Author + information
- Received May 27, 2018
- Revision received July 2, 2018
- Accepted August 7, 2018
- Published online December 17, 2018.
- Rajiv Mahajan, MD, PhDa,b,
- Adam Nelson, MBBSa,
- Rajeev K. Pathak, MBBS, PhDa,
- Melissa E. Middeldorpa,
- Christopher X. Wong, MBBS, PhDa,
- Darragh J. Twomey, MBBS, PhDa,
- Angelo Carbone, BSca,
- Karen Teo, MBBS, PhDa,
- Thomas Agbaedeng, BSca,
- Dominik Linz, MD, PhDa,
- Joris R. de Groot, MD, PhDc,
- Jonathan M. Kalman, MBBS, PhDd,e,
- Dennis H. Lau, MBBS, PhDa and
- Prashanthan Sanders, MBBS, PhDa,∗ ()
- aCentre for Heart Rhythm Disorders, South Australian Health and Medical Research Institute, University of Adelaide and Royal Adelaide Hospital, Adelaide, Australia
- bDepartment of Cardiology, Lyell McEwin Hospital, Adelaide, Australia
- cHeart Center, Department of Cardiology, Academic Medical Center, Amsterdam, the Netherlands
- dDepartment of Cardiology, Royal Melbourne Hospital, Melbourne, Australia
- eDepartment of Medicine, University of Melbourne, Melbourne, Australia
- ↵∗Address for correspondence:
Dr. Prashanthan Sanders, Centre for Heart Rhythm Disorders (CHRD), Department of Cardiology, Royal Adelaide Hospital, Port Road, Adelaide, SA 5000, Australia.
Objectives The aims of the study were to characterize: 1) electrical and electroanatomical remodeling in patients with atrial fibrillation (AF) with obesity; and 2) the impact of epicardial fat depots on adjacent atrial tissue.
Background Obesity is associated with an increased risk of AF.
Methods A total of 115 patients with AF who underwent AF ablation were screened. After exclusion, 26 patients were divided into 2 groups (obese: body mass index [BMI] ≥27 kg/m2 and reference: BMI <27 kg/m2). They underwent cardiac magnetic resonance (CMR) imaging and electroanatomic mapping of the left atrium (LA) in sinus rhythm before AF ablation. Atrial and ventricular epicardial adipose tissue (EAT) were assessed by CMR. The following electrophysiological parameters were assessed: global and regional voltage, conduction velocity (CV), electrogram fractionation, and CV heterogeneity. In addition, the regional relationship between LA EAT depots and the electrophysiological substrate was evaluated.
Results The BMIs of the obese and reference groups were 30.2 ± 2.6 and 25.2 ± 1.3 kg/m2, respectively (p < 0.001). There was no difference in the left ventricular ejection fraction and a nonsignificant increase in LA size with obesity. Obesity was associated with increase in all measures of EAT (p < 0.05), with a predominant distribution adjacent to the posterior LA and the atrioventricular groove. Obesity was associated with reduced global CV (0.86 ± 0.31 m/s vs. 1.26 ± 0.29 m/s; p < 0.001), with a nonsignificant increase in conduction heterogeneity (p = 0.10), increased fractionation (54 ± 17% vs. 25 ± 10%; p < 0.001), and regional alteration in voltage (p < 0.001). Although the global LA voltage was preserved, there was greater voltage heterogeneity (p = 0.001) and increased low-voltage areas (13.9% vs. 3.4%; p < 0.001) in the obese group compared with the reference group. The low voltage areas were predominantly seen in the posterior and/or inferior LA, which was similar to location of EAT on CMR imaging. Among various measures of obesity, LA EAT volume correlated best with posterior LA fractionation (r2 = 0.55 for LA EAT volume vs. r2 = 0.36 for BMI) and CV (r2 = 0.31 for LA EAT volume vs. r2 = 0.22 for BMI).
Conclusions Obesity is associated with electroanatomical remodeling of the atria, with areas of low voltage, conduction slowing, and greater fractionation of electrograms. These changes were more pronounced in regions adjacent to epicardial fat depots, which suggested a role for fat depots in the development of the AF substrate.
