Impact of abdominal obesity on outcomes of catheter ablation in Korean patients with atrial fibrillation

Effects of abdominal obesity on outcomes of atrial fibrillation (AF) ablation remains ill‐defined. Here, we evaluated the impact of abdominal obesity on the long‐term efficacy and safety of catheter AF ablation among Korean patients.


| INTRODUC TI ON
Atrial fibrillation (AF) is a significant public health problem that is associated with a greater risk of stroke and heart failure, reduced quality of life and increased mortality. The increasing prevalence of the condition may, in part, be attributable to rising trends of obesity.
A population-based study demonstrated a global increase in mean body mass index (BMI) over the past four decades in both males (21.7-24.2 kg/m 2 ) and females (22.1-24.4 kg/m 2 ). 1 Furthermore, the authors reported that the age-standardised prevalence of obesity increased significantly over the same duration (males: 3.2%-10.8%; females: 6.4%-14.9%).
Obesity is characterised by an accumulation of adipose tissue, distributed into two main compartments (subcutaneous adipose tissue and visceral adipose tissue) with different metabolic characteristics. There has been more attention on visceral adipose tissue due to its strong association with various cardiovascular pathologies such as AF. The role of obesity in AF per se is complex and likely multifactorial. For example, obesity has been linked to increased left atrial size and decreased left ventricular diastolic function, 2 leading to higher left atrial pressure. A separate mechanism by which obesity may be linked to AF is through the development of obstructive sleep apnoea. Overall, the aforementioned factors are known to promote the initiation and maintenance of AF.
The best anthropometric surrogate of visceral adiposity is abdominal obesity, as defined by waist circumference. This is supported by the fact that waist circumference has been shown to be a better predictor than BMI for cardiovascular risk factors, disease and mortality. 3 Furthermore, waist circumference is an independent component of metabolic syndrome and has been associated with an increased risk of AF. 4 In a meta-analysis of 29 prospective studies, Aune et al 5 found that every 10 cm increase in waist circumference was associated with an 18% greater relative risk of incident AF.
Nonetheless, there is limited evidence on the influence of abdominal obesity on AF ablation, especially in relation to long-term arrhythmia recurrence. In this study, we evaluate the impact of abdominal obesity on the long-term efficacy and safety outcomes of catheter ablation for AF.

| ME THODS
This study was a retrospective cohort analysis using the national health claims established by the National Health Insurance Service (NHIS) of Korea. The national health insurance system in South Korea was established in 1963 and requires compulsory participation from its citizens. At present, the NHIS is responsible for managing all Korean health service databases and discharging the national health examination programs which include a general medical examination for insured employees, or self-employed persons aged over 40 years and their dependents. These examinations are recommended at least biennially. This study was approved by the institutional review board, and the requirement for informed consent was waived. long-term redo AF intervention following catheter ablation but had no effects on total peri-procedural complications.

What's known
• Obesity is strongly linked to atrial fibrillation through various mechanisms.
• The best anthropometric surrogate of visceral adiposity is abdominal obesity, as defined by waist circumference, which has been shown to be a better predictor than body mass index for cardiovascular risk factors, disease and mortality.
• Nonetheless, there is limited evidence on the influence of abdominal obesity on outcomes of catheter ablation for atrial fibrillation.

What's new
• Based on our study, we found that abdominal obesity (defined as waist circumference ≥90 cm for males and ≥85 cm for females) was an independent risk factor for long-term recurrence of atrial fibrillation following catheter ablation.
• Furthermore, abdominal obesity was associated with significantly greater risk of long-term recurrence of atrial fibrillation after index ablation even among obese patients, as defined using body mass index.
• Interestingly, the presence of abdominal obesity was not related to an excess of peri-procedural complications.
Patients were categorised into two groups based on the presence or absence of abdominal obesity (defined as waist circumference ≥90 cm for males and ≥85 cm for females according to 2018 Guideline of Korean Society for the Study of Obesity). 7 Body mass index subgroups were based on the World Health Organization guidelines for the Asia-Pacific region (defined as underweight <18.5 kg/m 2 ; normal 18.5-22.9 kg/m 2 ; overweight 23.0-24.9 kg/m 2 ; and obese ≥25.0 kg/m 2 ). 8

| Covariates
Information regarding comorbid conditions was obtained from inpatient and outpatient hospital diagnoses. Baseline comorbidities were defined using medical claims and prescription medications before the index ablation. The patients were considered to have comorbidities when the condition was a discharge diagnosis or was confirmed at least twice in an outpatient setting, similar to previous studies using Korean NHIS data.

