Cryoballoon vs. Robotic Magnetic Navigation-Guided Radiofrequency Ablation in Patients with Persistent Atrial Fibrillation: 5-year outcomes

doi:10.21203/rs.3.rs-5163855/v1

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Cryoballoon vs. Robotic Magnetic Navigation-Guided Radiofrequency Ablation in Patients with Persistent Atrial Fibrillation: 5-year outcomes

https://doi.org/10.21203/rs.3.rs-5163855/v1

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Background

This study aimed to evaluate the long-term efficacy and clinical outcomes of catheter ablation performed with cryoballoon (CRYO) in comparison with robotic magnetic navigation (RMN) in patients with persistent atrial fibrillation (PersAF).

Methods and Results

A total of 200 patients with symptomatic PersAF were prospectively enrolled and assigned (1:1) to the CRYO or RMN guided-ablation group and then followed up over 5 years. The primary endpoint was freedom from atrial tachyarrhythmias (ATs) recurrence following a 3-month blanking period after the initial procedure. The secondary endpoints consisted of all-cause and cardiovascular rehospitalizations, rates of electrical cardioversions (ECs) and repeat ablations, new-onset neurological events, major bleeding events and the difference in CHA₂DS₂-VASc score at 5-year compared with baseline. After a median follow-up period of 60 months, 184 patients (93 in RMN, 91 in CRYO) completed the follow-up. Freedom from recurrent ATs was achieved in 44 out of 93 patients in the RMN group and 37 out of 91 patients in the CRYO group (47.3% vs. 40.7%, P = 0.32). There were no significant differences in the risk of all-cause and cardiovascular rehospitalizations, rates of ECs and repeat ablations, new-onset neurological events, and major bleeding at 5 years. OAC discontinuation was relatively common after ablation, 48.4% of patients with a CHA₂DS₂-VASc score ≥ 2 not on OAC therapy.

Conclusion

CRYO is comparable to RMN-guided ablation with respect to long-term freedom from ATs in patients with PersAF. Discontinuation of OAC after ablation is not rare even in patients at risk of stroke for continued OAC therapy.

Health sciences/Cardiology

Health sciences/Cardiology/Interventional cardiology

Health sciences/Diseases/Cardiovascular diseases

Health sciences/Diseases/Cardiovascular diseases/Arrhythmias/Atrial fibrillation

Atrial fibrillation

Catheter ablation

Cryoballoon

Long-term

Robotic magnetic navigation

Atrial fibrillation (AF) is the most prevalent arrhythmia in clinical practice, and is associated with the increasing occurrence of thromboembolisms, heart failure (HF) and mortality¹. Catheter ablation of AF has been demonstrated to be superior to antiarrhythmic drugs (AADs) in maintaining sinus rhythm on a mid- to long-term basis^2,3. Both cryoballoon (CRYO) and radiofrequency (RF) ablation are in routine clinical use for not only paroxysmal AF (PAF) but also persistent AF (PersAF) worldwide^4,5. A majority of studies have suggested that robotic magnetic navigation (RMN)-guided ablation for AF has similar success rate to that of the conventional manual technique, but with a reduced risk of major procedural complications^6–10. Randomized controlled trials have shown that CRYO ablation is noninferior to manual RF ablation regarding efficacy and clinical outcomes for PAF^11–13. Some studies have demonstrated a comparable efficacy between CRYO and RF ablation of PersAF with a relatively limited follow-up period^14–16. However, based on the available data, little is known about the long-term efficacy of CRYO ablation on AF recurrence compared to that using RMN for the treatment of PersAF. Our previous study reported that CRYO is equivalent to RMN-guided ablation with regard to AF freedom in PersAF patients at mid-term follow-up¹⁷. Hence, the aim of this sequential study was to compare the long-term efficacy of CRYO with RMN-guided ablation in PersAF patients at 5 years follow-up, as well as the long-term clinical outcomes, including all-cause and cardiovascular hospitalization, new-onset cardiovascular and neurological events, major bleeding and the change in CHA₂DS₂-VASc score. Furthermore, we evaluated the patterns of OAC use in patients after AF ablation.

