Joint association of left bundle branch block and cardiomyopathy with incident heart failure: a prospective UK Biobank cohort study

Background Left bundle branch block (LBBB) is frequently implicated in the progression to heart failure (HF). While LBBB often coexists with structural heart disease, it remains unclear whether a history of cardiomyopathy modifies the HF risk associated with LBBB on an additive scale in the general population Purpose We aimed to evaluate whether the history of cardiomyopathy modified the association of LBBB with the risk of HF in the general population from the UK Biobank. Methods This study included a total of 4,145 participants with diagnosed LBBB and matched with 12,876 control subjects without conduction disturbances. Multivariable Cox proportional hazards models estimated hazard ratios (HRs) for incident HF. Interaction was assessed via a multiplicative term and the Relative Excess Risk due to Interaction (RERI) to evaluate additive interaction. Results During a median follow-up period of 14.0 years, 1,264 incident HF cases were documented. In the fully adjusted model (Figure 1A), LBBB (aHR 4.51 [95% CI 3.86-5.26]) and history of cardiomyopathy (aHR 4.04 [95% CI 3.46-4.70]) were the strongest independent predictors of HF. A significant multiplicative interaction was observed (Pinteraction = 0.001), with the prognostic impact of LBBB being more pronounced in those without cardiomyopathy (aHR 4.15 [95% CI 3.52-4.89]) than in those with cardiomyopathy (aHR 3.37 [95% CI 2.20-5.17]). A significant addictive interaction between LBBB and cardiomyopathy with the risk of HF was observed (RERI 6.73 [95% CI 2.85-10.61]; Figure 1B). Conclusion Irrespective of cardiomyopathy status, LBBB confers a markedly elevated hazard of HF. Although the relative prognostic impact is stronger in structurally normal hearts, the significant positive additive interaction indicates that the co-occurrence of LBBB and cardiomyopathy generates substantial excess absolute risk. This suggests that LBBB serves as a critical early sentinel in the general population, while interventions targeting LBBB might yield the greatest absolute benefit in patients with pre-existing cardiomyopathy.