Comparison of Effectiveness and Safety between High-Power Short-Duration Ablation and Conventional Ablation for Atrial Fibrillation: A Systematic Review and Meta-Analysis

Aim We aimed to evaluate the effectiveness and safety between high-power short-duration (HPSD) radiofrequency ablation (RFA) and conventional RFA in patients with atrial fibrillation (AF). Methods Studies comparing HPSD and traditional applications in patients undergoing initial catheter ablation for atrial fibrillation from inception through December 2021 were searched on Pubmed, Medline, Cochrane, and Clinicaltrials.gov. Results The meta-analysis included seventeen studies with a total of 4934 patients. HPSD group decreased procedure duration (mean difference (MD) −38.28 min, P < 0.001), RF duration (MD −20.51 min, P < 0.001), fluoroscopy duration (MD −5.19 min, P < 0.001), and acute pulmonary vein reconnection (Odds ratio (OR) 0.40, P < 0.001), while improving the freedom from atrial arrhythmia at one year (OR 1.48, 95% confidence interval (CI) 1.12–1.94, P=0.005) and rates of first-pass isolation (OR 8.92, P=0.001). Compared with the conventional group, freedom from atrial arrhythmia at one-year follow-up was higher in the HPSD group without the guidance of AI/LSI (OR 1.66, P=0.01) and studies with a power setting of 40–50 W (OR 1.93, P=0.002). Nevertheless, the two groups had similar effectiveness with a power setting of 50 W in the HPSD RFA (OR 1.10, P=0.52). There was no difference in complications between the two groups (P=0.71). Conclusion HPSD RFA was associated with shorter procedure duration, higher freedom from atrial arrhythmia, and comparable safety compared to conventional RFA.


Introduction
Catheter ablation is recommended as an effective therapy for atrial fibrillation (AF) to reduce the risk of stroke, heart failure, and mortality and improve the quality of life [1]. As the cornerstone of AF catheter [2,3], pulmonary vein isolation (PVI) aims to produce continuous, transmural, and durable lesions around the pulmonary vein. Remarkably, pulmonary vein reconnection (PVR) could be a vital driver of AF recurrence [4,5]. )e High-power shortduration (HPSD) ablation strategy comprises the use of higher RF power (≥40 W) and shorter duration (5-15 s) of each RF energy application, and HPSD applications result in larger lesion diameters and smaller lesion depths compared to conventional (20-35 W, 10-30 s) applications [6]. Recent studies [7][8][9] demonstrate that HPSD is safe and efficient enough for treating AF which reduces radiofrequency catheter ablation (RFA) and procedure times without increasing major complication rates. Meta-analyses and randomized controlled studies comparing atrial arrhythmia recurrence and rates of PVR between HPSD and conventional RFA settings with or without the guidance of ablation Index (AI) or lesion size index (LSI) are lacking. )erefore, this meta-analysis compares the effectiveness and safety of HPSD and LPLD settings in RFA for AF [10].

Search Strategy and Study Selection.
)is meta-analysis was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines [11] (PRISMA 2009 checklist in Supplementary material online, Table S1). An all-round search was conducted in Pubmed, Medline, Cochrane, and Clinicaltrials. gov from inception through December 2021 by two reviewers (Shuyu Jin and Yumei Xue) independently. )e search involved the following keywords: ("Atrial fibrillation" OR AF) AND ("High power" OR "High-power shorterduration" OR HPSD)．

Inclusion and Exclusion
Criteria. )e studies included fulfilled the following criteria: (1) cohort study, case-control study, cross-sectional study, or randomized controlled trial (RCT) conducted in patients with age≥18, with paroxysmal and/or persistent AF undergoing initial catheter ablation; (2) comparison between HPSD RFA and conventional RFA; (3) studies must meet the following for each ablation strategy: HPSD settings: Power≥40 W, with ablation duration of 5 to 15 s per site including the posterior wall; conventional settings: Power ≤35 W, duration >10 s for any ablation; (4) reported outcome data including but not lcomparesdure time, freedom from atrial arrhythmia, total complications, redo-ablation procedure; (5) the follow-up duration was at least 6 months.
)e exclusion criteria were as follows: (1) conference abstracts, case reports, review articles, meta-analyses, editorials, or nonEnglish articles; (2) an equivocal study design or group allocation.

