Interatrial communication is one of the most common congenital heart malformations, including atrial septal defect (ASD) and patent foramen ovale (PFO) [1]. It is characterized by a deficiency in the septum that separates the two atria, allowing for a direct connection between the two atria and facilitating blood flow from the left to the right atrium [2]. ASD is typically categorized into a secundum, primum, sinus venosus, or coronary sinus defect. Among these, the ostium secundum atrial septal defect is the most prevalent, constituting roughly 7% of all congenital heart malformations [3]. In most cases, children and teenagers with ASD are symptom-free, but over time, complications such as arrhythmia, thromboembolism, pulmonary arterial hypertension and even right heart failure may occur. In addition, PFO is even more widespread, with a prevalence ranging from 25% to 27% among adults in the general population. Previous studies indicated PFO was associated with strokes, migraines, and platypnea-orthodeoxia syndrome, even leading to cryptogenic embolic strokes in young patients [4]. Numerous randomized controlled trials have indicated that, compared with oral anticoagulant and antiplatelet therapy, effective ASD/PFO closure can significantly reduce the occurrence of complications such as stroke [5, 6].

Atrial fibrillation (AF) is the most prevalent arrhythmia worldwide, and its increasing prevalence, driven by increased life expectancy, represents a significant public health challenge [7]. AF markedly deteriorates quality of life and is associated with severe complications, including stroke, heart failure, cognitive impairment, and cardiac arrest [8, 9]. Currently, oral anticoagulants (OACs) have been recommended as the first-line treatment for preventing thromboembolism in AF patients. Whereas, emerging studies have demonstrated that left atrial appendage closure (LAAC) can serve as an alternative to anticoagulant therapy for patients who are intolerant of oral anticoagulants, significantly reducing the incidence of cardiogenic stroke events in AF patients [10, 11].

Interestingly, ASD/PFO closure and LAAC both belong to the transarterial septal operation, allowing for the combination of the two interventions (‘One stop’ therapy) to be an available and practical approach. Whereas, previous studies may fail to provide reliable and comprehensive conclusions about the feasibility, efficacy and safety of ‘One stop’ therapy due to some limitations, such as lack of long-term follow-up and small sample size. Therefore, we performed this meta-analysis with the aim of further evaluating the performance of ‘One stop’ therapy on patients with interatrial communication and AF, and to screen for potential determinants for ‘One stop’ therapy.

We comprehensively evaluated a total of 156 patients from 7 original articles. Compared with previously published meta-analyses, we implemented more stringent screening criteria [21]. Our focus was on studies that presented findings regarding the efficacy and safety of combined ASD/PFO closure with LAAC in AF patients. Moreover, we reviewed multiple publications from the same trial or cohort and identified the study with the highest patient inclusion. The primary findings are summarized as follows: (1) The combination of ASD/PFO closure with LAAC demonstrates a notably high success rate. (2) ‘One stop’ closure exhibits a high level of long-term safety and a low occurrence of associated complications. (3) In the male proportion $\ge$50% and HAS-BLED score $>$3 subgroup, the incidence of bleeding events was relatively higher in ASD/PFO closure combined with LAAC.

Cardiogenic stroke has been reported to account for 25% of ischemic stroke worldwide, which often results in significant risks of high disability and mortality, seriously jeopardizing patients’ lives and health [22]. Furthermore, AF and interatrial communication play a leading role in cardiac stroke. Therefore, preventing strokes in patients with AF and ASD/PFO is of primary importance.

Oral anticoagulation is a well-established and widely accepted approach that effectively mitigates the occurrence of thromboembolic events in AF patients. However, this carries an increased susceptibility to bleeding complications. Recently, LAAC has emerged as a viable mechanical intervention for preventing thromboembolic events while minimizing bleeding risk [23]. Osmancik et al. [24, 25] followed patients with a high risk for stroke and increased risk of bleeding at both short-term (19 months) and long-term (4 years) levels and found that LAAC remains noninferior to new oral anticoagulants (NOACs) for preventing neurological, major cardiovascular, or bleeding events. Furthermore, LAAC significantly reduced nonprocedural bleeding.

Sun et al. [26] investigated the association between the presence of ASD/PFO and atrial vulnerability and found that atrial septal abnormalities were linked to a 2fold increase in the risk of atrial vulnerability among ischemic stroke patients. Previous studies have shown that in patients with ASD/PFO, atrial shunting increases the volume load on the heart, and long-term high load leads to myocardial fibrosis of the right atrium, structural and electrical remodeling, and promotes the occurrence of AF [27]. For AF patients with ASD/PFO, the older age and larger atrial size make the success rate of radiofrequency ablation low and the recurrence rate high. To prevent the occurrence of AF and stroke, closure of atrial septal defects is recommended for patients with congenital heart disease presenting with ASD/PFO.

However, for AF patients with ASD/PFO, closure of ASD/PFO alone does not significantly reduce thromboembolic complications [28]. Persistent AF remains a major contributor to thromboembolic events, requiring long-term oral anticoagulation therapy. Meanwhile, performing a split operation not only prolongs hospitalization but also significantly increases associated costs. On the other hand, the closure of ASD/PFO leaves an occluder umbrella at the atrial septal site, which makes subsequent interventional procedures for AF difficult to perform. Therefore, for AF patients complicated with ASD/PFO, ‘One stop’ ASD/PFO closure with LAAC can avoid the difficulty of atrial septal puncture in the long term after simple ASD/PFO closure, and to avoid the risk of bleeding caused by long-term anticoagulation therapy, and improve the long-term safety of patients after operation. It provides a novel treatment for AF patients with ASD/PFO. It is worth noting that after performing LAAC, a 10-minute observation was performed to ensure the stability of the occluder umbrella to prevent the occurrence of occluder detachment after ASD/PFO closure [20].

