Childhood bradycardia associates with atrioventricular conduction defects in older age: a longitudinal birth cohort study

Abstract

Abstract Background A high resting heart rate (RHR) has been associated with cardiovascular morbidity and mortality. However, little is known about the long-term effects of childhood bradycardia. Purpose This study aimed to explore the association between childhood bradycardia and later-life cardiac phenotype using longitudinal data from the 1946 Medical Research Council National Survey of Health and Development (NSHD) birth cohort. Methods RHR was recorded at ages 6 and 7 to provide the bradycardia exposure defined as a childhood RHR<75. Three outcomes were studied: i) echocardiographic data at 60–64 consisting of ejection fraction (EF), left ventricular mass index (LVmassi), myocardial contraction fraction index (MCFi) and E/e'; ii) electrocardiographic (ECG) evidence of atrio-ventricular (AV) conduction defects (Minnesota categories: 6-1, 6-2-1, 6-2-2, 6-2-3, 6-3, 6-8, 8-5-1, 8-5-2, 8-6-1, 8-6-2, 8-6-3 and 8-6-4) or ventricular conduction defects (any Minnesota group 7) by age 60–64; and iii) all-cause and cardiovascular mortality. Generalized linear models (glm) with gamma distribution were used for echocardiographic analyses, glms with binomial distribution for ECG analyses and Cox proportional hazards models for mortality. Adjustment was made for relevant demographic and health-related covariates, and for multiple testing. In order to account for within-subject correlated repeated measures at 6 and 7 years of age, mixed glms (glmms) were used as a sensitivity analysis. To explore any nonlinear relationships, we modeled each outcome as a sum of best fitting fractional polynomials of RHR at 6 and 7 (as continuous variables) and covariates using a “closed test procedure” with backward elimination. Results The number of participants included was: 4381 for mortality, 1631 for ECG and 1617 for echocardiography analyses. Childhood bradycardia was associated with male sex (p<0.0001) and higher BMI (p=0.009). In fully adjusted models, childhood bradycardia was associated with 2.91 higher odds of AV conduction defects (95% confidence interval [CI] 1.59–5.31, p=0.0005), even at a false discovery rate of 0.05. Associations persisted in random coefficients glmm models (odds ratio 2.50, 95% CI 1.01–4.31). The fractional polynomials analyses revealed that the log odds of AV conduction defects at 60–64 years of age were linearly associated with RHR at 7 years. There was no association between bradycardia in childhood and ventricular conduction defects, echocardiographic parameters or mortality outcomes. Conclusions Longitudinal data indicate that childhood bradycardia trebles the odds of having AV conduction defects, but does not influence mortality or heart size and function in older age. As one in three older adults with AV conduction defects will have been bradycardic in childhood, future research should concentrate on identifying children at risk, the potential mechanisms involved and whether AV blocking drugs accelerate nodal dysfunction. Funding Acknowledgement Type of funding sources: Private grant(s) and/or Sponsorship. Main funding source(s): British Heart Foundation (MyoFit46 Special Programme Grant SP/20/2/34841)