| Clinical outcome events and assessments
The primary endpoint was AF recurrence after index ablation which was determined using surrogate markers of cardioversion or repeat AF ablation. Secondary endpoints were ischemic stroke, intracranial haemorrhage and death. These endpoints were evaluated at  Table S2.

| Statistical analyses
The normality of continuous variables was assessed using Kolmogorov-Smirnov test. Variables with a normal distribution were presented with mean and standard deviations (SDs), and tested for differences with t test. Variables without normal distribution were presented with median and interquartile range (IQR), and tested for differences with Mann-Whitney U test. Categorical variables were presented with count and percentage and tested for differences with chi-squared or Fisher's exact test.
Event rates per 100 patient-years (PYs) were calculated for each study endpoint in the overall cohort and for subsets of patients according to heart failure status and age. Plots of Kaplan-Meier curves for study outcomes were performed and survival distributions were compared using log-rank test. Multivariable cox regression analyses were undertaken to identify independent predictors of AF recurrence following ablation. Multivariable cox regression models for the outcome of interest were created by including covariates that had a univariate significance of P < .10 for the outcome.
Plots of hazard ratios for the recurrence of AF after index ablation according to BMI and waist circumference were adjusted for age, sex, AF duration, cardiovascular implantable electronic device implantation, valvular heart disease, heart failure, hypertrophic cardiomyopathy, previous ischaemic stroke or transient ischaemic attack, previous myocardial infarction, hypertension, diabetes mellitus, chronic kidney disease, chronic obstructive pulmonary disease, liver disease, malignancy, dyslipidaemia, sleep apnoea, hypothyroidism and hyperthyroidism. Because of multicollinearity, waist circumference was excluded in the BMI model and BMI was excluded in the waist circumference model.
A two-sided P value of less than .05 was considered statistically significant. Analyses were performed using SAS version 9.3 (SAS Institute) and R version 3.3.2 (The R Foundation, www.R-proje ct.org).

| Outcomes of AF ablation
The rate of AF recurrence following index ablation was not statistically different among patients with abdominal obesity compared Medication use, n (%)  (Figure 3).
Plots of adjusted hazard ratios for the recurrence of AF after index ablation according to BMI and waist circumference is shown in

| BMI and waist circumference as continuous variables
Multivariable cox regression analyses of BMI and waist circumference as continuous variables demonstrated that both were significantly associated with long-term recurrence of AF after index ablation (

| Procedural complications of AF ablation
There was a total of 302 (5.6%) reported complications of AF ablation ( Table 4). The majority of these were due to pericardial effusion (4.3%).

| D ISCUSS I ON
In this study, we present novel results on the effects of abdominal obesity on long-term outcomes of catheter AF ablation in a large Asian cohort. The main findings were: (a) abdominal obesity was an independent risk factor for long-term AF recurrence following catheter AF ablation; (b) abdominal obesity was associated with a significantly greater risk of long-term AF recurrence after index ablation among obese patients by BMI; (c) abdominal obesity was linked to an increased risk of ischaemic stroke and intracranial haemorrhage but not all-cause death over long-term follow-up; and (d) abdominal obesity did not lead to an excess of overall peri-procedural complications. Furthermore, each 1 cm increase in waist circumference contributed to a 1% increase in the risk of long-term AF recurrence following ablation.

