Fig. 2.

Major pathophysiological hallmarks of exercise limitation in patients with PH. Alterations within the pulmonary circulation, combined with maladaptive responses of the right and partly the left ventricle, influence the respiratory and peripheral muscle systems as well as contributing directly to exercise limitation. In addition, alterations within the respiratory system such as increased dead space ventilation and ventilation/perfusion mismatch result in exercise-induced hypoxemia and thus exaggerate exercise limitation and the sensation of dyspnea. Moreover, reduced peripheral and respiratory muscle strength might lead to excessive muscle fatigability, increased ventilatory drive, and increased perception of effort.