An in silico guide for ventriculo-ventricular delay programming for left bundle branch-optimized cardiac resynchronization therapy

Left bundle branch pacing (LBBP)–optimized cardiac resynchronization therapy (LOT-CRT) can improve left ventricular (LV) activation when LBBP alone or conventional biventricular pacing are ineffective. However, the optimal programming settings for ventriculo-ventricular delay (VVD) for LOT-CRT are unknown. We aim to investigate how to optimally program VVD for LOT-CRT in the presence of various LV conduction substrates using computational modelling.

We simulated ventricular activation on 24 anatomies and validated the model against clinical data. Diffuse LV conduction system and intra-myocardial delay were simulated by slowing the conduction velocity of the LV His-Purkinje system and myocardium, respectively, alone or in combination with proximal left bundle branch block (LBBB). We simulated LOT-CRT with selective or myocardial capture (LV septal pacing, LVSP) with VVD ranging between −100 ms (LBBP/LVSP ahead) and +100 ms [LV epicardial lead (LVepiP), ahead]. Response was quantified with 95% LV activation times (LVAT95). In the presence of diffuse LV conduction system delay, the optimal VVD for LOT-CRT was always negative (LBBB: −42.5 ± 6.6 ms; no LBBB: −36.2 ± 5.6 ms), as delivering LBBP ahead of LVepiP compensates for the slow LV His-Purkinje. In the presence of LV intra-myocardial disease, the shortest LVAT95 with LOT-CRT was achieved by pacing the coronary sinus LV first (optimal VVD for LBBB: 23.3 ± 8.5 ms; no LBBB: 79.2 ± 18.0 ms). The type of capture for LOT-CRT affected the optimal VVD, with myocardial capture favouring negative VVDs (LVSP ahead).

The optimal VVD for LOT-CRT depends on the mechanism of delayed LV activation and type of capture achieved, highlighting the importance of VVD optimization.