| Impact of abdominal obesity on outcomes of AF ablation
In a prospective study of patients who underwent AF ablation, Shang et al 9 found that waist circumference was an independent predictor of AF recurrence after adjustment for other risk factors.
However, the study comprised only 100 patients with a relatively short follow-up duration of 13 months. Therefore, we regarded the results as hypothesis-generating and thus sought to confirm it in a large cohort of patients. Our current findings confirm that abdominal obesity is indeed an independent risk factor for AF recurrence TA B L E 2 Effects of abdominal obesity on outcomes of atrial fibrillation ablation at 1, 3 and 6 years follow-up

| Impact of BMI on outcomes of AF ablation
Unlike abdominal obesity, the effects of BMI as an anthropometric marker of visceral adiposity on outcomes of AF ablation have been evaluated on several occasions. Initial reports were conflicting as some studies demonstrated no association between these factors, 10 while others found that increased BMI led to a greater risk of AF recurrence post-ablation. 11 However, the majority were limited by either a small sample size or a relatively short duration of follow-up.
A study of 2715 patients undergoing AF ablation found that raised BMI was associated with an increased risk of AF recurrence over five years. 12 Indeed, two independent meta-analyses have confirmed that higher BMI is predictive of AF recurrence following ablation therapy. 13,14 Wong et al 13 reported that every five-unit increase in BMI was associated with a 13% excess risk of AF recurrence in the post-ablation period. However, these results which were based on a majority of studies with a Caucasian population may not be applicable in an Asian cohort. Thus, our study provides useful information in this regard. Here, we found that every unit increase in BMI was associated with a 3% excess risk of long-term AF recurrence following ablation.

| Comparison of abdominal obesity and BMI
Despite evidence supporting the role of BMI as a predictive marker for the outcomes of AF ablation, it has limited accuracy in the diagnosis of obesity and has been shown to "miss" more than half of patients with excess fat. 15 Furthermore, its implementation may lead to additional misclassification bias in certain populations. For example, Asians tend to have a higher percentage of abdominal adipose tissue for any given BMI compared with Whites. 16 In terms of clinical events, Hamada et al 17 found a significantly elevated risk of incident AF with increased waist circumference, independent of BMI and other risk factors. We have also previously demonstrated similar findings that were particularly evident among non-obese Asian patients. 18 These results suggest that waist circumference may be superior to BMI for the prediction of incident AF. Moreover, the study by Shang et al 9 reported that of seven obesity indices, waist circumference was the only independent predictor of AF recurrence following ablation. Our study adds to this as it demonstrates that among patients with obesity by BMI, the additional presence of abdominal obesity was associated with a significantly elevated risk of AF recurrence following ablation. Overall, abdominal obesity as determined by waist circumference is an important marker that may be used to risk stratify patients prior to AF ablation.

| Complications of AF ablation
In our study, the total peri-procedural complication rate was comparable between patients with or without abdominal obesity. Similar findings were reported elsewhere using BMI classification, 19

| Limitations
Our study has several limitations. First, the incidence of AF recurrence was relatively low compared with other studies. 10 This was likely related to the fact that AF recurrence was determined using rates of cardioversion and repeat ablation. The latter may also provide an explanation for the apparent finding that increasing age was associated with a reduced risk of AF recurrence, as older patients are often deemed less favourable candidates for invasive procedures. Nonetheless, we have proven that this method of assessment had a high positive predictive value for true AF recurrence as determined by electrocardiographic and Holter monitoring (Table S5)

| CON CLUS IONS
Abdominal obesity as indicated by waist circumference was associated with a greater burden of concomitant diseases and proved to be an independent risk factor for long-term redo AF intervention following catheter ablation among Korean patients though it had no significant impact on the rate of total peri-procedural complications.
Furthermore, among obese patients by BMI, the additional presence of abdominal obesity contributed to an increased risk of redo AF intervention post-ablation. Thus, waist circumference may provide a useful, simple marker for clinical risk stratification to guide clinical decision making in patients undergoing AF ablation and serve as a potentially modifiable risk factor to improve long-term outcomes.

AUTH O R CO NTR I B UTI O N S
BJ and GYHL contributed to the design of the study. PSY analysed and interpreted the data. WYD interpreted the data and drafted the manuscript. PSY, EJ, JHS, BJ and GYHL revised the manuscript critically for important intellectual content.

DATA AVA I L A B I L I T Y S TAT E M E N T
The data underlying this article will be shared on reasonable request to the corresponding author. TA B L E 4 Impact of abdominal obesity on complications of atrial fibrillation ablation