Anne-Marie Koop

6 227 INTRODUCTION Sustained pressure overload of the right ventricle (RV) is a major pathophysiological factor in several cardiovascular disorders, including pulmonary hypertension (PH). 1-3 It is noteworthy that RV failure due to pressure overload is the main determinant of the outcome of congenital heart diseases 4 and the most common cause of death in patients with severe pulmonary artery hypertension (PAH). Persistently increased RV afterload will eventually culminate in RV hypertrophy. Hypertrophic cardiac growth is believed to be an initial beneficial response to reduce wall stress, improve contractility, preserve cardiac output 5,6 and enhance capillary density in order to complywith the increased oxygen demand in the hypertrophied tissue. 7 However, as the disease progresses, the transition from RV adaptation to failure is inevitable. 3 RV failure, characterized as a progressive decrease in cardiac output, is accompanied by increased contractility, decreased diastolic function, and pathologic changes in capillary density and fibrosis. 8-10 Notwithstanding its worse prognosis, the impact of right ventricular function on the outcome of cardiovascular diseases has been neglected due to its less obvious involvement in disease processes. As a consequence of being connected to low impedance pulmonary circulation, the RV has thinner walls, lower oxygen demand and lower wall stress compared to the LV. 11 Therefore, even minor alterations in total pulmonary resistance may have a great impact on RV function in contrast to LV, which is less affected by larger changes in afterload. 12,13 The differences between the two ventricles range from molecular to structural and functional levels, and start as soon as cardiac embryonic development initiates. The primary heart field, by expressing T-box transcription factor 5 (Tbx5) and Heart- and neural crest derivatives-expressed protein 1 (Hand1), gives origin to the LV and the atria. Meanwhile, the secondary heart field leads to the development of the RV and RV outflow tract through expression of crucial RV-fate genes such as Heart- and neural-crest derivatives-expressed protein 2 (Hand2), Islet1 (Isl1) and fibroblast growth factor-10 (Fgf10). 14 These differences persist in to the adult heart and, because the healthy adult RV is connected to low-pressure high-volume system and the LV is associated with high-pressure system, during injury the RV is more sensitive to volume overload whereas the LV is more prone to pressure overload. 15 Although RV and LV share common features of maladaptive remodelling such as hypertrophy, capillary rarefaction and fibrosis, they demonstrate particular types of hypertrophic growth. For example, RV pathological remodelling is usually associated with an eccentric hypertrophy (new sarcomeres are added in-series ) and LV remodelling is commonly manifested by a concentric hypertrophy (new sarcomeres are added in-parallel ). 16 Interestingly, pathological RV remodelling