Cardiovascular magnetic resonance of total and atrial pericardial adipose tissue: a validation study and development of a 3 dimensional pericardial adipose tissue model

The increasing prevalence of atrial fibrillation (AF) has been in-part attributed to the aging population and its associated co-morbidities such as hypertension, coronary artery disease and heart failure. However, there is increasing evidence that obesity contributes to the burden of atrial fibrillation in our population. Analyses from the Framingham and Women Health Studies (WHS) suggest that obesity is associated with an increased risk of AF independent of other traditional risk factors [1, 2]. These population-based studies have utilized body mass index as a measure of obesity. Recently, pericardial adipose tissue (PAT), both total and atrial, has been demonstrated to predict AF risk independently of weight and other measures of obesity [3‐5]. This has two important implications. Firstly, PAT could have a causal relationship with the risk of AF and it has been hypothesized that this effect could be mediated locally [6‐8]. Secondly, a change in atrial PAT mass with weight change could be a better predictor of the risk of AF as compared to other measures of weight change. Although, ventricular paracardiac adipose tissue CMR measurement has been validated before, the validation of the patchy and smaller volume of atrial PAT with the gold standard of mass at autopsy has not been previously performed [9]. In this study we sought to validate the quantification of atrial and total PAT utilizing a three dimensional atrial PAT model.

Ten merino cross sheep with weight ranging from 67 to 103 kilograms were included in the study. All procedures were conducted in accordance with the guidelines outlined in the “Position of the American Heart Association on Research Animal Use” adopted on November 11, 1984 by the American Heart Association. The study protocol was reviewed and approved by the Animal Research Ethics Committees of University of Adelaide and Institute of Medical and Veterinary Services, Adelaide, Australia.

Ten sheep with a mean weight of 80 ± 8 kg were assessed for both CMR and autopsy pericardial adipose tissue assessment, however one sheep was excluded from further analyses due to CMR artifacts precluding accurate assessment. Mean CMR imaging time was 30 minutes per animal. The additional mean time duration to assess pericardial adipose tissue with the semi-automated software was 5 ± 1.4 minutes per animal. On CMR assessment atrial, ventricular and total adipose tissue were assessed as 37 ± 10, 250 ± 71, 287 ± 77 g, respectively. On autopsy, the corresponding values were 29 ± 8, 231 ± 70, 260 ± 74 g. Table 1 shows the pericardial adipose tissue CMR measures and the corresponding autopsy values.

To the best of our knowledge, this is the first study to validate a CMR technique to specifically assess atrial pericardial adipose tissue. Our findings demonstrate that: [1] CMR assessment of atrial, ventricular and total fat has high intra- and inter-observer reproducibility, and [2] CMR quantified atrial and ventricular adipose tissue strongly agrees with ex vivo adipose mass, validating its use as a robust measure of pericardial adiposity. Moreover, the findings were reproducible and the image sequences utilized were those which would normally be acquired during a standard clinical CMR scan. Importantly, this study validates a three dimensional model of atrial pericardial adipose tissue which can be utilized to study regional fat deposits with respect to underlying atrial electrophysiological properties.

Echocardiography and computed tomography have previously been utilized for pericardial fat assessment. However, echocardiography is limited by its inability to obtain pericardial volumes and often sub-optimal imaging windows [14]. Moreover, echocardiography has been limited to assessment of ventricular pericardial adipose tissue. Although, volumetric assessment of pericardial adipose tissue can be performed by CT, the exposure to ionizing radiation limits its use, especially if serial measurements are planned [15].

Obesity has been demonstrated, in several population based studies, to be a novel risk factor for atrial fibrillation [16‐19]. Its association with hypertension, obstructive sleep apnea, diabetes mellitus, coronary artery disease and congestive heart failure, clouds interpretation of the potential mechanisms by which obesity is linked to atrial fibrillation. Population level studies have suggested that the effect may be mediated through left atrial enlargement [16, 17], albeit evidence is mounting that pericardial adipose tissue, surrounding the heart, may also play a significant role in the development of atrial fibrillation. Batal et al suggested that computed-tomography (CT) measured pericardial fat thickness is associated with prevalent AF [5]. In participants of the Framingham Heart Study, a community-based cohort, Thanassoulis et al observed that higher pericardial fat volumes were associated with a nearly 40% higher odds of prevalent AF [3]. Wong et al have recently demonstrated that pericardial fat volume is a better predictor than body mass index in predicting severity of atrial fibrillation and even outcomes after ablation [4]. As adipose tissue is highly vascular, it is hypothesized that mediators of lipid metabolism and inflammation produced in the pericardial adipose tissue may affect the underlying atrial myocardium in a paracrine manner [8]. In addition, epicardial fat has been demonstrated to infiltrate underlying atrial musculature in an obese ovine model [20]. This fatty infiltration can mechanically separate muscle fibers and create an area of electrical silence promoting reentry and atrial fibrillation. A recent study has reported the association of elevated dominant frequency with epicardial fat location [21].

This study demonstrates that CMR assessment of pericardial fat is an accurate and reproducible measure that could be utilized in future larger clinical cohorts. Furthermore, three dimensional PAT model constructed from CMR slices, allows regional interpretation of local cardiac fat stores, that in future could be utilized in conjunction with electro-anatomic maps to investigate the atrial substrate for atrial fibrillation. This could potentially have implications for planning ablation strategies for atrial fibrillation ablation in obese individuals.

Ventricular paracardiac adipose tissue has previously been validated using CMR [9]. This current study, to the best of our knowledge, is the first to validate CMR measure of atrial pericardial fat. Furthermore, in the study by Nelson et al [9], the paracardiac adipose tissue was validated against the histological gold standard. In contrast, in the current study, the total pericardial fat volume was validated, as the epicardial adipose tissue was meticulously removed along with the paracardiac adipose tissue. This provided a more accurate comparison between autopsy and CMR pericardial adipose tissue measures. However, complete removal of epicardial adipose tissue was not possible due to its adherence to underlying myocardium in some cases, and this could be a reason for a small systematic over-estimation by CMR (Figure 3).

CMR measurement of atrial, ventricular and total pericardial adipose tissue via 3D modeling of fat stores is a reproducible and accurate measure of pericardial fat on autopsy. The measurement of local cardiac fat stores via this methodology could provide a more sensitive tool to examine the potential causal relationship between obesity and atrial fibrillation and examine the regional effect of fat deposition on atrial substrate.

Joseph B. Selvanayagam and Prashanthan Sanders are senior authors.