Pre-Ablation Rate Control Therapy and Direct-to-Catheter Ablation in Patients with Persistent Atrial Fibrillation: A DECAAF II Subanalysis

Pre-Ablation Rate Control Therapy and Direct-to-Catheter Ablation in Patients with Persistent Atrial Fibrillation: A DECAAF II Subanalysis | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Pre-Ablation Rate Control Therapy and Direct-to-Catheter Ablation in Patients with Persistent Atrial Fibrillation: A DECAAF II Subanalysis Radia Ksayer, Hadi Younes, Eli Tsakiris, Han Feng, Yishi Jia, and 7 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-7672338/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 06 Jan, 2026 Read the published version in Journal of Interventional Cardiac Electrophysiology → Version 1 posted You are reading this latest preprint version Abstract Background: For patients with persistent atrial fibrillation (PersAF), initial treatment strategies often involve rate or rhythm control before offering ablation. This study compared two approaches: (1) catheter ablation without prior medication (referred to as direct-to-catheter ablation, DTCA) and (2) catheter ablation after initial rate control with either diltiazem or metoprolol. Objective: This study included two independent comparative analyses of patients with persistent atrial fibrillation (PersAF) undergoing catheter ablation. Aimed at evaluating the potential impact of pre-ablation rate control medications including beta blockers and calcium channel blockers on post-ablation outcomes. Comparison 1: DTCA without prior beta-blocker use (n = 209) vs. metoprolol use prior to ablation (n = 260). Comparison 2: DTCA without prior calcium channel blocker use (n = 639) vs. diltiazem use prior to ablation (n = 55). Methods: Patients were followed for 18 months to evaluate primary outcome: recurrence of atrial fibrillation (AF) and secondary outcomes: Pre-ablation and Post-ablation left atrial percent fibrosis as seen on LGE MRI and Quality of life (QoL), measured with the SF-36 questionnaire. The Wilcoxon tests were conducted to compare the QoL and fibrosis among groups. Time to recurrence among the groups post ablation was assessed via Kaplan-Meier curves. Multivariable Cox models were developed to adjust for other confounders of AF recurrence. Results: In the beta-blocker analysis (n = 469), no significant difference in AF recurrence was observed between patients without prior beta-blocker use (DTCA group) and those treated with metoprolol (Kaplan-Meier, p > 0.05). Similarly, in the calcium channel blocker analysis (n = 694), no difference in recurrence was found between the DTCA group and those with prior diltiazem use (p > 0.05). Multivariable Cox models confirmed that neither metoprolol (p = 0.44) nor diltiazem (p = 0.34) independently predicted AF recurrence. Additionally, no significant differences were found in any fibrosis metrics or QoL between the groups in either comparison (all p > 0.05). Conclusion: Prior treatment with diltiazem or metoprolol before ablation of PersAF did not show additional benefits in reducing patient outcomes such as AF recurrence, fibrosis, or improving QoL. Figures Figure 1 Figure 2 Figure 3 Figure 4 Introduction Atrial fibrillation (AF) is the most common arrhythmia in the world, affecting nearly 1 in every 3–5 individuals worldwide. 1 While early detection and treatment improve outcomes, AF remains one of the most significant risk factors for cardiovascular events and increases the risk of ischemic stroke 5-fold. Medications acting on the atrio-ventricular (AV) node have historically served as first-line treatment for AF, with the 2023 AHA/ACC guidelines endorsing beta-blockers or nondihydropyridine calcium channel blockers as first-line rate control agents, with selection guided by underlying left ventricular function. 2 Utilization of these specific agents is termed rate control due to their function in decreasing ventricular rate independent of atrial rate. Alternatively, a second pharmacologic approach called rhythm control utilizes antiarrhythmic drugs (AADs) such as amiodarone, sotalol, and flecainide that affect cardiac contractility by acting on potassium and sodium channels. While considered interchangeable in efficacy for treatment of AF, rhythm control agents have been associated with more morbid side effects, and rate control agents demonstrated better symptomatic outcomes, particularly in older AF patients. 2 Minimally invasive catheter ablation is a proven safe and effective treatment for patients with a spectrum of AF phenotypes. The AHA/ACC 2023 guidelines endorse catheter ablation as a class 1 indication in young and healthy patients with paroxysmal atrial fibrillation(PAF). 2 Additionally, the recent ESC 2024 guidelines expanded the recommendation of early ablation as a first-line treatment for any patient with PAF. 3 This recommendation was based on studies demonstrating that early catheter ablation may benefit individuals with less advanced AF disease. 4 A direct-to-catheter approach (DTCA) describes treating AF with catheter ablation without a preceding trial of rate or rhythm control. In patients with PersAF, previous post hoc analysis of the DECAAF II trial has shown that rhythm control before catheter ablation did not improve outcomes. 5 We seek to evaluate whether rate control with metoprolol or diltiazem, the most commonly used beta blocker and CCB for AF respectively, preceding catheter ablation improves outcomes compared to DTCA in treatment of PersAF. Methods 2.1 DECAAF II Design DECAAF II is a randomized multi-center clinical trial that included 843 patients with PersAF who were randomly assigned to pulmonary vein isolation (PVI) plus MRI-guided atrial fibrosis ablation (421 patients) or PVI alone (422 patients). The primary tools used in these procedures were radiofrequency ablation (RFA) and cryoablation catheters. For those in the fibrosis-guided group, the process involved merging processed delayed-enhancement MRI images with a 3D mapping system during the ablation. This technique was essential for targeting fibrotic areas identified on the MRI. In contrast, the PVI-only group focused solely on the electrical isolation of all pulmonary veins, per the Heart Rhythm Society Consensus Statement. Additional ablation measures were available to address recurrent arrhythmias, at the operator's discretion, if a normal sinus rhythm was not restored post-PVI, even after cardioversion. Patients were followed over 12–18 months using a mobile single-lead ECG monitoring device to observe AF recurrence and burden. Patients were instructed to send one ECG recording from the device daily during the study period through a smartphone application. Patients underwent a delayed-enhancement MRI using the Merisight delayed-enhancement MRI protocol (MARREK Inc.) within 30 days before the ablation procedure and 3 months post-ablation. Quality of life was assessed at baseline and 12 months using the standardized Short Form Health Survey (SF-36). The complete methodology is further described in the DECAAF II protocol. 6 All patients in the DECAAF II trial provided written informed consent according to the trial protocol and local IRB/ethics committee approvals, in accordance with the Declaration of Helsinki. 6 2.2 Sub-Analysis Design: All patients in the DECAAF II study with complete data were considered for analysis. Two separate analyses were performed to evaluate the usage of metoprolol or diltiazem before catheter ablation. The first comparison evaluates the use of metoprolol; patients undergoing DTCA without a history of beta blocker use were compared to patients with a history of metoprolol use before ablation. The second comparison evaluates diltiazem use; patients undergoing DTCA without a history of CCB use were compared to patients with a history of diltiazem use before ablation. As described in DECAAF II, the primary endpoint of the study was the first confirmed recurrence of atrial arrhythmia (including AF, atrial flutter, or atrial tachycardia) lasting for at least 30 seconds after the 90-day blanking period, demonstrated by at least two consecutive 1-lead smartphone ECG device tracings, one positive reading on a clinical 12-lead ECG tracing, ambulatory monitor, or if the patient underwent repeat ablation. The daily smartphone ECGs were intended as the primary method for assessing atrial arrhythmia recurrence. Still, clinical and ambulatory ECGs served as backup methods for detecting recurrence in patients who failed to transmit smartphone ECG readings reliably. A core laboratory at the University of Washington adjudicated the ECG findings. This sub-analysis utilized the 36-item Short Form Survey (SF-36) score as the primary subjective outcome metric to evaluate the quality of life at baseline and 12 months. Baseline MRI results were utilized to quantify left atrial (LA) fibrosis and LA volume in all patients at baseline and the 3-month follow-up. LA Volume was indexed to body surface area. Patients were followed for 12–18 months. 