Losing Weight Helps Afib

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The obesity epidemic continues its relentless advance and is paralleled by an increase in the incidence of AF. Several epidemiological studies have highlighted obesity as an independent risk factor for the development of AF. This relationship is likely multifactorial through a number of interacting mechanisms. Weight loss through lifestyle changes or surgery has been associated with reverse remodelling of the atrial substrate and subsequent reduction in AF, making it an essential pillar in the management of AF in obese patients. In this review, the epidemiological data that support the obesity–AF relationship, the current insights into the underlying pathophysiological mechanism, the impact of weight loss on reverse remodelling and AF reduction, and the strategies to achieve weight loss in patients with AF are discussed.

Disclosure:JMK is supported by a practitioner fellowship from the NHMRC. He has received research support from Biosense Webster, Abbott and Medtronic, and has served on the advisory board of Biosense Webster. AMAK has no conflicts of interest to declare.

Atrial Fibrillation: What You Need To Know

The obesity epidemic continues its relentless advance, currently affecting 2 billion people.1 Obesity is associated with an increased burden of a spectrum of diseases, with the focus in this article being on AF. The health-related burden associated with obesity is estimated to have a substantial economic impact.2 In alignment with this epidemic, the prevalence of AF is increasing. In the US, a large observational study showed a significant increase in the incidence of new AF between 1980 and 2000, and estimated that the projected number of persons with AF in the US would exceed 10 million by 2050.3 Similar trends have been seen in Europe and Australia.4, 5 The pathophysiological mechanisms that underline the AF–obesity relationship remain incompletely understood. There are, however, consistent data that support weight management in improving AF outcomes. In this review, we discuss the AF–obesity relationship, the proposed underlying mechanisms, and the impact of weight loss on AF and its arrhythmogenic substrate.

A number of observational cohort studies have highlighted obesity as an independent risk factor for the development of AF.6–11 In the Framingham Heart Study, 526 out of 5, 282 participants developed AF over a mean follow-up of 13.7 years.11 Obesity was found to be an independent predictor for incident AF after adjusting for traditional risk factors. Similar findings were found in the Women’s Heart Study, where incident AF was confirmed in 2.4% of the cohort over a 12.9-year follow-up period.9 BMI was linearly associated with AF risk, with a 4.7% increase in risk with each kg/m2.

To examine the impact of the obesity-associated traditional risk factors on the AF risk, a recent retrospective Korean study studied the AF risk among a cohort of metabolically healthy obese individuals (no diabetes, hypertension and dyslipidaemia) compared with metabolically unhealthy obese and non-obese individuals.8 Compared with non-obese individuals, the metabolically healthy obese cohort had a 20% increased AF risk, whereas metabolic unhealthiness increased the AF risk by 40%. In addition, elevated BMI has been shown to be associated with AF clinical phenotype progression from paroxysmal to persistent.10 In the Olmsted County study, where 3, 248 patients with paroxysmal AF were followed up, 17% progressed to persistent AF. Obesity was independently associated with progression to persistent AF, even after adjusting for traditional risk factors, signalling its impact on the arrhythmogenic substrate of AF.

Hrs 2023: Weight Loss Prior To Catheter Ablation Improves Outcomes In Obese Af Patients

However, while the aforementioned evidence supports the obesity–AF relationship, the mechanism underpinning the impact of obesity on the incidence of AF remains incompletely understood and is likely multifactorial (

). In the next section, we discuss the potential mechanisms that underpin the obesity–AF relationship, highlighting the recent insights from both animal and human studies.

Obesity leads to left atrial and ventricular remodelling through a number of haemodynamic mechanisms. Obesity is associated with an increase in both cardiac output and systolic blood pressure with little change in the heart rate.12 This is related to both activation of the renin–angiotensin–aldosterone system and enhancement of the sympathetic nervous system.13 This increase in cardiac output will increase venous return to the heart, leading to enhanced atrial and ventricular wall stretch, and eventually dilatation.14 Moreover, obesity has a haemodynamic impact on the heart through the associated medical comorbidities, such as hypertension, sleep apnoea and insulin resistance. Hypertension increases left ventricular afterload, leading to further structural remodelling in the form of left ventricular hypertrophy, diastolic dysfunction and left atrial dilatation.15 Obesity-associated sleep-disordered breathing is associated with surges in symptomatic nervous system activity through intermittent episodes of hypoxia, which has been shown to be associated with a significant increase in the prevalence of both atrial and ventricular arrhythmia, even after adjusting for traditional risk factors.16

Outcomes Of Atrial Fibrillation Ablation In Morbidly Obese Patients Following Bariatric Surgery Compared With A Nonobese Cohort

