Association between non-sleep apnoea-related sleep indicators and recurrence of atrial fibrillation after catheter ablation: a systematic review protocol

Abstract

Background

Atrial fibrillation (AF) constitutes a growing public health challenge. Consequently, the exploration of modifiable risk factors is essential for advancing AF prevention and management. While obstructive sleep apnoea is established as a risk factor for AF recurrence following catheter ablation, and its treatment with continuous positive airway pressure therapy reduces recurrence rates, the influence of non-sleep apnoea-related sleep indicators remains unclear. This systematic review aims to elucidate the association between these non-sleep apnoea-related sleep indicators and AF recurrence to inform optimised management strategies.

Methods and analysis

A comprehensive search will be performed in databases, including PubMed, Embase, the Cochrane Library, Chinese National Knowledge Infrastructure, VIP Database and Wanfang Data, covering publications from database inception to 27 August 2024. Study selection will be performed independently by two reviewers using predefined eligibility criteria, with the screening process documented in a referred Reporting Items for Systematic Review and Meta-Analysis-compliant flow diagram. Data will be extracted using standardised forms and risk of bias of included studies will be assessed with the Risk Of Bias In Non-randomised Studies-of Interventions tool. Non-sleep apnoea-related sleep indicators, including sleep duration, sleep quality, sleep latency, sleep efficiency, REM (Rapid Eye Movement)/NREM (Non-Rapid Eye Movement), etc, serve as exposure factors. The primary outcome is defined as AF recurrence, whereas the secondary outcome comprises quality of life measures among AF patients. Should sufficient data be available, a meta-analysis will be performed using appropriate statistical methods; otherwise, a narrative synthesis will be conducted.

Ethics and dissemination

This study uses publicly available data, so ethical approval is not required. The findings will be disseminated through peer-reviewed journals and scholarly platforms to inform clinical practice and future research.

PROSPERO registration number

CRD42024607124.

STRENGTHS AND LIMITATIONS OF THIS STUDY.

• The protocol adheres to the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols guidelines, ensuring methodological rigour and transparency.

• The risk of bias will be appraised using the Risk Of Bias In Non-randomised Studies-of Interventions tool, which is specifically designed for non-randomised studies of exposures.

• The study focuses exclusively on papers published in English or Chinese, potentially overlooking relevant publications in other languages.

• The significant heterogeneity anticipated in the measurement tools, definitions and classifications of sleep indicators may pose challenges for quantitative meta-analysis.

Introduction

In recent years, the global prevalence of atrial fibrillation (AF) has increased significantly. According to the American College of Cardiology, the number of AF patients in the United States was 5.2 million in 2010 and is projected to reach 12.1 million by 2030.¹ Similarly, one study estimated that the prevalence of AF among adults aged 55 years and older in the European Union would rise from 8.8 million in 2010 to 17.9 million by 2060.² AF is associated with severe complications, including a heightened risk of extracranial systemic embolism,³ a four- to fivefold increase in the likelihood of ischaemic stroke,⁴ a fivefold higher risk of heart failure and nearly a twofold higher risk of myocardial infarction.⁵ Consequently, AF has become a major contributor to the growing global burden of cardiovascular disease. Given the significantly elevated risk of stroke among AF patients, anticoagulant therapy has become the cornerstone of comprehensive management. Traditional agents such as warfarin, as well as widely used direct oral anticoagulants including dabigatran, rivaroxaban and apixaban, effectively inhibit intracardiac thrombus formation. These agents reduce the risk of stroke and systemic embolism by approximately 60%–70%,⁶,⁹ leading to significant improvements in long-term patient outcomes.

Catheter ablation is a safe and effective therapeutic intervention for the management of AF.¹⁰ Compared with antiarrhythmic drugs, this procedure demonstrates superior efficacy in the maintenance of sinus rhythm¹¹ and is associated with significant improvements in clinical outcomes, including all-cause mortality, heart failure-related hospitalisation rates, left ventricular ejection fraction and quality of life in patients with AF.¹² However, a high recurrence rate after catheter ablation remains a significant clinical challenge, thereby necessitating further investigation.¹³ Addressing modifiable risk factors, such as hypertension,¹⁴ diabetes,^{15 16} obesity,^{17 18} smoking¹⁹ and sleep disorders, is essential to reducing postoperative recurrence rates in AF patients.

Obstructive sleep apnoea (OSA) has been recognised as an independent risk factor for the recurrence of AF after catheter ablation.²⁰,²² Furthermore, studies have demonstrated that continuous positive airway pressure therapy can effectively reduce postoperative recurrence rates in patients with AF combined with OSA.²²,²⁴ A prospective cohort study revealed that sleep durations of less than 6 hours and irregular sleep patterns are significantly associated with a higher incidence of AF.²⁵ Nevertheless, the relationship between non-sleep apnoea-related sleep indicators and AF recurrence following catheter ablation remains unclear. Heterogeneity in definitions, dimensions and mechanisms among various sleep indicators contributes to an incomplete understanding of the complex relationship between sleep and AF. This article presents a systematic review of publicly available literature, aiming to synthesise available evidence through qualitative or quantitative analysis to elucidate the impact of non-sleep apnoea-related sleep indicators on AF recurrence postablation, with the ultimate goal of informing sleep-focused interventions to reduce AF recurrence.

