Pathophysiology and Exercise Intolerance in Aberrant Pulmonary Vascular Conditions

Abstract

The primary focus of many cardiac diseases is often centred around the heart itself. However, factors up- or down-stream from the heart, may in some circumstances, be the predominant cause of clinical deterioration. Indeed, this is observed in the setting of aberrant pulmonary vascular conditions such as the Fontan circulation or pulmonary arterial hypertension. This thesis aims to investigate pathophysiology and exercise intolerance in these unique pulmonary vascular conditions. While there are some common factors associated with impaired exercise capacity, there are also significant differences in the physiology underlying exercise intolerance in the Fontan circulation (single ventricle circulation) compared to pulmonary arterial hypertension (biventricular circulation). Extracardiac factors, including respiratory muscle function, body composition, and physical inactivity, likely contribute to exercise intolerance in both situations. Understanding the physiological mechanisms of these factors may be particularly important to address exercise intolerance in the setting of pulmonary vascular dysfunction. Therefore, a series of studies were conducted in this thesis to investigate pathophysiology and exercise intolerance in the Fontan circulation and pulmonary arterial hypertension. In Chapter 3, we sought to investigate the body composition profile of a young Fontan cohort. Chapter 4 describes the natural history of exercise capacity in an Australian and New Zealand Fontan cohort. In Chapter 5, we aimed to characterise the common factors in people with a “Super-Fontan” phenotype. In Chapter 6, we investigated the effects of an eight-week inspiratory muscle training program in people with pulmonary arterial hypertension. Collectively, the studies described in this thesis contribute to our understanding of pathophysiology and exercise intolerance in two contrasting, aberrant pulmonary vascular conditions; the Fontan circulation and pulmonary arterial hypertension.