Clinical Outcomes With Personalized Accelerated Physiologic Pacing in Heart Failure With Preserved Ejection Fraction: Follow-up of the myPACE Trial.

IMPORTANCE

Patients with heart failure with preserved ejection fraction (HFpEF) and physiologic pacemakers may benefit from pacing rates above the standard 60 beats per minute (bpm).

OBJECTIVE

To compare adverse event accrual between personalized accelerated pacing and usual care in HFpEF.

DESIGN, SETTING, AND PARTICIPANTS: This was an observational extension of the myPACE randomized clinical trial with up to 4 years of follow-up in 100 patients with stage B or C HFpEF and preexisting physiologic pacemakers treated at the University of Vermont Medical Center. The myPACE study was conducted from June 2019 to December 2021; follow-up for this report was concluded in June 2023.

INTERVENTION

Participants in the original myPACE trial were randomly assigned to either personalized accelerated pacing (myPACE) or 60 bpm (usual care).

MAIN OUTCOMES AND MEASURES

The primary outcome was the accrual of first and recurrent adverse clinical events during the open-label follow-up phase-including urgent visits or hospitalizations for heart failure or atrial fibrillation, myocardial infarction, stroke, or death-assessed using an intention-to-treat (ITT) analysis and a prespecified per-protocol (PP) analysis of patients who continued their assigned treatment. Secondary outcomes included event-free survival in both ITT and PP analyses.

RESULTS

Among the 100 original trial participants (48 in myPACE and 52 in usual care), the ITT analysis demonstrated a trend toward slower event accrual with the myPACE intervention (15 vs 33 events; Lin-Wei-Ying-Yang estimate [LWYY], 0.48; 95% CI, 0.22-1.06; P = .07) and longer event-free survival (hazard ratio [HR], 0.63; 95% CI, 0.31-1.29; P = .20) but did not reach statistical significance. In the prespecified PP analysis, 87 remained on their assigned heart rate setting over the 4-year follow-up (39 in myPACE and 48 in usual care). The mean (SD) age was 74 (10) years, and 48 participants (55%) were male. In this PP analysis, myPACE was associated with a slower accrual of clinical events (5 vs 31 events; LWYY, 0.16; 95% CI, 0.04-0.67; P = .01) and longer event-free survival (HR, 0.30; 95% CI, 0.11-0.80; P = .02) compared to usual care. These results were primarily driven by heart failure-related events.

CONCLUSIONS AND RELEVANCE

In this observational clinical events analysis of the myPACE trial, analysis by ITT did not achieve statistical significance between study arms. However, PP analysis showed that personalized accelerated physiologic pacing was associated with a slower accrual of adverse clinical events compared with the standard 60-bpm setting. These results are hypothesis generating and warrant confirmation in larger multicenter trials.

TRIAL REGISTRATION

ClinicalTrials.gov Identifier: NCT04721314.