Geert Kleinnibbelink

Chapter 10 210 10.4.1 – Strain-area loop in pulmonary hypertension patients In a meta-analysis in this thesis ( Chapter 6 ), we demonstrated that peak RV longitudinal strain has independent prognostic value for a combined end-point and all-causemortality in patients with PH ( Figure 5 ). Recently, Hulshof et al. confirmed this independent prognostic value of peak RV longitudinal strain and demonstrated that the RV strain-area loop holds (independent) predictive capacity for all-cause mortality in pulmonary arterial hypertension patients ( Figure 5 ). 57 Moreover, they showed the ability of the RV strain-area loop to reclassify high-risk patients to intermediate-risk. 57 In another study, Hulshof et al . demonstrated that characteristics of the strain-area loop are related to afterload in PAH patients ( Figure 5 ). 58 In this thesis, we continued to apply this novel echocardiographic technique in PAH patients. We explored the acute and chronic cardiovascular responses to haemodynamic changes induced by invasive manipulations and pharmacological treatment. Specifically, in Chapter 7 , we investigated the effect of acute preload manipulation on seven patients with suspected PAH on the strain-area loop ( Figure 5 ). We showed that the non-invasive RV strain-area loop provides similar information compared to the invasive pressure-area loop with regards to loop shifts and the assessment of cardiac contractility. These findings show the potential of the non-invasive strain-area loop to comprehensively assess RV cardiac function and mechanics. These abilities may contribute to a potential clinical value in the risk assessment, evaluation and adjusting pharmacological therapy in PAH patients. In Chapter 8 , we tested the hypothesis whether the strain-area loop is able to detect changes after Selexipag induced afterload reduction ( Figure 5 ). In this explorative study, we demonstrated that Selexipag induced afterload reduction does not result in any changes in characteristics in the RV strain-area loop. However, when stratified to clinical responders (decreasedNYHA classification) vs. non-responders (similar or decreasedNYHA classification), we found a distinct effect of Selexipag on cardiac function between the two groups. Specifically, clinical responders showed an increase in RV longitudinal strain and uncoupling while the non-responders showed a decrease in RV longitudinal strain and uncoupling. Despite the low sample size, these pilot data suggest that changes in clinical status may relate to (changes in) RV function. This highlights the potential use of non- invasive echocardiography for patients with PAH to improve and personalise treatment.