Atrial fibrillation (AF) is the most common sustained arrhythmia known to affect humans; it results in significant morbidity and mortality (1). The identification of significant atrial remodeling, in the absence of apparent heart disease (2), has cast doubts on the existence of “lone AF” and reinforced the contribution of novel AF risk factors (3–6). Obesity is one such novel risk factor that has been established to be independently associated with AF (7–9). Although the pathogenic mechanisms linking obesity and AF are highly complex and remain incompletely understood, recent experimental studies have demonstrated the important contributory roles of diastolic dysfunction, atrial fibrosis, and conduction abnormalities with weight gain in an ovine model (4,10). We recently extended these observations to also demonstrate invasion of the atrial myocardium by adjacent epicardial adipose tissue (EAT), which forms a unique component of the substrate for AF (4). Although experimental studies have delineated electrical remodeling with obesity, there is a paucity of data in humans (11). Many studies have evaluated the relationship between systemic measures of adiposity and AF; however, cardiac ectopic fat depots have only recently been shown to be associated with a propensity and severity of AF (12–15). Experimental studies have demonstrated that EAT contributes to atrial substrate development by secreting pro-fibrotic cytokines (16) and directly infiltrates contiguous atrial tissue (4). In light of the preceding information, the aims of this clinical study were to characterize 1) the electrophysiological and electroanatomical remodeling of the atria due to obesity in patients with AF, and 2) to determine the impact of EAT on the electrophysiological properties of the adjacent atrial myocardium.
Consecutive patients who underwent catheter ablation of AF at the Centre for Heart Rhythm Disorders, University of Adelaide, and the Royal Adelaide Hospital, Adelaide, Australia, were screened for inclusion. The inclusion criterion was symptomatic AF refractory to at least 1 antiarrhythmic medication. To specifically look at the interaction between obesity and EAT and AF, concomitant conditions that could affect this relation were strictly excluded. The exclusion criteria were: 1) long-standing persistent AF; 2) previous left atrial (LA) ablation; 3) contraindication to cardiac magnetic resonance imaging (CMR); 4) restrictive or hypertrophic cardiomyopathy; 5) valvular heart disease; 6) left ventricular dysfunction (left ventricular ejection fraction [LVEF] <45%); 7) uncontrolled hypertension with LV hypertrophy (LV wall thickness ≥12 mm); 8) uncontrolled diabetes mellitus with glycosylated hemoglobin of >7%; 9) amiodarone use in previous 6 months; 10) LA thrombus; 11) atrial arrhythmia of >30 s in the 7 days before the procedure by continuous monitoring; 12) pregnancy; and 13) inability to provide informed consent.
The type of AF was defined in accordance to the Heart Rhythm Society Consensus Statement (17). Paroxysmal AF was defined as recurrent AF that terminated spontaneously within 7 days. Persistent AF was defined as AF that was sustained beyond 7 days, or lasted >48 h and <7 days but necessitated pharmacological or electrical cardioversion.
A sample size of minimum 10 patients per group provided 80% power (alpha = 0.05) to detect a 0.4 m/s difference (effect size = 1.33) in conduction velocity (CV), assuming a reference value of 1.3 ± 0.3 m/s (4). The enrolled patients provided written informed consent for the study protocol, which was approved by the Human Research Ethics Committee of the Royal Adelaide Hospital and the University of Adelaide, Adelaide, Australia.
The patients were allocated into the following 2 groups according to their body mass index (BMI): 1) obese group with a BMI ≥27 kg/m2; and 2) reference group with a BMI <27 kg/m2. All patients underwent detailed clinical evaluation, CMR imaging, and electrophysiological mapping before ablation. All antiarrhythmic drugs were held for >5 half-lives.
CMR protocol and analysis
The patients underwent CMR imaging (1.5-T, Siemens Avanto, Siemens Medical Solutions, Erlangen, Germany) within the 4 weeks before ablation. Sequential steady-state free precession short-axis cine sequences were acquired with 6-mm slice thickness and no interslice gaps through the atria, as well as 6-mm slice thickness with a 4-mm gap through the ventricles. Slices were taken from the most cranial aspect of the LA and sequentially to the cardiac apex at end expiration. The atria were also imaged in the horizontal long-axis plane with 6-mm slice thickness and no interslice gaps. Typical imaging parameters were echo time of 1.2 ms, repetition time of 63.7 ms, flip angle of 80°, matrix size of 192 × 156, and field of view of 360 to 440 mm.
