Metabolomics implicate eicosanoids in severe functional mitral regurgitation.

Autor: Hofbauer TM; Department of Cardiology, Internal Medicine II, Medical University of Vienna, Waehringer Guertel 18-20, A-1090, Vienna, Austria., Distelmaier K; Department of Cardiology, Internal Medicine II, Medical University of Vienna, Waehringer Guertel 18-20, A-1090, Vienna, Austria.; Herz Zentrum Waehring, Vienna, Austria., Muqaku B; Institute of Analytical Chemistry, University of Vienna, Vienna, Austria., Spinka G; Department of Cardiology, Internal Medicine II, Medical University of Vienna, Waehringer Guertel 18-20, A-1090, Vienna, Austria., Seidl V; Department of Cardiology, Internal Medicine II, Medical University of Vienna, Waehringer Guertel 18-20, A-1090, Vienna, Austria., Arfsten HT; Department of Cardiology, Internal Medicine II, Medical University of Vienna, Waehringer Guertel 18-20, A-1090, Vienna, Austria., Hagn G; Institute of Analytical Chemistry, University of Vienna, Vienna, Austria., Meier-Menches S; Institute of Analytical Chemistry, University of Vienna, Vienna, Austria.; Joint Metabolome Facility, University of Vienna and Medical University of Vienna, Vienna, Austria., Bartko PE; Department of Cardiology, Internal Medicine II, Medical University of Vienna, Waehringer Guertel 18-20, A-1090, Vienna, Austria., Pavo N; Department of Cardiology, Internal Medicine II, Medical University of Vienna, Waehringer Guertel 18-20, A-1090, Vienna, Austria., Hoke M; Department of Angiology, Internal Medicine II, Medical University of Vienna, Vienna, Austria., Prausmueller S; Department of Cardiology, Internal Medicine II, Medical University of Vienna, Waehringer Guertel 18-20, A-1090, Vienna, Austria., Heitzinger G; Department of Cardiology, Internal Medicine II, Medical University of Vienna, Waehringer Guertel 18-20, A-1090, Vienna, Austria., Pils D; Joint Metabolome Facility, University of Vienna and Medical University of Vienna, Vienna, Austria., Lang IM; Department of Cardiology, Internal Medicine II, Medical University of Vienna, Waehringer Guertel 18-20, A-1090, Vienna, Austria., Hengstenberg C; Department of Cardiology, Internal Medicine II, Medical University of Vienna, Waehringer Guertel 18-20, A-1090, Vienna, Austria., Hülsmann MP; Department of Cardiology, Internal Medicine II, Medical University of Vienna, Waehringer Guertel 18-20, A-1090, Vienna, Austria., Gerner C; Joint Metabolome Facility, University of Vienna and Medical University of Vienna, Vienna, Austria., Goliasch G; Department of Cardiology, Internal Medicine II, Medical University of Vienna, Waehringer Guertel 18-20, A-1090, Vienna, Austria.; Herz Zentrum Waehring, Vienna, Austria.
Jazyk: angličtina
Zdroj: ESC heart failure [ESC Heart Fail] 2023 Feb; Vol. 10 (1), pp. 311-321. Date of Electronic Publication: 2022 Oct 10.
DOI: 10.1002/ehf2.14160
Abstrakt: Aims: Secondary, or functional, mitral regurgitation (FMR) was recently recognized as a separate clinical entity, complicating heart failure with reduced ejection fraction (HFrEF) and entailing particularly poor outcome. Currently, there is a lack of targeted therapies for FMR due to the fact that pathomechanisms leading to FMR progression are incompletely understood. In this study, we sought to perform metabolomic profiling of HFrEF patients with severe FMR, comparing results to patients with no or mild FMR.
Methods and Results: Targeted plasma metabolomics and untargeted eicosanoid analyses were performed in samples drawn from HFrEF patients (n = 80) on optimal guideline-directed medical therapy. Specifically, 17 eicosanoids and 188 metabolites were analysed. Forty-seven patients (58.8%) had severe FMR, and 33 patients (41.2%) had no or non-severe FMR. Comparison of eicosanoid levels between groups, accounting for age, body mass index, and sex, revealed significant up-regulation of six eicosanoids (11,12-EET, 13(R)-HODE, 12(S)-HETE, 8,9-DiHETrE, metPGJ2, and 20-HDoHE) in severe FMR patients. Metabolites did not differ significantly. In patients with severe FMR, but not in those without severe FMR, levels of 8,9-DiHETrE above a cut-off specified by receiver-operating characteristic analysis independently predicted all-cause mortality after a median follow-up of 43 [interquartile range 38, 48] months [hazard ratio 12.488 (95% confidence interval 3.835-40.666), P < 0.0001].
Conclusions: We report the up-regulation of various eicosanoids in patients with severe FMR, with 8,9-DiHETrE appearing to predict mortality. Our observations may serve as a nucleus for further investigations into the causes and consequences of metabolic derangements in this important valvular abnormality.
(© 2022 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)
Databáze: MEDLINE
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