Nicole Habel

Background: Heart failure with preserved ejection fraction ≥50% is prevalent with few evidence‐based therapies. In a trial of patients with heart failure with preserved ejection fraction with specialized pacemakers, treatment with accelerated personalized pacing averaging 75 bpm (myPACE) markedly improved quality of life, NT‐proBNP (N‐terminal pro–brain natriuretic peptide), physical activity, and atrial fibrillation burden compared with the standard lower rate setting of 60 bpm (usual care). Methods and Results: In this exploratory study, provider‐initiated echocardiographic studies obtained before and after the trial were assessed for changes in left ventricular (LV) structure and function among participants who continued their pacing assignment. The analytic approach aimed to detect differences in standard and advanced echocardiographic parameters within and between study arms. Of the 100 participants, 16 myPACE and 20 usual care arm had a qualifying set of echocardiograms performed a mean (SD) 3 (2.0) years apart. Despite similar baseline echocardiogram measures, sustained exposure to moderately accelerated pacing resulted in reduced septal wall thickness (in cm: myPACE 1.1 [0.2] versus usual care 1.2 [0.2], P =0.008) and lower LV mass to systolic volume ratio (in g/mL: myPACE 4.8 [1.9] versus usual care 6.8 [3.1], P =0.038) accompanied by a minor reduction in LV ejection fraction (in %: myPACE 55 [5] versus usual care 60 [5], P =0.015). These changes were paralleled by improvements in heart failure‐related quality of life (myPACE Minnesota Living with Heart Failure Questionnaire improved by 16.1 [13.9] points, whereas usual care worsened by 6.9 [11.6] points, P <0.001). Markers of diastolic function and LV performance were not affected. Conclusions: Exposure to continuous accelerated pacing in heart failure with preserved ejection fraction is associated with a reduced LV wall thickness and a small amount of LV dilation with small reduction in ejection fraction.

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