Epicardial fat quantification
EAT volumes were measured offline by 2 blinded investigators (A.N., A.C.) using proprietary software (Argus, Siemens Medical Solutions, Erlangen, Germany). EAT was defined as regions of high-signal intensity between the myoepicardium and parietal pericardium (i.e., fat inside the pericardial sac) (18). The ventricular EAT was defined as EAT extending from the mitral valve hinge down to the ventricular apex, inclusive of the most inferior margin of the adipose tissue. The atrial EAT was defined as the EAT subtending to the atria and lying above the mitral valve hinge and below the right pulmonary artery (18). Areas of fat were manually traced on consecutive end-diastolic short-axis images and multiplied by the slice thickness to derive volume. Intra- and interobserver reproducibility with this technique was excellent (coefficient of variation: 3.5% and 4.9%, respectively). The following EAT measures were calculated: LA EAT, atrial EAT (sum of right and left EAT), and total EAT (sum of atrial and ventricular EAT). The EAT located between the left and right pulmonary veins was designated as posterior LA EAT. The EAT subtending to the LA appendage (LAA) was designated as LAA EAT (lateral segment). The LA EAT, which was predominantly distributed posteriorly and along the atrioventricular groove, was not further subdivided for quantitative analysis due to decreased reproducibility of smaller quantities of EAT.
Chamber volume analysis
The LV was manually traced at end-diastole and end-systole, with the most basal slice determined by at least 50% of ventricular myocardium surrounding the blood pool. The LA was manually traced using a disc summation method at ventricular end-systole and end-diastole. The borders of the LA were defined as the plane of the mitral valve and the visually apparent juncture of the LA with pulmonary veins.
Electroanatomic mapping was performed in fasting state before ablation. The following catheters were positioned: 1) 10-pole catheter (2-5-2 mm spacing; Daig Electrophysiology, Minnetonka, Minnesota) positioned in the coronary sinus as a reference electrode with the proximal bipole at the ostium of the coronary sinus in best septal left anterior oblique projection; and 2) a 3.5-mm tip Navi-Star ablation catheter (Biosense-Webster, Diamond Bar, California). The electroanatomic mapping system was previously described in detail (2).
Electroanatomic mapping of the LA and the analysis for the study was undertaken as previously described and validated (19). In brief, a LA map was created in sinus rhythm using a fill threshold of 15 mm. Contact at the site of point of acquisition was facilitated by fluoroscopy and catheter icon on the CARTO system (Biosense Webster, Diamond Bar, California). The points were acquired in the autofreeze mode, if the stability criteria in space (≤6 mm) and local activation time (≤5 ms) were satisfied. Editing of points was performed offline. Local activation time was manually annotated to the peak of the largest amplitude deflection on bipolar electrograms; in the presence of double potentials, this was annotated at the larger potential. If the bipolar electrogram displayed equivalent maximum positive and negative deflections, the maximum negative deflection on the simultaneously acquired unipolar electrogram was used to annotate the local activation time. Points that did not conform to the surface electrocardiogram P-wave morphology or <75% of the maximum voltage of the preceding electrogram were excluded. Points within the pulmonary veins were excluded. The map was edited to ensure an equitable distribution of points.
For the purposes of this analysis, the LA was segmented as posterior LA, anterior LA, septal LA, inferior LA, lateral LA, and LA roof, as previously described (4). Each point was binned according to location (region) to determine the following, as previously described (4,20).
Regional conduction velocity and conduction heterogeneity
An isochronal activation map (5-ms intervals) of the LA was created, and regional conduction velocity was determined in the direction of the wavefront propagation (least isochronal crowding). An approximation of CV was determined by expressing the distance between 2 points as a function of the difference in local activation time. Mean CV for each region was determined by averaging the CV between 3 and 5 pairs of points, as previously described (20).
The proportion of points that demonstrated complex electrograms was determined using the following definitions: 1) fractionated signals: complex activity of ≥50 ms duration with ≥3 deflections crossing the baseline; and 2) double potentials: potentials separated by an isoelectric interval when the total electrogram duration was ≥50 ms (4). Fractionated and double potentials were combined for analysis.
