Conventional and genetic associations between resting heart rate, cardiac morphology and function as assessed by magnetic resonance imaging: Insights from the UK biobank population study

Abstract

Aim: To examine the direction, strength and causality of the associations of resting heart rate (RHR) with cardiac morphology and function in 20,062 UK Biobank participants.

Methods and results: Participants underwent cardiac magnetic resonance (CMR) and we extracted CMR biventricular structural and functional metrics using automated pipelines. Multivariate linear regression adjusted for the main cardiovascular risk factors and Two-sample Mendelian Randomization analyses were performed to assess the potential relationship, grouped by heart rate and stratified by sex. Each 10 beats per minute increase in RHR was linked with smaller ventricular structure (lower biventricular end-diastolic volume and end-systolic volume), poorer left ventricular (LV) function (lower LV ejection fraction, global longitude strain and global function index) and unhealthy pattern of LV remodeling (higher values of myocardial contraction fraction), but there is no statistical difference in LV wall thickness. These trends are more pronounced among males and consistent with the causal effect direction of genetic variants interpretation. These observations reflect that RHR has an independent and broad impact on LV remodeling, however, genetically-predicted RHR is not statistically related to heart failure.

Conclusion: We demonstrate higher RHR cause smaller ventricular chamber volume, poorer systolic function and unhealthy cardiac remodeling pattern. Our findings provide effective evidence for the potential mechanism of cardiac remodeling and help to explore the potential scope or benefit of intervention.

Keywords: cardiac magnetic resonance; heart failure; left ventricular remodeling; mendelian randomization; resting heart rate.

Figure 1

Associations (β with 95% confidence interval) of per 10 beats per minute increase in resting heart rate and left ventricular magnetic resonance parameters grouped by resting heart rate level (<60 bpm, 60–69 bpm, 70–79 bpm, and ≥80 bpm) in the fully adjusted model. RHR, resting heart rate; bpm, beats per minute; LV, left ventricular; CMR, cardiac magnetic resonance, EDV, end-diastolic volume; ESV, end-systolic volume; SV, stroke volume; EF, ejection fraction; WT, wall thickness.

Figure 2

Clinical observation and two-sample Mendelian randomization analysis testing the effects of resting heart rate on left ventricular magnetic resonance structural parameters. The results are the causal estimates from inverse variance weighted approach and observational effects from multivariable linear regression model with 95% confidence interval, predicting per 10 beats per minute increase in resting heart rate on left ventricular parameters. The linear regression model was adjusted for age, sex, ethnicity, socioeconomic status, alcohol consumption, smoking, physical activity, body mass index, hypertension, diabetes, and heart rate modifying medications. MR, Mendelian randomization; LV, left ventricular; EDV, end-diastolic volume; ESV, end-systolic volume; EF, ejection fraction.