Exercise and Atrial Fibrillation: Current Evidence, Knowledge Gaps, and Future Directions

Abstract

Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia, contributing to significant morbidity and mortality worldwide. The relationship between physical exercise and AF is complex, with studies showing both beneficial and potentially adverse effects. Moreover, evidence suggests a U-shaped association between exercise intensity and AF risk. Moderate exercise has been shown to reduce AF burden by improving cardiovascular risk factors, enhancing autonomic regulation, and mitigating atrial fibrosis. In contrast, excessively high-intensity endurance exercise may increase AF risk, particularly in young athletes, due to atrial stretching, dilation, fibrosis, autonomic imbalances, and heightened inflammation. The current guidelines emphasize exercise as a core lifestyle intervention for AF management, recommending moderate-intensity aerobic activity for optimal outcomes. This review examines the current evidence on the effects of exercise on AF, identifies knowledge gaps, and proposes potential future research directions.

Keywords

atrial fibrillation (AF) / exercise intensity / moderate-intensity exercise / endurance exercise / AF burden / cardiorespiratory fitness (CRF) / cardiovascular risk

1. Introduction

Atrial fibrillation (AF) is the most common, sustained cardiac arrhythmia, contributing to a significant and growing global health burden [1]. In 2020, the estimated global prevalence of AF was approximately 50 million and is projected to increase further. This surging burden is driven by multiple factors, including the aging population, rising obesity rates, improved detection methods, and enhanced survival among individuals with AF and other cardiovascular diseases [2, 3]. AF is associated with increased morbidity and mortality, increasing the risk of stroke by 2.4-fold, heart failure by 5-fold, and overall mortality by 1.5- to 2-fold [1]. Prior literature has shown that physical exercise improves clinical outcomes in several cardiovascular diseases by reducing mortality and hospitalizations while enhancing cardiac function and quality of life across various exercise types and patient populations [4, 5, 6]. However, the relationship between exercise and AF is complex. It has a dose-dependent effect, with both beneficial and potentially adverse effects [7]. Evidence suggests a U-shaped relationship between exercise intensity and AF risk, with moderate exercise being protective and high-intensity endurance exercise potentially increasing the risk, particularly in athletes [8]. This review aimed to discuss the current understanding of the impact of different exercise intensities and modalities on AF and identify evidence gaps and future research directions.

2. Definition and Characteristics of Exercise

The 2020 European Society of Cardiology (ESC) Guidelines on Sports Cardiology and Exercise define exercise as a subset of physical activity that is planned, structured, repetitive, and purposeful, to improve or maintain physical fitness [9]. The fundamental principles of exercise prescription follow the “FITT” concept (frequency, intensity, time, and type), with the mode of exercise also being a key characteristic [9]. Exercise types are traditionally categorized into endurance and resistance training, which can be further classified based on modes of exercise, including metabolism (aerobic or anaerobic) and muscle contraction types (isotonic-isometric, dynamic-static, continuous-interval, or large-small muscle groups) [9]. Aerobic exercises, such as cycling, running, or swimming at low or moderate intensity, involve large muscle groups performing dynamic activities, significantly increasing heart rate and energy expenditure. These activities primarily rely on oxygen-dependent energy pathways [10, 11]. Aerobic training can be continuous or interval-based, with interval training offering greater physiological benefits but requiring careful application in cardiac patients due to the increased stress on the cardiovascular system [12]. In contrast, anaerobic activities, such as intermittent high-intensity exercise, require sustained isometric muscle and rely on anaerobic glycolysis for energy production, rather than oxygen [10, 11]. Exercise frequency is measured in sessions per week, with guidelines recommending moderate exercise on most days, totaling at least 150 minutes per week [9]. Exercise intensity is the most critical for achieving aerobic fitness and for having the most favorable impact on risk factors [13]. Exercise Intensity can be measured by energy expenditure (metabolic equivalents [METs]), percentage of maximal aerobic capacity (maximum oxygen consumption [VO₂ max]), heart rate (percentage of maximum heart rate [HRmax] or percentage of heart rate reserve [HRR]), rate of perceived exertion (Borg scale) or “talk test” (Table 1, Ref. [9, 10, 11, 14]). Training volume is determined by the product of intensity and duration, with gradual progression recommended (increase weekly either by 2.5% in intensity or 2 minutes duration) [9, 15].

3. Benefits of Exercise in AF Management

The benefits of exercise for AF are multifaceted and attributable to several mechanisms, primarily through lowering cardiovascular risk factors and modifying atrial substrate. Regular moderate exercise lowers heart rate, blood pressure, and improves glucose and lipid control, thereby reducing overall cardiovascular risk, a major contributor to AF development [8]. Additionally, weight management via exercise enhances cardiorespiratory fitness (CRF), which has been associated with a significant reduction in AF burden and symptom severity, particularly in patients with obesity [16]. Beyond metabolic benefits, exercise exerts anti-inflammatory effects through pathways including cytokine modulation, AMP-activated protein kinase activation, and autonomic regulation; collectively reducing systemic inflammation, a known driver of AF pathogenesis [17, 18, 19]. Endothelial dysfunction plays a critical role in the pathophysiology of AF by promoting an atrial arrhythmic substrate and predicting adverse outcomes [20, 21, 22]. Exercise enhances endothelial function, which supports vascular health and reduces atrial stretch and fibrosis, thereby mitigating AF progression [8]. Prior studies in both rats and humans indicated that aerobic interval training can decrease age-related atrial fibrosis, a significant factor in AF vulnerability [23, 24]. This reduction in fibrosis leads to improved atrial conduction velocity and longer action potentials, ultimately decreasing susceptibility to AF [23]. Furthermore, regular exercise can improve autonomic balance by increasing parasympathetic activity and reducing sympathetic activity, stabilizing the atrial electrical environment [8]. Animal studies have demonstrated that exercise training restores parasympathetic modulation, improves baroreceptor reflex control, and enhances cardiac vagal tone, even with persistent ventricular dysfunction [25, 26].