2.3 Statistical Analysis Demographics and common comorbidities were compared between each group pairing within their respective analysis (metoprolol group vs no beta-blocker group, and diltiazem group vs no CCB group). Normality was assessed using the Shapiro-Wilk test for continuous variables, with Wilcoxon and t-tests conducted accordingly, depending on normality. Continuous variables are presented as median with standard deviation in parentheses. Categorical variables were tested with Chi-square tests and presented with counts and percentages of the specific study group. The Kaplan-Meier curve was used to evaluate the univariate effect of the independent variable, use of rate control agent before ablation, on the primary outcome of AF recurrence after ablation. Corresponding p-values are generated using the log-rank test. Two separate multivariable Cox models, one for each analysis, assessed the independent effects of clinically relevant variables. They were selected based on individual significance in t-tests assessing their impact on the primary outcomes. All statistical analysis was performed using R (version 4.3.0) software, with a 2-sided significance level of 0.05. Results 3.1 Baseline Characteristics: A total of 760 patients within DECAAF II were considered for analysis, with 199 excluded for insufficient LGE MRI data. The mean age of patients was 62.0 ± 9.0 years, and 79.5% were males. 260 patients taking metoprolol before catheter ablation were identified and compared to 209 patients not taking any beta blocker before ablation. 55 patients taking diltiazem before ablation were identified and compared to 639 patients not taking any CCB before ablation. Baseline characteristics of all groups, in their respective comparison pairings, are shown in Tables 1 and 2 . Table 1 Demographics (Direct-to-Catheter vs. Pre-ablation Metoprolol groups) Variable Direct-to-Catheter without prior Beta Blocker (N = 209) Pre-ablation Metoprolol (N = 260) p -value Age, years 62.0 ± 8.9 62.4 ± 9.5 0.54 Sex (male) 164 (78.5%) 199 (76.5%) 0.62 BMI 30.8 ± 5.6 32.4 ± 6.9 0.006 Left atrial volume (mL) 126.6 ± 37.6 130.0 ± 40.9 0.016 Baseline fibrosis (%) 18.6 ± 7.4 19.1 ± 7.3 0.52 Diabetes Mellitus 15 (7.2%) 37 (14.2%) 0.016 Congestive Heart Failure 24 (11.5%) 54 (20.8%) 0.007 Hypertension 105 (50.2%) 159 (61.2%) 0.018 Coronary Artery Disease 22 (10.5%) 32 (12.3%) 0.55 Vascular Disease 14 (6.7%) 33 (12.7%) 0.032 Stroke history 16 (7.7%) 31 (11.9%) 0.13 Aldosterone Inhibitor Use 14 (6.7%) 16 (6.2%) 0.81 Randomized treatment group : 0.40 Conventional PVI 111 (53.1%) 128 (49.2%) PVI + Fibrosis-guided Ablation 98 (46.9%) 132 (50.8%) Table 2 Demographics (Direct-to-Catheter vs. Pre-ablation Diltiazem groups) Variable Direct-to-Catheter without prior Calcium Channel Blocker (N = 639) Pre-ablation Diltiazem (N = 55) p -value Age, years 61.5 ± 9.2 64.4 ± 8.1 0.048 Sex (male) 513 (80.3%) 41 (74.5%) 0.31 BMI 31.0 ± 6.1 34.2 ± 9.0 < 0.001 Left atrial volume (mL) 129.5 ± 41.4 137.4 ± 37.5 0.092 Baseline fibrosis (%) 18.9 ± 7.6 18.7 ± 7.6 0.78 Diabetes Mellitus 56 (8.8%) 9 (16.4%) 0.06 Congestive Heart Failure 122 (19.1%) 15 (27.3%) 0.14 Hypertension 331 (51.8%) 41 (74.5%) < 0.001 Coronary Artery Disease 73 (11.4%) 8 (14.5%) 0.49 Vascular Disease 62 (9.7%) 2 (3.6%) 0.14 Stroke history 52 (8.1%) 5 (9.1%) 0.81 Aldosterone Inhibitor Use 54 (8.5%) 1 (1.8%) 0.08 Randomized treatment group : 0.50 Conventional PVI 318 (49.8%) 30 (54.5%) PVI + Fibrosis-guided Ablation 321 (50.2%) 25 (45.5%) 3.2 Use of Metoprolol Before Ablation: Patients taking pre-ablation metoprolol group had higher BMI (32.4 vs 30.8, p = .006) higher rates of congestive heart failure (20.8% vs 11.5%, p = .007), vascular disease (12.7% vs 6.7%, P = .032), diabetes mellitus (14.2% vs 7.2%, p = .016) and hypertension (61.2% vs 50.2%, p = .018) as compared to those undergoing DTCA without Beta-blocker. Kaplan Meier survival analysis showed no significant difference in AF recurrence following ablation (p = .44) between these two groups (Fig. 1 ) . Mean quality of life as measured by SF36 scores was also similar between both groups at 12 months (p = .89) ( Fig. 2 ) . Left atrial volume index (LAVI) decrease at 12 months after ablation was also similar between groups (11.4 mm 3 vs 10.4 mm 3 , p = .298). Additionally, on LGE-MRI there were no significant differences of baseline fibrosis (19.1% vs 18.6%, p = 0.52), residual fibrosis post-ablation (15.0% vs 14.1%, p = 0.27), or fibrosis reduction (4.1% vs 4.1%, p = 0.65) between the two groups ( Table 3 ). Table 3 Direct-to-Catheter vs. Pre-ablation Metoprolol: Fibrosis Variable DTCA (No BB) (N = 209) Pre-ablation Metoprolol (N = 260) Total (N = 469) p-value Fibrosis Baseline fibrosis (%) 18.6 ± 7.4 19.1 ± 7.3 18.9 ± 7.3 0.52 Residual fibrosis (%) 14.1 ± 5.9 15.0 ± 6.5 14.6 ± 6.2 0.27 Fibrosis reduction (%) 4.1 ± 2.4 4.1 ± 2.3 4.1 ± 2.3 0.65 3.3 Use of Diltiazem Before Ablation: Patients taking pre-ablation diltiazem were slightly older (64.4 vs 61.5, p = 0.048), had higher BMI (34.3 vs 30.9, p < 0.001), and had higher rates of hypertension (74.5% vs 51.8%, p < 0.001) as compared to those undergoing DTCA without CCB. Kaplan Meier survival analysis showed no significant difference in AF recurrence following ablation (p = .34) between patients taking diltiazem before ablation and those not taking any CCB before ablation (Fig. 3 ). Mean quality of life scores were similar between both groups (p = .31) (Fig. 4 ). LAVI was also similar at 12 months post-ablation. Additionally, no significant differences were seen on LGE MRI for baseline fibrosis (18.7% vs 18.9%, p = 0.78), residual fibrosis post ablation (14.3% vs 14.7%, p = 0.61) or fibrosis reduction (3.8% vs 4.0%, p = 0.49) ( Table 4 ). Table 4 Direct-to-Catheter vs. Pre-ablation Diltiazem: Fibrosis Variable DTCA (No CCB) (N = 639) Pre-ablation Diltiazem (N = 55) Total (N = 694) p-value Fibrosis Baseline fibrosis (%) 18.9 ± 7.6 18.7 ± 7.6 18.9 ± 7.6 0.78 Residual fibrosis (%) 14.7 ± 6.5 14.3 ± 7.0 14.7 ± 6.5 0.61 Fibrosis reduction (%) 4.0 ± 2.3 3.8 ± 2.1 4.0 ± 2.3 0.49 3.4 Multivariable Cox Regression In both Cox Regression analysis and multivariable linear regression, the use of diltiazem before ablation had no significant effect on AF recurrence (p = .10). Both male sex (HR = .635, p = .002) and pre-ablation LA volume (HR = 1.013, p < .001) emerged as statistically significant predictors. Using the same models for the other comparator, use of metoprolol prior to ablation had no statistically significant effect (p = .76), and pre-ablation LA volume had the most significant effect on AF recurrence (HR = 1.012, p < .0001). Discussion At 12-month follow-up, a direct-to-catheter approach appears similarly effective to pre-ablation rate control treatment with either diltiazem or metoprolol with respect to AF recurrence following ablation. 4.2 The Role of Rate Control Agents Before Catheter Ablation Historically, rate control has been a foundational approach to managing AF. The AFFIRM trial established that rate control was non-inferior to rhythm control with respect to all-cause mortality in AF patients. 7 However, more recent trials, such as EAST-AFNET 4, demonstrated that early rhythm control, including ablation, significantly reduced cardiovascular events. 4 Similarly, CABANA showed that catheter ablation reduced AF recurrence and improved symptoms compared to drug therapy, although mortality benefits were not statistically significant. 8 Post-hoc analyses of CABANA and results from STOP-AF and EARLY-AF further support ablation earlier in the disease course. 4 , 8 ,9 Findings from DECAAF II revealed no added value from pharmacologic rhythm control before ablation. 5 According to the 2023 AHA/ACC/HRS guidelines, rate control remains appropriate in minimally symptomatic patients or those unsuitable for rhythm control. However, catheter ablation holds a Class I recommendation for patients with symptomatic AF, without requiring a prior pharmacologic trial. 2 Our findings suggest that beta-blockers and CCBs do not meaningfully alter post-ablation outcomes and may delay effective intervention. Early rhythm control, as supported by EAST-AFNET 4, is associated with fewer cardiovascular events and supports earlier use of ablation. 10 The SARA trial also demonstrated superiority to ablation over AAD for maintaining sinus rhythm at 12 months after intervention, although Guidelines emphasize individualized therapy based on AF burden, comorbidities, and access to procedural care. This study contributes to the growing evidence supporting DTCA as a practical and effective first-line strategy for PersAF management. 