Geert Kleinnibbelink

Chapter 8 172 INTRODUCTION Pulmonary arterial hypertension (PAH) is a progressive pulmonary vascular disease, characterised by an increased pulmonary artery pressure, which is associated with a poor 5-year survival-rate. 1 The primary cause of death is related to deterioration of right ventricular (RV) function, caused by the inability of the RV to overcome the increased afterload. 2 For this reason, drug-induced reduction of RV afterload is the cornerstone in the treatment of patients with PAH. Selexipag (Uptravi®), an oral prostacycline-receptor agonist, resulted in a 30% reduction in pulmonary vascular resistance (i.e. afterload) upon 17 weeks treatment. 3 The GRIPHON trial showed a hazard ratio of 0.60 in time to clinical worsening after Selexipag treatment compared to placebo. 4 The clinical benefits of Selexipag may relate to improvements in RV function, given the strong relation between RV function and disease prognosis. 5 Nonetheless, echocardiography is rarely used in the follow-up of patients with PAH to evaluate the impact of (pharmacological) treatment. 6 Recently, we introduced a non-invasive echocardiographic assessment of the dynamic relationship between RV longitudinal strain and RV area across the cardiac cycle, i.e. strain- area loop. 7 We demonstrated that RV strain-area loop characteristics; i. relate to increasing levels of pulmonary vascular resistance, and ii. predict clinical outcome in PAH. 8-10 In this study, we hypothesise that Selexipag-induced changes in the RV strain-area loop relate to clinical outcomes within individuals, which may ultimately contribute to optimal patient management. Therefore, the aim of this exploratory study was to evaluate the impact of 17-weeks Selexipag use on strain-area loop characteristics and, subsequently, relate these outcomes to changes in clinical status in patients with PAH. METHODS We recruited 12 individuals (59±18 years of age, 67% female) for the study. Participants were eligible to take part in this study if they were diagnosed with PAH (WHO group 1), were aged ≥ 18 years or older, were in NYHA class II or III and the clinical pulmonary hypertension team decided to initiate treatment with Selexipag according to current guidelines. 6 Exclusion criteria were patients with pulmonary hypertension WHO group 2 to 5, usage of another prostacyclin-analog within 1 month of inclusion, moderate or severe obstructive lung disease, severe restrictive lung disease, moderate or severe