Prognostic factors, treatment goals and clinical endpoints in pediatric pulmonary arterial hypertension

Pulmonary arterial hypertension (PAH), increased blood pressure in the pulmonary arteries, is a serious life-threatening disease. In this incurable disease, narrowing and stiffening of the pulmonary arteries cause an afterload burden on the right heart, leading to right–sided heart failure and death. The available supportive drugs for adults have barely been tested in children as clinical trials are hampered by a lack of validated endpoints.

In any severe disease, valid indicators of disease severity, progression and prognosis are essential for evaluating treatment success and for appropriate timing of major therapeutic decisions such as therapy escalation or lung transplantation. Such indicators are also required for the definition of endpoints in clinical trials. In pediatric PAH, such indicators have been virtually absent, hampering adequate clinical decision making and clinical trial design.

The studies presented in this thesis have yielded several indicators for clinical monitoring of children with PAH. For instance, the degree of exercise intolerance, right ventricular function assessed by echocardiography and serum measurements reflecting stretch of cardiac tissue have been identified as valid indicators to be used for guiding therapeutic decisions. Additionally, pulmonary arterial stiffness and growth retardation appear accurate indicators of disease severity and prognosis in these children.

The availability of these indicators paves the way for guidelines on how and when to intensify treatment, or when to consider early lung-transplantation in this vulnerable patient population. Moreover, these indicators allow for the design of pediatric clinical trials, to enable the development of safe and effective treatments for children with this devastating disease.

Dissertation: http://hdl.handle.net/11370/d905d8bf-542e-484a-8aa1-6f555ee2dfc1