Evaluating the Impact of Catheter Ablation on Cardiovascular and Cerebral Outcomes in Atrial Fibrillation with Heart Failure and Preserved Ejection Fraction

Evaluating the Impact of Catheter Ablation on Cardiovascular and Cerebral Outcomes in Atrial Fibrillation with Heart Failure and Preserved Ejection Fraction | 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 Article Evaluating the Impact of Catheter Ablation on Cardiovascular and Cerebral Outcomes in Atrial Fibrillation with Heart Failure and Preserved Ejection Fraction Wei-Chieh Lee, Wan-Hsuan Hsu, Chih-Cheng Lai, Wei-Ting Chang, and 5 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-6488852/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Background Evidence supporting catheter ablation (CA) for atrial fibrillation (AF) in heart failure with preserved ejection fraction (HFpEF) is limited. This study evaluated the impact of CA on clinical outcomes in patients with AF and HFpEF using a global clinical database. Methods The TriNetX research network identified patients aged ≥18 years with AF and HFpEF (February 2014–June 2024). Patients were categorized by whether they underwent CA for AF. Primary outcomes included all-cause mortality, heart failure (HF) with acute exacerbation, and ischemic stroke. Secondary outcomes included progression to mildly reduced or reduced ejection fraction (EF) during follow-up. Results Patients receiving CA showed lower incidences of all-cause mortality, HF exacerbation, and ischemic stroke. There was a trend of less patients with progression to reduced EF in patients with CA. The reduction in mortality was consistent across all subgroups, while stroke reduction was more significant in females, those with better EF, without chronic kidney disease (CKD) or diabetes mellitus (DM), with hypertension (HTN), and with paroxysmal AF. The benefits in reducing HF exacerbation were particularly notable in females, those with better EF, without CKD, and with HTN. Conclusions In patients with AF and HFpEF, CA provided cardiovascular and cerebral benefits and might reduce the risk of progression to HFrEF over five years of follow-up. Additionally, CA was associated with a reduction in all-cause mortality in patients with AF and HFpEF. Health sciences/Cardiology Health sciences/Health care Health sciences/Medical research Atrial fibrillation Heart failure with preserved ejection fraction Catheter ablation Heart failure with acute exacerbation Ischemic stroke Figures Figure 1 Figure 2 Background Due to an aging population, the prevalence of atrial fibrillation (AF) is increasing, and recent evidence of cardiovascular and cerebral benefits of early rhythm control strategies, making catheter ablation (CA) a reasonable method for rhythm control, especially at the earlier stages of AF. 1 – 3 Landmark trials have demonstrated the safety and efficacy of CA in patients with AF and heart failure (HF). 4 – 6 Moreover, CA has been shown to reduce the progression to persistent AF. 7 As a result, there is growing interest in shifting from rate control approaches to rhythm control strategies earlier in the disease course of AF. In population with AF and end-stage HF, the combination of CA and guideline-directed medical therapy was associated with a lower likelihood of a composite of all-cause mortality, implantation of a left ventricular assist device, or urgent heart transplantation than medical therapy alone. 6 Furthermore, CA also provides the largest improvement in left ventricular ejection fraction (LVEF) in patients with HF with reduced ejection fraction (HFrEF). 8 In a small population study, CA improves invasive exercise hemodynamic parameters, exercise capacity, and quality of life in patients with AF and heart failure with preserved ejection fraction (HFpEF). 9 , 10 However, a meta-analysis found that CA had limited or no benefit in terms of HF events and cardiovascular mortality for patients with AF and HFpEF. 11 Therefore, the clinical benefits of CA in terms of cardiovascular and cerebral outcomes appear to be controversial and inconsistent in patients with AF and HFpEF. Accordingly, we aimed to explore the effects of CA on clinical outcomes in patients with AF and HFpEF by using a real-world and global federated health network. Methods Patient population and data source The study design and participant selection process for a global collaborative network analysis conducted within the TriNetX platform, which includes data from 120 healthcare organizations (HCOs) worldwide (Supplemental Figure 1). This study retrieved data on June 24, 2024, from a total of 128,873,996 patients. From this population, 65,160,687 patients aged 18 and older who visited HCOs three or more times since February 1, 2014, were identified. Among these, 32,024 patients were diagnosed with HFpEF and AF. The associated diagnosis codes were listed in supplemental table 1. The exclusion criteria applied were as follows:1. patients who did not receive anticoagulant treatment (n = 14,284), 2. patients who ever received heart valve replacement (n = 753), 3. patients diagnosed with chronic kidney disease (CKD) stage 5 or end-stage renal disease (ESRD) (n = 894), and 4. patients diagnosed with supraventricular tachycardia (SVT) or atrial flutter alone (n = 2,020). After applying these criteria, 1,234 patients received CA for AF, while 13,500 patients did not receive CA. Propensity score matching (PSM) (1:1) was performed based on age, gender, race, ethnicity, comorbid conditions, medications, and laboratory features (supplemental table 2). The index date for the ablation group was defined as the first date of receiving CA, and the index date for the without ablation group was defined as the first date of diagnosis of AF and HFpEF. This matching process resulted in two groups: 1,152 patients in the ablation group and 1,152 patients in the without ablation group. Ethical statement The authors analyzed and interpreted the data, and all authors reviewed the manuscript to confirm the accuracy and completeness of the information. The protocol was exempt from institutional review board approval by the Chi Mei Medical Center, as aggregate de-identified data from a research network database were used. The study findings are reported in accordance with the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) guidelines for cohort studies. Study outcomes The primary composite outcome of this study included HF with acute exacerbation (defined by International Classification of Diseases (ICD) codes or the need for intravenous diuretics), ischemic stroke, and all-cause mortality (supplemental table 3). Outcomes were analyzed over a period of 3 months to 5 years following the index AF ablation to account for a 3-month blanking period after the index event in the ablation population and after the diagnosis of AF and HFpEF in the without ablation population. Statistical analysis The patient population was stratified into two cohorts: those with ablation and those without ablation. Continuous variables are presented as mean ± standard difference (SD) and were compared between the cohorts using independent-sample t-tests. Categorical variables are reported as numbers (percentages) and were compared using the Chi-squared test. To control baseline differences between the cohorts, 1:1 PSM was performed using a built-in PSM algorithm, which employs the greedy nearest-neighbor method with a caliper of 0.1 pooled SDs. Any characteristic with a standardized mean difference of <0.1 between cohorts was considered well-matched. Adjusted hazard ratios (HRs) with 95% confidence intervals (CIs) were calculated for outcomes. Survival analysis was conducted by plotting Kaplan-Meier curves and using log-rank tests to compare the two cohorts. Statistical significance was set at a two-sided P value of <0.05. Subgroup analyses were undertaken based on age, sex, LVEF, presence of coexisting comorbid conditions, including CKD, hypertension (HTN), type 2 diabetes mellitus (DM), and dyslipidemia, and types of AF (supplemental table 4). All statistical analyses were performed using the TriNetX online platform and Stata 18.0 for statistical computing. Results Comparison of baseline characteristics between patients with ablation or without ablation The baseline characteristics of patients in the ablation and without ablation groups were listed in Table 1 and revealed significant disparities prior to PSM. Before PSM, the ablation group had a younger age (67.7 ± 9.7 years) compared to the without ablation group (73.1 ± 11.8 years), with a standardized difference of 0.500. There were also notable differences in the prevalence of paroxysmal AF, which was significantly higher in the ablation group (76.6% vs. 27.8%, standardized difference of 1.119). Additionally, the use of beta-blockers (79.9% in the ablation group vs. 61.2% in the without ablation group, standardized difference of 0.419) and anti-arrhythmic drugs (74.5% vs. 54.2%, standardized difference of 0.434) was higher in the ablation group. After PSM, these differences in the baseline characteristics were substantially minimized, resulting in a more balanced in the baseline characteristics between the two groups. For example, the average age was nearly equalized (68.3 ± 9.2 years in the ablation group vs. 68.1 ± 13.2 years in the without ablation group, standardized difference of 0.019). The prevalence of paroxysmal AF also became comparable (74.9% in the ablation group vs. 74.5% in the without ablation group, standardized difference of 0.010). The use of beta-blockers (78.8% vs. 78.3%, standardized difference of 0.013) and anti-arrhythmic drugs (73.6% vs. 72.9%, standardized difference of 0.016) was balanced as well. These adjustments indicate that PSM effectively reduced the baseline disparities between the ablation and without ablation groups, ensuring that the subsequent analyses of clinical outcomes are more robust and reliable. The significant differences observed by pre-PSM highlight the inherent variabilities in patient characteristics, while the post-PSM balance underscores the successful application of matching techniques to create equivalent comparison groups. Comparison of clinical outcomes between patients with and without ablation after propensity score matching The HRs and incidences of clinical outcomes between patients with and without ablation during a five-year follow-up period after PSM (Table 2). Notably, patients who underwent ablation had significantly lower all-cause mortality (6.1% vs. 16.9%, HR: 0.34, 95% CI: 0.26-0.44, p <0.0001) and reduced incidence of ischemic stroke (10.1% vs. 12.8%, HR: 0.72, 95% CI: 0.57-0.92, p =0.0080). Additionally, HF with acute exacerbation was significantly less frequent in the ablation group (22.7% vs. 27.0%, HR: 0.78, 95% CI: 0.67-0.92, p =0.0035). Moreover, there was a trend of less patients with progression to reduced EF in patients with CA. Kaplan-Meier curve analysis of the HF with acute exacerbation, ischemic stroke, and all-cause mortality between patients with and without ablation after propensity score matching Three Kaplan-Meier curves comparing outcomes between patients with and without ablation presented in Figure 1. The survival probability for all-cause mortality over five years demonstrated higher survival rates in patients with ablation, with a significant log-rank p -value of <0.0001 (Figure 1A). Specifically, the one-year survival probability is 0.9800 for those with ablation and 0.9358 for those without ablation. The cumulative probability of stroke over five years demonstrated a lower stroke rate in patients with ablation, with a significant log-rank p -value of 0.0080 (Figure 1B). The one-year cumulative probability is 0.0625 for those with ablation compared to 0.0825 for those without ablation ( p -value, 0.0275). The cumulative probability of HF with acute exacerbation over five years, with patients who underwent ablation experiencing fewer events, marked by a significant log-rank p -value of 0.0035 (Figure 1C). The one-year cumulative probability of HF with acute exacerbation is 0.1354 for patients with ablation and 0.1571 for those without ablation ( p -value, 0.0379). Overall, these figures indicate the beneficial impact of ablation on reducing mortality, stroke, and HF with acute exacerbation in patients with AF. Subgroup analysis of HF with acute exacerbation, ischemic stroke, and all-cause mortality between patients with and without ablation A subgroup analysis for all-cause mortality of various patient characteristics showed the comparison of patients with ablation versus without ablation (Figure 2). Subgroup analysis showed significantly reduced mortality for patients with ablation across all categories, including different age, sex, LVEF, CKD, HTN, DM, dyslipidemia, and different AF types (Figure 2A). A subgroup analysis for ischemic stroke of various patient characteristics presented a comparison of patients with ablation versus without ablation (Figure 2B). The analysis showed ablation was associated with significantly lower HRs in females (HR 0.69, p= 0.0402), patients with LVEF ≥57% (HR 0.66, p= 0.0474), those without CKD (HR 0.74, p= 0.0235), those with HTN (HR 0.72, p =0.0182), and those with paroxysmal AF (HR 0.72, p =0.0131). A subgroup analysis for HF with acute exacerbation of various patient characteristics showed a comparison of patients with ablation versus patients without ablation (Figure 2C). The analysis showed that ablation was associated with significantly lower HRs in females (HR 0.73, p =0.0086), patients with LVEF ≥57% (HR 0.73, p =0.0094), those without CKD (HR 0.76, p =0.0063), patients with HTN (HR 0.74, p =0.0015), and those with dyslipidemia (HR 0.72, p =0.0012). The subgroup analyses highlighted the heterogeneous impact of ablation therapy across different patient subgroups and indicated that the benefits of ablation may be more pronounced in specific populations. Discussion The benefits of CA for patients with HFpEF and AF remain a controversial issue, with current evidence being insufficient for a definitive conclusion. In this study, we observed a lower incidence of all-cause mortality, stroke, and HF with acute exacerbation in patients with HFpEF and AF following CA. Additionally, there was a trend towards a lower incidence of progression to HFrEF after CA. The reduction in mortality was consistent across all subgroups, while the reduction in stroke and HF exacerbation was more significant in specific groups, particularly females, those with better LVEF, without CKD, with HTN, and in patients with paroxysmal AF. These findings suggest that ablation therapy's benefits may vary, being more pronounced in certain populations. CA provided the benefit of reducing HF hospitalizations and may slow the progression to reduced LVEF In patients with AF and HFrEF, several randomized controlled trials and meta-analyses have demonstrated the effectiveness of CA in improving survival, HF hospitalizations, functional capacity, and quality of life, with acceptable safety. 2, 10-14 In patients with LVEF < 50%, 75.0% showed improvement in LVEF following CA for AF. 15 Predictors of this improvement included a smaller left ventricular volume and the absence of low voltage zones in the left atrium. 15, 16 CA also slowed the progression of LA remodeling. 7, 17 However, the improvement of LVEF observed in some studies was not confirmed in patients with HFpEF following CA. One meta-analysis reported that CA had limited or no benefit in reducing cardiovascular and all-cause mortality for patients with AF and HFpEF. 11 However, another meta-analysis showed different results from more studies, showing that CA reduced HF hospitalizations and increased the prevalence of maintaining sinus rhythm. 