Right vEntricular Dysfunction in tEtralogy of Fallot: INhibition of the rEnin-angiotensin-aldosterone system*

The prevalence of adult patients with congenital heart disease (CHD) has
steadily increased over the last decades, due to the advances in cardiac
surgery. A large number of these patients cope with right ventricular (RV)
volume or pressure overload, largely caused by residual lesions after cardiac
surgery in childhood. Longstanding RV overload eventually leads to symptomatic
RV dysfunction in the majority of these young adults. These findings warrant
close surveillance of RV function, and adequate and evidence-based
pharmacological therapy to reduce both morbidity and mortality in this young
patient group. The renin-angiotensin-aldosterone system (RAAS) is activated in
patients with ventricular failure, irrespective of the effected (left or right)
ventricle. Angiotensin converting enzyme (ACE) inhibitors and angiotensin II
receptor blockers (ARB*s) are drugs which act as inhibitors of RAAS.
Previously, large trials have demonstrated the beneficial effect of angiotensin
converting enzyme (ACE) inhibitors on morbidity and mortality in patients with
acquired left ventricular (LV) dysfunction. ARB*s have a similar effect as ACE
inhibitors in patients with acquired LV dysfunction but discontinuation because
of side effects such as cough is less frequent. Current guidelines advise
empiric use of RAAS inhibitors for right ventricular dysfunction in adult
patients with congenital heart disease. However, the actual effect of RAAS
inhibition on right ventricular failure in adult patients with congenital heart
disease has not been sufficiently investigated. Therefore, we set-up the
proposed study, and hypothesize that ARB*s have a beneficial effect on RV
function in adult patients with RV dysfunction due to Tetralogy of Fallot.

to improve RV function adult patients with RV dysfunction due to tetralogy of
Fallot

a prospective, multicenter, double-blind, randomized, placebo-controlled trial.
Follow up two years

After randomisation one group (n=60) will receive 150mg losartan once daily for
two years. The other group will receive placebo in the same regimen.

All investigations, except blood analysis, are non-invasive and free of risk.
The burden for the patients mainly consists of the time that is consumed by the
investigations. Namely: history taking and physical investigation (15 minutes);
quality of life score (15 minutes); laboratory tests (6 times venapunction,
total amount of blood withdrawn approximately 90ml); cardiopulmonary exercise
test (1hour); CMR (45 minutes).
Adverse effects from losartan are usually limited and consist of dizziness due
to hypotension, renal impairment, hyperkalemia and liver impairment.
We expect no change or an increase in RV function in the intervention group
compared to the control group over the two-year follow up period, which would
be a great benefit for this young study population.