A porcine large animal model of radiofrequency ablation-induced left bundle branch block
Authors: Wiedmann F , Jamros M , Herlt V , Paasche A , Kraft M , Beck M , Frey N , Schmidt C 
Published: May 2024

Abstract

Funding Acknowledgements
Type of funding sources: Private company. Main funding source(s): Medtronic

Background and Objective
ECG features of left bundle branch (LBB) block (LBBB) can be observed in up to 20–30 % of patients that suffer from heart failure with reduced ejection fraction. The resulting mechanical intraventricular asynchrony contributes to the worsening of left ventricular hemodynamics and has a relevant impact on the prognosis of the affected patients. The fact that we still cannot accurately predict which LBBB patients will benefit from cardiac resynchronization therapy (CRT) underscores that our understanding of the pathophysiology of LBBB remains incomplete. Here, a translational animal model of LBBB could be a major contributor to improving our knowledge of the molecular and translational pathomechanisms underlying LBBB.

Methods
A total of 15 male pigs underwent RF catheter ablation of the LBB, guided by fluoroscopy and intracardiac ECG signals. Before LBBB induction and after a follow-up period of one week or three weeks, a thorough clinical characterization was performed including 12-lead ECG, echocardiography, and electroanatomical mapping. To further test the feasibility of cardiac resynchronization in our model, 3 pigs were implanted with a CRT pacemaker on day seven after LBB ablation.

Results
Upon LBB ablation, 12-lead ECGs displayed typical characteristics of LBBB like a QRS broadening, a QRS slurring in left lateral leads, and a change of the QRS axis. The QRS width was prolonged from 64.2±4.2 ms to 93,4±7.4 ms and the R wave peak time in V6 was extended from 19.3±3.9 ms to 42.7±4.2 ms. Cardiac electromechanical asynchrony was further confirmed by echocardiography, where the appearance of a septal flash, the prolongation of the septal to posterior wall movement delay and extended left ventricular as well as interventricular electromechanical delays were documented. Electroanatomical mapping demonstrated a shift of the left ventricular breakthrough site. After LBBB-induction, left ventricular activation times, defined as the average of the maximum 10 % of activation times minus the average of the minimum 10 % of activation times were significantly prolonged from 36.3±7.1 ms to 60.8±10.2 ms while right ventricular activation times remained unchanged. Finally, RF-induced LBBB persisted over an observation period of three weeks. The pigs that underwent CRT showed a reduction in QRS duration from 99.1±8.2 ms on day seven after LBBB induction to 75.5±8.2 ms and echocardiography provided additional evidence of successful resynchronization.

Conclusions
In summary, our porcine large animal model accurately recapitulates the electrical and electromechanical phenotype, observed in LBBB patients. This closed-chest model of LBBB therefore provides an experimental platform to study both, molecular and translational characteristics of cardiac electromechanical asynchrony in a reproducible and clinically relevant setting.