Low resting heart rate is associated with recurrence in persistent atrial fibrillation after catheter ablation

Low resting heart rate is associated with recurrence in persistent atrial fibrillation after catheter ablation | 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 Low resting heart rate is associated with recurrence in persistent atrial fibrillation after catheter ablation Wanting Qin, Kangning Han, Liu He, Xia Li, Biao Fu, Wei Wang, and 6 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-8468599/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted 10 You are reading this latest preprint version Abstract Background: Resting heart rate (RHR)is critical for identifying high-risk patients with atrial fibrillation (AF). However, the association between resting heart rate (RHR) and AF recurrence after catheter ablation remains unknown. Objective: This study was to evaluate the association between RHR and recurrence in patients with persistent atrial fibrillation (PeAF) after catheter ablation. Methods: Data from the China-AF registry (ChiCTR-OCH-13003729) from January 2018 to December 2023 at Beijing Anzhen Hospital were retrospectively analyzed. The primary outcome was the recurrence of AF, defined as an episode of atrial tachyarrhythmia lasting >30 seconds after a 3-month blanking period. The secondary outcome was the composite of heart failure, ischemic stroke, and cardiovascular death. Cox regression was used to assess the association between RHR and outcomes. Results: Our study included 2,432 patients with PeAF undergoing catheter ablation. Cox regression demonstrated that RHR of 40-60 bpm was associated with an increased risk of recurrence after adjusting the confounders (HR=2.08, 95% CI:1.16-3.74, P= 0.014). Additionally, we showed that patients with low RHR (40-60 bpm) had a higher risk of the composite of heart failure, ischemic stroke, and cardiovascular death (HR=11.69, 95% CI:3.01-45.43, P< 0.001). Conclusion: Low RHR is associated with recurrence in PeAF after catheter ablation, where RHR of 40-60 bpm exhibits a higher risk. Atrial fibrillation resting heart rate catheter ablation recurrence prognosis Figures Figure 1 Figure 2 Introduction Atrial fibrillation (AF) represents the most common sustained cardiac arrhythmia in clinical practice, posing a significant risk of stroke and heart failure. Heart rate control constitutes a fundamental component of AF management even for patients who will get rhythm control. Particularly, resting heart rate (RHR) serves as a vital, readily accessible clinical indicator for assessing the adequacy of heart rate control and for identifying individuals with AF who may be at an elevated risk. Previous investigations have demonstrated an association between an increased RHR and unfavorable outcomes in the general AF population( 1 , 2 ). However, their applicability to patients after catheter ablation is not straightforward, as the ablation induces significant physiological changes to cardiac autonomic innervation, a key determinant of RHR. Catheter ablation could have direct impact on the auto nervous system by decreasing the parasympathetic activity( 3 ). This provides a strong physiological rationale for expecting alterations in RHR following ablation, and suggests that the changes of RHR could potentially correlate with recurrence. Detecting the relationship between RHR and AF recurrence after catheter ablation is important since the catheter ablation has emerged as an increasingly recommended and effective rhythm control intervention for AF. Despite the escalating use and success of catheter ablation, AF recurrence remains a significant clinical challenge. Ideally, using the RHR to predict the recurrence of AF is easily accessible and could provide therapeutic indication of the management of RHR. The relationship between RHR and recurrence after catheter ablation may theoretically follow the same pattern with the relationship between RHR and the initial development of AF in the general population. Previous study showed there was a U-shaped relationship between RHR and the risk of developing AF, with both low and high RHR being associated with the development of AF. However, some research indicates that an increase in RHR following ablation may be associated with a lower likelihood of AF recurrence but the detailed relationship is still unknown. This counterintuitive finding, contrasting with the general cardiovascular principle that a lower RHR is often preferable strongly underscores the necessity for more definitive research. Therefore, in the study we used the large sample size data of patients with persistent AF (PeAF) undergoing catheter ablation to detect the relationship between RHR and the recurrence of AF. Methods This study was a single-center, retrospective analysis derived from China-AF registry (ChiCTR-OCH-13003729) which is a prospective observational study of patients with AF. Patients with PeAF undergoing catheter ablation at Beijing Anzhen Hospital from January 2018 to December 2023 were enrolled. Ethics approval was obtained from the Human Research Ethics Committees at Beijing Anzhen Hospital. All participants in the cohort obtained written informed consent. The primary outcome was the recurrence of AF, defined as an episode of atrial tachyarrhythmia lasting > 30 seconds after a 3-month blanking period. The secondary outcome was the composite of heart failure, ischemic stroke, and cardiovascular death. Cardiovascular death includes death caused by acute myocardial infarction, sudden cardiac death, heart failure, stroke, or other cardiovascular causes. Follow-up surveys were conducted at the third, sixth, and twelfth month after treatment through telephone interviews and out-patients. Detection of AF recurrence was performed using a three-component strategy. Firstly, patients adhered to a scheduled follow-up protocol involving electrocardiograms (ECGs) and 24-hour Holter monitoring. Secondly, symptom-driven ECGs were conducted whenever a patient reported episodes of tachycardia. Thirdly, any incidental ECG or Holter recordings obtained for unrelated clinical indications were also analyzed. All antiarrhythmic drugs (AADs) were stopped for at least five half-lives before ablation. Patients with a history of pacemaker implantation were excluded. Radiofrequency ablation guided by a three-dimensional electroanatomic mapping system (CARTO, Biosense-Webster, Inc.) were performed. All patients underwent pulmonary vein isolation (PVI) and the majority of patients were treated with an optimized linear ablation and ethanol infusion via the vein of Marshall, known as the '2C3L' procedure( 4 ). This technique has been previously published and was demonstrated to significantly increase the success rate compared to PVI alone( 5 ). Cardioversion was performed if AF persisted or converted to an organized atrial tachyarrhythmia following the ablation. The RHR was measured in a resting state on the morning of the first day after ablation. Only the patients with successfully converted to sinus rhythm and with RHR recorded in sinus rhythm were included. RHR was categorized into five different groups: 40–60 bpm, 61–70 bpm, 71–80 bpm, 81–90 bpm and 91–100 bpm. Continuous variables are summarized as mean ± standard deviation (SD) or median with interquartile range, as appropriate based on data distribution. Comparisons among the five groups were performed using one-way analysis of variance (ANOVA) for normally distributed data or the Kruskal-Wallis H test for non-normally distributed data. To further explore inter-group differences, pairwise post-hoc comparisons were performed for all baseline variables. Following ANOVA, Tukey's Honestly Significant Difference test was applied. For variables analyzed with the Kruskal-Wallis test, Dunn's test for multiple comparisons was utilized. For categorical variables, pairwise comparisons were conducted using the Chi-squared test. To account for multiple comparisons in these pairwise analyses, all p-values were adjusted using the Benjamini-Hochberg method to control the False Discovery Rate. Cumulative incidence curves were visualized using the Kaplan–Meier analyses, and the log-rank test was performed. Multivariable Cox proportional hazard analyses were performed to compute the hazard ratio with a 95% confidence interval by adjusting for age, gender, history of hypertension, diabetes, coronary heart disease, valvular AF, heart failure, cerebrovascular disease, chronic kidney disease, smoking, drinking, left atrial anteroposterior diameter, left ventricular ejection fraction, AF duration, AADs (moracizine, propafenone, sotalol, amiodarone), rate control agents (β blocker, calcium channel blocker, digoxin), oral anticoagulant (warfarin, rivaroxaban, dabigatran, edoxaban), antiplatelet (aspirin, clopidogrel, ticagrelor), glucose lowering agents (oral hypoglycemic drugs, insulin), and angiotensin converting enzyme inhibitors/angiotensin 2 receptor blockers (ACEI/ARB). A two-sided adjusted p-value of less than 0.05 was considered statistically significant. The statistical analyses were performed using R version 4.5.0 (The R Project for Statistical Computing, Vienna, Austria). Results A total of 2,432 patients were included in the final analysis, with a median follow-up of 375 (346–741) days. Among them, 72.1% were men and the mean age was 63 years. At baseline, the distribution of RHR was as follows: 22 patients (0.9%) had an RHR of 40–60 bpm, 326 (13.4%) had an RHR of 61–70 bpm, 1,625 (66.8%) had an RHR of 71–80 bpm, 390 (16.0%) had an RHR of 81–90 bpm, and 69 (2.9%) had an RHR of 91–100 bpm. Baseline characteristics of these groups are shown in Table 1 . Patients with RHR of 40–60 bpm were more likely to be female (72.7%; P < 0.001). During the follow-up period, a total of 817 (33.6%) patients experienced AF recurrence. The recurrence rate significantly differed across groups ( P = 0.027). Patients with RHR of 40–60 bpm exhibited the highest recurrent rate (63.6%), followed by those with 91–100 bpm (39.1%). Post-hoc analysis showed patients with 40–60 bpm group had a significantly lower proportion of male patients compared to the 61–70 bpm group (27.3% vs. 70.6%, respectively; adjusted P < 0.001). Regarding the primary outcome, patients in the 40–60 bpm group experienced a significantly higher rate of AF recurrence than those in the 61–70 bpm group (63.6% vs. 33.4%; adjusted P = 0.0278) (Supplemental Table 1). Table 1 Baseline characteristics of the study population Variables Total (n = 2432) 40–60 bpm (n = 22) 61–70 bpm (n = 326) 71–80 bpm (n = 1625) 81–90 bpm (n = 390) 91–100 bpm (n = 69) P Male sex, n (%) 1754 (72.1) 6 (27.3) 230 (70.6) 1175 (72.3) 288 (73.8) 55 (79.7) < 0.001 Age (years) 63.0 [56.0–69.0] 69.0 [62.0-75.5] 63.0 [56.0–69.0] 63.0 [56.0–69.0] 63.0 [56.0–69.0] 63.0 [54.0–68.0] 0.144 Previous history, n (%) Smoking 159 (6.5) 1 (4.5) 22 (6.7) 98 (6.0) 34 (8.7) 4 (5.8) 0.413 Drinking 218 (9.0) 0 (0.0) 22 (6.7) 143 (8.8) 44 (11.3) 9 (13.0) 0.086 Hypertension 1397 (57.4) 12 (54.5) 200 (61.3) 936 (57.6) 218 (55.9) 31 (44.9) 0.140 Diabetes 449 (18.5) 2 (9.1) 57 (17.5) 304 (18.7) 73 (18.7) 13 (18.8) 0.813 Coronary artery disease 345 (14.2) 4 (18.2) 49 (15.0) 225 (13.8) 59 (15.1) 8 (11.6) 0.862 Heart failure 423 (17.4) 5 (22.7) 66 (20.2) 283 (17.4) 60 (15.4) 9 (13.0) 0.369 Cerebrovascular disease 258 (10.6) 2 (9.1) 36 (11.0) 173 (10.6) 39 (10.0) 8 (11.6) 0.987 CKD 64 (2.6) 1 (4.5) 13 (4.0) 43 (2.6) 7 (1.8) 0 (0.0) 0.232 Valvular AF, n (%) 33 (1.4) 1 (4.5) 6 (1.8) 21 (1.3) 3 (0.8) 2 (2.9) 0.340 Left atrium diameter (mm) 44.0 [40.0–47.0] 45.0 [41.3–47.8] 44.0 [40.0–48.0] 44.0 [41.0–47.0] 44.0 [40.0–48.0] 43.0 [40.0–47.0] 0.714 LVEF (%). 