2.1 Study design

The trial was a single-center, prospective, non-randomized and concurrent controlled study that compared the long-term efficacy and clinical outcomes of CRYO to RMN-guided ablation in patients with PersAF at a 5-year follow-up. The study design and full inclusion/exclusion criteria have been described in detail in our previous study¹⁷. All participating patients provided written informed consent. This study was approved by the ethics committee of our institution, in accordance with the principles of the Declaration of Helsinki. In brief, eligible patients were enrolled from June 2016 through October 2019 and assigned 1:1 to RMN-guided or CRYO ablation groups to undergo AF catheter ablation. Patients assigned to the RMN group underwent circumferential pulmonary vein isolation (PVI) guided by a 3-D mapping system (CARTO 3, Biosense Webster, USA) and the RMN Niobe ES system (Stereotaxis Inc., USA) using an irrigated RF ablation catheter (Navistar RMT ThermoCool, Biosense Webster, USA). Circumferential ablation lesions were delivered around each of the pulmonary vein (PV) ostia until each vein was electrically isolated to achieved bidirectional conduction block in all PVs. Patients assigned to the CRYO group underwent PVI using a second-generation 23- or 28- mm cryoballoon (Medtronic, USA) guided by a 3-D mapping system (Ensite system, Abbott, USA). The balloon was placed at each PV until it was occluded, and then the tissue was cooled until conduction block was achieved. A single “bonus” freeze was delivered to each vein following the rewarming phase of the successful lesion. An electrical PVI and bidirectional block was confirmed with the Achieve catheter (Medtronic, USA). If AF organized into atrial tachycardia or flutter, a combination of activation and entrainment mapping was performed with targeted ablation as necessary with a Freezor Max (Medtronic, USA) or RF catheter in both groups. All patients were followed for 5 years after the ablation procedure.

2.2 Primary and secondary endpoints

The primary endpoint of the study was the freedom from any documented atrial tachyarrhythmias (ATs), including AF, atrial flutter (AFL), and atrial tachycardia lasting ≥ 30 seconds after a 3-month blanking period at 5 years after the initial ablation procedure. The key secondary endpoints were defined as all-cause and cardiovascular rehospitalizations, rates of EC and repeat ablation, new-onset neurological events, major bleeding events and the difference in CHA₂DS₂-VASc score at 5-year compared with baseline.

2.3 Follow-up and data collection

After the index procedure, patients were discharged on AADs, together with OAC. OAC was continued for at least 3 months after ablation, then re-evaluated in the fourth month, and the continuation of OAC was decided based on their rhythm and CHA₂DS₂-VASc score according to current guidelines. Class I/III AADs (including propafenone, amiodarone and sotalol) were maintained for 3 months and thereafter withdrawn if free from arrhythmia-related symptoms. Patients were observed for routine follow-up at 1 and 3 months, and then every 3 to 6 months (or earlier, if symptoms occurred) during the first year after ablation. Then, clinical appointments were scheduled every 6 months. Study visits included a medical history, physical examination, 12-lead electrocardiogram, and 24-hour Holter recordings. Clinical events occurring during the follow-up were recorded and evaluated. In addition, ambulatory electrograms were recorded when the patient had any symptoms during the study period. The patients received electrical cardioversions (ECs) if they suffered PersAF recurrences within a 90-day blanking period after ablation and received either repeat ablations or continuing Class I/III AADs outside the blanking period according to the patients’ willingness. Moreover, the status of OAC therapy was recorded at the 5-year follow-up.