Data Extraction and Quality Assessment.
A standardized data collection form was extracted by two investigators independently to obtain the following data from each study including name of the first author, year of publication, country of origin, study population, inclusion and exclusion criteria, demographic data of participants, and ablation procedure details. Disagreements were arbitrated by a third person in rereview. )e original author was contacted by mail for access if the full text could be obtained. For literature in which the same study populations were reported many times or repeatedly published, only one with the most complete data was included. )e quality of these studies was evaluated by two investigators (Shuyu Jin and Yumei Xue) using the Newcastle Ottawa scale (NOS) for observational studies [12] and the Cochrane Collaboration tool for assessing risk of bias of randomized controlled studies (RCTs) [13].

Definitions
HPSD RFA : ablation power ≥40 W, including the posterior wall, with ablation duration of 5 to 15 s per site. Conventional RFA : ablation power limited to 20-35 W, with a longer ablation duration of 10-30 s per site.
Procedure time: time from the application of local anesthesia to the withdrawal of all catheters. RF time: total time from the first to the last ablation site. Fluoroscopy time: total time for fluoroscopy from the start to the end of the procedure. First-pass PVI : rate of complete PVI after first-pass circumferential RF delivery. Atrial arrhythmia recurrence: any symptomatic or asymptomatic atrial arrhythmia lasting >30 s after completing the blanking period post ablation. Acute PVR : acute reconnection was assessed at 20-30 minutes post ablation, and adenosine was administered intravenously (dosed to achieve transient heart block) or waiting for 30 minutes following the last RF application to assess PV reconnection, including spontaneous reconnection and dormant conduction. Major complication: complications that required any intervention or prolonged hospital stay including pericarditis, complete atrioventricular block, sinus node dysfunction, phrenic nerve palsy, stroke, ptocardial effusion, vascular access issues, steam pop, esophageal lesions, and death.

Statistical
Analysis. Binary variables were expressed as odds ratios (ORs) with 95% confidence intervals (CIs). Continuous variables were analyzed using the mean difference (MD) and the corresponding 95% CI was estimated using the inverse-variance method. A two-sided P-value ≤0.05 was considered statistically significant. )e fixed-effects model and the random-effects model were considered based on the level of heterogeneity. )e heterogeneity of studies was evaluated by Cochran's Q and the I 2 statistic. I 2 lies between 0% and 100% with larger values showing increasing heterogeneity. I 2 value > 50% was considered high degrees of heterogeneity and the random model was used in the subgroup analysis or sensitivity analysis excluding the trials that potentially biased the results to avoid publication bias, otherwise, a fixed-effects model was used [14,15]. We performed sensitivity analysis by omitting one study successively to evaluate the impact of the individual studies on the pooled effect size. Publication bias was assessed using funnel plot and Egger's regression tests (p < 0.05 was considered significant). In addition to using the STATA 17.0 statistical software (College Station, TX) for funnel plots and Egger's regression tests, the rest of the statistical analyses were performed using the RevMan version 5.3 (Nordic Cochrane Center; )e Cochrane Collaboration, 2014).

Study Characteristics.
Baseline characteristics among these studies are shown in Tables 1 and 2. )ere were 2397 who underwent HPSD RFA and 2537 who underwent conventional ablation procedures. In the HPSD group and conventional group, the mean age was 63.53 and 61.88 years, with 67.58% and 70.40% males, respectively. )e baseline characteristics were not a significant difference between the two groups and the followup duration was at least 6 months. Study quality assessed by NOS demonstrated that seven studies scored 9 and ten studies scored 8, which indicated the good quality of the included studies (Table 3).
)ere was significant heterogeneity with I 2 >50% for the outcomes of procedure duration (93%), RF duration (98%), fluoroscopy duration (95%), first-pass isolation (81%), freedom from atrial arrhythmia (73%), and acute PVR (72%). All summary estimates from pooled analyses were made using a random-effects model rather than a fixed-effects model to reduce the influence of heterogeneity between studies. Sensitivity analysis demonstrated the robustness of the above results during the sequential exclusion of studies except for first-pass isolation, freedom from atrial arrhythmia, and acute PVR. Low heterogeneity following exclusion of two studies   Journal of Interventional Cardiology    [28,31] based on freedom from atrial arrhythmia (I 2 � 2%) and one study [32] based on acute PVR (I 2 � 0). Despite reduced heterogeneity, there were no changes in the results of differences between two the groups. Funnel plots and Egger's regression tests of the outcomes of the primary pooled analysis are shown in Supplementary Materials, Figure S1.

