Atrial fibrillation in patients with obesity: How can we optimize management?

OBESITY AND ATRIAL FIBRILLATION

An estimated 60 million people worldwide have atrial fibrillation, a number projected to rise by more than 60% by 2050.¹ More than half of adults globally are classified as having overweight or obesity, and obesity is the second strongest predictor that an individual will develop atrial fibrillation, after hypertension.¹ Obesity increases the risk of new-onset atrial fibrillation by 50%, and each 5-unit rise in body mass index (BMI) increases atrial fibrillation incidence by 30%, underscoring the growing burden of obesity-related atrial fibrillation.¹

Class I obesity (BMI 30–34.9 kg/m²) is associated with a 54% higher risk of progressing from paroxysmal to permanent atrial fibrillation, while class II obesity (BMI 35.0–39.9 kg/m²) is associated with an 87% higher risk.² Higher BMI is positively associated with left atrial enlargement due to chronic volume overload and elevated cardiac output, leading to sustained pressure, wall stress, and atrial remodeling.³ This remodeling, characterized by stretching of myocytes and fibrosis, disrupts conduction pathways, promotes reentry, and activates stretch-sensitive ion channels.³ Left atrial enlargement and conduction abnormalities are also linked to poorer ablation outcomes and higher atrial fibrillation recurrence rates.³

HEART RATE CONTROL

Although obesity has been shown to alter the pharmacokinetics of lipophilic beta-blockers, such as altering the volume and distribution of the drugs, clinical studies show that it does not significantly affect their therapeutic efficacy.¹ Currently, there are no formal recommendations for beta-blocker dose adjustments for patients with obesity; however, tailoring the dose based on clinical response and possibly monitoring pharmacokinetics may be indicated in patients with obesity who are using beta-blockers.⁵

In those with heart failure with preserved ejection fraction, lower beta-blocker doses and personalized regimens may help avoid excessive rate control and ventricular rates below 75 beats per minute.⁶

HEART RHYTHM CONTROL

In patients with obesity, an increased joule threshold is needed to achieve successful electrical cardioversion and control heart rhythm due to greater body weight and increased distance to the atrium.⁷ Routine use of adhesive patches at 200 J is less likely to be successful in patients with obesity, suggesting that other electrical cardioversion strategies, such as using paddles at 360 J, may be more efficacious.⁷

Patients with obesity and atrial fibrillation have a higher rate of atrial fibrillation recurrence after catheter ablation to control heart rhythm, even if the procedure is successful.⁸ Patients with morbid (class III) obesity undergoing ablation experience higher complication rates, longer hospital stays, and greater 30-day hospitalization costs compared with patients with class I obesity and those without overweight or obesity.⁸ Preablation weight loss lowers the rate of 1-year atrial fibrillation recurrence in patients with and without obesity.⁹

ANTICOAGULATION

Post hoc analyses and large studies have shown that direct oral anticoagulants are as safe and effective as warfarin across all weight groups, including class III obesity.¹⁰ Therefore, direct oral anticoagulants are preferred for stroke prevention in patients with obesity, except in those with moderate-to-severe mitral stenosis or with a prosthetic heart valve.¹¹ Limited data exist on direct oral anticoagulant use after bariatric surgery in patients with atrial fibrillation; warfarin may be preferred in this population until more evidence emerges.¹²

OBSTRUCTIVE SLEEP APNEA SCREENING AND TREATMENT

Obstructive sleep apnea is highly prevalent, and underdiagnosed, in patients with obesity and recurrent atrial fibrillation, especially after ablation.¹ Repetitive upper airway obstruction leads to cyclical oxygen desaturation and intermittent hypoxia, which trigger norepinephrine surges that increase sympathetic nervous system activity and heart rate variability and after-load.^13,14 Closed airways generate markedly negative intrathoracic pressure (−60 to −80 mm Hg), increasing atrial wall stress and pulmonary venous return and triggering electrical remodeling.¹³ Changes in autonomic tone, mediated via vagal and sympathetic nerves, modulate ion channel expression, which enhances atrial fibrillation vulnerability.¹³

Routine obstructive sleep apnea screening and home sleep apnea testing are recommended to identify undiagnosed obstructive sleep apnea,^15,16 especially after ablation or cardioversion. The STOP-BANG (snoring, tiredness, observed apnea, blood pressure, BMI, age, neck circumference, and gender) assessment is the preferred screening method due to its higher sensitivity—around 90% for various levels of obstructive sleep apnea severity—but its specificity is notably low, around 36%.¹⁷ Treatment with continuous positive airway pressure is advised, as it reduces the risk of progression to permanent atrial fibrillation.¹⁶

BARIATRIC SURGERY

Bariatric surgery is associated with lower incidence of new-onset atrial fibrillation, demonstrating a measurable reduction in long-term atrial fibrillation risk. In a retrospective study with an average 12 years of follow-up, patients with no history of atrial fibrillation who underwent bariatric surgery had a lower risk of developing new-onset atrial fibrillation and a higher rate of atrial fibrillation resolution, compared with patients who did not undergo bariatric surgery.¹⁸ Because bariatric surgery significantly reduces the risk of developing atrial fibrillation and obesity, we recommend this procedure for patients at high risk of developing new-onset or recurrent atrial fibrillation.