The 2023 American College of Cardiology (ACC)/American Heart Association (AHA)/American College of Chest Physicians (ACCP)/Heart Rhythm Society (HRS) guidelines introduce a paradigm shift in AF management, emphasizing personalized risk factor modification and lifestyle interventions, with physical inactivity identified as one of the key targets [1, 27]. Regular physical exercise offers numerous benefits for patients with AF, including reducing arrhythmia burden, improving symptoms, lowering AF recurrence, improving functional capacity and quality of life (QoL), and lowering mortality and morbidity risks [1, 27]. These benefits are supported by several randomized clinical trials (RCTs). The CARDIO-FIT study enrolled 308 obese individuals with AF, with a mean age of 61 \pm 9 years, and a mean body mass index (BMI) of 33 \pm 5 kg/m², demonstrating that improved CRF significantly reduces arrhythmia recurrence. The greatest arrhythmia-free survival was observed in those who achieved a fitness gain of \ge2 METs, as those patients had an 89% arrhythmia-free survival rate compared to 40% for those patients who gained 2 METs (p 0.001). In fact, every MET gained was associated with a 9% decline in the risk of arrhythmia recurrence even after multifactorial adjustment (hazard ratio [HR] per 1-MET change: 0.90; 95% CI, 0.83–1.00; p = 0.036). Additionally, AF burden and symptom severity were notably lower in patients with high CRF compared to those with adequate or low fitness levels [28]. Prior studies have also shown that moderate-intensity aerobic training reduced AF incidence and burden in patients with non-permanent (paroxysmal and persistent) AF, and improved exercise capacity and overall QoL in those with non-permanent and permanent AF [1, 29]. Similarly, aerobic continuous training (moderate-intensity continuous training, MICT) has been linked to a lower risk of developing AF, with HRs ranging from 0.72 to 0.90 compared to physical inactivity. MICT has also been shown to reduce symptom burden and enhance QoL [1, 30, 31]. High-intensity interval training (HIIT), alternating short bursts of high-intensity exercise with recovery periods, offers comparable or slightly better improvements in CRF and symptom control than MICT. However, its long-term safety in AF is less established, and even with some evidence of elevated AF occurrence in patients with hypertension or kidney disease [30, 32]. Though not extensively studied, resistance training, especially moderate-intensity isometric and isotonic exercises, is generally safe for most AF patients without structural heart disease and can be part of a broader exercise regimen. However, its direct effect on AF burden remains unclear [33].

The ACTIVE-AF (A Lifestyle-based, PhysiCal AcTIVity IntErvention for Patients With Symptomatic Atrial Fibrillation) RCT, which followed 120 patients with paroxysmal or persistent (non-permanent) AF over 12 months, demonstrated that a 6-month exercise-based intervention combining home and supervised aerobic exercise reduced AF recurrence in both men (HR 0.52 [95% CI, 0.29–0.91]) and women (HR 0.47 [95% CI, 0.23–0.95]). Furthermore, symptom severity scores were significantly lower in the exercise group compared to controls, with women experiencing the highest benefit [16]. Moreover, a nationwide population-based cohort study in Korea showed that patients with newly diagnosed AF who started or maintained regular exercise had significantly lower risks of heart failure (HR 0.95 [95% CI, 0.90–0.99] and 0.92 [95% CI, 0.88–0.96], respectively) and all-cause mortality (HR 0.82 [95% CI, 0.73–0.91] and 0.61 [95% CI, 0.55–0.67], respectively) compared to non-exercisers [34]. Several meta-analyses have further reinforced these findings. A meta-analysis from thirteen RCTs by Oesterle et al. [35] found that supervised exercise training significantly reduces AF recurrence (relative risk 0.77 [95% CI, 0.60–0.99]) and improves QoL and CRF in participants with AF. This analysis included various exercise modalities, including cardiac rehabilitation, aerobic training, and yoga, highlighting the broad applicability of exercise-based interventions [35]. Another meta-analysis by Shi et al. [36] further highlighted improvements in physical functioning (standardized mean difference [SMD] 0.63 [95% CI, 0.18–1.09]; p = 0.006), general health perceptions (SMD 0.64 [95% CI, 0.35–0.93]; p 0.001), vitality (SMD 0.51 [95% CI, 0.31–0.71]; p 0.001), as well as increased performance in the 6-minute walk test (SMD 0.69 [95% CI, 0.19–1.11]; p = 0.007) and peak oxygen uptake (SMD 0.37 [95% CI, 0.16–0.57]; p 0.001). Much of the benefit may be derived from the extended duration of physical exercise, being at least 60 minutes per session [36]. These findings highlight the integral role of exercise in AF management and provide strong evidence for its implementation as a core therapeutic strategy.

4. Risks Associated With High-Intensity Exercise

The increased risk of AF associated with high-intensity, long-duration exercise is not fully understood. This phenomenon involves a complex interplay of atrial structural and electrical changes, increased vagal tone, and heightened inflammation [37]. Chronic endurance exercise leads to atrial dilation and fibrosis, driven by elevated atrial pressures and stretch from repeated strenuous activity [38, 39]. This mechanical stress causes microtears and subsequent fibrosis, contributing to atrial remodeling and creating a substrate conducive to AF [40]. Experimental models have shown atrial-specific extracellular matrix remodeling in endurance exercise, with increased collagen deposition and fibrosis, particularly in the right atrium. This process is load-dependent and correlates with increased AF susceptibility [39, 41]. Molecular studies in animal models have also shown the upregulation of transforming growth factor-beta 1 (TGF-\beta1) and matrix metalloproteinase 2 (MMP-2) in both atria after 16 weeks of intensive exercise, paralleling increased collagen content and fibrosis [39, 42]. In 1 human study, serum TGF-\beta levels have been found to correlate with left atrial volume and reduced strain in athletes, supporting its role as a biomarker of subclinical fibrosis [43]. Excessive endurance exercise may also increase vagal tone to a level that promotes AF through vagal-mediated remodeling [41, 44]. This autonomic imbalance prolongs atrial conduction while shortening the atrial refractory period, further predisposing to AF [39]. Inflammatory mechanisms also play a role, as prolonged endurance exercise has been associated with elevated levels of C-reactive protein and troponin, indicating systemic inflammation [45]. This inflammatory response, mediated through TNF\alpha-dependent pathways involving NF\kappaB and p38MAPK activation, promotes atrial hypertrophy, fibrosis, and macrophage infiltration, creating a pro-arrhythmic substrate for AF [44, 46, 47]. Furthermore, endurance exercise affects ion channel expression and function (ion channel remodeling), with downregulation of L-type calcium channels (ICaL) and an increase in inward rectifier potassium current (IK1), leading to shortened action potentials and increased susceptibility to reentry [39]. Enhanced sensitivity of the acetylcholine-regulated potassium current (IKACh) further increases vagal tone, increasing predisposition to AF [39].

