Pilot Study of the Safety and Efficacy of Carvedilol in Pulmonary Arterial Hypertension

Phase 1

Completed

Brief Summary: The purpose of this study is to determine whether carvedilol treatment of patients with pulmonary arterial hypertension and associated right heart failure is safe and results in an improved function of the right heart.

Detailed Description: Patients with pulmonary arterial hypertension (PAH) will be treated with carvedilol for 24 weeks. During this time, carvedilol will be titrated from an initial dose of 3.125mg BID to a maximal dose of 25mg BID. At the start and end of the study, we will obtain cardiac MRI, 6 minute walk distance, brain natriuretic peptide (serum), echocardiogram, and functional class assessment. Our primary outcome is a change in right ventricular ejection fraction with cardiac MRI.

Recruitment & Eligibility

Inclusion Criteria

idiopathic, familial or associated PAH, WHO group 1
NYHA class II or III
clinically stable with optimized PAH treatment for at least 3 months
no or minimal evidence of fluid overload or volume depletion, with or without diuretic treatment
age > 18 years
mean pulmonary artery pressure (mPAP) > 25 mmHg
6 minute walk distance (6MWD) over 100m

Exclusion Criteria

Structural heart disease unrelated to PAH
Recent (<3 months) treatment with an intravenous positive inotropic agent
current use of β-blockers
history of reactive airways disease
history of adverse reaction to β-blockers
heart block on ECG or resting heart rate < 60 bpm
cardiac index < 1.8 l/min/m2
systemic hypotension (systolic pressure < 90 mmHg)
pulmonary capillary wedge pressure > 15 mmHg
inability to give informed consent
contraindications to CT and/or PET scanning
coagulopathy (INR>1.5 or platelet count<50000/mm3)
severe renal insufficiency (creatinine clearance <30 ml/min/m2)
malignancy or any co-morbidity limiting survival or conditions predicting inability to complete the study.

Arm && Interventions

Group	Intervention	Description
carvedilol	Carvedilol	Carvedilol is titrated from a dose of 3.125mg twice daily to a maximal dose of 25mg twice daily over 24 weeks. Patients are evaluated to their response with 6 minute walk testing, echocardiography, and cardiac MRI

Primary Outcome Measures

Name	Time	Method
Absolute Change in Right Ventricular Ejection Fraction	baseline, 6 months	Change in right ventricular ejection fraction is measured by cardiac magnetic resonance imaging, using the method of disks with the reading radiologist being blinded to before and after images. Cardiac magnetic resonance imaging was done at baseline and 6 months only

Secondary Outcome Measures

Name	Time	Method
Change in Right Ventricular End Systolic Volume	baseline and 6 months	right ventricular end systolic volume determined by MRI
Change in 6 Minute Walk Distance	baseline and 6 months
Change in Tricuspid Annular Plane Systolic Excursion	baseline and 6 months	Higher values indicate a better outcome.