4.3. Mechanistic Insights Rate control agents such as metoprolol and diltiazem effectively slow ventricular response to AF, reducing the risk of tachycardia-induced cardiomyopathy, left ventricular (LV) remodeling, and improving symptoms. 11 , 12 However, they may not protect against LA remodeling since the LA is still subjected to the rapid depolarizations of AF. While these agents prevent electrical propagation to the ventricles, they do not prevent foci from firing. Accordingly, even with a decrease in ventricular rate, the LA may still be subject to the same remodeling forces experienced by a patient not treated with rate control. Since LA remodeling, such as dilation and low voltage, has been most consistently associated with the risk of early recurrence, it is understandable that such rate control agents may not significantly lower the risk of early recurrence following ablation. 13 While beta-blockers have been shown to improve all-cause mortality in patients with AF regardless of heart failure presence, there is no rigorous study finding any effects on LA fibrosis. 14 AF is a progressive disease as described by the concept “AF begets AF,” in which AF episodes cause consequent arrhythmogenic changes in the LA, which promote further AF episodes. 15 , 16 , 17 Accordingly, symptomatic improvement with rate control agents that delay catheter ablation may unnecessarily subject a patient to further remodeling of the LA while awaiting definitive treatment. Particularly in the PersAF population, according to our analysis of DECAAF II, the extent of LA remodeling may render the effect of rate control on recurrence after ablation negligible. In patients with such advanced disease, isolation of causative foci is likely the only mode of treatment, and it may be reasonable to consider a DTCA approach in select patients. 4.4. Limitations and Future Directions Our analysis of DECAAF II is limited by its retrospective nature. A lack of long-term follow-up makes it difficult to draw conclusions on differences in the long-term efficacy of ablation between groups. An analysis of non-selective beta blockers and other CCBs may give a fuller picture of the differences in effects within each drug class. Strong RCTs examining the impact of rate control before catheter ablation on LA fibrosis and AF recurrence will help better elucidate the role of a DTCA approach. Pre- and post-ablation imaging of patients with a spectrum of AF phenotypes, compared to our sole PersAF cohort, will help establish any variance in rate control effect on outcomes. Analysis of an optimal treatment length before ablation will be valuable in ensuring best practices. As rate control agents have more established effects on ventricular remodeling, future investigation should also analyze their role in pre-ablation treatment for patients with AF and concomitant HF. Conclusion Our analysis of PersAF patients undergoing catheter ablation found that pretreatment with metoprolol or diltiazem did not confer additional benefits in reducing AF recurrence, LA fibrosis, or improving Qol over a 12-month follow-up period. These results suggest that DTCA may be a reasonable alternative to pre-ablation rate control with beta-blockers or calcium channel blockers. Declarations Funding: No specific funding was received for this work. Consent to Participate: All patients in the DECAAF II trial provided written informed consent according to the trial protocol and local IRB/ethics committee approvals. 6 References Linz D, Gawalko M, Betz K, et al. Atrial fibrillation: epidemiology, screening and digital health. The Lancet Regional Health – Europe . 2024;37. doi:10.1016/j.lanepe.2023.100786 Joglar JA, Chung MK, Armbruster AL, et al. 2023 ACC/AHA/ACCP/HRS Guideline for the Diagnosis and Management of Atrial Fibrillation: A Report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines. Circulation . 2024;149(1):e1-e156. doi:10.1161/CIR.0000000000001193 Boriani G, Mei DA, Vitolo M, Imberti JF. The 2024 ESC guidelines on atrial fibrillation: essential updates for everyday clinical practice. Intern Emerg Med . 2025;20(5):1299-1306. doi:10.1007/s11739-025-04006-1 Kirchhof P, Camm AJ, Goette A, et al. Early Rhythm-Control Therapy in Patients with Atrial Fibrillation. 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EP Europace . 2023;25(2):260-262. doi:10.1093/europace/euad010 Sabbah HN. The cellular and physiologic effects of beta blockers in heart failure. Clin Cardiol . 1999;22 Suppl 5:V16-20. Garvanski I, Simova I, Angelkov L, Matveev M. Predictors of Recurrence of AF in Patients After Radiofrequency Ablation. Eur Cardiol . 2019;14(3):165-168. doi:10.15420/ecr.2019.30.2 Strauss MH, Hall AS, Narkiewicz K. The Combination of Beta-Blockers and ACE Inhibitors Across the Spectrum of Cardiovascular Diseases. Cardiovasc Drugs Ther . 2023;37(4):757-770. doi:10.1007/s10557-021-07248-1 Lu Z, Scherlag BJ, Lin J, et al. Atrial Fibrillation Begets Atrial Fibrillation. Circulation: Arrhythmia and Electrophysiology . 2008;1(3):184-192. doi:10.1161/CIRCEP.108.784272 Allessie M, Ausma J, Schotten U. Electrical, contractile and structural remodeling during atrial fibrillation. Cardiovasc Res . 2002;54(2):230-246. doi:10.1016/s0008-6363(02)00258-4 Wijffels MC, Kirchhof CJ, Dorland R, Allessie MA. Atrial fibrillation begets atrial fibrillation. A study in awake chronically instrumented goats. Circulation . 1995;92(7):1954-1968. doi:10.1161/01.cir.92.7.1954 Additional Declarations No competing interests reported. Cite Share Download PDF Status: Published Journal Publication published 06 Jan, 2026 Read the published version in Journal of Interventional Cardiac Electrophysiology → Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. 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14:27:35","extension":"xml","order_by":11,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":68925,"visible":true,"origin":"","legend":"","description":"","filename":"f80978dd0a494f70bec2372c06a6113b1structuring.xml","url":"https://assets-eu.researchsquare.com/files/rs-7672338/v1/2a9d9e1ac6e19eb1cfe9033c.xml"},{"id":93339680,"identity":"5f3a1937-2250-423c-a570-608c6e4979d2","added_by":"auto","created_at":"2025-10-12 14:27:35","extension":"html","order_by":12,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":79578,"visible":true,"origin":"","legend":"","description":"","filename":"earlyproof.html","url":"https://assets-eu.researchsquare.com/files/rs-7672338/v1/4e6ddb82224ad37e66c3268b.html"},{"id":93339663,"identity":"c9ead696-ba15-400e-8ca5-e3d599f6ee03","added_by":"auto","created_at":"2025-10-12 14:27:35","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":82363,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eComparison of AF Recurrence Following Catheter Ablation (Pre-ablation Metoprolol vs Direct to Catheter Ablation with no Prior Beta Blocker)\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eA Kaplan Meier curve comparing the risk of atrial fibrillation recurrence, in days, following catheter ablation between pre-ablation metoprolol vs direct-to-catheter ablation with no prior beta blocker. No significant difference was found in recurrence between the two groups (p = 0.44)\u003c/p\u003e","description":"","filename":"floatimage1.png","url":"https://assets-eu.researchsquare.com/files/rs-7672338/v1/919263ab25fe0210746b2185.png"},{"id":93339664,"identity":"59cdf339-06f0-4980-bf54-be486657e847","added_by":"auto","created_at":"2025-10-12 14:27:35","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":165039,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eComparison of Quality-of-Life Following Ablation (Pre-ablation Metoprolol vs Direct to Catheter Ablation with no Prior Beta Blocker)\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eA box plot demonstrating similar quality of life, as measured by the SF 36 questionnaire, between the pre-ablation metoprolol group and the direct-to-catheter ablation without prior beta blocker group (p=.88)\u003c/p\u003e","description":"","filename":"floatimage2.png","url":"https://assets-eu.researchsquare.com/files/rs-7672338/v1/d745ef89cdc5f9a659a0dea6.png"},{"id":93340804,"identity":"c3b01ab4-11cf-4761-aa54-827872cbcd53","added_by":"auto","created_at":"2025-10-12 14:35:35","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":101184,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eComparison of Quality-of-Life Following Ablation (Pre-ablation Diltiazem vs Direct to Catheter Ablation with no Prior Calcium Channel Blocker)\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eA Kaplan Meier curve comparing the risk of atrial fibrillation recurrence, in days, following catheter ablation between pre-ablation diltiazem, vs direct-to-catheter ablation with no prior calcium channel blocker (CCB). No significant difference was found in recurrence between the two groups (p = 0.34)\u003c/p\u003e","description":"","filename":"floatimage3.png","url":"https://assets-eu.researchsquare.com/files/rs-7672338/v1/9de8c796a8fa81cda004b082.png"},{"id":93339671,"identity":"8a998eec-afff-4666-b8ea-703247df9c9d","added_by":"auto","created_at":"2025-10-12 14:27:35","extension":"png","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":42702,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eComparison of Quality-of-Life Following Ablation (Pre-ablation Diltiazem vs Direct to Catheter Ablation with no Prior Calcium Channel Blocker)\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eA box plot demonstrating similar quality of life, as measured by the SF 36 questionnaire, between the pre-ablation diltiazem group and the direct-to-catheter ablation without prior calcium channel blocker group (p=.31)\u003c/p\u003e","description":"","filename":"floatimage4.png","url":"https://assets-eu.researchsquare.com/files/rs-7672338/v1/1c24cfe4e6ccb9b496675a81.png"},{"id":100069237,"identity":"ae7b737a-dcda-4412-b5c4-6f7664361d2f","added_by":"auto","created_at":"2026-01-12 16:11:40","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1552906,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-7672338/v1/f1198546-f641-4efd-aeef-759cba4a06dc.