Abstract

Background: Despite recent advances, heart failure (HF) remains a high burden disease and is largely treated with a “one-size-fits-all” approach. Two phenotypes are recognized: HF with reduced ejection fraction (HFrEF) and HF with preserved ejection fraction (HFpEF). To develop HF disease-specific approaches to define and guide treatment, distinguishing biomarkers are needed. Methods: We conducted quantitative, targeted LC/MS plasma metabolomics on 787 samples collected by the Penn Medicine BioBank from patients with HFrEF (n=219), HFpEF (n=357), and matched non-failing Controls (n=211). Sample collection time from last meal was not controlled. A total of 97 metabolites were analyzed, comprising 30 amino acids, 8 organic acids, and 59 acylcarnitines classified by carbon length. Results: 3-hydroxybutyrate (3-HBA) was uniquely and significantly elevated in the HFrEF group [mean +/- SEM: HFpEF, 108.7(+/-7.15); HFrEF, 148.0(+/-12.4); Control, 86.29(+/-8.01); p <.0001]. The 3-HBA metabolite C4-OH butyryl-carnitine also showed a similar HFrEF-specific pattern. Consistent with previous studies, long/very-long chain acylcarnitines were elevated in the HFrEF group to a much greater extent than the HFpEF group compared to Controls. Branched-chain amino acid (BCAA) levels were not different across the groups; however, acylcarnitine species indicative of BCAA degradation, including C04 Isobutyryl, C04-DC Methylmalonyl, C04-DC Succinyl, and C05 2-Methylbutyryl, were significantly elevated in both HF groups compared to Controls. Lastly, we found that the amino acid, asymmetric dimethylarginine, which promotes endothelial dysfunction and vasoconstriction, was uniquely elevated in the HFpEF cohort [mean +/- SEM: HFpEF, 1.236(+/- .019); HFrEF, 1.105(+/- .027); Control, 1.077(+/- .022); p < .0001]. Conclusions: Taken together, these results identify plasma metabolite signatures that potentially distinguish between HFrEF and HFpEF and suggest patterns of metabolic re-programming in extra-cardiac tissue in the context of heart failure. Future studies will be necessary to define the utility of these metabolites as biosignatures to help guide therapeutics and to identify the underlying physiology responsible for these observations.

Full Text
Published version (Free)

Talk to us

Join us for a 30 min session where you can share your feedback and ask us any queries you have

Schedule a call