Personalized pacing for diastolic dysfunction and heart failure with preserved ejection fraction: Design and rationale for the my PACE randomized controlled trial

Margaret Infeld, Kramer Wahlberg, Jillian Cicero, Sean Meagher, Nicole Habel, Anand Muthu Krishnan, Daniel N Silverman, Daniel L Lustgarten, Markus Meyer, Margaret Infeld, Kramer Wahlberg, Jillian Cicero, Sean Meagher, Nicole Habel, Anand Muthu Krishnan, Daniel N Silverman, Daniel L Lustgarten, Markus Meyer

Abstract

Background: Patients with pacemakers and heart failure with preserved ejection fraction (HFpEF) or isolated diastolic dysfunction (DD) may benefit from a higher backup heart rate (HR) setting compared with the standard setting of 60 bpm.

Objective: The purpose of this study was to assess the effects of a personalized backup HR setting (myPACE group) compared with 60 bpm (control group).

Methods: In this prospective, blinded, randomized controlled study, pacemaker patients with DD or HFpEF and atrial pacing with intrinsic ventricular conduction or conduction system or biventricular pacing are randomized to the myPACE group or control group for 1 year. The primary outcome is the change in Minnesota Living with Heart Failure Questionnaire (MLHFQ) scores. Secondary endpoints include changes in N-terminal pro-brain natriuretic peptide levels, physical and emotional MLHFQ subscores, and pacemaker-detected atrial arrhythmia burden, patient activity levels, and thoracic impedance; hospitalization for heart failure, atrial fibrillation, cerebrovascular accident, or myocardial infarction; and loop diuretic or antiarrhythmic medication initiation or up-titration. A sample size of 118 subjects is expected to allow detection of a 5-point change in MLHFQ score in an intention-to-treat analysis and allow initial assessment of clinical outcomes and subgroup analyses.

Results: Enrollment began in July 2019. As of November 2020, 107 subjects have been enrolled. It is projected that the 1-year follow-up will be completed by December 2021.

Conclusion: Atrial pacing with intrinsic ventricular conduction or advanced ventricular pacing at a higher, personalized backup HR may be a therapeutic target for patients with isolated DD or HFpEF. The myPACE trial is designed to test this hypothesis.

Keywords: Diastolic dysfunction; Heart failure with preserved ejection fraction; Heart rate; Pacing.

© 2021 Heart Rhythm Society. Published by Elsevier Inc.

Figures

Figure 1
Figure 1
Pacing at moderately higher heart rates improves myocardial relaxation and decreases filling pressures in patients with heart failure with preserved ejection fraction or isolated diastolic dysfunction. Conduction system or biventricular pacing that optimizes ventricular synchrony avoids deleterious effects that could be seen with a high burden of right ventricular pacing. ECG = electrocardiogram; LV = left ventricle; RV = right ventricle.
Figure 2
Figure 2
Personalized heart rate (HR) algorithm in myPACE. We developed a HR algorithm based on physiological resting HRs in healthy adults to provide a customized backup HR to pacemaker patients based on height (5th percentile, median, and 95th percentile) in both women (left) and men (right), and modified by ejection fraction.
Figure 3
Figure 3
myPACE study flowchart. Patients scheduled in our pacemaker clinic are consecutively screened. Those patients who are enrolled complete a baseline MLHFQ quality-of-life score, NTproBNP, and a pacemaker interrogation. Patients are randomized to either the myPACE or the control group. NTproBNP was repeated at 1 month, and MLHFQ was repeated at 1 month and 1 year. Pacemaker-detected data and clinical outcomes are monitored during the 1-year study period. MLHFQ = Minnesota Living with Heart Failure Questionnaire; NTproBNP = N-terminal pro–brain natriuretic peptide; PPM = permanent pacemaker.
Figure 4
Figure 4
Schematic left ventricular pressure–volume (PV) loops derived from hemodynamic studies in patients with heart failure with preserved ejection fraction. Effects of a heart rate (HR) increase from the pacemaker backup rate of 60 bpm to normal HRs are shown. Higher HRs lower left ventricular end-diastolic volume and pressure by a shortened left ventricular filling time and leftward shift of the PV loop.

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Source: PubMed

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