Eicosanoids in coronary sinus negatively correlate with natriuretic peptides in heart failure with reduced ejection fraction: insights from Eicosanoids in Human Heart Failure Study

Abstract Background The diagnostic and therapeutic potential of eicosanoids, metabolites of arachidonic acid with positive cardio-renal activity in preclinical heart failure models, remains unclear in human chronic heart failure with reduced ejection fraction (HFrEF). Purpose The aim of this part of a traslational Eicosanoids in Human Heart Failure Study was to investigate levels of eicosanoids in different body compartments and their relation to natriuretic peptides. Methods Eleven consecutive patients with HFrEF indicated to cardiac resynchronisation therapy (CRT) were enrolled to measure plasmatic 14,15-epoxyeicosatrienoic acid (14,15-EET) and 14,15-dihydroxyicosatrienoic acid (14,15-DHET) levels from venous, arterial, and coronary sinus (CS) blood samples and correlate them with N-terminal pro B-type natriuretic peptide (NT-proBNP) from the same compartments. Results In CS, NT-proBNP levels negatively correlated with plasmatic 14,15-EET levels (r = -0.63, p = 0.03) and positively with the DHET/EET ratio (r = 0.73, p = 0.02). This correlation was not found in the other compartments. Plasmatic 14,15-EET nor 14,15-DHET levels in measured compartments did not differ statistically (p = 0.21, p = 0,64, respectively). In individual patients, the levels of both eicosanoids correlated across all compartments. Peripheral plasma 14,15-EET levels in controls were lower compared to HF patients. Conclusion Peripheral venous eicosanoid (14,15-EET, 14,15-DHET) levels correlate and do not differ from arterial and CS levels in patients with HFrEF indicated to CRT. In CS, NT-proBNP levels negatively correlated with plasmatic 14,15-EET levels and positively with the DHET/EET ratio, an indirect soluble epoxide hydrolase activity parameter.Graphical AbstractFigures