Targeted metabolomic analysis of serum amino acids in the adult Fontan patient with a dominant left ventricle

Miriam Michel,Christina Salvador,Andreas Entenmann,Daniela Karall,Christian Niederwanger,Karl-Otto Dubowy,Ralf Geiger,Kai Thorsten Laser,Udo Müller,Manuela Zlamy,Mark Gordian Adam,Irena Odri Komazec,Sabine Scholl-Bürgi

doi:10.1038/s41598-020-65852-x

Abstract

Growing interest lies in the assessment of the metabolic status of patients with a univentricular circulation after Fontan operation, especially in changes of amino acid metabolism. Using targeted metabolomic examinations, we investigated amino acid metabolism in a homogeneous adult Fontan-patient group with a dominant left ventricle, seeking biomarker patterns that might permit better understanding of Fontan pathophysiology and early detection of subtle ventricular or circulatory dysfunction. We compared serum amino acid levels (42 analytes; AbsoluteIDQ p180 kit, Biocrates Life Sciences, Innsbruck, Austria) in 20 adult Fontan patients with a dominant left ventricle and those in age- and sex-matched biventricular controls. Serum concentrations of asymmetric dimethylarginine, methionine sulfoxide, glutamic acid, and trans-4-hydroxyproline and the methionine sulfoxide/methionine ratio (Met-SO/Met) were significantly higher and serum concentrations of asparagine, histidine, taurine, and threonine were significantly lower in patients than in controls. Met-SO/Met values exhibited a significant negative correlation with oxygen uptake during exercise. The alterations in amino acid metabolome that we found in Fontan patients suggest links between Fontan pathophysiology, altered cell energy metabolism, oxidative stress, and endothelial dysfunction like those found in biventricular patients with congestive heart failure. Studies of extended amino acid metabolism may allow better understanding of Fontan pathophysiology that will permit early detection of subtle ventricular or circulatory dysfunction in Fontan patients.

Highlights

Growing interest lies in the assessment of the metabolic status of patients with a univentricular circulation after Fontan operation, especially in changes of amino acid metabolism
With the help of targeted metabolomic examinations we elected to investigate amino acid metabolism in a homogeneous adult Fontan-patient group with a dominant left ventricle, seeking biomarker patterns that might permit a better understanding of Fontan pathophysiology or early detection of ventricular or circulatory dysfunction
The same is true for threonine, a major component of proteins, e.g., of collagen and immunoglobulins: We found decreased serum threonine levels, and decreased plasma levels are described in patients with chronic heart failure[17]

Summary

Introduction

Growing interest lies in the assessment of the metabolic status of patients with a univentricular circulation after Fontan operation, especially in changes of amino acid metabolism. We investigated amino acid metabolism in a homogeneous adult Fontanpatient group with a dominant left ventricle, seeking biomarker patterns that might permit better understanding of Fontan pathophysiology and early detection of subtle ventricular or circulatory dysfunction. Interest has grown recently in the metabolic status of Fontan patients: besides reported abnormalities in Fontan patients’ glucose metabolism[7], to date their handling of lipids has been best studied, with important changes shown, especially in the cholesterol, lipoprotein, and phospholipid pathways, hinting at chronic low-level inflammation and at altered cell signalling and energy metabolism as are found in biventricular patients with congestive heart failure[8,9]. With the help of targeted metabolomic examinations we elected to investigate amino acid metabolism in a homogeneous adult Fontan-patient group with a dominant left ventricle, seeking biomarker patterns that might permit a better understanding of Fontan pathophysiology or early detection of ventricular or circulatory dysfunction

Methods

Results

Discussion

Conclusion