Plasma lipid signatures in recent-onset dilated cardiomyopathy: a targeted lipidomics study

Background Dilated cardiomyopathy (DCM) is a leading cause of heart failure, yet treatment response in recent-onset DCM (RODCM) remains heterogeneous. Current parameters inadequately predict early reversibility. We characterised plasma lipid signatures to identify metabolic determinants of myocardial dysfunction. Purpose To identify distinct plasma lipid profiles distinguishing RODCM from healthy controls and explore associations with myocardial mechanics. Methods Forty-eight RODCM patients (diagnosed ≤6 months, left ventricular ejection fraction [LVEF] <45%) and 48 age-, sex-, body mass index-matched healthy controls were prospectively enrolled. Fasting plasma was analysed by targeted liquid chromatography-tandem mass spectrometry (LC-MS/MS). After quality control (coefficient of variation <20%), 119 lipids were retained. Multivariate analyses included principal component analysis (PCA) and orthogonal partial least squares discriminant analysis (OPLS-DA). Differential lipids were identified using variable importance in projection >1 and P<0.05 with false discovery rate correction. Results Forty-eight RODCM patients and 48 healthy controls were analysed. Principal component analysis demonstrated clear separation between groups (R²Y=0.863, Q²=0.509, P<0.01). Glycerolipids constituted the predominant lipid class (60.51%), dominated by triacylglycerols (TAG, 58.72%). Orthogonal partial least squares discriminant analysis confirmed distinct metabolic profiles, with TAG 56:8_FA18, 57:3_FA18, 58:10_FA18 and 58:9_FA18 showing highest VIP scores (2.05–2.10). Differential analysis (VIP>1 and P<0.05) identified 51 significantly altered lipids: 44 upregulated and 7 downregulated in RODCM (Figure 1). Upregulated lipids comprised predominantly TAG species including TAG 52:2_FA20, 54:1_FA20, 56:2_FA16 and 58:10_FA22, whereas downregulated lipids included phosphatidylethanolamine PE(18:1_20:1), ceramide CER(d18:1/24:0) and diacylglycerol DAG (20:0_22:6). Hierarchical cluster analysis demonstrated distinct clustering patterns separating RODCM from controls. Conclusions RODCM is characterised by distinct plasma lipid signatures featuring triacylglycerol accumulation and phospholipid depletion, correlating with subclinical myocardial dysfunction and attenuated early reverse remodeling. Targeted lipidomics may enable early metabolic phenotyping and risk stratification in RODCM.