study of placebo or bosentan to treat patients with single ventricle physiology.

Conditions: Hypoplastic Left Heart Syndrome; Tricuspid Atresia; Other Specified Congenital Anomalies of Heart

Summary: the purpose of this study is to determine whether bosentan is an effective and safe treatment to adolescent and adult (15 years and older) patients, born with one ventricle of the heart instead of two (single ventricle physiology) and who have undergone tcpc as a palliative surgical treatment. the aim of the tcpc operation is to use the one functioning ventricle to pump the blood flow to the body, while the blood to the lungs is received directly from the caval veins, and is thus a passive flow, without the aid of a ventricle to actively pump the blood through the pulmonary circulation. the resistance in the pulmonary circulation is therefore critical to these patients. these patients have markedly lower work capacity in bicycle test than the general public. furthermore they have a high risk of developing complications e.g. loss of protein from the intestines. bosentan is a medication that lowers the resistance in the pulmonary circulation. it is routinely used for patients with pulmonary hypertension. some studies have shown that drugs that lower the pulmonary resistance can increase exercise capacity significantly in patients with single ventricle physiology. in this study 80 patients will receive either placebo or bosentan for 14 weeks. before and after the treatment, bicycle test along with blood samples, stool samples and quality of life interviews will be performed. every four weeks during the study blood samples, physical exam and interviews will be performed to ensure the safety of the treatment. the investigators expect to find a significant increase in work capacity after 14 weeks in the treatment group compared with the placebo group. moreover the investigators hope to find a decrease in intestinal protein loss and an improved quality of life.

in the statistical analysis the investigators wish to analyse interactions between the primary endpoint and predefined subgroups in order to distinguish responders from non-responders to the treatment. the predefined subgroups are: nt-probnp \> 100 (yes/no) ventricular anatomy (rv/lv) ct-proendothelin-1. in the latter, the investigators do not wish to predefine a specific value, due to limited experience with this analysis. we wish to use the data from the study to find a cut-off value, that is able to predict positive response to treatment.

Eligibility criteria:
inclusion criteria: * tcpc operated * age \> 15 years old * clinical stability \> 3 months, evaluated by investigator from clinical record * for women: negative s-hcg and use of contraception exclusion criteria: * severe heart failure (nyha-class iv) * oxygen saturation \< 85 % at rest * pre-existing liver condition (transaminases 2x \> reference) * renal failure (creatinin \> 150 mmol/l) * obstruction of tcpc circulation * history of work induced severe arrhythmia * systolic blood pressure below 80% of reference (bt \< 88 mmhg) * use of any of following drugs: fluconazol, ketoconazole, ciclosporina, lopinavir, ritonavir, rifampicin, carbamazepin and phenytoin * significant extra-cardiac condition e.g. neurological impairment

Keywords: single ventricle physiology fontan procedure