The Effect of Vericiguat on Recurrence after Catheter Ablation of Atrial Fibrillation

The Effect of Vericiguat on Recurrence after Catheter Ablation of Atrial Fibrillation | Authorea try { document.documentElement.classList.add('js'); } catch (e) { } var _gaq = _gaq || []; _gaq.push(['_setAccount', 'G-8VDV14Y67G']); _gaq.push(['_trackPageview']); (function() { var ga = document.createElement('script'); ga.type = 'text/javascript'; ga.async = true; ga.src = ('https:' == document.location.protocol ? 'https://ssl' : 'http://www') + '.google-analytics.com/ga.js'; var s = document.getElementsByTagName('script')[0]; s.parentNode.insertBefore(ga, s); })(); Skip to main content Preprints Collections Wiley Open Research IET Open Research Ecological Society of Japan All Collections About About Authorea FAQs Contact Us Quick Search anywhere Search for preprint articles, keywords, etc. Search Search ADVANCED SEARCH SCROLL This is a preprint and has not been peer reviewed. Data may be preliminary. 8 August 2025 V1 Latest version Share on The Effect of Vericiguat on Recurrence after Catheter Ablation of Atrial Fibrillation Authors : Jia-Ling Yin , Rilang Peng 0009-0001-3874-633X , Jia-Wei Chen , Yun Xiao , Yuan Shu 0009-0003-0754-9143 , Xi-Chen Liu , Lu-Yao Mao , Kai Chen , and Ru Ying 0000-0001-6443-3903 [email protected] Authors Info & Affiliations https://doi.org/10.22541/au.175462399.96735228/v1 227 views 107 downloads Contents Abstract Abstract Introduction Methods Results Follow-up during the blanking period Primary Outcome Analysis Postoperative 12-month follow-up Secondary Endpoint Analysis Conclusions and Future Perspectives Information & Authors Metrics & Citations View Options References Figures Tables Media Share Abstract Objectives: Atrial fibrillation (AF) is one of the most common arrhythmias in China. For patients with symptomatic paroxysmal atrial fibrillation, catheter ablation has become a first-line treatment option. This study aims to investigate whether oral vericiguat treatment can reduce the recurrence of atrial fibrillation/atrial tachycardia (AF/AT) following catheter ablation for atrial fibrillation. Methods: According to the patients’ wishes, a total of 39 patients were divided into two groups: a control group and a group receiving oral vericiguat treatment. Both groups received guideline-directed medical therapy for atrial fibrillation. Follow-up was arranged at 1-3 months, 6 months and 12 months after the operation. The primary endpoint was the occurrence of atrial tachyarrhythmias after a 3-month blanking period. Secondary endpoints included left ventricular ejection fraction (LVEF), left atrial anterior-posterior diameter (LAAPD), right ventricular diameter, right ventricular outflow tract, aortic root, ascending aortic diameter, interventricular septal thickness, left ventricular posterior wall thickness, left ventricular end-diastolic diameter (LVEDD), and pulmonary artery diameter. Results: At 12 months post-procedure, vericiguat reduced the recurrence rate of AF/AT and decreased the LAAPD and LVEDD. However, vericiguat did not reduce the recurrence rate of AF/AT during the blanking period or at 6 months post-procedure, and no improvement in LVEF was observed. Conclusion: Vericiguat may reduce the long-term recurrence rate of atrial fibrillation after catheter ablation by inhibiting atrial and ventricular remodeling. These findings provide experimental evidence for the potential application of vericiguat in the management of patients following atrial fibrillation ablation. Jialing Yin 1,2,# , Rilang Peng 3,# , Jiawei Chen 1,2 , Yun Xiao 1,2 , Yuan Shu 1,2 , Xichen Liu 1,2 , Luyao Mao 1,2 , Kai Chen 1,2 and Ru Ying 1,2,* 1 Department of Cardiology, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, 330006, China 2 Hypertension Research Institute of Jiangxi Province (or Jiangxi Hypertension Research Institute), Nanchang, Jiangxi, 330006, China 3 The First Clinical Medical College, Jiangxi Medical College, Nanchang University, Nanchang 330006, China # Jialing Yin and Rilang Peng contributed equally to this work. * Correspondence: Ru Ying, [email protected] Data Availability Statement: The data that support the findings of this study are available from the corresponding author upon reasonable request. Funding Statement: This research work was financially supported by the following grants: the National Natural Science Foundation of China (Nos. 82200363), Science and Technology Program of Jiangxi Province (No. 20242BAB25428), and Clinical research training program of the First Affiliated Hospital of Nanchang University (No. YFYLCYJPY202429） Ethics Approval Statement: The study was conducted in accordance with the Declaration of Helsinki, and approved by the Ethics Committee of the First Affiliated Hospital of Nanchang University (Ethics Approval No. IIT-2023-326).” Conflict of Interest Disclosure: The authors declare that they have no known competing financial interests or personal relationships that could have influenced the study reported in this paper. Abstract Objectives: Atrial fibrillation (AF) is one of the most common arrhythmias in China. For patients with symptomatic paroxysmal atrial fibrillation, catheter