18 Additionally, another report showed various benefits of CA for patients with HFrEF and HF with mildly reduced EF, including improved LVEF, increased walking distance, reduced AF recurrence, and lower all-cause mortality. 19 In our study, we found that the incidence of HF with acute exacerbation was significantly lower in patients who underwent CA compared to those who received medical treatment alone, especially in the subgroups of female, EF ≥ 57%, with HTN, and without CKD. These findings suggested that CA could still be beneficial in the management of HF by reducing the frequency of hospital admissions in patients with HFpEF in real-world practice. Although CA showed potential in slowing the progression to reduced EF, the difference was not statistically significant. This finding indicated that while CA offered certain benefits in the management of HF in patients with HFpEF, its impact on LVEF progression requires further investigation. The impact of CA on Risk Reduction of Stroke in HFpEF and AF Reducing the burden of arrhythmia is a reasonable strategy as it may help decrease the risk of stroke. In a randomized controlled study on early rhythm control of AF, a lower incidence of stroke was observed in the population receiving early rhythm control through medications or CA. 3 However, the benefit of rhythm control of AF by CA was not observed in studies for patients with HFrEF, although there may still be a trend toward a reduced risk of stroke. 4 CA could increase the rate of maintenance of sinus rhythm and improved quality of life in patients with AF and HFpEF. 20, 21 Additionally, one meta-analysis concluded that CA significantly reduced the risk of stroke compared to medical therapy alone. 22 While the contribution of CA to stroke reduction in AF patients remains a controversial issue, there may be a trend toward its benefit in some studies. 23, 24 In this study of CA for AF in patients with HFpEF, we observed that the one-year and five-year stroke risks were significantly reduced in the ablation group compared to the non-ablation group. This study showed that CA provided some benefit in reducing stroke events in specific population, especially in females, patients with an EF ≥ 57%, patients without CKD, patients with HTN, patients without type 2 DM, and patients with paroxysmal AF. Study limitations The first limitation, inherent to all observational studies, is residual unmeasured confounding factors. Additionally, our data were obtained retrospectively from electronic medical records, which rely on the accurate documentation of diagnostic codes, introducing potential limitations due to miscoding. Furthermore, the database only captures outcomes if a patient remains within the same or another participating healthcare organization, which means some outcomes may have been missed. However, the bias should have affected in both study groups equally. Lastly, social determinants of health and other unmeasurable confounding factors may have influenced the outcomes, which we were unable to account for. Even though PSM was performed to reduce bias, there are still unmeasured confounding factors that may affect the results. These unmeasured factors could potentially influence the outcomes in ways that were not accounted for in the analysis, highlighting the inherent limitations of observational studies despite advanced statistical techniques like PSM. Conclusions In patients with AF and HFpEF, CA provided cardiovascular and cerebral benefits and might reduce the risk of progression to HFrEF over five years of follow-up. Additionally, CA was associated with a reduction in all-cause mortality in patients with AF and HFpEF. Declarations Author contributions Wei-Chieh Lee contributed to the study concept and design, literature review, data interpretation, drafting of the manuscript, and final approval of the submitted version. Wan-Hsuan Hsu was responsible for statistical analysis, data curation, and provided critical input on methodological aspects of the study. Chih-Cheng Lai, Wei-Ting Chang, Chia-Te Liao, Jhih-Yuan Shih, and Zhih-Cherng Chen participated in study coordination and contributed to data interpretation and figure preparation. Hsiu-Yu Fang was involved in manuscript revision, statistical quality control, and proofreading. Mien-Cheng Chen supervised the entire project, critically reviewed the manuscript, and approved the final version for publication. All authors reviewed the manuscript. Informed Consent The IRB waived the requirement for written informed consent due to the retrospective nature of the study. Conflict of interest None Acknowledgments The authors express their gratitude to Wan-Hsuan Hsu for providing statistical support and extend their appreciation for the assistance received from the Biostatistics Center at Chi Mei Medical Center in the study design, data monitoring, analysis, and interpretation. Availability of data and material Data from this study can be obtained from the corresponding authors upon reasonable request. This research utilized data from the TriNetX research network. The analyses, interpretations, and conclusions drawn in this study do not reflect the views of Chi Mei Medical Center. Competing interests None Funding This research was funded by the Chi-Mei Medical Center in Tainan City, Taiwan. Wei-Chieh Lee received support through grants from the Chi-Mei Medical Center (CMFHR11164, CMFHR112079). Potential conflicts of interest for each author None References Kim, D., Yang, P. S. & Joung, B. Optimal Rhythm Control Strategy in Patients With Atrial Fibrillation. Korean Circ. J. 52 (7), 496–512 (2022). Kirchhof, P. et al. Early Rhythm-Control Therapy in Patients with Atrial Fibrillation. N Engl. J. Med. 383 (14), 1305–1316 (2020). Jensen, M. et al. 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Atrial Fibrillation Ablation and Reduction of Stroke Events: Understanding the Paradoxical Lack of Evidence. Stroke 50 (10), 2970–2976 (2019). Tables Table 1 Baseline characteristics in with ablation and without ablation groups before and after propensity score matching Before PSM After PSM With ablation ( n = 1,234) Without abaltion ( n = 13,500) Std diff. With ablation ( n = 1,152) Without abaltion ( n = 1,152) Std diff. Demographics Age at Index (y/o) 67.7 ± 9.7 73.1 ± 11.8 0.500 68.3 ± 9.2 68.1 ± 13.2 0.019 Sex Male 660 (53.50) 6,784 (50.30) 0.065 605 (52.50) 614 (53.30) 0.016 Female 571 (46.30) 6,667 (49.40) 0.062 545 (47.30) 535 (46.40) 0.017 Race White 1,106 (89.60) 11,548 (85.50) 0.124 1,033 (89.70) 1,036 (89.90) 0.009 Black or African American 55 (4.50) 915 (6.80) 0.101 53 (4.60) 47 (4.10) 0.026 Asian 18 (1.50) 219 (1.60) 0.013 17 (1.50) 15 (1.30) 0.015 Native Hawaiian or Other Pacific Islander 10 (0.80) 10 (0.10) 0.111 10 (0.90) 10 (0.90) < 0.001 American Indian or Alaska Native 10 (0.80) 23 (0.20) 0.092 10 (0.90) 10 (0.90) < 0.001 Other Race 20 (1.60) 364 (2.70) 0.074 18 (1.60) 20 (1.70) 0.014 Unknown Race 30 (2.40) 421 (3.10) 0.042 26 (2.30) 29 (2.50) 0.017 Ethnicity Not Hispanic or Latino 1,158 (93.80) 12,568 (93.10) 0.030 1,087 (94.40) 1,081 (93.80) 0.022 Hispanic or Latino 45 (3.60) 429 (3.20) 0.026 39 (3.40) 40 (3.50) 0.005 Unknown Ethnicity 31 (2.50) 503 (3.70) 0.070 26 (2.30) 31 (2.70) 0.028 Comorbid conditions Cardiovascular diseases Hypertensive diseases 1,022 (82.80) 9,483 (70.20) 0.300 956 (83.00) 943 (81.90) 0.030 Ischemic heart diseases 610 (49.40) 6,988 (51.80) 0.047 577 (50.10) 588 (51.00) 0.019 Acute diastolic heart failure 150 (12.20) 849 (6.30) 0.204 133 (11.50) 118 (10.20) 0.042 Paroxysmal atrial fibrillation 945 (76.60) 3,755 (27.80) 1.119 863 (74.90) 858 (74.50) 0.010 Metabolic disorders Dyslipidemia 828 (67.10) 7,561 (56.00) 0.229 779 (67.60) 752 (65.30) 0.050 Overweight and obesity 566 (45.90) 3,569 (26.40) 0.413 511 (44.40) 525 (45.60) 0.024 Type 2 diabetes mellitus 456 (37.00) 4,527 (33.50) 0.072 426 (37.00) 434 (37.70) 0.014 Disorders of thyroid gland 365 (29.60) 3,146 (23.30) 0.143 343 (29.80) 345 (29.90) 0.004 Chronic kidney diseases Stage 3 139 (11.30) 2,089 (15.50) 0.124 135 (11.70) 136 (11.80) 0.003 Stage 4 26 (2.10) 533 (3.90) 0.108 25 (2.20) 32 (2.80) 0.039 Cerebral infarction 183 (14.80) 2,206 (16.30) 0.042 178 (15.40) 190 (16.50) 0.028 Medications Beta-blockers 986 (79.90) 8,261 (61.20) 0.419 908 (78.80) 902 (78.30) 0.013 Anti-arrhythmic 919 (74.50) 7,312 (54.20) 0.434 848 (73.60) 840 (72.90) 0.016 Diuretics 804 (65.20) 7,980 (59.10) 0.125 749 (65.00) 718 (62.30) 0.056 Statin 651 (52.80) 6,806 (50.40) 0.047 613 (53.20) 593 (51.50) 0.035 Anti-Platelet 558 (45.20) 7,130 (52.80) 0.152 545 (47.30) 541 (47.00) 0.007 ARBs 372 (30.10) 2,490 (18.40) 0.275 325 (28.20) 351 (30.50) 0.050 ACE inhibitors 342 (27.70) 3,284 (24.30) 0.077 321 (27.90) 323 (28.00) 0.004 Insulin 337 (27.30) 4,365 (32.30) 0.110 325 (28.20) 329 (28.60) 0.008 Digitalis 170 (13.80) 781 (5.80) 0.271 152 (13.20) 151 (13.10) 0.003 Metformin 153 (12.40) 1,384 (10.30) 0.068 145 (12.60) 148 (12.80) 0.008 SGLT2 inhibitors 78 (6.30) 265 (2.00) 0.220 59 (5.10) 53 (4.60) 0.024 Glipizide 38 (3.10) 442 (3.30) 0.011 36 (3.10) 38 (3.30) 0.010 Laboratory values Creatinine (mg/dL) 1.1 ± 0.4 1.2 ± 1.3 0.148 1.1 ± 0.5 1.1 ± 0.6 0.016 LDL (mg/dL) 86.0 ± 36.0 82.2 ± 35.7 0.105 85.9 ± 35.8 82.5 ± 34.0 0.097 HbA1c ≥ 7% 140 (11.30) 1,749 (13.00) 0.049 134 (11.60) 132 (11.50) 0.005 BNP ≥ 150 pg/mL 295 (23.90) 2,376 (17.60) 0.156 265 (23.00) 269 (23.40) 0.008 NT-proBNP ≥ 450 pg/mL 296 (24.00) 2,787 (20.60) 0.080 279 (24.20) 270 (23.40) 0.018 LVEF (%) 58.9 ± 6.5 59.8 ± 9.5 0.119 58.8 ± 6.5 59.3 ± 10.2 0.062 Values are mean ± standard difference or number (%). Any characteristic with a standard difference between cohorts < 0.10 was considered to be well matched. Abbreviation: PSM: propensity score matching; SD.: standardized difference; LDL-C: Low density lipoprotein-Cholesterol; BNP: B-type natriuretic peptide; ACEIs: angiotensin-converting enzyme inhibitors; ARBs: angiotensin receptor blockers; SGLT2: sodium-glucose co-transporter 2; HMG-CoA: Hydroxymethylglutaryl-CoA. Table 2 The hazard ratios and incidences for comparing matched with ablation and without ablation group during the five-year follow-up period No. (%) of patients with outcome HR (95% CI) Log-rank p -value With ablation ( n = 1,152 ) Without ablation ( n = 1,152 ) All-cause mortality (%) 70 (6.1) 195 (16.9) 0.34 (0.26,0.44) < 0.0001 HF exacerbation (%) 262 (22.7) 311 (27.0) 0.78 (0.67,0.92) 0.0035 LVEF progress to mildly reduced EF (%) 129 (11.2) 123 (10.7) 1.02 (0.79,1.30) 0.8926 LVEF progress to reduced EF (%) 57 (4.9) 75 (6.5) 0.72 (0.51,1.02) 0.0634 Ischemic stroke (%) 116 (10.1) 148 (12.8) 0.72 (0.57,0.92) 0.0080 Data are expressed as number (percentage). Abbreviation: HR: hazard ratio; CI: confidence interval; HF: heart failure; LVEF: left ventricular ejection fraction. Additional Declarations No competing interests reported. Supplementary Files Supplementaltables.docx SuppllementalFigure1.jpg Supplemental Figure legends Figure 1. Flowchart of study population selection and propensity score matching This flowchart illustrated the selection process of the study population from the Global Collaborative Network in TriNetX, which includes 120 healthcare organizations (HCOs) worldwide. Data were retrieved on June 24, 2024, encompassing a total of 128,873,996 individuals. From this dataset, patients aged 18 years or older who had visited HCOs at least three times since February 1, 2014, were identified (n = 65,160,687). Among these, patients diagnosed with heart failure with preserved ejection fraction (HFpEF) and atrial fibrillation were selected (n = 32,024). The following exclusion criteria were applied: Patients who did not receive anticoagulant treatment (n = 14,284) Patients who had ever received heart valve replacement (n = 753) Patients diagnosed with chronic kidney disease (CKD) stage 5 or end-stage renal disease (ESRD) (n = 894) Patients diagnosed with supraventricular tachycardia (SVT) or atrial flutter alone (n = 2,020) After applying these criteria, patients were divided into two groups: those who received ablation therapy (n = 1,234) and those who did not receive ablation therapy (n = 13,500). Propensity score matching (1:1) was performed by age, gender, race, ethnicity, comorbid conditions, medications, and laboratory features, resulting in 1,152 patients in each cohort. The index date was defined as the first date of receiving ablation for the ablation group and as the first date of diagnosis of AF with HFpEF for the without ablation group. Abbreviation: HCOs: healthcare organizations; HFpEF: heart failure with preserved ejection fraction; CKD: chronic kidney disease; ESRD: end-stage renal disease; SVT: supraventricular tachycardia. Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. 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-6488852","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":452550823,"identity":"b6f7d441-2d83-4c2c-b81b-a4f7b1fccaf0","order_by":0,"name":"Wei-Chieh Lee","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAABB0lEQVRIie3RsWoCMRjA8S8EdAlkzdGX+ETQCuKLuAiFbgFHJ4kEzkXrqou+Qrt10yPQqeoDuCi+gKPKDX4nlSKYSrdS8p8Cl19C7gMIhf5gyJldN7AKwLkBZhQt7pE8/8Bd85l2smuivETmGtFw52h5Jt9fvKTMBRYFLuuyS/sP7491mQe2bR2hjbPbpGIFbgWu9NAxw/qfSo8s8ML8BZSPoDvfstKGCGex0q8OclGnB6r0A3kQuNCTC5neJ9nzcUaHX27hRMzeTyo2+8n4pN+IJH0i9Chb6BgVTT2kLBMaZVrT46VL1oe4rQcDl2xMWpWRuU2u+jo2G1DsHYu39NciFAqF/m8nh5Zcno/aLqQAAAAASUVORK5CYII=","orcid":"","institution":"Chi Mei Medical Center","correspondingAuthor":true,"prefix":"","firstName":"Wei-Chieh","middleName":"","lastName":"Lee","suffix":""},{"id":452550824,"identity":"b0fd7e02-7abe-4e79-9fc5-b83c03466202","order_by":1,"name":"Wan-Hsuan Hsu","email":"","orcid":"","institution":"Chi Mei Medical Center","correspondingAuthor":false,"prefix":"","firstName":"Wan-Hsuan","middleName":"","lastName":"Hsu","suffix":""},{"id":452550825,"identity":"794267dc-afa1-4627-adfe-81540d3ae14a","order_by":2,"name":"Chih-Cheng Lai","email":"","orcid":"","institution":"Chi Mei Medical Center","correspondingAuthor":false,"prefix":"","firstName":"Chih-Cheng","middleName":"","lastName":"Lai","suffix":""},{"id":452550826,"identity":"e78ad36c-d5c5-43bd-9171-73d5c93b7248","order_by":3,"name":"Wei-Ting Chang","email":"","orcid":"","institution":"Chi Mei Medical Center","correspondingAuthor":false,"prefix":"","firstName":"Wei-Ting","middleName":"","lastName":"Chang","suffix":""},{"id":452550827,"identity":"8c1c2ac5-5c72-4a2b-af09-90028a519110","order_by":4,"name":"Chia-Te Liao","email":"","orcid":"","institution":"Chi Mei Medical Center","correspondingAuthor":false,"prefix":"","firstName":"Chia-Te","middleName":"","lastName":"Liao","suffix":""},{"id":452550828,"identity":"c39ccd9a-71cd-468f-ae50-b09c7ec3f4c2","order_by":5,"name":"Jhih-Yuan Shih","email":"","orcid":"","institution":"Chi Mei Medical Center","correspondingAuthor":false,"prefix":"","firstName":"Jhih-Yuan","middleName":"","lastName":"Shih","suffix":""},{"id":452550829,"identity":"34aa803c-14cf-403b-8b89-d5f8f8447f1f","order_by":6,"name":"Zhih-Cherng Chen","email":"","orcid":"","institution":"Chi Mei Medical Center","correspondingAuthor":false,"prefix":"","firstName":"Zhih-Cherng","middleName":"","lastName":"Chen","suffix":""},{"id":452550830,"identity":"e04f9341-2bb4-4247-9279-9b5b08731297","order_by":7,"name":"Hsiu-Yu Fang","email":"","orcid":"","institution":"Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine","correspondingAuthor":false,"prefix":"","firstName":"Hsiu-Yu","middleName":"","lastName":"Fang","suffix":""},{"id":452550831,"identity":"59a04fb2-f5a5-4e68-ae23-72aea82110c6","order_by":8,"name":"Mien-Cheng Chen","email":"","orcid":"","institution":"Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine","correspondingAuthor":false,"prefix":"","firstName":"Mien-Cheng","middleName":"","lastName":"Chen","suffix":""}],"badges":[],"createdAt":"2025-04-20 10:53:14","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-6488852/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-6488852/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":82356027,"identity":"11e03d4b-d5ec-42cf-ba04-382510dac27c","added_by":"auto","created_at":"2025-05-09 11:16:38","extension":"jpg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":373312,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eKaplan-Meier curves for all-cause mortality, stroke, and HF exacerbation\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003ePanel A:\u003c/strong\u003e Kaplan-Meier survival curves for all-cause mortality among patients with HFpEF and AF, comparing those who received ablation therapy (blue line) and those who did not (red line). Survival probability at 1 year, 3 years, and 5 years was higher in the ablation group compared to the non-ablation group. The log-rank test indicated a significant difference (p \u0026lt; 0.0001) between the two groups.