Altered serum bile acid composition is associated with cardiac dysfunction in cirrhosis

Abstract

Background: Elevated serum bile acids (BA) are harmful to the heart and alterations in the BA composition have been suggested to cause cardiovascular disturbances in cirrhosis. Aim: To investigate any associations between specific groups or individual serum BA and structural and functional cardiac abnormalities in patients with cirrhosis. Methods: An explorative study in 86 patients with cirrhosis. All participants underwent extensive cardiac assessment, including cardiac MRI with quantification of myocardial extracellular volume (ECV), which is indicative of diffuse myocardial fibrosis. A panel of 15 individual serum BA and C4, a marker of de novo bile acid synthesis, were assessed.Results: Patients with advanced cirrhosis had higher levels of total BA and conjugated BA, as well as lower C4 levels (p < 0.001). Conjugated BA levels were higher in patients with a high cardiac index (p < 0.001), increased left atrial volume index (LAVI) (p < 0.001), and in those with an abnormal myocardial ECV (p < 0.05). We also found several strong correlations between conjugated BA, both as a group and individually, and parameters of cardiac dysfunction. In a model adjusted for sex, age, BMI and MELD, conjugated BA remained significantly associated with LAVI, septal e′, left ventricular volumes and cardiac index. In addition, taurocholic acid correlated closely with hepatic venous pressure gradient (HVPG) (p = 0.01). Conclusions: Increased serum concentrations of conjugated BA are associated with several cardiac parameters, indicating a potential role in the development of hyperdynamic circulation and cardiac dysfunction in cirrhosis. Moreover, taurine-conjugated BA are associated with portal hypertension.

Taurocholic acid ameliorates hypertension through the activation of TGR5 in the hypothalamic paraventricular nucleus

“…11,12 However, in some cases, higher conjugated BA levels were correlated with a high cardiac index, increased left atrial volume index and abnormal myocardial fibrosis. 29 In this study, by comparing the different compositions of the bile acid pools in hypertensive and normotensive rats, we found a group of differentially produced bile acids in the PVN (Fig. 1).…”

“…The different pools of bile acids in different organs serve distinct functions, and in the same organ or tissue, changes in the pool of bile acids may be indicators of diseases. 11,29 In the cardiovascular system, many bile acids, including the primary and secondary ones, are beneficial. For example, UDCA can protect against the cardiac dysfunction that occurs in diseases complicated by liver cirrhosis, which causes abnormalities in bile acid metabolism.…”

Left atrial strain and ventricular global longitudinal strain in cirrhotic patients using the new criteria of Cirrhotic Cardiomyopathy Consortium

“…Hyperdynamic cardiac contractility in cirrhotic patients has been associated with elevated bile acid levels, while various pathophysiological mechanisms have been proposed for this association. 46,47 An interesting finding in our own study was the correlation of LV-GLS with bilirubin, since in the univariate analysis patients with LV-GLS ≥22.7% had significantly higher total bilirubin values than patients with LV-GLS <22.7%. Although total bilirubin was not remained an independent factor in multivariate analysis, further studies are needed to shed light on this potentially interesting association.…”

Editorial: The interplay of bile acids and the heart—another piece in the puzzle of cirrhotic cardiomyopathy

“…In this issue, Wiese et al 4 investigate the association of BA levels with alteration in cardiac structure and function among 86 patients with cirrhosis using two well‐established imaging modalities: echocardiogram and cardiac magnetic resonance imaging (CMR). They showed positive association between conjugated BA and cardiac structural and functional markers including but not limited to left ventricular (LV) volumes, left atrium volume index (LAVI), cardiac index and e′‐velocity.…”