Patients with left ventricular relaxation impairment display lower levels of primary conjugated bile acids in the context of cirrhosis

O. M. Chavez Talavera (Düsseldorf)¹, C. Angendohr (Düsseldorf)², D. Herebian (Düsseldorf)³, L. Baensch (Düsseldorf)¹, A. Polzin (Düsseldorf)¹, V. Keitel (Magdeburg)⁴, C. Engelmann (Berlin)⁵, F. Tacke (Berlin)⁵, A. Tailleux (Lille)⁶, B. Staels (Lille)⁶, A. Kunstein (Düsseldorf)², J. G. Bode (Düsseldorf)², M. Kelm (Düsseldorf)¹, T. Lüdde (Düsseldorf)², L. K. Dannenberg (Düsseldorf)¹
¹Universitätsklinikum Düsseldorf Klinik für Kardiologie, Pneumologie und Angiologie Düsseldorf, Deutschland; ²Department of Gastroenterology, Hepatology and Infectiology University Hospital Düsseldorf. Düsseldorf, Deutschland; ³Clinic of general Pediatrics, Neonatology and pediatric Cardiology, University Hospital Düsseldorf. Düsseldorf, Deutschland; ⁴Clinic of Gastroenterology, Hepatology, and Infectiology, University Hospital Magdeburg, Germany Magdeburg, Deutschland; ⁵Department of Hepatology and Gastroenterology, La Charité Berlin, Deutschland; ⁶Univ. Lille, Inserm, CHU Lille, Institut Pasteur de Lille, U1011 - EGID Lille, Frankreich

Background: Patients with cirrhosis display changes in circulating bile acids, and up to 50% develop a cirrhotic cardiomyopathy which, among other cardiovascular abnormalities, includes a left ventricular diastolic dysfunction. We hypothesize that the cirrhosis-induced bile acid changes contribute to the development of cirrhotic cardiomyopathy. To test this, we assessed the correlation between echocardiographic heart function parameters and fasting plasma bile acid concentrations.

Methods: This mono-center study included 35 patients with cirrhosis prior to TIPS treated in the Department of Gastroenterology of the University Hospital Dusseldorf. 18 bile acid species were measured using liquid chromatography coupled with tandem mass spectrometry in fasting peripheral plasma. A transthoracic echocardiographic assessment including systolic and diastolic function analyses was conducted. The correlation between bile acids and echocardiographic parameters was assessed. Additionally, the patients were classified into two groups: a group with relaxation impairment (n=9) and another without relaxation impairment (n=26) according to their septal early diastolic mitral annular velocity (e‘) using a cutoff value of 7 cm/s, and the different bile acid species were compared between both groups.

Results: Among the echocardiographic parameters for diastolic dysfunction, the e‘ septal and e‘ lateral showed a strong positive correlation with primary conjugated, but not with secondary free bile acids. In line, the group of patients with left ventricular relaxation impairment showed significantly lower levels of primary conjugated bile acids, whereas secondary free bile acids did not show statistically significant differences. Interestingly, both free and conjugated species of ursodeoxycholic acid showed a negative correlation with the end systolic volume.

Conclusion: The observed correlation between heart dysfunction and hepatic-derived primary conjugated bile acid species suggests that cirrhosis-induced alterations in the bile acid pool and the heart-liver-intestine axis may contribute to the pathogenesis of cirrhotic cardiomyopathy. However, further research is needed to establish whether bile acids play a causal role in this disease and to elucidate the mechanisms by which bile acids modulate cardiovascular dysfunction in the context of cirrhosis. A comprehensive understanding of the role of bile acids in cardiac function could facilitate the development of therapeutic strategies aimed at preventing or treating cirrhotic cardiomyopathy.

Patients with left ventricular relaxation impairment display lower levels of primary conjugated bile acids in the context of cirrhosis

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