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003ePanel B:\u003c/strong\u003e Cumulative probability of ischemic stroke over time for patients with HFpEF and AF, comparing those who received ablation therapy (blue line) and those who did not (red line). The cumulative probability of stroke was lower in the ablation group at 1 year, 3 years, and 5 years. The log-rank test showed a significant difference (p = 0.0080).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003ePanel C:\u003c/strong\u003e Cumulative probability of HF with acute exacerbation over time for patients with HFpEF and AF, comparing those who received ablation therapy (blue line) and those who did not (red line). The cumulative probability of worsening of HF was lower in the ablation group at 1 year, 3 years, and 5 years. The log-rank test showed a significant difference (p = 0.0001).\u003c/p\u003e\n\u003cp\u003eEach panel includes shaded areas representing the 95% confidence intervals for the survival and event probability estimates.\u003c/p\u003e\n\u003cp\u003eAbbreviation: HFpEF: heart failure with preserved ejection fraction; AF: atrial fibrillation; HF: heart failure.\u003c/p\u003e","description":"","filename":"Figure1.jpg","url":"https://assets-eu.researchsquare.com/files/rs-6488852/v1/842ccd7d42f7b590f8268c1b.jpg"},{"id":82358507,"identity":"d58a5dfe-dea5-4c6b-a091-33e0217c8b0d","added_by":"auto","created_at":"2025-05-09 11:24:37","extension":"jpg","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":594506,"visible":true,"origin":"","legend":"\u003cp\u003eSubgroup analysis of HF with acute exacerbation, ischemic stroke, and all-cause mortality between patients with and without ablation\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003ePanel A:\u003c/strong\u003e Subgroup analysis of hazard ratios for all-cause mortality between patients with ablation versus without ablation\u003c/p\u003e\n\u003cp\u003eThe HRs indicate a significantly lower risk of all-cause mortality for patients who received ablation therapy across all subgroups, with all log-rank \u003cem\u003ep\u003c/em\u003e-values being \u0026lt;0.001, indicating high statistical significance.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003ePanel B:\u003c/strong\u003e Subgroup analysis of hazard ratios for ischemic stroke between patients with ablation versus without ablation\u003c/p\u003e\n\u003cp\u003eThe HRs indicate a varying degree of risk for ischemic stroke across different subgroups, with some subgroups showing a significant reduction in risk for the ablation group. Specifically, females (HR 0.69, \u003cem\u003ep\u003c/em\u003e=0.0402), patients with LVEF ≥57% (HR 0.66, \u003cem\u003ep\u003c/em\u003e=0.0474), with HTN (HR 0.72, \u003cem\u003ep\u003c/em\u003e=0.0182), without DM (HR 0.70, \u003cem\u003ep\u003c/em\u003e=0.0367), and paroxysmal AF (HR 0.72, \u003cem\u003ep\u003c/em\u003e=0.0131).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003ePanel C:\u003c/strong\u003e Subgroup analysis of hazard ratios for HF with acute exacerbation with ablation versus without ablation\u003c/p\u003e\n\u003cp\u003eThe HRs indicate a varying degree of risk for HF exacerbation across different subgroups, with some subgroups showing a significant reduction in risk for the ablation group. Specifically, females (HR 0.73, \u003cem\u003ep\u003c/em\u003e=0.0086), patients with LVEF ≥57% (HR 0.73, \u003cem\u003ep\u003c/em\u003e=0.0094), without CKD (HR 0.76, \u003cem\u003ep\u003c/em\u003e=0.0063), with HTN (HR 0.74, \u003cem\u003ep\u003c/em\u003e=0.0015).\u003c/p\u003e\n\u003cp\u003eAbbreviation: HF: heart failure; HR: hazard ratio; CI: confidence interval; LVEF: left ventricular ejection fraction; CKD: chronic kidney disease; HTN: hypertension; DM: diabetes mellitus; AF: atrial fibrillation.\u003c/p\u003e","description":"","filename":"Figure2.jpg","url":"https://assets-eu.researchsquare.com/files/rs-6488852/v1/eac680a9e2830f406abb013a.jpg"},{"id":90964951,"identity":"5dcdfe48-3e7d-4ea7-90d3-4e302f39b8a7","added_by":"auto","created_at":"2025-09-10 06:18:49","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":2326938,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-6488852/v1/0ae0c8b9-bcdf-4452-ad9e-70f40560ac4f.pdf"},{"id":82356012,"identity":"b32398fa-541a-46f1-b37f-dd5839dfa564","added_by":"auto","created_at":"2025-05-09 11:16:37","extension":"docx","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":32343,"visible":true,"origin":"","legend":"","description":"","filename":"Supplementaltables.docx","url":"https://assets-eu.researchsquare.com/files/rs-6488852/v1/b9b36286be42b4d9e455d8a3.docx"},{"id":82358509,"identity":"b8296a3d-167b-46d6-917c-5567110668c5","added_by":"auto","created_at":"2025-05-09 11:24:37","extension":"jpg","order_by":2,"title":"","display":"","copyAsset":false,"role":"supplement","size":741975,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eSupplemental Figure legends\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eFigure 1. Flowchart of study population selection and propensity score matching\u003c/p\u003e\n\u003cp\u003eThis flowchart illustrated the selection process of the study population from the Global Collaborative Network in TriNetX, which includes 120 healthcare organizations (HCOs) worldwide. Data were retrieved on June 24, 2024, encompassing a total of 128,873,996 individuals. From this dataset, patients aged 18 years or older who had visited HCOs at least three times since February 1, 2014, were identified (n = 65,160,687). Among these, patients diagnosed with heart failure with preserved ejection fraction (HFpEF) and atrial fibrillation were selected (n = 32,024).\u003c/p\u003e\n\u003cp\u003eThe following exclusion criteria were applied:\u003c/p\u003e\n\u003cul\u003e\n \u003cli\u003ePatients \u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp;who did not receive anticoagulant treatment (n = 14,284)\u003c/li\u003e\n \u003cli\u003ePatients \u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp;who had ever received heart valve replacement (n = 753)\u003c/li\u003e\n \u003cli\u003ePatients \u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp;diagnosed with chronic kidney disease (CKD) stage 5 or end-stage renal \u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp;disease (ESRD) (n = 894)\u003c/li\u003e\n \u003cli\u003ePatients \u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp;diagnosed with supraventricular tachycardia (SVT) or atrial flutter alone \u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp;(n = 2,020)\u003c/li\u003e\n\u003c/ul\u003e\n\u003cp\u003eAfter applying these criteria, patients were divided into two groups: those who received ablation therapy (n = 1,234) and those who did not receive ablation therapy (n = 13,500). Propensity score matching (1:1) was performed by age, gender, race, ethnicity, comorbid conditions, medications, and laboratory features, resulting in 1,152 patients in each cohort. The index date was defined as the first date of receiving ablation for the ablation group and as the first date of diagnosis of AF with HFpEF for the without ablation group.\u003c/p\u003e\n\u003cp\u003eAbbreviation: HCOs: healthcare organizations; HFpEF: heart failure with preserved ejection fraction; CKD: chronic kidney disease; ESRD: end-stage renal disease; SVT: supraventricular tachycardia.\u003c/p\u003e","description":"","filename":"SuppllementalFigure1.jpg","url":"https://assets-eu.researchsquare.com/files/rs-6488852/v1/585cba113d6091b8bfa2bed4.jpg"}],"financialInterests":"No competing interests reported.","formattedTitle":"Evaluating the Impact of Catheter Ablation on Cardiovascular and Cerebral Outcomes in Atrial Fibrillation with Heart Failure and Preserved Ejection Fraction","fulltext":[{"header":"Background","content":"\u003cp\u003eDue to an aging population, the prevalence of atrial fibrillation (AF) is increasing, and recent evidence of cardiovascular and cerebral benefits of early rhythm control strategies, making catheter ablation (CA) a reasonable method for rhythm control, especially at the earlier stages of AF. \u003csup\u003e\u003cspan additionalcitationids=\"CR2\" citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e\u003c/sup\u003e Landmark trials have demonstrated the safety and efficacy of CA in patients with AF and heart failure (HF). \u003csup\u003e\u003cspan additionalcitationids=\"CR5\" citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e\u003c/sup\u003e Moreover, CA has been shown to reduce the progression to persistent AF. \u003csup\u003e\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e\u003c/sup\u003e As a result, there is growing interest in shifting from rate control approaches to rhythm control strategies earlier in the disease course of AF. In population with AF and end-stage HF, the combination of CA and guideline-directed medical therapy was associated with a lower likelihood of a composite of all-cause mortality, implantation of a left ventricular assist device, or urgent heart transplantation than medical therapy alone. \u003csup\u003e\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e\u003c/sup\u003e Furthermore, CA also provides the largest improvement in left ventricular ejection fraction (LVEF) in patients with HF with reduced ejection fraction (HFrEF). \u003csup\u003e\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e\u003c/sup\u003e In a small population study, CA improves invasive exercise hemodynamic parameters, exercise capacity, and quality of life in patients with AF and heart failure with preserved ejection fraction (HFpEF). \u003csup\u003e\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e, \u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e\u003c/sup\u003e However, a meta-analysis found that CA had limited or no benefit in terms of HF events and cardiovascular mortality for patients with AF and HFpEF. \u003csup\u003e\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e\u003c/sup\u003e Therefore, the clinical benefits of CA in terms of cardiovascular and cerebral outcomes appear to be controversial and inconsistent in patients with AF and HFpEF. Accordingly, we aimed to explore the effects of CA on clinical outcomes in patients with AF and HFpEF by using a real-world and global federated health network.\u003c/p\u003e"},{"header":"Methods","content":"\u003cp\u003e\u003cstrong\u003ePatient population and data source\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe study design and participant selection process for a global collaborative network analysis conducted within the TriNetX platform, which includes data from 120 healthcare organizations (HCOs) worldwide (Supplemental Figure 1). This study retrieved data on June 24, 2024, from a total of 128,873,996 patients. From this population, 65,160,687 patients aged 18 and older who visited HCOs three or more times since February 1, 2014, were identified. Among these, 32,024 patients were diagnosed with HFpEF and AF. The associated diagnosis codes were listed in supplemental table 1.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eThe exclusion criteria applied were as follows:1. patients who did not receive anticoagulant treatment (n = 14,284), 2. patients who ever received heart valve replacement (n = 753), 3. patients diagnosed with chronic kidney disease (CKD) stage 5 or end-stage renal disease (ESRD) (n = 894), and 4. patients diagnosed with supraventricular tachycardia (SVT) or atrial flutter alone (n = 2,020).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eAfter applying these criteria, 1,234 patients received CA for AF, while 13,500 patients did not receive CA. Propensity score matching (PSM) (1:1) was performed based on age, gender, race, ethnicity, comorbid conditions, medications, and laboratory features (supplemental table 2). The index date for the ablation group was defined as the first date of receiving CA, and the index date for the without ablation group was defined as the first date of diagnosis of AF and HFpEF. This matching process resulted in two groups: 1,152 patients in the ablation group and 1,152 patients in the without ablation group.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthical statement\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors analyzed and interpreted the data, and all authors reviewed the manuscript to confirm the accuracy and completeness of the information. The protocol was exempt from institutional review board approval by the Chi Mei Medical Center, as aggregate de-identified data from a research network database were used. The study findings are reported in accordance with the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) guidelines for cohort studies.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eStudy outcomes\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe primary composite outcome of this study included HF with acute exacerbation (defined by International Classification of Diseases (ICD) codes or the need for intravenous diuretics), ischemic stroke, and all-cause mortality (supplemental table 3). Outcomes were analyzed over a period of 3 months to 5 years following the index AF ablation to account for a 3-month blanking period after the index event in the ablation population and after the diagnosis of AF and HFpEF in the without ablation population.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eStatistical analysis\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe patient population was stratified into two cohorts: those with ablation and those without ablation. Continuous variables are presented as mean ± standard difference (SD) and were compared between the cohorts using independent-sample t-tests. Categorical variables are reported as numbers (percentages) and were compared using the Chi-squared test. To control baseline differences between the cohorts, 1:1 PSM was performed using a built-in PSM algorithm, which employs the greedy nearest-neighbor method with a caliper of 0.1 pooled SDs. Any characteristic with a standardized mean difference of \u0026lt;0.1 between cohorts was considered well-matched. Adjusted hazard ratios (HRs) with 95% confidence intervals (CIs) were calculated for outcomes. Survival analysis was conducted by plotting Kaplan-Meier curves and using log-rank tests to compare the two cohorts. Statistical significance was set at a two-sided \u003cem\u003eP\u003c/em\u003e value of \u0026lt;0.05. \u0026nbsp;Subgroup analyses were undertaken based on age, sex, LVEF, presence of coexisting comorbid conditions, including CKD, hypertension (HTN), type 2 diabetes mellitus (DM), and dyslipidemia, and types of AF (supplemental table 4). All statistical analyses were performed using the TriNetX online platform and Stata 18.0 for statistical computing.