Geert Kleinnibbelink

Summary 11 227 In Chapter 9 , we compared 1-year mortality rates between patients with primary PH who were prescribed CR or exercise programmes versus a propensity-matched control group of primary PH without prescription for CR or exercise programmes. We demonstrated that CR in patients with PH is associated with a 40% lower odds of 1-year mortality compared to patients who did not receive CR. Part lll – General discussion In Chapter 10 , we integrated findings of this thesis with insights from other studies, and discussed directions for future research. We have identified five key messages. First, the additional value of stress echocardiography in the evaluation of cardiac responses to exercise was discussed. Based on this thesis, and recent other studies, stress echocardiography shows additional value in the detection of EICF after short duration high-intensity exercise but also in the discrimination of physiological from pathophysiological cardiac conditions. Further studies should explore its potential in the diagnosis or prognosis of cardiovascular disease. Second, acute cardiovascular responses to exercise seem to closely relate to adaptations to chronic exercise training. Adopting this approach may be a potential strategy to better understand the hypothesis that repetitive exposure to high training volumes of exercise may lead to maladaptive remodelling of the RV in certain individuals. Furthermore, PEH may be used as a proxy to identify responders to the blood pressure lowering effect of exercise training. Third, we concluded that the RV does not simply mirror the LV in both acute and chronic responses to exercise. Not only the in-exercise response vary but also the magnitude of EICF may differ between the RV and LV. Integrating our findings with existing literature, we discussed the cardiac structural remodelling hypothesis suggesting the presence of a distinct pathway of structural RV and LV remodelling to exercise related to the level of training of an individual. Moreover, we discussed the added value of the strain-value loop in providing insight into cardiac mechanics upon exercise training. Fourth, we summarized and integrated our findings of the echocardiographic RV strain- area loop in patients with PH. The strain-area loop has potential but future studies should