Accelerated pacing rates to improve exercise tolerance, quality of life, and arrhythmia burden in patients with evidence of heart failure with preserved ejection fraction: the PACE-UP rationale and design

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Background Patients with permanent pacemakers (PPM) often present with early or established heart failure with preserved ejection fraction (HFpEF). Increasing the lower pacing rate has demonstrated improvements in quality of life and patient physical activity, whilst lowering the burden of atrial arrhythmias. However, the impact on objective measures of exercise tolerance and cardiac function are not well established. Objectives This study aims to assess the impact of an accelerated lower rate setting on peak oxygen consumption (VO 2peak ) in patients with stage B/C HFpEF. Methods The PACE-UP study (Accelerated Pacing Rates to Improve Exercise Tolerance, Quality of Life and Arrhythmia Burden in Patients with Evidence of Heart Failure with Preserved Ejection Fraction) is a multicentre, prospective, two-arm randomised controlled trial recruiting 160 participants. Participants will be randomised to accelerated pacing rate (75 beats per minute (bpm) - Hi-PACE) or usual care (60 bpm - Lo-PACE), with follow-up assessments at 4-weeks and 52-weeks post-randomisation. Results The primary endpoint is VO 2peak obtained during cardiopulmonary exercise testing at 52-weeks post-randomisation. Secondary endpoints include change in N-terminal pro-B-type natriuretic peptide, Minnesota Living with Heart Failure Questionnaire, device-detected atrial arrhythmias and physical activity, resting and exercise transthoracic echocardiography, and Montreal Cognitive Assessment. Conclusion This trial will be the first randomised trial to assess the impact of a high lower rate pacing on objective exercise tolerance and cardiac function in patients with stage B/C HFpEF. We anticipate the findings to improve our knowledge and will guide pacemaker programming for patients with HFpEF.