ablation has become a first-line treatment option. This study aims to investigate whether oral vericiguat treatment can reduce the recurrence of atrial fibrillation/atrial tachycardia (AF/AT) following catheter ablation for atrial fibrillation. Methods: According to the patients’ wishes, a total of 39 patients were divided into two groups: a control group and a group receiving oral vericiguat treatment. Both groups received guideline-directed medical therapy for atrial fibrillation. Follow-up was arranged at 1-3 months, 6 months and 12 months after the operation. The primary endpoint was the occurrence of atrial tachyarrhythmias after a 3-month blanking period. Secondary endpoints included left ventricular ejection fraction (LVEF), left atrial anterior-posterior diameter (LAAPD), right ventricular diameter, right ventricular outflow tract, aortic root, ascending aortic diameter, interventricular septal thickness, left ventricular posterior wall thickness, left ventricular end-diastolic diameter (LVEDD), and pulmonary artery diameter. Results: At 12 months post-procedure, vericiguat reduced the recurrence rate of AF/AT and decreased the LAAPD and LVEDD. However, vericiguat did not reduce the recurrence rate of AF/AT during the blanking period or at 6 months post-procedure, and no improvement in LVEF was observed. Conclusion: Vericiguat may reduce the long-term recurrence rate of atrial fibrillation after catheter ablation by inhibiting atrial and ventricular remodeling. These findings provide experimental evidence for the potential application of vericiguat in the management of patients following atrial fibrillation ablation. Keywords: Atrial Fibrillation, Ablation, Vericiguat, Recurrence Introduction Atrial fibrillation (AF) is one of the most common arrhythmias. As of 2017, the global prevalence of AF was 37.57 million [1]. From 2001 to 2012, the prevalence of AF among Chinese people aged 20 and above was 0.2 per 100 people, increasing with age. The prevalence among those over 80 years old was 0.77 per 100 people, with a higher prevalence among women than men in those over 70 years old [2]. The treatment methods for AF include drug therapy, catheter ablation, and surgical intervention. The primary pharmacological management includes anticoagulation therapy (e.g., novel oral anticoagulants or warfarin) for stroke prevention, rate control (e.g., β-blockers, calcium channel blockers), and rhythm control (e.g., amiodarone). For symptomatic paroxysmal AF patients, catheter ablation has become the first-line treatment option [3]. Currently, the main catheter ablation techniques are radiofrequency ablation, cryoablation, and pulsed field ablation. There is no significant difference in AF recurrence after these three ablation techniques [4-7]. Sultan et al. identified that atrial fibrillation type, in-hospital AF recurrence, and comorbidities (e.g., renal failure and valvular heart disease) were independent predictors of AF recurrence during the 1-year follow-up (1-y-FU) in female AF patients [8]. Studies have confirmed that hypertension and left atrial diameter are strong predictors of AF recurrence after circumferential pulmonary vein ablation. Furthermore, blanking-period AF recurrence (regardless of antiarrhythmic drug use) is a strong independent predictor of long-term AF recurrence [9, 10]. With the development and maturity of AF catheter ablation techniques, the issue of postoperative recurrence has attracted increasing attention. We are eager to explore new methods to effectively reduce the postoperative recurrence rate and improve patient prognosis. Vericiguat is a novel oral soluble guanylate cyclase (sGC) agonist. The VICTORIA trial (2020) enrolled 5,050 patients aged ≥18 years with heart failure with reduced ejection fraction (HFrEF, left ventricular ejection fraction [LVEF] <45%) and recent signs of clinical worsening, classified as New York Heart Association (NYHA) class II–IV. Participants were randomly assigned to vericiguat or control groups, with a median follow-up of 10.8 months. The study found that vericiguat significantly reduced the risk of the composite endpoint of cardiovascular death or first hospitalization for heart failure in high-risk heart failure patients compared with the control group. Vericiguat exerts beneficial effects on heart failure with reduced LVEF by inhibiting the progression of ventricular hypertrophy and fibrosis, providing a new option for the treatment of chronic heart failure and prevention of heart failure exacerbation [11]. Another study evaluated the therapeutic effect of vericiguat in patients with heart failure and AF. The results showed that vericiguat had significant benefits on the primary composite endpoint (cardiovascular death or first hospitalization for heart failure) in all AF status groups, and the effect was not affected by the AF status. Therefore, vericiguat is expected to become a basic treatment drug for patients with heart failure and atrial fibrillation [12]. Although some studies have shown that vericiguat inhibits myocardial fibrosis, no study has proved its effect on AF and atrial fibrosis. The purpose of this article is to investigate in a prospective