1 Introduction

Atrial fibrillation (AF) is a globally escalating cardiac condition, witnessing a tripling in prevalence over the past 50 years, with estimates indicating around 46.3 million individuals affected worldwide in 2016 [1]. In the United States, the AF population is projected to swell to between 6 and 16 million by 2050, and in Europe, the prevalence among those over 55 is expected to rise from approximately 9 million in 2010 to 14 million by 2060 [2]. The diagnosis of AF is tightly associated with increased risks of serious health complications, including heightened mortality, stroke, heart failure, and more frequent hospital admissions, significantly undermining patients’ mental health and quality of life [3, 4]. Yet, through effective anticoagulation strategies, alongside rhythm and/or heart rate control in selected patients, notable improvements in mental health, quality of life, and significant health outcomes can be achieved [3,4,5].

Antiarrhythmic drug (AAD) therapy and various types of catheter ablation represent established therapeutic avenues for cardiac rhythm management. Evidence suggests that catheter ablation, when compared to medication therapy, yields lower rates of atrial arrhythmia recurrence, and reduced associated symptoms, with similar adverse effects, despite being an invasive procedure. It is currently recommended for patients who remain symptomatic even with AAD use [3, 4]. However, the impact of catheter ablation on the quality of life and, especially, on the mental health of patients with AF is still unclear.

The landscape of previous meta-analyses [6, 7] focusing on mental health and quality of life in patients with AF undergoing catheter ablation or drug therapy has been limited, with new randomized clinical trials (RCTs) emerging subsequently. These earlier analyses [6, 7], while comprehensive, often neglected to incorporate a broad spectrum of mental health and quality of life scales tailored to AF or to consider the type of AF when assessing outcomes in mental health and quality of life. Addressing this oversight and prevailing uncertainties, we conducted an updated meta-analysis to assess the effects of catheter ablation versus medical therapy (with rate or rhythm control) on mental health and quality of life in patients with AF. This examination spans diverse populations with varying types of AF and evaluates the influence of distinct mental health and quality of life scales on the findings, aligning closely with the expanded focus of our study to encapsulate mental health alongside quality of life.

2 Methods

This systematic review with meta-analysis was registered in the international prospective register of systematic reviews (PROSPERO) under protocol CRD42024497135. This study was designed and conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) reporting guideline [8].

2.1 Study eligibility

Inclusion in this meta-analysis was restricted to studies that met all the following eligibility criteria: (1) RCT, (2) patients with AF (3) studies comparing the approaches: catheter ablation versus medical therapy, (4) studies available for review in English and in full-text, and (5) reported functional outcomes using a clinical scoring systems or health-related quality of life scale, such as Hospital Anxiety and Depression Scale (HADS), the 36-Item Short Form Survey (SF-36), the Atrial Fibrillation Effect on Quality-of-life Questionnaire (AFEQT), the Minnesota Living with Heart Failure Questionnaire (MLHFQ), the EuroQol 5 Dimensions (EQ-5D). Studies were excluded if they were non-randomized controlled trials, single-armed papers assessing catheter ablation or medical therapy or studies that did not provide outcome measures related to mental health and quality of life.

2.2 Search strategy and data extraction

We systematically searched PubMed, Embase, and Cochrane Central Register of Controlled Trials from inception to December 2023 with the following search terms: “atrial fibrillation”, “AF”, “pulsed field ablation”, “PFA”, “catheter ablation”, “radiofrequency”, “cryoballoon”, “cryoablation”, “anti-arrhythmia agents”, “anti-arrhythmic drugs”, “antiarrhythmic drugs”, “AAD”, “amiodarone”, “sotalol”, “flecainide”, “propafenone”, “drug therapy”, “rate control”. In addition, the references of included studies, reviews and meta-analysis were evaluated for additional studies. The data was independently extracted by two authors [RM, EB] following predefined search criteria and quality assessment. Disagreements were resolved by consensus and with senior author (CG).

The primary outcome was a change in functional scores. The outcomes collected were HADS, SF-36, AFEQT, MLHFQ, EQ5D and AF recurrence. The EQ5D and SF-36 were used as generic health-related quality of life scores, providing versatile quantification when assessing quality of life from a biopsychosocial perspective. The SF-36 reports eight general components (bodily pain, general health, mental health, physical functioning, role emotional, role physical, social functioning, and vitality), as well as two summary components for mental and physical health – the mental component summary and the physical component summary, respectively. The HADS provides a deeper and more specific analysis of mental health in participants with AF. The AFEQT is more specific to the atrial fibrillation population. The MLHFQ better captures limitations and improvements in patients with heart failure. Also, AF recurrence was defined as the return of AF episodes lasting 30 s or more after a 90-day blanking period.

