Serum Bile Acids in Repaired Tetralogy of Fallot: A Marker for Liver and Heart?

Abstract

Background and aims: Patients with repaired tetralogy of Fallot may develop chronic right ventricular dysfunction and hepatic congestion over time. We hypothesized that bile acid metabolism is altered in repaired tetralogy of Fallot patients and therefore sought to correlate right ventricular indices with serum bile acid levels.

Methods: Indexed right ventricular end diastolic volume, as assessed by cardiac magnetic-resonance imaging, was classified as <100ml/m2 (Group 1, n = 5), 100-150ml/m2 (Group 2, n = 18), and >150ml/m2 (Group 3, n = 6) in 29 patients with repaired tetralogy of Fallot. Pulmonary regurgitation fraction and right ventricular ejection fraction were calculated. The serum bile acid profile, including 15 species, in these patients was determined by liquid chromatography coupled with mass spectrometry.

Results: Serum bile acid levels increased from Group 1 to Group 3 (2.5 ± 0.7; 4.1 ± 2.5; 6.0 ± 2.8 μmol/l, respectively) with significantly increased bile acid values in Group 3 compared to Group 1 (p≤0.05). In Group 3, but not in Group 1 and 2, a significant increase in glycine-conjugated bile acids was observed. Pulmonary regurgitation fraction increased (12 ± 1; 28 ± 16; 43 ± 3%, Groups 1-3, respectively) and right ventricular ejection fraction decreased (48.4 ± 6.4; 48.5 ± 6.5; 42.1 ± 5.3%, Groups 1-3, respectively) with rising indexed right ventricular end diastolic volume.

Conclusions: These preliminary results suggest that serum bile acid levels are positively correlated with indexed right ventricular end-diastolic volume in patients with repaired tetralogy of Fallot; however, this needs to be confirmed in a larger patient cohort.

Fig 1. Total BA levels in TOF patients with RVEDVi (1) <100 ml/m², (2) 100–150 ml/m², and (3) >150 ml/m².

BA levels were significantly elevated in Group 3 compared to Group 1 (p≤0.05). Total BA levels rose in TOF patients with increasing RVEDVi.

Fig 2. BA pool composition in patients with RVEDVi (1) <100 ml/m², (2) 100–150 ml/m², and (3) >150 ml/m².

In Group 2 T-conjugated and G-conjugated BA were increased compared to Group 1. In Group 3 T-conjugates were increased compared to Group 1, but decreased compared to Group 2. G-conjugates were significantly increased in Group 3 compared to Group 1 (p≤0.05). GCDCA was the predominant BA in all 3 groups, rising with increasing RVEDVi. White: unconjugated BA, light grey: G-conjugated BA, dark grey: T-conjugated BA. Abbreviations: BA, bile acids; G, glycine; T, taurine; RVEDVi, right ventricular end-diastolic volume.

Fig 3. Correlation of total BA levels with RVEDVi.

Together with increasing RVEDVi, total BA values also increased (r = 0.4; p≤0.05). Abbreviations: BA, bile acids; RVEDVi, indexed right ventricular end-diastolic volume.