PrEcision Pacing in HFpEF: the PEP-HFpEF Trial

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.