Geert Kleinnibbelink

General Introduction and Outline of Thesis 19 1 structural alterations, and is known as cardiac plasticity. 8, 26, 27 The process of these changes is also referred to as cardiac remodelling or cardiac adaptation and can be distinguished into a physiological and pathophysiological variant. A variety or stimuli can induce this remodelling through alterations in preload, afterload and contractility. 5, 26 Physiological remodelling Cardiac remodelling to exercise is a form of physiological adaptation. During recreational or competitive exercise, the repetitive participation in vigorous physical exercise stimulates adaptive changes in cardiac structure and function. 6, 28 These changes vary among individuals and is based on a number of factors, including type (static versus dynamic), duration and intensity of exercise, but also differ between ethnicities, genetics and sex. 28 All these factors influence the haemodynamic challenges to the heart and the subsequent nature and magnitude of cardiac remodelling. In the past, research examining exercise-induced cardiac remodelling was primarily focused on the LV. In 1975, the Morganroth hypothesis stated that resistance and endurance training cause divergent patterns of remodelling. 29, 30 The assumption was that resistance and endurance exercise would lead to a concentric (increase in LV mass, equal EDV) and eccentric (increase in LV mass and EDV) type of remodelling, respectively. Over years, more research has been undertaken and this hypothesis has become obsolete with the paradigm shifting towards a dose-dependent relation between the amount of haemodynamic stress exposure (time x intensity) and cardiac remodelling. 6 Importantly, the Morganroth hypothesis did not consider the RV. As a result, the RV has been neglected for many years regarding exercise-induce cardiac remodelling. For obvious reasons, the RV and LV are strongly coupled and are ultimately exposed to the same volume of cardiac output. As a result, traditionally it has been supposed that RV follows the LV adaption pathway, however, important differences exist between both ventricles for other haemo- and cardiodynamic stimuli. For example, the acute haemodynamic response during exercise appeared to induce a relative higher increase in wall stress compared to the LV, which possible underly a rationale for the side-specific cardiac remodelling hypothesis ( Figure 4 ). 24 La Gerche et al. demonstrated that during rest the end-systolic wall stress is higher in the LV compared to the RV, but that during exercise the relative increase in wall stress is higher in the RV compared to the LV ( Figure 4 ). 24 Therefore, a central hypothesis