Observational studyJournal of the American Heart Association2025
Dysregulated Tricarboxylic Acid Cycle Metabolism Is Associated With Right Ventricular Maladaptation in Pulmonary Vascular Disease.
Observational study in Journal of the American Heart Association, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
5 citing papers in PubMed.
- Mitochondrial Dysfunction: From Molecular Mechanisms to Modern Approaches for Basic and Clinical Research.Biomedicines · 2026Review
- Metabolic Markers as Potential Risk Factors in Pulmonary Hypertension.Pulmonary circulation · 2026Article
- Cardiometabolic reprogramming in pulmonary arterial hypertension: Implications for right ventricular dysfunction and therapeutic strategies.Chinese herbal medicines · 2026Review
- Metabolomic Network Analysis Reveals Reorganization of Lipid and Steroid Programs Linked to Right Ventricular-Pulmonary Vascular Function in Pulmonary Hypertension.bioRxiv : the preprint server for biology · 2026Article
- Metabolomics of Right Ventricular Function in Pulmonary Hypertension.Circulation research · 2026Article
Corrections and comments
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Authors and funding
27 authors.
Funding
Abstract
backgroundRight ventricular (RV) maladaptation to elevated pulmonary afterload is the primary determinant of outcomes in pulmonary artery (PA) hypertension; however, the pathobiological mechanisms underlying RV decompensation remain poorly understood.
methodsWe performed global untargeted metabolomics on plasma from 55 patients who underwent gold-standard RV-PA coupling measurements using multibeat pressure volume loop assessment in a single-center cohort and from 1027 patients with coupling surrogate measurements in a larger multicenter cohort, the PVDOMICS (Pulmonary Vascular Disease Phenomics) study. Age and sex-adjusted linear regression was performed to identify associations between metabolites and coupling metrics. Additionally, we performed a metabolic flux analysis using gene expression data from RV tissue in an independent cohort of 32 patients. Partial least squares-discriminant analysis was used to identify metabolites and reactions characteristic of the decompensated RV.
resultsRV-PA coupling was negatively associated with tricarboxylic acid (TCA) cycle intermediate levels. Specifically, plasma α-ketoglutarate and fumarate were significantly associated with all coupling metrics in both cohorts. Metabolic flux analysis indicated that decompensated RVs exhibited aberrant TCA cycle activity, including reduced acetyl coenzyme A entry and increased lactate elimination, suggesting a shift from the TCA cycle toward glycolysis at the RV tissue level.
conclusionsWe identify an association between circulating TCA cycle intermediate levels and RV-PA uncoupling in 2 independent cohorts, and dysregulated TCA cycle metabolism in decompensated PA hypertension RVs, suggesting that aberrant TCA cycle metabolism could represent a hallmark of RV maladaptation in PA hypertension. Further study of this pathway is warranted to develop novel biomarkers of RV function or RV-targeted therapies.
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