2.4 Statistical analysis

Continuous variables were presented as the mean ± standard deviation for normally distributed data and analyzed with the Student’s t-test or Wilcoxon rank-sum test, as appropriate. Categorical variables were expressed as percentages and compared using a chi-square test or Fisher’s exact test. The Kaplan– Meier method was used to determine cumulative estimates of arrhythmia recurrence from the time of enrollment through subsequent follow-up according to the treatment group. The log-rank test was used to compare the cumulative event rates between CRYO and RMN groups. The Cox proportional hazards model was applied to test the consistency of the group effect, while accounting for patient age and gender. Left atrium volume (LAV) was measured by contrast computed tomography scan of the left atrium. Univariable and multivariable Cox regression models were performed to determine which variables were significant by themselves in predicting arrhythmia recurrence. Logistic regression analysis was performed to investigate the risk factors associated with stroke prevalence at baseline and new-onset stroke. All statistical tests were two-sided, and a p-value < 0.05 was considered to indicate statistical significance. Statistical analysis was performed using R (R version 4.3.2).

3.1 Patient characteristics and completeness of follow-up

The primary analysis included 200 patients whose demographics and baseline characteristics have been previously published¹⁷. There were no significant differences in baseline characteristics between the two groups. Overall, 92% of patients (184/200) completed their follow-up at 5 years after a single AF ablation procedure, including 93 patients in the RMN group and 91 in the CRYO group. The median and maximum follow-up time were 60 months and 81 months, respectively. The patient flow diagram is shown in Fig. 1.

3.2 Primary endpoint

Following an initial AF ablation procedure, off Class I/III AADs, the long-term success rates at 5 years were 47.3% in the RMN group and 40.7% in the CRYO group, respectively. ATs free survival curves were shown in Fig. 2A. There was no significant difference in freedom from ATs between the two groups (47.3% vs. 40.7%, P = 0.32). Furthermore, we performed a pairwise subgroup analysis to determine the interaction between the two ablation techniques and clinical or demographic factors (Fig. 2B). The results suggested that RMN-guided ablation might be a better choice for patients presenting with a larger LAV (when LAV ≥ 143ml, P = 0.04).

3.3 Predictors of AF recurrence

Among those patients (103) with recurrence, 50 (50/103) patients suffered from PAF and/or AFL, and 53 (53/103) were still in PersAF. The proportion of PersAF was slightly higher in the CRYO group compared with the RMN group, but without statistical difference (29% vs. 24%, P = 0.423). Additionally, there were 27 patients (14 in CRYO and 13 in RMN) who experienced AF recurrence and continued with class I/III AADs. The Cox regression analysis was used to identify risk factors correlated with AF recurrence (Table 1). In the univariable analysis, LAV was found to be significantly predictive of AF recurrence (hazard ratio (HR), 1.006 [95% confidence interval (CI), 1.000-1.011], P = 0.037). Moreover, the multivariable analysis also demonstrated that LAV significantly increased the risk of AF recurrence (HR, 1.006 [95% CI, 1.000-1.012], P = 0.041).

Table 1

Cox regression analysis of AF recurrence
	Univariate analysis		Multivariate analysis
	HR (95% CI)	p value	HR (95% CI)	p value
Age	0.994 (0.976–1.014)	0.567	0.995 (0.962–1.028)	0.742
Male	0.952 (0.610–1.485)	0.828	0.756 (0.354–1.614)	0.47
BMI	1.016 (0.954–1.082)	0.619	0.994 (0.922–1.072)	0.877
Hypertension	1.327 (0.900-1.957)	0.153	1.420 (0.706–2.858)	0.325
Diabetes mellitus	0.999 (0.558–1.789)	0.997	1.012 (0.413–2.482)	0.978
Stroke/TIA/thrombo-embolism	0.494 (0.157–1.559)	0.229	0.508 (0.078–3.323)	0.479
Vascular disease	0.815 (0.554-1.200)	0.3	0.872 (0.424–1.796)	0.711
LVEF	1.019 (0.987–1.053)	0.25	1.019 (0.984–1.054)	0.288
LAV	1.006 (1.000-1.011)	0.037	1.006 (1.000-1.012)	0.041
CHA₂DS₂-VASc score	0.960 (0.832–1.108)	0.579	0.922 (0.519–1.640)	0.783
CRYO	1.216 (0.826–1.792)	0.322	1.237 (0.807–1.897)	0.328
BMI, body mass index; CI, confidence interval; CRYO, cryoballoon; HR, hazard ratio; LAV, left atrium volume; LVEF, left ventricular ejection fraction; TIA, transient ischemic attack;.

