Long-Term Prognosis and Impact Factors of Metoprolol Treatment in Children with Vasovagal Syncope

<b>Objective:</b> To investigate long-term prognosis and impact factors in children with vasovagal syncope (VVS) receiving metoprolol therapy. <b>Methods:</b> This retrospective study included children with VVS who underwent metoprolol therapy at the Pediatric Syncope Unit of Peking University First Hospital between January 2012 and November 2023. Baseline demographic data, pre-treatment indices, including head-up tilt test (HUTT) and 24 h Holter monitoring, were collected. All participants received standardized metoprolol therapy for a minimum duration of one month. Follow-up was conducted between June and July 2025, with syncope recurrence as the primary endpoint. Multivariable Cox proportional hazards regression analysis was performed to identify independent impact factors of prognosis and to construct a Prognostic Risk Score (PRS) model. The model's performance was rigorously validated through receiver operating characteristic (ROC) curve analysis, decision curve analysis (DCA), and Bootstrap resampling (1000 iterations). Furthermore, children were stratified into high- and low-risk groups based on median PRS values. Kaplan-Meier survival analysis was then performed to assess the model's discriminative efficacy. <b>Results:</b> This study included 97 children diagnosed with VVS. The median duration of metoprolol therapy was 2.5 months (interquartile range [IQR]: 2.0-3.0 months), with a median follow-up period of 59 months (IQR: 25.5-72 months). During follow-up, syncope recurrence was observed in 37 patients, while 60 patients remained symptom-free. COX regression analysis showed that time-domain indices of heart rate variability (HRV), including the standard deviation of all NN intervals (SDNN) and the triangular index (TR), as well as the frequency-domain index of HRV very low frequency (VLF), were relative factors of the long-term prognosis in children with VVS treated with metoprolol. Based on the above three identified factors, the PRS model was calculated as: PRS = 0.03 × SDNN - 0.02 × VLF - 0.1 × TR. ROC showed that the area under the curve (AUC) for discriminative power related to long-term prognosis was 0.808 (<i>p</i> < 0.01). The cumulative recurrence rate of symptoms in the high-risk score group was significantly higher than that in the low-risk score group (<i>p</i> < 0.01). The DCA curve demonstrated the clinical applicability of the model. Bootstrap internal verification indicated high stability, with the bias-corrected and accelerated (Bca) confidence interval (CI) of the C index ranging from 0.71 to 0.89. <b>Conclusions:</b> After metoprolol treatment, 38.1% of children with VVS experienced syncope recurrence during a median follow-up period of 59 months. Baseline HRV index, SDNN, TR, and VLF were identified as factors associated with the long-term prognosis of children with VVS treated with metoprolol. The PRS model based on the above indices demonstrated good value in linking to the individual long-term prognosis.