Studies with 50 W vs 40-50 W in the High-Power Short-Duration Radio Frequency Ablation Group.
In the HPSD RFA group, there were 9 studies [16, 17, 23-25, 27-29, 32] where ablation was performed with a setting of 50 W, while 7 studies [18,19,21,22,26,30,31] with a power setting of 40-50 W. To reduce heterogeneity, two studies [20,32] exceeding the power of 50 W were excluded. Without increased complication rates, freedom from atrial arrhythmia at one year was higher in the HPSD RFA group with the power setting of 40-50 W (P � 0.03), conversely, no difference was found in this endpoint between the two groups with the power setting of 50 W (P � 0.52) (Supplementary Materials, Figure S3). At 50 W or 40-50 W, total procedure duration (P < 0.001), total RF duration (P < 0.001), and fluoroscopy duration (P < 0.001) (Supplementary Materials, Figure S4) were both significantly shorter in the HPSD RFA group.

Discussion
)is meta-analysis provides a more comprehensive assessment of HPSD RFA and conventional RFA in patients with AF. As in the previous studies [8,9,33,34], our results suggest that HPSD RFA may be more effective with higher first-pass isolation and freedom from atrial arrhythmia and lower acute PVR when compared with conventional RFA. Additionally, there was no difference in safety outcomes between the two groups. However, our study had more findings. In our study, there was no difference in PVR between the two groups that described redo procedures. In subgroup analysis, there was no difference between the two groups using AI/LSI-guided ablation for freedom from atrial arrhythmia. And HPSD group with a power setting of 40-50 W other than 50 W had better efficacy when compared with the conventional group.
PVI is the cornerstone of AF ablation [35], however, PVR is frequent and is mostly the result of catheter instability, tissue edema, and a reversible nontransmural injury [36]. One of the main reasons for AF recurrence is the recovery of the conduction between the pulmonary veins and left atrium [37], so continuous and transmural lines are Dikdan et al. [16] key to the success of ablation. In animal studies, the lesions were wider and HPSD ablation resulted in 100% contiguous lines with transmural lesions which improved lesion-tolesion uniformity [38]. In 6 swine, HPSD ablation was performed using the QDOT MICRO TM Catheter at a setting of 90 W for 4 s and conventional ablation was delivered using a )ermocool Smarttouch SF Catheter at a setting of 30 W for 30 s, Barkagan et al. found that all lines remained intact after 30 days in HPSD ablation, while none of the lines were continuous in conventional ablation [39]. Although there was variation in the definition of freedom from arrhythmia in each study and the use of AADs, our analysis favors the HPSD RFA strategy over the LPLD RFA strategy for lower acute PVR, higher first-pass isolation, and higher  freedom from atrial arrhythmia. Nevertheless, in our analysis, there was no difference between the two groups in PVR during the redo procedure. Some patients might have had recurrence during the followup period, but they did not undergo redo procedures. Furthermore, the followup was determined to be one year, therefore all the reasons above may underestimate the rate of chronic PVR. However, the appropriate power for the RF ablation is not clear. One study [32] used higher power of 70 W for 5-7 s and demonstrated significantly less arrhythmia recurrence during one-year followup (26.9% vs 34.9%, P < 0.013) with no major complications. )e QDOT-FAST trial [40] used 90 W for 4 s per site in 52 patients with paroxysmal atrial fibrillation and 94.2% of patients were in sinus rhythm at 3 months with one pseudoaneurysm and one asymptomatic thromboembolism. In our meta-analysis, mostly half of the studies of HPSD RFA used 50 W, and the others used 45-50 W. For freedom from atrial arrhythmia at one year, the HPSD RFA group demonstrated higher efficacy with the power setting of 45-50 W, whereas the two groups were similar with the power setting of 50 W. To reduce complications when ablating with 50 W on the posterior atrial wall, ablation duration was shorter than that of 40/ 45 W. Transmural damage may not be achieved because the lesion is shallower，as well as in less total energy, resulting in no difference in the recurrence rate between the two  groups [41]. Winkle et al. [42] reported that 6 independent predictors affected the outcomes for HPSD ablation including age, gender, type of AF, left atrial size, type of catheter, and posterior wall isolation. )erefore, further studies will be required to explore the most optimal power and duration for HPSD RFA to bring the highest clinical value.
Previous studies indicate force-time integral (FTI) as a target value to achieve permanent PVI, while not considering power settings. Consequently, only 72% of PVs remained isolated in 3 months [43]. AI is a novel ablation quality marker that incorporates contact force (CF), time, and power in a weighted formula and LSI is a multiparametric index incorporating CF and radiofrequency current data across time. Many reports demonstrated that AI or LSI can be used as the correlation index of pulmonary vein persistent isolation [44,45]. HPSD group had a lower recurrence of atrial arrhythmia at 12 months, higher firstpass isolation, lower acute PVR, and similar complication rates in the AI-guided group compared with a non AIguided group [33,46]. Moreover, HPSD-AI or LSI groups might increase freedom from atrial arrhythmia for patients with additional ablation beyond PVI [33]. Okamatsu et al. [47] studied a group of persistent AF patients undergoing AI-guided PVI with target values of 550 for anterior and 400 for posterior left atrial regions, with 22% patients demonstrating late PVR during repeat procedures after 2 months and 95% patients were in sinus rhythm at 12 months. However, freedom from atrial arrhythmia and acute PVR failed to demonstrate a significant advantage with AI or LSI in our analysis. Regrettably, only 5 studies were included in our subgroup analysis with AI or LSI-guided procedure, of which only 4 studies and 2 studies respectively illustrated freedom from atrial arrhythmia at one year and acute PVR rates, and each study had different ablation strategies, antiarrhythmic drug use, and recurrence of arrhythmia definition which might influence these results. We did not analyze first-pass isolation because only one study reported this data. )erefore, more well-designed and large-scale RCTs are required to confirm these findings.
Safety during elective PVI procedures is of worthwhile concern. Radiofrequency catheter ablation is a technique where conductive and resistive heating are delivered through electrode catheters to myocardial tissue creating a thermal lesion. Irreversible myocardial tissue injury with cellular death occurs once the temperature of approximately 50°C has been reached, whereas conductive heating transfers thermal energy directly to deeper tissue [48]. Unlike conventional ablation, the HPSD ablation strategy results in a higher resistive heating and lower conductive heating, which may reduce collateral injury to surrounding structures such as the esophagus [38,49]. Late gadolinium enhancement MRI of the esophagus in 574 patients following AF ablation using HPSD settings of 50 W for 5 seconds reported a 14.3% incidence of moderate to severe thermal oesophageal late gadolinium enhancement with no fistulas [23]. Takemoto et al. [50] reported that high-power settings based on the AI or LSI might reduce the collateral thermal damage by Baher   comparing the use of 20 W and 40 W with the same AI or LSI for RF applications. In 10284 patients, HPSD RFA strategies performed at 45-50 W have very low complication rates with 1 death due to an atrioesophageal fistula and 33 cases of cardiac tamponade [51]. In our analysis, only one case of cardiac tamponade occurring in the conventional RFA group was reported by Hamsom et al. [25], and cases of aterioesophageal fistula were not observed in each group. Our results demonstrated that the HPSD RFA strategy appears to be as safe as the conventional RFA strategy. In terms of procedure duration, RF duration, and fluoroscopy time, the HPSD RFA strategy represents distinct advantages compared with the conventional RFA strategy whether in the subgroup analysis or not. Additionally, the reduction in procedure times can decrease the intravenous fluid volumes administered to patients which may benefit patients with cardiac insufficiency. Finally, less radiation exposure will also benefit both patients and physicians [9].
To conclude, our results of the pooled analysis favor the use of HPSD settings over conventional settings. However, more RCT studies are needed to further assess the above results.

