Serum metabolomic signatures integrating sphingosine-1-phosphate and tetrahydrocortisone improve prognostic assessment in non-ischemic cardiomyopathy.

Authors

Fanglu Wang, Benchen Ye, Ligang Fang, Wei Chen, Ning-Yi Shao, Xiaowei Yan, Xue Lin

Published in

Metabolomics : Official journal of the Metabolomic Society. Volume 22. Issue 4. Jul 01, 2026. Epub Jul 01, 2026.

Abstract

Dilated cardiomyopathy (DCM) and left ventricular non-compaction (LVNC) are major non-ischemic cardiomyopathy (NICM) subtypes with heterogeneous outcomes. Conventional clinical and echocardiographic markers remain insufficient for long-term risk stratification.
This study aimed to identify serum metabolites associated with adverse cardiovascular outcomes and evaluate their incremental prognostic value in NICM.
Thirty-two patients with DCM or LVNC and left ventricular ejection fraction < 50% were enrolled and followed for a median of 45.5 months. The primary endpoint was a composite of cardiovascular death, heart failure-related hospitalization, or clinically indicated cardiovascular device implantation. Baseline serum samples underwent liquid chromatography-mass spectrometry-based untargeted metabolomic profiling. Differential metabolites were identified using OPLS-DA and KEGG enrichment analysis. Prognostic metabolites were screened using Cox regression, Kaplan-Meier analysis, correlation filtering, and ROC analysis. An integrated Cox model combining clinical and metabolic markers was evaluated using bootstrapping, calibration, and time-dependent ROC analysis.
A total of 299 differential metabolites were identified and enriched in bile secretion, steroid hormone biosynthesis, and neuroactive ligand-receptor interaction pathways. Sphingosine-1-phosphate (S1P) and tetrahydrocortisone (THE) were selected as final prognostic metabolite biomarkers, with ROC AUCs of 0.777 and 0.793, respectively. The integrated model incorporating S1P, THE, tricuspid annular plane systolic excursion, and total protein achieved a bootstrap-corrected C-index of 0.772, with time-dependent AUCs of 0.92 and 0.86 at 3 and 5 years.
Serum metabolomics may provide complementary prognostic information in NICM. S1P and THE are exploratory biomarkers linked to remodeling and stress, supporting risk stratification in NICM with reduced ejection fraction.

PMID:
42384285
Bibliographic data and abstract were imported from PubMed on 01 Jul 2026.

Read full publication at:
Please sign in to see all details.

Stats

1-terrible, 9-excellent. How would you rate this publication? Sign in in to submit your rating.

Post a comment

You need to be signed in to post comments. You can sign in here.

Comments

There are no comments yet.