1. Male or female age 21 years or older. (Note: Women of child bearing potential must have a negative urine pregnancy test at study entry and must use effective contraception during study participation.)
2. NYHA Class II-IV HF with LVSD (most recent LVEF < 0.40). The most recent LVEF must have been measured within the 12 months prior to eligibility assessment, using any of the following techniques: echocardiography (transthoracic preferred, but transesophageal is acceptable); contrast ventriculography; radionuclide ventriculography (either Multi Gated Acquisition Scan (MUGA) or Single-photon emission computed tomography (SPECT); gated cardiac computed axial tomography (CT); or cardiac magnetic resonance imaging
3. At high risk of future clinical instability, indicated by EITHER:
a. A hospitalization for the primary reason of decompensated HF within the 12 months prior to screening;
b. A plasma BNP level ≥ 300 pg/ml or NT-proBNP ≥1800pg/ml measured during a period of clinical stability in the 3 months prior to screening.
4. Documented secondary PH within the last 6 months defined as:
a. RV systolic pressure ≥ 40 mmHg calculated from 4*(peak tricuspid regurgitation Doppler velocity)2 + 5 mmHg at rest;
b. Mean PAP of ≥ 25 mmHg at rest calculated from either
-Doppler measurements of RV outflow tract acceleration time Mean PAP = 79 - (0.45 x RVOT acceleration time); OR
-Pulmonic regurgitation (PR) velocity:
Mean PAP = 4∙(peak velocity of PR jet)2 + 5 mmHg
c. Mean PAP ≥ 25 mmHg at rest or ≥ 35 mmHg with supine or upright exercise measured by right heart catheterization.
5. Medication and device treatment according to current AHA/ACC guidelines. Additional treatments beyond those specified by the guidelines are acceptable.
6. Stable medical therapy for 30 days prior to randomization
a. No addition or discontinuation of ACE-inhibitors, ARBs, beta-blockers, calcium channel blockers (CCBs), or diuretics.
b. No change in dosage of ACE-inhibitors, ARBs, beta-blockers, CCBs, or diuretics of more than 100%.
c. Changes in diuretic dose guided by a patient-directed flexible dosing program are considered as stable medical therapy.
7. African-American patients intolerant of or otherwise unable or unwilling to utilize isosorbide dinitrate/hydralazine therapy will be included.
a. AHA/ACC guidelines recommend treatment of African-American Class III-IV HF patients with isosorbide dinitrate (ISDN) and hydralazine as first line therapy.
b. Tadalafil treatment is contraindicated in subjects receiving ISDN, and these patients cannot be enrolled in PITCH HF. African-American subjects who are not able to tolerate ISDN or other nitrate therapy, or are unwilling to utilize such therapy, are eligible for enrollment. The reason that a Class III-IV African-American subject is not taking ISDN/hydralazine (e.g. allergic reaction, intolerance related to a side effect) will be recorded on the screening case report form.
8. Willingness to comply with protocol, attend follow-up appointments, complete all study assessments and provide written informed consent.