Background

Atrial fibrillation (AF) is the most common arrhythmia in adults, and it is present in 1-2% of the United States population.¹ The condition is responsible for one in six strokes and over $6 billion in direct annual healthcare spending.^1-3

The initial management of AF was extensively investigated in 2020. Three major randomized clinical trials (EAST-AFNET, STOP-AF, and EARLY-AF) published in the New England Journal of Medicine focused on pharmacologic and invasive rhythm control strategies in the first 12 months after AF diagnosis.^4-6 Meanwhile in 2020, the American Heart Association (AHA) issued a scientific statement calling attention to comprehensive lifestyle and risk factor modification in atrial fibrillation.⁷

Epidemiologic studies have identified risk factors for the development and progression of AF. The subset that is considered modifiable includes hypertension, obesity, diabetes mellitus, alcohol consumption, obstructive sleep apnea, sedentary lifestyle, and tobacco use.^1,8 There have been few randomized trials examining modification of these risk factors for AF management, but a large body of evidence is emerging. More data and increased recognition are urgently needed for risk factor modification in atrial fibrillation so that widespread prevention initiatives can be successful.

Lifestyle Modification as Initial Treatment for Atrial Fibrillation

The 2019 Focused Update on the 2014 AHA/ACC/HRS Guideline for the Management of Patients with Atrial Fibrillation includes a class IB recommendation for weight loss in obese patients.⁹ This recommendation is based on growing evidence that weight loss can reduce AF burden, independent of other rhythm control strategies.

The non-randomized, prospective LEGACY study enrolled patients with body mass index (BMI) >27 kg/m² in a weight management program independent of their arrhythmia management.¹⁰ Those who achieved >10% weight loss had significantly greater freedom from AF as determined by 7-day cardiac monitors. Over a median follow-up of 48 months, 45% of patients who lost >10% body weight – and did not received ablation or anti-arrhythmic drugs – achieved freedom from AF compared to 13% of those who gained weight or lost <3% body weight. The REVERSE-AF study examined the same cohort and found that among patients who continue to have AF, many who achieved weight loss experienced reduced burden and "regressed" from persistent to paroxysmal AF.¹¹

Improved cardiorespiratory fitness reduces AF burden after diagnosis. The non-randomized CARDIO-FIT study analyzed just over 300 patients with BMI >27 kg/m² who underwent tailored exercise programs.¹² In patients who did not receive ablation or anti-arrhythmic drugs, every metabolic equivalent (MET) gained through the exercise program (as assessed by exercise stress testing) was associated with a 13% reduction in AF burden, even after controlling for concomitant weight loss.

The association between alcohol consumption and AF incidence or recurrence is well known.¹³ A recent randomized, controlled trial showed that abstinence from alcohol could reduce AF burden.¹⁴ Patients with AF and baseline alcohol consumption of at least ten standard drinks per week were randomized to continue their drinking habits or abstain from alcohol. The abstinence group showed an absolute risk reduction of 20% for AF recurrence (53% vs. 73%, p=0.005). Many other AF risk factors remain to be studied in a similarly rigorous manner.

Lifestyle Modification to Improve Success of Rhythm Control

Whereas weight loss, cardiorespiratory training and alcohol abstinence have been studied for their stand-alone impact on AF burden, many more studies have been conducted on the impact of risk factor modification in combination with other management strategies. The LEGACY study showed that many people could achieve regression or freedom from AF with weight loss alone, but the best results were seen in patients who achieved >10% weight loss and had catheter ablation or used anti-arrhythmic drugs. The use of these strategies was at the discretion of the treating physician and could include multiple ablation procedures. The overall AF-free survival with a combined strategy was 86.2% over a median 42 months.¹⁰

The ARREST-AF study specifically examined risk factor modification in patients undergoing AF ablation. Ablation patients who also completed a risk factor modification program with diet, smoking, alcohol, blood pressure, cholesterol, diabetes, and sleep apnea treatment as indicated had an 87% arrythmia-free survival, whereas those who had risk factors managed according to standard care achieved 18% arrythmia-free survival.¹⁵

Obstructive sleep apnea (OSA) increases the risk of AF recurrence following treatment, and continuous positive airway pressure therapy (CPAP) helps mitigate the risk. In one study with 12 months of follow-up after cardioversion, AF recurred in 82% of patients who had OSA but were not using CPAP and only 42% in those who used CPAP.¹⁶ A meta-analysis found 25% greater risk of AF recurrence following catheter ablation in patients with OSA.¹⁷ In one prospective cohort of patients who underwent sleep studies immediately following catheter ablation, those without evidence of OSA had 22% recurrence over a median 18 months, whereas those with OSA who used CPAP had 30% recurrence, and those with OSA who did not use CPAP had 53% recurrence.¹⁸

Conclusion

Risk factors for the development of AF have been established by large cohort studies. Several of these risk factors have been studied in rigorous, prospective trials. We now know that multi-faceted risk factor modification helps reduce AF burden and should be used as first-line treatment. Risk factor modification also increases success rates of other management strategies including rate control, pharmacologic rhythm control, and catheter ablation. More studies are needed to help guide effective prevention initiatives.

