Premature Ventricular Complexes and Epicardial Adipose Tissue ― A Fatty and Funny Relationship ―
Article ID: CJ-23-0825
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Article ID: CJ-23-0825
Growing evidence has shown that epicardial adipose tissue (EAT) affects cardiac pathophysiology. Recent studies have linked both increased EAT and obesity to myocardial impairments characteristic of heart failure with preserved ejection fraction (HFpEF),1–4 impairments that include left ventricular hypertrophy, diastolic dysfunction and left atrial dilatation.1,2 Some longitudinal studies have shown that higher EAT at baseline is associated with new-onset HFpEF, as well as a worse prognosis in those with established HFpEF,3 independent of overall obesity and important comorbidities.4,5
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In addition, EAT is an important proarrhythmic substrate for atrial fibrillation (AF) and may partly explain the clinical association between obesity and AF.6–10 Expansion of EAT, often a consequence of weight gain, predicts a higher risk of AF development and severity, as well as poorer outcomes after rhythm control strategies.6 Recent data have raised the intriguing idea of a possible paracrine communication between EAT and adjacent myocardial tissue,7–10 which is not so surprising given its anatomical location adjacent to myocardial tissue with no separating fascia.
Accumulation of EAT is associated with increased myocardial fibrosis, a histological hallmark of atrial structural remodeling. The secretome of human EAT has been shown to induce global interstitial fibrosis in rat atria pretreated with an ex vivo rat atrial organo-culture.7,9 Importantly, no such changes were observed in atrial tissue pretreated with subcutaneous fat, suggesting that EAT predominantly has a paracrine effect capable of inducing fibrosis.
These studies have indicated the EAT-induced disruption of cardiac ultrastructure and electrophysiological properties could lead to functional impairment of the myocardium. However, direct evidence for an association between EAT and premature ventricular complexes (PVCs) remains unknown.
In this issue of the Journal, Wang et al11 set out to answer this question by analyzing the data of patients undergoing radiofrequency catheter ablation (RFCA) for PVCs. PVCs are a common cardiac arrhythmia, and understanding the factors that contribute to their recurrence is paramount to improving patient outcomes.12 Their retrospective analysis of 401 PVC patients undergoing RFCA with pre-ablation non-contrast computed tomography (CT) data provides valuable insight into the relationship between EAT and PVC recurrence. The main findings are as follows.
1. EAT volume predicts PVC recurrence after RFCA: Larger EAT volume independently predicts PVC recurrence as determined by multivariable Cox analysis. This finding suggests that assessment of EAT volume by non-contrast CT, a relatively accessible and noninvasive procedure, could potentially be a valuable tool for clinicians in risk stratification of PVC patients.
2. Increasing risk of PVC recurrence is associated with EAT volume: The risk of PVC recurrence increases with increasing EAT volume, as shown by Kaplan-Meier analysis and restricted cubic spline analysis. This dose-response relationship highlights the clinical importance of EAT volume as a predictor.
3. EAT and PVC origin: Patients with PVCs originating from epicardial sites were found to have larger EAT volumes, which suggests a mechanistic link between EAT and the arrhythmogenic potential of certain PVC origins, an interesting area for further investigation.
These findings presented by Wang et al11 are consistent with a growing body of research investigating the association between EAT and cardiac arrhythmias. EAT has been associated with AF recurrence after ablation,13 and has been shown to influence ventricular arrhythmia susceptibility, particularly in the right ventricular outflow tract.14 The mechanisms underlying this association include EAT altering cardiac electrophysiology, creating anatomical barriers and promoting inflammation (Figure).
Epicardial adipose tissue (EAT) adjacent to myocardial tissue without a separating fascia could alter cardiac electrophysiology, create anatomical barriers and promote inflammation leading to premature ventricular complexes (PVCs).
The methodology used in this study (i.e., using non-contrast CT for EAT volume quantification) is an accessible and practical means of assessing EAT in the clinical setting. It has several advantages, including reduced radiation exposure and better suitability for a wider patient population.
Although the findings are promising, it’s important to acknowledge some limitations, such as the single-center, retrospective nature of the study, potential selection bias, and the relatively short follow-up. In addition, further research is needed to explore the precise mechanisms by which EAT contributes to PVC recurrence and to validate the clinical utility of EAT volume assessment in larger, more diverse patient populations.
Nevertheless, the findings from Wang et al11 strengthen the evidence for a pathogenic role of EAT in PVCs and present EAT as a potential new treatment target of PVCs. More importantly, therapies used to treat obesity and type II diabetes, including diet, exercise, bariatric surgery, GLP-1 receptor agonists and SGLT-2 inhibitors, appear to reduce EAT volume and its pro-inflammatory nature.15 Future research should investigate whether the reduction in EAT observed with these therapies is associated with better outcomes in patients with PVCs.
None.
N.T. is a member of Circulation Journal’s Editorial Team.
