Epicardial fat and liver disease; the contribution of cardio autonomic nervous system function

Epicardial fat, cardiac geometry and cardiac function in patients with non-alcoholic fatty liver disease: Association with the severity of liver diseaseJournal of HepatologyVol. 62Issue 4PreviewNon-alcoholic fatty liver disease (NAFLD) is increasing worldwide, affecting roughly 20–30% of the general population [1]. In addition to an expected risk for disease progression from non-alcoholic steatohepatitis (NASH) to bridging fibrosis, cirrhosis and its complications [1], NAFLD patients are also at higher risk of early asymptomatic cardiovascular alterations and/or frank cardiovascular disease [2]. Specifically, NAFLD, diagnosed either by ultrasonography or by liver biopsy, has been associated with a higher prevalence of low coronary flow reserve [3], coronary calcification [4], and carotid atherosclerosis [5–7], well before the occurrence of cardiovascular events. Full-Text PDF Epicardial fat in patients with non-alcoholic fatty liver diseaseJournal of HepatologyVol. 62Issue 5PreviewWe recently reported that epicardial fat thickness is significantly associated with the severity of liver fibrosis in patients with non-alcoholic fatty liver disease (NAFLD), and that in this clinical setting, morphological and functional cardiac alterations by echocardiography are inversely related with the severity of liver damage [1]. Of note, these associations were maintained after correction for both cardiometabolic and hepatic confounders including visceral adiposity. Full-Text PDF Open Access We read with great interest, the recent article by Petta et al. [[1]Petta S. Argano C. Colomba D. Cammà C. Marco V.D. Cabibi D. et al.Epicardial fat, cardiac geometry and cardiac function in patients with non-alcoholic fatty liver disease: association with the severity of liver disease.J Hepatol. 2015; 62: 928-933Abstract Full Text Full Text PDF PubMed Scopus (135) Google Scholar]. The authors show a positive relationship between higher epicardial fat thickness and the severity of liver fibrosis in patients with non-alcoholic fatty liver disease (NAFLD), which may indicate a possible pathogenic role of ectopic fat depots in whole body organ damage. They also stated that morphological and functional cardiac alterations were more pronounced according to the severity of fibrosis. In our letter, we would like to highlight another possible mechanism between epicardial fat and liver disease; the contribution of cardio autonomic nervous system function (CAF). In the literature, Chiang et al. evaluated the association between cardiovascular autonomic functions and time-to-death (TTD) in patients with terminal hepatocellular carcinoma. They concluded that the inclusion of HRV measurement in the prognostic models may improve accuracy in TTD prediction and, hence, facilitate medical decision making in hospital care [[2]Chiang J.K. Koo M. Kuo T.B. Fu C.H. Association between cardiovascular autonomic functions and time to death in patients with terminal hepatocellular carcinoma.J Pain Symptom Manage. 2010; 39: 673-679Abstract Full Text Full Text PDF PubMed Scopus (53) Google Scholar]. Liu et al. investigated the influence of NAFLD on autonomic changes and they clearly showed that NAFLD is associated with autonomic neural modulation of cardiac function in the sympathetic direction. The former association was independent of conventional cardiovascular risk factors and serum biomarkers (insulin resistance and leptin). They recommended further risk stratication of autonomic dysfunction by the HRV parameters in patients with NAFLD [[3]Liu Y.C. Hung C.S. Wu Y.W. Lee Y.C. Lin Y.H. Lin C. et al.Influence of non-alcoholic fatty liver disease on autonomic changes evaluated by the time domain, frequency domain, and symbolic dynamics of heart rate variability.PLoS One. 2013; 8: e61803Crossref PubMed Scopus (67) Google Scholar]. The results of these previous studies, indicate that impairment in autonomic nervous system function may play a role in the development of NAFLD. Several studies show a close relation between epicardial fat and cardiac autonomic function [4Zhou Q. Zhang L. Wang K. Xu X. Ji M. Zhang F. et al.Effect of interconnection between cervical vagus trunk, epicardial fat pad on sinus node function, and atrial fibrillation.Pacing Clin Electrophysiol. 2014; 37: 356-363Crossref PubMed Scopus (16) Google Scholar, 5Carnevali L. Graiani G. Rossi S. Al Banchaabouchi M. Macchi E. Quaini F. et al.Signs of cardiac autonomic imbalance and proarrhythmic remodeling in FTO deficient mice.PLoS One. 2014; 9: e95499https://doi.org/10.1371/journal.pone.0095499Crossref PubMed Scopus (36) Google Scholar, 6Balcioğlu A.S. Cıçek D. Akinci S. Eldem H.O. Bal U.A. Okyay K. et al.Arrhythmogenic evidence for epicardial adipose tissue: heart rate variability and turbulence are influenced by epicardial fat thickness.Pacing Clin Electrophysiol. 2015; 38: 99-106Crossref PubMed Scopus (48) Google Scholar]. It was shown that the cardiac ganglionated plexus in the epicardial fat integrates the autonomic innervation between the extrinsic and intrinsic cardiac autonomic nervous system and affects atrial electrophysiology and pathophysiology [[4]Zhou Q. Zhang L. Wang K. Xu X. Ji M. Zhang F. et al.Effect of interconnection between cervical vagus trunk, epicardial fat pad on sinus node function, and atrial fibrillation.Pacing Clin Electrophysiol. 2014; 37: 356-363Crossref PubMed Scopus (16) Google Scholar]. Carnevali et al. concluded that epicardial fat deficiency in mice leads to an imbalance of the autonomic neural modulation of cardiac function in the sympathetic direction and to a potentially proarrhythmic remodeling of electrical and structural properties of the heart [[5]Carnevali L. Graiani G. Rossi S. Al Banchaabouchi M. Macchi E. Quaini F. et al.Signs of cardiac autonomic imbalance and proarrhythmic remodeling in FTO deficient mice.PLoS One. 2014; 9: e95499https://doi.org/10.1371/journal.pone.0095499Crossref PubMed Scopus (36) Google Scholar]. Additionally, Balcioğlu et al. showed that sympathovagal imbalance, detected by heart rate variability and turbulence parameters, is related to epicardial fat thickness. As sympathovagal imbalance is a predictor of arrhythmic events, epicardial fat may play an important arrhythmogenic role [[6]Balcioğlu A.S. Cıçek D. Akinci S. Eldem H.O. Bal U.A. Okyay K. et al.Arrhythmogenic evidence for epicardial adipose tissue: heart rate variability and turbulence are influenced by epicardial fat thickness.Pacing Clin Electrophysiol. 2015; 38: 99-106Crossref PubMed Scopus (48) Google Scholar]. As a consequence, we believe that the impairment of the cardiac autonomic nervous system function may be helpful in explaining the results of the article by Petta et al., [[1]Petta S. Argano C. Colomba D. Cammà C. Marco V.D. Cabibi D. et al.Epicardial fat, cardiac geometry and cardiac function in patients with non-alcoholic fatty liver disease: association with the severity of liver disease.J Hepatol. 2015; 62: 928-933Abstract Full Text Full Text PDF PubMed Scopus (135) Google Scholar]. We hope that the above-mentioned items would add to the value of the well-written article of Petta et al. on the relationship between epicardial fat and NAFLD. The authors declared that they do not have anything to disclose regarding funding or conflict of interest with respect to this manuscript.