60.0 [56.0–65.0] 60.0 [58.0–64.0] 60.0 [55.0–64.0] 60.0 [56.0–65.0] 60.0 [56.0–64.0] 63.0 [57.0-66.3] 0.236 Duration of AF diagnosis (years) 2.0 [0.5-5.0] 3.0 [0.5–6.8] 2.0 [0.5-5.0] 2.0 [0.5-5.0] 2.0 [0.5-5.0] 3.0 [0.3-7.0] 0.807 AF recurrence, n (%) 817 (33.6) 14 (63.6) 109 (33.4) 546 (33.6) 121 (31.0) 27 (39.1) 0.027 AADs, n (%) 1625 (66.8) 12 (54.5) 208 (63.8) 1090 (67.1) 267 (68.5) 48 (69.6) 0.464 Rate control agents, n (%) 808 (33.2) 11 (50.0) 102 (31.3) 539 (33.2) 126 (32.3) 30 (43.5) 0.149 Oral anticoagulant, n (%) 2196 (90.3) 22 (100.0) 284 (87.1) 1474 (90.7) 355 (91.0) 61 (88.4) 0.138 Antiplatelet, n (%) 121 (5.0) 0 (0.0) 17 (5.2) 73 (4.5) 28 (7.2) 3 (4.3) 0.195 Glucose lowering agents, n (%) 410 (16.9) 2 (9.1) 49 (15.0) 279 (17.2) 68 (17.4) 12 (17.4) 0.746 ACEI/ARB, n (%) 806 (33.1) 6 (27.3) 115 (35.3) 534 (32.9) 131 (33.6) 20 (29.0) 0.801 CKD chronic kidney disease, AF atrial fibrillation, LVEF left ventricular ejection fraction, AADs antiarrhythmic drugs, ACEI angiotensin converting enzyme inhibitors, ARB angiotensin 2 receptor blockers. For the primary outcome, univariable Cox regression (61–70 bpm reference) revealed a significantly elevated HR in 40–60 bpm (HR = 2.57, 95% CI:1.47–4.49, P < 0.001). Additionally, there was a trend of increased HR in 91–100 bpm (HR = 1.52, 95% CI:1.00-2.32, P = 0.052). Multivariable Cox regression revealed that RHR of 40–60 bpm was significantly associated with AF recurrence (HR = 2.08, 95% CI:1.16–3.74, P = 0.014) (Table 2 ). Kaplan-Meier curves showed lower recurrence-free survival in RHR of 40–60 bpm, indicating higher AF recurrent risk (Fig. 1 ). Table 2 Univariable and multivariable regression analyses according to the RHR Events (n, %) Unadjusted HR (95% CI) P Adjusted HR (95% CI) P Primary outcome 40–60 bpm 14 (63.6%) 2.57 1.47–4.49 < 0.001 2.08 1.16–3.74 0.014 61–70 bpm 109 (33.4%) Reference 71–80 bpm 546 (33.6%) 1.07 0.87–1.31 0.536 1.05 0.85–1.29 0.668 81–90 bpm 121 (31.0%) 1.03 0.80–1.34 0.812 1.00 0.77–1.31 0.971 91–100 bpm 27 (39.1%) 1.52 1.00-2.32 0.052 1.47 0.96–2.25 0.077 Secondary outcome 40–60 bpm 4 (18.2%) 2.71 4.03–55.94 < 0.001 11.69 3.01–45.43 < 0.001 61–70 bpm 5 (1.5%) 71–80 bpm 41 (2.5%) 1.73 0.69–4.39 0.246 2.00 0.78–5.10 0.149 81–90 bpm 16 (4.1%) 3.12 1.14–8.52 0.027 3.79 1.36–10.52 0.001 91–100 bpm 2 (2.9%) 2.34 0.45–12.06 0.311 2.01 0.36–11.11 0.422 Multivariable regression was adjusted for age, gender, history of hypertension, diabetes, coronary heart disease, valvular AF, heart failure, cerebral infarction, chronic kidney disease, smoking, drinking, left atrial anteroposterior diameter, left ventricular ejection fraction, AF duration, AADs, rate control agents, oral anticoagulant, antiplatelet, glucose lowering agents and angiotensin converting enzyme inhibitors / angiotensin 2 receptor blockers. For the secondary outcome, univariable Cox regression (61–70 bpm reference) revealed a significantly elevated HRs in 40–60 bpm (HR = 2.71, 95% CI:4.03–55.94, P < 0.001) and 81–90 bpm (HR = 3.12, 95% CI:1.14–8.52, P = 0.027), whereas the other two groups showed no significant differences ( P = 0.246 and 0.311, respectively). Multivariable Cox regression also revealed that RHR of 40–60 bpm (HR = 11.69, 95% CI:3.01–45.43, P < 0.001) and 81–90 bpm (HR = 3.79, 95% CI:1.36–10.52, P = 0.001) maintained a significantly positive association with the secondary outcome (Table 2 ). Kaplan-Meier curves showed patients with RHR of 40–60 bpm were more susceptible to secondary outcomes (Fig. 2 ). Discussion The findings of this study elucidate a significant association between low RHR and recurrence for PeAF patients after catheter ablation. Specifically, RHR in the range of 40–60 bpm confers an elevated risk of recurrence. There is also a trend of recurrence in patients with high RHR of 91–100 bpm ( P = 0.077). Postoperative RHR represented a non-invasive and readily accessible reliable predictor for AF recurrence, enabling early screening of high-risk populations. We identified specific ranges of RHR associated with elevated recurrence risk, which highlights the clinical imperative to prioritize comprehensive management for patients with low RHR of 40–60 bpm, including more intensive or prolonged heart rate monitoring for this individual. Additionally, timely intervention for patients with high-risk RHR after ablation is essential to reduce recurrence and improve long-term outcomes. Regarding the selection of RHR acquisition time, most current studies rely on preoperative or long-term RHR, overlooking the critical immediate postoperative period. Postoperative RHR, as a non-invasive and readily accessible predictive marker for AF recurrence, exhibits substantial clinical value, particularly for patients with PeAF who inherently have a higher propensity for recurrence. Postoperative RHR can more intuitively reflect the patient's postoperative status, establish a reliable correlation between RHR and recurrence, and screen out patients with high risk of recurrence in the early postoperative period, enabling timely interventions to reduce the recurrence rate. Some studies analyzed the change in RHR before and after ablation. Killu AM et al.'s self-controlled study found a weak correlation between the relative change in overall RHR after ablation and AF recurrence ( P = 0.067). Patients were further divided into quartiles based on the relative change in RHR, and the upper quartile with the largest relative increase in RHR had a significantly lower AF recurrence rate than the lower quartile. Nilsson B et al. conducted an RCT on RHR changes after PVI in AF patients, showing that PVI may lead to RHR increase, which is positively correlated with ablation success( 6 ). Goff ZD et al. more precisely indicated that an increase in RHR ≥ 15 bpm after PVI was associated with 1-year freedom from AF( 7 ). These prior investigations have unequivocally established that an elevated postoperative RHR confers a protective effect against recurrence( 6 – 8 ). However, they failed to delineate the association between the exact RHR range in the immediate postoperative period and AF recurrence after ablation. Our study revealed that patients with postoperative RHR maintained within 61–90 bpm exhibit a diminished risk of recurrence and superior long-term prognosis. Meanwhile, by explicitly selecting RHR within 24 hours after ablation for analysis, our study excludes the interference of preoperative RHR monitoring methods compared with previous studies analyzing RHR changes before and after ablation, which not only can better represent the AF population after catheter ablation, but also can reflect the immediate postoperative status more intuitively. The relationship between RHR and recurrence in this study may involve multiple mechanisms. Ablation directly influences the autonomic nervous system by reducing parasympathetic activity( 9 , 10 ). Low RHR (40–60 bpm) may reflect autonomic dysfunction after ablation, particularly excessive vagal tone, which impacts atrial electrophysiological characteristics. This may increase atrial vulnerability to reentry by shortening action potential duration and enhancing conduction heterogeneity, thereby promoting AF recurrence. Conversely, higher RHR with shortening of myocardial action potential duration may be accompanied by calcium handling abnormalities (such as calcium overload), which in turn facilitates ectopic electrical activity associated with delayed after depolarization. This mechanism provides the electrophysiological substrate for the recurrence of AF. Additionally, extreme RHR may impair atrial mechanical function, leading to hemodynamic instability and further exacerbating AF recurrence( 11 – 13 ). Previous studies have documented a non-linear correlation between RHR and the occurrence of AF. Consistently, our study identified a similar pattern of association between RHR and recurrence of AF, which may suggest a shared underlying mechanism for AF development and recurrence. Morten W. Skov et al. found a U-shaped association between RHR and incident AF using electrocardiograms from 281,451 primary care patients excluding AF/atrial flutter, with this association being strongest for the outcome lone AF( 14 ). A previous meta-analysis using 68–80 bpm as the reference showed that both low and high RHR were associated with an increased risk of AF( 15 ). Although there are differences in the RHR ranges defining high AF risk across these studies( 14 – 16 ), the U/J-shaped association between RHR and AF incidence has shown high consistency. This bears similarity to the association established in our study between RHR and recurrence of AF, suggesting shared underlying mechanisms for incidence and recurrence, such as autonomic dysfunction or electrical remodeling. Previous study with a 1.5-year follow-up has shown that the progression of paroxysmal or persistent AF to a more sustained form was closely associated with faster heart rates( 17 ). This indicates that RHR is valuable not only for predicting AF incidence but also for forecasting disease progression. However, the optimal target range for RHR control in clinical practice remains undefined. The 2020 European Society of Cardiology guidelines recommend a standard heart rate control target of < 110 bpm( 18 ), yet the validity of this range and the necessity for strict heart rate control require further validation( 9 , 19 – 21 ). Undeniably, RHR demonstrates critical observational value in the progression of AF. Our cohort study further extends this to AF recurrence, highlighting the role of RHR in maintaining the arrhythmogenic substrate. The findings to some extent demonstrate the consistency of disease characteristics across different stages. RHR