and clinical study whether short-term use of vericiguat after radiofrequency ablation of atrial fibrillation can inhibit atrial fibrosis and reduce the recurrence of atrial fibrillation. Methods Trial design This study is a prospective, patient preference-based, single-center clinical research. The research subjects were selected from patients who underwent catheter ablation for atrial fibrillation at the First Affiliated Hospital of Nanchang University from January 1, 2023 to December 31, 2024. They were screened strictly in accordance with the inclusion and exclusion criteria. The inclusion criteria were age ≥ 18 years and disappearance of P wave recorded in a single lead electrocardiogram (≥ 30 s) or 12-lead electrocardiogram (≥ 10 s), replaced by irregular fibrillation waves (f waves) with irregular size, shape and duration, and absolute irregular RR intervals. The exclusion criteria included refractory atrial fibrillation after cardioversion; atrial fibrillation combined with rheumatic valvular disease; patients receiving long-term intravenous infusion therapy, implanted with left heart assist devices, or awaiting heart transplantation; definite, complex, ongoing clinical comorbidities; estimated glomerular filtration rate (eGFR) < 15 mL/min/1.73m 2 or undergoing dialysis; combined use of other sGC stimulators; pregnant or lactating women; use of phosphodiesterase type 5 (PDE-5） inhibitors; severe anemia; systolic blood pressure < 90 mmHg; severe liver dysfunction. Grouping and Intervention Protocols Before ablation, patients underwent 12-lead/24-hour ambulatory electrocardiogram, transthoracic echocardiography, computed tomography venography of left atrium and pulmonary veins or transesophageal echocardiography, chest CT or chest X-ray examination, and blood routine, liver and kidney function, coagulation function, thyroid function, electrolyte, NT-pro-BNP and other test indicators were detected to determine possible exclusion criteria. All patients underwent catheter ablation for atrial fibrillation. Antiarrhythmic drugs were discontinued 3–5 days prior to the procedure, except for rate-controlling medications administered for other indications (e.g., hypertension, ischemic heart disease, or systolic dysfunction). All patients underwent 12-lead electrocardiography within 48 hours post-ablation and received continuous oral anticoagulant (OAC) or vitamin K antagonist therapy for at least 4 weeks before and 3 months after the procedure. After catheter ablation surgery, patients were divided into two groups according to their wishes. One group was the vericiguat group, which received 12-week oral vericiguat treatment, and the other group was the control group. The other treatment measures of the two groups were kept consistent except for the study drugs. Both groups received drug treatment based on atrial fibrillation guidelines. The dosing regimen of vericiguat was started from 2.5 mg once daily, for two consecutive weeks, and then 5 mg once daily, for a continuous period of 10 weeks. The study protocol was approved by the Ethics Committee of the First Affiliated Hospital of Nanchang University (Ethics Approval No. IIT-2023-326). Patient Follow-up All patients were scheduled for research visits before surgery and at 1-3 months, 6 months and 12 months after surgery. Patients were encouraged to record all symptoms related to arrhythmias and to undergo electrocardiogram (ECG) examinations promptly when symptoms occurred. Telephone follow-ups were conducted at 1-3 months after surgery to inquire about the recurrence of atrial fibrillation-related clinical symptoms. Twelve-lead ECG or 24-hour ambulatory ECG monitoring was performed at the time of pre-ablation, 6 months and 12 months after surgery, and transthoracic echocardiography was conducted at the time of pre-ablation and 12 months after surgery. If the duration of arrhythmia symptoms was long, patients were advised to seek medical attention promptly for cardioversion within 48 hours. If patients took anti-arrhythmic drugs other than the study drugs (Class I C or III) during the blank period (3 months after ablation), they were encouraged to stop taking them at the end of the 3-month blank period. Patients were required to take OAC or warfarin for at least 3 months after ablation. Primary and Secondary Outcomes The primary outcome of the trial was the occurrence of atrial tachyarrhythmia (AF, atrial flutter, or atrial tachycardia) documented by single-lead electrocardiogram (≥30 s) or 12-lead electrocardiogram (≥10 s) after the 3-month blanking period post-procedure. Secondary outcomes included changes in echocardiographic parameters: LVEF, left atrial anterior-posterior diameter (LAAPD), right ventricular internal diameter, right ventricular outflow tract diameter, aortic root diameter, ascending aortic diameter, interventricular septal thickness, left ventricular posterior wall thickness, left ventricular end-diastolic diameter (LVEDD), and pulmonary artery diameter. Patients who underwent repeat ablation during the blanking period due to refractory recurrent atrial tachycardia (unresponsive to antiarrhythmic drugs) and cardioversion were considered as having met