A Study to Evaluate Whether Macitentan is an Effective and Safe Treatment for Patients With Heart Failure With Preserved Ejection Fraction and Pulmonary Vascular Disease

Inclusion Criteria:

- Signs or symptoms of Heart Failure (HF) (NYHA FC I I and II I ) requiring treatment
with at least one oral diuretic (any type)

- Left ventricular ejection fraction (LVEF) ≥ 40% (by echocardiography at Screening)

- Structural heart disease consistent with heart failure with preserved ejection
fraction (HFpEF) established by echocardiography at Screening

- HF hospitalization within 12 months prior to Screening and/or cardiac catheterization
performed within 6 months prior to Screening showing PAWP or LVEDP > 15 mmHg

- Elevated NT-proBNP

- Pulmonary vascular disease or right ventricular dysfunction

Exclusion Criteria:

- Any prior measurement of LVEF < 40%.

- Cardiovascular co-morbidities (e.g., significant unrepaired structural valvular heart
disease; acute coronary syndrome, coronary artery bypass graft (CABG) or percutaneous
coronary intervention (PCI) within 3 months of Screening; uncontrolled heart rate from
atrial fibrillation or atrial flutter, history of serious life-threatening or
hemodynamically significant arrhythmia; history of or anticipated heart transplant or
ventricular assist device implantation, etc)

- Systolic blood pressure (SBP) ≥ 180 mmHg, or diastolic blood pressure (DBP) ≥ 110 mmHg
during Screening

- Body mass index (BMI) ≥ 45 kg/m2

- Hemoglobin < 100g/L (< 10 g/dl) at Screening.

- Significant parenchymal lung disease (e.g., severe COPD, moderate or severe
restrictive lung disease, diffuse interstitial fibrosis or alveolitis, pulmonary
thromboembolism)

- Severe renal dysfunction with an estimated Glomerular Filtration Rate (eGFR) < 30
mL/min per 1.73 m2

- Severe hepatic impairment, e.g., Child Pugh Class C.

Other protocol-defined inclusion/exclusion criteria may apply.