A 48-week Study of the Effect of Dual Therapy (Inhaled Treprostinil and Tadafafil) Versus Monotherapy (Tadalafil).

Exclusion Criteria

• •1. Group II - V pulmonary hypertension.
• •2. PAH with unrepaired congenital heart defect.
• •3. Current or prior PAH treatments within the last 6-12 months including experimental PAH therapies (including but not limited to tyrosine kinase inhibitors, rho-kinase inhibitors, phosphodiesterase inhibitors, prostacycline, or cGMP modulators).
• •4. TLC \< 60% predicted; if TLC b/w 60 and 70% predicted, high resolution computed tomography must be available to exclude significant interstitial lung disease.
• •5. FEV1 / FVC \< 70% predicted and FEV1 \< 60% predicted
• •6. Significant left-sided heart disease (based on pre-trial Echocardiogram):
• •1. Significant aortic or mitral valve disease
• •2. Diastolic dysfunction ; Grade II C.LV systolic function \< 45%
• •d. Pericardial constriction e. Restrictive cardiomyopathy f. Significant coronary disease with demonstrable ischemia
• •7. Chronic renal insufficiency defined as an estimated creatinine clearance \< 30 ml/min (by MDRD equation)
• •8. Current atrial arrhythmias
• •9. Uncontrolled systemic hypertension: SBP \> 160 mm or DBP \> 100mm
• •10. Severe hypotension: SBP \< 80 mmHg.
• •11. Pregnant or breast-feeding
• •12. Psychiatric, addictive, or other disorder that compromises patient's ability to provide informed consent, follow study protocol, and adhere to treatment instructions
• •13. Co-morbid conditions that would impair a patient's exercise performance and ability to assess WHO functional class, including but not limited to chronic low-back pain or peripheral musculoskeletal problems.
• •14. Contraindications for magnetic resonance imaging, including significant claustrophobia, implanted metallic objects, or others as per Appendix X).
• •15. Known allergy to treprostinil or tadalafil.
• •16. Active oral nitrate use.
• •17. Diabetes mellitus.
• •18. Planned initiation of cardiac or pulmonary rehabilitation during period of study.