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Introduction <p>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.</p> Objectives <p>This study aimed to identify serum metabolites associated with adverse cardiovascular outcomes and evaluate their incremental prognostic value in NICM.</p> Methods <p>Thirty-two patients with DCM or LVNC and left ventricular ejection fraction &lt; 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.</p> Results <p>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.</p> Conclusions <p>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.</p>

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

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年7月1日

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

摘要

Introduction

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.

Objectives

This study aimed to identify serum metabolites associated with adverse cardiovascular outcomes and evaluate their incremental prognostic value in NICM.

Methods

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.

Results

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.

Conclusions

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.