Strain-area loop in drug-induced (Selexipag (Uptravi(®))) afterload reduction of the right ventricular in pulmonary arterial hypertension

Pulmonary arterial hypertension (PAH) is a rare, progressive disease with a
rather poor prognosis. In PAH patients, there is an increased resistance in the
pulmonary artery, forcing the right ventricle to produce increased pressure to
circulate the same amount of blood. This influence the right ventricle
hemodynamics. Due to the increased pressure, the right ventricle become
hypertrophic, thereafter dilated and finally results in right heart failure.
Drug therapy in PAH aims to reduce the pulmonary resistance. Current methods to
determine the vascular resistance reliable are invasive and therefore not
practical to evaluate therapeutic success.
The introduction of Specke tracking echocardiography provides the opportunity
to measure wall deformation (so called strain). By combining concomitant
temporal echocardiographic measures of strain and area of the ventricles a
strain-area loop can be constructed. With this strain-area loop it is possible
to measure hemodynamical changes in the heart. Previous studies showed that the
strain-area loop characteristics changes as the invasive measured pulmonary
artery pressure raises.
To explore the usability of this new non-invasive technique, we will examine
whether drug-induces afterload reduction with Selexipag, a prostaglandin
receptor antagonist, will influence the characteristics of the strain-area loop
in PAH patients. In the future, this could be useful to follow-up PAH patients.
Besides this, we will examine whether or not changes in characteristics of the
strain-area loop have prognostic value.

Our primary objective is to determine whether drug-induced reduction in
pulmonary afterload causes a change in strain-area loop after 17 weeks of use
of selexipag (maximum tolerable dose 2dd 1600 micrograms / day).
Secondary objective is to investigate whether the drug-induced changes of the
strain-area loop have prognostic value regarding the occurrence of
cardiovascular events (death, hospitalization due to exacerbation of PAH) and
disease progression based on NYHA classification and a 6MWD test within two
years.

Explorative prospective study in which 25 PAH patients (WHO 1, NYHA II-III)
will undergo a non-invasive echocardiogram before and 17 weeks after the start
of selexipag to obtain strain-area loops. The occurrence of clinical
cardiovascular events, hospital admissions and disease progression based on
functional NYHA classification and the 6 MWD test will be reported for two
years.

Test subjects will be treated with Selexipag on clinical grounds according to
international guidelines and on the advice of the multidisciplinary pulmonary
hypertension team of the Radboudumc Expertise center for pulmonary
hypertension. Previous studies have shown that PAH patients benefit from this
drug, which results of a reduction in mortality and from complications related
to PAH. This study also shows that Selexipag is safe whereby the chance of
serious adverse events is not increased. A few adverse events, mostly
gastrointestinal side effects, occurred more frequently. These complaints
outweigh the possible positive effects on health.
Subjects will undergo several echocardiograms. This measurement is non-invasive
and does not involve any degree of risk.
This study provides not only more insight into PAH and the effects of drug
treatment, but may also indicate the application of a simple, non-invasive
measurement that can be used during the follow-up of PAH patients to determine
the effectiveness of the drug. These are potentially important benefits.