Predictive value of atrial high-rate episodes for arterial stiffness and endothelial dysfunction in dual-chamber pacemaker patients

Background Various pacing studies have demonstrated an association between right ventricular pacing (RVp) and atrial fibrillation (AF), even after preserving atrioventricular (AV) synchrony. We aimed to assess the interaction between arterial stiffness, endothelial function and atrial high-rate episodes (AHRE) in patients with dual-chamber pacemakers. Methods We studied 101 patients with dual-chamber pacemakers incorporated with sophisticated AF detection and therapy algorithms. Macrovascular endothelial dysfunction (ED) was measured by the relative change in aortic augmentation index (AIx), using carotid artery applanation tonometry in response to inhaled salbutamol and sublingual glyceryl trinitrate. Microvascular ED was measured by cutaneous laser Doppler flowmetry (LDF) in response to acetylcholine (Ach, endothelium dependent) and sodium nitroprusside (SNP, endothelium independent). Arterial stiffness was measured using carotid-femoral pulse wave velocity (PWVcf). ‘Reservoir pressure’ (Pr, MATLAB) describes the aortic ‘cushioning’ properties. Results Mean age of the cohort was 72·1 ± 10·8 years; men (n = 69) 68·3%. Of 101 dual-chamber pacemaker patients, 23·8% (n = 24) had AHRE detected on the baseline pacemaker interrogation. PP, PWVcf and Pr were significantly higher in patients with AHRE compared with those without AHRE. The change in AIx with salbutamol (∆% AIx Sal) and acetylcholine-induced changes in LDF (Δ%LDF Ach) were lower in patients with AHRE compared with those without AHRE. In patients with AHRE, significant correlations were observed between%Vp and Δ%LDF Ach (P = 0·03) as well as between PP and Δ%LDF Ach (P = 0·05). On multivariate analysis, PP, Pr, PWVcf and ∆% AIx Sal remained as independent predictors of AHRE. Conclusion In patients with dual-chamber pacemakers, both higher arterial stiffness and greater endothelial dysfunction independently predicted AHRE, irrespective of the degree (or mode) of pacing. Arterial stiffness and endothelial dysfunction may potentially contribute to the perpetuation of atrial arrhythmias beyond the adverse effects of ventricular pacing alone.