Reflex Syncope and the Role of Cardiac Pacing: A Systematic Review and Meta-Analysis

Abstract

Reflex syncope is a common cause of transient loss of consciousness, often leading to injuries and a reduced quality of life. Despite the benign nature of isolated episodes, recurrent syncope poses significant clinical challenges. Cardiac pacing has been investigated as a treatment modality, particularly in patients with cardioinhibitory phenotypes, yet prior studies have shown heterogeneous outcomes. A systematic review and meta-analysis were conducted to evaluate the efficacy of permanent cardiac pacing in preventing recurrent reflex syncope. Comprehensive searches of PubMed and the Cochrane Library were performed up to September 2024 using the terms "reflex syncope" and "cardiac pacing." Eligible studies included randomised controlled trials (RCTs) involving adult patients with recurrent reflex syncope undergoing permanent pacemaker implantation. Systematic reviews, narrative reviews, case reports or series, editorials, and conference abstracts were excluded from the review. Two independent reviewers screened studies and extracted data using Covidence, with discrepancies resolved by consensus. A meta-analytical synthesis was performed using odds ratios (ORs) for recurrent syncope, employing a random- and fixed-effects model. Heterogeneity was assessed using Cochran's Q, I² statistic, and τ². Seven RCTs were included, comprising a total of 458 patients. The primary outcomes showed a pooled analysis indicating a significant protective effect of pacing in reducing syncope recurrence compared to controls (OR 0.37; 95% CI: 0.22-0.62; p = 0.009), supporting the efficacy of permanent cardiac pacing in this population. Heterogeneity was low (Q = 6.60, p = 0.36; I² = 38%; τ² = 0.051), supporting the use of a fixed-effects model, which showed a similar outcome (Log(OR) 0.378 (95% CI, 0.229-0.624; p < 0.001)). The included trials varied in pacing modality (dual-chamber pacing (DDD), closed-loop stimulation (CLS), rate-drop response (RDR)), patient selection criteria, and diagnostic approaches. Secondary outcomes included reductions in pre-syncopal symptoms and delayed recurrence of syncope with pacing, along with a low incidence of device-related adverse events. However, inconsistent reporting limited the comprehensive meta-analysis of these endpoints. Permanent pacing reduces the risk of recurrent syncope in selected patients with reflex syncope, particularly those with documented asystole or cardioinhibitory phenotypes. CLS and RDR pacing algorithms may provide enhanced protection compared to conventional DDD pacing; however, variability in patient selection and device programming across studies limits the generalisability of these findings. Larger, standardised RCTs are needed to refine patient selection criteria and optimise pacing strategies for reflex syncope.

Keywords: cardiac pacing; cardioinhibitory syncope; closed-loop stimulation; pacemaker therapy; reflex syncope.

Figure 1. PRISMA flow diagram demonstrating study selection and exclusion.

PRISMA = Preferred Reporting Items for Systematic Reviews and Meta-Analyses

Figure 2. Funnel plot of standard error (SE) versus log odds ratio (log OR) for the effect of permanent cardiac pacing on recurrent reflex syncope. Each point represents an individual study included in the meta-analysis. The vertical line denotes the pooled log OR estimate. The diagonal lines represent pseudo 95% confidence limits (±1.96 × SE), forming the boundaries of the expected distribution in the absence of publication bias. The symmetric distribution of studies suggests a low risk of small-study effects or publication bias.

Figure 3. Random-effect forest plot for the meta-analysis of the benefit of permanent cardiac pacing on recurrent reflex syncope. The value <1 denotes that pacemaker therapy reduces the odds of recurrent syncope compared to the control.

OR = odds ratio Source: [14-20]

Figure 4. Fixed-effect forest plot for the meta-analysis of the benefit of permanent cardiac pacing on recurrent reflex syncope. The value <1 denotes that pacemaker therapy reduces the odds of recurrent syncope compared to the control.

OR = odds ratio Source: [14-20]