A Novel Lipid Biomarker Panel for the Detection of Heart Failure with Reduced Ejection Fraction

Abstract

OBJECTIVES:In this study we aimed to identify novel metabolomic biomarkers suitable for improved diagnosis of heart failure with reduced ejection fraction (HFrEF). METHODS:We prospectively recruited 887 individuals consisting of HFrEF patients with either ischemic (ICMP, n ϭ 257) or nonischemic cardiomyopathy (NICMP, n ϭ 269), healthy controls (n ϭ 327), and patients with pulmonary diseases (n ϭ 34). A singlecenter identification (n ϭ 238) was followed by a multicenter confirmation study (n ϭ 649). Plasma samples from the single-center study were subjected to metabolite profiling analysis to identify metabolomic features with potential as HFrEF biomarkers. A dedicated analytical protocol was developed for the routine analysis of selected metabolic features in the multicenter cohort. RESULTS:In the single-center study, 92 of 181 metabolomic features with known chemical identity (51%) were significantly changed in HFrEF patients compared to healthy controls (P Ͻ0.05). Three specific metabolomic features belonging to the lipid classes of sphingomyelins, triglycerides, and phosphatidylcholines were selected as the cardiac lipid panel (CLP) and analyzed in the multicenter study using the dedicated analytical protocol. The combination of the CLP with N-terminal pro-B-type natriuretic peptide (NT-proBNP) distinguished HFrEF patients from healthy controls with an area under the curve (AUC) of 0.97 (sensitivity 80.2%, specificity 97.6%) and was significantly superior compared to NTproBNP alone (AUC ϭ 0.93, sensitivity 81.7%, specificity 88.1%, P Ͻ0.001), even in the subgroups with mildly reduced left ventricular EF (0.94 vs 0.87; P Ͻ0.001) and asymptomatic patients (0.95 vs 0.91; P Ͻ0.05). CONCLUSIONS:The new metabolomic biomarker panel has the potential to improve HFrEF detection, even in mild and asymptomatic stages. The observed changes further indicate lipid alterations in the setting of HFrEF.

Heart Failure with Preserved and Reduced Ejection Fraction in Hemodialysis Patients: Prevalence, Disease Prediction and Prognosis

“…The interpretation of NT pro-BNP in HD patients thus remains a complex issue not only due to its renal elimination but also due to a described increase in states of fluid overload [29]. Yet, it has previously been shown to be associated with higher mortality in HD patients [30] and has recently been successfully been implemented in the diagnostic process of HFrEF together with a lipid panel analysis and might therefore remain a practical tool for HF diagnosis in HD patients [31]. …”

Cardiovascular Implications of Sphingomyelin Presence in Biological Membranes

“…Furthermore, in a recent study enrolling patients with either ischaemic or non-ischaemic cardiomyopathy, healthy controls and patients with pulmonary diseases, three specific metabolomic features belonging to the lipid classes of SMs, triglycerides and phosphatidylcholines together with N-terminal pro-B-type natriuretic peptide (NT-proBNP) distinguished patients with HF from healthy controls. 51 In addition, the diagnostic accuracy of this combination was significantly superior compared with the diagnostic accuracy of NT-proBNP alone. 51…”

Novel heart failure biomarkers: why do we fail to exploit their potential?

“…In HF, both myocardial and systemic changes in glucose oxidation, catabolism, b-oxidation, and the urea cycle are responsible for observed alterations in metabolite levels [177]. Several studies have shown that a collection of metabolites can serve as diagnostic tools for HF [178][179][180][181]. However, changes in metabolite profiles seem not to be disease specific, because similar differences were observed in serum samples of patients with diseases such as nonHodgkin lymphoma, congestive HF, and communityacquired pneumonia (CAP) [182].…”