3.4 Secondary endpoints

The results of secondary endpoints are summarized in Table 2. 54 all-cause rehospitalizations occurred in 43 patients (43/91; 47.3%) in the CRYO group when compared with 56 all-cause rehospitalizations that occurred in 46 patients (46/93; 49.5%) in the RMN group. No statistically significant difference was observed (P = 0.764). When examining cardiovascular rehospitalizations, it demonstrates that 39 cardiovascular rehospitalizations occurred in 31 subjects (31/91; 34.1%) of the CRYO group, whereas 36 cardiovascular rehospitalizations occurred in 28 subjects (28/93; 30.1%) of the RMN group. Also, no significant difference was found in the risk of cardiovascular rehospitalizations between the two groups (P = 0.565).

Table 2

Secondary endpoints
	Total	RMN	CRYO	p value
	n = 184	n = 93	n = 91	p value
All-cause rehospitalizations, n (%)	89 (48.4)	46 (49.5)	43 (47.3)	0.764
Cardiovascular rehospitalizations, n (%)	59 (32.1)	28 (30.1)	31 (34.1)	0.565
Electrical Cardioversions, n (%)	22 (11.9%)	9 (9.7%)	13 (14.3)	0.335
Repeat ablations, n (%)	24 (13.0%)	12 (12.9%)	12 (13.2)	0.954
New-onset stroke, n (%)	4 (2.2)	1 (1.1)	3 (3.3)	0.598
Major bleeding, n (%)	0 (0)	0 (0)	0 (0)	-
Δ CHA₂DS₂-VASc score				0.483
0	113 (61.4)	54 (58.1)	59 (64.8)
1	64 (34.8)	35 (37.6)	29 (31.9)
2	6 (3.3)	4 (4.3)	2 (2.2)
3	1 (0.5)	0 (0)	1 (1.1)
CRYO, cryoballoon; RMN, robotic magnetic navigation.

15 ECs were administered during follow-up to 13 subjects (13/91; 14.3%) in the CRYO group, whereas 9 ECs were given to 9 subjects (9/93; 9.7%) in the RMN group. The frequency of ECs did not differ between the two groups, although there was a trend for a lower rate in the RMN group than that of the CRYO group (P = 0.335). 13 repeat ablations were conducted in 12 subjects (12/91; 13.2%) in the CRYO group and 12 repeat ablations were conducted in 12 subjects (12/93; 12.9%) in the RMN group. Likewise, there was no significant difference in the rate of repeat ablations between the two groups (P = 0.954).

The cumulative 5-year incidence of new-onset stroke was 2.2% (4/184) and there was no major bleeding event occurring during follow-up. Compared with baseline, there was no difference in the change of CHA₂DS₂-VASC score at 5 years between the two groups. Among 184 patients, CHA₂DS₂-VASc score remained the same as baseline in 113 (61.4%) patients. There were 71 (38.6%) patients whose differences of CHA₂DS₂-VASc score increased by ≥ 1 at 5 years compared with baseline. A total of △CHA₂DS₂-VASc score was 79 shown by pie chart (Fig. 3). There were five risk factors contributing to the differences of CHA₂DS₂-VASc score, mainly due to the increase in age (68.4%), neurological events (10.1%), and new-onset cardiovascular events, including hypertension (12.7%), diabetes mellitus (3.8%), and HF (5.1%).