Regional bipolar voltage and voltage heterogeneity
Previously standardized definitions of scar and regions of low voltage were used (20). Scar was defined as the absence of electrical activity above the noise level of the system (<0.05 mV). Areas of low voltage were defined as areas with a bipolar voltage of ≤0.5 mV. The heterogeneity of bipolar voltage was determined by calculating the CV of the different regions in the LA.
Normally distributed data were expressed as mean ± SD. A mixed effects model was used for all analyses that contained multiple regional measures within each patient (e.g., CV, voltage). Generalized estimating equations were used for nested categorical variables (e.g., percentage of fractionation, percentage of low voltage). To investigate LA regional patterns in both approaches, region (posterior LA, anterior LA, septal LA, inferior LA, lateral LA, and LA roof) and group (obese and reference) were modeled as fixed effects with an interaction term (region × group). If a significant interaction was present, mixed effects post hoc test p values were reported.
A conventional unpaired t test was used for data without multiple measures or levels of data within an individual (e.g., fat mass, LA size, LVEF). Linear regressions between predictor variables of total EAT, atrial EAT, LA EAT, and BMI were correlated with mean posterior LA CV, mean posterior LA voltage, and percent fractionation of the posterior LA. All analyses were performed using SPSS/PASW, version 21 (IBM, Armonk, New York). Statistical significance was set as p < 0.05.
A total of 115 patients were screened for the study. Figure 1 provides the CONSORT diagram for patient screening and recruitment. After pre-specified exclusions, 33 patients consented to the study. However, a further 7 patients had to be excluded for suboptimal quality CMR (n = 3) and presence of AF at the procedure (n = 4). The remaining 26 patients were included in the analysis and allocated into the 2 groups: 1) obese group with a BMI ≥27 kg/m2 (n = 16); and 2) reference group with a BMI <27 kg/m2 (n = 10).
The baseline patient characteristics are shown in Table 1. The body weight of the obese and reference groups was 94 ± 13 and 74 ± 9 kg, respectively (p < 0.001). The BMIs were 30.2 ± 2.6 and 25.2 ± 1.3 kg/m2 in the obese and reference groups, respectively (p < 0.001). The 2 groups did not differ in age or the presence of other comorbidities. There was a similar distribution of the AF type between the 2 groups (p = 0.42).
Electrophysiological atrial remodeling with obesity
The LA electroanatomic maps consisted of 74 ± 15 and 70 ± 11 points in the obese and reference groups, respectively (p = 0.6). The LA activation time tended to be longer in the obese group compared with the reference group (87 ± 16 ms vs. 74 ± 20 ms; p = 0.09). Table 2 summarizes the atrial electrophysiological remodeling in obesity.
The LA CV was reduced in the obese group compared with the reference group (0.86 ± 0.31 m/s vs. 1.26 ± 0.29 m/s; p < 0.001). The CVs were uniformly depressed in all segments (interactive p [group × region] = 0.67) (Figure 2, Table 2). There was a nonsignificant increase in conduction heterogeneity in the obese group compared with the reference group (33 ± 29% vs. 17 ± 13%; p = 0.10).
There were more complex fractionated signals and double potentials in the obese group compared with the reference group (54 ± 17% vs. 25 ± 10%; p < 0.001). The increase in fractionation was uniform across different regions in the obese patients (Figure 2, Table 2).
Figure 3 shows representative LA voltage maps of the obese and reference groups, the distribution of regional voltage (mean), and low voltages areas in the different segments of the LA.
The mean global voltage was similar in the obese and reference groups (2.2 ± 1.5 mV vs. 2.2 ± 1.9 mV; p = 0.8). However, there were significant regional differences between the 2 groups (interactive [group × region] p < 0.001). The posterior and the inferior LA walls had lower regional mean voltages in the obese group compared with the reference group (Figure 3, Table 2), which reached significance for the posterior LA region (p < 0.05). The lateral LA region, which represented the appendage, had increased regional mean voltage in the obese group compared with the reference group (p = 0.01).
Low voltage areas
A total of 13.9% of all points were low voltage in the obese group compared with 3.4% in the reference group (p < 0.001). There were significantly greater low voltage points in all regions, notably, the posterior and inferior LA regions (p < 0.001).
