. It is possible that sympathetic activity control immediately after RF application may be important for long-term AF prevention, but the underlying mechanism remains unclear.
This study has several limitations. First, the amount of landiolol administered in this study was lower than that in previous reports. High-dose landiolol administration may have anti-inflammatory activity and may exert more preventative effects compared to low-dose landiolol. Second, the preventive value of oral β-blocker use was not investigated in the present study. Recent reports showed that the selective β1 receptor antagonist bisoprolol is more effective than carvedilol in decreasing the incidence of AF after coronary artery bypass grafting [21] and severe heart failure [22]. β1-Selective oral antagonist administration may also suppress immediate AF recurrence after catheter ablation. Finally, landiolol administration tended to improve the mid-term prognosis compared to placebo in the present study. If this study included many more subjects, the preventative effect of landiolol might have been confirmed during mid-term follow up.
5. Conclusion
Prophylactic low-dose landiolol (0.5 μg kg−1min−1) therapy within 3 d of RF catheter ablation is effective and safe for preventing immediate AF recurrence within 3 d after AF ablation. This result indicated the relationship between sympathetic nervous activity and immediate AF recurrence after catheter ablation.
Conflict of interest
None.
Acknowledgments
This research was supported, in part, by a grant-in-aid for Scientific Research (No. 25461039) from the Ministry of Education, Culture, Sports, Science, and Technology of Japan.
Footnotes
Supplementary data associated with this article can be found in the online version at doi:10.1016/j.joa.2015.02.003.
Appendix A. Supporting information
Supplementary data
References
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