Kynurenines in Heart Failure With Preserved Ejection Fraction: An Influence of Type 2 Diabetes

Abstract

Background:Due to their connection to inflammation and oxidative stress, tryptophan metabolites via the kynurenine pathway (KP) relate to important aspects of the pathophysiology of heart failure with preserved ejection fraction (HFpEF) and type 2 diabetes (T2D). The study aimed to examine the relationship between parameters of HFpEF, measured with transesophageal echocardiography (TTE), and metabolites of the KP. Methods: One hundred and twenty subjects, 60 with T2D and 60 without, and 55 healthy controls were prospectively included in the current study. Liquid chromatography was used to quantify metabolites of KP in plasma. TTE was performed to assess the systolic and diastolic function of the left ventricle (LV). Results: Patients with T2D and HFpEF showed an increase in TRP, KYN, and AA concentrations (p=0.001, p<0.0001, p<0.0001, respectively) with a concomitant decrease in 3-HKYN (p=0.0009), and QA (p=0.0029) compared with those with HFpEF without diabetes. There were no significant differences in the morphology of the LV or left atrium, and even the parameters of LV diastolic function were comparable in both subgroups (HFpEF with T2D and HFpEF without T2D). Left ventricular global longitudinal strain (LVGLS) was significantly lower in HFpEF with T2D than in the subgroup of HFpEF patients without T2D (p=0.0026). Conclusion: Plasma levels of the kynurenine pathway metabolites were elevated in patients with HFpEF, and especially in patients with HFpEF and T2D. An increase in KP plasma metabolite concentrations were associated with LV remodeling and diastolic dysfunction.