Lower heart rates and beta-blockers are associated with new-onset atrial fibrillation

Abstract

Abstract Background Lower heart rates (HRs) prolong diastole, thereby raising filling pressures and wall stress (1,2), slowing myocardial relaxation (3), and increasing central blood pressure via superposition of reflected peripheral pressure waves onto systole (2,4). As a result, lower HRs may be associated with higher brain natriuretic peptide (BNP) levels and incident atrial fibrillation (AF). Beta-blockers (BBs) may thereby increase the risk for AF. Purpose Examine the relationships of HR, BNP, BB use and new-onset AF in the REVEAL-AF and SPRINT cohort of subjects at risk for developing AF. Methods In REVEAL-AF, 383 subjects (52% male, mean age 71.5±9.8 years) without a history of AF and a mean CHA2DS2VASC score of 4.4±1.3 received an insertable cardiac monitor and were followed up to 30 months. Baseline HRs were averaged between 8AM and 8PM for the first week post-implantation. Adjudicated AF lasting ≥6 minutes was defined as new-onset AF. In SPRINT, 7595 patients (64% male, mean age 67.5±9.2 years) without prior history of AF and a mean CHA2DS2VASC score of 2.3±1.2 were followed for up to 60 months. Baseline average HR was derived from three seated measurements taken at the initial clinical visit. 12-lead ECG at baseline, 2 years, 4 years and close-out visit were used to determine presence of AF. Based on longitudinal medication inventories BB use was categorized into “on BB” vs “never on BB” for the duration of the trial. Results The median daytime HR in the REVEAL-AF cohort was 75bpm [interquartile range, IQR 68–83]. Subjects with below median HRs had 2.4-fold higher BNP levels when compared to subjects with above median HRs (median BNP [IQR]: 62pg/dl [37–112] vs. 26pg/dl [13–53], p<0.001). Below median HRs were associated with a higher incidence of AF: 37% vs. 27%, p=0.047. This was validated in the SPRINT cohort after adjusting for AF risk factors (age, HR, sex, body mass index, coronary artery disease, intensive vs standard blood pressure therapy, chronic kidney disease). Both a HR<75bpm and BB use were independently associated with a higher rate of AF: 1.9 vs 0.7%, p<0.001 and 2.5% vs. 0.6%, p<0.001, respectively. The hazard ratio for patients on BB to develop AF was 3.72 [CI 2.32, 5.96], p<0.001. Conclusion Lower HRs and BB use are associated with higher BNP levels and incident AF, supporting the hypothesis that lower HRs mimic and/or exacerbate the hemodynamic effects of diastolic dysfunction and promote atrial myopathy. The effects of BBs on clinical outcomes in patient populations outside the context of heart failure with reduced ejection fraction will need to be reassessed. Funding Acknowledgement Type of funding sources: Public grant(s) – National budget only. Main funding source(s): National Institute of Health