has been demonstrated to facilitate the screening of AF patients at high risk of cardiovascular adverse events. Both elevated and depressed RHR correlate with poor long-term prognosis( 22 , 23 ). Higher RHR is associated with an increased long-term risk of cardiovascular events (especially heart failure) and all-cause mortality, while lower RHR is associated with a greater risk of future permanent pacemaker implantation( 24 ). A retrospective analysis of the Atrial Fibrillation Rhythm Management (AFFIRM) study showed that RHR ≥ 80 bpm was associated with increased mortality risk in AF patients( 10 ). During a median follow-up of 24 months, Benjamin A. Steinberg et al. found a non-linear relationship between longitudinally measured RHR and mortality in patients with permanent AF, with an inflection point at 65 bpm. All-cause mortality increased as RHR deviated from 65 bpm( 19 ). In patients with AF and heart failure with reduced ejection fraction, high RHR (> 81 bpm) was associated with a progressive increase in mortality risk( 25 , 26 ). By contrast, in patients with AF and heart failure with preserved ejection fraction, RHR exhibited a U-shaped association with cardiovascular adverse events, where lower RHR also elevated mortality( 26 ). Collectively, these findings fully confirm that both excessively high and low RHR portend poor outcomes in AF. Study limitations Although this study enhanced the reliability of findings by employing a large sample size (2,468 patients) and multivariate models (adjusting for clinical confounders), robustly validating the relationship between RHR and AF recurrence, several limitations still remain: ( 1 ) As an observational cohort study, it cannot establish a causal relationship between RHR and AF recurrence. ( 2 ) Without continuous monitoring via insertable cardiac monitor, single RHR measurement within 24 hours postoperatively may fail to capture temporal variability. ( 3 ) Although the study used a large sample size so far, the sample size is still relatively small, with fewer secondary outcomes in certain RHR intervals (e.g., 91–100 bpm). Notwithstanding statistical significance was not achieved, the risk in this subgroup should not be overlooked. Conclusions This study confirms that low RHR is associated with recurrence in PeAF after catheter ablation, where RHR of 40–60 bpm exhibits a higher risk. Prospective studies are warranted to validate RHR as a therapeutic target and optimize individualized management strategies for preventing AF recurrence. Abbreviations AF: Atrial fibrillation PeAF: Persistent atrial fibrillation RHR: Resting heart rate AADs: Antiarrhythmic drugs ACEI: Angiotensin converting enzyme inhibitors ARB: Angiotensin 2 receptor blockers PVI: Pulmonary vein isolation ECGs: Electrocardiograms SD: Standard deviation ANOVA: One-way analysis of variance HR: Hazard ratio CI: Confidence interval CKD: Chronic kidney disease LVEF: Left ventricular ejection fraction RCT: Randomized controlled trial AFFIRM: Atrial Fibrillation Rhythm Management study RACE II: Rate control efficacy in permanent atrial fibrillation II study Declarations Data Availability Statement Data are available from the authors upon reasonable request and with permission of Beijing Anzhen Hospital, Capital Medical University. Funding Statement This study was supported by the Noncommunicable Chronic Diseases-National Science and Technology Major Project (2023ZD0504200). Conflict of Interest Disclosure The authors declare no conflict of interests. Ethics Approval Statement Ethics approval was obtained from the Human Research Ethics Committees at Beijing Anzhen Hospital. (NCT06987825). The study was conducted in accordance with the principles of the Declaration of Helsinki. P atient C onsent S tatement Informed consent was obtained from all patients. Author Contributions WQ, KH: investigation, original draft preparation, and formal analysis. WQ: data curation. KH: visualization. KH, XL, BF: methodology. LH, WW, TL, CJ, RT, CS, CM: supervision. DL: conceptualization and funding acquisition. All authors have read and agreed to the published version of the manuscript. References Van Gelder IC, Groenveld HF, Crijns HJGM, Tuininga YS, Tijssen JGP, Alings AM, et al. Lenient versus strict rate control in patients with atrial fibrillation. N Engl J Med. (2010) Apr 15;362(15):1363–73. Han K, Li X, Fu B, Li M, Liu T, Jiang C, et al. Longitudinal Association Between Resting Heart Rate and Mortality in Atrial Fibrillation. 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(2008) Nov;29(22):2772–81. Ho JE, Larson MG, Ghorbani A, Cheng S, Coglianese EE, Vasan RS, et al. Long-term cardiovascular risks associated with an elevated heart rate: The framingham heart study. J Am Heart Assoc. (2014) May 8;3(3):e000668. Suzuki S, Motoki H, Kanzaki Y, Maruyama T, Hashizume N, Kozuka A, et al. Prognostic significance of resting heart rate in atrial fibrillation patients with heart failure with reduced ejection fraction. Heart Vessels. (2020) Aug;35(8):1109–15. Song S, Ko JS, Lee HA, Choi EK, Cha MJ, Kim TH, et al. Clinical implications of heart rate control in heart failure with atrial fibrillation: Multi-center prospective observation registry (CODE-AF registry). Front Cardiovasc Med. (2022) Mar 22;9:787869. Additional Declarations No competing interests reported. Supplementary Files SupplementaryTable1.docx Cite Share Download PDF Status: Under Review Version 1 posted Editorial decision: Revision requested 14 Jan, 2026 Reviews received at journal 13 Jan, 2026 Reviewers agreed at journal 06 Jan, 2026 Reviews received at journal 30 Dec, 2025 Reviewers agreed at journal 30 Dec, 2025 Reviewers invited by journal 30 Dec, 2025 Editor invited by journal 30 Dec, 2025 Editor assigned by journal 29 Dec, 2025 Submission checks completed at journal 29 Dec, 2025 First submitted to journal 28 Dec, 2025 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. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-8468599","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":567320141,"identity":"4c037fe3-1b91-4895-b298-83fde18594f3","order_by":0,"name":"Wanting Qin","email":"","orcid":"","institution":"Beijing An Zhen Hospital: Capital Medical University Affiliated Anzhen Hospital","correspondingAuthor":false,"prefix":"","firstName":"Wanting","middleName":"","lastName":"Qin","suffix":""},{"id":567320146,"identity":"ba723671-a5b3-4bfe-8434-38cc154552e9","order_by":1,"name":"Kangning Han","email":"","orcid":"","institution":"Beijing An Zhen 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12:46:31","extension":"html","order_by":9,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":104115,"visible":true,"origin":"","legend":"","description":"","filename":"earlyproof.html","url":"https://assets-eu.researchsquare.com/files/rs-8468599/v1/6424a5a4467c45b57cc98672.html"},{"id":99788548,"identity":"514bf678-cd07-4fc2-90e7-5ff3cd36ee8a","added_by":"auto","created_at":"2026-01-08 12:47:04","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":263302,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eKaplan-Meier curve for AF recurrence by RHR group.\u003c/strong\u003e\u003c/p\u003e","description":"","filename":"floatimage1.png","url":"https://assets-eu.researchsquare.com/files/rs-8468599/v1/2dca9d2a55dd2f2337d89bb1.png"},{"id":99341213,"identity":"ccb1437e-a6a4-468c-ad33-7f050459caa1","added_by":"auto","created_at":"2026-01-01 06:19:08","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":48304,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eKaplan-Meier curve for the secondary outcomes by RHR group.\u003c/strong\u003e\u003c/p\u003e","description":"","filename":"floatimage2.png","url":"https://assets-eu.researchsquare.com/files/rs-8468599/v1/1fdf5055714d90fb612cb056.png"},{"id":99801922,"identity":"4996a8e4-9e42-4555-bdd1-1dc3ad0ddb60","added_by":"auto","created_at":"2026-01-08 14:07:40","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1080577,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-8468599/v1/55949571-b897-4b94-979d-7fc5b2574fed.pdf"},{"id":99788800,"identity":"003a666b-e407-40a8-a042-a5a1890eb0de","added_by":"auto","created_at":"2026-01-08 12:47:54","extension":"docx","order_by":0,"title":"","display":"","copyAsset":false,"role":"supplement","size":19270,"visible":true,"origin":"","legend":"","description":"","filename":"SupplementaryTable1.docx","url":"https://assets-eu.researchsquare.com/files/rs-8468599/v1/013de0732ccb5afc5093e804.docx"}],"financialInterests":"No competing interests reported.","formattedTitle":"Low resting heart rate is associated with recurrence in persistent atrial fibrillation after catheter ablation","fulltext":[{"header":"Introduction","content":"\u003cp\u003eAtrial fibrillation (AF) represents the most common sustained cardiac arrhythmia in clinical practice, posing a significant risk of stroke and heart failure. Heart rate control constitutes a fundamental component of AF management even for patients who will get rhythm control. Particularly, resting heart rate (RHR) serves as a vital, readily accessible clinical indicator for assessing the adequacy of heart rate control and for identifying individuals with AF who may be at an elevated risk.\u003c/p\u003e \u003cp\u003ePrevious investigations have demonstrated an association between an increased RHR and unfavorable outcomes in the general AF population(\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e). However, their applicability to patients after catheter ablation is not straightforward, as the ablation induces significant physiological changes to cardiac autonomic innervation, a key determinant of RHR. Catheter ablation could have direct impact on the auto nervous system by decreasing the parasympathetic activity(\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e). This provides a strong physiological rationale for expecting alterations in RHR following ablation, and suggests that the changes of RHR could potentially correlate with recurrence. Detecting the relationship between RHR and AF recurrence after catheter ablation is important since the catheter ablation has emerged as an increasingly recommended and effective rhythm control intervention for AF.