Abstract
BACKGROUND: New biomarkers are needed to improve risk prediction in patients with acute heart failure. We aimed to identify serum lipids with prognostic value and clinical utility in patients hospitalized due to acute heart failure. METHODS: Targeted mass spectrometry-based lipidomics was performed on serum samples from 315 (discovery) and 139 (validation) patients prospectively enrolled in 2 observational acute heart failure studies. Prognostic lipids were identified by consolidating orthogonal partial least squares discriminant analysis, least absolute shrinkage and selection operator regression, and random forest (Boruta) results into a single ranking using TopKSignal. RESULTS: In the discovery cohort, lysophosphatidylethanolamine 20:4, lysophosphatidylcholine 20:4, lysophosphatidylcholine 14:0, and lysophosphatidylethanolamine 18:1 were most strongly associated with in-hospital mortality. Serum concentrations were significantly lower in nonsurvivors, and these inverse associations remained significant after adjustment in both cohorts, except for lysophosphatidylethanolamine 18:1 after adjustment for OPTIMIZE-HF (Organized Program to Initiate Lifesaving Treatment in Hospitalized Patients With Heart Failure) in the validation cohort. These lipids demonstrated moderate discriminative performance (area under the curve, 0.72-0.76 in the discovery and 0.71-0.77 in the validation cohort) and provided additional prognostic value beyond ADHERE (Acute Decompensated Heart Failure National Registry), GWTG-HF (Get With The Guidelines Heart Failure), and OPTIMIZE-HF (Δarea under the curve, 0.04-0.17) scores. Decision curve analyses showed improved net clinical benefit for mortality prediction across threshold probabilities of 12% to 35% in the discovery and 15% to 28% in the validation cohort. CONCLUSIONS: Low serum levels of lysophosphatidylethanolamine 20:4, lysophosphatidylcholine 20:4, lysophosphatidylcholine 14:0, and lysophosphatidylethanolamine 18:1 were independently associated with in-hospital mortality in acute heart failure. These findings suggest that specific lysophospholipids may serve as novel prognostic biomarkers, warranting validation in larger studies to confirm their clinical applicability.