\u003c/p\u003e"},{"header":"Results","content":"\u003cp\u003e\u003cstrong\u003eComparison of baseline characteristics between\u0026nbsp;\u003c/strong\u003e\u003cstrong\u003epatients with ablation or without ablation\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe baseline characteristics of patients in the ablation and without ablation groups were listed in Table 1 and revealed significant disparities prior to PSM. Before PSM, the ablation group had a younger age (67.7 ± 9.7 years) compared to the without ablation group (73.1 ± 11.8 years), with a standardized difference of 0.500. There were also notable differences in the prevalence of paroxysmal AF, which was significantly higher in the ablation group (76.6% vs. 27.8%, standardized difference of 1.119). Additionally, the use of beta-blockers (79.9% in the ablation group vs. 61.2% in the without ablation group, standardized difference of 0.419) and anti-arrhythmic drugs (74.5% vs. 54.2%, standardized difference of 0.434) was higher in the ablation group.\u003c/p\u003e\n\u003cp\u003eAfter PSM, these differences in the baseline characteristics were substantially minimized, resulting in a more balanced in the baseline characteristics between the two groups. For example, the average age was nearly equalized (68.3 ± 9.2 years in the ablation group vs. 68.1 ± 13.2 years in the without ablation group, standardized difference of 0.019). The prevalence of paroxysmal AF also became comparable (74.9% in the ablation group vs. 74.5% in the without ablation group, standardized difference of 0.010). The use of beta-blockers (78.8% vs. 78.3%, standardized difference of 0.013) and anti-arrhythmic drugs (73.6% vs. 72.9%, standardized difference of 0.016) was balanced as well. These adjustments indicate that PSM effectively reduced the baseline disparities between the ablation and without ablation groups, ensuring that the subsequent analyses of clinical outcomes are more robust and reliable. The significant differences observed by pre-PSM highlight the inherent variabilities in patient characteristics, while the post-PSM balance underscores the successful application of matching techniques to create equivalent comparison groups.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eComparison of clinical outcomes between patients with and without ablation after propensity score matching\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe HRs and incidences of clinical outcomes between patients with and without ablation during a five-year follow-up period after PSM (Table 2). Notably, patients who underwent ablation had significantly lower all-cause mortality (6.1% vs. 16.9%, HR: 0.34, 95% CI: 0.26-0.44, \u003cem\u003ep\u003c/em\u003e\u0026lt;0.0001) and reduced incidence of ischemic stroke (10.1% vs. 12.8%, HR: 0.72, 95% CI: 0.57-0.92, \u003cem\u003ep\u003c/em\u003e=0.0080). Additionally, HF with acute exacerbation was significantly less frequent in the ablation group (22.7% vs. 27.0%, HR: 0.78, 95% CI: 0.67-0.92, \u003cem\u003ep\u003c/em\u003e=0.0035). Moreover, there was a trend of less patients with progression to reduced EF in patients with CA.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eKaplan-Meier curve analysis of\u003c/strong\u003e\u003cstrong\u003e\u0026nbsp;the HF with acute exacerbation, ischemic stroke, and all-cause mortality\u0026nbsp;\u003c/strong\u003e\u003cstrong\u003ebetween patients with and without ablation\u0026nbsp;\u003c/strong\u003e\u003cstrong\u003eafter\u0026nbsp;\u003c/strong\u003e\u003cstrong\u003epropensity score matching\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThree Kaplan-Meier curves comparing outcomes between patients with and without ablation presented in Figure 1. The survival probability for all-cause mortality over five years demonstrated higher survival rates in patients with ablation, with a significant log-rank \u003cem\u003ep\u003c/em\u003e-value of \u0026lt;0.0001 (Figure 1A). Specifically, the one-year survival probability is 0.9800 for those with ablation and 0.9358 for those without ablation. The cumulative probability of stroke over five years demonstrated a lower stroke rate in patients with ablation, with a significant log-rank \u003cem\u003ep\u003c/em\u003e-value of 0.0080 (Figure 1B). The one-year cumulative probability is 0.0625 for those with ablation compared to 0.0825 for those without ablation (\u003cem\u003ep\u003c/em\u003e-value, 0.0275). The cumulative probability of HF with acute exacerbation over five years, with patients who underwent ablation experiencing fewer events, marked by a significant log-rank \u003cem\u003ep\u003c/em\u003e-value of 0.0035 (Figure 1C). The one-year cumulative probability of HF with acute exacerbation is 0.1354 for patients with ablation and 0.1571 for those without ablation (\u003cem\u003ep\u003c/em\u003e-value, 0.0379). Overall, these figures indicate the beneficial impact of ablation on reducing mortality, stroke, and HF with acute exacerbation in patients with AF.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eSubgroup analysis of HF with acute exacerbation, ischemic stroke, and all-cause mortality\u0026nbsp;\u003c/strong\u003e\u003cstrong\u003ebetween patients with and without ablation\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eA subgroup analysis for all-cause mortality of various patient characteristics showed the comparison of patients with ablation versus without ablation (Figure 2). Subgroup analysis showed significantly reduced mortality for patients with ablation across all categories, including different age, sex, LVEF, CKD, HTN, DM, dyslipidemia, and different AF types (Figure 2A).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eA subgroup analysis for ischemic stroke of various patient characteristics presented a comparison of patients with ablation versus without ablation (Figure 2B). The analysis showed ablation was associated with significantly lower HRs in females (HR 0.69, \u003cem\u003ep=\u003c/em\u003e0.0402), patients with LVEF ≥57% (HR 0.66, \u003cem\u003ep=\u003c/em\u003e0.0474), those without CKD (HR 0.74, \u003cem\u003ep=\u003c/em\u003e0.0235), those with HTN (HR 0.72, \u003cem\u003ep\u003c/em\u003e=0.0182), and those with paroxysmal AF (HR 0.72, \u003cem\u003ep\u003c/em\u003e=0.0131).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eA subgroup analysis for HF with acute exacerbation of various patient characteristics showed a comparison of patients with ablation versus patients without ablation (Figure 2C). The analysis showed that ablation was associated with significantly lower HRs in females (HR 0.73, \u003cem\u003ep\u003c/em\u003e=0.0086), patients with LVEF ≥57% (HR 0.73, \u003cem\u003ep\u003c/em\u003e=0.0094), those without CKD (HR 0.76, \u003cem\u003ep\u003c/em\u003e=0.0063), patients with HTN (HR 0.74, \u003cem\u003ep\u003c/em\u003e=0.0015), and those with dyslipidemia (HR 0.72, \u003cem\u003ep\u003c/em\u003e=0.0012).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eThe subgroup analyses highlighted the heterogeneous impact of ablation therapy across different patient subgroups and indicated that the benefits of ablation may be more pronounced in specific populations.\u0026nbsp;\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eThe benefits of CA for patients with HFpEF and AF remain a controversial issue, with current evidence being insufficient for a definitive conclusion. In this study, we observed a lower incidence of all-cause mortality, stroke, and HF with acute exacerbation in patients with HFpEF and AF following CA. Additionally, there was a trend towards a lower incidence of progression to HFrEF after CA. The reduction in mortality was consistent across all subgroups, while the reduction in stroke and HF exacerbation was more significant in specific groups, particularly females, those with better LVEF, without CKD, with HTN, and in patients with paroxysmal AF. These findings suggest that ablation therapy's benefits may vary, being more pronounced in certain populations.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCA provided the benefit of reducing HF hospitalizations and may slow the progression to reduced LVEF\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eIn patients with AF and HFrEF, several randomized controlled trials and meta-analyses have demonstrated the effectiveness of CA in improving survival, HF hospitalizations, functional capacity, and quality of life, with acceptable safety. \u003csup\u003e2, 10-14\u003c/sup\u003e In patients with LVEF \u0026lt; 50%, 75.0% showed improvement in LVEF following CA for AF. \u003csup\u003e15\u003c/sup\u003e Predictors of this improvement included a smaller left ventricular volume and the absence of low voltage zones in the left atrium. \u003csup\u003e15, 16\u003c/sup\u003e CA also slowed the progression of LA remodeling. \u003csup\u003e7, 17\u003c/sup\u003e However, the improvement of LVEF observed in some studies was not confirmed in patients with HFpEF following CA. One meta-analysis reported that CA had limited or no benefit in reducing cardiovascular and all-cause mortality for patients with AF and HFpEF. \u003csup\u003e11\u003c/sup\u003e However, another meta-analysis showed different results from more studies, showing that CA reduced HF hospitalizations and increased the prevalence of maintaining sinus rhythm. \u003csup\u003e18\u0026nbsp;\u003c/sup\u003eAdditionally, another report showed various benefits of CA for patients with HFrEF and HF with mildly reduced EF, including improved LVEF, increased walking distance, reduced AF recurrence, and lower all-cause mortality. \u003csup\u003e19\u003c/sup\u003e In our study, we found that the incidence of HF with acute exacerbation was significantly lower in patients who underwent CA compared to those who received medical treatment alone, especially in the subgroups of female, EF ≥ 57%, with HTN, and without CKD. These findings suggested that CA could still be beneficial in the management of HF by reducing the frequency of hospital admissions in patients with HFpEF in real-world practice. Although CA showed potential in slowing the progression to reduced EF, the difference was not statistically significant. This finding indicated that while CA offered certain benefits in the management of HF in patients with HFpEF, its impact on LVEF progression requires further investigation.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eThe impact of CA on Risk Reduction of Stroke in HFpEF and AF\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eReducing the burden of arrhythmia is a reasonable strategy as it may help decrease the risk of stroke. In a randomized controlled study on early rhythm control of AF, a lower incidence of stroke was observed in the population receiving early rhythm control through medications or CA. \u003csup\u003e3\u003c/sup\u003e However, the benefit of rhythm control of AF by CA was not observed in studies for patients with HFrEF, although there may still be a trend toward a reduced risk of stroke. \u003csup\u003e4\u003c/sup\u003e CA could increase the rate of maintenance of sinus rhythm and improved quality of life in patients with AF and HFpEF. \u003csup\u003e20, 21\u003c/sup\u003e Additionally, one meta-analysis concluded that CA significantly reduced the risk of stroke compared to medical therapy alone. \u003csup\u003e22\u003c/sup\u003e While the contribution of CA to stroke reduction in AF patients remains a controversial issue, there may be a trend toward its benefit in some studies. \u003csup\u003e23, 24\u003c/sup\u003e In this study of CA for AF in patients with HFpEF, we observed that the one-year and five-year stroke risks were significantly reduced in the ablation group compared to the non-ablation group. This study showed that CA provided some benefit in reducing stroke events in specific population, especially in females, patients with an EF ≥ 57%, patients without CKD, patients with HTN, patients without type 2 DM, and patients with paroxysmal AF.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eStudy limitations\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe first limitation, inherent to all observational studies, is residual unmeasured confounding factors. Additionally, our data were obtained retrospectively from electronic medical records, which rely on the accurate documentation of diagnostic codes, introducing potential limitations due to miscoding. Furthermore, the database only captures outcomes if a patient remains within the same or another participating healthcare organization, which means some outcomes may have been missed. However, the bias should have affected in both study groups equally. Lastly, social determinants of health and other unmeasurable confounding factors may have influenced the outcomes, which we were unable to account for. Even though PSM was performed to reduce bias, there are still unmeasured confounding factors that may affect the results. These unmeasured factors could potentially influence the outcomes in ways that were not accounted for in the analysis, highlighting the inherent limitations of observational studies despite advanced statistical techniques like PSM.\u003c/p\u003e"},{"header":"Conclusions","content":"\u003cp\u003eIn patients with AF and HFpEF, CA provided cardiovascular and cerebral benefits and might reduce the risk of progression to HFrEF over five years of follow-up. Additionally, CA was associated with a reduction in all-cause mortality in patients with AF and HFpEF.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eAuthor contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWei-Chieh Lee contributed to the study concept and design, literature review, data interpretation, drafting of the manuscript, and final approval of the submitted version. Wan-Hsuan Hsu was responsible for statistical analysis, data curation, and provided critical input on methodological aspects of the study. Chih-Cheng Lai, Wei-Ting Chang, Chia-Te Liao, Jhih-Yuan Shih, and Zhih-Cherng Chen participated in study coordination and contributed to data interpretation and figure preparation. Hsiu-Yu Fang was involved in manuscript revision, statistical quality control, and proofreading. Mien-Cheng Chen supervised the entire project, critically reviewed the manuscript, and approved the final version for publication. All authors reviewed the manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eInformed Consent\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe IRB waived the requirement for written informed consent due to the retrospective nature of the study.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConflict of interest\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNone\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgments\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors express their gratitude to Wan-Hsuan Hsu for providing statistical support and extend their appreciation for the assistance received from the Biostatistics Center at Chi Mei Medical Center in the study design, data monitoring, analysis, and interpretation.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of data and material\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eData from this study can be obtained from the corresponding authors upon reasonable request. This research utilized data from the TriNetX research network. The analyses, interpretations, and conclusions drawn in this study do not reflect the views of Chi Mei Medical Center.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNone\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis research was funded by the Chi-Mei Medical Center in Tainan City, Taiwan. Wei-Chieh Lee received support through grants from the Chi-Mei Medical Center (CMFHR11164, CMFHR112079).