Epicardial fat measures of adiposity
Epicardial fat and obesity
All EAT measures (i.e., total, ventricular, atrial, and LA EAT) were consistently greater in the obese group compared with the reference group (Table 1). There was strong correlation between different measures of EAT (LA and atrial EAT volume: r2 = 0.86; p < 0.001; LA and total EAT volume: r2 = 0.48; p < 0.001). However, the correlation between EAT measures and BMI was only modest (LA EAT: r2 = 0.38; p = 0.002; total atrial EAT: r2 = 0.40; p = 0.001; and total EAT: r2 = 0.44; p = 0.002).
Figure 4 demonstrates the representative CMR images showing the LA EAT distribution in the obese and reference groups. LA EAT was predominantly located as a fat pad contiguous with the posterior and inferior LA and along the atrioventricular groove. Typically, there was minimal EAT deposits subtending to the LAA. The EAT deposits along the atrioventricular groove anteriorly could represent the anterior fat pad. Overall, the spatial contiguity of LA EAT deposits was most prominent with the posterior LA and was lacking with the LAA. Although the volume of adipose tissue differed between the obese and reference groups, the regional distribution was similar.
Relationship of regional epicardial fat depot with the electrophysiological substrate
The different EAT measures and BMI were correlated with LA conduction abnormalities. Compared with BMI, LA EAT correlated better with fractionation (LA EAT: r2 = 0.55; p < 0.001; atrial EAT: r2 = 0.62; p < 0.001; total EAT: r2 = 0.52; p < 0.001; BMI: r2 = 0.37; p = 0.001) (Figure 5). Similarly, LA, atrial EAT, and BMI correlated modestly but significantly with mean LA conduction (LA EAT: r2 = 0.30; p = 0.008; atrial EAT: r2 = 0.27; p = 0.013; BMI: r2 = 0.26; p = 0.008). Because the posterior LA had a close spatial relationship to the posterior LA epicardial fat pad, we evaluated the relationship between EAT measures and posterior LA CV. Of these measures, LA EAT best predicted the change in posterior LA CV (LA EAT: r2 = 0.31; p = 0.007; atrial EAT: r2 = 0.20; p = 0.032; total EAT: r2 = 0.16; p = 0.063; BMI: r2 = 0.22; p = 0.014) (Figure 5).
This study provided new information on the electroanatomical remodeling in the obese human atria. The major findings are as follows:
• Obesity was associated with a global reduction in CV and increased electrogram fractionation in all regions of the LA, as well as regional reduction in voltage and an increase in the low-voltage area.
• EAT was increased in the obese patients, with the posterior epicardial fat pad largely contiguous with the posterior and inferior LA wall. The LAA had minimal overlying EAT.
• In comparison to BMI, the EAT measures correlated better with LA conduction abnormalities. In particular, LA EAT was the best predictor of conduction abnormalities in the contiguous posterior LA wall. Low atrial voltage was noted in the posterior, and the inferior LA was adjacent to the posteriorly located fat pad in obese patients.
In summary, obesity-related conduction abnormalities were most prominent in the posterior LA, which was in close contact with the epicardial fat pad.
Association of obesity, epicardial fat, and AF
Epidemiological studies established the independent role of obesity as a risk factor for AF (7,8,21,22). Although these studies reporting the association have used BMI, other studies have shown that EAT measures were more precise in predicting AF (12–15,23,24). The term “pericardial and epicardial fat” has been used interchangeably in the AF literature, with some studies defining fat inside the pericardial sac as pericardial fat (12,15) or epicardial fat (23), whereas others defined pericardial fat as a sum of epicardial (fat inside the pericardial sac) and para-cardial adipose tissue (outside the pericardial sac) (14). In the present study, EAT measures defined as fat inside the pericardial sac. We chose to use this measure because, unlike the para-cardial fat, it shares a common embryological origin with the myocardium (25). Overall, these studies showed that cardiac ectopic fat depots predicted the presence and severity of AF independently of the traditional measures of obesity. This has laid the foundation for the postulate that local cardiac fat deposits play a pathogenic role in the substrate for AF.
Relationship among epicardial fat, BMI, and electroanatomic remodeling in obesity
Structural remodeling and its electrophysiological consequences have emerged as the major feature of substrate development in patients with risk factors for AF. The diffuse atrial fibrosis and conduction abnormalities have been shown to be the cornerstone and unifying feature of this “remodeling of a different sort” (26) both in preclinical (4,27) and clinical studies (20,28). Similar conduction abnormalities and fibrosis have been observed with progressive weight gain (10). In addition, regulation of pro-fibrotic markers, increased atrial fibrosis, and infiltration of the posterior LA with EAT have been demonstrated to play a role in substrate development for AF in sustained obesity (4).