3.5 The status of OAC therapy at 5-year

All of the patients were on OAC for at least for 3 months following the initial procedure. The status and types of OAC therapy at 5 years were depicted in Fig. 4. Among 184 patients, 58 (31.5%, 29 in RMN and 29 in CRYO) continued OAC use, including those who were always on OAC and those who retook it after an occurrence. However, the remaining 126 (68.5%, 64 in RMN and 62 in CRYO) patients stopped OAC according to the doctor's prescription or on their own decision. Among the 126 patients who discontinued OAC, 61 (48.4%, 35 in RMN and 26 in CRYO) at risk of stroke with a CHA₂DS₂-VASc score of ≥ 2 stopped OAC use.

3.6 New-onset stroke in association with OAC discontinuation

There were 9 (9/200) patients suffering from stroke events before the procedure. No clinical or demographic factors were found to be significantly predictive of stroke prevalence (Table 3). New-onset stroke occurred in 4 (2.2%, 1 in RMN and 3 in CRYO) patients at the 5-year follow-up. Nevertheless, they all experienced AF recurrences, with a mean CHA₂DS₂-VASc score of 2, however, they were on OAC use before the new-onset stroke. Further, we performed the logistic regression analysis, which did not show any risk factors related to these new-onset stroke events, including the status of OAC therapy (Table 4).

Table 3

Logistic regression analysis of stroke prevalence
	Univariate analysis		Multivariate analysis
	OR (95% CI)	p value	OR (95% CI)	p value
Age	1.012 (0.947–1.093)	0.746	1.000 (0.997–1.003)	0.991
Male	0.653 (0.165–3.187)	0.557	0.955 (0.896–1.018)	0.161
BMI	1.098 (0.886–1.348)	0.38	1.003 (0.994–1.013)	0.477
Hypertension	2.021 (0.517–9.794)	0.33	1.031 (0.973–1.093)	0.303
Diabetes mellitus	-	-	0.940 (0.861–1.027)	0.173
Vascular disease	1.938 (0.496–9.393)	0.359	1.008 (0.951–1.068)	0.784
LVEF	0.987 (0.887–1.115)	0.824	0.999 (0.995–1.004)	0.773
LAV	0.996 (0.974–1.015)	0.723	1.000 (0.999-1.000)	0.387
Smoke-like echo	1.490 (0.305–5.878)	0.583	1.014 (0.950–1.082)	0.678
BMI, body mass index; CI, confidence interval; LAV, left atrium volume; LVEF, left ventricular ejection fraction; OR, odds ratio.

Table 4

Logistic regression analysis of stroke onset
	Univariate analysis		Multivariate analysis
	OR (95% CI)	p value	OR (95% CI)	p value
Age	0.995 (0.912–1.109)	0.923	1.000 (0.996–1.004)	0.918
Male	0.909 (0.113–18.654)	0.935	0.990 (0.903–1.086)	0.835
BMI	1.052 (0.754–1.451)	0.761	1.000 (0.991–1.009)	0.957
Hypertension	1.024 (0.121–8.688)	0.982	0.993 (0.912–1.081)	0.876
Diabetes mellitus	2.533 (0.122–20.890)	0.43	1.048 (0.939–1.170)	0.405
Vascular disease	0.977 (0.115–8.293)	0.982	1.015 (0.932–1.105)	0.737
LVEF	0.911 (0.793–1.061)	0.194	0.998 (0.994–1.002)	0.272
LAV	1.010 (0.985–1.031)	0.394	1.000 (0.999–1.001)	0.866
Smoke-like echo	3.649 (0.426–31.250)	0.203	1.037 (0.974–1.104)	0.26
CHA₂DS₂-VASc score	1.039 (0.426–2.187)	0.925	0.992 (0.927–1.061)	0.806
CRYO	3.293 (0.412–67.284)	0.306	1.027 (0.976–1.080)	0.304
Take anticoagulant
Keep taking	-	-	1.127 (0.814–1.560)	0.474
Retake after recurrence	-	-	1.058 (0.671–1.669)	0.807
Withdrawal	-	-	1.030 (0.746–1.423)	0.856
BMI, body mass index; CI, confidence interval; CRYO, cryoballoon; LAV, left atrium volume; LVEF, left ventricular ejection fractions; OR, odds ratio.