NEUROHORMONAL CONTROL WITH BOTULINUM TOXIN INJECTION

Within epicardial fat are multiple ganglionic plexuses (ie, clusters of nerve cell bodies) that integrate vagal and sympathetic signals to control heart rate and contractility.¹ Increased epicardial fat volume and thickness independently predict higher risk of atrial fibrillation recurrence after ablation, likely mediated by inflammatory cytokines, fibrotic remodeling, and changes in neurohormonal conduction in the ganglionic plexuses.^1,19 Hyperactivity in the ganglionic plexuses promotes atrial fibrillation by stimulating the vagal nerve, which increases heterogeneity in the time interval during which the atria are unresponsive to electrical stimulation, ie, the atrial refractory period, and by activating the sympathetic nervous system, which enhances the movement of calcium in and out of cardiac myocytes, shortening the refractory period.¹ Hypoxemia, hyperleptinemia, and insulin resistance further augment activation of the sympathetic nervous system.¹

Injecting botulinum toxin into the ganglionic plexuses in epicardial fat pads to suppress autonomic activity has been shown to effectively control atrial tachyarrhythmia after surgery, especially in patients who have undergone cardiac surgery.¹ In patients with a history of paroxysmal atrial fibrillation who underwent coronary artery bypass grafting, this intervention significantly reduced incident postoperative atrial fibrillation during the first 30 days after surgery, with an absolute risk reduction of 23% (number needed to treat 4.3) and relative risk reduction of 78% compared with placebo.²⁰ Up to 1 year after surgery, none of the patients who received botulinum toxin injection had recurrent atrial fibrillation, and no complications were observed.^20–22

ROLE OF GLP-1 RECEPTOR AGONISTS AND SGLT-2 INHIBITORS

In addition to promoting weight loss and controlling diabetes in patients with obesity, GLP-1 receptor agonists and SGLT-2 inhibitors reduce epicardial fat and inflammatory neurohormonal activity.^23,24 In a meta-analysis, patients taking the GLP-1 receptor agonist semaglutide had a 17% reduction in new-onset atrial fibrillation incidence (odds ratio 0.83, 95% confidence interval 0.70–0.98, P = .03).²⁵ This reduction was more pronounced in those taking the oral formulation, which reduced atrial fibrillation incidence by 52% (odds ratio 0.48, 95% confidence interval 0.24–0.95, P = .04). However, meta-regression analysis found no link between the reduced risk of atrial fibrillation and BMI, suggesting the effect may not be solely mediated by weight loss.²⁵ In another meta-analysis, SGLT-2 inhibitors reduced the risk of incident atrial fibrillation by 24% even with minimal weight loss,²⁶ again suggesting that other mechanisms beyond weight reduction may account for the lower risk, such as hemodynamic effects and anti-inflammatory pathways.²⁵ GLP-1 receptor agonists and SGLT-2 inhibitors may offer adjunctive treatment for atrial fibrillation in patients with obesity by targeting underlying metabolic and structural factors.

TAKE-HOME POINTS

• Adjusting beta-blocker doses may not be warranted, but some patients with obesity and atrial fibrillation may benefit from personalized lower-dose regimens.

• Direct oral anticoagulants are generally suitable for anticoagulation, but warfarin is preferable after bariatric surgery.

• Using paddles at 360 J for electrical cardioversion may be more efficacious in patients with obesity.

• Losing weight before catheter ablation reduces atrial fibrillation recurrence and improves catheter ablation success rates.

• Bariatric surgery should be considered more often.

• Patients should be routinely screened for obstructive sleep apnea and treated with continuous positive airway pressure, as needed.

• Injecting botulinum toxin into epicardial fat pads may help control atrial tachyarrhythmias, particularly after cardiac surgery.

• GLP-1 receptor agonists and SGLT-2 inhibitors offer effective adjunctive treatment for atrial fibrillation in patients with obesity by reducing weight and inflammation and reducing the risk of atrial fibrillation onset and recurrence.

DISCLOSURES

The authors report no relevant financial relationships which, in the context of their contributions, could be perceived as a potential conflict of interest.