References

1. Andrade J, Khairy P, Dobrev D, Nattel S. The clinical profile and pathophysiology of atrial fibrillation: relationships among clinical features, epidemiology, and mechanisms. Circ Res 2014;114:1453-68.
2. Hart RG, Palacio S, Pearce LA. Atrial fibrillation, stroke, and acute antithrombotic therapy: analysis of randomized clinical trials. Stroke 2002;33:2722-27.
3. Coyne KS, Paramore C, Grandy S, Mercader M, Reynolds M, Zimetbaum P. Assessing the direct costs of treating nonvalvular atrial fibrillation in the United States. Value Health 2006;9:348-56.
4. Kirchhof P, Camm AJ, Goette A, et al. Early rhythm-control therapy in patients with atrial fibrillation. N Engl J Med 2020;383:1305-16.
5. Wazni OM, Dandamudi G, Sood N, et al. Cryoballoon ablation as initial therapy for atrial fibrillation. N Engl J Med 2021;384:316-24.
6. Andrade JG, Wells GA, Deyell MW, et al. Cryoablation or drug therapy for initial treatment of atrial fibrillation. N Engl J Med 2021;384:305-15.
7. Chung MK, Eckhardt LL, Chen LY, 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.
8. Miller JD, Aronis KN, Chrispin J, et al. Obesity, exercise, obstructive sleep apnea, and modifiable atherosclerotic cardiovascular disease risk factors in atrial fibrillation. J Am Coll Cardiol 2015;66:2899-2906.
9. January CT, Wann LS, Calkins H, et al. 2019 AHA/ACC/HRS focused update of the 2014 AHA/ACC/HRS guideline for the management of patients with atrial fibrillation: a report of the American College of Cardiology/American Heart Association task force on clinical practice guidelines and the Heart Rhythm Society. J Am Coll Cardiol 2019;74:104-132.
10. Pathak RK, Middeldorp ME, Meredith M, et al. Long-term effect of goal-directed weight management in an atrial fibrillation cohort: a long-term follow-up study (LEGACY). J Am Coll Cardiol 2015;65:2159-69.
11. Middeldorp ME, Pathak RK, Lau DH, Sanders P. PREVEntion and regReSsive effect of weight-loss and risk factor modification on atrial fibrillation: the REVERSE-AF study-authors' reply. Europace 2019;21:990-91.
12. Pathak RK, Elliott A, Middeldorp ME, et al. Impact of CARDIOrespiratory FITness on arrhythmia recurrence in obese individuals with atrial fibrillation: the CARDIO-FIT study. J Am Coll Cardiol 2015;66:985-96.
13. Csengeri D, Sprunker NA, Di Castelnuovo A, et al. Alcohol consumption, cardiac biomarkers, and risk of atrial fibrillation and adverse outcomes. Eur Heart J 2021;Jan 13:[Epub ahead of print].
14. Voskoboinik A, Kalman JM, De Silva A, et al. Alcohol abstinence in drinkers with atrial fibrillation. N Engl J Med 2020;382:20-28.
15. Pathak RK, Middeldorp ME, Lau DH, et al. Aggressive risk factor reduction study for atrial fibrillation and implications for the outcome of ablation: the ARREST-AF cohort study. J Am Coll Cardiol 2014;64:2222-31.
16. Kanagala R, Murali NS, Friedman PA, et al. Obstructive sleep apnea and the recurrence of atrial fibrillation. Circulation 2003;107:2589-94.
17. Ng CY, Liu T, Shehata M, Stevens S, Chugh SS, Wang X. Meta-analysis of obstructive sleep apnea as predictor of atrial fibrillation recurrence after catheter ablation. Am J Cardiol 2011;108:47-51.
18. Naruse Y, Tada H, Satoh M, et al. Concomitant obstructive sleep apnea increases the recurrence of atrial fibrillation following radiofrequency catheter ablation of atrial fibrillation: clinical impact of continuous positive airway pressure therapy. Heart Rhythm 2013;10:331-37.

Clinical Topics: Arrhythmias and Clinical EP, Cardiovascular Care Team, Diabetes and Cardiometabolic Disease, Dyslipidemia, Prevention, EP Basic Science, SCD/Ventricular Arrhythmias, Atrial Fibrillation/Supraventricular Arrhythmias, Lipid Metabolism, Nonstatins, Exercise, Hypertension, Sleep Apnea

Keywords: Dyslipidemias, Body Mass Index, Anti-Arrhythmia Agents, Atrial Fibrillation, Continuous Positive Airway Pressure, Weight Loss, Metabolic Equivalent, Electric Countershock, Blood Pressure, Numbers Needed To Treat, Follow-Up Studies, American Heart Association, Weight Reduction Programs, Catheter Ablation, Sleep Apnea, Obstructive, Obesity, Risk Factors, Hypertension, Diabetes Mellitus, Stroke, Tobacco Use, Cholesterol, Cholesterol, Alcohol Drinking, Delivery of Health Care, Exercise Therapy, Pharmaceutical Preparations, Reference Standards, Sleep

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