Metabolomic and Genomic Insights Into Adverse Events in Paroxysmal Atrial Tachycardia.
Abstract
Paroxysmal atrial tachycardia (PAT) is a supraventricular arrhythmia associated with increased risk of atrial fibrillation (AF) and adverse cardiovascular events, but mechanisms underlying adverse outcomes remain unclear. We integrated serum metabolomics (LC-MS/MS), pathway enrichment, transcriptomic profiling, and in vitro validation in a PAT-onset cohort (five patients and five matched controls) and a PAT-events cohort (10 with and 10 without adverse events). Differential metabolites and pathways were identified, and GSEA focused on ABC transporters and alanine, aspartate, and glutamate metabolism. PAT exhibited metabolic dysregulation enriched in amino-acid metabolism and inflammation. Taurocholic acid was increased in PAT with adverse events and showed strong predictive value. Integrative analyses highlighted ABC transporter and alanine/aspartate/glutamate metabolism pathways. ABCA9 was upregulated, whereas ABCB10 and ABCC6 were downregulated in patient data and tachycardia transcriptomics, and these changes were confirmed in paced HL-1 atrial myocytes. ADSS1, AGXT2, and ASS1 were downregulated, indicating disrupted aspartate-linked metabolism; reduced ABCB10 suggested impaired mitochondrial homeostasis. Overall, PAT is characterized by metabolic remodeling involving ABC transporter dysfunction, amino-acid metabolic impairment, mitochondrial dysfunction, and vascular instability, supporting biomarker-guided risk stratification and targeted intervention.
What are the key findings of this study?
Paroxysmal atrial tachycardia (PAT) is a heart condition that can lead to serious health problems. Researchers looked at changes in metabolites (small molecules) and genes in patients to understand why some people have worse outcomes. They found that certain metabolic pathways were disrupted, especially those related to amino acids and inflammation. This information can help doctors identify patients at risk and guide treatments better. 🫀