To the best of our knowledge, this is the first prospective, observational and controlled trial that directly compares the long-term efficacy and clinical outcomes after catheter ablation using RMN or CRYO in patients with PersAF. Moreover, this is one of the longest follow-ups available for an RMN study regarding either PAF or PersAF ablation. Our main findings are as follows: First, there is no significant difference in the freedom from ATs at 5 years between the two groups. Cox regression analysis demonstrates that LAV is an important prognostic factor, significantly correlated with the risk of AF recurrence. Second, there are no significant differences in the risk of all-cause and cardiovascular rehospitalizations, rates of ECs and repeat ablations, incidences of new-onset neurological events and major bleeding, as well as the change in CHA₂DS₂-VASc score at the 5-year follow-up. Finally, despite guideline recommendations advocating for continued OAC use in patients at risk of stroke, OAC discontinuation after ablation is common, 48.4% of patients with a CHA2DS2 VASc score ≥ 2 stopping OAC after ablation. However, the cumulative 5-year incidence of stroke is extremely low (2.2%), with an annual rate of 0.4%, despite the high rate of OAC withdrawal.

4.1 Long-term efficacy and clinical predictors for AF recurrence

In the present study, we demonstrated a comparable long-term efficacy in terms of freedom from ATs by directly comparing the two different ablation techniques in patients with PersAF. The 5-year event-free rate after an initial procedure off Class I/III AADs was 40.7% in the CRYO group, which was in line with that of other investigations. They reported a single-procedure 5-year clinical success rates of 46.9%¹⁸ and 41.4%¹⁹ respectively following a second-generation CRYO ablation for treatment of PersAF. However, the long-term success rate of RMN-guided ablation in this trial was 47.3%, which seemed higher than that from earlier studies. Notably, our study demonstrated the longest mean follow-up of RMN-guided ablation for PersAF with a medium number of patient cohort. The freedom rate of AF was only 13% after a mean follow-up of 2.3 ± 2.3 years²⁰. Likewise, another trial reported that AF-free rates was 42% at 3.5 years post ablation²¹. There might be some explanations for the difference in long-term efficacy by using RMN. Firstly, previous studies used earlier generations of the RMN system, non-irrigated or first generation irrigated-tip ablation catheters. Secondly, the patients enrolled in our study were younger with a mean age of 59.1 years and smaller mean LA diameter (43.1 mm), which might significantly improve the ablation effect. Although no difference in overall ATs recurrence was observed between the two groups, the proportion of AF recurrence in persistent form was higher in the CRYO group. The lesion size, depth, durability, and even lesions covering the posterior wall of the LA created by CRYO might differ from RMN-guided ablation and lead to different presenting patterns of AF²². These issues demanded further investigation.

Recent studies and meta-analyses have highlighted that an increase in LAV is associated with an increase in therapeutic ineffectiveness in both CRYO and RF ablation for AF^23–25. We also identified LAV as a risk factor remarkably predicting AF recurrence, which was consistent with previous findings. Regarding the probability of recurrence in a given patient, the LAV should therefore be considered one of the most important factors in this prediction. In addition, Ikenouchi²⁶ et al. first reported the impact of LA size on selection of catheter ablation methods for AF. The results showed that the efficacy was comparable between the two methods without LA enlargement, but CRYO was inferior to RF ablation in patients with LA enlargement. Likewise, we found that RMN-guided ablation might favor patients presenting with a larger LAV (when LAV ≥ 143ml) by performing a pairwise subgroup analysis.