Limitations.
We acknowledge several limitations in our study. First, we have only one RCT included in our metaanalysis while the rest were nonrandomized comparative studies. Although, all included studies were of good quality based on the Newcastle Ottawa scale, reflecting a real-world experience, more randomized controlled trials would provide better evidence for the difference in outcomes between two groups. Second, there were variations in each study in terms of power, types of catheters, contact force, target temperature, antiarrhythmic drug use, and the definition of freedom from atrial arrhythmia, resulting in significant heterogeneity between groups. And seldom included studies analyzed total energy during ablation procedure which we could not compare between two groups. )ird, the included studies not only performed PVI but also additional linear ablation and different surgical methods might affect the maintenance of sinus rhythm. At last, we have a limited number of studies that reported PVR during redo procedures and with the guidance of AI/LSI. Finally, the exact anatomical locations of PVR were not clearly described in each study, so we could not analyze the specific locations of PVR.

Conclusions
High-power short-duration RFA was related to better procedural effectiveness and higher freedom from atrial arrhythmia with comparable safety when compared with conventional RFA. Additionally, HPSD RFA decreases procedural, RF, and fluoroscopy durations. Meanwhile, in the subgroup analysis, HPSD RFA demonstrates a feasible, effective and safe approach for AF ablation.

Data Availability
)e data used to support the findings of this study are included within the article.

Conflicts of Interest
)e authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as potential conflicts of interest.