Bosentan improves clinical Outcome of adults with congenital heart disease or mitral valve lesions who undergo CArdiac surgery

Cardiac surgery relieves symptoms and increases life expectancy in cardiac
patients, with and without congenital heart disease (CHD). However, surgery
involves many risks of complications, including right ventricular failure.
Right ventricular failure is often difficult to treat and is characterized by
edema, oliguria, hypotension, and in severe cases shock, multi organ failure
and death. Clinical factors contributing to right ventricular failure are
mechanical pulmonary ventilation, pre-existing pulmonary hypertension, having
CHD or mitral valve lesions and undergoing cardiac surgery.
Cardiac surgery exposes patients to high partial pressures of oxygen, air
embolism, and the release of cytokines. The endothelin-1 cytokine release,
initiated by the cardiopulmonary bypass, induces vasoconstriction of the
pulmonary arterioles resulting in elevation of the pulmonary vascular
resistance (PVR). Heart failure patients with higher PVR have been shown to
have significantly lower exercise capacity measured by peak V*O2. Interventions
affecting the PVR influence the right ventricular function, as shown in
patients with chronic thrombo-embolic pulmonary hypertension before and after
surgery. Moreover, studies on cardiac surgery have shown a decline in systolic
right ventricular function post-operatively compared to pre-operative values,
when cardiopulmonary bypass was used. This decline can persist for many years,
emphasizing the importance of RV protection peri-operatively.
Reducing the right ventricular afterload, the PVR, is shown to be effective in
patients with pulmonary arterial hypertension treated with bosentan, an
endothelin-1 receptor antagonist. We hypothesize treatment of patients peri-
operatively with bosentan will reduce the PVR, which consequently improves the
clinical outcome measured by exercise capacity.

To investigate whether an endothelin-1 receptor antagonist improves exercise
capacity (peak V*O2) in adults with CHD or with mitral valve lesions who
undergo cardiac surgery.

A prospective randomized open label assessment with blinded end-points
(PROBE-design). Total duration of the study is 17 weeks with 5 weeks
pre-operative and 12 weeks post-operative treatment with bosentan.

The treatment group receives a starting dose of 62.5 mg tablet bosentan twice
daily for four weeks followed by 125 mg tablet of bosentan twice daily one week
prior to and 12 weeks after surgery. The other group receives no study
medication.

The trial medication has a low but potential risk of reversible liver damage,
which will be monitored regularly (by laboratory testing of liver
transaminases). Other side effects of bosentan are rare, the most common being
headache, dizziness and peripheral edema, The additional burden for the
patients mainly consists of the time needed for the investigations: history
taking + physical examination (15 min) and cardiopulmonary exercise testing (60
min).