the primary endpoint of recurrence in the analysis, even if these events occurred during the blanking period. Statistics Fisher’s exact test was used to compare the proportion of patients with recurrence between the vericiguat group and the control group at 3-month, 6-month, and 12-month follow-ups. Baseline continuous data were presented as mean ± standard deviation (SD) or median (interquartile range [IQR]). The Kolmogorov-Smirnov test was applied to assess normality, with intergroup comparisons performed using independent samples t-tests for normally distributed data and the Wilcoxon-Mann-Whitney nonparametric test for non-normally distributed data. Secondary endpoint data (including LVEF, LAAPD, LVEDD, and pulmonary artery diameter) were similarly tested for normality using the Kolmogorov-Smirnov test, with appropriate intergroup comparisons (independent/paired samples t-tests or nonparametric tests). Patients who were lost to follow-up or died before completing the 12-month follow-up were excluded from the primary endpoint analysis. Two-sided/one-sided tests were selected as appropriate, with a P value analyses were performed using SPSS 27.0 and RStudio statistical software. Results Study Population The study enrolled a total of 45 patients who underwent catheter ablation for atrial fibrillation at the First Affiliated Hospital of Nanchang University. Among them, 12 patients were assigned to the vericiguat group and 33 to the control group. During the 12-month follow-up period, 6 patients in the control group were lost to follow-up. Comparison of baseline characteristics between the two groups revealed statistically significant differences in the prevalence of heart failure (P = 0.013) and NYHA functional classification (P = 0.007). However, no significant differences were observed in other baseline characteristics, including age, sex, body mass index (BMI), LVEF, left atrial anteroposterior diameter, and left ventricular end-diastolic diameter (all P > 0.05). Detailed data are presented in Tables 3.1 and 3.2. Furthermore, comparison of postoperative medication use between the two groups showed no statistically significant differences (all P > 0.05), as demonstrated in Table 3.3. Table 1 Baseline data of the two groups of patients. Female 19 (70.4%) 7 (58.3%) 0.486 Persistent AF 19 (70.4%) 5 (41.7%) 0.153 Diabetes 3 (11.1%) 4 (33.3%) 0.172 Hypertension 10 (37.0%) 8 (66.7%) 0.163 Transient ischemic attack/apoplexy 5 (18.5%) 1 (8.3%) 0.645 Ischemic heart disease 4 (14.8%) 2 (16.7%) 1.000 Heart failure 13 (48.1%) 11 (91.7%) 0.013* Smoke 8 (29.6%) 3 (25.0%) 1.000 Previous history of AF ablation 2 (7.4%) 0 (0.0%) 1.000 NYHA class 0.007* Ⅰ 14 (51.9%) 1 (8.3%) Ⅱ 8 (29.6%) 10 (83.3%) Ⅲ 4 (14.8%) 1 (8.3%) Ⅳ 1 (3.7%) (0.0%) * P<0.05. Abbreviations: atrial fibrillation (AF), New York Heart Association (NYHA). Table 2 Baseline data of the two groups of patients Age (yr) 62.26 (11.21) 63.42 (8.52) 0.752 BMI (kg/m 2 ) 25.74 (3.84) 24.52 (3.05) 0.340 Heart rate (bpm) 85.89 (24.29) 71.42 (12.70) 0.060 Albumin (g/L) 42.30 [38.80, 43.80] 42.85 [38.85, 44.23] 0.670 Creatinine (μmol/L) 84.53 (16.70) 76.68 (16.05) 0.179 ALT (U/L) 27.00 [16.50, 37.65] 19.85 [17.10, 22.90] 0.132 AST (U/L) 26.00 [23.15, 36.50] 22.90 [22.28, 30.30] 0.411 INR 1.03 [0.96, 1.09] 0.98 [0.96, 1.00] 0.152 HDL (mmol/L) 1.16 (0.29) 1.28 (0.39) 0.308 LDL (mmol/L) 2.41 (0.74) 2.34 (0.76) 0.783 LVEF (%) 60.00 [54.00, 64.50] 62.00 [59.00, 64.00] 0.583 Left atrial anterior-posterior diameter (mm) 41.11 (6.16) 41.42 (7.12) 0.892 Right ventricular internal diameter (mm) 22.59 (2.61) 23.75 (2.18) 0.188 Right ventricular outflow tract (mm) 28.52 (3.69) 30.42 (3.58) 0.143 Aortic root (mm) 24.00 [22.00, 26.50] 23.00 [22.00, 27.25] 0.807 Ascending aorta diameter (mm) 32.04 (4.35) 30.67 (4.40) 0.371 Interventricular septal thickness (mm) 10.00 [9.00, 10.00] 9.00 [9.00, 9.25] 0.140 Left ventricular posterior wall thickness (mm) 10.00 [9.00, 10.00] 9.00 [8.75, 9.50] 0.279 Left ventricular end-diastolic diameter (mm) 48.15 (5.52) 49.58 (4.42) 0.433 Pulmonary artery diameter (mm) 22.11 (2.36) 22.67 (3.26) 0.551 CHA 2 DS 2 -VASc score 2.00 [1.00, 4.50] 3.50 [2.00, 5.00] 0.300 Abbreviations: body mass index (BMI), alanine aminotransferase (ALT), aspartate aminotransferase (AST), international normalized ratio (INR), high-density lipoprotein (HDL), low-density lipoprotein (LDL), left ventricular ejection fraction (LVEF). Table 3 Postoperative medication use in the control and vericiguat group ACEIs/ARBs/ARNIs 13 (48.1%) 5 (41.7%) 0.742 Dapagliflozin 4 (14.8%) 2 (16.7%) 1.000 β-blockers 23 (85.2%) 7 (58.3%) 0.102 Calcium channel blockers 5 (18.5%) 3 (25.0%) 0.682 Spironolactone 8 (29.6%) 3 (25.0%) 1.000 Furosemide 6 (22.2%) 3 (25.0%) 1.000 Digoxin 6 (22.2%) 4 (33.3%) 0.693 Amiodarone 16 (59.3%) 11 (91.7%) 0.063 Abbreviations: angiotensin-converting enzyme inhibitors (ACEIs), angiotensin II receptor blockers (ARBs), angiotensin receptor-neprilysin inhibitors (ARNIs). Follow-up during the blanking period During the blanking period (first 3 months post-procedure), AF/atrial tachycardia (AT) episodes (symptomatic or asymptomatic) were recorded in 6/27 (22.2%) control group patients versus 1/12 (8.3%) vericiguat group patients (contingency table shown in Table 3.4). Given the small sample size, Fisher’s exact test was employed to compare between-group recurrence rates, yielding a one-sided P-value=0.289. At α=0.05 significance level, we failed to reject the null hypothesis (that vericiguat group’s recurrence rate was not inferior to controls). Further analysis demonstrated an odds ratio (OR) of 0.318 [95% CI: 0.034-2.986]. While the point estimate OR<1, the 95% confidence interval included 1, indicating no statistically significant difference. We therefore conclude that vericiguat and control groups showed comparable AF/AT recurrence rates during the blanking period (Figure 3.1). Table 4 Comparison of the patients with relapse during the blank period between the vericiguat and the control group Control group 21 (77.8%) 6 (22.2%) 27 Vericiguat 11 (91.7%) 1 (8.3%) 12 Total 32 7 39 Figure 1 Comparison of the patients with relapse during the blank period between the vericiguat and the control group Primary Outcome Analysis A total of 39 patients completed the final follow-up and were eligible for primary endpoint analysis. At the 6-month follow-up, AF/AT episodes (symptomatic or asymptomatic) were documented in 5/27 (18.5%) patients in the control group and 2/12 (16.7%) in the vericiguat group. By the 12-month follow-up, these episodes were recorded in 11/27 (40.7%) control group patients versus 1/12 (8.3%) vericiguat group patients. It is noteworthy that while no statistically significant difference in recurrence rates was observed between groups at 6 months post-procedure, a significant intergroup difference emerged at 12 months (P < 0.05). Postoperative 6-month follow-up At the 6-month follow-up, 2 patients in the vericiguat group and 5 patients in the control group experienced AF/AT episodes (symptomatic or asymptomatic), as shown in Table 3.5. Fisher’s exact test was performed, yielding a one-sided P-value of 0.635. At the significance level of α=0.05, we failed to reject the null hypothesis (that the recurrence rate in the vericiguat group was not inferior to the control group). Further analysis showed an OR of 0.880 [95% CI: 0.145-5.335]. While OR<1, the 95% confidence interval included 1, indicating no statistically significant difference. We therefore concluded that there was no significant difference in AF/AT recurrence rates between the vericiguat and control groups at the 6-month follow-up (Figure 3.2). Table 5 Comparison of disease recurrence between vericiguat and control group at 6-month follow-up Control group 22 (81.5%) 5 (18.5%) 27 Vericiguat 10 (83.3%) 2 (16.7%) 12 Total 32 7 39 Figure 2 Comparison of disease recurrence between vericiguat and control group at 6-month follow-up Postoperative 12-month follow-up A total of 39 patients completed the 12-month follow-up, with 12 patients in the vericiguat group (1 case of AF/AT recurrence [symptomatic or asymptomatic] recorded) and 27 patients in the control group (11 recurrences recorded), as shown in the contingency table (Table 3.6). Fisher’s exact test analysis yielded a one-sided P-value = 0.044. At the significance level of α = 0.05, with P < 0.05, we rejected the null hypothesis (that the recurrence rate in the vericiguat group was not inferior to the control group). Further calculation of the OR = 0.138 [0.000, 0.958], with OR < 1 and the 95% confidence interval excluding 1, indicated that the vericiguat group had a significantly lower recurrence risk than the control group. We therefore concluded that the vericiguat group showed significantly lower AF/AT recurrence rates compared to the control group at 12 months post-procedure (Figure 3.3). These findings suggest that vericiguat may help reduce late AF/AT recurrence rates following catheter ablation in atrial fibrillation patients. Table 6 Comparison of disease recurrence between vericiguat and control group at 12-month follow-up Control group 16 (59.3%) 11 (40.7%) 27 Vericiguat 11 (91.7%) 1 (8.3%) 12 Total 27 12 39 Figure 3 Comparison of disease recurrence between vericiguat and control group at 12-month follow-up. Secondary Endpoint Analysis All enrolled patients underwent transthoracic echocardiography before ablation and at 12 months post-procedure to compare changes in secondary endpoints, including LVEF, LAAPD, right ventricular internal diameter, right ventricular outflow tract, ascending aortic diameter, interventricular septal thickness, left ventricular posterior wall thickness, LVEDD, and pulmonary artery diameter. Two patients in the control group and two in the vericiguat group were excluded from secondary endpoint analysis due to unavailability of 12-month echocardiographic data. In the vericiguat group, parameters including LAAPD, right ventricular internal diameter, right ventricular outflow tract, ascending aortic diameter, LVEDD, and pulmonary artery diameter met normality assumptions. Paired t-tests revealed statistically significant reductions in LAAPD (P = 0.024) and LVEDD (P = 0.021) at 12 months compared to baseline (both P 0.05, Table 3.7). For non-normally distributed parameters (LVEF, aortic root diameter, interventricular septal thickness, and left ventricular posterior