In the present study, we compared obese with nonobese patients who underwent AF ablation. The 2 groups had a similar mean age and prevalence of other risk factors of AF. The exclusion criteria were stringent to exclude patients with structural heart disease, LV dysfunction, and uncontrolled diabetes, as well as hypertensive patients with LV hypertrophy. In obese patients, compared with the reference group, we observed conduction abnormalities and increased fractionation of local electrograms. The mean global voltage was similar in both obese and reference patients, in keeping with the findings of Munger et al (11). However, the present study further analyzed regional voltage differences and demonstrated a reduction in voltage in the posterior and/or inferior LA and increased voltage in the lateral segment (LAA). The low voltage and electrical scarring were spatially related to the contiguous EAT. The increase in voltage in the lateral LA segment (LAA) might represent hypertrophy as a consequence of the hemodynamic overload described in obesity (10,11). The occurrence of a severe conduction abnormality in the posterior LA, a region in a close spatial relationship with the fat pad, raised the possibility of fat infiltration of the LA myocardium by contiguous fat depots, a phenomenon previously described by our group in an ovine model (4,29). Alternatively, different input from the autonomic ganglia that reside in the fat pads could not be excluded. The changes might have also resulted from the paracrine pro-fibrotic effect of EAT (4,16). This is also in agreement with findings of Munger et al., who showed slower conduction from the LA entering into the pulmonary veins in obese patients who underwent AF ablation (11). Furthermore, a previous study described the spatial relationship of EAT with high-dominant frequency sites but poor correlation with complex fractionated signals during AF (30). In contrast, the present study demonstrated significant correlation between LA EAT and electrogram fractionation in sinus rhythm that was superior to BMI.
Potential mechanistic role of epicardial fat
Several studies demonstrated that obesity directly contributes to the AF substrate through diastolic dysfunction, activation of pro-fibrotic pathways, atrial fibrosis, and abnormalities in connexin expression (4,5,31). Our group recently demonstrated infiltration by contiguous EAT into the posterior LA myocardium in a sheep model with weight gain and obesity (4,5). This EAT was contiguous with atrial myocytes without a separating fascia and shared the same blood supply with the adjacent atrial muscle (32). It was postulated that fat cell infiltration could separate muscle fibers and create electrically inert regions that promoted conduction abnormality akin to the effect of fibrosis (4,33). Furthermore, the absence of fascial barriers between EAT and the atrial musculature, common vascular supply, and fat infiltration might facilitate paracrine action (32). Venteclef et al. (16) provided insights into this association and demonstrated that the paracrine action might be mediated by a pro-fibrotic cytokine activin A, a member of the tumor growth factor−β superfamily. It was also plausible that profibrotic cytokines could be released into the pericardiac sac and could explain the diffuse atrial fibrosis and consequent conduction abnormalities.
In obese patients, EAT volume and electroanatomical remodeling were most pronounced in the posterior LA, which might represent an important substrate for AF in this patient subgroup. Potentially, an ablation strategy that targets posterior wall isolation in addition to pulmonary vein isolation might improve outcomes of AF ablation in obese individuals. In addition, risk factor modification, including weight loss, might be another strategy to target EAT depots associated with regional, extensive electroanatomical changes to favorably influence reverse remodeling (9,34–37).
The focus of this study was to assess the AF substrate in obesity, without the influence of other risk factors. However, this led to several exclusions and a small sample size. Furthermore, high-density mapping was not used for electroanatomic mapping.
During the analysis of the electroanatomic maps, the LA was segmented into 6 regions for analysis. However, similar segmentation was not performed for EAT due to the lack of sufficient interobserver and intraobserver reproducibility of EAT measures that were smaller than the LA EAT volume. This was unlike a previous study that segmented the LA in 22 parts and demonstrated an association between EAT location and high-dominant frequency (30). Nevertheless, the EAT pad was distinctly distributed contiguous to the posterior and/or inferior LA and was absent around the appendage that allowed us to draw conclusions.
