Geert Kleinnibbelink

Chapter 2 54 in autonomic tone and vasodilation, which may result in post-exercise tachycardia and hypotension, respectively. These (para)sympathetic imbalance factors likely influence cardiac functionmeasurements such as strain, and therefore potentiallymask the presence of EICF. Evaluation of cardiac function during the high-intensity exercise, therefore, is preferred. However, one should consider the practical aspects (e.g. echocardiography is impossible during running) and that reliable speckle tracking is extremely challenging with higher heart rates (i.e. 70% of maximum HR). 40 Low-to-moderate intensity cycling exercise at a semi-recumbent bike is both feasible and reliable, and allows to examine cardiac function during exercise. Utilising this approach, our data indicates that, with short durations of high-intensity exercise, EICF occurs when assessment of cardiac function is performed during an exercise challenge. Impact of exercise under hypoxia Under hypoxic conditions, less oxygen is bound to haemoglobin, and will, therefore, increase the demand on the cardiovascular system. In our population, this was reflected by a higher resting HR under hypoxia versus normoxia and the less distance covered under hypoxia versus normoxia during the exercise despite it being matched for relative intensity. More importantly, hypoxia has been shown to induce vasoconstriction of the pulmonary vasculature, leading to higher relative PVR resulting in a higher PAP, and consequently a higher RV wall stress. Elevated PAP has been previously demonstrated at conditions at 3000m altitude. 23 Although we were unable to directly measure PAP, we demonstrated shorter PAT and a larger RA size which indirectly supports the presence of an increase in PAP and, therefore potentially wall stress. Also, the strain-area loop showed less uncoupling in late diastole and a trend for a less steep systolic slope under hypoxia. In line with a previous study in PAH patients, these changes are associated with a higher PVR at rest. 28 Although we adopted a non-invasive approach and one should consider alternative explanations (i.e. related to the assessment), these findings support the presence of an elevated wall stress in our study under hypoxia. That aside, our hypothesis was rejected as the 45-minute high-intensity running exercise under hypoxia did not exaggerate RV EICF compared to exercise under normoxia. This suggests that changing cardiac workload does not necessarily change the magnitude of RV EICF and may not be the principle mechanism for RV EICF. One potential explanation for the lack of an impact