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"\u003cp\u003ePre-Ablation Rate Control Therapy and Direct-to-Catheter Ablation in Patients with Persistent Atrial Fibrillation: A DECAAF II Subanalysis\u003c/p\u003e","fulltext":[{"header":"Introduction","content":"\u003cp\u003eAtrial fibrillation (AF) is the most common arrhythmia in the world, affecting nearly 1 in every 3\u0026ndash;5 individuals worldwide.\u003csup\u003e\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e\u003c/sup\u003e While early detection and treatment improve outcomes, AF remains one of the most significant risk factors for cardiovascular events and increases the risk of ischemic stroke 5-fold. Medications acting on the atrio-ventricular (AV) node have historically served as first-line treatment for AF, with the 2023 AHA/ACC guidelines endorsing beta-blockers or nondihydropyridine calcium channel blockers as first-line rate control agents, with selection guided by underlying left ventricular function.\u003csup\u003e\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e\u003c/sup\u003e Utilization of these specific agents is termed rate control due to their function in decreasing ventricular rate independent of atrial rate. Alternatively, a second pharmacologic approach called rhythm control utilizes antiarrhythmic drugs (AADs) such as amiodarone, sotalol, and flecainide that affect cardiac contractility by acting on potassium and sodium channels. While considered interchangeable in efficacy for treatment of AF, rhythm control agents have been associated with more morbid side effects, and rate control agents demonstrated better symptomatic outcomes, particularly in older AF patients.\u003csup\u003e\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e\u003c/sup\u003e\u003c/p\u003e\u003cp\u003eMinimally invasive catheter ablation is a proven safe and effective treatment for patients with a spectrum of AF phenotypes. The AHA/ACC 2023 guidelines endorse catheter ablation as a class 1 indication in young and healthy patients with paroxysmal atrial fibrillation(PAF).\u003csup\u003e\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e\u003c/sup\u003e Additionally, the recent ESC 2024 guidelines expanded the recommendation of early ablation as a first-line treatment for any patient with PAF.\u003csup\u003e\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e\u003c/sup\u003e This recommendation was based on studies demonstrating that early catheter ablation may benefit individuals with less advanced AF disease.\u003csup\u003e\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e\u003c/sup\u003e A direct-to-catheter approach (DTCA) describes treating AF with catheter ablation without a preceding trial of rate or rhythm control. In patients with PersAF, previous post hoc analysis of the DECAAF II trial has shown that rhythm control before catheter ablation did not improve outcomes.\u003csup\u003e\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e\u003c/sup\u003e We seek to evaluate whether rate control with metoprolol or diltiazem, the most commonly used beta blocker and CCB for AF respectively, preceding catheter ablation improves outcomes compared to DTCA in treatment of PersAF.\u003c/p\u003e"},{"header":"Methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e\u003ch2\u003e2.1 DECAAF II Design\u003c/h2\u003e\u003cp\u003eDECAAF II is a randomized multi-center clinical trial that included 843 patients with PersAF who were randomly assigned to pulmonary vein isolation (PVI) plus MRI-guided atrial fibrosis ablation (421 patients) or PVI alone (422 patients). The primary tools used in these procedures were radiofrequency ablation (RFA) and cryoablation catheters. For those in the fibrosis-guided group, the process involved merging processed delayed-enhancement MRI images with a 3D mapping system during the ablation. This technique was essential for targeting fibrotic areas identified on the MRI. In contrast, the PVI-only group focused solely on the electrical isolation of all pulmonary veins, per the Heart Rhythm Society Consensus Statement. Additional ablation measures were available to address recurrent arrhythmias, at the operator's discretion, if a normal sinus rhythm was not restored post-PVI, even after cardioversion.\u003c/p\u003e\u003cp\u003ePatients were followed over 12\u0026ndash;18 months using a mobile single-lead ECG monitoring device to observe AF recurrence and burden. Patients were instructed to send one ECG recording from the device daily during the study period through a smartphone application. Patients underwent a delayed-enhancement MRI using the Merisight delayed-enhancement MRI protocol (MARREK Inc.) within 30 days before the ablation procedure and 3 months post-ablation. Quality of life was assessed at baseline and 12 months using the standardized Short Form Health Survey (SF-36). The complete methodology is further described in the DECAAF II protocol.\u003csup\u003e\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e\u003c/sup\u003e\u003c/p\u003e\u003cp\u003e All patients in the DECAAF II trial provided written informed consent according to the trial protocol and local IRB/ethics committee approvals, in accordance with the Declaration of Helsinki. \u003csup\u003e6\u003c/sup\u003e\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec4\" class=\"Section2\"\u003e\u003ch2\u003e2.2 Sub-Analysis Design:\u003c/h2\u003e\u003cp\u003eAll patients in the DECAAF II study with complete data were considered for analysis. Two separate analyses were performed to evaluate the usage of metoprolol or diltiazem before catheter ablation. The first comparison evaluates the use of metoprolol; patients undergoing DTCA without a history of beta blocker use were compared to patients with a history of metoprolol use before ablation. The second comparison evaluates diltiazem use; patients undergoing DTCA without a history of CCB use were compared to patients with a history of diltiazem use before ablation. As described in DECAAF II, the primary endpoint of the study was the first confirmed recurrence of atrial arrhythmia (including AF, atrial flutter, or atrial tachycardia) lasting for at least 30 seconds after the 90-day blanking period, demonstrated by at least two consecutive 1-lead smartphone ECG device tracings, one positive reading on a clinical 12-lead ECG tracing, ambulatory monitor, or if the patient underwent repeat ablation. The daily smartphone ECGs were intended as the primary method for assessing atrial arrhythmia recurrence. Still, clinical and ambulatory ECGs served as backup methods for detecting recurrence in patients who failed to transmit smartphone ECG readings reliably. A core laboratory at the University of Washington adjudicated the ECG findings. This sub-analysis utilized the 36-item Short Form Survey (SF-36) score as the primary subjective outcome metric to evaluate the quality of life at baseline and 12 months. Baseline MRI results were utilized to quantify left atrial (LA) fibrosis and LA volume in all patients at baseline and the 3-month follow-up. LA Volume was indexed to body surface area. Patients were followed for 12\u0026ndash;18 months.