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

Purpose: To investigate the progressive remodelling that develops over time in an animal model of LBBB.

Methods: Fifteen 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 5 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 (+83%, p<0.0001) and LBBB-like mechanical dyssynchrony, with mild early-systolic notching and preserved systolic shortening of the septal wall. Early lateral wall pre-stretch was followed by increasing systolic shortening. No acute changes in LV end-diastolic volume, LVEF or septal or lateral wall thickness were observed (all p>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 shortening was reduced compared to baseline (p<0.05). QRS duration progressively increased by +15% (week 8) and +26% (week 16) (all p<0.001). End-diastolic volumes had increased by +38% (week 8) and +74% (week 16), whereas LVEF had decreased by –35% (week 8) and –55% (week 16) (all p<0.001). Septal wall thickness had reduced by –18% (week 8) and –29% (week 16), while lateral wall thickness had increased by +13% (week 8) and +24% (week 16) (all p<0.05).

Conclusion: A persisting LBBB induces progressive changes in LV deformation patterns, and triggers morphological and electrical remodelling, strengthening the concept of LBBB-induced cardiomyopathy. In the clinic, patients with mild dysfunction should be closely monitored for potential disease progression in order to treat dyssynchrony as soon as guideline indications are reached. Further studies need to show if earlier CRT-implantation might prevent further LV deterioration.