The Assessment of Right Ventricular Contractility in Response to Sildenafil

The Hospital for Sick Children

Status and phase

Terminated

Phase 3

Conditions

Hypertension

Treatments

Drug: Sildenafil

Study type

Interventional

Funder types

Other

Identifiers

NCT00742014

1000012265

Details and patient eligibility

About

The primary objective of this study is to examine the effects of Sildenafil, administered during cardiac catheterization, on right ventricular contractility in children with pulmonary arterial hypertension.

Full description

The effectiveness of Sildenafil as a pulmonary vasodilator in children with heart disease was first reported in detail during cardiac catheterization and postoperatively in 2003. It is now used frequently for long-term treatment of children with pulmonary arterial hypertension at The Hospital for Sick Children and it is now a routine part of the hospital's testing protocol for all patients being evaluated for pulmonary hypertension in the cardiac catheterization laboratory.

The beneficial effects of Sildenafil in pulmonary hypertension are thought to result predominantly from relative vasodilatory and antiproliferative effects on the pulmonary vasculature. On the basis of early data showing lack of significant PDE5 expression in the normal heart, PDE5 was thought to be expressed in the coronary vessels but not in the human myocardium. Very recently, it was reported for the first time that PDE5 is markedly upregulated in hypertrophied right ventricular myocardium in humans and that in the rat PDE5 inhibition with Sildenafil increases contractility in hypertrophied right ventricular myocardium but not in normal right ventricle, which lacks PDE5 expression. The assessment of right ventricular contractility in humans is a challenge, but we have developed several techniques that are recognized as 'state of the art' assessment of right ventricular function.

The purpose of this study is to examine the effects of Sildenafil, which is routinely administered during cardiac catheterization to assess pulmonary vascular resistance, on right ventricular contractility in children with pulmonary arterial hypertension.

Enrollment

10 estimated patients

Sex

All

Ages

1 to 18 years old

Volunteers

No Healthy Volunteers

Inclusion criteria

Significant pulmonary arterial hypertension (mean pulmonary artery pressure > 25 mm Hg)
Patients aged 4-18 years
Routine cardiac catheterization clinically indicated for deciding therapeutic treatment
Informed assent/consent from patient/parent

Exclusion criteria

Suprasystemic pulmonary artery pressures
Evidence of right heart failure
History of ventricular arrhythmia
Known vascular access arrhythmia
Contraindication to Sildenafil
Concurrent inotropic / PDE administration
Other medical, psychological or social circumstances which complicate a regular participation in the study, and/or increase the risk for the patients themselves
No consent/assent
Pregnancy or unwillingness to comply with contraceptive advice