\u003c/p\u003e \u003cp\u003eDespite the escalating use and success of catheter ablation, AF recurrence remains a significant clinical challenge. Ideally, using the RHR to predict the recurrence of AF is easily accessible and could provide therapeutic indication of the management of RHR. The relationship between RHR and recurrence after catheter ablation may theoretically follow the same pattern with the relationship between RHR and the initial development of AF in the general population. Previous study showed there was a U-shaped relationship between RHR and the risk of developing AF, with both low and high RHR being associated with the development of AF. However, some research indicates that an increase in RHR following ablation may be associated with a lower likelihood of AF recurrence but the detailed relationship is still unknown. This counterintuitive finding, contrasting with the general cardiovascular principle that a lower RHR is often preferable strongly underscores the necessity for more definitive research. Therefore, in the study we used the large sample size data of patients with persistent AF (PeAF) undergoing catheter ablation to detect the relationship between RHR and the recurrence of AF.\u003c/p\u003e"},{"header":"Methods","content":"\u003cp\u003eThis study was a single-center, retrospective analysis derived from China-AF registry (ChiCTR-OCH-13003729) which is a prospective observational study of patients with AF. Patients with PeAF undergoing catheter ablation at Beijing Anzhen Hospital from January 2018 to December 2023 were enrolled. Ethics approval was obtained from the Human Research Ethics Committees at Beijing Anzhen Hospital. All participants in the cohort obtained written informed consent.\u003c/p\u003e \u003cp\u003eThe primary outcome was the recurrence of AF, defined as an episode of atrial tachyarrhythmia lasting\u0026thinsp;\u0026gt;\u0026thinsp;30 seconds after a 3-month blanking period. The secondary outcome was the composite of heart failure, ischemic stroke, and cardiovascular death. Cardiovascular death includes death caused by acute myocardial infarction, sudden cardiac death, heart failure, stroke, or other cardiovascular causes. Follow-up surveys were conducted at the third, sixth, and twelfth month after treatment through telephone interviews and out-patients.\u003c/p\u003e \u003cp\u003eDetection of AF recurrence was performed using a three-component strategy. Firstly, patients adhered to a scheduled follow-up protocol involving electrocardiograms (ECGs) and 24-hour Holter monitoring. Secondly, symptom-driven ECGs were conducted whenever a patient reported episodes of tachycardia. Thirdly, any incidental ECG or Holter recordings obtained for unrelated clinical indications were also analyzed.\u003c/p\u003e \u003cp\u003eAll antiarrhythmic drugs (AADs) were stopped for at least five half-lives before ablation. Patients with a history of pacemaker implantation were excluded. Radiofrequency ablation guided by a three-dimensional electroanatomic mapping system (CARTO, Biosense-Webster, Inc.) were performed. All patients underwent pulmonary vein isolation (PVI) and the majority of patients were treated with an optimized linear ablation and ethanol infusion via the vein of Marshall, known as the '2C3L' procedure(\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e). This technique has been previously published and was demonstrated to significantly increase the success rate compared to PVI alone(\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e). Cardioversion was performed if AF persisted or converted to an organized atrial tachyarrhythmia following the ablation.\u003c/p\u003e \u003cp\u003eThe RHR was measured in a resting state on the morning of the first day after ablation. Only the patients with successfully converted to sinus rhythm and with RHR recorded in sinus rhythm were included. RHR was categorized into five different groups: 40\u0026ndash;60 bpm, 61\u0026ndash;70 bpm, 71\u0026ndash;80 bpm, 81\u0026ndash;90 bpm and 91\u0026ndash;100 bpm.\u003c/p\u003e \u003cp\u003eContinuous variables are summarized as mean\u0026thinsp;\u0026plusmn;\u0026thinsp;standard deviation (SD) or median with interquartile range, as appropriate based on data distribution. Comparisons among the five groups were performed using one-way analysis of variance (ANOVA) for normally distributed data or the Kruskal-Wallis H test for non-normally distributed data. To further explore inter-group differences, pairwise post-hoc comparisons were performed for all baseline variables. Following ANOVA, Tukey's Honestly Significant Difference test was applied. For variables analyzed with the Kruskal-Wallis test, Dunn's test for multiple comparisons was utilized. For categorical variables, pairwise comparisons were conducted using the Chi-squared test. To account for multiple comparisons in these pairwise analyses, all p-values were adjusted using the Benjamini-Hochberg method to control the False Discovery Rate.\u003c/p\u003e \u003cp\u003eCumulative incidence curves were visualized using the Kaplan\u0026ndash;Meier analyses, and the log-rank test was performed. Multivariable Cox proportional hazard analyses were performed to compute the hazard ratio with a 95% confidence interval by adjusting for age, gender, history of hypertension, diabetes, coronary heart disease, valvular AF, heart failure, cerebrovascular disease, chronic kidney disease, smoking, drinking, left atrial anteroposterior diameter, left ventricular ejection fraction, AF duration, AADs (moracizine, propafenone, sotalol, amiodarone), rate control agents (β blocker, calcium channel blocker, digoxin), oral anticoagulant (warfarin, rivaroxaban, dabigatran, edoxaban), antiplatelet (aspirin, clopidogrel, ticagrelor), glucose lowering agents (oral hypoglycemic drugs, insulin), and angiotensin converting enzyme inhibitors/angiotensin 2 receptor blockers (ACEI/ARB). A two-sided adjusted p-value of less than 0.05 was considered statistically significant. The statistical analyses were performed using R version 4.5.0 (The R Project for Statistical Computing, Vienna, Austria).\u003c/p\u003e"},{"header":"Results","content":"\u003cp\u003eA total of 2,432 patients were included in the final analysis, with a median follow-up of 375 (346\u0026ndash;741) days. Among them, 72.1% were men and the mean age was 63 years. At baseline, the distribution of RHR was as follows: 22 patients (0.9%) had an RHR of 40\u0026ndash;60 bpm, 326 (13.4%) had an RHR of 61\u0026ndash;70 bpm, 1,625 (66.8%) had an RHR of 71\u0026ndash;80 bpm, 390 (16.0%) had an RHR of 81\u0026ndash;90 bpm, and 69 (2.9%) had an RHR of 91\u0026ndash;100 bpm. Baseline characteristics of these groups are shown in Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e. Patients with RHR of 40\u0026ndash;60 bpm were more likely to be female (72.7%; \u003cem\u003eP\u0026thinsp;\u0026lt;\u003c/em\u003e\u0026thinsp;0.001). During the follow-up period, a total of 817 (33.6%) patients experienced AF recurrence. The recurrence rate significantly differed across groups (\u003cem\u003eP\u0026thinsp;=\u003c/em\u003e\u0026thinsp;0.027). Patients with RHR of 40\u0026ndash;60 bpm exhibited the highest recurrent rate (63.6%), followed by those with 91\u0026ndash;100 bpm (39.1%). Post-hoc analysis showed patients with 40\u0026ndash;60 bpm group had a significantly lower proportion of male patients compared to the 61\u0026ndash;70 bpm group (27.3% vs. 70.6%, respectively; adjusted \u003cem\u003eP\u0026thinsp;\u0026lt;\u003c/em\u003e\u0026thinsp;0.001). Regarding the primary outcome, patients in the 40\u0026ndash;60 bpm group experienced a significantly higher rate of AF recurrence than those in the 61\u0026ndash;70 bpm group (63.6% vs. 33.4%; adjusted \u003cem\u003eP\u0026thinsp;=\u003c/em\u003e\u0026thinsp;0.0278) (Supplemental Table\u0026nbsp;1).\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\u003eBaseline characteristics of the study population\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"8\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c8\" colnum=\"8\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVariables\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eTotal\u003c/p\u003e \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;2432)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003e40\u0026ndash;60 bpm\u003c/p\u003e \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;22)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003e61\u0026ndash;70 bpm\u003c/p\u003e \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;326)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003e71\u0026ndash;80 bpm\u003c/p\u003e \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;1625)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003e81\u0026ndash;90 bpm\u003c/p\u003e \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;390)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c7\"\u003e \u003cp\u003e91\u0026ndash;100 bpm\u003c/p\u003e \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;69)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c8\"\u003e \u003cp\u003e\u003cem\u003eP\u003c/em\u003e\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMale sex, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1754 (72.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e6 (27.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e230 (70.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e1175 (72.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e288 (73.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e55 (79.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\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\u003eAge (years)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e63.0 [56.0\u0026ndash;69.0]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e69.0 [62.0-75.5]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e63.0 [56.0\u0026ndash;69.0]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e63.0 [56.0\u0026ndash;69.0]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e63.0 [56.0\u0026ndash;69.0]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e63.0 [54.0\u0026ndash;68.0]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e0.144\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePrevious history, n (%)\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=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSmoking\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e159 (6.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e1 (4.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e22 (6.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e98 (6.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e34 (8.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e4 (5.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e0.413\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDrinking\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e218 (9.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0 (0.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e22 (6.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e143 (8.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e44 (11.