Several studies have suggested that while moderate exercise is protective against AF, excessive endurance training, particularly among elite athletes and individuals engaging in long-term, high-intensity exercise, may paradoxically increase AF risk [41, 48]. The 2023 ACC/AHA/ACCP/HRS guidelines note that high-volume endurance athleticism (defined as greater than 45 metabolic equivalent hours per week) is associated with a higher prevalence of AF, particularly in young athletes [1]. Epidemiological data indicate a significantly higher prevalence of AF among endurance athletes, such as marathon runners and cyclists, compared to the general population, with an odds ratio (OR) of 2.34. This risk is more pronounced in men (OR 4.03 [95% CI, 1.73–9.42]) and younger athletes under 60 years (OR 3.24 [95% CI, 1.23–8.55]) [49]. However, elite female endurance athletes also face an elevated risk compared to the general population, with an adjusted HR of 3.67 (95% CI, 1.71–7.87), highlighting that this association between intense exercise and AF extends to both sexes [50]. A 12-week RCT in 76 patients with paroxysmal/persistent AF found that high-intensity physical exercise was not superior to low-intensity physical exercise in reducing the burden of AF (incidence rate ratio 0.742 [95% CI, 0.29–1.91]) [51]. Furthermore, extreme levels of exercise have been associated with a higher incidence of AF. An observational cohort study of 52,755 long-distance cross-country skiers with a 16-year follow-up (1989–2005) found a higher AF risk among male participants with greater race participation (HR 1.29 [95% CI, 1.04–1.61]) and faster finishing times (HR 1.20 [95% CI, 0.93–1.55]) [52].

This relationship between AF and high-intensity exercise appears to be dose-dependent, following a U-shaped pattern, with the highest incidence observed in individuals with extensive training histories or significant cumulative lifelong exercise exposure [1]. Specifically, those with a history of 2000 or more hours of cumulative high-intensity endurance training have a higher risk of AF compared to sedentary individuals (OR 3.88 [95% CI, 1.55–9.73]) [53]. However, HIIT may improve functional capacity and QoL without increasing AF burden compared to moderate to vigorous intensity continuous training [32]. Interpretation of these findings should consider the heterogeneity in methods used to assess exercise intensity, including self-reported data, which is inherently prone to recall bias.

Anticoagulation management in patients with AF who participate in high-intensity exercise also presents a unique challenge, requiring balancing the prevention of thromboembolic events with the risk of bleeding, particularly from exercise-related injuries [1, 54, 55]. Previous studies have shown that the CHA₂DS₂-VASc score may be a useful tool for assessing exercise intolerance in patients with AF. Those with exercise intolerance had significantly higher scores compared to those without (3.1 \pm 1.3 vs. 2.0 \pm 1.5, p 0.0001), with the effect being more pronounced in younger and middle-aged male patients under 65 years old (OR 3.30, 95% CI, 1.76–6.19, p 0.0001) [56]. Anticoagulation decisions should be individualized based on the specific sport, trauma risk, and the patient’s preferences. Direct oral anticoagulants (DOACs) are generally preferred over vitamin K antagonists due to their more predictable effects and lower risk of bleeding complications [57]. It is important to consider that pharmacologic rate control agents, such as beta-blockers, may reduce exercise tolerance and are less favored in this population due to their potential to hinder athletic performance [58]. In contrast, rhythm control strategies, including catheter ablation, are often prioritized to maintain exercise capacity and improve quality of life. This approach is especially beneficial for young athletes who may not tolerate or prefer to avoid long-term medication use [1].

5. Sex Difference in AF Risk With Exercise

Evidence suggests that high levels of vigorous physical activity in men are associated with an increased risk of developing AF. A meta-analysis supported this finding, showing that men engaging in vigorous physical activity had a significantly increased risk of AF (pooled OR 3.30, 95% CI, 1.97–4.63) [59]. Another study concluded that male athletes have more pronounced atrial remodeling and higher sympathetic tone, possibly contributing to the increased risk of AF [60]. Conversely, moderate to intense physical activity in women can be protective against AF. Women performing moderate physical activity were found to have an 8.6% lower risk of developing AF compared to those with a sedentary lifestyle (OR 0.91, 95% CI, 0.78–0.97), and those engaging in intense exercise had a 28% lower risk (OR 0.72, 95% CI, 0.57–0.88) [59]. Additionally, a meta-analysis found that total physical activity exposure was associated with a decreased risk of AF in women (relative risk 0.92, 95% CI, 0.87–0.97) [61]. These differences could be attributable to sex differences in autonomic adaptations to exercise, particularly increased parasympathetic tone, with men having more pronounced autonomic changes and being more susceptible to AF triggered by high vagal tone from endurance exercise, while women appear less prone to this effect [62, 63]. Other contributing factors may include sex-related differences in exercise-induced hormonal modulation or inflammatory responses, though these mechanisms are not well characterized in clinical studies and warrant further investigation [45, 64]. These age and gender-specific differences highlight the importance of tailored exercise recommendations based on age and sex to reduce the risk of AF.

6. Guidelines and Recommendations

The 2023 ACC/AHA/ACCP/HRS guidelines recommend moderate- to vigorous-intensity exercise, with a target of 210 minutes per week for individuals with AF. Aerobic activities such as walking, cycling, or swimming are preferred and can be divided into sessions of 30 minutes on most days of the week. This exercise regimen aims to reduce the frequency and duration of AF episodes while improving cardiorespiratory fitness and symptom severity [1, 16]. Before prescribing exercise, an initial evaluation should be conducted to determine the patient’s exercise capacity and identify any comorbid conditions that may affect exercise tolerance [1]. Exercise prescription should be tailored based on patients’ comorbidities, such as obesity, hypertension, and diabetes, to optimize outcomes [28]. For example, AF patients with obesity should focus on achieving significant weight loss through a combination of aerobic and resistance training, with a target of at least 10% weight loss to reduce AF symptoms, burden, recurrence, and progression to persistent AF [1, 28, 65, 66]. For AF patients with diabetes, a gradual approach is recommended, starting with low-to-moderate-intensity activities such as walking, cycling, or swimming and gradually increasing in duration and intensity as tolerated [1]. Furthermore, exercise training may also be incorporated into multidisciplinary cardiac rehabilitation, which has been shown to improve QoL and functional capacity without increasing the risk of AF recurrence, particularly in patients undergoing ablation [67, 68]. HIIT may also be considered in selected patients, provided it is well-tolerated and monitored closely [7]. In patients with hypertension or chronic kidney disease, moderate-intensity exercise is preferred, since HIIT may paradoxically increase AF occurrence in these subgroups [30].

