Comparison of Inhaled Nitric Oxide and Oxygen in Patient Reactivity During Acute Pulmonary Vasodilator Testing

• Cardiac Output [ Time Frame: baseline 1, after treatment 1, after treatment 2, at baseline 2, and after treatment 3 ] [ Designated as safety issue: No ]
• Hemodynamic measurements [ Time Frame: baseline 1, after treatment 1, after treatment 2, at baseline 2, and after treatment 3 ] [ Designated as safety issue: No ]

• Surgical Procedures at 1 Year [ Time Frame: 1 year after treatment ] [ Designated as safety issue: No ]
  The 1 year follow-up survival assessment consisted of a telephone call to subjects to obtain information on surgeries received pertaining to pulmonary or cardiac disease
• Adverse Events [ Time Frame: treatment 1 through treatment 3 ] [ Designated as safety issue: Yes ]
• Serious Adverse Events [ Time Frame: 12 hours after discontinuation of gas or dischange (whichever comes first) ] [ Designated as safety issue: Yes ]
• Surgical Procedures at 3 Years [ Time Frame: 3 years after treatment ] [ Designated as safety issue: No ]
  The 3 year follow-up survival assessment consisted of a telephone call to subjects to obtain information on surgeries received pertaining to pulmonary or cardiac disease

• Adverse Events [ Time Frame: treatment 1 through treatment 3 ] [ Designated as safety issue: Yes ]
• Serious Adverse Events [ Time Frame: 12 hours after discontinuation of gas or dischange (whichever comes first) ] [ Designated as safety issue: Yes ]

A minimum of 100 patients will be enrolled in the study to demonstrate which diagnostic treatment (oxygen or nitric oxide) is most capable of identifying patients with a reactive pulmonary vascular bed. Each patient will be given all three treatment regimen, nitric oxide, oxygen, and the comparison treatment (nitric oxide plus oxygen), with a wash out period of 10 minutes between each dose. Patients will be randomized at the time of enrollment to determine which comparison treatment they will receive.

This is an open, randomized, prospective, multi-center study designed to demonstrate which diagnostic treatment is most capable of identifying patients with a reactive pulmonary vascular bed. A minimum of 100 patients will be enrolled in the study to compare the number of patients with reversible pulmonary hypertension (vasoreactivity) due to nitric oxide for inhalation and oxygen as compared to 100% oxygen. This primary objective will be obtained by measuring the decrease in mean pulmonary arterial pressure (PAPm) ≥ 20% and no decrease in cardiac index (within 5%) in patients with Idiopathic Pulmonary Arterial Hypertension (IPAH) or Congenital Heart Disease (CHD) who do not have an unrestricted shunt at the level of the ventricle or ductus arteriosis, and by measuring the decrease in PAPm ≥ 20% and no decrease in cardiac index (within 5%) and decrease in pulmonary vascular resistance index (PVRI) ≥ 25% and no decrease in cardiac index (within 5%) in patients with cardiomyopathy or CHD who have unrestricted shunt at the level of the ventricle or ductus arteriosis. Additionally, comparison of the incidence and types of drug related and serious adverse events as well as the number of patients with reversible pulmonary hypertension due to nitric oxide for inhalation alone compared to 100% oxygen and to oxygen with nitric oxide for inhalation will also be assessed.

• Idiopathic Pulmonary Arterial Hypertension
• Congenital Heart Disease With Pulmonary Hypertension
• Cardiomyopathy

• Drug: Nitric Oxide for inhalation
  Nitric Oxide (NO) for inhalation, given at 80ppm over 10 minutes using an INOvent®
  Other Name: INOmax®
• Drug: Oxygen
  100% oxygen (O2) for inhalation, given at 80ppm over 10 minutes using an INOvent®
  Other Name: Oxygen
• Drug: Nitric Oxide plus Oxygen
  Nitric Oxide (NO) for inhalation plus oxygen, given at 80ppm over 10 minutes using an INOvent® delivery system
  Other Name: Inhaled Nitric Oxide, Oxygen

• Active Comparator: Nitric Oxide
  Nitric Oxide
  Intervention: Drug: Nitric Oxide for inhalation
• Sham Comparator: Oxygen
  Oxygen
  Intervention: Drug: Oxygen
• Active Comparator: Nitric Oxide plus Oxygen
  Intervention: Drug: Nitric Oxide plus Oxygen

Inclusion Criteria:

1. must have any one of these three disease categories:

   • Idiopathic Pulmonary Arterial Hypertension

     • PAPm > 25mmHg at rest , pulmonary capillary wedge pressure (PCWP) ≤ 15mmHg, and PVRI> 3 u•m^2 or diagnosed clinically with no previous catheterization

   • CHD with pulmonary hypertension repaired and unrepaired

     • PAPm > 25mmHg at rest and PVRI> 3 u•m^2 or diagnosed clinically with no previous catheterization

   • Cardiomyopathy

     • PAPm > 25mmHg at rest and PVRI> 3 u•m^2 or diagnosed clinically with no previous catheterization
2. Scheduled to undergo right heart catheterization to assess pulmonary vasoreactivity by acute pulmonary vasodilation testing.
3. Male or female, ages 4 weeks to 18 years, inclusive
4. Signed informed consent/assent

Exclusion Criteria:

1. Focal pulmonary infiltrates on chest radiograph.
2. Diagnosed with severe obstructive or restrictive pulmonary disease that is significantly contributing to the patient's pulmonary hypertension.
3. Received treatment with nitric oxide for inhalation within 30 dyas prior to study initiation, are on other investigational medications, nitroglycerin, sodium nitroprusside, sildenafil, other PDE-5 inhibitors, or prostacyclin
4. Pregnant (urine human chorionic gonadotropin (HCG +) positive)
5. Baseline PCWP > 20 mmHg