Beta Blockers for Treatment of Pulmonary Arterial Hypertension in Children

This study will determine the safety and feasibility of using a β-blocker (in this case carvedilol) in the treatment of pediatric patients with Left Heart Failure (LHF) in children with Pulmonary Arterial Hypertension (PAH). Carvedilol affects the nervous system, the same system that is highly activated in response to stress in patients with PAH. Each patient is administered a dosage of carvedilol, according to their weight. This dosage is increased incrementally over the span of the study, if the patient responds well to the drug. The study will determine whether the potential adverse side effects of carvedilol outweigh the possible positive results in reducing LHF. The hypothesis of this study predicts that carvedilol will have positive effects in treating LHF, similar to their use in treatment of Right Heart Failure (RHF). This is a single-centered pilot study. Each patient will be studied for approximately 31 weeks.


Eligibility Criteria:
Inclusion Criteria:

* Patients must be ≥ 8 and ≤ 17.5 years of age at the time of study enrollment.
* Patients must have a mean pulmonary artery pressure of greater than 25mmHg at rest in a setting of normal pulmonary arterial wedge pressure of 15mmHg or less with a PVR index greater than 3 Woods units•m2 at last hemodynamic study.
* Patients must be diagnosed with any of the following:Idiopathic PAH (IPAH), PAH associated with repaired congenital heart disease, PAH associated with minor congenital heart disease (small interventricular communication, small interarterial communication, small ductus arteriosis)
* Patients must be clinically stable (i.e. no treatment changes) for the last 3 months
* Patients must have no or minimal evidence of fluid overload or volume depletion judged by clinical evaluation (with or without diuretic treatment)
* Written informed consent

Exclusion Criteria:

* Patients who are unable to perform a six minute walk test (6MWT)
* Patients with a known history of pulmonary hypertension secondary to venoocclusive disease and/or capillary hemangiomatosis; pulmonary hypertensions owing to left heart disease
* Patients who have previously received treatment with an intravenous positive inotropic agent in the last 3 months
* Patients who are currently receiving β-blockers
* Patients with a known history of reactive airways disease (bronchial asthma or relate bronchospastic conditions)
* Patients with chronic obstructive pulmonary disease (COPD)
* Patients with a known history of adverse reaction to β-blockers
* Patients with a heart block on ECG or resting heart rate \< 60 bpm
* Patients with systemic hypotension (below 5th percentile for age) are not eligible as follows: 1-10 years old: systolic blood pressure defined as \< \[70 + (2 x age in years)\] mmHg; Older than 10 years: systolic blood pressure \< 90 mmHg
* Patients with coagulopathy (INR \< 1.5 or platelet count \<50,000/mm3)
* Patients with a known history of severe hepatic impairment (defined by the presence of ascites, esophageal varices, jaundice or spider angiomata)
* Patients with severe renal insufficiency (defined as creatinine clearance \< 30 mL/min/m2)
* Patients with a known malignancy or other co-morbidity expected to limit survival or to limit the ability to complete the study
* Patients with trisomy 21
* Patients with a known history of sick sinus syndrome
* Patients with a known history of moderate or severe primary obstructive valvular heart disease
* Patients with a known history of diabetes
* Female patients who are pregnant of breast-feeding