2.3 Quality assessment

The methodological quality of all included studies was evaluated independently by three authors (MD, CB, and AF) in accordance with the Cochrane Collaboration’s tool. Risk of bias and quality assessment of individual studies were analyzed with the Cochrane Collaboration’s tool for assessing risk of bias in randomized studies. Disagreements were resolved by recruiting a third author to attain consensus [9–10].

We evaluated the analysis of publication bias through funnel plot analysis and Egger’s test for the outcomes: AFEQT score and the Mental Component Summary of the SF-36 score.

2.4 Sensitivity analysis

2.4.1 Data analysis

Pooled treatment effects for continuous outcomes were compared using MD (Mean Difference) or SMD (Standardized Mean Difference) with a 95% confidence interval. For the analysis of mental scores, only final means of SF-36 and HADS scores were included, excluding baseline changes. Heterogeneity was examined with Cochran’s Q test, I2 statistics. Heterogeneity was reported as low (I 2=0–25%), moderate (I 2=26–50%), or high (I 2>50%). The random-effects model for studies with moderate to high heterogeneity (I 2>25%). In pooled outcomes with high heterogeneity, DerSimonian and Laird random-effects model was used. All statistical analyses were conducted in the R program (version 4.3.2).

3 Results

3.1 Study selection and characteristics

As detailed in Fig. 1, the initial search yielded 4,670 results. After removal of duplicate records and ineligible studies, 50 remained and were fully reviewed based on inclusion criteria. Of these, a total of 24 RCTs comprising 6,353 patients [11,12,13,14,15,16,17,18,19,20,21,22,23,24,25,26,27,28,29,30,31,32,33,34]. A total of 3,271 (51.4%) patients received catheter ablation and 3,082 (48.5%) received medical therapy. Study characteristics are reported in Table 1. In the ablation group, the majority employed radiofrequency ablation, whereas in the pharmacotherapy group, the predominant medical treatment was rhythm control with AAD. Among the studies, only four exclusively used cryoballoon ablation for catheter-based procedures [12, 13, 26, 32], and a single study utilized hot balloon ablation [29]. Regarding drug therapy, solely five studies implemented rate control alone as their strategy [16, 18, 20, 25, 27]. The follow-up period ranged from 3 months to 5 years, and 71.1% of the participants were male. Furthermore, information on the comorbidities of the population from the included studies, such as coronary artery disease, BMI, and sleep apnea can be found in Supplementary Table 1.

Fig. 1
figure 1

PRISMA flow diagram of study screening and selection

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Table 1 Baseline characteristics of included studies
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3.2 Mental health scores

In the quantitative synthesis of the mental health outcomes, incorporating both the Hospital Anxiety and Depression Scale (HADS) and the mental component of the SF-36, catheter ablation significantly improved mental health indicators compared to drug therapy (SMD 0.34; 95% CI 0.05–0.63; p = 0.02; I² = 91%; Fig. 2A). A subgroup analysis showed no significant differences in the mental health impact of catheter ablation between patients with paroxysmal or persistent AF (p = 0.29; Fig. 2A).

Fig. 2
figure 2

Comparison between HADS scores and MCS for catheter ablation or medical therapy, alongside an individual analysis of the MCS for each treatment approach

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3.3 Mental and physical components of SF-36

The pooled results of the mental component of the SF-36 indicated an improvement for patients undergoing catheter ablation compared to those receiving medical therapy (MD 3.60; 95% CI 0.34–6.87; p = 0.03; I² = 91%; Fig. 2B), with no statistically significant differences between the subgroups of paroxysmal and persistent AF (p = 0.82; Fig. 2B), nor between subgroups of follow-up durations of 12 months or more and less than 12 months (p = 0.29; Fig. 3A). Furthermore, in the subgroup analysis for the type of medical treatment, rate or rhythm control, patients treated with rhythm control showed greater benefit in the medication therapy group compared to those treated with rate control, who favored catheter ablation more (p < 0.01; Supplementary Fig. 1A).

Fig. 3
figure 3

Analysis of the MCS with subgroups related to the time after the ablation procedure and analysis of the PCS with subgroups related to the type of AF.

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The combined results from the physical component of the SF-36 indicate a significant quality of life improvement for patients undergoing catheter ablation when compared to those receiving medical therapy (MD 2.64; 95% CI 1.06–4.23; p = 0.01; I² = 60%; Fig. 3B), with no significant difference between patients with paroxysmal or persistent forms of AF (p = 0.81; Fig. 3B). Also, in the subgroup analysis by type of medical therapy, there were no differences between rhythm and rate control (p = 0.31, Supplementary Fig. 2).