Regular monitoring of cardiovascular status is essential, including heart rate or symptoms such as palpitations or dizziness, as well as blood glucose levels, especially in patients with diabetes. The American Heart Association recommends targeting a heart rate of 80 bpm at rest and 110 bpm during moderate exercise to improve ventricular function and exercise capacity and to prevent tachycardiomyopathy [69]. Careful ventricular rate control is necessary during exercise to prevent atrial myopathy associated with excessive training [1]. Patients should be educated on recognizing symptoms that warrant cessation of exercise and medical consultation. High-intensity activities that may exacerbate AF or cause significant blood glucose fluctuations should be avoided [1, 70]. The exercise regimen should be adjusted based on the patient’s response during follow-up visits, particularly in those with heart failure or coronary artery disease [1].

The 2020 ESC Guidelines on sports cardiology and exercise recommend engaging in regular physical activity, with at least 150 minutes of moderate-intensity aerobic exercise per week, to prevent AF [9]. While both the 2023 ACC/AHA and 2020 ESC guidelines emphasize the benefits of moderate-intensity exercise in reducing AF burden and improving cardiovascular fitness, the 2020 ESC explicitly cautions against excessive high-intensity endurance training, especially for middle-aged men, due to its potential to increase AF risk [8, 9]. Additionally, the 2020 ESC guidelines highlight the importance of evaluation and management of underlying conditions, such as structural heart disease, thyroid dysfunction, alcohol or drug abuse, or other primary causes of AF, before engaging in sports [9]. In contrast, the 2023 ACC/AHA guidelines provide more detailed recommendations for tailoring exercise regimens based on comorbidities, such as obesity and diabetes [1]. Both guidelines emphasize the importance of rate control during exercise, but the 2023 ACC/AHA guidelines specify target heart rate thresholds to ensure safety and performance optimization [1, 9]. Finally, the ESC also provides specific recommendations on sports participation for anticoagulated patients, advising against high-contact or trauma-prone activities [9]. The 2020 Canadian Cardiovascular Society guidelines recommend that AF patients engage in at least 200 minutes per week of moderate-intensity aerobic exercise, complemented by resistance and flexibility training. These guidelines emphasize the importance of individualized exercise prescriptions, considering factors such as exercise intensity, duration, and patient-specific characteristics [71]. Guidelines recommendations are summarized in Table 2.

7. Evidence Gaps

The relationship between exercise and AF has been extensively studied, yet several evidence gaps persist. A major challenge is the heterogeneity in exercise protocols, including aerobic training, resistance training, and HIIT, making it difficult to establish standardized recommendations. Inconsistencies in study designs, including varying intensity metrics (VO₂ max percentages, METs, Borg scales), different adherence monitoring methods (self-reports, supervised sessions, wearable devices), and outcome measures further complicated efforts to identify the most effective exercise strategies for AF management [35, 51, 72]. Additionally, most studies have short follow-up durations, limiting the understanding of the long-term effects of exercise on AF recurrence, burden, and cardiovascular outcomes [35, 72]. The optimal exercise intensity and type for reducing AF burden without increasing risk are also not well-defined; while MICT is generally recommended, the role and long-term safety of HIIT require further exploration [7, 72]. Lastly, while there is evidence linking exercise to changes in atrial remodeling, autonomic tone, and inflammation, significant gaps remain in understanding the precise mechanisms and their clinical implications [8].

8. Future Direction

Future research on the effects of different exercise modalities and intensities on AF outcomes should address several key areas. Large, multicenter RCTs with long-term follow-up are needed to assess the impact of different exercise modalities on AF outcomes and to establish optimal exercise prescription for AF patients [31, 35, 72]. For example, the ongoing Cologne ExAfib trial is investigating the feasibility and safety of various exercise interventions, including HIIT, MICT, and strength training in patients with paroxysmal AF [30, 31]. Longitudinal studies are equally important to assess the long-term impact of exercise training on AF outcomes, as existing evidence suggests potential benefits in rate control, functional capacity, and QoL. However, further confirmation is needed [73]. Continuous ambulatory monitoring should be integrated into future studies to assess AF burden and exercise effects accurately [24]. Wearable technology and mobile health (mHealth) advances can improve exercise monitoring by providing real-time heart rate and rhythm data, enabling personalized, data-driven exercise recommendations. This approach can minimize recall bias while providing objective quantitative analyses [74]. Future research should also focus on developing personalized exercise programs tailored to maximize benefits, based on individual risk profiles, including age, sex, comorbidities, and baseline fitness levels [1, 34]. Exploration of exercise-related genetic polymorphisms, particularly in the peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1\alpha), and their impact on AF risk may offer novel insights into patient-specific responses to exercise and further personalize therapeutic strategies [75]. A more in-depth investigation of the underlying mechanisms by which exercise affects AF, such as metabolism, inflammation, atrial stretch, and autonomic modulation, is necessary to identify biomarkers and refine interventions [8, 45].

9. Conclusion

Moderate exercise can improve cardiovascular health and QoL in patients with AF while reducing the burden of AF. However, the effects of high-intensity exercise remain uncertain and may vary among individuals. Ongoing research should focus on refining exercise recommendations, aiming to optimize clinical outcomes by balancing the benefits of physical activity with potential risks in AF management.

References

[1] Joglar JA, Chung MK, Armbruster AL, Benjamin EJ, Chyou JY, Cronin EM, et al. 2023 ACC/AHA/ACCP/HRS Guideline for the Diagnosis and Management of Atrial Fibrillation: A Report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines. Circulation. 2024; 149: e1–e156. https://doi.org/10.1161/CIR.0000000000001193.

