Amino acid profiling to predict prognosis in patients with heart failure: an expert review

Abstract

Heart failure is a complex disease with a poor prognosis. A number of widely used prognostic tools have limitations, so efforts to identify novel predictive markers and measures are important. As a metabolomics tool, amino acid profiling has shown promise in predicting heart failure prognosis; however, the evidence has not yet been sufficiently evaluated. We describe the utilization of amino acids in the healthy heart and in heart failure before reviewing the literature on amino acid profiling for prognostic prediction. We expertly interpret the findings and provide suggestions for future research to advance the understanding of the prognostic potential of amino acid profiling in heart failure. Our analysis revealed correlations between amino acid biomarkers and traditional prognostic factors, the additional prognostic value of amino acid biomarkers over traditional prognostic factors, and the successful use of amino acid biomarkers to distinguish heart failure aetiology. Although certain amino acid biomarkers have demonstrated additional prognostic value over traditional measures, such as New York Heart Association functional class, these measures are deeply rooted in clinical practice; thus, amino acid biomarkers may be best placed as additional prognostic tools to improve current risk stratification rather than as surrogate tools. Once the metabolic profiles of different heart failure aetiologies have been clearly delineated, the amino acid biomarkers with the most value in prognostic prediction should be determined. Amino acid profiling could be useful to evaluate the pathophysiology and metabolic status of different heart failure cohorts, distinguish heart failure aetiologies, and improve risk stratification and prognostic prediction.

Keywords: Amino acid profiling; Heart failure; Metabolomics; Prognosis; Risk stratification.

Figure 1

Schematic illustrating the relationship between heart failure and amino acid plasma levels. Heart failure is a complex syndrome characterized by its aetiology (e.g. coronary heart disease, valvular heart disease, and dilated cardiomyopathy), stage of progression, patient background (e.g. sex and age), and comorbidities (e.g. hypertension, atrial fibrillation, and chronic kidney disease). Heart failure leads to a state of systemic inflammation, hormonal dysregulation, and multi‐organ dysfunction that in turn causes a systemic imbalance between a catabolic and anabolic state favouring global catabolism. As a result, atrophy of multiple tissues as well as insulin and growth hormone resistance lead to sarcopenia, cachexia, protein degradation, and release of amino acid from tissues into the systemic circulation. This is further exacerbated by reduced kidney and hepatic clearance of amino acids due to tissue hypoperfusion. Given the central phenomenon of tissue breakdown in heart failure and subsequent changes to systemic amino acid levels, metabolomics and amino acid profiling hold great potential as diagnostic, prognostic, and therapeutic tools in heart failure. Specifically, the plasma leucine/phenylalanine ratio, Fischer's ratio (ratio of branched‐chain amino acid to aromatic amino acid levels), and levels of individual amino acids have been shown to have prognostic value in heart failure.