Lower Heart Rates and Beta-Blockers Are Associated with New-Onset Atrial Fibrillation

Background: Lower heart rates (HRs) prolong diastole, which increases filling pressures and wall stress. As a result, lower HRs may be associated with higher brain natriuretic peptide (BNP) levels and incident atrial fibrillation (AF). Beta-blockers may thereby increase the risk for AF. Objective: Examine the relationships of HR, BNP, beta-blockers and new-onset AF in the REVEAL-AF and SPRINT cohort of subjects at risk for developing AF. Methods: In REVEAL-AF, 383 subjects without history of AF and a mean CHA2DS2VASC score of 4.4{plus minus}1.3 received an insertable cardiac monitor and were followed up to 30months. In SPRINT, 7595 patients without prior history of AF and a mean CHA2DS2VASC score of 2.3{plus minus}1.2 were followed up to 60months. Results: The median daytime HR in the REVEAL-AF cohort was 75bpm [IQR 68-83]. Subjects with below-median HRs had 2.4-fold higher BNP levels compared to subjects with above-median HRs (median BNP [IQR]: 62pg/dl [37-112] vs. 26pg/dl [13-53], p<0.001). HRs<75bpm were associated with a higher incidence of AF: 37% vs. 27%, p<0.05. This was validated in the SPRINT cohort after adjusting for AF risk factors. Both a HR<75bpm and beta-blockers use were 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 beta-blockers to develop AF was 3.72 [CI 2.32, 5.96], p<0.001. Conclusions: Lower HRs are associated with higher BNP levels and incident AF, mimicking the hemodynamic effects of diastolic dysfunction. This may explain why beta-blockers are associated with a higher risk for new-onset AF. Funding Information: This research was supported by grant R01 HL-122744 from the National Institutes of Health (Dr. Meyer). Declaration of Interests: Dr. Meyer reports having licensed patents on the use of pacemakers to prevent and treat heart failure with preserved ejection fraction; the relationship is modest. Jodi Koehler and Paul Ziegler are employees and shareholders of Medtronic. The remaining authors have no disclosure. Ethics Approval Statement: The REVEAL-AF study was supported by Medtronic and conducted in compliance with applicable local laws and regulation of each participating country. The SPRINT trial was sponsored by the NHLBI and approved by the institutional review board at each participating study site.