\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec5\" class=\"Section2\"\u003e\u003ch2\u003e2.3 Statistical Analysis\u003c/h2\u003e\u003cp\u003eDemographics and common comorbidities were compared between each group pairing within their respective analysis (metoprolol group vs no beta-blocker group, and diltiazem group vs no CCB group). Normality was assessed using the Shapiro-Wilk test for continuous variables, with Wilcoxon and t-tests conducted accordingly, depending on normality. Continuous variables are presented as median with standard deviation in parentheses. Categorical variables were tested with Chi-square tests and presented with counts and percentages of the specific study group. The Kaplan-Meier curve was used to evaluate the univariate effect of the independent variable, use of rate control agent before ablation, on the primary outcome of AF recurrence after ablation. Corresponding p-values are generated using the log-rank test. Two separate multivariable Cox models, one for each analysis, assessed the independent effects of clinically relevant variables. They were selected based on individual significance in t-tests assessing their impact on the primary outcomes. All statistical analysis was performed using R (version 4.3.0) software, with a 2-sided significance level of 0.05.\u003c/p\u003e\u003c/div\u003e"},{"header":"Results","content":"\u003cdiv id=\"Sec7\" class=\"Section2\"\u003e\u003ch2\u003e3.1 Baseline Characteristics:\u003c/h2\u003e\u003cp\u003eA total of 760 patients within DECAAF II were considered for analysis, with 199 excluded for insufficient LGE MRI data. The mean age of patients was 62.0\u0026thinsp;\u0026plusmn;\u0026thinsp;9.0 years, and 79.5% were males. 260 patients taking metoprolol before catheter ablation were identified and compared to 209 patients not taking any beta blocker before ablation. 55 patients taking diltiazem before ablation were identified and compared to 639 patients not taking any CCB before ablation. Baseline characteristics of all groups, in their respective comparison pairings, are shown in Tables\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e and \u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e.\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eDemographics (Direct-to-Catheter vs. Pre-ablation Metoprolol groups)\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"4\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u003cp\u003eVariable\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003eDirect-to-Catheter without prior Beta Blocker (N\u0026thinsp;=\u0026thinsp;209)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003ePre-ablation Metoprolol (N\u0026thinsp;=\u0026thinsp;260)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u003cp\u003e\u003cem\u003ep\u003c/em\u003e-value\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eAge, years\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e62.0\u0026thinsp;\u0026plusmn;\u0026thinsp;8.9\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e62.4\u0026thinsp;\u0026plusmn;\u0026thinsp;9.5\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.54\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eSex (male)\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e164 (78.5%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e199 (76.5%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.62\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eBMI\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e30.8\u0026thinsp;\u0026plusmn;\u0026thinsp;5.6\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e32.4\u0026thinsp;\u0026plusmn;\u0026thinsp;6.9\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.006\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eLeft atrial volume (mL)\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e126.6\u0026thinsp;\u0026plusmn;\u0026thinsp;37.6\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e130.0\u0026thinsp;\u0026plusmn;\u0026thinsp;40.9\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.016\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eBaseline fibrosis (%)\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e18.6\u0026thinsp;\u0026plusmn;\u0026thinsp;7.4\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e19.1\u0026thinsp;\u0026plusmn;\u0026thinsp;7.3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.52\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eDiabetes Mellitus\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e15 (7.2%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e37 (14.2%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.016\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eCongestive Heart Failure\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e24 (11.5%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e54 (20.8%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.007\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eHypertension\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e105 (50.2%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e159 (61.2%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.018\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eCoronary Artery Disease\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e22 (10.5%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e32 (12.3%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.55\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eVascular Disease\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e14 (6.7%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e33 (12.7%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.032\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eStroke history\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e16 (7.7%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e31 (11.9%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.13\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eAldosterone Inhibitor Use\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e14 (6.7%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e16 (6.2%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.81\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cem\u003eRandomized treatment group\u003c/em\u003e:\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.40\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eConventional PVI\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e111 (53.1%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e128 (49.2%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003ePVI\u0026thinsp;+\u0026thinsp;Fibrosis-guided Ablation\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e98 (46.9%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e132 (50.8%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eDemographics (Direct-to-Catheter vs. Pre-ablation Diltiazem groups)\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"4\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u003cp\u003eVariable\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003eDirect-to-Catheter without prior Calcium Channel Blocker (N\u0026thinsp;=\u0026thinsp;639)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003ePre-ablation Diltiazem (N\u0026thinsp;=\u0026thinsp;55)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u003cp\u003e\u003cem\u003ep\u003c/em\u003e-value\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eAge, years\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e61.5\u0026thinsp;\u0026plusmn;\u0026thinsp;9.2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e64.4\u0026thinsp;\u0026plusmn;\u0026thinsp;8.1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.048\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eSex (male)\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e513 (80.3%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e41 (74.5%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.31\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eBMI\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e31.0\u0026thinsp;\u0026plusmn;\u0026thinsp;6.1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e34.2\u0026thinsp;\u0026plusmn;\u0026thinsp;9.0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eLeft atrial volume (mL)\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e129.5\u0026thinsp;\u0026plusmn;\u0026thinsp;41.4\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e137.4\u0026thinsp;\u0026plusmn;\u0026thinsp;37.5\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.092\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eBaseline fibrosis (%)\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e18.9\u0026thinsp;\u0026plusmn;\u0026thinsp;7.6\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e18.7\u0026thinsp;\u0026plusmn;\u0026thinsp;7.6\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.78\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eDiabetes Mellitus\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e56 (8.8%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e9 (16.4%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.06\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eCongestive Heart Failure\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e122 (19.1%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e15 (27.3%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.14\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eHypertension\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e331 (51.8%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e41 (74.5%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eCoronary Artery Disease\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e73 (11.4%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e8 (14.5%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.49\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eVascular Disease\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e62 (9.7%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e2 (3.6%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.14\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eStroke history\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e52 (8.1%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e5 (9.1%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.81\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eAldosterone Inhibitor Use\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e54 (8.5%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e1 (1.8%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.08\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cem\u003eRandomized treatment group\u003c/em\u003e:\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.50\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eConventional PVI\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e318 (49.8%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e30 (54.5%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003ePVI\u0026thinsp;+\u0026thinsp;Fibrosis-guided Ablation\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e321 (50.2%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e25 (45.5%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec8\" class=\"Section2\"\u003e\u003ch2\u003e3.2 Use of Metoprolol Before Ablation:\u003c/h2\u003e\u003cp\u003ePatients taking pre-ablation metoprolol group had higher BMI (32.4 vs 30.8, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;.006) higher rates of congestive heart failure (20.8% vs 11.5%, p\u0026thinsp;=\u0026thinsp;.007), vascular disease (12.7% vs 6.7%, P\u0026thinsp;=\u0026thinsp;.032), diabetes mellitus (14.2% vs 7.2%, p\u0026thinsp;=\u0026thinsp;.016) and hypertension (61.2% vs 50.2%, p\u0026thinsp;=\u0026thinsp;.018) as compared to those undergoing DTCA without Beta-blocker. Kaplan Meier survival analysis showed no significant difference in AF recurrence following ablation (p\u0026thinsp;=\u0026thinsp;.44) between these two groups (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e1\u003c/span\u003e\u003cb\u003e)\u003c/b\u003e. Mean quality of life as measured by SF36 scores was also similar between both groups at 12 months (p\u0026thinsp;=\u0026thinsp;.89) \u003cb\u003e(\u003c/b\u003eFig.\u0026nbsp;\u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e2\u003c/span\u003e\u003cb\u003e)\u003c/b\u003e. Left atrial volume index (LAVI) decrease at 12 months after ablation was also similar between groups (11.4 mm\u003csup\u003e3\u003c/sup\u003e vs 10.4 mm\u003csup\u003e3\u003c/sup\u003e, p\u0026thinsp;=\u0026thinsp;.298). Additionally, on LGE-MRI there were no significant differences of baseline fibrosis (19.1% vs 18.6%, p\u0026thinsp;=\u0026thinsp;0.52), residual fibrosis post-ablation (15.0% vs 14.1%, p\u0026thinsp;=\u0026thinsp;0.27), or fibrosis reduction (4.1% vs 4.1%, p\u0026thinsp;=\u0026thinsp;0.65) between the two groups \u003cb\u003e(\u003c/b\u003eTable\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e\u003cb\u003e).\u003c/b\u003e\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab3\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eDirect-to-Catheter vs. Pre-ablation Metoprolol: Fibrosis\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"5\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\"\u0026plusmn;\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\"\u0026plusmn;\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\"\u0026plusmn;\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u003cp\u003eVariable\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003eDTCA (No BB) (N\u0026thinsp;=\u0026thinsp;209)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003ePre-ablation Metoprolol (N\u0026thinsp;=\u0026thinsp;260)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u003cp\u003eTotal (N\u0026thinsp;=\u0026thinsp;469)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c5\"\u003e\u003cp\u003ep-value\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u003cp\u003eFibrosis\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/th\u003e\u003cth align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eBaseline fibrosis (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e\u003cp\u003e18.6\u0026thinsp;\u0026plusmn;\u0026thinsp;7.4\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e\u003cp\u003e19.1\u0026thinsp;\u0026plusmn;\u0026thinsp;7.3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e\u003cp\u003e18.9\u0026thinsp;\u0026plusmn;\u0026thinsp;7.3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.52\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eResidual fibrosis (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e\u003cp\u003e14.1\u0026thinsp;\u0026plusmn;\u0026thinsp;5.9\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e\u003cp\u003e15.0\u0026thinsp;\u0026plusmn;\u0026thinsp;6.5\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e\u003cp\u003e14.6\u0026thinsp;\u0026plusmn;\u0026thinsp;6.2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.27\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eFibrosis reduction (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e\u003cp\u003e4.1\u0026thinsp;\u0026plusmn;\u0026thinsp;2.4\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e\u003cp\u003e4.1\u0026thinsp;\u0026plusmn;\u0026thinsp;2.3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e\u003cp\u003e4.1\u0026thinsp;\u0026plusmn;\u0026thinsp;2.3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.65\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec9\" class=\"Section2\"\u003e\u003ch2\u003e3.3 Use of Diltiazem Before Ablation:\u003c/h2\u003e\u003cp\u003ePatients taking pre-ablation diltiazem were slightly older (64.4 vs 61.5, p\u0026thinsp;=\u0026thinsp;0.048), had higher BMI (34.3 vs 30.9, p\u0026thinsp;\u0026lt;\u0026thinsp;0.001), and had higher rates of hypertension (74.5% vs 51.8%, p\u0026thinsp;\u0026lt;\u0026thinsp;0.001) as compared to those undergoing DTCA without CCB. Kaplan Meier survival analysis showed no significant difference in AF recurrence following ablation (p\u0026thinsp;=\u0026thinsp;.34) between patients taking diltiazem before ablation and those not taking any CCB before ablation (Fig.\u0026nbsp;\u003cspan refid=\"Fig6\" class=\"InternalRef\"\u003e3\u003c/span\u003e). Mean quality of life scores were similar between both groups (p\u0026thinsp;=\u0026thinsp;.31) (Fig.\u0026nbsp;\u003cspan refid=\"Fig8\" class=\"InternalRef\"\u003e4\u003c/span\u003e\u003cb\u003e).\u003c/b\u003e LAVI was also similar at 12 months post-ablation. Additionally, no significant differences were seen on LGE MRI for baseline fibrosis (18.7% vs 18.9%, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.78), residual fibrosis post ablation (14.3% vs 14.7%, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.61) or fibrosis reduction (3.8% vs 4.0%, \u003cem\u003ep\u0026thinsp;=\u003c/em\u003e\u0026thinsp;0.49) \u003cb\u003e(\u003c/b\u003eTable\u0026nbsp;\u003cspan refid=\"Tab4\" class=\"InternalRef\"\u003e4\u003c/span\u003e\u003cb\u003e).