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e9 (13.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e0.086\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHypertension\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1397 (57.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e12 (54.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e200 (61.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e936 (57.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e218 (55.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e31 (44.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e0.140\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDiabetes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e449 (18.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e2 (9.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e57 (17.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e304 (18.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e73 (18.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e13 (18.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e0.813\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCoronary artery disease\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e345 (14.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e4 (18.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e49 (15.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e225 (13.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e59 (15.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e8 (11.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e0.862\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHeart failure\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e423 (17.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e5 (22.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e66 (20.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e283 (17.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e60 (15.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e9 (13.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e0.369\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCerebrovascular disease\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e258 (10.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e2 (9.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e36 (11.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e173 (10.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e39 (10.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e8 (11.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e0.987\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCKD\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e64 (2.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e1 (4.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e13 (4.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e43 (2.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e7 (1.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e0 (0.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e0.232\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eValvular AF, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e33 (1.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e1 (4.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e6 (1.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e21 (1.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e3 (0.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e2 (2.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e0.340\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLeft atrium diameter (mm)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e44.0 [40.0\u0026ndash;47.0]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e45.0 [41.3\u0026ndash;47.8]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e44.0 [40.0\u0026ndash;48.0]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e44.0 [41.0\u0026ndash;47.0]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e44.0 [40.0\u0026ndash;48.0]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e43.0 [40.0\u0026ndash;47.0]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e0.714\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLVEF (%).\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e60.0 [56.0\u0026ndash;65.0]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e60.0 [58.0\u0026ndash;64.0]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e60.0 [55.0\u0026ndash;64.0]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e60.0 [56.0\u0026ndash;65.0]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e60.0 [56.0\u0026ndash;64.0]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e63.0 [57.0-66.3]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e0.236\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDuration of AF diagnosis (years)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e2.0 [0.5-5.0]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e3.0 [0.5\u0026ndash;6.8]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e2.0 [0.5-5.0]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e2.0 [0.5-5.0]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e2.0 [0.5-5.0]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e3.0 [0.3-7.0]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e0.807\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAF recurrence, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e817 (33.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e14 (63.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e109 (33.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e546 (33.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e121 (31.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e27 (39.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e0.027\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAADs, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1625 (66.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e12 (54.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e208 (63.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e1090 (67.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e267 (68.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e48 (69.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e0.464\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eRate control agents, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e808 (33.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e11 (50.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e102 (31.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e539 (33.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e126 (32.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e30 (43.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e0.149\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eOral anticoagulant, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e2196 (90.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e22 (100.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e284 (87.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e1474 (90.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e355 (91.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e61 (88.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e0.138\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAntiplatelet, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e121 (5.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0 (0.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e17 (5.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e73 (4.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e28 (7.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e3 (4.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e0.195\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGlucose lowering agents, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e410 (16.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e2 (9.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e49 (15.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e279 (17.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e68 (17.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e12 (17.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e0.746\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eACEI/ARB, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e806 (33.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e6 (27.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e115 (35.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e534 (32.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e131 (33.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e20 (29.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e0.801\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"8\"\u003e\u003cem\u003eCKD\u003c/em\u003e chronic kidney disease, \u003cem\u003eAF\u003c/em\u003e atrial fibrillation, \u003cem\u003eLVEF\u003c/em\u003e left ventricular ejection fraction, \u003cem\u003eAADs\u003c/em\u003e antiarrhythmic drugs, \u003cem\u003eACEI\u003c/em\u003e angiotensin converting enzyme inhibitors, \u003cem\u003eARB\u003c/em\u003e angiotensin 2 receptor blockers.