Abstract

Introduction: Identifying low-voltage areas (LVAs) within left atrium (LA) is crucial for predicting atrial fibrillation (AF) recurrence after pulmonary vein isolation (PVI). Animal studies have shown that the parasympathetic neurotransmitter vasoactive intestinal peptide (VIP) affects atrial electrophysiological remodeling. Hypothesis: Thus, we hypothesized that elevated serum VIP levels might contribute to the development of LVAs and that serum VIP concentrations could serve as a biomarker for LVA presence in AF patients. Aims: The aim of this study is to investigate the relationship between the blood levels of VIP and the presence of LVAs in AF patients with electroanatomical mapping (EAM). Methods: We conducted an observational, prospective cross-sectional study on AF patients undergoing PVI between 2021 and 2023. Blood samples for VIP were collected before atrial septal puncture, and EAM was performed using CARTO 3® before PVI. VIP concentrations were measured using an enzyme-linked immunosorbent assay kit. Patients were divided into two groups based on LVA presence (≥5% or <5%) as determined by EAM. Results: Among the 108 patients, 51 (47%) had LVA. VIP levels were significantly higher in patients with LVA compared to those without (median [interquartile range]: 335.1 [274.1-456.5] pg/mL vs. 247.7 [196.1-294.0] pg/mL, p<0.001). No difference was observed in VIP levels by LVA sites. Multivariate logistic regression identified VIP and sex as independent predictors of LVA (per 50 pg/mL, odds ratio [OR]: 1.44, 95% confidence interval [CI]: 1.13-1.83, p<0.001, OR: 4.67, 95% CI: 1.69-12.89, p=0.002, respectively). Females with high VIP had lower conduction velocity compared to other groups. (low VIP male: 0.9 [0.6-1.0] m/s, high VIP male: 0.9 [0.7-1.1] m/s, low VIP female: 0.8 [0.7-1.0] m/s, high VIP female: 0.7 [0.3-0.8] m/s, p=0.013). Incorporating VIP levels (≥288 pg/mL) into an existing predictive score (age ≥65 years, female, and LA volume index ≥57 mL/m 2 ) significantly improved LVA detection (area under the curve: 0.784 vs. 0.707, p<0.001). Conclusions: Serum VIP levels are higher in patients with LVAs, and VIP is a reliable predictor of LVA presence. Incorporating VIP levels into existing predictive models enhances the power for identifying LVAs in AF patients. Serum VIP measurement could be valuable for detecting LVAs, improving risk stratification, and tailoring strategies in AF management.

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