\u003c/b\u003e\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab4\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 4\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eDirect-to-Catheter vs. Pre-ablation Diltiazem: Fibrosis\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"5\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\"\u0026plusmn;\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\"\u0026plusmn;\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\"\u0026plusmn;\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u003cp\u003eVariable\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003eDTCA (No CCB) (N\u0026thinsp;=\u0026thinsp;639)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003ePre-ablation Diltiazem (N\u0026thinsp;=\u0026thinsp;55)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u003cp\u003eTotal (N\u0026thinsp;=\u0026thinsp;694)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c5\"\u003e\u003cp\u003ep-value\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u003cp\u003eFibrosis\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/th\u003e\u003cth align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eBaseline fibrosis (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e\u003cp\u003e18.9\u0026thinsp;\u0026plusmn;\u0026thinsp;7.6\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e\u003cp\u003e18.7\u0026thinsp;\u0026plusmn;\u0026thinsp;7.6\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e\u003cp\u003e18.9\u0026thinsp;\u0026plusmn;\u0026thinsp;7.6\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.78\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eResidual fibrosis (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e\u003cp\u003e14.7\u0026thinsp;\u0026plusmn;\u0026thinsp;6.5\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e\u003cp\u003e14.3\u0026thinsp;\u0026plusmn;\u0026thinsp;7.0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e\u003cp\u003e14.7\u0026thinsp;\u0026plusmn;\u0026thinsp;6.5\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.61\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eFibrosis reduction (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e\u003cp\u003e4.0\u0026thinsp;\u0026plusmn;\u0026thinsp;2.3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e\u003cp\u003e3.8\u0026thinsp;\u0026plusmn;\u0026thinsp;2.1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e\u003cp\u003e4.0\u0026thinsp;\u0026plusmn;\u0026thinsp;2.3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.49\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec10\" class=\"Section2\"\u003e\u003ch2\u003e3.4 Multivariable Cox Regression\u003c/h2\u003e\u003cp\u003eIn both Cox Regression analysis and multivariable linear regression, the use of diltiazem before ablation had no significant effect on AF recurrence (p\u0026thinsp;=\u0026thinsp;.10). Both male sex (HR\u0026thinsp;=\u0026thinsp;.635, p\u0026thinsp;=\u0026thinsp;.002) and pre-ablation LA volume (HR\u0026thinsp;=\u0026thinsp;1.013, p\u0026thinsp;\u0026lt;\u0026thinsp;.001) emerged as statistically significant predictors. Using the same models for the other comparator, use of metoprolol prior to ablation had no statistically significant effect (p\u0026thinsp;=\u0026thinsp;.76), and pre-ablation LA volume had the most significant effect on AF recurrence (HR\u0026thinsp;=\u0026thinsp;1.012, p\u0026thinsp;\u0026lt;\u0026thinsp;.0001).\u003c/p\u003e\u003c/div\u003e"},{"header":"Discussion","content":"\u003cp\u003eAt 12-month follow-up, a direct-to-catheter approach appears similarly effective to pre-ablation rate control treatment with either diltiazem or metoprolol with respect to AF recurrence following ablation.\u003c/p\u003e\u003cdiv id=\"Sec12\" class=\"Section2\"\u003e\u003ch2\u003e4.2 The Role of Rate Control Agents Before Catheter Ablation\u003c/h2\u003e\u003cp\u003eHistorically, rate control has been a foundational approach to managing AF. The AFFIRM trial established that rate control was non-inferior to rhythm control with respect to all-cause mortality in AF patients.\u003csup\u003e\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e\u003c/sup\u003e However, more recent trials, such as EAST-AFNET 4, demonstrated that early rhythm control, including ablation, significantly reduced cardiovascular events.\u003csup\u003e\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e\u003c/sup\u003e Similarly, CABANA showed that catheter ablation reduced AF recurrence and improved symptoms compared to drug therapy, although mortality benefits were not statistically significant.\u003csup\u003e\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e\u003c/sup\u003e\u003c/p\u003e\u003cp\u003ePost-hoc analyses of CABANA and results from STOP-AF and EARLY-AF further support ablation earlier in the disease course.\u003csup\u003e\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e,\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e,9\u003c/sup\u003e Findings from DECAAF II revealed no added value from pharmacologic rhythm control before ablation.\u003csup\u003e\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e\u003c/sup\u003e\u003c/p\u003e\u003cp\u003e According to the 2023 AHA/ACC/HRS guidelines, rate control remains appropriate in minimally symptomatic patients or those unsuitable for rhythm control. However, catheter ablation holds a Class I recommendation for patients with symptomatic AF, without requiring a prior pharmacologic trial.\u003csup\u003e\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e\u003c/sup\u003e\u003c/p\u003e\u003cp\u003eOur findings suggest that beta-blockers and CCBs do not meaningfully alter post-ablation outcomes and may delay effective intervention. Early rhythm control, as supported by EAST-AFNET 4, is associated with fewer cardiovascular events and supports earlier use of ablation.\u003csup\u003e10\u003c/sup\u003e The SARA trial also demonstrated superiority to ablation over AAD for maintaining sinus rhythm at 12 months after intervention, although\u003c/p\u003e\u003cp\u003e Guidelines emphasize individualized therapy based on AF burden, comorbidities, and access to procedural care. This study contributes to the growing evidence supporting DTCA as a practical and effective first-line strategy for PersAF management.\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec13\" class=\"Section2\"\u003e\u003ch2\u003e4.3. Mechanistic Insights\u003c/h2\u003e\u003cp\u003eRate control agents such as metoprolol and diltiazem effectively slow ventricular response to AF, reducing the risk of tachycardia-induced cardiomyopathy, left ventricular (LV) remodeling, and improving symptoms.\u003csup\u003e\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e11\u003c/span\u003e,\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e12\u003c/span\u003e\u003c/sup\u003e However, they may not protect against LA remodeling since the LA is still subjected to the rapid depolarizations of AF. While these agents prevent electrical propagation to the ventricles, they do not prevent foci from firing. Accordingly, even with a decrease in ventricular rate, the LA may still be subject to the same remodeling forces experienced by a patient not treated with rate control. Since LA remodeling, such as dilation and low voltage, has been most consistently associated with the risk of early recurrence, it is understandable that such rate control agents may not significantly lower the risk of early recurrence following ablation.\u003csup\u003e\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e13\u003c/span\u003e\u003c/sup\u003e While beta-blockers have been shown to improve all-cause mortality in patients with AF regardless of heart failure presence, there is no rigorous study finding any effects on LA fibrosis.\u003csup\u003e\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e14\u003c/span\u003e\u003c/sup\u003e\u003c/p\u003e\u003cp\u003eAF is a progressive disease as described by the concept \u0026ldquo;AF begets AF,\u0026rdquo; in which AF episodes cause consequent arrhythmogenic changes in the LA, which promote further AF episodes.\u003csup\u003e\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e15\u003c/span\u003e,\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e16\u003c/span\u003e,\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e17\u003c/span\u003e\u003c/sup\u003e Accordingly, symptomatic improvement with rate control agents that delay catheter ablation may unnecessarily subject a patient to further remodeling of the LA while awaiting definitive treatment. Particularly in the PersAF population, according to our analysis of DECAAF II, the extent of LA remodeling may render the effect of rate control on recurrence after ablation negligible. In patients with such advanced disease, isolation of causative foci is likely the only mode of treatment, and it may be reasonable to consider a DTCA approach in select patients.\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec14\" class=\"Section2\"\u003e\u003ch2\u003e4.4. Limitations and Future Directions\u003c/h2\u003e\u003cp\u003eOur analysis of DECAAF II is limited by its retrospective nature. A lack of long-term follow-up makes it difficult to draw conclusions on differences in the long-term efficacy of ablation between groups. An analysis of non-selective beta blockers and other CCBs may give a fuller picture of the differences in effects within each drug class. Strong RCTs examining the impact of rate control before catheter ablation on LA fibrosis and AF recurrence will help better elucidate the role of a DTCA approach. Pre- and post-ablation imaging of patients with a spectrum of AF phenotypes, compared to our sole PersAF cohort, will help establish any variance in rate control effect on outcomes. Analysis of an optimal treatment length before ablation will be valuable in ensuring best practices. As rate control agents have more established effects on ventricular remodeling, future investigation should also analyze their role in pre-ablation treatment for patients with AF and concomitant HF.