[2] Tsao CW, Aday AW, Almarzooq ZI, Anderson CAM, Arora P, Avery CL, et al. Heart Disease and Stroke Statistics-2023 Update: A Report From the American Heart Association. Circulation. 2023; 147: e93–e621. https://doi.org/10.1161/CIR.0000000000001123.

[3] Chugh SS, Havmoeller R, Narayanan K, Singh D, Rienstra M, Benjamin EJ, et al. Worldwide epidemiology of atrial fibrillation: a Global Burden of Disease 2010 Study. Circulation. 2014; 129: 837–847. https://doi.org/10.1161/CIRCULATIONAHA.113.005119.

[4] Dibben G, Faulkner J, Oldridge N, Rees K, Thompson DR, Zwisler AD, et al. Exercise-based cardiac rehabilitation for coronary heart disease. The Cochrane Database of Systematic Reviews. 2021; 11: CD001800. https://doi.org/10.1002/14651858.CD001800.pub4.

[5] Zhang Y, Qi L, Xu L, Sun X, Liu W, Zhou S, et al. Effects of exercise modalities on central hemodynamics, arterial stiffness and cardiac function in cardiovascular disease: Systematic review and meta-analysis of randomized controlled trials. PloS One. 2018; 13: e0200829. https://doi.org/10.1371/journal.pone.0200829.

[6] Rijal A, Nielsen EE, Adhikari TB, Dhakal S, Maagaard M, Piri R, et al. Effects of adding exercise to usual care in patients with either hypertension, type 2 diabetes or cardiovascular disease: a systematic review with meta-analysis and trial sequential analysis. British Journal of Sports Medicine. 2023; 57: 930–939. https://doi.org/10.1136/bjsports-2022-106002.

[7] Wang Y, Wang Y, Xu D. Effects of different exercise methods and intensities on the incidence and prognosis of atrial fibrillation. Trends in Cardiovascular Medicine. 2024; 34: 510–515. https://doi.org/10.1016/j.tcm.2024.01.002.

[8] Gorenek B, Pelliccia A, Benjamin EJ, Boriani G, Crijns HJ, Fogel RI, et al. European Heart Rhythm Association (EHRA)/European Association of Cardiovascular Prevention and Rehabilitation (EACPR) position paper on how to prevent atrial fibrillation endorsed by the Heart Rhythm Society (HRS) and Asia Pacific Heart Rhythm Society (APHRS). Europace. 2017; 19: 190–225. https://doi.org/10.1093/europace/euw242.

[9] Pelliccia A, Sharma S, Gati S, Bäck M, Börjesson M, Caselli S, et al. 2020 ESC Guidelines on sports cardiology and exercise in patients with cardiovascular disease. European Heart Journal. 2021; 42: 17–96. https://doi.org/10.1093/eurheartj/ehaa605.

[10] Vanhees L, Rauch B, Piepoli M, van Buuren F, Takken T, Börjesson M, et al. Importance of characteristics and modalities of physical activity and exercise in the management of cardiovascular health in individuals with cardiovascular disease (Part III). European Journal of Preventive Cardiology. 2012; 19: 1333–1356. https://doi.org/10.1177/2047487312437063.

[11] Vanhees L, Geladas N, Hansen D, Kouidi E, Niebauer J, Reiner Z, et al. Importance of characteristics and modalities of physical activity and exercise in the management of cardiovascular health in individuals with cardiovascular risk factors: recommendations from the EACPR. Part II. European Journal of Preventive Cardiology. 2012; 19: 1005–1033. https://doi.org/10.1177/1741826711430926.

[12] Arena R, Myers J, Forman DE, Lavie CJ, Guazzi M. Should high-intensity-aerobic interval training become the clinical standard in heart failure? Heart Failure Reviews. 2013; 18: 95–105. https://doi.org/10.1007/s10741-012-9333-z.

[13] Lee DC, Brellenthin AG, Lanningham-Foster LM, Kohut ML, Li Y. Aerobic, resistance, or combined exercise training and cardiovascular risk profile in overweight or obese adults: the CardioRACE trial. European Heart Journal. 2024; 45: 1127–1142.

[14] Arnett DK, Blumenthal RS, Albert MA, Buroker AB, Goldberger ZD, Hahn EJ, et al. 2019 ACC/AHA Guideline on the Primary Prevention of Cardiovascular Disease: Executive Summary: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. Journal of the American College of Cardiology. 2019; 74: 1376–1414. https://doi.org/10.1016/j.jacc.2019.03.009.

[15] Thomaes T, Thomis M, Onkelinx S, Goetschalckx K, Fagard R, Lambrechts D, et al. Genetic predisposition scores associate with muscular strength, size, and trainability. Medicine and Science in Sports and Exercise. 2013; 45: 1451–1459. https://doi.org/10.1249/MSS.0b013e31828983f7.

[16] Elliott AD, Verdicchio CV, Mahajan R, Middeldorp ME, Gallagher C, Mishima RS, et al. An Exercise and Physical Activity Program in Patients With Atrial Fibrillation: The ACTIVE-AF Randomized Controlled Trial. JACC. Clinical Electrophysiology. 2023; 9: 455–465. https://doi.org/10.1016/j.jacep.2022.12.002.

[17] Pedersen BK. Anti-inflammatory effects of exercise: role in diabetes and cardiovascular disease. European Journal of Clinical Investigation. 2017; 47: 600–611. https://doi.org/10.1111/eci.12781.

[18] Zhang M, Alemasi A, Zhao M, Xu W, Zhang Y, Gao W, et al. Exercise Training Attenuates Acute β-Adrenergic Receptor Activation-Induced Cardiac Inflammation via the Activation of AMP-Activated Protein Kinase. International Journal of Molecular Sciences. 2023; 24: 9263. https://doi.org/10.3390/ijms24119263.

[19] Shimojo G, Joseph B, Shah R, Consolim-Colombo FM, De Angelis K, Ulloa L. Exercise activates vagal induction of dopamine and attenuates systemic inflammation. Brain, Behavior, and Immunity. 2019; 75: 181–191. https://doi.org/10.1016/j.bbi.2018.10.005.

