Effect of physical activity level on the association of LBBB, heart failure, and mortality

Abstract Background The beneficial effect of physical activity (PA) on adverse cardiovascular outcomes in patients with heart failure (HF) and left bundle branch block (LBBB) is well established. Yet, the impact of PA on individuals with LBBB without evident HF remains unexplored. Our objective is to investigate how PA modifies the outcomes of new-onset LBBB patients concerning HF-related hospitalizations and mortality. Methods Among the UK Biobank participants without a diagnosis of HF, we identified individuals with new-onset LBBB and available PA quantification. Patients were dichotomized into normal QRS and LBBB groups, following by stratification according to summed minutes of PA per week. The primary outcome was all-cause mortality, and HF-related hospitalizations. Cox proportional hazard model and Kaplan-Meier survival analysis were applied. Results The final cohort comprised 367,934 individuals, with a mean age of 56.6±8.2 years and 47% male. Among them, 3,427 (0.9%) developed new-onset LBBB, characterized by advanced age, male predominance, and higher rates of comorbidities. Median summed PA minutes per week were 100 (IQR: 125-180), with no significant difference between normal QRS and LBBB patients. Over a median follow-up of 13.8 years (IQR: 13-14.5), 26,304 patients (7.15%) died. Kaplan-Meier analysis revealed higher mortality risk with reduced PA level and/or LBBB (log-rank p<0.001 for both). Multivariate Cox analysis adjusted for age, sex, and comorbidities showed LBBB patients had over 3.5-fold increased risk of death (HR 3.67, 95% CI 3.39-3.97, p<0.001) compared to normal QRS. The association of LBBB with mortality was modified by weekly PA minutes; those with <150 minutes had nearly 40% higher risk compared to those with ≥150 minutes (HR 3.78, 95% CI 3.43–4.15, p<0.001; HR 3.4, 95% CI 2.93–3.95, p<0.001; p for interaction=0.035). The protective effect of PA was 6% among normal QRS patients, compared to 22% among individuals with LBBB (HR 0.94, 95% CI 0.91 – 0.96, p<0.001 vs. HR 0.78, 95% CI 0.66 – 0.93, p=0.004). Similar findings were observed for HF hospitalizations. Conclusions Although the correlation between LBBB and adverse cardiovascular outcomes remained consistent across both levels of physical activity (PA), it was more pronounced among patients with low PA levels. When assessing the risk in patients with newly diagnosed LBBB, particular attention should be directed towards their PA status.