wall thickness), nonparametric tests demonstrated no statistically significant changes between baseline and 12-month measurements (Table 3.8). These findings suggest that vericiguat may inhibit atrial and ventricular remodeling through reductions in LAAPD and LVEDD. Table 7 Comparison of Echocardiographic Parameters in the Vericiguat Group Before Ablation and at 1-Year Follow-up Average SD Average standard error 95% confidence interval for the difference Lower Upper LAAPD 4.100 4.795 1.516 0.670 7.530 2.704 9 0.024* Right ventricular internal diameter 1.100 1.912 0.605 -0.268 2.468 1.819 9 0.102 Right ventricular outflow tract 1.900 4.122 1.303 -1.049 4.849 1.458 9 0.179 Ascending aortic diameter -2.300 6.111 1.932 -6.672 2.072 1.190 9 0.264 LVEDD 3.500 3.979 1.258 0.654 6.346 2.782 9 0.021* Pulmonary artery internal diameter 0.000 3.464 1.095 -2.478 2.478 0.000 9 1.000 Abbreviations: left atrial anterior-posterior diameter (LAAPD), left ventricular end-diastolic diameter (LVEDD). Table 8 Comparison of Echocardiographic Parameters in the Vericiguat Group Before Ablation and at 1-Year Follow-up Median (IQR) -3.5 (-6.75, 0.25) -2.5 (-4.25, 3.25) -1.0 (-1.00, 0.50) -0.5 (-1.25, 1.25) Asymptotic significance (two-tailed) 0.126 0.610 0.615 0.720 In the control group, paired t-tests were applied to normally distributed parameters including LVEF, LAAPD, ascending aortic diameter, LVEDD, and pulmonary artery diameter. The analysis revealed no statistically significant differences in LVEF, LAAPD, ascending aortic diameter, LVEDD, or pulmonary artery diameter between baseline and 1-year measurements (all P > 0.05, Table 3.9). Nonparametric tests were applied to analyze data that did not conform to a normal distribution, including right ventricular internal diameter, right ventricular outflow tract, aortic root diameter, interventricular septal thickness, and left ventricular posterior wall thickness. The results revealed no statistically significant differences in these parameters (right ventricular internal diameter, right ventricular outflow tract, aortic root diameter, interventricular septal thickness, and left ventricular posterior wall thickness) between preoperative baseline measurements and assessments at 1 year after surgery in the control group (Table 3.10). Table 9 Comparison of Echocardiographic Parameters in the Control Group Before Ablation and at 1-Year Follow-up Average SD Average standard error 95% confidence interval for the difference Lower Upper LVEF% -2.800 10.012 2.002 -6.933 1.333 1.398 24 0.175 LAAPD 1.280 4.542 0.908 -0.595 3.155 1.409 24 0.172 Ascending aortic diameter -0.480 4.547 0.909 -2.357 1.397 0.528 24 0.602 LVEDD 0.120 6.119 1.224 -2.406 2.646 0.098 24 0.923 Pulmonary artery internal diameter -0.720 3.143 0.629 -2.017 0.577 1.146 24 0.263 Table 10 Comparison of Echocardiographic Parameters in the Control Group Before Ablation and at 1-Year Follow-up Median (IQR) -1.0 (-2.5, 1.5) -1.0 (-3.5, 3.0) 1.0 (-1.0, 4.5) 0.0 (-1.0, 0.5) 0.0 (-1.0, 0.5) Asymptotic significance (two-tailed) 0.150 0.583 0.063 0.444 0.726 Finally, intergroup comparisons of baseline-to-1-year changes were performed. Normality tests confirmed that the differences in LVEF, LAAPD, LVEDD, pulmonary artery diameter, right ventricular internal diameter, right ventricular outflow tract, and aortic root diameter followed normal distributions, whereas differences in ascending aortic diameter, interventricular septal thickness, and left ventricular posterior wall thickness did not. Independent samples t-tests for normally distributed data revealed a significant intergroup difference in right ventricular internal diameter changes (P = 0.037 < 0.05), while no statistically significant differences were observed in other parameters (Table 3.11). Nonparametric tests for non-normally distributed data demonstrated no significant differences in ascending aortic diameter, interventricular septal thickness, or left ventricular posterior wall thickness changes between groups (all P > 0.05, Table 3.12). Table 11 Comparison of Echocardiographic Parameters Between Groups Lower Upper LVEF% 1.000 3.443 -6.004 8.004 0.290 33 0.773 LAAPD -2.820 1.726 -6.331 0.691 1.634 33 0.112 LVEDD -3.380 2.102 -7.656 0.896 1.608 33 0.117 Pulmonary artery internal diameter -0.720 1.210 -3.182 1.742 0.595 33 0.556 Right ventricular internal diameter -1.820 0.839 -3.527 -0.113 2.169 33 0.037* Right ventricular outflow tract -2.300 1.461 -5.272 0.672 1.575 33 0.125 Aortic root 1.680 1.533 -1.439 4.799 1.096 33 0.281 Table 12 Comparison of Echocardiographic Parameters Between Groups Median (IQR) 0.37 (-2.25, 2.00) 0.00 (-1.00, 2.50) 0.00 (-1.00, 0.79) Asymptotic significance (two-tailed) 0.521 0.544 0.720 Discussion This prospective clinical trial aimed to evaluate whether short-term oral vericiguat administration reduces AF recurrence following catheter ablation. The study demonstrated that at 12 months post-procedure, vericiguat significantly reduced AF/AT recurrence rates and decreased LAAPD and LVEDD. However, vericiguat showed no significant effects on reducing AF/AT recurrence during the blanking period or at 6-month follow-up, nor did it improve LVEF. The VICTORIA trial