\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eFor the primary outcome, univariable Cox regression (61\u0026ndash;70 bpm reference) revealed a significantly elevated HR in 40\u0026ndash;60 bpm (HR\u0026thinsp;=\u0026thinsp;2.57, 95% CI:1.47\u0026ndash;4.49, \u003cem\u003eP\u0026thinsp;\u0026lt;\u003c/em\u003e\u0026thinsp;0.001). Additionally, there was a trend of increased HR in 91\u0026ndash;100 bpm (HR\u0026thinsp;=\u0026thinsp;1.52, 95% CI:1.00-2.32, \u003cem\u003eP\u0026thinsp;=\u003c/em\u003e\u0026thinsp;0.052). Multivariable Cox regression revealed that RHR of 40\u0026ndash;60 bpm was significantly associated with AF recurrence (HR\u0026thinsp;=\u0026thinsp;2.08, 95% CI:1.16\u0026ndash;3.74, \u003cem\u003eP\u0026thinsp;=\u003c/em\u003e\u0026thinsp;0.014) (Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e). Kaplan-Meier curves showed lower recurrence-free survival in RHR of 40\u0026ndash;60 bpm, indicating higher AF recurrent risk (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\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\u003eUnivariable and multivariable regression analyses according to the RHR\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"8\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" 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=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c8\" colnum=\"8\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eEvents (n, %)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eUnadjusted HR\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003e(95% CI)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cem\u003eP\u003c/em\u003e\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003eAdjusted HR\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c7\"\u003e \u003cp\u003e(95% CI)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c8\"\u003e \u003cp\u003e\u003cem\u003eP\u003c/em\u003e\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003ePrimary outcome\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e40\u0026ndash;60 bpm\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e14 (63.6%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2.57\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1.47\u0026ndash;4.49\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e2.08\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e1.16\u0026ndash;3.74\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e0.014\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e61\u0026ndash;70 bpm\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e109 (33.4%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"6\" nameend=\"c8\" namest=\"c3\"\u003e \u003cp\u003eReference\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e71\u0026ndash;80 bpm\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e546 (33.6%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.07\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.87\u0026ndash;1.31\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.536\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e1.05\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.85\u0026ndash;1.29\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e0.668\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e81\u0026ndash;90 bpm\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e121 (31.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.03\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.80\u0026ndash;1.34\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.812\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e1.00\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.77\u0026ndash;1.31\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e0.971\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e91\u0026ndash;100 bpm\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e27 (39.1%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.52\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1.00-2.32\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.052\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e1.47\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.96\u0026ndash;2.25\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e0.077\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eSecondary outcome\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e40\u0026ndash;60 bpm\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e4 (18.2%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2.71\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e4.03\u0026ndash;55.94\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e11.69\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e3.01\u0026ndash;45.43\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\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\u003e61\u0026ndash;70 bpm\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e5 (1.5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"3\" nameend=\"c5\" namest=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colspan=\"3\" nameend=\"c8\" namest=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e71\u0026ndash;80 bpm\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e41 (2.5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.73\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.69\u0026ndash;4.39\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.246\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e2.00\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.78\u0026ndash;5.10\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e0.149\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e81\u0026ndash;90 bpm\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e16 (4.1%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3.12\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1.14\u0026ndash;8.52\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.027\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e3.79\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e1.36\u0026ndash;10.52\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e91\u0026ndash;100 bpm\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e2 (2.9%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2.34\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.45\u0026ndash;12.06\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.311\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e2.01\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.36\u0026ndash;11.11\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e0.422\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"8\"\u003eMultivariable regression was adjusted for age, gender, history of hypertension, diabetes, coronary heart disease, valvular AF, heart failure, cerebral infarction, chronic kidney disease, smoking, drinking, left atrial anteroposterior diameter, left ventricular ejection fraction, AF duration, AADs, rate control agents, oral anticoagulant, antiplatelet, glucose lowering agents and angiotensin converting enzyme inhibitors / angiotensin 2 receptor blockers.\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eFor the secondary outcome, univariable Cox regression (61\u0026ndash;70 bpm reference) revealed a significantly elevated HRs in 40\u0026ndash;60 bpm (HR\u0026thinsp;=\u0026thinsp;2.71, 95% CI:4.03\u0026ndash;55.94, \u003cem\u003eP\u0026thinsp;\u0026lt;\u003c/em\u003e\u0026thinsp;0.001) and 81\u0026ndash;90 bpm (HR\u0026thinsp;=\u0026thinsp;3.12, 95% CI:1.14\u0026ndash;8.52, \u003cem\u003eP\u0026thinsp;=\u003c/em\u003e\u0026thinsp;0.027), whereas the other two groups showed no significant differences (\u003cem\u003eP\u0026thinsp;=\u003c/em\u003e\u0026thinsp;0.246 and 0.311, respectively). Multivariable Cox regression also revealed that RHR of 40\u0026ndash;60 bpm (HR\u0026thinsp;=\u0026thinsp;11.69, 95% CI:3.01\u0026ndash;45.43, \u003cem\u003eP\u0026thinsp;\u0026lt;\u003c/em\u003e\u0026thinsp;0.001) and 81\u0026ndash;90 bpm (HR\u0026thinsp;=\u0026thinsp;3.79, 95% CI:1.36\u0026ndash;10.52, \u003cem\u003eP\u0026thinsp;=\u003c/em\u003e\u0026thinsp;0.001) maintained a significantly positive association with the secondary outcome (Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e). Kaplan-Meier curves showed patients with RHR of 40\u0026ndash;60 bpm were more susceptible to secondary outcomes (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eThe findings of this study elucidate a significant association between low RHR and recurrence for PeAF patients after catheter ablation. Specifically, RHR in the range of 40\u0026ndash;60 bpm confers an elevated risk of recurrence. There is also a trend of recurrence in patients with high RHR of 91\u0026ndash;100 bpm (\u003cem\u003eP\u0026thinsp;=\u003c/em\u003e\u0026thinsp;0.077). Postoperative RHR represented a non-invasive and readily accessible reliable predictor for AF recurrence, enabling early screening of high-risk populations. We identified specific ranges of RHR associated with elevated recurrence risk, which highlights the clinical imperative to prioritize comprehensive management for patients with low RHR of 40\u0026ndash;60 bpm, including more intensive or prolonged heart rate monitoring for this individual. Additionally, timely intervention for patients with high-risk RHR after ablation is essential to reduce recurrence and improve long-term outcomes.\u003c/p\u003e \u003cp\u003eRegarding the selection of RHR acquisition time, most current studies rely on preoperative or long-term RHR, overlooking the critical immediate postoperative period. Postoperative RHR, as a non-invasive and readily accessible predictive marker for AF recurrence, exhibits substantial clinical value, particularly for patients with PeAF who inherently have a higher propensity for recurrence. Postoperative RHR can more intuitively reflect the patient's postoperative status, establish a reliable correlation between RHR and recurrence, and screen out patients with high risk of recurrence in the early postoperative period, enabling timely interventions to reduce the recurrence rate.\u003c/p\u003e \u003cp\u003eSome studies analyzed the change in RHR before and after ablation. Killu AM et al.'s self-controlled study found a weak correlation between the relative change in overall RHR after ablation and AF recurrence (\u003cem\u003eP\u0026thinsp;=\u003c/em\u003e\u0026thinsp;0.067). Patients were further divided into quartiles based on the relative change in RHR, and the upper quartile with the largest relative increase in RHR had a significantly lower AF recurrence rate than the lower quartile. Nilsson B et al. conducted an RCT on RHR changes after PVI in AF patients, showing that PVI may lead to RHR increase, which is positively correlated with ablation success(\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e). Goff ZD et al. more precisely indicated that an increase in RHR\u0026thinsp;\u0026ge;\u0026thinsp;15 bpm after PVI was associated with 1-year freedom from AF(\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e). These prior investigations have unequivocally established that an elevated postoperative RHR confers a protective effect against recurrence(\u003cspan additionalcitationids=\"CR7\" citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e). However, they failed to delineate the association between the exact RHR range in the immediate postoperative period and AF recurrence after ablation.\u003c/p\u003e \u003cp\u003eOur study revealed that patients with postoperative RHR maintained within 61\u0026ndash;90 bpm exhibit a diminished risk of recurrence and superior long-term prognosis. Meanwhile, by explicitly selecting RHR within 24 hours after ablation for analysis, our study excludes the interference of preoperative RHR monitoring methods compared with previous studies analyzing RHR changes before and after ablation, which not only can better represent the AF population after catheter ablation, but also can reflect the immediate postoperative status more intuitively.