MELODY

Main Inclusion Criteria:

(1) Males or females ≥ 18 years of age.

(2) Chronic heart failure fulfilling all of the following criteria:

a. Relevant structural heart disease and/or diastolic dysfunction [ESC Guidelines 2012].

b. Ejection fraction ≥ 30% measured by echocardiography.

c. New York Heart Association (NYHA) functional Class II or III.

(3) Pulmonary hypertension (PH) in WHO group 2 (Nice classification) with a pulmonary artery wedge pressure

(PAWP) of > 15 mmHg confirmed by any previous right heart catheterization (RHC).

(4)  RHC within 12 weeks prior to the Screening visit or during the Screening period showing the following:

a. Mean pulmonary artery pressure (mPAP) ≥ 25 mmHg at rest.

b. PAWP or left ventricular end diastolic pressure ≤ 25 mmHg.

c. Pulmonary vascular resistance (PVR) at rest ≥ 240 dyn∙sec/cm5

d. Diastolic pulmonary vascular pressure gradient (DPG) ≥ 7 mmHg.

(5) 6-minute walk distance ≥ 150 m at Screening or Randomization.

Main exclusion criteria:

(1) PH associated with significant unrepaired structural valvular heart disease (i.e., moderate or severe aortic

stenosis, aortic insufficiency, mitral stenosis, mitral regurgitation still persisting after fluid control).

(2) Evidence of pulmonary edema; Presence of orthopnea.

(3) Presence of moderate to severe peripheral edema despite optimal diuretic therapy

(4) History of pulmonary thromboembolism with segmental defect on ventilation/perfusion scan.

(5) Systemic hypertension, i.e., systolic blood pressure (SBP) > 180 mmHg or diastolic blood pressure (DBP) > 100 mmHg; SBP < 90 mmHg; Uncontrolled heart rate from atrial fibrillation (> 100 beats per minute).

(6) Severe obstructive lung disease defined as: forced expiratory volume in 1 second / forced vital capacity (FEV1/FVC) < 0.7 associated with FEV1 < 50% of predicted value after bronchodilator administration;  Known severe emphysema, e.g., total lung capacity > 120% of predicted value.

(7)  Myocardial infarction within 6 months prior to Randomization.