The role of His-Purkinje system activation in preventing malignant reentrant ventricular arrhythmias during left bundle branch area pacing: Reverse electrical remodeling or restored left ventricular activation?

BACKGROUND: Mechanistic differences in arrhythmia vulnerability between left bundle branch area pacing (LBBAP) and biventricular pacing (BiVP) are unclear. OBJECTIVE: Using computational models and clinical cases for hypothesis-generating support, we investigated whether reverse electrical remodeling or restored left ventricular (LV) activation from LBBAP lowers arrhythmia vulnerability. METHODS: In a human biventricular model with combinations of electrical remodeling from heart failure (HF), left bundle branch block (LBBB), and lateral LV scar, we compared LV activation during His pacing (HisP) with selective LBBAP, nonselective LBBAP, and BiVP. Arrhythmia vulnerability windows (AVWs) were constructed for reentries lasting >2 seconds induced using a clinical S1S2S3 protocol. S1 pacing was administered to the HisP, LBBAP, or BiVP locations, followed by Single S2 and S3 pulses delivered to the LV endocardial apex. Arrhythmia outcome was compared with LBBAP in patients with a history of ventricular arrhythmias. RESULTS: In silico, HisP activation differed with LBBB, but not with HF or LV scar. Selective LBBAP activation in the LV myocardium and His-Purkinje system resembled HisP, whereas nonselective LBBAP and BiVP did not. Sustained reentry was observed only in HF models. Compared to HisP, LBBAP reduced AVWs in HF models with LBBB by 50%-70%. Compared to BiVP, LBBAP reduced AVWs in all HF models by 14%-55%. In patients with and without conduction abnormalities or LV scar, LBBAP reduced ventricular arrhythmia burden at >6-month follow-up. CONCLUSION: Simulations suggest that LBBAP lowers arrhythmia vulnerability by restoring LV activation after LBBB and/or reversing electrical remodeling in patients with HF. Clinical validation through prospective studies is required.