[20] Black N, Mohammad F, Saraf K, Morris G. Endothelial function and atrial fibrillation: A missing piece of the puzzle? Journal of Cardiovascular Electrophysiology. 2022; 33: 109–116. https://doi.org/10.1111/jce.15277.

[21] Qin S, Boidin M, Buckley BJR, Lip GYH, Thijssen DHJ. Endothelial dysfunction and vascular maladaptation in atrial fibrillation. European Journal of Clinical Investigation. 2021; 51: e13477. https://doi.org/10.1111/eci.13477.

[22] Wong CX, Ganesan AN, Selvanayagam JB. Epicardial fat and atrial fibrillation: current evidence, potential mechanisms, clinical implications, and future directions. European Heart Journal. 2017; 38: 1294–1302. https://doi.org/10.1093/eurheartj/ehw045.

[23] Malmo V, Kelly A, Garten KS, Stolen T, Rolim NPL, Wisloff U, et al. Aerobic Interval Training Prevents Age-Dependent Vulnerability to Atrial Fibrillation in Rodents. Frontiers in Physiology. 2018; 9: 206. https://doi.org/10.3389/fphys.2018.00206.

[24] Kim S, Lee S, Han D, Jeong I, Lee HH, Koh Y, et al. One-year Aerobic Interval Training Improves Endothelial Dysfunction in Patients with Atrial Fibrillation: A Randomized Trial. Internal Medicine (Tokyo, Japan). 2023; 62: 2465–2474. https://doi.org/10.2169/internalmedicine.0947-22.

[25] Dellacqua LO, Gomes PM, Batista JS, Michelini LC, Antunes VR. Exercise-induced neuroplasticity in autonomic nuclei restores the cardiac vagal tone and baroreflex dysfunction in aged hypertensive rats. Journal of Applied Physiology (Bethesda, Md.: 1985). 2024; 136: 189–198. https://doi.org/10.1152/japplphysiol.00433.2023.

[26] Ichige MHA, Santos CR, Jordão CP, Ceroni A, Negrão CE, Michelini LC. Exercise training preserves vagal preganglionic neurones and restores parasympathetic tonus in heart failure. The Journal of Physiology. 2016; 594: 6241–6254. https://doi.org/10.1113/JP272730.

[27] Pham HN, Ibrahim R, Truong HH, Sainbayar E, Tran VN, Abdelnabi M, et al. Advances in Atrial Fibrillation Management: A Guide for General Internists. Journal of Clinical Medicine. 2024; 13: 7846. https://doi.org/10.3390/jcm13247846.

[28] Pathak RK, Elliott A, Middeldorp ME, Meredith M, Mehta AB, Mahajan R, et al. Impact of CARDIOrespiratory FITness on Arrhythmia Recurrence in Obese Individuals With Atrial Fibrillation: The CARDIO-FIT Study. Journal of the American College of Cardiology. 2015; 66: 985–996. https://doi.org/10.1016/j.jacc.2015.06.488.

[29] Malmo V, Nes BM, Amundsen BH, Tjonna AE, Stoylen A, Rossvoll O, et al. Aerobic Interval Training Reduces the Burden of Atrial Fibrillation in the Short Term: A Randomized Trial. Circulation. 2016; 133: 466–473. https://doi.org/10.1161/CIRCULATIONAHA.115.018220.

[30] Chung MK, Eckhardt LL, Chen LY, Ahmed HM, Gopinathannair R, Joglar JA, et al. Lifestyle and Risk Factor Modification for Reduction of Atrial Fibrillation: A Scientific Statement From the American Heart Association. Circulation. 2020; 141: e750–e772. https://doi.org/10.1161/CIR.0000000000000748.

[31] Zacher J, Dillschnitter K, Freitag N, Kreutz T, Bjarnason-Wehrens B, Bloch W, et al. Exercise training in the treatment of paroxysmal atrial fibrillation: study protocol of the Cologne ExAfib Trial. BMJ Open. 2020; 10: e040054. https://doi.org/10.1136/bmjopen-2020-040054.

[32] Reed JL, Terada T, Vidal-Almela S, Tulloch HE, Mistura M, Birnie DH, et al. Effect of High-Intensity Interval Training in Patients With Atrial Fibrillation: A Randomized Clinical Trial. JAMA Network Open. 2022; 5: e2239380. https://doi.org/10.1001/jamanetworkopen.2022.39380.

[33] Fletcher GF, Ades PA, Kligfield P, Arena R, Balady GJ, Bittner VA, et al. Exercise standards for testing and training: a scientific statement from the American Heart Association. Circulation. 2013; 128: 873–934. https://doi.org/10.1161/CIR.0b013e31829b5b44.

[34] Ahn HJ, Lee SR, Choi EK, Han KD, Jung JH, Lim JH, et al. Association between exercise habits and stroke, heart failure, and mortality in Korean patients with incident atrial fibrillation: A nationwide population-based cohort study. PLoS Medicine. 2021; 18: e1003659. https://doi.org/10.1371/journal.pmed.1003659.

[35] Oesterle A, Giancaterino S, Van Noord MG, Pellegrini CN, Fan D, Srivatsa UN, et al. Effects of Supervised Exercise Training on Atrial Fibrillation: A META-ANALYSIS OF RANDOMIZED CONTROLLED TRIALS. Journal of Cardiopulmonary Rehabilitation and Prevention. 2022; 42: 258–265. https://doi.org/10.1097/HCR.0000000000000665.

[36] Shi S, Shi J, Jia Q, Shi S, Yuan G, Hu Y. Efficacy of Physical Exercise on the Quality of Life, Exercise Ability, and Cardiopulmonary Fitness of Patients With Atrial Fibrillation: A Systematic Review and Meta-Analysis. Frontiers in Physiology. 2020; 11: 740. https://doi.org/10.3389/fphys.2020.00740.

[37] Guasch E, Mont L, Sitges M. Mechanisms of atrial fibrillation in athletes: what we know and what we do not know. Netherlands Heart Journal: Monthly Journal of the Netherlands Society of Cardiology and the Netherlands Heart Foundation. 2018; 26: 133–145. https://doi.org/10.1007/s12471-018-1080-x.

[38] Peritz DC, Catino AB, Csecs I, Kaur G, Kheirkhahan M, Loveless B, et al. High-intensity endurance training is associated with left atrial fibrosis. American Heart Journal. 2020; 226: 206–213. https://doi.org/10.1016/j.ahj.2020.05.015.

