LC-MS-based serum fingerprinting reveals significant dysregulation of phospholipids in chronic heart failure

Cardiac and extracardiac lipid metabolism is known to be significantly altered in the course of the heart failure with reduced ejection fraction (HF-REF), however the precise mechanisms are not fully elucidated. The aim of the study was to use of untargeted metabolomics to identify and validate changes in the blood metabolites profile, occurring as a result of HF-REF development. The analyses were performed first in the derivation set (36 chronic HF-REF patients and 19 controls without the disease) and repeated in validation cohort (31 chronic HF-REF patients and 20 controls). Independent analyses of both sets revealed statistically significant decline in intensities of phosphatidylcholine (PC): 34:4 and 36:5, lysophosphatidylcholine (lyso-PC): 14:0, 15:0, 18:0, 18:2, 20:3, lysophosphatidylethanolamine (lyso-PE): 18:1 and 18:2 in chronic HF-REF patients. More symptomatic patients and those with ischaemic etiology of HF-REF presented greater deficit in phospholipids (PLs) intensities. The decrease of identified PLs intensities (as compared to controls) correlated with decreased serum cholesterol level, impaired renal function, reduced exercise capacity, enhanced ventilatory response and metabolic parameters associated with altered fatty acids oxidation. In multiple regression analysis PLs deficit was significantly associated with age, carnitines serum intensity, renal function, uric acid, cholesterol level. In conclusion, HF-REF is associated with significant disturbances in phospholipids metabolism. Greater reduction in serum intensities of particular identified PLs is associated with older age, worse clinical condition, impaired oxidative muscle metabolism and enhanced catabolic status.