Sequential left ventricular electro-mechanical changes in presence of left bundle branch block
Authors: Duchenne J , Calle S , Puvrez A , Rega F , Timmermans F , Voigt J U 
Published: October 2021

Abstract

Introduction
Recent cross-sectional studies suggest a relationship between persisting left bundle branch block (LBBB) and the extent of left ventricular (LV) electro-mechanical alterations over time. When patients are referred for cardiac resynchronization therapy (CRT), temporal data during the sub-clinical phase of disease is often missing. A longitudinal study using an animal model would provide a better understanding of the relationship between the onset of LBBB and the electro-mechanical changes.

Purpose
To investigate the sequential alterations in LV structure and function that develop over time in an animal model of LBBB.

Methods
Thirteen sheep were subjected to rapid DDD pacing (180 bpm; leads on right atrium and right ventricular free wall) in order to induce a LBBB-like conduction delay. All animals underwent an 8-week pacing protocol, whereas 4 of them were subjected to 16 weeks of pacing in total. Echocardiographic speckle tracking was used to assess circumferential strain of the septal and lateral wall. Septal and lateral wall thickness were measured at end-diastole. Cardiac magnetic resonance imaging was used to determine LV volumes and ejection fraction (LVEF). Examinations took place at baseline (before and after start of pacing), and after 8 and 16 weeks of pacing. All examinations were performed at a physiologic heart rate of 110 bpm.

Results
At baseline, DDD pacing induced an increase in QRS duration (+85%, p&lt;0.0001) and LBBB-like mechanical dyssynchrony, with mild early-systolic notching and preserved systolic shortening of the septal wall. The lateral wall demonstrated early pre-stretch followed by increasing systolic shortening. No acute changes in LV end-diastolic volume, LVEF or septal or lateral wall thickness were observed (all p&gt;0.05). After 8 weeks of DDD pacing, mechanical dyssynchrony worsened: septal notching increased, followed by reduced systolic shortening. After 16 weeks, the initial septal shortening was followed by profound stretching throughout systole. Lateral wall systolic shortening was reduced compared to baseline. QRS duration increased further by +12% (week 8) and +20% (week 16) (all p&lt;0.001). End-diastolic volumes had increased by +39% (week 8) and +72% (week 16), whereas LVEF had decreased by −48% (week 8) and −56% (week 16) (all p&lt;0.001). Septal wall thickness had reduced by −24% (week 8) and −33% (week 16), while lateral wall thickness had increased by +21% (week 8) and +30% (week 16) (all p&lt;0.05).

Conclusion
A persisting LBBB-like conduction delay induces sequential changes in LV deformation patterns, and triggers morphological and electrical remodelling. These changes are similar to those observed in patients with LBBB and different degrees of LV dysfunction. Our data suggest a continuum due to the progression of LBBB-induced LV disease. In the clinic, patients with mild dysfunction should be closely monitored in order to treat dyssynchrony as soon as guideline indications are reached.

Funding Acknowledgement
Type of funding sources: Other. Main funding source(s): This work was supported by a KU Leuven research grant