PrEcision Pacing in HFpEF: the PEP-HFpEF Trial

November 9, 2026 updated by: Tufts Medical Center

The PEP-HFpEF study is a prospective, single-center mechanistic study evaluating personalized heart rate pacing (myPACE) in patients with heart failure with preserved ejection fraction (HFpEF) and existing cardiac physiologic pacemakers. Participants will undergo sequential periods of standard and personalized pacing with serial physiologic assessments to evaluate the effects of myPACE on exercise capacity, cardiac function, biomarkers, quality of life, and clinical outcomes.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Estimated)

36

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Age ≥18 years.
  • Diagnosis of heart failure with preserved ejection fraction (HFpEF), defined as left ventricular ejection fraction (LVEF) ≥50% with symptoms and signs consistent with heart failure as determined by the treating investigator.
  • New York Heart Association (NYHA) Class II or III symptoms despite stable, maximally tolerated guideline-directed medical therapy.
  • Pre-existing FDA-approved cardiac physiologic pacemaker (e.g., conduction system pacing or cardiac resynchronization therapy) implanted for a standard clinical indication and capable of individualized lower-rate programming.
  • Expected to require ongoing pacemaker therapy throughout the study period.
  • Clinically stable at enrollment, without recent major changes in heart failure status that, in the opinion of the investigator, would interfere with interpretation of study outcomes.
  • Able and willing to provide written informed consent.
  • Able and willing to comply with all study procedures, including pacemaker programming, cardiopulmonary exercise testing (CPET), echocardiography, blood pressure measurements, autonomic testing, blood collection, and follow-up visits.

Exclusion Criteria:

  • Age <18 years.
  • Left ventricular ejection fraction <50%.
  • Pregnancy, breastfeeding, or women of childbearing potential unwilling to use an acceptable method of contraception during study participation.
  • Inability or unwillingness to provide informed consent.
  • Inability to safely perform study procedures, including CPET or autonomic testing, in the opinion of the investigator.
  • Any medical condition or life expectancy that, in the opinion of the investigator, would make participation unsafe or would substantially interfere with completion of the study or interpretation of study results.
  • Enrollment in another interventional clinical trial that, in the opinion of the investigators, could interfere with this study or confound interpretation of the results.
  • Prisoners, wards of the state, or other individuals for whom participation would not be permissible under applicable regulations or institutional policy.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Individualized myPACE Pacing

Participants will undergo a 3-month baseline period with their pacemaker programmed to standard-of-care settings (lower rate limit of 60 beats per minute), followed by individualized programming using the myPACE heart-rate algorithm for 12 months. Following completion of the 12-month intervention period, pacemakers will be reprogrammed to standard-of-care settings (60 bpm) for an additional 3 months. Participants will undergo study assessments and monitoring throughout the entire 18-month study period.
Device: Individualized myPACE pacemaker programming

The myPACE intervention uses an individualized heart-rate algorithm to determine a personalized pacemaker backup rate within the normal range of adult resting heart rates. The algorithm estimates an individualized resting heart rate based on participant height and left ventricular ejection fraction (LVEF). The algorithm is designed to provide a modest increase in resting heart rate tailored to individual physiologic characteristics, including LVEF.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Peak Oxygen Consumption (Peak VO₂)
Time Frame: Baseline, 12 months

Change in peak oxygen consumption (peak VO2) during upright bicycle cardiopulmonary exercise testing (CPET), from conventional 60 bpm pacing (at baseline) to personalized physiologic pacing (myPACE) (at 12 months). Peak VO2 will be measured in mL/kg/min.
Baseline, 12 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Ventilatory Efficiency (VE/VCO₂ Slope)
Time Frame: Baseline, 12 months

Change in the VE/VCO₂ slope during upright bicycle CPET from conventional pacing at 60 bpm to personalized physiologic pacing (myPACE).
Baseline, 12 months
Oxygen Pulse
Time Frame: Baseline, 12 months

Change in oxygen pulse during upright bicycle CPET from conventional pacing at 60 bpm to personalized physiologic pacing (myPACE), measured in mL/beat.
Baseline, 12 months
Arterial Elastance (Ea)
Time Frame: Baseline, 12 months

Change in arterial elastance (Ea), measured in mmHg/mL, calculated from echocardiographic measurements and non-invasive blood pressure measurements, from conventional pacing at 60 bpm at baseline to personalized physiologic pacing (myPACE) at 12 months.
Baseline, 12 months
End-Systolic Elastance (Ees)
Time Frame: Baseline, 12 months