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003ePotential conflicts of interest for each author\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNone\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eKim, D., Yang, P. S. \u0026amp; Joung, B. Optimal Rhythm Control Strategy in Patients With Atrial Fibrillation. \u003cem\u003eKorean Circ. J.\u003c/em\u003e \u003cb\u003e52\u003c/b\u003e (7), 496\u0026ndash;512 (2022).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKirchhof, P. et al. Early Rhythm-Control Therapy in Patients with Atrial Fibrillation. \u003cem\u003eN Engl. J. Med.\u003c/em\u003e \u003cb\u003e383\u003c/b\u003e (14), 1305\u0026ndash;1316 (2020).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eJensen, M. et al. Early rhythm-control therapy for atrial fibrillation in patients with a history of stroke: a subgroup analysis of the EAST-AFNET 4 trial. \u003cem\u003eLancet Neurol.\u003c/em\u003e \u003cb\u003e22\u003c/b\u003e (1), 45\u0026ndash;54 (2023).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMarrouche, N. F. et al. Catheter Ablation for Atrial Fibrillation with Heart Failure. \u003cem\u003eN Engl. J. Med.\u003c/em\u003e \u003cb\u003e378\u003c/b\u003e (5), 417\u0026ndash;427 (2018).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003ePacker, D. L. et al. Ablation Versus Drug Therapy for Atrial Fibrillation in Heart Failure: Results From the CABANA Trial. \u003cem\u003eCirculation\u003c/em\u003e \u003cb\u003e143\u003c/b\u003e (14), 1377\u0026ndash;1390 (2021).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSohns, C. et al. Catheter Ablation in End-Stage Heart Failure with Atrial Fibrillation. \u003cem\u003eN Engl. J. Med.\u003c/em\u003e \u003cb\u003e389\u003c/b\u003e (15), 1380\u0026ndash;1389 (2023).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKuck, K. H. et al. Catheter ablation or medical therapy to delay progression of atrial fibrillation: the randomized controlled atrial fibrillation progression trial (ATTEST). \u003cem\u003eEuropace\u003c/em\u003e \u003cb\u003e23\u003c/b\u003e (3), 362\u0026ndash;369 (2021).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMekhael, M. et al. Catheter ablation improved ejection fraction in persistent AF patients: a DECAAF-II sub analysis. \u003cem\u003eEuropace\u003c/em\u003e \u003cb\u003e25\u003c/b\u003e (3), 889\u0026ndash;895 (2023).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eChieng, D. et al. Atrial Fibrillation Ablation for Heart Failure With Preserved Ejection Fraction: A Randomized Controlled Trial. \u003cem\u003eJACC Heart Fail.\u003c/em\u003e \u003cb\u003e11\u003c/b\u003e (6), 646\u0026ndash;658 (2023).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eXie, Z. et al. Ablation for atrial fibrillation improves the outcomes in patients with heart failure with preserved ejection fraction. \u003cem\u003eEuropace\u003c/em\u003e \u003cb\u003e26\u003c/b\u003e (1), euad363 (2023).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eOraii, A. et al. 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Electrophysiol.\u003c/em\u003e \u003cb\u003e7\u003c/b\u003e (1), 31\u0026ndash;38 (2014).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003ePrabhu, S. et al. Catheter Ablation Versus Medical Rate Control in Atrial Fibrillation and Systolic Dysfunction: The CAMERA-MRI Study. \u003cem\u003eJ. Am. Coll. Cardiol.\u003c/em\u003e \u003cb\u003e70\u003c/b\u003e (16), 1949\u0026ndash;1961 (2017).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eZhao, X. et al. Predictors of improvement in left ventricular systolic function after catheter ablation in patients with persistent atrial fibrillation complicated with heart failure. \u003cem\u003eBMC Cardiovasc. Disord\u003c/em\u003e. \u003cb\u003e24\u003c/b\u003e (1), 178 (2024).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eUkita, K. et al. Predictors of improvement of left ventricular systolic function after catheter ablation of persistent atrial fibrillation in patients with heart failure with reduced ejection fraction. \u003cem\u003eHeart Vessels\u003c/em\u003e. \u003cb\u003e36\u003c/b\u003e (8), 1212\u0026ndash;1218 (2021).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLo, L. W. \u0026amp; Chen, S. A. Cardiac Remodeling After Atrial Fibrillation Ablation. \u003cem\u003eJ. Atr. Fibrillation\u003c/em\u003e. \u003cb\u003e6\u003c/b\u003e (1), 877 (2013).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eGu, G. et al. Catheter ablation of atrial fibrillation in patients with heart failure and preserved ejection fraction: A meta-analysis. \u003cem\u003eClin. Cardiol.\u003c/em\u003e \u003cb\u003e45\u003c/b\u003e (7), 786\u0026ndash;793 (2022).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLee, W. C. et al. Outcomes of catheter ablation vs. medical treatment for atrial fibrillation and heart failure: a meta-analysis. \u003cem\u003eFront. Cardiovasc. Med.\u003c/em\u003e \u003cb\u003e10\u003c/b\u003e, 1165011 (2023).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMachino-Ohtsuka, T. et al. Relationships between maintenance of sinus rhythm and clinical outcomes in patients with heart failure with preserved ejection fraction and atrial fibrillation. \u003cem\u003eJ. Cardiol.\u003c/em\u003e \u003cb\u003e74\u003c/b\u003e (3), 235\u0026ndash;244 (2019).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eRattka, M. et al. Restoration of sinus rhythm by pulmonary vein isolation improves heart failure with preserved ejection fraction in atrial fibrillation patients. \u003cem\u003eEuropace\u003c/em\u003e \u003cb\u003e22\u003c/b\u003e (9), 1328\u0026ndash;1336 (2020).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSaglietto, A. et al. Impact of atrial fibrillation catheter ablation on mortality, stroke, and heart failure hospitalizations: A meta-analysis. \u003cem\u003eJ. Cardiovasc. Electrophysiol.\u003c/em\u003e \u003cb\u003e31\u003c/b\u003e (5), 1040\u0026ndash;1047 (2020).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eAkerstr\u0026ouml;m, F. et al. Association between catheter ablation of atrial fibrillation and mortality or stroke. \u003cem\u003eHeart\u003c/em\u003e \u003cb\u003e110\u003c/b\u003e (3), 163\u0026ndash;169 (2024).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBarra, S. et al. Atrial Fibrillation Ablation and Reduction of Stroke Events: Understanding the Paradoxical Lack of Evidence. \u003cem\u003eStroke\u003c/em\u003e \u003cb\u003e50\u003c/b\u003e (10), 2970\u0026ndash;2976 (2019).\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"},{"header":"Tables","content":"\u003cdiv class=\"gridtable\"\u003e\n \u003cdiv align=\"left\" class=\"colspec\"\u003e\u003cbr\u003e\u003c/div\u003e\u0026nbsp;\u003ctable id=\"Tab1\" border=\"1\"\u003e\n \u003ccaption language=\"En\"\u003e\n \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e\n \u003cdiv class=\"CaptionContent\"\u003e\n \u003cdiv class=\"SimplePara\"\u003eBaseline characteristics in with ablation and without ablation groups before and after propensity score matching\u003c/div\u003e\n \u003c/div\u003e\n \u003c/caption\u003e\n \u003ccolgroup cols=\"10\"\u003e\u003c/colgroup\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003cth align=\"left\" rowspan=\"2\" style=\"width: 21.2525%;\"\u003e\u0026nbsp;\u003c/th\u003e\n \u003cth align=\"left\" colspan=\"3\" style=\"width: 32.2964%;\"\u003e\n \u003cdiv class=\"SimplePara\"\u003eBefore PSM\u003c/div\u003e\n \u003c/th\u003e\n \u003cth align=\"left\" colspan=\"3\" style=\"width: 26.6353%;\"\u003e\n \u003cdiv class=\"SimplePara\"\u003eAfter PSM\u003c/div\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003cth align=\"left\" style=\"width: 16.1482%;\"\u003e\n \u003cdiv class=\"SimplePara\"\u003eWith ablation\u003c/div\u003e\n \u003cdiv class=\"SimplePara\"\u003e( n\u0026thinsp;=\u0026thinsp;1,234)\u003c/div\u003e\n \u003c/th\u003e\n \u003cth align=\"left\" style=\"width: 10.5799%;\"\u003e\n \u003cdiv class=\"SimplePara\"\u003eWithout abaltion\u003c/div\u003e\n \u003cdiv class=\"SimplePara\"\u003e( n\u0026thinsp;=\u0026thinsp;13,500)\u003c/div\u003e\n \u003c/th\u003e\n \u003cth align=\"left\" style=\"width: 5.5684%;\"\u003e\n \u003cdiv class=\"SimplePara\"\u003eStd diff.\u003c/div\u003e\n \u003c/th\u003e\n \u003cth align=\"left\" style=\"width: 9.0022%;\"\u003e\n \u003cdiv class=\"SimplePara\"\u003eWith ablation\u003c/div\u003e\n \u003cdiv class=\"SimplePara\"\u003e( n\u0026thinsp;=\u0026thinsp;1,152)\u003c/div\u003e\n \u003c/th\u003e\n \u003cth align=\"left\" style=\"width: 10.7655%;\"\u003e\n \u003cdiv class=\"SimplePara\"\u003eWithout abaltion\u003c/div\u003e\n \u003cdiv class=\"SimplePara\"\u003e( n\u0026thinsp;=\u0026thinsp;1,152)\u003c/div\u003e\n \u003c/th\u003e\n \u003cth align=\"left\" style=\"width: 6.9604%;\"\u003e\n \u003cdiv class=\"SimplePara\"\u003eStd diff.\u003c/div\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" style=\"width: 21.2525%;\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003eDemographics\u003c/span\u003e\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 16.1482%;\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 10.5799%;\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 5.5684%;\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 9.0022%;\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 10.7655%;\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 6.9604%;\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" style=\"width: 21.2525%;\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Italic\" class=\"Italic\" name=\"Emphasis\"\u003eAge at Index (y/o)\u003c/span\u003e\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 16.1482%;\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e67.7\u0026thinsp;\u0026plusmn;\u0026thinsp;9.7\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 10.5799%;\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e73.1\u0026thinsp;\u0026plusmn;\u0026thinsp;11.8\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\" style=\"width: 5.5684%;\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e0.500\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 9.0022%;\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e68.3\u0026thinsp;\u0026plusmn;\u0026thinsp;9.2\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 10.7655%;\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e68.1\u0026thinsp;\u0026plusmn;\u0026thinsp;13.2\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\" style=\"width: 6.9604%;\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e0.019\u003c/div\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" style=\"width: 21.2525%;\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Italic\" class=\"Italic\" name=\"Emphasis\"\u003eSex\u003c/span\u003e\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 16.1482%;\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 10.5799%;\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 5.5684%;\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 9.0022%;\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 10.7655%;\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 6.9604%;\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" style=\"width: 21.2525%;\"\u003e\n \u003cdiv class=\"SimplePara\"\u003eMale\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 16.1482%;\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e660 (53.50)\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 10.5799%;\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e6,784 (50.30)\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\" style=\"width: 5.5684%;\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e0.065\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 9.0022%;\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e605 (52.50)\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 10.7655%;\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e614 (53.30)\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\" style=\"width: 6.9604%;\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e0.016\u003c/div\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" style=\"width: 21.2525%;\"\u003e\n \u003cdiv class=\"SimplePara\"\u003eFemale\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 16.1482%;\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e571 (46.30)\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 10.5799%;\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e6,667 (49.40)\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\" style=\"width: 5.5684%;\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e0.062\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 9.0022%;\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e545 (47.30)\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 10.7655%;\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e535 (46.40)\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\" style=\"width: 6.9604%;\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e0.017\u003c/div\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" style=\"width: 21.2525%;\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Italic\" class=\"Italic\" name=\"Emphasis\"\u003eRace\u003c/span\u003e\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 16.1482%;\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 10.5799%;\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 5.5684%;\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 9.0022%;\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 10.7655%;\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 6.9604%;\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" style=\"width: 21.2525%;\"\u003e\n \u003cdiv class=\"SimplePara\"\u003eWhite\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 16.1482%;\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e1,106 (89.60)\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 10.5799%;\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e11,548 (85.50)\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\" style=\"width: 5.5684%;\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e0.124\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 9.0022%;\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e1,033 (89.70)\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 10.7655%;\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e1,036 (89.90)\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\" style=\"width: 6.9604%;\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e0.009\u003c/div\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" style=\"width: 21.2525%;\"\u003e\n \u003cdiv class=\"SimplePara\"\u003eBlack or African American\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 16.1482%;\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e55 (4.50)\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 10.5799%;\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e915 (6.80)\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\" style=\"width: 5.5684%;\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e0.101\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 9.0022%;\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e53 (4.60)\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 10.7655%;\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e47 (4.10)\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\" style=\"width: 6.9604%;\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e0.026\u003c/div\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" style=\"width: 21.2525%;\"\u003e\n \u003cdiv class=\"SimplePara\"\u003eAsian\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 16.1482%;\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e18 (1.50)\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 10.5799%;\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e219 (1.60)\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\" style=\"width: 5.5684%;\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e0.013\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 9.0022%;\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e17 (1.50)\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 10.7655%;\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e15 (1.30)\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\" style=\"width: 6.9604%;\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e0.015\u003c/div\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" style=\"width: 21.2525%;\"\u003e\n \u003cdiv class=\"SimplePara\"\u003eNative Hawaiian or Other Pacific Islander\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 16.1482%;\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e10 (0.80)\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 10.5799%;\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e10 (0.10)\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\" style=\"width: 5.5684%;\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e0.111\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 9.0022%;\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e10 (0.90)\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 10.7655%;\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e10 (0.90)\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\" style=\"width: 6.9604%;\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e\u0026lt;\u0026thinsp;0.001\u003c/div\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" style=\"width: 21.2525%;\"\u003e\n \u003cdiv class=\"SimplePara\"\u003eAmerican Indian or Alaska Native\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 16.1482%;\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e10 (0.80)\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 10.5799%;\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e23 (0.20)\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\" style=\"width: 5.5684%;\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e0.092\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 9.0022%;\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e10 (0.90)\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 10.7655%;\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e10 (0.90)\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\" style=\"width: 6.9604%;\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e\u0026lt;\u0026thinsp;0.001\u003c/div\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" style=\"width: 21.2525%;\"\u003e\n \u003cdiv class=\"SimplePara\"\u003eOther Race\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 16.1482%;\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e20 (1.60)\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 10.5799%;\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e364 (2.70)\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\" style=\"width: 5.5684%;\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e0.074\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 9.0022%;\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e18 (1.60)\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 10.7655%;\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e20 (1.70)\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\" style=\"width: 6.9604%;\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e0.014\u003c/div\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" style=\"width: 21.2525%;\"\u003e\n \u003cdiv class=\"SimplePara\"\u003eUnknown Race\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 16.1482%;\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e30 (2.40)\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 10.5799%;\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e421 (3.10)\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\" style=\"width: 5.5684%;\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e0.042\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 9.0022%;\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e26 (2.30)\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 10.7655%;\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e29 (2.50)\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\" style=\"width: 6.9604%;\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e0.017\u003c/div\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" style=\"width: 21.2525%;\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Italic\" class=\"Italic\" name=\"Emphasis\"\u003eEthnicity\u003c/span\u003e\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 16.1482%;\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 10.5799%;\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 5.5684%;\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 9.0022%;\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 10.7655%;\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 6.9604%;\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" style=\"width: 21.2525%;\"\u003e\n \u003cdiv class=\"SimplePara\"\u003eNot Hispanic or Latino\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 16.1482%;\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e1,158 (93.80)\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 10.5799%;\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e12,568 (93.10)\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\" style=\"width: 5.5684%;\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e0.030\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 9.0022%;\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e1,087 (94.40)\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 10.7655%;\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e1,081 (93.80)\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\" style=\"width: 6.9604%;\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e0.022\u003c/div\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" style=\"width: 21.2525%;\"\u003e\n \u003cdiv class=\"SimplePara\"\u003eHispanic or Latino\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 16.1482%;\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e45 (3.60)\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 10.5799%;\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e429 (3.20)\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\" style=\"width: 5.5684%;\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e0.026\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 9.0022%;\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e39 (3.40)\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 10.7655%;\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e40 (3.50)\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\" style=\"width: 6.9604%;\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e0.005\u003c/div\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" style=\"width: 21.2525%;\"\u003e\n \u003cdiv class=\"SimplePara\"\u003eUnknown Ethnicity\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 16.1482%;\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e31 (2.50)\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 10.5799%;\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e503 (3.70)\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\" style=\"width: 5.5684%;\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e0.070\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 9.0022%;\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e26 (2.30)\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 10.7655%;\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e31 (2.70)\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\" style=\"width: 6.9604%;\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e0.028\u003c/div\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" style=\"width: 21.2525%;\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003eComorbid conditions\u003c/span\u003e\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 16.1482%;\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 10.5799%;\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 5.5684%;\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 9.0022%;\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 10.7655%;\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 6.9604%;\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" style=\"width: 21.2525%;\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Italic\" class=\"Italic\" name=\"Emphasis\"\u003eCardiovascular diseases\u003c/span\u003e\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 16.1482%;\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 10.5799%;\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 5.5684%;\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 9.0022%;\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 10.7655%;\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 6.9604%;\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" style=\"width: 21.2525%;\"\u003e\n \u003cdiv class=\"SimplePara\"\u003eHypertensive diseases\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 16.1482%;\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e1,022 (82.80)\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 10.5799%;\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e9,483 (70.20)\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\" style=\"width: 5.5684%;\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e0.300\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 9.0022%;\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e956 (83.00)\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 10.7655%;\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e943 (81.90)\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\" style=\"width: 6.9604%;\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e0.030\u003c/div\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" style=\"width: 21.2525%;\"\u003e\n \u003cdiv class=\"SimplePara\"\u003eIschemic heart diseases\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 16.1482%;\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e610 (49.40)\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 10.5799%;\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e6,988 (51.80)\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\" style=\"width: 5.5684%;\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e0.047\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 9.0022%;\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e577 (50.10)\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 10.7655%;\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e588 (51.00)\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\" style=\"width: 6.9604%;\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e0.019\u003c/div\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" style=\"width: 21.2525%;\"\u003e\n \u003cdiv class=\"SimplePara\"\u003eAcute diastolic heart failure\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 16.1482%;\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e150 (12.20)\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 10.5799%;\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e849 (6.30)\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\" style=\"width: 5.5684%;\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e0.204\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 9.0022%;\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e133 (11.50)\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 10.7655%;\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e118 (10.20)\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\" style=\"width: 6.9604%;\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e0.042\u003c/div\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" style=\"width: 21.2525%;\"\u003e\n \u003cdiv class=\"SimplePara\"\u003eParoxysmal atrial fibrillation\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 16.1482%;\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e945 (76.60)\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 10.5799%;\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e3,755 (27.80)\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\" style=\"width: 5.5684%;\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e1.119\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 9.0022%;\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e863 (74.90)\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 10.7655%;\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e858 (74.50)\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\" style=\"width: 6.9604%;\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e0.010\u003c/div\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" style=\"width: 21.2525%;\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Italic\" class=\"Italic\" name=\"Emphasis\"\u003eMetabolic disorders\u003c/span\u003e\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 16.1482%;\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 10.5799%;\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 5.5684%;\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 9.0022%;\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 10.7655%;\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 6.9604%;\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" style=\"width: 21.2525%;\"\u003e\n \u003cdiv class=\"SimplePara\"\u003eDyslipidemia\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 16.1482%;\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e828 (67.10)\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 10.5799%;\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e7,561 (56.00)\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\" style=\"width: 5.5684%;\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e0.229\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 9.0022%;\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e779 (67.60)\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 10.7655%;\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e752 (65.30)\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\" style=\"width: 6.9604%;\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e0.050\u003c/div\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" style=\"width: 21.2525%;\"\u003e\n \u003cdiv class=\"SimplePara\"\u003eOverweight and obesity\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 16.1482%;\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e566 (45.90)\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 10.5799%;\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e3,569 (26.40)\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\" style=\"width: 5.5684%;\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e0.413\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 9.0022%;\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e511 (44.40)\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 10.7655%;\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e525 (45.60)\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\" style=\"width: 6.9604%;\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e0.024\u003c/div\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" style=\"width: 21.2525%;\"\u003e\n \u003cdiv class=\"SimplePara\"\u003eType 2 diabetes mellitus\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 16.1482%;\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e456 (37.00)\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 