Conduction system versus right ventricular pacing for atrioventricular block: a reconstructed individual participant data meta-analysis
Authors: Reddy R K , Leong A , Naraen A , Liang Y , Ravendren A , Aggour H , Song Z , Saleh K , Kuramitsu S , Ahmad Y , Howard J P , Shun-Shin M J , Keene D , Whinnett Z I , Arnold A D 
Published: October 2024

Abstract

Background
Right ventricular pacing (RVP) is typically offered to patients with established or impending atrioventricular block (AVB) in the absence of left ventricular systolic dysfunction. Direct stimulation of His-Purkinje fibres via conduction system pacing (CSP) is an emerging alternative to RVP to prevent pacing-induced cardiomyopathy.

Purpose
To perform a systematic review and meta-analysis testing CSP versus RVP in patients with AVB and a left ventricular ejection fraction ≥35%.

Methods
Observational studies comparing CSP with RVP that reported clinical outcomes were systematically identified. The primary outcome was time-to-first all-cause mortality, heart failure hospitalisation (HFH) or upgrade to biventricular pacing. Secondary endpoints included the individual components of the primary endpoint. Individual participant time-to-event data (IPD) was obtained through data-sharing agreements or reconstructed from digitisation of Kaplan-Meier curves where available. Mixed-effects Cox proportional hazards regression that modelled between-study heterogeneity as a random intercept to account for differing baseline hazards between distinct study populations was performed on these data. Conventional pairwise random effects meta-analyses were also performed. This analysis was prospectively registered.

Results
12 eligible studies enrolling 4627 patients were included. In reconstructed IPD pooled survival analyses, CSP associated with a 38% reduced hazard of the primary endpoint compared with RVP [hazard ratio 0.62, 95% CI 0.51 to 0.76, p&lt;0.001] (Figure 1). In pairwise meta-analyses, CSP associated with a 46% risk reduction in the primary endpoint [relative risk (RR) 0.54, 95% CI 0.41 to 0.71, p&lt;0.001] (Figure 2A). CSP also associated with reductions in risk of all-cause mortality [RR 0.60, 95% CI 0.45 to 0.80, p&lt;0.001], HFH [RR 0.39, 95% CI 0.28 to 0.55, p&lt;0.001] and upgrade to biventricular pacing [RR 0.19, 95% CI 0.07 to 0.52, p=0.001] compared with RVP (Figure 2B-D).

Conclusions
In reconstructed IPD pooled survival analyses, CSP associated with reductions in the primary composite endpoint of all-cause mortality, heart failure hospitalisation or upgrade to biventricular pacing compared with RVP, independent of ventricular pacing burden. This was mirrored in conventional meta-analyses of the primary composite endpoint, and when individual components of the composite were analysed. It may not be necessary to predict which patients will have an elevated pacing burden when applying this therapy. Until randomised data from the PROTECT-HF trial becomes available, this analysis offers the most precise summary estimate of the comparative effects of CSP versus RVP in patients with an AVB indication for pacing, but no evidence of heart failure.Kaplan-Meier plot comparing CSP vs RVPForest plots for major endpoints