The SF-36 subcomponent analysis showed improvements in bodily pain (MD 7.00; 95% CI 2.11–11.90; p < 0.01; I² = 96%, Supplementary Fig. 3) and physical functioning (MD 7.53; 95% CI 2.29–12.77; p < 0.01; I² = 94%, Supplementary Fig. 4), role emotional (MD 3.88; 95% CI 1.26–6.50; p < 0.01; I² = 60%, Supplementary Fig. 5), and social functioning (MD 6.23; 95% CI 1.25–11.22; p = 0.01; I² = 91%, Supplementary Fig. 6), along with vitality (MD 4.45; 95% CI 2.27–6.63; p < 0.01; I² = 56%, Supplementary Fig. 7). However, general Health (MD -1.70; 95% CI -16.83 to -13.44; p = 0.83; I² = 100%, Supplementary Fig. 8) and role physical (MD 6.81; 95% CI -1.35 to 14.96; p = 0.10; I² = 98%, Supplementary Fig. 9) showed no statistically significant improvements. The mental health subcomponent showed no significant difference between treatments, but with a potential trend towards improvement (MD 2.67; 95% CI -0.28 to 5.61; p = 0.08; I² = 84%, Supplementary Fig. 10). Detailed analyses, including plots and tables for each subcomponent, are available in the supplementary material accompanying this study.

3.4 AFEQT

In the AFEQT score, a questionnaire that has been specifically developed to assess the impact of AF on patients’ quality of life, catheter ablation also significantly improved quality of life compared to medical therapy (MD 6.24; 95% CI 4.43–8.05; p < 0.01; I² = 22%; Fig. 4A), with consistent results in the subgroup analysis comparing paroxysmal and persistent AF(p = 0.09; Fig. 4A). Additionally, in the subgroup analysis according to the type of medical therapy, no differences were observed between rhythm and rate control (p = 0.66, Supplementary Fig. 11).

Fig. 4
figure 4

Analysis of AFEQT, EQ5D, and MLHFQ scores, respectively

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3.5 EQ5D

For the EQ5D score, the meta-analysis indicates a marginal but statistically significant improvement in the quality of life for patients receiving catheter ablation compared to those on medical therapy (MD 0.03; 95% CI 0.00-0.06; p = 0.04; I² = 47%; Fig. 4B). A test for subgroup differences was not applicable, given that the analysis exclusively included patients with paroxysmal AF.

3.6 MLHFQ

In the MLHFQ score, the data suggests a significant improvement for patients with persistent AF undergoing catheter ablation compared to those receiving medical therapy (MD 9.22; 95% CI 0.53–17.90; p = 0.04; I² = 74%; Fig. 4C). There was no test for subgroup differences as the analysis was conducted solely on patients with persistent AF.

3.7 AF recurrence

The overall meta-analysis for AF recurrence shows that catheter ablation is associated with a lower odds of recurrence compared to medical therapy (OR 0.22; 95% CI 0.12–0.41; p < 0.001; I² = 93%; Supplementary Fig. 12). In the subgroup analysis for types of AF, the subgroups with paroxysmal AF, as well as combined paroxysmal and persistent AF, showed greater effectiveness of catheter ablation compared to the subgroup with persistent AF alone (p < 0.01, Supplementary Fig. 12A). Furthermore, a subgroup analysis based on follow-up duration indicates that the effect of ablation in preventing AF recurrence diminishes over the long term compared to the short term (p = 0.02, Supplementary Fig. 13).

3.8 Quality assessment

Supplementary Table 2 outlines the quality appraisal of each individual RCT. All studies were considered at risk for performance bias, given the impossibility to perform patient and investigator blinding in the trials. The leave-one-out sensitivity analysis, involving the iterative removal of each study, demonstrated results consistent with our overall analysis in terms of the quality of life outcomes evaluated by the physical component of the SF-36 and the AFEQT (Supplementary Fig. 14). However, in the analysis of mental health indicators, it is observed that the removal of either the Al-Kaisey [11] or Jais [17] studies results in a loss of statistical significance. Also, following the removal of Wazni [31], one of the studies with the smallest population, a substantial reduction in heterogeneity was observed across the SF-36 score components. Concurrently, there was an increase in statistical significance, enhancing the evidence favoring catheter ablation over medical therapy. These refined results, which underscore the consistency of the benefit associated with catheter ablation, can be found detailed in the supplementary material. There was no definitive evidence of publication bias in the funnel plots (Supplementary Figs. 15 and 16).

4 Discussion

This systematic review and meta-analysis of 24 RCT, involving 6,353 patients with AF, compared the impact of catheter ablation versus medical therapy on mental health and quality of life. Our key findings were: (1) catheter ablation was associated with a significant improvement in mental health indicators compared to clinical treatment; (2) patients undergoing ablation also experienced an enhancement in general quality of life; (3) patients treated with catheter ablation also showed lower recurrence of AF; (4) there was no difference in quality-of-life outcomes between subgroups of paroxysmal or persistent AF; and (5) there was no difference in the mental health improvement between patients undergoing ablation within less than 12 months and those with more than 12 months of treatment.