The local autonomic ganglia, namely, the left superior, left inferior, and right inferior ganglia, are all located in the EAT adjacent to the posterior and/or inferior LA. We did not evaluate the role of the autonomic ganglia located in the fat deposit. The impact of obesity on the structure and function of these ganglia was also not well described. In addition, a systemic effect of obesity could not be excluded. Furthermore, the effective refractory periods for different atrial regions were not evaluated during the electrophysiology study because of the propensity to easily induce AF during testing, which could potentially alter the atrial electrophysiological features.
Obesity is associated with diffuse LA conduction abnormalities and scarring. These changes were more pronounced in regions adjacent to EAT pads, which suggested a role of these fat deposits in the development of the AF substrate. This also provided important information for further studies to guide AF ablation in obese individuals.
COMPETENCY IN MEDICAL KNOWLEDGE: The study provided information on the electrical substrate for AF in obesity. The pronounced remodeling in the LA contiguous with expanded epicardial fat pads in obese individuals confirmed a potential local impact of the EAT depots.
TRANSLATIONAL OUTLOOK: Obesity results in expansion of EAT and marked electroantomic remodeling of the LA, creating a substrate for AF. The association of EAT depots with regional extensive atrial remodeling provides the opportunity to explore and potentially modify the paracrine function of EAT to favorably promote reverse remodeling. Considering that the substrate for AF may be reversible, therapies targeted at modulating EAT burden and its secretory function may be clinically relevant.
This study was supported by funds from the Centre of Heart Rhythm Disorders at the University of Adelaide. This study was presented at the Annual Scientific Sessions of the Heart Rhythm Society, May 2015, Boston, Massachusetts and was awarded the Eric Prystowsky Clinical Research Award. Drs. Mahajan, Pathak, and Wong are supported by Early Career Fellowships from the National Health and Medical Research Council (NHMRC). Dr. Mahajan is supported by the National Heart Foundation (NHF) of Australia and by the Leo J. Mahar Lectureship from the University of Adelaide. Ms. Middeldorp is supported by a post-graduate scholarship from the NHMRC and the Robert J. Craig Scholarship from the University of Adelaide. Mr. Agbaedeng is supported by the Leo J. Mahar Scholarship from the University of Adelaide. Dr. Linz is supported by a Beacon Fellowship from the University of Adelaide. Dr. Lau is supported by the Robert J. Craig Lectureship from the University of Adelaide. Dr. Sanders is supported by Practitioner Fellowships from the NHMRC and NHF of Australia. This study was supported by funds from the Centre of Heart Rhythm Disorders at the University of Adelaide. This study was presented at the Annual Scientific Sessions of the Heart Rhythm Society, May 2015, Boston, Massachusetts and was awarded the Eric Prystowsky Clinical Research Award.
Dr. Mahajan reports that the University of Adelaide has received on his behalf lecture and/or consulting fees and research funding from Abbott and Medtronic. Dr. de Groot has been a consultant for Atricure and Daiichi Sankyo; and has received research grants from Boston Scientific, Medtronic, Abbott, and St. Jude Medical. Dr. Lau reports that the University of Adelaide has received on his behalf lecture and/or consulting fees from Abbott, Pfizer, Bayer, and Boehringer Ingelheim; and has received research funding from Abbott. Dr. Sanders has served on the advisory board of Biosense-Webster, Medtronic, Abbott, Boston Scientific, and CathRx; reports that the University of Adelaide has received on his behalf lecture and/or consulting fees from Biosense-Webster, Medtronic, Abbott, and Boston Scientific; and that the University of Adelaide has received on his behalf research funding from Medtronic, Abbott, Boston Scientific, Biotronik, and Liva Nova. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose. William Stevenson, MD, served as Guest Editor for this paper.
All authors attest they are in compliance with human studies committees and animal welfare regulations of the authors’ institutions and Food and Drug Administration guidelines, including patient consent where appropriate. For more information, visit the JACC: Clinical Electrophysiology author instructions page.
- Abbreviations and Acronyms
- atrial fibrillation
- conduction velocity
- cardiac magnetic resonance
- epicardial adipose tissue
- left atrium
- left atrial appendage
- left ventricular ejection fraction
- Received May 27, 2018.
- Revision received July 2, 2018.
- Accepted August 7, 2018.
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