Objective

This systematic review aims to explore the association between non-sleep apnoea-related sleep indicators and AF recurrence following catheter ablation. The review will address the following questions:

1. What non-sleep apnoea-related sleep indicators are included in the relevant studies?

2. What are the characteristics of these indicators, and can they be categorised or summarised?

3. What is the relationship between different sleep indicators and AF recurrence after catheter ablation?

4. What is the association between non-sleep apnoea-related sleep indicators and quality of life in patients with AF following catheter ablation?

Methodology

The systematic review will be conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines,²⁶ ensuring a comprehensive and transparent presentation of the research process and findings. Prior to initiating the review, relevant studies were searched in the International Prospective Register of Systematic Reviews (PROSPERO) to avoid duplication. The review was officially registered with PROSPERO on 8 November 2024 (Registration number: CRD42024607124).

This protocol adheres to the 2015 Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols (PRISMA-P) statement.^{27 28}

Patient and public involvement

This study does not involve the direct participation of patients or members of the general public.

Eligibility criteria

The literature that meets the following criteria will be considered for inclusion in this systematic review.

Study designs

Both randomised controlled trials (RCTs) that report on associations between non-sleep apnoea-related sleep indicators and AF recurrence in secondary or post hoc analyses and observational studies, including prospective cohort, retrospective cohort and case-control designs, will be included. While conference papers, reviews, animal studies and other irrelevant research will be excluded.

Population

This systematic review will enrol patients who have undergone catheter ablation for non-valvular AF, irrespective of age, gender or ethnic background.

Interventions/exposures

The primary exposures of interest in this review are non-sleep apnoea-related sleep indicators, which are classified into three distinct categories: (1) Self-reported subjective sleep indicators, such as the Pittsburgh Sleep Quality Index, which evaluates seven dimensions including subjective sleep quality, sleep latency, sleep duration, sleep efficiency, sleep disturbances, use of sleep medications and daytime dysfunction. (2) Objective sleep parameters, measured using instrumentation, such as polysomnography, portable sleep monitoring devices and actigraphy, which provide data on sleep stages (REM/NREM), sleep duration, sleep efficiency, sleep latency, frequency and duration of awakenings, respiratory and heart rate parameters, oxygen saturation and activity levels. (3) Digitally derived sleep indicators, obtained through emerging technologies, including mobile apps, mattress sensors and artificial intelligence analysis, which capture measures including sleep duration, sleep stages, sleep onset time, number of awakenings, heart rate, respiratory rate and environmental factors like noise and light. Studies primarily focused on sleep apnoea, such as obstructive or central sleep apnoea, will be excluded.

Outcomes

Primary outcome

The primary outcome was defined as the recurrence of AF, characterised by any sustained atrial arrhythmia (including AF, atrial flutter or atrial tachycardia) lasting longer than 30 s, as detected on 12-lead electrocardiograms or 24-hour Holter monitoring performed at least 3 months after catheter ablation.

Secondary outcome

The secondary outcome consisted of quality of life among AF patients, which was assessed using validated instruments including the Atrial Fibrillation Effect on Quality-of-Life (AFEQT) questionnaire, the EuroQol five-dimension questionnaire and the 36-Item Short Form Health Survey (SF-36).

Information sources and search strategy

The initial search strategy was constructed using core keywords such as ‘atrial fibrillation’, ‘catheter ablation’ and ‘sleep’ combined with subject headings and free-text terms. The strategy was subsequently refined through iterative revisions informed by existing search methodologies in Cochrane systematic reviews to ensure comprehensive and precise study identification. Databases including PubMed, Embase, the Cochrane Library, Chinese National Knowledge Infrastructure, VIP Database and Wanfang Data were selected as information sources. Search syntax was customised according to the specific requirements and controlled vocabulary of each database, with the search period set from database inception to 27 August 2024, and limited to studies published in English and Chinese. Additionally, to ensure comprehensiveness, grey literature²⁹ was searched through Google Scholar, and references lists of included studies were manually screened. Detailed search strategies are provided in online supplemental appendix 1.

Study selection

The studies retrieved from the selected databases will be imported into EndNote X9 software for duplicate removal. To minimise bias, two reviewers will independently perform study selection, eligibility assessment and inclusion processes. Initially, titles and abstracts will be screened to eliminate irrelevant studies. Subsequently, the full text of the eligible literature will be rigorously assessed against the inclusion criteria. Detailed reasons for exclusion will be documented during the full-text review. Finally, the included studies will be confirmed. Any discrepancies encountered during the process will be addressed through discussions between the two reviewers. If a consensus cannot be reached, a third reviewer will be consulted to help mediate and resolve the issue. The process of study selection will be illustrated using a PRISMA flow diagram (figure 1).

