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.

Incremental Value of a Metabolic Risk Score for Heart Failure Mortality: A Population-Based Study

“…The median (interquartile range) MAGGIC score was 24 (20)(21)(22)(23)(24)(25)(26)(27)(28)(29), NT-proBNP (N-terminal pro-B-type natriuretic peptide) level was 8899 (4184-16351) pg/mL, and 43% of the patients had an EF <50%. Most patients were hypertensive and more than a third were diagnosed with diabetes.…”

“…19,20 We also found BCAAs (valine, leucine, and isoleucine) provided a protective contribution to our MRS. BCAAs are essential amino acids associated with protein metabolism in the heart and skeletal muscles, which have been studied in muscle wasting disorders. 21,22 Previous studies using different panels of metabolites similarly identified BCAAs as key risk indicators, 6 leading to hypothesize that these associations could reflect the systemic skeletal muscle response in advanced HF states. Our group previously reported on an association between the Metabolic Malnutrition Index, which includes BCAAs, and an increased risk of mortality in this HF community cohort.…”

Low Valine Serum Levels Predict Increased 1-Year Mortality in Acute Heart Failure Patients

“…Cellular catabolism of BCAA includes deamination to yield branched-chain alpha-keto acids (BCKA), which undergo conversion mediated by BCKA dehydrogenase to the precursors of energy metabolism molecules such as acetyl-CoA and succinyl-CoA. While BCKA dehydrogenase kinase phosphorylates BCKA dehydrogenase and inactivates the enzyme, dephosphorylation by a specific phosphatase restores the enzyme activity [ 23 , 24 ]. Endotoxins and inflammatory cytokines, whose levels are increased in HF, are strong inducers of BCKA dehydrogenase activity in the skeletal muscle [ 23 , 25 , 26 ].…”

Tyrosine to threonine ratio was related to heart failure with reduced or mildly reduced ejection fraction

“…9,14 In fact, a wide range of AAs are produced from protein metabolism and tissue degradation, and these AAs can be measured to inform the state of metabolism in HF and adverse events. 15,16 Nevertheless, little is known about the association between the ratio of tyrosine (Tyr) to threonine (Thr) and HF disease, especially with different HF aetiology. The purpose of our study was to examine the relationship between Tyr/Thr ratio and stable chronic HF (HFrEF or HFmrEF), meanwhile, comparing it with the FR index for better managing HF disease in the future.…”

“…In fact, a wide range of AAs are produced from protein metabolism and tissue degradation, and these AAs can be measured to inform the state of metabolism in HF and adverse events 15,16 . Nevertheless, little is known about the association between the ratio of tyrosine (Tyr) to threonine (Thr) and HF disease, especially with different HF aetiology.…”