Heart Failure Clinical Trials

• Chronic heart failure, defined as:

‣ Symptoms of HF requiring current (intermittent or continuous) treatment with diuretics for \>30 days, AND

⁃ NYHA class II with a history of \>NYHA class II in the past year, NYHA class III, or ambulatory NYHA class IV symptoms (paroxysmal nocturnal dyspnea, orthopnea, dyspnea on mild or moderate exertion) at screening or signs of HF (any rales post cough, chest x-ray demonstrating pulmonary congestion), AND

⁃ At least one of the following:

• i. ≥1 HF hospital admission (with HF as the primary diagnosis) including treatment with intravenous (IV) diuretics or urgent unplanned treatment with IV diuretics in healthcare facility within past 12 months, OR ii. NT-proBNP \>300 pg/ml in normal sinus rhythm (\>450 pg/ml in atrial fibrillation or flutter) within the past 6 months; BNP \>100 pg/ml in normal sinus rhythm (\>300 pg/ml in atrial fibrillation or flutter) within the past 6 months, OR iii. Right heart catheterization (RHC) with PCWP ≥ with PCWP ≥18 mmHg at rest or 25 mmHg during exercise at the time of the screening RHC.

• Ongoing stable GDMT HF management (unless unable to tolerate GDMT) and management of potential comorbidities according to the 2022 ACCF/AHA Guideline for the Management of Heart Failure (Class 1 and 2a recommendations), with no significant changes \[≥100% increase or ≥50% decrease\] for a minimum of 1 month (30 days) prior to screening, that is expected to be maintained without change for at least 6 months. Participants cannot have started a glucagon-like peptide (GLP)-1 or gastric inhibitory peptide (GIP) agonist within the last 6 months or plan to start a GLP-1 or GIP agonist within the ensuing 6 months after enrollment.

• LVEF ≥50% (site-determined by transthoracic echocardiography) within the past 6 months.

• Age ≥40 years.

• Subject is willing and able to provide appropriate study-specific informed consent, follow protocol procedures, and comply with follow-up visit requirements.