Figure 1. Flow diagram of study selection. CNKI, Chinese National Knowledge Infrastructure.

Data extraction

A standardised data extraction form (online supplemental appendix 2) will be used to collect the following information: (1) Basic details of the included studies: title, first author, publication year, country, institution, journal, and study type. (2) Key characteristics of the included studies: sample size, age, gender, type of AF, procedure type, exposure factors, methods of exposure factors assessment, grouping of exposure factors, primary outcome, outcome evaluation methods, AF recurrence criteria, follow-up methods and follow-up duration. (3) Results of the included studies: including the HR or OR for AF recurrence and quality of life between the exposed group and control group, along with their 95% CIs, p values and other major findings, as well as results from subgroup and sensitivity analyses. Data extraction will be carried out independently by two reviewers, with any discrepancies addressed through discussion or by consulting a third reviewer. Where necessary, the corresponding authors of the primary studies will be contacted via email to obtain any missing or unreported data.

Risk of bias assessment

The risk of bias of the included studies will be independently assessed by two reviewers using the Risk Of Bias In Non-randomised Studies-of Interventions,³⁰ which is specifically designed to evaluate the risk of bias in estimates of the comparative effectiveness of an intervention from non-randomised studies.³¹ Each study will receive an overall risk of bias of judgement (low, moderate, serious or critical) and any discrepancies between reviewers will be resolved through discussion or by arbitration from a third reviewer to ensure consistency and scientific rigour.

Data synthesis

The synthesis method will be determined based on the heterogeneity observed among the included studies. In cases of substantial heterogeneity, a narrative synthesis will be performed to systematically summarise the features and results of the included studies. Conversely, if the studies exhibit low heterogeneity or a sufficient degree of homogeneity, a meta-analysis will be performed using RevMan 5.4 software to quantitatively pool the data.

Given that this study encompasses various questionnaire scales—including subjective sleep assessments and quality of life instruments—the synthesis approach will prioritise meta-analysis for studies employing identical questionnaires. For studies assessing similar constructs with different validated instruments, standardised mean differences will be calculated to allow for comparative analysis.

Heterogeneity will be assessed using the χ² test and the I² statistic.^{32 33} The χ² test will qualitatively evaluate heterogeneity, with p<0.01 indicating the presence of significant heterogeneity. The I² statistic will quantify the degree of heterogeneity: I²<50% is defined as low heterogeneity and will be analysed using a fixed-effects model, whereas I²≥50% is defined as high heterogeneity and will be analysed using a random-effects model. To explore potential sources of heterogeneity, subgroup analyses will be performed based on sleep indicators (eg, sleep duration, insomnia symptoms), population characteristics (eg, age, sex), procedural methods (eg, radiofrequency ablation vs cryoballoon ablation), study type (eg, RCTs, observational studies) and questionnaire type (eg, AFEQT, SF-36). Sensitivity analyses will also be conducted by excluding low-quality, high risk of bias or small-sample studies to verify the robustness of the results. An additional sensitivity analysis will be performed to evaluate the influence of questionnaire selection on the pooled results.

If 10 or more studies are included, publication bias will be assessed visually through funnel plots and statistically using Egger’s and Begg’s tests. Furthermore, if sufficient data are available, dose-response relationships between sleep indicators (eg, sleep duration) and AF recurrence risk will be explored to analyse potential nonlinear effects, providing a more comprehensive understanding of the impact of sleep indicators on postcatheter ablation AF recurrence.

Ethics and dissemination

This study uses publicly available data, so ethical approval is not required. The findings will be disseminated through peer-reviewed journals and scholarly platforms to inform clinical practice and future research.

Discussion

With the global ageing population and the rising burden of chronic diseases, the prevalence of AF is increasing rapidly, leading to a growing disease burden. The occurrence and recurrence of AF are multifactorial, among which sleep has been identified as a significant and modifiable risk factor receiving increasing attention. Current research has established that patients with OSA have an elevated risk of AF recurrence after catheter ablation. Nevertheless, the relationship between other sleep indicators, such as sleep duration, sleep quality and insomnia symptoms, and AF recurrence after ablation remains insufficiently studied.

This study aims to clarify the relationship between non-sleep apnoea-related sleep indicators and AF recurrence after catheter ablation through a secondary analysis of published literature. The research addresses a significant knowledge gap in the field while highlighting the critical role of sleep as a modifiable clinical factor in AF recurrence. The findings will facilitate the optimisation of risk stratification and postoperative management strategies for AF patients, potentially reducing recurrence rates and improving patient quality of life and clinical outcomes. Furthermore, the study seeks to systematically summarise and integrate sleep-related indicators, exploring the intrinsic connections between different sleep parameters. It will provide scientific evidence for developing a standardised sleep assessment framework, which is both clinically viable and necessary. The establishment of such a framework will lay the groundwork for future research on sleep and AF, thereby advancing this evolving field.