demonstrated that vericiguat may inhibit ventricular remodeling by enhancing the cGMP signaling pathway, offering a novel therapeutic option for heart failure (HF). Notably, vericiguat significantly reduced the composite endpoint of cardiovascular death or HF hospitalization, particularly in high-risk patients who remained symptomatic despite standard therapies, with its efficacy being independent of concomitant sacubitril/valsartan use [11,13]. AF is one of the most prevalent arrhythmias in the natural course of HFrEF. Recommended HF therapies—such as angiotensin-converting enzyme inhibitors, β-blockers, or mineralocorticoid receptor antagonists—may reduce AF incidence in HFrEF patients [14,15]. Furthermore, studies suggest that vericiguat may attenuate AF- and HF-related oxidative stress by promoting NO-mediated vasodilation and reducing myocardial oxygen demand, thereby protecting against myocardial injury [16]. These mechanisms provide a theoretical basis for vericiguat’s potential to reduce post-ablation AF recurrence. The trial results demonstrated no significant differences in secondary outcomes—including LVEF, LAAPD, right ventricular internal diameter, right ventricular outflow tract, and LVEDD—between baseline and 12-month measurements in the control group. In contrast, the vericiguat group showed significant reductions in LAAPD and LVEDD after 3-month oral vericiguat intervention. These reductions indicate improved atrial and ventricular remodeling, which may directly contribute to vericiguat’s ability to reduce AF recurrence risk. AF progression is closely associated with atrial fibrosis, Ca²⁺ overload, Calcium–calmodulin-dependent protein kinase II (CaMKII) activation, and NOD-like receptor family pyrin domain-containing 3 inflammasome activation [17]. Excessive CaMKII activity increases AF susceptibility, while its inhibition attenuates atrial fibrosis and electrical remodeling, thereby reducing recurrence risk. Animal studies using C57BL/6 mice have demonstrated that vericiguat mitigates post-MI left ventricular remodeling and arrhythmias via CaMKII signaling modulation [18-20]. By improving calcium homeostasis and structural remodeling, vericiguat reduces arrhythmogenesis, providing mechanistic support for its observed clinical effects. Our findings—reduced late (12-month) AF/AT recurrence rates and decreased LAAPD/LVEDD—further validate that vericiguat may suppress structural remodeling to prevent post-ablation AF recurrence. Compared with the control group, the vericiguat group showed no significant reduction in AF/AT recurrence rates during the blanking period or at 6-month follow-up. This phenomenon may be attributed to baseline disparities: significant intergroup differences existed in HF prevalence and NYHA class distribution. The vericiguat group had a higher proportion of HF patients, predominantly in NYHA class II, whereas HF patients in the control group were mainly NYHA class I-II. Consequently, the vericiguat group exhibited poorer cardiac function at baseline. Given that HF patients often present with structural and electrical remodeling—factors potentially increasing AF recurrence risk—we speculate that vericiguat’s antiarrhythmic effects might have been partially masked during early follow-up periods. This led to no statistically significant difference in recurrence rates between the two groups during the blanking period and at the 6-month follow-up. Vericiguat exhibited no significant therapeutic effect during the early postoperative phase (the blank period and 6-month follow-up). However, the delayed therapeutic effect of vericiguat became evident at 12-month follow-up, with significantly reduced AF/AT recurrence rates. This suggests that vericiguat’s suppression of AF recurrence may manifest predominantly in long-term outcomes, effectively targeting late post-ablation recurrences. These findings indicate vericiguat’s potential for sustained AF suppression. Such delayed protection could persistently reduce AF/AT recurrence risks beyond the blanking period, thereby lowering healthcare costs associated with post-ablation recurrence management (e.g., hospitalization and cardioversion), offering a novel strategy for postoperative AF care. Although our study suggests that vericiguat reduces late AF recurrence rates post-ablation, potentially through suppressing atrial and ventricular remodeling, several limitations should be acknowledged. First, the small sample size (n=39 completing follow-up) may have resulted in insufficient statistical power to detect intergroup differences, particularly influencing the nonsignificant recurrence rate differences observed during the blanking period and at 6-month follow-up. Second, the lack of continuous ECG monitoring during follow-up—relying solely on 12-lead ECGs or 24-hour Holter monitoring—might have missed asymptomatic recurrences. Third, restricted transthoracic echocardiography to preoperative and 12-month postoperative assessments (due to economic constraints and patient compliance issues) prevented evaluation of dynamic changes in LAAPD, LVEDD, and LVEF during the blanking period and at 6 months, obscuring potential early effects of vericiguat. Finally, as