Animal studies have consistently demonstrated the presence of an arrhythmogenic substrate in association with obesity. In an ovine model, progressive changes in electrical and structural atrial remodelling were seen in a cohort of 30 sheep being fed a high-calorie diet over an 8-month period.17 Increasing weight was associated with increasing left atrial (LA) volume, LA fibrosis and upregulation of inflammatory markers. The net effect was decreased conduction velocity and an increase in conduction heterogeneity, with an associated increase in both inducible and spontaneous AF. Other animal studies noted that a high-fat diet could increase AF duration due to slow atrial conduction and reduced pulmonary vein refractoriness. These changes could occur without necessarily being accompanied by development of obesity.18, 19

Similar abnormal substrate has been seen in human studies. A large observational longitudinal study found that obesity was a strong predictor of LA enlargement, after adjusting for age and sex.5 Moreover, Mahajan et al. characterised the electroanatomic atrial remodelling and epicardial adipose tissue in a cohort of obese patients and compared it with a non-obese cohort.20 Obesity was associated with an increase in all measures of epicardial adipose tissue, with a predominant distribution adjacent to the posterior left atrium and the atrioventricular groove. Obese patients had reduced global conduction velocity, increased fractionation and increased low-voltage areas. Low-voltage areas were predominantly seen in the posterior and/or inferior LA, matching the location of epicardial adipose tissue (EAT) on cardiovascular MRI.

The availability of cross-sectional imaging modalities such as cardiac computed tomography has enabled us to examine the relationship between the quantity and quality of the EAT and AF. This layer of adipose tissue is located between the visceral pericardial and the epicardial surface, and there is no fascial layer that separates the EAT and the myocardium. Epidemiological studies utilising non-invasive imaging with a focus on the abundance of EAT have consistently demonstrated an independent association between EAT volume and incident AF, even after adjusting for AF risk factors, including BMI and LA enlargement.21, 22 Beyond predicting AF, this association appears to impact on the outcome of AF ablation.23 However, the underlying electrophysiological, cellular and molecular mechanisms that link epicardial adipose tissue with AF progression remain poorly defined, and a number of mechanistic theories have been proposed.

How To Treat Atrial Fibrillation: Can Natural Remedies Help?

The proximity of the EAT layer to the myocardium means the EAT can exert important paracrine and vasocrine effects on neighbouring cardiomyocytes.24, 25 In chronic inflammatory disorders, the epicardium becomes a site of deranged adipogenesis, leading to secretion of pro-inflammatory adipokines, such as interleukin-1β, interleukin-6, activin-A and tumour necrosis factor-alpha, which may play an important role in the development of atrial fibrosis.26 In an ovine model, Mahajan et al. demonstrated that sustained obesity resulted in global biatrial endocardial electrical and structural remodelling, and associated EAT infiltration in the posterior LA wall.27 A cohort of 10 sheep fed a calorie-dense diet to induce obesity were compared with 10 lean sheep, and all 20 sheep underwent invasive and non-invasive assessments of their atrial substrate. Compared with the lean sheep cohort, the obese sheep demonstrated both abnormal structural (increased LA volume and pressure) and electrical (reduced atrial conduction velocity, increased conduction heterogeneity, increased fractionated electrograms and decreased posterior LA voltage) remodelling. This was associated with more frequent, prolonged and greater cumulative duration of AF. Epicardial fat was seen to infiltrate the posterior LA in the obese group, and was associated with reduced endocardial voltage in this region.

Prior tissue culture studies have shown that epicardial adipose tissue is capable of releasing adipo-fibrokines, promoting atrial fibrosis and its associated electrical substrate.28, 29 The critical role local EAT has on the atrial substrate was elegantly demonstrated in a recent study.30 In a cohort of patients undergoing cardiac surgery without AF, higher local epicardial adipose tissue volume on imaging correlated with slowed conduction, greater electrogram fractionation, increased fibrosis and lateralisation of cardiomyocyte connexin-40 (

). Moreover, atrial conduction heterogeneity was increased with more extensive myocardial adipose infiltration. Cardiomyocyte culture studies using multielectrode arrays showed that cardiac adipose tissue-secreted factors slowed conduction velocity and contained proteins with capacity to disrupt intermyocyte electromechanical integrity.

