Heart Failure with Preserved Ejection Fraction (HFpEF) Clinical Trials

• Age ≥ 40 years

• Documented EF ≥50% within the preceding 12 months

• HFpEF defined as:

‣ Documented worsening HF episode (either HF hospitalization or documented urgent clinic visit for HF with intravenous diuretics) within 12-months prior to baseline visit OR

⁃ Dyspnea on exertion and New York Heart Association (NYHA) ≥ class II symptoms AND AT LEAST ONE OF THE FOLLOWING CRITERIA:

• Interstitial / pulmonary edema on prior chest imaging in the last year AND current loop diuretic use for heart failure

∙ Elevated NT-proBNP in the last year defined as \>400 pg/m for patients with no AF or paroxysmal AF, or \>900 pg/ml for patients with ≥persistent AF

∙ Mean pulmonary capillary wedge pressure (PCWP) ≥15 mm Hg or LVEDP ≥16 mm Hg at rest on cardiac catheterization OR pulmonary artery diastolic and wedge pressure (PADP) ≥15 mm Hg at rest on implantable monitor (e.g., CardioMEMs)

∙ Echo criteria defined by ≥2 of:

‣ LV wall thickness ≥ 12 mm

⁃ LV mass index (BSA indexed LVH): sex at birth male \>115 g/m2, sex at birth female \>95 g/m2

⁃ Relative wall thickness ≥0.42

⁃ E/e' ≥15 in sinus rhythm (or \> 11 in the setting of atrial fibrillation) OR septal \<7 cm/s or lateral e' \<10cm/s

⁃ Tricuspid regurgitation (TR) velocity \>2.8 m/s

⁃ Left atrial (LA) enlargement, defined by LA volume index \>34 ml/m2

• Patient is on stable guideline indicated HF medical therapy (Class I recommendations) for at least 30 days

• Patient's average heart rate on baseline ambulatory electrocardiographic monitor is at least 5 bpm lower than their calculated personalized cardiac pacing rate (e.g. if a patient's personalized cardiac pacing rate is 70 bpm and their average heart rate on the ambulatory electrocardiographic monitor is less than or equal to 65 bpm the patient is eligible)

• Patient is willing and able to adhere to the protocol (e.g., patient is able to ambulate independently at baseline).