a clinical trial, this study did not assess additional endpoints such as quality of life, NYHA class improvement, or hospitalization rates, nor did it include mechanistic investigations. Future studies should enlarge the sample size, implement more frequent follow-ups with extended monitoring (e.g., implantable loop recorders), incorporate mechanistic studies, and evaluate comprehensive clinical endpoints to further validate vericiguat’s antiarrhythmic efficacy. Conclusions and Future Perspectives Conclusions This study provides preliminary evidence that vericiguat reduces late AF recurrence rates and decreases LAAPD/LVEDD in patients undergoing radiofrequency catheter ablation for atrial fibrillation. Based on these findings, we hypothesize that vericiguat may exert long-term antiarrhythmic effects by suppressing atrial and ventricular remodeling in both paroxysmal and persistent AF patients following ablation, potentially mitigating late post-procedural recurrence. Clinical Implications and Future Directions Vericiguat’s potential to reduce AF recurrence rates and improve cardiac structural remodeling offers novel insights for clinical management. Although no significant effect was observed within the short-term (6-month) period, its demonstrated benefits at long-term (12-month) follow-up suggest that vericiguat may serve as an effective adjunctive therapy for post-ablation AF management. Future studies should further investigate vericiguat’s efficacy across AF subtypes (e.g., paroxysmal vs. persistent) and explore potential synergistic effects when combined with other antiarrhythmic drugs or non-pharmacological therapies. Additionally, vericiguat’s safety and tolerability require validation in larger-scale clinical trials. While no severe adverse events were observed in this study, potential side effects associated with prolonged use necessitate continued monitoring. In conclusion, this study provides preliminary evidence supporting vericiguat’s application in post-ablation AF care, indicating its ability to reduce late recurrence rates through attenuation of atrial and ventricular structural remodeling. Further research should elucidate its mechanistic pathways and optimize clinical implementation strategies. 1-y-FU 1-year follow-up sGC Soluble Guanylate Cyclase HF heart failure HFrEF heart failure with reduced ejection fraction LVEF left ventricular ejection fraction NYHA New York Heart Association eGFR estimated glomerular filtration rate PDE-5 phosphodiesterase type 5 OAC oral anticoagulant ECG electrocardiogram LAAPD left atrial anterior-posterior diameter LVEDD left ventricular end-diastolic diameter SD standard deviation IQR interquartile range BMI body mass index AT atrial tachycardia OR odds ratio Author Contributions: Conceptualization, Ru Ying and Jialing Yin; methodology, Jialing Yin; software, Jiawei Chen; validation, Yun Xiao, Yuan Shu and Xichen Liu; formal analysis, Luyao Mao; investigation, Kai Chen; resources, Jiawei Chen; data curation, Yun Xiao; writing—original draft preparation, Jialing Yin; writing—review and editing, Rilang Peng; visualization, Yuan Shu; supervision, Ru Ying; project administration, Jialing Yin and Rilang Peng; All authors have read and agreed to the published version of the manuscript.” Acknowledgments I sincerely thank Professor Ying Shi for her meticulous guidance and selfless assistance throughout the entire process of my thesis, including the selection of the topic, the determination of the research methods, and the writing and revision of the thesis. 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Physiological and unappreciated roles of CaMKII in the heart [J]. Basic Res Cardiol, 2018, 113(4): 29. Information & Authors Information Version history V1 Version 1 08 August 2025 Copyright This work is licensed under a Non Exclusive No Reuse License. Keywords basic: atrial fibrillation/atrial arrhythmias clinical: catheter ablation – atrial fibrillation clinical: pharmacology – pharmacokinetics/dynamics Authors Affiliations Jia-Ling Yin The First Affiliated Hospital of Nanchang University View all articles by this author Rilang Peng 0009-0001-3874-633X Nanchang University Jiangxi Medical College View all articles by this author Jia-Wei Chen The First Affiliated Hospital of Nanchang University View all articles by this author Yun Xiao The First Affiliated Hospital of Nanchang University View all articles by this author Yuan Shu 0009-0003-0754-9143 The First Affiliated Hospital of Nanchang University View all articles by this author Xi-Chen Liu The First Affiliated Hospital of Nanchang University View all articles by this author Lu-Yao Mao The First Affiliated Hospital of Nanchang University View all articles by this author Kai Chen The First Affiliated Hospital of Nanchang University View all articles by this author Ru Ying 0000-0001-6443-3903 [email protected] The First Affiliated Hospital of Nanchang University View all articles by this author Metrics & Citations Metrics Article Usage 227 views 107 downloads .FvxKWukQNSOunydq8rnd { width: 100px; } Citations Download citation Jia-Ling Yin, Rilang Peng, Jia-Wei Chen, et al. 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