The results of our meta-analysis of randomized studies are consistent with the findings of previous observational studies and reinforce the positive impact of catheter ablation on psychological stress parameters, as well as the deleterious effect of AF on mental health [35, 36]. This relationship between psychological distress and AF has been demonstrated and better clarified in recent decades. Cohort studies indicate a bidirectional connection, where individuals with depression and anxiety have a higher likelihood of developing AF and in such cases, they also experience a greater symptomatic burden due to the arrhythmia compared to individuals with preserved mental health [37, 38]. On the other hand, and in accordance with the findings of our study, evidence derived from small observational studies and one randomized trial also suggests that the treatment of AF with rhythm control, especially through catheter ablation, is associated with an improvement in symptoms of anxiety, depression, and overall emotional stress [11, 39, 40].

The overall improvement in quality of life demonstrated by patients undergoing catheter ablation, as opposed to those receiving medical therapy, also aligns with findings from previous meta-analyses [6, 7]. This improvement is observed in both general quality of life questionnaires and in a specific questionnaire for AF (AFEQT) and is likely associated with the lower recurrence of AF also observed in our analysis. When compared to medication therapy, catheter ablation is associated with symptomatic improvement, lower recurrence rates of arrhythmias, and reduced healthcare resource utilization [13, 41]. These factors may justify the perception of better quality of life in the catheter ablation group.

In our subgroup analysis regarding the type of AF, we observed that both patients with persistent and paroxysmal AF showed lower recurrence of AF with catheter ablation treatment. However, there was a significant difference between the subgroups, suggesting that the benefit would be greater in paroxysmal AF. This finding was also reported in previous studies, which have indicated lower efficacy in symptomatic control and higher recurrence of atrial arrhythmias in patients with persistent AF treated with catheter ablation, compared to those with paroxysmal AF. [42]. However, in our analysis, an improvement in quality of life was observed in both subgroups, with no statistically significant difference between them, in both mental component and physical component summaries of the SF-36 questionnaire. This observation could be explained by the fact that, even though less effective, the reduction of AF burden promoted by ablation is significant enough, as suggested by our data, to impact the well-being of patients with persistent AF. Another possibility that should be taken into consideration is the placebo effect of undergoing an invasive procedure, which may distort the perception of overall well-being and influence how patients report their experiences.

In some studies, a reduction in the improvement of quality of life was observed over a long-term follow-up, possibly driven by a higher recurrence rate of AF [6, 26, 43]. To assess this hypothesis, we conducted a subgroup analysis, comparing outcomes within less than 12 months and after 12 months post-catheter ablation using the mental component summary of the SF-36 questionnaire. The results were consistent with the overall analysis, showing better scores in the catheter ablation group and no significant difference between the subgroups. This difference in findings may be explained by the fact that studies demonstrating an attenuation of improvement in the ablation group over time had significant rates of cross-over from patients previously treated clinically, compromising the comparison between the groups. This analysis, therefore, suggests persistent improvement in quality of life, at least related to components of mental health, in patients with AF undergoing catheter ablation.

Our meta-analysis has limitations. Firstly, substantial heterogeneity is observed in the outcomes assessed by the SF-36 score, likely due to diverse baseline characteristics of each study’s population. Since the SF-36 is a generic score, its values are influenced by comorbidities beyond AF, such as sleep apnea, obesity, and coronary artery diseases, explaining increased variability across studies. To address this, a ‘leave-one-out’ sensitivity analysis was conducted, revealing that after iterative removal of the Jais [17] or Al-Kaisey [11] studies, the mental health outcome loses statistical significance. This could be justified by the fact that the former study is older, and even though the use of AAD is similar compared to others, it’s possible that the treatment of other conditions, such as structural heart diseases, was less optimized, thereby increasing the difference between the groups. On the other hand, the latter study probably had a greater impact because it used the HADS score, which is more specific for evaluating mental health. However, other outcome measures showed low heterogeneity, reinforcing key findings. Secondly, the lack of blinding and control by a sham procedure in the studies may bias patients’ perception and symptom reporting. Additionally, most included studies predominantly feature male and relatively young populations, underrepresenting females and the elderly, especially those above 75 years old. Moreover, we did not include the pulsed field ablation method, equally effective and apparently safer, due to a lack of eligible studies [44]. Therefore, our study should be interpreted considering these limitations, acknowledging inconsistent results in the literature, especially regarding mental health outcomes, and limited data about underrepresented populations.

5 Conclusion

This meta-analysis of RCTs suggests that in patients with AF, catheter ablation was associated with a significant improvement in indicators of mental health and quality of life compared to patients treated with AAD, with no difference noted between paroxysmal or persistent AF. Therefore, considering the potential expansion of the indication for catheter ablation, studies should be conducted to assess the impact of this procedure on patients with AF and mental health problems such as depression and anxiety.