4.2 Long-term clinical outcomes and the change in CHA₂DS₂-VASc score

In the present trial, the cumulative all-cause rehospitalizations were nearly 50% and the cumulative cardiovascular rehospitalizations rates were more than 30% following AF ablation, with 12% readmission due to early AF recurrences requiring ECs within a 90-day blanking period, 13% underwent repeat ablations and 15% resuming Class I/III AADs outside the blanking period. However, very similar rates were found across the entire study for all-cause rehospitalizations, cardiovascular rehospitalizations, rates of ECs and repeat ablations over 5 years, suggesting the two different ablation techniques were comparable in PersAF patients. FIRE AND ICE trial have shown that all-cause rehospitalizations rate is 32.6% (CYRO) and 41.5% (RF) respectively throughout the 30 months of follow-up. Moreover, there were significant differences in favor of CRYO ablation with respect to fewer reinterventions, lower all-cause and cardiovascular rehospitalization rates²⁷. In contrast, the CIRCA-DOSE study demonstrated the incidence of rehospitalization within 1 year was 14.5%. Additionally, no difference between CRYO and RF is observed on health care utilization (emergency department visits, rehospitalizations, ECs, AADs use, and repeat ablations)^28,29. By comparison, the rate of all-cause and cardiovascular rehospitalizations were lower compared previous studies mainly due to younger age, lower rates of concomitant diseases and CHA₂DS₂-VAS_C score in our trial, hence, they might be healthier and have lower incidences of hospital admissions. Moreover, the lower incidence of repeat ablations might relate to the patients’ unwillingness to receive second procedures considering economic costs.

Moreover, our study revealed a trend towards low incidence of new-onset neurological events and major bleeding events during follow-up. Additionally, there were 38.6% of patients whose differences of CHA₂DS₂-VASc score increased by ≥ 1 at 5 years compared with baseline. We found five risk factors contributing to the differences in CHA₂DS₂-VASc scores, mainly due to increasing age, new-onset cardiovascular and neurological events.

4.3 The status of OAC therapy after ablation in real-world

In the present observational study, the rate of discontinuation of OAC after AF procedure was 68.5% at 5 years, probably according to doctor's prescription or on their own decision, thus reflecting real clinical practice. Among those stopping OAC, 48.4% of patients were at risk of stroke with a CHA₂DS₂-VASc score ≥ 2. The high rate of OAC withdrawal led to no major bleeding event. However, at the same time, the cumulative 5-year incidence of stroke was 2.2%, with annual rate of 0.4%. Similarly, Kawaji³⁰ et al. reported 10-year clinical outcomes after AF ablation, in which they showed the incidence of ischemic stroke was also extremely low (4.2%) with an annual incidence of only 0.3%. A previous study has revealed that the risk of ischemic stroke on the assumption of no-OAC population was estimated about 2.0% per year based on the mean CHA₂DS₂-VASc score of 2.0³¹. Thus, the rate of stroke in our study was low considering the high rate of OAC discontinuation. On the other hand, in our study, all the patients who experienced new-onset ischemic stroke suffered from AF recurrences, though they remained on OAC before stroke. Catheter ablation of AF could be useful not only to relieve patients' symptoms but also to prevent cardiogenic stroke by maintaining sinus rhythm³². Hence, we postulated that the risk of stroke was highly relevant to arrhythmia recurrence despite OAC use. Therefore, our findings have shown that recommendations are commonly not being followed in clinical practice, reflecting a lack of randomized trial data to guide practice and equipoise with regards to the appropriate stroke prevention strategy after AF procedure. This suggests a critical need to further evaluate the association between OAC discontinuation after AF ablation and subsequent outcomes.

4.4 Study limitations

There are several limitations in the present study. Firstly, our study is a prospective, observational design, but not a randomized control trial. Patients are assigned to groups based on their own preferences. However, consecutive patients are enrolled and clinical features are similar in both groups. All baseline characteristics between the two groups are revealed not to affect the endpoints. Secondly, AF recurrence rate and asymptomatic episodes might have been underestimated since no continuous or long-duration monitoring for detecting arrhythmia recurrence is systematically used. Thirdly, our study further strengthens that the two different ablation techniques are comparable in PersAF patients; however, with a limited size in a single center. These findings still show the real outcomes of daily ablation practice and confirm the results of previous trials. Large-scale randomized clinical trials are demanded to further confirm the conclusions of this study.

