Serum Vasoactive Intestinal Peptide as a Novel Biomarker for Low-Voltage Areas in Patients With Atrial Fibrillation

Background Low-voltage areas in the left atrium predict atrial fibrillation recurrence after catheter ablation and are associated with adverse outcomes like death, heart failure, and stroke. Detecting low-voltage areas (LVAs) typically requires invasive procedures, highlighting the need for a simple, minimally invasive marker. Vasoactive intestinal peptide (VIP), a neuropeptide released during parasympathetic stimulation, affects electrophysiological remodeling in atrial fibrillation. We hypothesized that serum VIP could serve as a biomarker for detecting LVAs in these patients. Methods and Results This prospective, cross-sectional study was conducted at Hokkaido University Hospital between August 2021 and September 2023. We included 108 patients with atrial fibrillation scheduled for catheter ablation. Blood samples were collected during ablation to measure VIP using an ELISA. Electroanatomical mapping identified LVAs, defined as regions with bipolar voltage <= 0.5 mV and occupying >5% of the left atrial surface. Statistical analyses evaluated the relationship between VIP and LVAs. Fifty-one patients (47%) had LVAs, with significantly higher serum VIP levels than those without (335.1 versus 247.7 pg/mL, P<0.001). VIP levels and female sex were statistically significant factors of LVAs. Adding VIP to the existing score significantly improved its discrimination (area under the curve: 0.784 versus 0.707, P<0.001). Conclusions Serum VIP levels are higher in patients with atrial fibrillation with LVAs, suggesting its potential as a noninvasive biomarker for detecting these areas and improving clinical management.