Polarity-dependent repolarization during LBBAP across conduction phenotypes

Background Left bundle branch area pacing (LBBAP) is emerging as a viable alternative to traditional right ventricular pacing, as it facilitates more natural ventricular activation. Nonetheless, the impact of LBBAP on ventricular repolarization, especially concerning pacing polarity and pre-existing conduction disorders, has not been extensively explored. This research sought to examine the variations in repolarization parameters between unipolar and bipolar LBBAP across different intraventricular conduction disorders, utilizing ultra-high frequency electrocardiography (UHF-ECG). Objective The study aims to evaluate whether unipolar (uLBBAP) versus bipolar (bLBBAP) left bundle branch area pacing (LBBAP) has a different impact on ventricular repolarization (VR) dispersion compared to spontaneous intraventricular conduction (SIVC). Methods This is a single center, case-crossover design with a follow-up period of three months. Each patient in the sequence underwent both 12-lead ECG and UHF-ECG assessments in three different conditions: SIVC, uLBBAP, and bLBBAP without anodal capture. The primary measure is the Tpeak–Tend (TpTe) interval. Secondary measures include TpTe/QTc, QTc, JTc, and the activation–recovery interval (ARI) with spatial variability, assessed by the coefficient of variation. Linear mixed models were employed, with Holm-adjusted post-hoc tests, and sensitivity analyses were performed using the Fridericia correction. Results Seventy-five patients participated in the study, categorized as follows: normal intraventricular conduction (NIVC, n=36), left bundle branch block (LBBB, n=18), and right bundle branch block (RBBB, n=21). In the LBBB group, both configurations led to a similar reduction in QRS duration; however, bLBBAP resulted in a more streamlined repolarization pattern compared to uLBBAP, evidenced by a shorter TpTe (Δ=−7.4 ms; 95%; p=0.043) and a decreased CV-ARI (Δ=−4.6; 95%; p=0.002). Compared to SIVC, bLBBAP also reduced TpTe (−12.4 ms; 95%; p=0.039). In the RBBB group, uLBBAP significantly decreased TpTe compared to SIVC (−10.7 ms; 95%; p=0.0014), but the direct comparison of TpTe between uLBBAP and bLBBAP was not statistically significant (Δ=+5.38 ms; 95%CI −13.5 to +2.0; p=0.255). bLBBAP demonstrated a lower CV-ARI (Δ=−1.45; 95%CI −2.87 to −0.03; p=0.046). In the NIVC group, polarity did not significantly impact dispersion. These findings were consistent with the Fridericia correction. Conclusions The polarity of stimulation during LBBAP influences repolarization markers based on the initial conduction phenotype. In cases of LBBB, bLBBAP was linked to reduced dispersion, while in RBBB, uLBBAP significantly decreased TpTe. Incorporating UHF-ECG could offer a basis for tailoring LBBAP programming by selecting the setup that minimizes dispersion. Future studies are necessary to confirm if optimization guided by repolarization markers leads to clinical advantages and a lower arrhythmic burden.grafical abstract