[39] Guasch E, Benito B, Qi X, Cifelli C, Naud P, Shi Y, et al. Atrial fibrillation promotion by endurance exercise: demonstration and mechanistic exploration in an animal model. Journal of the American College of Cardiology. 2013; 62: 68–77. https://doi.org/10.1016/j.jacc.2013.01.091.

[40] Redpath CJ, Backx PH. Atrial fibrillation and the athletic heart. Current Opinion in Cardiology. 2015; 30: 17–23. https://doi.org/10.1097/HCO.0000000000000130.

[41] Gorman RA, Yakobov S, Polidovitch N, Debi R, Sanfrancesco VC, Hood DA, et al. The effects of daily dose of intense exercise on cardiac responses and atrial fibrillation. The Journal of Physiology. 2024; 602: 569–596. https://doi.org/10.1113/JP285697.

[42] Benito B, Gay-Jordi G, Serrano-Mollar A, Guasch E, Shi Y, Tardif JC, et al. Cardiac arrhythmogenic remodeling in a rat model of long-term intensive exercise training. Circulation. 2011; 123: 13–22. https://doi.org/10.1161/CIRCULATIONAHA.110.938282.

[43] Yıldırım A, Tokgözoğlu SL, Yıldırım M, Şener YZ, Okşul M, Akçay D, et al. Role of echocardiography on early diagnosis of atrial remodelling and fibrosis in elite athletes. The International Journal of Cardiovascular Imaging. 2023; 39: 1299–1306. https://doi.org/10.1007/s10554-023-02845-7.

[44] Aschar-Sobbi R, Izaddoustdar F, Korogyi AS, Wang Q, Farman GP, Yang F, et al. Increased atrial arrhythmia susceptibility induced by intense endurance exercise in mice requires TNFα. Nature Communications. 2015; 6: 6018. https://doi.org/10.1038/ncomms7018.

[45] Dorian D, Gustafson D, Quinn R, Bentley RF, Dorian P, Goodman JM, et al. Exercise-Dependent Modulation of Immunological Response Pathways in Endurance Athletes With and Without Atrial Fibrillation. Journal of the American Heart Association. 2024; 13: e033640. https://doi.org/10.1161/JAHA.123.033640.

[46] Lakin R, Polidovitch N, Yang S, Parikh M, Liu X, Debi R, et al. Cardiomyocyte and endothelial cells play distinct roles in the tumour necrosis factor (TNF)-dependent atrial responses and increased atrial fibrillation vulnerability induced by endurance exercise training in mice. Cardiovascular Research. 2023; 119: 2607–2622. https://doi.org/10.1093/cvr/cvad144.

[47] Lakin R, Polidovitch N, Yang S, Guzman C, Gao X, Wauchop M, et al. Inhibition of soluble TNFα prevents adverse atrial remodeling and atrial arrhythmia susceptibility induced in mice by endurance exercise. Journal of Molecular and Cellular Cardiology. 2019; 129: 165–173. https://doi.org/10.1016/j.yjmcc.2019.01.012.

[48] Giacomantonio NB, Bredin SSD, Foulds HJA, Warburton DER. A systematic review of the health benefits of exercise rehabilitation in persons living with atrial fibrillation. The Canadian Journal of Cardiology. 2013; 29: 483–491. https://doi.org/10.1016/j.cjca.2012.07.003.

[49] Li X, Cui S, Xuan D, Xuan C, Xu D. Atrial fibrillation in athletes and general population: A systematic review and meta-analysis. Medicine. 2018; 97: e13405. https://doi.org/10.1097/MD.0000000000013405.

[50] Drca N, Larsson SC, Grannas D, Jensen-Urstad M. Elite female endurance athletes are at increased risk of atrial fibrillation compared to the general population: a matched cohort study. British Journal of Sports Medicine. 2023; 57: 1175–1179. https://doi.org/10.1136/bjsports-2022-106035.

[51] Skielboe AK, Bandholm TQ, Hakmann S, Mourier M, Kallemose T, Dixen U. Cardiovascular exercise and burden of arrhythmia in patients with atrial fibrillation - A randomized controlled trial. PloS One. 2017; 12: e0170060. https://doi.org/10.1371/journal.pone.0170060.

[52] Andersen K, Farahmand B, Ahlbom A, Held C, Ljunghall S, Michaëlsson K, et al. Risk of arrhythmias in 52 755 long-distance cross-country skiers: a cohort study. European Heart Journal. 2013; 34: 3624–3631. https://doi.org/10.1093/eurheartj/eht188.

[53] Calvo N, Ramos P, Montserrat S, Guasch E, Coll-Vinent B, Domenech M, et al. Emerging risk factors and the dose-response relationship between physical activity and lone atrial fibrillation: a prospective case-control study. Europace. 2016; 18: 57–63. https://doi.org/10.1093/europace/euv216.

[54] Sainbayar E, Pham HN, Beauti W, Shahid M, Hickerson N, Hassan K, et al. Regional Disparities and Death Trends Related to Hemopericardial Cardiovascular Mortality. The American Journal of Cardiology. 2024; 210: 8–10. https://doi.org/10.1016/j.amjcard.2023.10.013.

[55] Pham HN, Sainbayar E, Ibrahim R, Lee JZ. Intracerebral hemorrhage mortality in individuals with atrial fibrillation: a nationwide analysis of mortality trends in the United States. Journal of Interventional Cardiac Electrophysiology: an International Journal of Arrhythmias and Pacing. 2024; 67: 1117–1125. https://doi.org/10.1007/s10840-023-01674-x.

[56] Yi JE, Lee YS, Choi EK, Cha MJ, Kim TH, Park JK, et al. CHA₂DS₂-VASc score predicts exercise intolerance in young and middle-aged male patients with asymptomatic atrial fibrillation. Scientific Reports. 2018; 8: 18039. https://doi.org/10.1038/s41598-018-36185-7.

[57] Minardi S, Sciarra L, Robles AG, Scara A, Sciarra F, De Masi De Luca G, et al. Thromboembolic prevention in athletes: management of anticoagulation in sports players affected by atrial fibrillation. Frontiers in Pharmacology. 2024; 15: 1384213. https://doi.org/10.3389/fphar.2024.1384213.