\u003c/p\u003e\u003c/div\u003e"},{"header":"Conclusion","content":"\u003cp\u003eOur analysis of PersAF patients undergoing catheter ablation found that pretreatment with metoprolol or diltiazem did not confer additional benefits in reducing AF recurrence, LA fibrosis, or improving Qol over a 12-month follow-up period. These results suggest that DTCA may be a reasonable alternative to pre-ablation rate control with beta-blockers or calcium channel blockers.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003e\u003cu\u003eFunding:\u003c/u\u003e\u003c/strong\u003e No specific funding was received for this work.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cu\u003eConsent to Participate:\u003c/u\u003e\u003c/strong\u003e All patients in the DECAAF II trial provided written informed consent according to the trial protocol and local IRB/ethics committee approvals.\u0026nbsp;\u003csup\u003e6\u003c/sup\u003e\u003c/p\u003e\n"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eLinz D, Gawalko M, Betz K, et al. Atrial fibrillation: epidemiology, screening and digital health. \u003cem\u003eThe Lancet Regional Health \u0026ndash; Europe\u003c/em\u003e. 2024;37. doi:10.1016/j.lanepe.2023.100786\u003c/li\u003e\n\u003cli\u003eJoglar JA, Chung MK, Armbruster AL, et al. 2023 ACC/AHA/ACCP/HRS Guideline for the Diagnosis and Management of Atrial Fibrillation: A Report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines. \u003cem\u003eCirculation\u003c/em\u003e. 2024;149(1):e1-e156. doi:10.1161/CIR.0000000000001193\u003c/li\u003e\n\u003cli\u003eBoriani G, Mei DA, Vitolo M, Imberti JF. The 2024 ESC guidelines on atrial fibrillation: essential updates for everyday clinical practice. \u003cem\u003eIntern Emerg Med\u003c/em\u003e. 2025;20(5):1299-1306. doi:10.1007/s11739-025-04006-1\u003c/li\u003e\n\u003cli\u003eKirchhof P, Camm AJ, Goette A, et al. Early Rhythm-Control Therapy in Patients with Atrial Fibrillation. \u003cem\u003eN Engl J Med\u003c/em\u003e. 2020;383(14):1305-1316. doi:10.1056/NEJMoa2019422\u003c/li\u003e\n\u003cli\u003eYounes H, Ademi B, Tsakiris E, et al. Direct-to-catheter ablation versus second line catheter ablation for persistent atrial fibrillation: Effect on arrhythmia recurrence, AF burden, early left atrium remodeling and quality of life. \u003cem\u003eJ Interv Card Electrophysiol\u003c/em\u003e. Published online September 12, 2024. doi:10.1007/s10840-024-01916-6\u003c/li\u003e\n\u003cli\u003eMarrouche NF, Greene T, Dean JM, et al. Efficacy of LGE-MRI-guided fibrosis ablation versus conventional catheter ablation of atrial fibrillation: The DECAAF II trial: Study design. \u003cem\u003eJ Cardiovasc Electrophysiol\u003c/em\u003e. 2021;32(4):916-924. doi:10.1111/jce.14957\u003c/li\u003e\n\u003cli\u003eWyse DG, Waldo AL, DiMarco JP, et al. A comparison of rate control and rhythm control in patients with atrial fibrillation. \u003cem\u003eN Engl J Med\u003c/em\u003e. 2002;347(23):1825-1833. doi:10.1056/NEJMoa021328 \u003c/li\u003e\n\u003cli\u003eMeyer M, Lustgarten D. Beta-blockers in atrial fibrillation\u0026mdash;trying to make sense of unsettling results. \u003cem\u003eEP Europace\u003c/em\u003e. 2023;25(2):260-262. doi:10.1093/europace/euad010\u003c/li\u003e\n\u003cli\u003eSabbah HN. The cellular and physiologic effects of beta blockers in heart failure. \u003cem\u003eClin Cardiol\u003c/em\u003e. 1999;22 Suppl 5:V16-20.\u003c/li\u003e\n\u003cli\u003eGarvanski I, Simova I, Angelkov L, Matveev M. Predictors of Recurrence of AF in Patients After Radiofrequency Ablation. \u003cem\u003eEur Cardiol\u003c/em\u003e. 2019;14(3):165-168. doi:10.15420/ecr.2019.30.2\u003c/li\u003e\n\u003cli\u003eStrauss MH, Hall AS, Narkiewicz K. The Combination of Beta-Blockers and ACE Inhibitors Across the Spectrum of Cardiovascular Diseases. \u003cem\u003eCardiovasc Drugs Ther\u003c/em\u003e. 2023;37(4):757-770. doi:10.1007/s10557-021-07248-1\u003c/li\u003e\n\u003cli\u003eLu Z, Scherlag BJ, Lin J, et al. Atrial Fibrillation Begets Atrial Fibrillation. \u003cem\u003eCirculation: Arrhythmia and Electrophysiology\u003c/em\u003e. 2008;1(3):184-192. doi:10.1161/CIRCEP.108.784272\u003c/li\u003e\n\u003cli\u003eAllessie M, Ausma J, Schotten U. Electrical, contractile and structural remodeling during atrial fibrillation. \u003cem\u003eCardiovasc Res\u003c/em\u003e. 2002;54(2):230-246. doi:10.1016/s0008-6363(02)00258-4\u003c/li\u003e\n\u003cli\u003eWijffels MC, Kirchhof CJ, Dorland R, Allessie MA. Atrial fibrillation begets atrial fibrillation. A study in awake chronically instrumented goats. \u003cem\u003eCirculation\u003c/em\u003e. 1995;92(7):1954-1968. doi:10.1161/01.cir.92.7.1954\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"","lastPublishedDoi":"10.21203/rs.3.rs-7672338/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-7672338/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground:\u003c/h2\u003e\u003cp\u003eFor patients with persistent atrial fibrillation (PersAF), initial treatment strategies often involve rate or rhythm control before offering ablation. This study compared two approaches: (1) catheter ablation without prior medication (referred to as direct-to-catheter ablation, DTCA) and (2) catheter ablation after initial rate control with either diltiazem or metoprolol.\u003c/p\u003e\u003ch2\u003eObjective:\u003c/h2\u003e\u003cp\u003eThis study included two independent comparative analyses of patients with persistent atrial fibrillation (PersAF) undergoing catheter ablation. Aimed at evaluating the potential impact of pre-ablation rate control medications including beta blockers and calcium channel blockers on post-ablation outcomes. Comparison 1: DTCA without prior beta-blocker use (n\u0026thinsp;=\u0026thinsp;209) vs. metoprolol use prior to ablation (n\u0026thinsp;=\u0026thinsp;260). Comparison 2: DTCA without prior calcium channel blocker use (n\u0026thinsp;=\u0026thinsp;639) vs. diltiazem use prior to ablation (n\u0026thinsp;=\u0026thinsp;55).\u003c/p\u003e\u003ch2\u003eMethods:\u003c/h2\u003e\u003cp\u003ePatients were followed for 18 months to evaluate primary outcome: recurrence of atrial fibrillation (AF) and secondary outcomes: Pre-ablation and Post-ablation left atrial percent fibrosis as seen on LGE MRI and Quality of life (QoL), measured with the SF-36 questionnaire. The Wilcoxon tests were conducted to compare the QoL and fibrosis among groups. Time to recurrence among the groups post ablation was assessed via Kaplan-Meier curves. Multivariable Cox models were developed to adjust for other confounders of AF recurrence.\u003c/p\u003e\u003ch2\u003eResults:\u003c/h2\u003e\u003cp\u003eIn the beta-blocker analysis (n\u0026thinsp;=\u0026thinsp;469), no significant difference in AF recurrence was observed between patients without prior beta-blocker use (DTCA group) and those treated with metoprolol (Kaplan-Meier, p\u0026thinsp;\u0026gt;\u0026thinsp;0.05). Similarly, in the calcium channel blocker analysis (n\u0026thinsp;=\u0026thinsp;694), no difference in recurrence was found between the DTCA group and those with prior diltiazem use (p\u0026thinsp;\u0026gt;\u0026thinsp;0.05). Multivariable Cox models confirmed that neither metoprolol (p\u0026thinsp;=\u0026thinsp;0.44) nor diltiazem (p\u0026thinsp;=\u0026thinsp;0.34) independently predicted AF recurrence. Additionally, no significant differences were found in any fibrosis metrics or QoL between the groups in either comparison (all p\u0026thinsp;\u0026gt;\u0026thinsp;0.05).\u003c/p\u003e\u003ch2\u003eConclusion:\u003c/h2\u003e\u003cp\u003ePrior treatment with diltiazem or metoprolol before ablation of PersAF did not show additional benefits in reducing patient outcomes such as AF recurrence, fibrosis, or improving QoL.\u003c/p\u003e","manuscriptTitle":"Pre-Ablation Rate Control Therapy and Direct-to-Catheter Ablation in Patients with Persistent Atrial Fibrillation: A DECAAF II Subanalysis","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-10-12 14:27:30","doi":"10.21203/rs.3.rs-7672338/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"f19d25f9-f2db-4f9f-b516-1271325ec141","owner":[],"postedDate":"October 12th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2026-01-12T16:02:19+00:00","versionOfRecord":{"articleIdentity":"rs-7672338","link":"https://doi.org/10.1007/s10840-025-02218-1","journal":{"identity":"journal-of-interventional-cardiac-electrophysiology","isVorOnly":false,"title":"Journal of Interventional Cardiac Electrophysiology"},"publishedOn":"2026-01-06 15:57:46","publishedOnDateReadable":"January 6th, 2026"},"versionCreatedAt":"2025-10-12 14:27:30","video":"","vorDoi":"10.1007/s10840-025-02218-1","vorDoiUrl":"https://doi.org/10.1007/s10840-025-02218-1","workflowStages":[]},"version":"v1","identity":"rs-7672338","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-7672338","identity":"rs-7672338","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}