Peripheral plasma histidine ≤4.71 µg/mL predicted AF recurrence with 76.3% sensitivity, 76.5% specificity, and was associated with 66% lower recurrence risk (OR 0.34, p=0.01).
Does plasma histidine level predict atrial fibrillation recurrence after catheter ablation?
Plasma histidine levels may serve as a novel predictive biomarker for atrial fibrillation recurrence following catheter ablation.
Absolute Event Rate: 0% vs 0%
Abstract Background Atrial fibrillation (AF) is associated with complex and multifaceted aetiology including neural modulation that alters atrial electrophysiology. Purpose To explore potential biomarkers for AF and AF recurrence. Methods We measured four groups of neurotransmitters and their precursors/metabolites—histidine and histamine, tyrosine and norepinephrine, 5-hydroxyindoleacetic acid (5-HIAA), and acetylcholine—in blood samples from the peripheral circulation, right atrium, left atrium, and coronary sinus of patients with paroxysmal or persistent atrial fibrillation (PaAF/PeAF) and paroxysmal supraventricular tachycardia (PSVT) using liquid chromatography-mass spectrometry (LC-MS). A sheep model of AF induced by subcutaneous pacemaker implantation was employed to investigate whether electrical cardiac remodelling affects left atrial histidine metabolism. Additionally, neonatal rat cardiomyocytes were isolated to assess the impact of histidine on cardiac toxicity. Results Peripheral histidine levels were highest among all sampling sites in patients with PaAF and PeAF. Cardiac histamine levels were significantly lower in both PaAF and PeAF compared to patients with PSVT. The 5-HIAA levels at all four sites were consistently and positively correlated with CHA2DS2-VASc. Receiver operating characteristic (ROC) analysis demonstrated that peripheral histidine was predictive of AF recurrence, with an optimal cutoff value of ≤ 4.71 µg/mL, yielding a sensitivity of 76.3% and a specificity of 76.5%. The area under the ROC curve (AUC) was 0.75 (95% CI, 0.59–0.90). After adjusting for covariates, peripheral histidine was robustly associated with a lower incidence of AF recurrence (OR 0.34, 95% CI 0.14 – 0.71, p=0.01). Our results from the sheep AF model showed that while 3-methylhistidine, a known biomarker of muscular degradation, was significantly elevated in atrial tissues of the AF group, no significant changes in histidine levels were observed. However, histidine concentrations ranging from 1 to 100 nM enhanced the viability of neonatal rat cardiomyocytes, both in the presence and absence of doxorubicin, whereas, at 10 μM, a decline in viability was observed. Bulk RNA-seq Gene Set Enrichment Analysis (GSEA) revealed that histidine downregulated genes are involved in ribosomal function and oxidative processes when co-administered with doxorubicin. Furthermore, the abundance of cleaved Caspase-3 was significantly elevated under histidine treatment in the presence of doxorubicin. Conclusion Plasma histidine may serve as a potential biomarker for predicting AF recurrence. Additionally, our study demonstrates that histidine exerts biphasic effects on cardiomyocyte viability, and further research is required to elucidate the underlying mechanisms.
Xu et al. (Sat,) reported a other. Peripheral plasma histidine ≤4.71 µg/mL predicted AF recurrence with 76.3% sensitivity, 76.5% specificity, and was associated with 66% lower recurrence risk (OR 0.34, p=0.01).