Angiotensin II receptor blockers in patients with systemic right ventricles.

Nowadays, there are over 25,000 adult patients with a systemic right ventricle
due to a congenitally or surgically corrected transposition of the great
arteries in the Western World. This means that in these patients the right
ventricle is responsible for maintaining the circulation of the body. These
patients have an increased risk of various cardiac disorders, causing
deterioration of their clinical condition and contributing to their premature
deaths. The latter is mainly caused by progressive heart failure of the
systemic right ventricle, which is present in 90% of all adults with a systemic
right ventricle. It has been demonstrated that the degree of the right
ventricular dysfunction correlates with the extent of myocardial fibrosis and
right ventricular hypertrophy.
Angiotensin II receptor blockers (ARB*s) have a proven beneficial effect in
patients with left ventricular dysfunction. They protect the myocardium by
decreasing myocardial fibrosis and ventricular hypertrophy. Until now, these
findings have not been proven to be applicable to patients with a systemic
right ventricle. Only one study was performed that found no benefits on the
exercise capacity and the serum neurohormone levels in these patients. However,
from this study it is difficult to draw definite conclusions on the role of
ARB*s in patients with a systemic right ventricle, as the study was
inadequately powered (only 29 patients), had a short follow-up period (only 15
weeks) and had inappropriate and inaccurate endpoints. Therefore, a large
scale, long term trial, with clear and accurate endpoints is essential to
provide an optimal and evidence-based long term treatment and a better future
for these patients.

The results of the proposed study helps to guide the long-term treatment of
this unique patient population by accurately determining the impact of ARBs on
the systemic right ventricular function. To prevent progressive dysfunction of
the systemic right ventricle, improve the quality of life and postpone the
premature deaths of these young patients would be major triumphs in modern
medicine.

To study whether ARB's (valsartan) improves functional (contractile,
electrophysiologic) performance of the right ventricle in adult patients with a
systemic right ventricle.

Randomized, double-blind, prospective, multi-centre trial, follow-up 3 years.

Valsartan start dose 160mg 1dd1, will be increased to 160 mg 2dd1 with a two
week interval.

The investigations that will be performed on the patients are all non-invasive,
except for the blood tests, and free of risk. The burden for the patients will
mainly be the time consumed by the various investigations.
The number of side effects from valsartan are low. The most common side effect
is dizziness due to a decrease of blood preasure (> 1:100 and < 1:10
patients). Serious of fatal side effects have not been described.