10.5799%;\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e4,527 (33.50)\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\" style=\"width: 5.5684%;\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e0.072\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 9.0022%;\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e426 (37.00)\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 10.7655%;\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e434 (37.70)\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\" style=\"width: 6.9604%;\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e0.014\u003c/div\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" style=\"width: 21.2525%;\"\u003e\n \u003cdiv class=\"SimplePara\"\u003eDisorders of thyroid gland\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 16.1482%;\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e365 (29.60)\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 10.5799%;\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e3,146 (23.30)\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\" style=\"width: 5.5684%;\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e0.143\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 9.0022%;\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e343 (29.80)\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 10.7655%;\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e345 (29.90)\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\" style=\"width: 6.9604%;\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e0.004\u003c/div\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" style=\"width: 21.2525%;\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Italic\" class=\"Italic\" name=\"Emphasis\"\u003eChronic kidney diseases\u003c/span\u003e\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 16.1482%;\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 10.5799%;\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 5.5684%;\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 9.0022%;\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 10.7655%;\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 6.9604%;\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" style=\"width: 21.2525%;\"\u003e\n \u003cdiv class=\"SimplePara\"\u003eStage 3\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 16.1482%;\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e139 (11.30)\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 10.5799%;\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e2,089 (15.50)\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\" style=\"width: 5.5684%;\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e0.124\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 9.0022%;\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e135 (11.70)\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 10.7655%;\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e136 (11.80)\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\" style=\"width: 6.9604%;\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e0.003\u003c/div\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" style=\"width: 21.2525%;\"\u003e\n \u003cdiv class=\"SimplePara\"\u003eStage 4\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 16.1482%;\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e26 (2.10)\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 10.5799%;\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e533 (3.90)\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\" style=\"width: 5.5684%;\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e0.108\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 9.0022%;\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e25 (2.20)\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 10.7655%;\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e32 (2.80)\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\" style=\"width: 6.9604%;\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e0.039\u003c/div\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" style=\"width: 21.2525%;\"\u003e\n \u003cdiv class=\"SimplePara\"\u003eCerebral infarction\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 16.1482%;\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e183 (14.80)\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 10.5799%;\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e2,206 (16.30)\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\" style=\"width: 5.5684%;\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e0.042\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 9.0022%;\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e178 (15.40)\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 10.7655%;\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e190 (16.50)\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\" style=\"width: 6.9604%;\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e0.028\u003c/div\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" style=\"width: 21.2525%;\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003eMedications\u003c/span\u003e\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 16.1482%;\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 10.5799%;\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 5.5684%;\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 9.0022%;\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 10.7655%;\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 6.9604%;\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" style=\"width: 21.2525%;\"\u003e\n \u003cdiv class=\"SimplePara\"\u003eBeta-blockers\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 16.1482%;\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e986 (79.90)\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 10.5799%;\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e8,261 (61.20)\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\" style=\"width: 5.5684%;\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e0.419\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 9.0022%;\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e908 (78.80)\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 10.7655%;\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e902 (78.30)\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\" style=\"width: 6.9604%;\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e0.013\u003c/div\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" style=\"width: 21.2525%;\"\u003e\n \u003cdiv class=\"SimplePara\"\u003eAnti-arrhythmic\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 16.1482%;\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e919 (74.50)\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 10.5799%;\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e7,312 (54.20)\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\" style=\"width: 5.5684%;\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e0.434\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 9.0022%;\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e848 (73.60)\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 10.7655%;\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e840 (72.90)\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\" style=\"width: 6.9604%;\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e0.016\u003c/div\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" style=\"width: 21.2525%;\"\u003e\n \u003cdiv class=\"SimplePara\"\u003eDiuretics\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 16.1482%;\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e804 (65.20)\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 10.5799%;\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e7,980 (59.10)\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\" style=\"width: 5.5684%;\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e0.125\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 9.0022%;\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e749 (65.00)\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 10.7655%;\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e718 (62.30)\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\" style=\"width: 6.9604%;\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e0.056\u003c/div\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" style=\"width: 21.2525%;\"\u003e\n \u003cdiv class=\"SimplePara\"\u003eStatin\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 16.1482%;\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e651 (52.80)\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 10.5799%;\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e6,806 (50.40)\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\" style=\"width: 5.5684%;\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e0.047\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 9.0022%;\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e613 (53.20)\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 10.7655%;\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e593 (51.50)\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\" style=\"width: 6.9604%;\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e0.035\u003c/div\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" style=\"width: 21.2525%;\"\u003e\n \u003cdiv class=\"SimplePara\"\u003eAnti-Platelet\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 16.1482%;\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e558 (45.20)\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 10.5799%;\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e7,130 (52.80)\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\" style=\"width: 5.5684%;\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e0.152\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 9.0022%;\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e545 (47.30)\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 10.7655%;\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e541 (47.00)\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\" style=\"width: 6.9604%;\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e0.007\u003c/div\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" style=\"width: 21.2525%;\"\u003e\n \u003cdiv class=\"SimplePara\"\u003eARBs\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 16.1482%;\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e372 (30.10)\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 10.5799%;\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e2,490 (18.40)\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\" style=\"width: 5.5684%;\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e0.275\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 9.0022%;\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e325 (28.20)\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 10.7655%;\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e351 (30.50)\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\" style=\"width: 6.9604%;\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e0.050\u003c/div\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" style=\"width: 21.2525%;\"\u003e\n \u003cdiv class=\"SimplePara\"\u003eACE inhibitors\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 16.1482%;\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e342 (27.70)\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 10.5799%;\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e3,284 (24.30)\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\" style=\"width: 5.5684%;\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e0.077\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 9.0022%;\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e321 (27.90)\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 10.7655%;\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e323 (28.00)\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\" style=\"width: 6.9604%;\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e0.004\u003c/div\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" style=\"width: 21.2525%;\"\u003e\n \u003cdiv class=\"SimplePara\"\u003eInsulin\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 16.1482%;\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e337 (27.30)\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 10.5799%;\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e4,365 (32.30)\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\" style=\"width: 5.5684%;\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e0.110\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 9.0022%;\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e325 (28.20)\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 10.7655%;\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e329 (28.60)\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\" style=\"width: 6.9604%;\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e0.008\u003c/div\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" style=\"width: 21.2525%;\"\u003e\n \u003cdiv class=\"SimplePara\"\u003eDigitalis\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 16.1482%;\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e170 (13.80)\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 10.5799%;\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e781 (5.80)\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\" style=\"width: 5.5684%;\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e0.271\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 9.0022%;\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e152 (13.20)\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 10.7655%;\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e151 (13.10)\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\" style=\"width: 6.9604%;\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e0.003\u003c/div\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" style=\"width: 21.2525%;\"\u003e\n \u003cdiv class=\"SimplePara\"\u003eMetformin\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 16.1482%;\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e153 (12.40)\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 10.5799%;\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e1,384 (10.30)\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\" style=\"width: 5.5684%;\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e0.068\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 9.0022%;\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e145 (12.60)\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 10.7655%;\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e148 (12.80)\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\" style=\"width: 6.9604%;\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e0.008\u003c/div\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" style=\"width: 21.2525%;\"\u003e\n \u003cdiv class=\"SimplePara\"\u003eSGLT2 inhibitors\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 16.1482%;\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e78 (6.30)\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 10.5799%;\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e265 (2.00)\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\" style=\"width: 5.5684%;\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e0.220\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 9.0022%;\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e59 (5.10)\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 10.7655%;\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e53 (4.60)\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\" style=\"width: 6.9604%;\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e0.024\u003c/div\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" style=\"width: 21.2525%;\"\u003e\n \u003cdiv class=\"SimplePara\"\u003eGlipizide\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 16.1482%;\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e38 (3.10)\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 10.5799%;\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e442 (3.30)\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\" style=\"width: 5.5684%;\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e0.011\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 9.0022%;\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e36 (3.10)\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 10.7655%;\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e38 (3.30)\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\" style=\"width: 6.9604%;\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e0.010\u003c/div\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" style=\"width: 21.2525%;\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Bold\" class=\"Bold\" name=\"Emphasis\"\u003eLaboratory values\u003c/span\u003e\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 16.1482%;\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 10.5799%;\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 5.5684%;\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 9.0022%;\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 10.7655%;\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 6.9604%;\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" style=\"width: 21.2525%;\"\u003e\n \u003cdiv class=\"SimplePara\"\u003eCreatinine (mg/dL)\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 16.1482%;\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e1.1\u0026thinsp;\u0026plusmn;\u0026thinsp;0.4\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 10.5799%;\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e1.2\u0026thinsp;\u0026plusmn;\u0026thinsp;1.3\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\" style=\"width: 5.5684%;\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e0.148\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 9.0022%;\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e1.1\u0026thinsp;\u0026plusmn;\u0026thinsp;0.5\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 10.7655%;\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e1.1\u0026thinsp;\u0026plusmn;\u0026thinsp;0.6\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\" style=\"width: 6.9604%;\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e0.016\u003c/div\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" style=\"width: 21.2525%;\"\u003e\n \u003cdiv class=\"SimplePara\"\u003eLDL (mg/dL)\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 16.1482%;\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e86.0\u0026thinsp;\u0026plusmn;\u0026thinsp;36.0\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 10.5799%;\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e82.2\u0026thinsp;\u0026plusmn;\u0026thinsp;35.7\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\" style=\"width: 5.5684%;\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e0.105\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 9.0022%;\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e85.9\u0026thinsp;\u0026plusmn;\u0026thinsp;35.8\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 10.7655%;\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e82.5\u0026thinsp;\u0026plusmn;\u0026thinsp;34.0\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\" style=\"width: 6.9604%;\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e0.097\u003c/div\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" style=\"width: 21.2525%;\"\u003e\n \u003cdiv class=\"SimplePara\"\u003eHbA1c\u0026thinsp;\u0026ge;\u0026thinsp;7%\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 16.1482%;\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e140 (11.30)\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 10.5799%;\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e1,749 (13.00)\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\" style=\"width: 5.5684%;\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e0.049\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 9.0022%;\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e134 (11.60)\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 10.7655%;\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e132 (11.50)\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\" style=\"width: 6.9604%;\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e0.005\u003c/div\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" style=\"width: 21.2525%;\"\u003e\n \u003cdiv class=\"SimplePara\"\u003eBNP\u0026thinsp;\u0026ge;\u0026thinsp;150 pg/mL\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 16.1482%;\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e295 (23.90)\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 10.5799%;\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e2,376 (17.60)\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\" style=\"width: 5.5684%;\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e0.156\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 9.0022%;\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e265 (23.00)\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 10.7655%;\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e269 (23.40)\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\" style=\"width: 6.9604%;\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e0.008\u003c/div\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" style=\"width: 21.2525%;\"\u003e\n \u003cdiv class=\"SimplePara\"\u003eNT-proBNP\u0026thinsp;\u0026ge;\u0026thinsp;450 pg/mL\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 16.1482%;\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e296 (24.00)\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 10.5799%;\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e2,787 (20.60)\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\" style=\"width: 5.5684%;\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e0.080\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 9.0022%;\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e279 (24.20)\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 10.7655%;\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e270 (23.40)\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\" style=\"width: 6.9604%;\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e0.018\u003c/div\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" style=\"width: 21.2525%;\"\u003e\n \u003cdiv class=\"SimplePara\"\u003eLVEF (%)\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 16.1482%;\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e58.9\u0026thinsp;\u0026plusmn;\u0026thinsp;6.5\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 10.5799%;\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e59.8\u0026thinsp;\u0026plusmn;\u0026thinsp;9.5\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\" style=\"width: 5.5684%;\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e0.119\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 9.0022%;\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e58.8\u0026thinsp;\u0026plusmn;\u0026thinsp;6.5\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" style=\"width: 10.7655%;\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e59.3\u0026thinsp;\u0026plusmn;\u0026thinsp;10.2\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\" style=\"width: 6.9604%;\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e0.062\u003c/div\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003ctfoot\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"7\" style=\"width: 81.9476%;\"\u003eValues are mean\u0026thinsp;\u0026plusmn;\u0026thinsp;standard difference or number (%). Any characteristic with a standard difference between cohorts\u0026thinsp;\u0026lt;\u0026thinsp;0.10 was considered to be well matched.\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"7\" style=\"width: 81.9476%;\"\u003eAbbreviation: PSM: propensity score matching; SD.: standardized difference; LDL-C: Low density lipoprotein-Cholesterol; BNP: B-type natriuretic peptide; ACEIs: angiotensin-converting enzyme inhibitors; ARBs: angiotensin receptor blockers; SGLT2: sodium-glucose co-transporter 2; HMG-CoA: Hydroxymethylglutaryl-CoA.\u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tfoot\u003e\n \u003c/table\u003e\n\u003c/div\u003e\n\u003cp\u003e\u003c/p\u003e\u0026nbsp;\u003ctable id=\"Tab2\" border=\"1\"\u003e\n \u003ccaption language=\"En\"\u003e\n \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e\n \u003cdiv class=\"CaptionContent\"\u003e\n \u003cdiv class=\"SimplePara\"\u003eThe hazard ratios and incidences for comparing matched with ablation and without ablation group during the five-year follow-up period\u003c/div\u003e\n \u003c/div\u003e\n \u003c/caption\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003cth align=\"left\" rowspan=\"2\"\u003e\u0026nbsp;\u003c/th\u003e\n \u003cth align=\"left\" colspan=\"2\"\u003e\n \u003cdiv class=\"SimplePara\"\u003eNo. (%) of patients with outcome\u003c/div\u003e\n \u003c/th\u003e\n \u003cth align=\"left\" rowspan=\"2\"\u003e\n \u003cdiv class=\"SimplePara\"\u003eHR (95% CI)\u003c/div\u003e\n \u003c/th\u003e\n \u003cth align=\"left\" rowspan=\"2\"\u003e\n \u003cdiv class=\"SimplePara\"\u003eLog-rank\u003c/div\u003e\n \u003cdiv class=\"SimplePara\"\u003e\u003cspan type=\"Italic\" class=\"Italic\" name=\"Emphasis\"\u003ep\u003c/span\u003e-value\u003c/div\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003cth align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003eWith ablation\u003c/div\u003e\n \u003cdiv class=\"SimplePara\"\u003e( n\u0026thinsp;=\u0026thinsp;1,152 )\u003c/div\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003eWithout ablation\u003c/div\u003e\n \u003cdiv class=\"SimplePara\"\u003e( n\u0026thinsp;=\u0026thinsp;1,152 )\u003c/div\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003eAll-cause mortality (%)\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e70 (6.1)\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e195 (16.9)\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e0.34 (0.26,0.44)\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e\u0026lt;\u0026thinsp;0.0001\u003c/div\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003eHF exacerbation (%)\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e262 (22.7)\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e311 (27.0)\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e0.78 (0.67,0.92)\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e0.0035\u003c/div\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003eLVEF progress to mildly reduced EF (%)\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e129 (11.2)\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e123 (10.7)\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e1.02 (0.79,1.30)\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e0.8926\u003c/div\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003eLVEF progress to reduced EF (%)\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e57 (4.9)\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e75 (6.5)\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e0.72 (0.51,1.02)\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e0.0634\u003c/div\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cdiv class=\"SimplePara\"\u003eIschemic stroke (%)\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e116 (10.1)\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e148 (12.8)\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e0.72 (0.57,0.92)\u003c/div\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cdiv class=\"SimplePara\"\u003e0.0080\u003c/div\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003ctfoot\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"5\"\u003eData are expressed as number (percentage).\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"5\"\u003eAbbreviation: HR: hazard ratio; CI: confidence interval; HF: heart failure; LVEF: left ventricular ejection fraction.\u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tfoot\u003e\n\u003c/table\u003e\n\u003cp\u003e\u003c/p\u003e\n\u003cp\u003e\u003cbr\u003e\u003c/p\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Atrial fibrillation, Heart failure with preserved ejection fraction, Catheter ablation, Heart failure with acute exacerbation, Ischemic stroke","lastPublishedDoi":"10.21203/rs.3.rs-6488852/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-6488852/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eBackground\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eEvidence supporting catheter ablation (CA) for atrial fibrillation (AF) in heart failure with preserved ejection fraction (HFpEF) is limited. This study evaluated the impact of CA on clinical outcomes in patients with AF and HFpEF using a global clinical database.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMethods\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe TriNetX research network identified patients aged ≥18 years with AF and HFpEF (February 2014–June 2024). Patients were categorized by whether they underwent CA for AF. Primary outcomes included all-cause mortality, heart failure (HF) with acute exacerbation, and ischemic stroke. Secondary outcomes included progression to mildly reduced or reduced ejection fraction (EF) during follow-up.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eResults\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003ePatients receiving CA showed lower incidences of all-cause mortality, HF exacerbation, and ischemic stroke. There was a trend of less patients with progression to reduced EF in patients with CA. The reduction in mortality was consistent across all subgroups, while stroke reduction was more significant in females, those with better EF, without chronic kidney disease (CKD) or diabetes mellitus (DM), with hypertension (HTN), and with paroxysmal AF. The benefits in reducing HF exacerbation were particularly notable in females, those with better EF, without CKD, and with HTN.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eIn patients with AF and HFpEF, CA provided cardiovascular and cerebral benefits and might reduce the risk of progression to HFrEF over five years of follow-up. Additionally, CA was associated with a reduction in all-cause mortality in patients with AF and HFpEF.\u003c/p\u003e","manuscriptTitle":"Evaluating the Impact of Catheter Ablation on Cardiovascular and Cerebral Outcomes in Atrial Fibrillation with Heart Failure and Preserved Ejection Fraction","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-05-09 11:16:33","doi":"10.21203/rs.3.rs-6488852/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"a0212507-17b4-4826-b8a1-51b596f32aeb","owner":[],"postedDate":"May 9th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[{"id":48125567,"name":"Health sciences/Cardiology"},{"id":48125568,"name":"Health sciences/Health care"},{"id":48125569,"name":"Health sciences/Medical research"}],"tags":[],"updatedAt":"2025-09-10T05:54:39+00:00","versionOfRecord":[],"versionCreatedAt":"2025-05-09 11:16:33","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-6488852","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-6488852","identity":"rs-6488852","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}