Whereas, there are still insufficient studies on the feasibility, safety and effectiveness of ‘One stop’ interventional therapy for ASD/PFO closure combined with LAAC. Our study illustrates that ‘One stop’ closure is highly safe and effective, with a success rate of 1. It may be an optimal option for the prevention of stroke and other thrombotic complications in non-valvular atrial fibrillation (NVAF) patients with ASD/PFO.

In addition, outcomes of ‘One stop’ ASD/PFO closure combined with LAAC were analyzed as well. During the follow-up period, the incidences of cerebrovascular events, thromboembolic events, and all-cause death were notably low at 0.00 and the incidence of bleeding events and device-related events was 0.02, indicating a promising long-term prognosis and reliable safety performance. Bleeding events after ‘One stop’ ASD/PFO closure with LAAC may be closely related to postoperative antithrombotic regimens. However, optimal antithrombotic therapy after ‘One stop’ closure is not well established as no randomized evaluation has been performed to date. The current recommended antithrombotic regimen following LAAC involves 45 days of OACs or warfarin in combination with aspirin, followed by 4.5 months on dual antiplatelet therapy involving aspirin and clopidogrel. Subsequently, aspirin alone should be continued indefinitely from 6 months post-implantation onward [29, 30]. The anticoagulation strategies in the studies we included predominantly followed this regimen (Supplementary Material 2). Further research is needed to comprehensively evaluate the optimal postoperative antithrombotic strategy.

Subgroup analyses were also performed for individual long-term adverse events. Notably, in the male proportion $\ge$50% subgroup and HAS-BLED score $\ge$3 subgroup, ASD/PFO closure combined with LAAC demonstrated increased bleeding events (p = 0.045 and p = 0.033, respectively). A previous cohort study indicated that the efficacy of OACs treatment in individuals with AF was comparable between male and female, as there were no significant differences observed in complications such as systemic embolism or stroke. However, it was noted that males had a significantly higher risk of major bleeding compared to females [31]. While Nakashima et al. [32] demonstrated that the absence of prior catheter ablation, a history of major bleeding, and baseline anemia were independent predictive factors for late bleeding events after LAAC and sex did not impact post-LAAC bleeding outcomes. Meanwhile, Zhao et al. [33] found no association between gender and post-LAAC bleeding. The impact of gender on bleeding events during ‘one-stop’ closure has not been thoroughly investigated to date. Our results preliminarily indicate a higher risk of bleeding with ‘one-stop’ closure in male patients. However, further research is required to validate this finding.

The HAS-BLED score is widely utilized for the assessment of bleeding risk in patients with AF during anticoagulant therapy [34]. The HAS-BLED score is influenced by various factors, including hypertension, abnormal liver and kidney function, stroke, etc. rendering it a dynamic assessment tool for patients. Concurrently, research has demonstrated a positive correlation between high HAS-BLED scores and an elevated risk of bleeding and a HAS-BLED score $\ge$3 indicates a significant propensity for bleeding. Our study also demonstrated a positive correlation between higher HAS-BLED scores and an increased risk of bleeding following the ‘One stop’ closure. Hence, according to the current latest guidelines for AF management, it is imperative for AF patients to optimize the risk factors in the HAS-BLED score prior to undergoing ‘One stop’ closure [34].

Several limitations should be emphasized. First, studies enrolled in this meta-analysis are nonrandomized, observational design, thus selection bias cannot be completely ruled out. Second, a total of 7 articles were included, and 2 of which had a sample size of less than 10, which might have affected the distribution of the results. Moreover, only 3 studies had a follow up period of more than 12 months, adding to the instability of the long-term complication results of the ‘One stop’ closure. In addition, ‘One stop’ ASD/PFO closure combined with LAAC is more complicated than conventional surgery. The success rate of surgery is also affected by different regions, hospitals and medical teams.

Our study suggests that ‘One stop’ ASD/PFO closure combined with LAAC is effective and safe for AF patients with interatrial communication.

The data which support the findings of this study are available from the corresponding author upon reasonable request.

HL and XSG contributed to the design and conception of this study, while ZYZ and FL conducted the literature search and drafted the initial manuscript. CG, YQC, and SLP organized and analyzed the selected literature data. YTZ and YZ provided guidance on research methods. All authors made editorial revisions to the manuscript. All authors have thoroughly examined and endorsed the conclusive rendition of the manuscript. Each author has actively contributed to this endeavor and consented to assume accountability for all its facets.

Not applicable.

We would like show sincere appreciation to the reviewers for their critical comments on this article.

We sincerely appreciate the support of the Natural Science Foundation of the Jiangsu Higher Education Insititutions of China (24KJD320003), the applied basic research (medical and health) science and technology innovation project of Suzhou (SYW2024086), the Suzhou Science and Technology Plan Project (SKY2022151), and in part by grants from the National Natural Science Foundation of China (82170831, 82300438) and the Gusu Health Talent Program (GSWS2023099).

The authors declare no conflict of interest.

Supplementary material associated with this article can be found, in the online version, at https://doi.org/10.31083/RCM26662.