\u003c/p\u003e \u003cp\u003eThe relationship between RHR and recurrence in this study may involve multiple mechanisms. Ablation directly influences the autonomic nervous system by reducing parasympathetic activity(\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e, \u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e). Low RHR (40\u0026ndash;60 bpm) may reflect autonomic dysfunction after ablation, particularly excessive vagal tone, which impacts atrial electrophysiological characteristics. This may increase atrial vulnerability to reentry by shortening action potential duration and enhancing conduction heterogeneity, thereby promoting AF recurrence. Conversely, higher RHR with shortening of myocardial action potential duration may be accompanied by calcium handling abnormalities (such as calcium overload), which in turn facilitates ectopic electrical activity associated with delayed after depolarization. This mechanism provides the electrophysiological substrate for the recurrence of AF. Additionally, extreme RHR may impair atrial mechanical function, leading to hemodynamic instability and further exacerbating AF recurrence(\u003cspan additionalcitationids=\"CR12\" citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e).\u003c/p\u003e \u003cp\u003ePrevious studies have documented a non-linear correlation between RHR and the occurrence of AF. Consistently, our study identified a similar pattern of association between RHR and recurrence of AF, which may suggest a shared underlying mechanism for AF development and recurrence. Morten W. Skov et al. found a U-shaped association between RHR and incident AF using electrocardiograms from 281,451 primary care patients excluding AF/atrial flutter, with this association being strongest for the outcome lone AF(\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e). A previous meta-analysis using 68\u0026ndash;80 bpm as the reference showed that both low and high RHR were associated with an increased risk of AF(\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e). Although there are differences in the RHR ranges defining high AF risk across these studies(\u003cspan additionalcitationids=\"CR15\" citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e), the U/J-shaped association between RHR and AF incidence has shown high consistency. This bears similarity to the association established in our study between RHR and recurrence of AF, suggesting shared underlying mechanisms for incidence and recurrence, such as autonomic dysfunction or electrical remodeling.\u003c/p\u003e \u003cp\u003ePrevious study with a 1.5-year follow-up has shown that the progression of paroxysmal or persistent AF to a more sustained form was closely associated with faster heart rates(\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e). This indicates that RHR is valuable not only for predicting AF incidence but also for forecasting disease progression. However, the optimal target range for RHR control in clinical practice remains undefined. The 2020 European Society of Cardiology guidelines recommend a standard heart rate control target of \u0026lt;\u0026thinsp;110 bpm(\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e), yet the validity of this range and the necessity for strict heart rate control require further validation(\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e, \u003cspan additionalcitationids=\"CR20\" citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e). Undeniably, RHR demonstrates critical observational value in the progression of AF. Our cohort study further extends this to AF recurrence, highlighting the role of RHR in maintaining the arrhythmogenic substrate. The findings to some extent demonstrate the consistency of disease characteristics across different stages.\u003c/p\u003e \u003cp\u003eRHR has been demonstrated to facilitate the screening of AF patients at high risk of cardiovascular adverse events. Both elevated and depressed RHR correlate with poor long-term prognosis(\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e, \u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e). Higher RHR is associated with an increased long-term risk of cardiovascular events (especially heart failure) and all-cause mortality, while lower RHR is associated with a greater risk of future permanent pacemaker implantation(\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e). A retrospective analysis of the Atrial Fibrillation Rhythm Management (AFFIRM) study showed that RHR\u0026thinsp;\u0026ge;\u0026thinsp;80 bpm was associated with increased mortality risk in AF patients(\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e). During a median follow-up of 24 months, Benjamin A. Steinberg et al. found a non-linear relationship between longitudinally measured RHR and mortality in patients with permanent AF, with an inflection point at 65 bpm. All-cause mortality increased as RHR deviated from 65 bpm(\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e). In patients with AF and heart failure with reduced ejection fraction, high RHR (\u0026gt;\u0026thinsp;81 bpm) was associated with a progressive increase in mortality risk(\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e, \u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e). By contrast, in patients with AF and heart failure with preserved ejection fraction, RHR exhibited a U-shaped association with cardiovascular adverse events, where lower RHR also elevated mortality(\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e). Collectively, these findings fully confirm that both excessively high and low RHR portend poor outcomes in AF.\u003c/p\u003e\n\u003ch3\u003eStudy limitations\u003c/h3\u003e\n\u003cp\u003eAlthough this study enhanced the reliability of findings by employing a large sample size (2,468 patients) and multivariate models (adjusting for clinical confounders), robustly validating the relationship between RHR and AF recurrence, several limitations still remain: (\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e) As an observational cohort study, it cannot establish a causal relationship between RHR and AF recurrence. (\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e) Without continuous monitoring via insertable cardiac monitor, single RHR measurement within 24 hours postoperatively may fail to capture temporal variability. (\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e) Although the study used a large sample size so far, the sample size is still relatively small, with fewer secondary outcomes in certain RHR intervals (e.g., 91\u0026ndash;100 bpm). Notwithstanding statistical significance was not achieved, the risk in this subgroup should not be overlooked.\u003c/p\u003e"},{"header":"Conclusions","content":"\u003cp\u003eThis study confirms that low RHR is associated with recurrence in PeAF after catheter ablation, where RHR of 40\u0026ndash;60 bpm exhibits a higher risk. Prospective studies are warranted to validate RHR as a therapeutic target and optimize individualized management strategies for preventing AF recurrence.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cp\u003eAF: Atrial fibrillation\u003c/p\u003e\n\u003cp\u003ePeAF: Persistent atrial fibrillation\u003c/p\u003e\n\u003cp\u003eRHR: Resting heart rate\u003c/p\u003e\n\u003cp\u003eAADs: Antiarrhythmic drugs\u003c/p\u003e\n\u003cp\u003eACEI: Angiotensin converting enzyme inhibitors\u003c/p\u003e\n\u003cp\u003eARB: Angiotensin 2 receptor blockers\u003c/p\u003e\n\u003cp\u003ePVI: Pulmonary vein isolation\u003c/p\u003e\n\u003cp\u003eECGs: Electrocardiograms\u003c/p\u003e\n\u003cp\u003eSD: Standard deviation\u003c/p\u003e\n\u003cp\u003eANOVA: One-way analysis of variance\u003c/p\u003e\n\u003cp\u003eHR: Hazard ratio\u003c/p\u003e\n\u003cp\u003eCI: Confidence interval\u003c/p\u003e\n\u003cp\u003eCKD: Chronic kidney disease\u003c/p\u003e\n\u003cp\u003eLVEF: Left ventricular ejection fraction\u003c/p\u003e\n\u003cp\u003eRCT: Randomized controlled trial\u003c/p\u003e\n\u003cp\u003eAFFIRM: Atrial Fibrillation Rhythm Management study\u003c/p\u003e\n\u003cp\u003eRACE II: Rate control efficacy in permanent atrial fibrillation II study\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eData Availability Statement\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eData are available from the authors upon reasonable request and with permission of Beijing Anzhen Hospital, Capital Medical University.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003cstrong\u003e\u0026nbsp;Statement\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis study was supported by the Noncommunicable Chronic Diseases-National Science and Technology Major Project (2023ZD0504200).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConflict of Interest Disclosure\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare no conflict of interests.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthics Approval Statement\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eEthics approval was obtained from the Human Research Ethics Committees at Beijing Anzhen Hospital. (NCT06987825). The study was conducted in accordance with the principles of the Declaration of Helsinki.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eP\u003c/strong\u003e\u003cstrong\u003eatient\u0026nbsp;\u003c/strong\u003e\u003cstrong\u003eC\u003c/strong\u003e\u003cstrong\u003eonsent\u0026nbsp;\u003c/strong\u003e\u003cstrong\u003eS\u003c/strong\u003e\u003cstrong\u003etatement\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eInformed consent was obtained from all patients.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthor Contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWQ, KH: investigation, original draft preparation, and formal analysis. WQ: data curation. KH: visualization. KH, XL, BF: methodology. LH, WW, TL, CJ, RT, CS, CM: supervision. DL: conceptualization and funding acquisition. All authors have read and agreed to the published version of the manuscript.