Geert Kleinnibbelink

Chapter 2 56 contribution to area change, in combination with a lack of RV dilatation, supports that the reduction in peak longitudinal strain post-exercise (i.e. EICF) is more likely representative of intrinsic dysfunction. Perspectives The mechanisms underlying EICF are likely multifactorial, and importantly may differ between the RV and LV. Previous research has proposed several influencing factors varying from β -adrenergic receptor desensitization, oxidative stress, impaired calcium metabolism to altered post-exercise loading. The influence of afterload conditions on RV EICF have rarely been explored. This study demonstrated that, under hypoxic conditions at 3000m altitude (FiO 2 14.5%), the magnitude of EICF is not augmented and thus it may be less likely that a role for elevated RV wall stress is relevant. Although knowledge about the clinical long-term consequences of these temporary post-exercise reductions in cardiac function is lacking, it has been hypothesized that this may be associated with myocardial damage and worse clinical outcome. The absence of an effect in EICF between exercising at sea level (normoxia) and 3000m altitude (hypoxia) is interesting, but long-term studies that link these findings to prolonged follow-up is needed to better understand these findings. The novel strain-area loop, introduced to assess haemodynamics non-invasively, provided substantial added value in this study where it was sensitive enough to detect changes due to hypoxia. This novel technique seems promising in providing physiological and pathophysiological insight andmight be of added value in clinical practice. 5, 27, 28, 37, 45-48 Limitations This study implemented a standardized exercise challenge to prevent a pre- and post- exercise (para)sympathetic imbalance during echocardiographic evaluation. Instead of the methodology of Stewart et al. 14 (aiming at 100 bpm), we set our target HR at 110- 120 bpm during the exercise challenge, to better mimic cardiac function during exercise. This higher HR may impede speckle tracking quality. With current frame rates used, we experienced that tracking was still good to excellent for LV global longitudinal strain and RV free wall strain. A further limitation is that we did not obtain direct measures of RV wall stress as this would require invasive procedures. Alternatively, we used only non- invasive echocardiographic, indirect measures to estimate any potential difference in