Change in end-systolic elastance (Ees), measured in mmHg/mL, calculated from echocardiographic measurements and non-invasive blood pressure measurements, from conventional pacing at 60 bpm at baseline to personalized physiologic pacing (myPACE) at 12 months.
Baseline, 12 months
Ventriculo-Arterial Coupling (Ea/Ees Ratio)
Time Frame: Baseline, 12 months

Change in the Ea/Ees ratio, calculated from arterial elastance (Ea) and end-systolic elastance (Ees), from conventional pacing at 60 bpm at baseline to personalized physiologic pacing (myPACE) at 12 months.
Baseline, 12 months
Low-Frequency Blood Pressure Variability
Time Frame: Baseline, 12 months

Change in low-frequency blood-pressure variability during standardized autonomic nervous system testing from conventional pacing at 60 bpm at baseline to personalized physiologic pacing (myPACE) at 12 months.
Baseline, 12 months
Orthostatic Blood Pressure Recovery
Time Frame: Baseline, 12 months

Change in orthostatic blood pressure recovery during standardized autonomic nervous system testing from conventional pacing at 60 bpm at baseline to personalized physiologic pacing (myPACE) at 12 months.
Baseline, 12 months
Passive Leg Raise Response
Time Frame: Baseline, 12 months

Change in the passive-leg-raise response during standardized autonomic nervous system testing from conventional pacing at 60 bpm at baseline to personalized physiologic pacing (myPACE) at 12 months.
Baseline, 12 months
NTproBNP
Time Frame: Baseline, 6 months, 12 months, 15 months

NTproBNP level change from baseline to 12 months
Baseline, 6 months, 12 months, 15 months
Minnesota Living with Heart Failure Questionnaire Score
Time Frame: Baseline, 12 months

Change in total score on the Minnesota Living with Heart Failure Questionnaire (MLHFQ), a 21-item questionnaire assessing the impact of heart failure on health-related quality of life. The total score ranges from 0 to 105, with higher scores indicating worse health-related quality of life and greater impairment. Change in total score will be assessed from baseline to 12 months to evaluate the effect of personalized physiologic pacing compared with conventional pacing at 60 beats per minute.
Baseline, 12 months
Hospitalization or Invasive Outpatient Intervention for Heart Failure
Time Frame: Through 18 months

Throughout the duration of the study the study team will review intercurrent clinical management events that may occur as part of the natural history and clinical management of HFpEF, including hospitalization or invasive outpatient intervention for heart failure.
Through 18 months
Heart Failure Management Events
Time Frame: Through 18 months

Changes in heart failure management, including diuretic initiation, dose escalation, reduction, or discontinuation, and urgent medical visits for heart failure. Clinical events will be assessed through participant interviews and medical record review throughout study participation and formally assessed during each follow-up Assessment Window.
Through 18 months
Abnormal Heart Rhythm Management Events
Time Frame: Through 18 months

Throughout the duration of the study the study team will record changes in abnormal heart rhythm management, including initiation of antiarrhythmic medication, cardioversion, ablation, urgent medical visits for abnormal heart rhythms, or hospitalization for abnormal heart rhythms. Clinical events will be assessed through participant interviews and medical record review throughout study participation and formally assessed during each follow-up Assessment Window.
Through 18 months
Serious Cardiovascular Events
Time Frame: Through 18 months

Throughout the duration of the study the study team will review serious cardiovascular events, including heart attack, stroke, or death. Clinical events will be assessed through participant interviews and medical record review throughout study participation and formally assessed during each follow-up Assessment Window.
Through 18 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Tufts Medical Center

Investigators

  • Principal Investigator: Margaret Infeld, MD, MS, Tufts Medical Center

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Estimated)

November 1, 2026

Primary Completion (Estimated)

March 1, 2029

Study Completion (Estimated)

September 1, 2029

Study Registration Dates

First Submitted

August 14, 2026

First Submitted That Met QC Criteria

October 2, 2026

First Posted (Actual)

October 8, 2026

Study Record Updates

Last Update Posted (Actual)

November 10, 2026

Last Update Submitted That Met QC Criteria

November 9, 2026

Last Verified

November 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • STUDY00007273: PEP-HFpEF
  • 26CDA1621876 (Other Grant/Funding Number: American Heart Association)

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

Yes

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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