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eVan Gelder IC, Groenveld HF, Crijns HJGM, Tuininga YS, Tijssen JGP, Alings AM, et al. Lenient versus strict rate control in patients with atrial fibrillation. N Engl J Med. (2010) Apr 15;362(15):1363\u0026ndash;73. \u003c/li\u003e\n\u003cli\u003eHan K, Li X, Fu B, Li M, Liu T, Jiang C, et al. Longitudinal Association Between Resting Heart Rate and Mortality in Atrial Fibrillation. The American Journal of Cardiology. (2024) Oct;S0002-9149(24)00743-4. \u003c/li\u003e\n\u003cli\u003eStavrakis S, Po S. Ganglionated Plexi Ablation: Physiology and Clinical Applications. Arrhythm Electrophysiol Rev. (2017);6(4):186. \u003c/li\u003e\n\u003cli\u003eDong JZ, Sang CH, Yu RH, Long DY, Tang RB, Jiang CX, et al. Prospective randomized comparison between a fixed \u0026ldquo;2C3L\u0026rdquo; approach vs. stepwise approach for catheter ablation of persistent atrial fibrillation. Europace. (2015) Dec;17(12):1798\u0026ndash;806. \u003c/li\u003e\n\u003cli\u003eSang C, Liu Q, Lai Y, Xia S, Jiang R, Li S, et al. Pulmonary Vein Isolation with Optimized Linear Ablation vs Pulmonary Vein Isolation Alone for Persistent AF. JAMA. (2024) Nov 18;e2424438. \u003c/li\u003e\n\u003cli\u003eNilsson B, Chen X, Pehrson S, Hilden J, Svendsen JH. Increased resting heart rate following radiofrequency catheter ablation for atrial fibrillation. Europace. (2005) Sept;7(5):415\u0026ndash;20. \u003c/li\u003e\n\u003cli\u003eGoff ZD, Laczay B, Yenokyan G, Sivasambu B, Sinha SK, Marine JE, et al. Heart rate increase after pulmonary vein isolation predicts freedom from atrial fibrillation at 1 year. Cardiovasc electrophysiol. (2019) Dec;30(12):2818\u0026ndash;22. \u003c/li\u003e\n\u003cli\u003eKillu AM, Witt CM, Sugrue AM, Vaidya V, Monahan KH, Barnes S, et al. Sinus rhythm heart rate increase after atrial fibrillation ablation is associated with lower risk of arrhythmia recurrence. Pacing Clinical Electrophis. (2021) Apr;44(4):651\u0026ndash;6. \u003c/li\u003e\n\u003cli\u003eSoejima K, Akaishi M, Mitamura H, Ogawa S, Sakurada H, Okazaki H, et al. Increase in heart rate after radiofrequency catheter ablation is mediated by parasympathetic nervous withdrawal and related to site of ablation. J Electrocardiol. (1997) July;30(3):239\u0026ndash;46. \u003c/li\u003e\n\u003cli\u003eTang LYW, Hawkins NM, Ho K, Tam R, Deyell MW, Macle L, et al. Autonomic alterations after pulmonary vein isolation in the CIRCA‐DOSE (cryoballoon vs irrigated radiofrequency catheter ablation) study. JAHA. (2021) Mar 2;10(5):e018610. \u003c/li\u003e\n\u003cli\u003eHeijman J, Voigt N, Nattel S, Dobrev D. Cellular and molecular electrophysiology of atrial fibrillation initiation, maintenance, and progression. Circ Res. (2014) Apr 25;114(9):1483\u0026ndash;99. \u003c/li\u003e\n\u003cli\u003eLiu T, Xiong F, Qi XY, Xiao J, Villeneuve L, Abu-Taha I, et al. Altered calcium handling produces reentry-promoting action potential alternans in atrial fibrillation-remodeled hearts. JCI Insight. (2020) Apr 7;5(8):e133754, 133754. \u003c/li\u003e\n\u003cli\u003eNattel S, Dobrev D. The multidimensional role of calcium in atrial fibrillation pathophysiology: Mechanistic insights and therapeutic opportunities. Eur Heart J. (2012) Aug;33(15):1870\u0026ndash;7. \u003c/li\u003e\n\u003cli\u003eSkov MW, Bachmann TN, Rasmussen PV, Olesen MS, Pietersen A, Graff C, et al. Association between heart rate at rest and incident atrial fibrillation (from the copenhagen electrocardiographic study). Am J Cardiol. (2016) Sept 1;118(5):708\u0026ndash;13. \u003c/li\u003e\n\u003cli\u003eLiu X, Guo N, Zhu W, Zhou Q, Liu M, Chen C, et al. Resting heart rate and the risk of atrial fibrillation. Int Heart J. (2019) July 27;60(4):805\u0026ndash;11. \u003c/li\u003e\n\u003cli\u003eMorseth B, Graff-Iversen S, Jacobsen BK, J\u0026oslash;rgensen L, Nyrnes A, Thelle DS, et al. Physical activity, resting heart rate, and atrial fibrillation: The troms\u0026oslash; study. Eur Heart J. (2016) Aug 1;37(29):2307\u0026ndash;13. \u003c/li\u003e\n\u003cli\u003eHolmqvist F, Kim S, Steinberg BA, Reiffel JA, Mahaffey KW, Gersh BJ, et al. Heart rate is associated with progression of atrial fibrillation, independent of rhythm. Heart. (2015) June;101(11):894\u0026ndash;9. \u003c/li\u003e\n\u003cli\u003eHindricks G, Potpara T, Dagres N, Arbelo E, Bax JJ, Blomstr\u0026ouml;m-Lundqvist C, et al. 2020 ESC guidelines for the diagnosis and management of atrial fibrillation developed in collaboration with the european association for cardio-thoracic surgery (EACTS): The task force for the diagnosis and management of atrial fibrillation of the european society of cardiology (ESC) developed with the special contribution of the european heart rhythm association (EHRA) of the ESC. Eur Heart J. (2021) Feb 1;42(5):373\u0026ndash;498. \u003c/li\u003e\n\u003cli\u003eSteinberg BA, Kim S, Thomas L, Fonarow GC, Gersh BJ, Holmqvist F, et al. Increased heart rate is associated with higher mortality in patients with atrial fibrillation (AF): Results from the outcomes registry for better informed treatment of AF (ORBIT-AF). J Am Heart Assoc. (2015) Sept 14;4(9):e002031. \u003c/li\u003e\n\u003cli\u003eGroenveld HF, Crijns HJGM, Van den Berg MP, Van Sonderen E, Alings AM, Tijssen JGP, et al. The effect of rate control on quality of life in patients with permanent atrial fibrillation: Data from the RACE II (rate control efficacy in permanent atrial fibrillation II) study. J Am Coll Cardiol. (2011) Oct 18;58(17):1795\u0026ndash;803. \u003c/li\u003e\n\u003cli\u003eVan Gelder IC, Wyse DG, Chandler ML, Cooper HA, Olshansky B, Hagens VE, et al. Does intensity of rate-control influence outcome in atrial fibrillation? An analysis of pooled data from the RACE and AFFIRM studies. Europace. (2006) Nov;8(11):935\u0026ndash;42. \u003c/li\u003e\n\u003cli\u003eAndrade JG, Roy D, Wyse DG, Tardif JC, Talajic M, Leduc H, et al. Heart rate and adverse outcomes in patients with atrial fibrillation: A combined AFFIRM and AF-CHF substudy. Heart Rhythm. (2016) Jan;13(1):54\u0026ndash;61. \u003c/li\u003e\n\u003cli\u003eTverdal A, Hjellvik V, Selmer R. Heart rate and mortality from cardiovascular causes: A 12 year follow-up study of 379,843 men and women aged 40-45 years. Eur Heart J. (2008) Nov;29(22):2772\u0026ndash;81. \u003c/li\u003e\n\u003cli\u003eHo JE, Larson MG, Ghorbani A, Cheng S, Coglianese EE, Vasan RS, et al. Long-term cardiovascular risks associated with an elevated heart rate: The framingham heart study. J Am Heart Assoc. (2014) May 8;3(3):e000668. \u003c/li\u003e\n\u003cli\u003eSuzuki S, Motoki H, Kanzaki Y, Maruyama T, Hashizume N, Kozuka A, et al. Prognostic significance of resting heart rate in atrial fibrillation patients with heart failure with reduced ejection fraction. Heart Vessels. (2020) Aug;35(8):1109\u0026ndash;15. \u003c/li\u003e\n\u003cli\u003eSong S, Ko JS, Lee HA, Choi EK, Cha MJ, Kim TH, et al. Clinical implications of heart rate control in heart failure with atrial fibrillation: Multi-center prospective observation registry (CODE-AF registry). Front Cardiovasc Med. (2022) Mar 22;9:787869. \u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"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":"bmc-cardiovascular-disorders","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"bcar","sideBox":"Learn more about [BMC Cardiovascular Disorders](http://bmccardiovascdisord.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/bcar/default.aspx","title":"BMC Cardiovascular Disorders","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"Atrial fibrillation, resting heart rate, catheter ablation, recurrence, prognosis","lastPublishedDoi":"10.21203/rs.3.rs-8468599/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-8468599/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eBackground: \u003c/strong\u003eResting heart rate (RHR)is critical for identifying high-risk patients with atrial fibrillation (AF). However, the association between resting heart rate (RHR) and AF recurrence after catheter ablation remains unknown.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eObjective: \u003c/strong\u003eThis study was to evaluate the association between RHR and recurrence in patients with persistent atrial fibrillation (PeAF) after catheter ablation.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMethods: \u003c/strong\u003eData from the China-AF registry (ChiCTR-OCH-13003729) from January 2018 to December 2023 at Beijing Anzhen Hospital were retrospectively analyzed. The primary outcome was the recurrence of AF, defined as an episode of atrial tachyarrhythmia lasting \u0026gt;30 seconds after a 3-month blanking period. The secondary outcome was the composite of heart failure, ischemic stroke, and cardiovascular death. Cox regression was used to assess the association between RHR and outcomes.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eResults: \u003c/strong\u003eOur study included 2,432 patients with PeAF undergoing catheter ablation. Cox regression demonstrated that RHR of 40-60 bpm was associated with an increased risk of recurrence after adjusting the confounders (HR=2.08, 95% CI:1.16-3.74, \u003cem\u003eP=\u003c/em\u003e0.014). Additionally, we showed that patients with low RHR (40-60 bpm) had a higher risk of the composite of heart failure, ischemic stroke, and cardiovascular death (HR=11.69, 95% CI:3.01-45.43, \u003cem\u003eP\u0026lt;\u003c/em\u003e0.001).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusion: \u003c/strong\u003eLow RHR is associated with recurrence in PeAF after catheter ablation, where RHR of 40-60 bpm exhibits a higher risk.\u003c/p\u003e","manuscriptTitle":"Low resting heart rate is associated with recurrence in persistent atrial fibrillation after catheter ablation","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2026-01-01 06:19:03","doi":"10.21203/rs.3.rs-8468599/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2026-01-14T10:25:55+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-01-13T12:02:46+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"222750664717329234386371251326758756926","date":"2026-01-07T04:40:11+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-12-30T11:26:25+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"332171397414616982923853909255496521058","date":"2025-12-30T09:21:50+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2025-12-30T09:13:48+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2025-12-30T08:05:37+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2025-12-29T06:12:20+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2025-12-29T06:11:39+00:00","index":"","fulltext":""},{"type":"submitted","content":"BMC Cardiovascular Disorders","date":"2025-12-29T02:38:28+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"bmc-cardiovascular-disorders","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"bcar","sideBox":"Learn more about [BMC Cardiovascular Disorders](http://bmccardiovascdisord.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/bcar/default.aspx","title":"BMC Cardiovascular Disorders","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"1e83d402-b200-4c2c-a617-8bbf60b5a152","owner":[],"postedDate":"January 1st, 2026","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"under-review","subjectAreas":[],"tags":[],"updatedAt":"2026-01-27T11:08:45+00:00","versionOfRecord":[],"versionCreatedAt":"2026-01-01 06:19:03","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-8468599","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-8468599","identity":"rs-8468599","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}