Effect Of Weight Loss On Recurrence Of Atrial Fibrillation After Ablative Therapy: A Systematic Review And Meta Analysis

Recently, non-invasive assessment of the EAT activity on CT has gained significant interest. As inflammation increases, a significant change in the degree of epicardial fat attenuation values represented by Hounsfield units can be detected.31 This suggests that EAT attenuation may serve as a

Animal studies have consistently demonstrated the presence of an arrhythmogenic substrate in association with obesity. In an ovine model, progressive changes in electrical and structural atrial remodelling were seen in a cohort of 30 sheep being fed a high-calorie diet over an 8-month period.17 Increasing weight was associated with increasing left atrial (LA) volume, LA fibrosis and upregulation of inflammatory markers. The net effect was decreased conduction velocity and an increase in conduction heterogeneity, with an associated increase in both inducible and spontaneous AF. Other animal studies noted that a high-fat diet could increase AF duration due to slow atrial conduction and reduced pulmonary vein refractoriness. These changes could occur without necessarily being accompanied by development of obesity.18, 19

Similar abnormal substrate has been seen in human studies. A large observational longitudinal study found that obesity was a strong predictor of LA enlargement, after adjusting for age and sex.5 Moreover, Mahajan et al. characterised the electroanatomic atrial remodelling and epicardial adipose tissue in a cohort of obese patients and compared it with a non-obese cohort.20 Obesity was associated with an increase in all measures of epicardial adipose tissue, with a predominant distribution adjacent to the posterior left atrium and the atrioventricular groove. Obese patients had reduced global conduction velocity, increased fractionation and increased low-voltage areas. Low-voltage areas were predominantly seen in the posterior and/or inferior LA, matching the location of epicardial adipose tissue (EAT) on cardiovascular MRI.

The availability of cross-sectional imaging modalities such as cardiac computed tomography has enabled us to examine the relationship between the quantity and quality of the EAT and AF. This layer of adipose tissue is located between the visceral pericardial and the epicardial surface, and there is no fascial layer that separates the EAT and the myocardium. Epidemiological studies utilising non-invasive imaging with a focus on the abundance of EAT have consistently demonstrated an independent association between EAT volume and incident AF, even after adjusting for AF risk factors, including BMI and LA enlargement.21, 22 Beyond predicting AF, this association appears to impact on the outcome of AF ablation.23 However, the underlying electrophysiological, cellular and molecular mechanisms that link epicardial adipose tissue with AF progression remain poorly defined, and a number of mechanistic theories have been proposed.

How To Treat Atrial Fibrillation: Can Natural Remedies Help?

The proximity of the EAT layer to the myocardium means the EAT can exert important paracrine and vasocrine effects on neighbouring cardiomyocytes.24, 25 In chronic inflammatory disorders, the epicardium becomes a site of deranged adipogenesis, leading to secretion of pro-inflammatory adipokines, such as interleukin-1β, interleukin-6, activin-A and tumour necrosis factor-alpha, which may play an important role in the development of atrial fibrosis.26 In an ovine model, Mahajan et al. demonstrated that sustained obesity resulted in global biatrial endocardial electrical and structural remodelling, and associated EAT infiltration in the posterior LA wall.27 A cohort of 10 sheep fed a calorie-dense diet to induce obesity were compared with 10 lean sheep, and all 20 sheep underwent invasive and non-invasive assessments of their atrial substrate. Compared with the lean sheep cohort, the obese sheep demonstrated both abnormal structural (increased LA volume and pressure) and electrical (reduced atrial conduction velocity, increased conduction heterogeneity, increased fractionated electrograms and decreased posterior LA voltage) remodelling. This was associated with more frequent, prolonged and greater cumulative duration of AF. Epicardial fat was seen to infiltrate the posterior LA in the obese group, and was associated with reduced endocardial voltage in this region.

Prior tissue culture studies have shown that epicardial adipose tissue is capable of releasing adipo-fibrokines, promoting atrial fibrosis and its associated electrical substrate.28, 29 The critical role local EAT has on the atrial substrate was elegantly demonstrated in a recent study.30 In a cohort of patients undergoing cardiac surgery without AF, higher local epicardial adipose tissue volume on imaging correlated with slowed conduction, greater electrogram fractionation, increased fibrosis and lateralisation of cardiomyocyte connexin-40 (

). Moreover, atrial conduction heterogeneity was increased with more extensive myocardial adipose infiltration. Cardiomyocyte culture studies using multielectrode arrays showed that cardiac adipose tissue-secreted factors slowed conduction velocity and contained proteins with capacity to disrupt intermyocyte electromechanical integrity.

Effect Of Weight Loss On Recurrence Of Atrial Fibrillation After Ablative Therapy: A Systematic Review And Meta Analysis

Recently, non-invasive assessment of the EAT activity on CT has gained significant interest. As inflammation increases, a significant change in the degree of epicardial fat attenuation values represented by Hounsfield units can be detected.31 This suggests that EAT attenuation may serve as a