Exercise as an end-point in pulmonary hypertension trials

With recent advances in our understanding of pulmonary hypertension and with ever increasing therapeutic options at our disposal, it remains disappointing that clinical markers of disease progression remain dated. There has long been a search for a more robust clinical correlate than the 6 minute walk test. Resting right heart pressures do not increase linearly with worsening disease, limiting their use as primary endpoints. Some progress has been made however, with 'time to clinical worsening' a composite endpoint of several markers of disease severity. Trials have also been undertaken to evaluate the merits of echocardiographic indices, cardio pulmonary exercise testing and cardiac MRI, with mixed results. With the lack of a sensitive and specific biomarker for pulmonary hypertension, the goal of finding a reproducible endpoint that accurately reflects disease severity and prognosis remains elusive. In this article we discuss relevant endpoints and focus on exercise haemodynamics as a primary endpoint for clinical trials.