Metabolomic Signatures and Advanced Echocardiography Highlight Clinical Risk and Early Cardiac Changes in Systemic Lupus Erythematosus: Six-Year Follow-Up

Background/Objectives: Cardiovascular involvement drives morbidity and mortality in systemic lupus erythematosus (SLE). Echocardiography has limited predictive value for long-term outcomes, and subclinical right ventricular (RV) remodeling is poorly characterized. Metabolic dysregulation may influence immune activation and myocardial injury. This study investigates whether baseline metabolomic profiles are associated with longitudinal RV changes and disease progression in SLE. Methods: In this prospective, single-center study, patients with established SLE and no known cardiac disease underwent baseline clinical assessment, plasma metabolomic profiling, and advanced echocardiography, including 3D RV analysis. Echocardiography was repeated after 6 years. Metabolomics was performed using NMR spectroscopy and GC–MS. Disease progression was assessed via the SLICC/ACR damage index (SDI), defining clinical stability as ΔSDI = 0 and worsening as ΔSDI ≥ 1. Results: Twenty-five patients completed the follow-up (88% female; mean age 51 ± 13 years). Despite normal echocardiographic values, subtle but significant RV changes were observed, remaining within reference ranges, including mild declines in fractional area change and septal longitudinal strain (p < 0.05). Clinically worsened patients showed reduced TAPSE, while stable patients had slight increases (p < 0.05). Multivariate metabolomic analysis distinguished stable from worsened patients (R2Y = 0.772; Q2 = 0.483), primarily driven by higher 2-aminoheptanedioic acid values in those with progression (p < 0.05), along with trends toward higher fumarate and lower fructose and glucopyranose. Conclusions: Baseline metabolomic and advanced echocardiographic profiling may identify SLE patients at risk of disease progression. Longitudinal echocardiography enables monitoring of subtle RV changes, supporting personalized surveillance to detect early subclinical trajectories before overt dysfunction develops.