[58] Ulimoen SR, Enger S, Pripp AH, Abdelnoor M, Arnesen H, Gjesdal K, et al. Calcium channel blockers improve exercise capacity and reduce N-terminal Pro-B-type natriuretic peptide levels compared with beta-blockers in patients with permanent atrial fibrillation. European Heart Journal. 2014; 35: 517–524. https://doi.org/10.1093/eurheartj/eht429.

[59] Mohanty S, Mohanty P, Tamaki M, Natale V, Gianni C, Trivedi C, et al. Differential Association of Exercise Intensity With Risk of Atrial Fibrillation in Men and Women: Evidence from a Meta-Analysis. Journal of Cardiovascular Electrophysiology. 2016; 27: 1021–1029. https://doi.org/10.1111/jce.13023.

[60] Wilhelm M, Roten L, Tanner H, Wilhelm I, Schmid JP, Saner H. Gender differences of atrial and ventricular remodeling and autonomic tone in nonelite athletes. The American Journal of Cardiology. 2011; 108: 1489–1495. https://doi.org/10.1016/j.amjcard.2011.06.073.

[61] Zhu WG, Wan R, Din Y, Xu Z, Yang X, Hong K. Sex Differences in the Association Between Regular Physical Activity and Incident Atrial Fibrillation: A Meta-analysis of 13 Prospective Studies. Clinical Cardiology. 2016; 39: 360–367. https://doi.org/10.1002/clc.22531.

[62] Guasch E, Mont L. Diagnosis, pathophysiology, and management of exercise-induced arrhythmias. Nature Reviews. Cardiology. 2017; 14: 88–101. https://doi.org/10.1038/nrcardio.2016.173.

[63] Wilhelm M. Atrial fibrillation in endurance athletes. European Journal of Preventive Cardiology. 2014; 21: 1040–1048. https://doi.org/10.1177/2047487313476414.

[64] Odening KE, Deiß S, Dilling-Boer D, Didenko M, Eriksson U, Nedios S, et al. Mechanisms of sex differences in atrial fibrillation: role of hormones and differences in electrophysiology, structure, function, and remodelling. Europace. 2019; 21: 366–376. https://doi.org/10.1093/europace/euy215.

[65] Ibrahim R, Pham HN, Vest AR, William P. Managing Obesity in Heart Failure: Latest Evidence and Knowledge Gaps. Current Treatment Options in Cardiovascular Medicine. 2024; 26: 355–367.

[66] Pathak RK, Middeldorp ME, Meredith M, Mehta AB, Mahajan R, Wong CX, et al. Long-Term Effect of Goal-Directed Weight Management in an Atrial Fibrillation Cohort: A Long-Term Follow-Up Study (LEGACY). Journal of the American College of Cardiology. 2015; 65: 2159–2169. https://doi.org/10.1016/j.jacc.2015.03.002.

[67] Kato M, Ogano M, Mori Y, Kochi K, Morimoto D, Kito K, et al. Exercise-based cardiac rehabilitation for patients with catheter ablation for persistent atrial fibrillation: A randomized controlled clinical trial. European Journal of Preventive Cardiology. 2019; 26: 1931–1940. https://doi.org/10.1177/2047487319859974.

[68] Risom SS, Zwisler AD, Sibilitz KL, Rasmussen TB, Taylor RS, Thygesen LC, et al. Cardiac Rehabilitation for Patients Treated for Atrial Fibrillation With Ablation Has Long-Term Effects: 12-and 24-Month Follow-up Results From the Randomized CopenHeart_R⁢F⁢A Trial. Archives of Physical Medicine and Rehabilitation. 2020; 101: 1877–1886. https://doi.org/10.1016/j.apmr.2020.06.026.

[69] Manolis AS, Manolis TA, Manolis AA, Melita H. Atrial fibrillation-induced tachycardiomyopathy and heart failure: an underappreciated and elusive condition. Heart Failure Reviews. 2022; 27: 2119–2135. https://doi.org/10.1007/s10741-022-10221-1.

[70] Kanaley JA, Colberg SR, Corcoran MH, Malin SK, Rodriguez NR, Crespo CJ, et al. Exercise/Physical Activity in Individuals with Type 2 Diabetes: A Consensus Statement from the American College of Sports Medicine. Medicine and Science in Sports and Exercise. 2022; 54: 353–368. https://doi.org/10.1249/MSS.0000000000002800.

[71] Andrade JG, Aguilar M, Atzema C, Bell A, Cairns JA, Cheung CC, et al. The 2020 Canadian Cardiovascular Society/Canadian Heart Rhythm Society Comprehensive Guidelines for the Management of Atrial Fibrillation. The Canadian Journal of Cardiology. 2020; 36: 1847–1948. https://doi.org/10.1016/j.cjca.2020.09.001.

[72] Risom SS, Zwisler AD, Johansen PP, Sibilitz KL, Lindschou J, Gluud C, et al. Exercise-based cardiac rehabilitation for adults with atrial fibrillation. The Cochrane Database of Systematic Reviews. 2017; 2: CD011197. https://doi.org/10.1002/14651858.CD011197.pub2.

[73] Reed JL, Mark AE, Reid RD, Pipe AL. The effects of chronic exercise training in individuals with permanent atrial fibrillation: a systematic review. The Canadian Journal of Cardiology. 2013; 29: 1721–1728. https://doi.org/10.1016/j.cjca.2013.09.020.

[74] McConnell MV, Turakhia MP, Harrington RA, King AC, Ashley EA. Mobile Health Advances in Physical Activity, Fitness, and Atrial Fibrillation: Moving Hearts. Journal of the American College of Cardiology. 2018; 71: 2691–2701. https://doi.org/10.1016/j.jacc.2018.04.030.

[75] Montes-de-Oca-García A, Corral-Pérez J, Velázquez-Díaz D, Perez-Bey A, Rebollo-Ramos M, Marín-Galindo A, et al. Influence of Peroxisome Proliferator-Activated Receptor (PPAR)-gamma Coactivator (PGC)-1 alpha gene rs8192678 polymorphism by gender on different health-related parameters in healthy young adults. Frontiers in Physiology. 2022; 13: 885185. https://doi.org/10.3389/fphys.2022.885185.