Patient-reported Outcomes in Vericiguat-treated Patients With HFpEF

Inclusion Criteria:

- Previous diagnosis of chronic heart failure (HF)

- HF decompensation within 6 months prior to randomization, defined as hospitalization
for HF or intravenous (IV) diuretic treatment for HF without hospitalization.

- N-terminal pro brain natriuretic peptide (NT-proBNP) ≥300 or brain natriuretic peptide
(BNP) ≥100 pg/mL in sinus rhythm, or NT-proBNP

≥600 or BNP ≥200 pg/mL in atrial fibrillation within 30 days prior to randomization

- Diagnostic criteria of HFpEF by echocardiography assessed within 12 months prior to
randomization (most recent measurement must be used to determine eligibility with no
interim event signaling potential deterioration in ejection fraction)

- Left ventricular ejection fraction (LVEF) ≥45% and

- Structural changes indicated by at least one of the following parameters:

- Left ventricle (LV) hypertrophy (any of the following: intraventricular
septal or posterior wall thickness ≥1.1 cm, and/or LV mass index ≥115 g/m*2
in male and ≥95 g/m*2 in female), or

- Left atrium (LA) enlargement (any of the following: left atrial volume (LAV)
index ≥29 ml/m*2, or LAV >58 mL in male and >52 mL in female patients, or LA
area >20 cm*2, or LA diameter >40 mm in male and >38 mm in female patients)

- NYHA class II or III at randomization

Exclusion Criteria:

- Clinical instability at randomization, defined by

- Any IV treatment within 24h prior to randomization, and/or

- SBP ≥160 mmHg

- SBP <110 mmHg and/or DBP <40 mmHg and/or symptomatic hypotension

- Resting heart rate (HR) <50 or ≥100 beats per minute (bpm)

- Use of IV inotropes at any time between qualifying HF event and randomization

- Previous diagnosis of reduced ejection fraction (EF) (EF <40%)

- Hypertrophic obstructive cardiomyopathy, acute myocarditis, amyloidosis, sarcoidosis,
or pericardial disease

- Primary valvular heart disease requiring surgery or intervention, or within 3 months
after valvular surgery or intervention, or active endocarditis

- Acute coronary syndrome, including unstable angina, Non ST-elevation myocardial
infarction or ST-elevation myocardial infarction, or Coronary artery bypass grafting
(CABG) within 60 days prior to randomization, or indication for Percutaneous coronary
intervention or CABG at the time of randomization

- Symptomatic carotid stenosis, or transient ischemic attack or stroke within 60 days
prior to randomization

- Complex congenital heart disease

- Non-cardiac comorbidity (any of the following)

- Estimated glomerular filtration rate (eGFR) <30 ml/min/1.73 m*2 calculated by
Modification of Diet in Renal Disease formula

- Hepatic insufficiency classified as Child-Pugh B or C

- Morbid obesity with a body mass index >45 kg/m*2

- Malignancy or other non-cardiac condition limiting life expectancy to <1 year,
per physician judgment

- Requires continuous home oxygen for severe pulmonary disease or has interstitial
lung disease

- Patients with allergies, intolerance or hypersensitivity to investigational drug
or any of the excipients

- Concurrent or anticipated use of nitrates or NO donors, phosphodiesterase type V
(PDE5) inhibitors, or a Soluble guanylate cyclase (sGC) stimulator