Our findings show that CRYO is comparable to RMN-guided ablation with respect to long-term freedom from ATs in patients with PersAF. In addition, there are no significant differences in the risk of all-cause or cardiovascular rehospitalizations, rates of EC and repeat ablations, and incidences of new-onset neurological events during subsequent follow-up. Notably, OAC discontinuation after ablation remains relatively common, despite guideline recommendations for continued OAC therapy in patients at risk of stroke with a CHA₂DS₂-VASc score ≥ 2. However, the cumulative 5-year incidence of stroke was extremely low.

Conflicts of Interest

The authors declare no conflict of interest.

Funding

This research was funded by Shanghai Municipal Education Commission-Gaofeng Clinical Medicine, grant number 20161404 and Clinical Research Plan for Shanghai Hospital Development Center, grant number SHD2020CR4096.

Author Contribution

Conceptualization, Q.L. and X.L.; methodology, Y.X., Y.B., Y.W., C.L., Z.L., N.Z., T.L., K.C., W.P., L.W. and Q.J.; software, Q.L. and X.L.; validation, Q.L. and X.L.; formal analysis, Q.L. and X.L.; investigation, Q.L. and X.L.; resources, Q.L. and X.L.; data curation, Q.L. and X.L.; writing—original draft preparation, Q.L.; writing—review and editing, X.L.; supervision, Q.J.; project administration, L.W. and Q.J.; funding acquisition, L.W. and Q.J. All authors have read and agreed to the published version of the manuscript.

Acknowledgement

None

Data Availability

The data presented in this study will be shared on reasonable request to the corresponding author. The data are not publicly available due to ethical requirements.

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No competing interests reported.

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You are reading this latest preprint version

Cryoballoon vs. Robotic Magnetic Navigation-Guided Radiofrequency Ablation in Patients with Persistent Atrial Fibrillation: 5-year outcomes

Status:

Version 1

Abstract

Background

Methods and Results

Conclusion

Figures

1. Introduction

2 Methods

2.1 Study design

2.2 Primary and secondary endpoints

2.3 Follow-up and data collection

2.4 Statistical analysis

3 Results

3.1 Patient characteristics and completeness of follow-up

3.2 Primary endpoint

3.3 Predictors of AF recurrence

3.4 Secondary endpoints

3.5 The status of OAC therapy at 5-year

3.6 New-onset stroke in association with OAC discontinuation

4 Discussion

4.1 Long-term efficacy and clinical predictors for AF recurrence

4.2 Long-term clinical outcomes and the change in CHA₂DS₂-VASc score

4.3 The status of OAC therapy after ablation in real-world

4.4 Study limitations

5 Conclusions

Declarations

Conflicts of Interest

Funding

Author Contribution

Acknowledgement

Data Availability

References

Additional Declarations

Status:

Version 1

Cryoballoon vs. Robotic Magnetic Navigation-Guided Radiofrequency Ablation in Patients with Persistent Atrial Fibrillation: 5-year outcomes

Status:

Version 1

Abstract

Background

Methods and Results

Conclusion

Figures

1. Introduction

2 Methods

2.1 Study design

2.2 Primary and secondary endpoints

2.3 Follow-up and data collection

2.4 Statistical analysis

3 Results

3.1 Patient characteristics and completeness of follow-up

3.2 Primary endpoint

3.3 Predictors of AF recurrence

3.4 Secondary endpoints

3.5 The status of OAC therapy at 5-year

3.6 New-onset stroke in association with OAC discontinuation

4 Discussion

4.1 Long-term efficacy and clinical predictors for AF recurrence

4.2 Long-term clinical outcomes and the change in CHA2DS2-VASc score

4.3 The status of OAC therapy after ablation in real-world

4.4 Study limitations

5 Conclusions

Declarations

Conflicts of Interest

Funding

Author Contribution

Acknowledgement

Data Availability

References

Additional Declarations

Status:

Version 1

4.2 Long-term clinical outcomes and the change in CHA₂DS₂-VASc score