Geert Kleinnibbelink

Chapter 8 180 to systole. In healthy subjects, compliance of the ventricle wall contributes to RV filling, which leads to dissociation between systolic and the diastolic phase (uncoupling). Patients with PAH present an increased RV diastolic stiffness due to (eccentric) hypertrophic remodelling to compensate for the increased afterload. To offset for the increased stiffness, increased relaxation in the longitudinal plane may be required to facilitate diastolic filling. Previously it has been shown that patients with PAH had less uncoupling, and possess therefore an increased diastolic filling drive, compared to controls. 8 Therefore, the greater uncoupling in responders following Selexipag treatment may be suggestive of increased RV compliance secondary to a reduced afterload. In contrary, the non-responders show opposite changes in these strain-area loopcharacteristics, suggesting further deterioration of RV function in the presence of unaltered afterload. We can speculate that a further reduction in RV compliance has led to an increased diastolic stiffness and impaired filling, hence increased coupling and a leftward shift. Previous work has demonstrated that coupling (as part of the RV-loop score) has independent predictive capacity for all-cause mortality in patients with precapillary pulmonary hypertension. 10 Interestingly, conventional RV functional indices did not change upon treatment at group level or respective sub-groups. Nath et al . also addressed the relation between improvement in clinical status (NYHA classification) and change in RV function upon pharmacological treatment (with epoprostenol) in PAH patients (n=20, 16 females). 16 They failed to demonstrate an association between a change in NYHA classification and RV function measured with conventional indices (while RV strain was not assessed). This suggest a potential relation between clinical responders and improvement in RV function measured with novel echocardiographic indices such as the strain-area loop whilst absent when measured with conventional indices. However, given the limited sample size, this should be further explored in larger studies. Clinical relevance. We demonstrated a potential relationship between improvement in clinical status and improvement in RV function measured with novel echocardiographic indices. Risk stratification and follow-up of patients with PAH is traditionally based on clinical assessment using functional NYHAclassification, 6MWTandNT-proBNPassessment as conventional echocardiographic assessment of RV function fall short. Incorporation of a more comprehensive assessment of RV function using the strain-area loop may improve