Pulmonary arterial hypertension (PAH) is characterised by pathological changes in the pulmonary vasculature that cause an increase in pulmonary vascular resistance (PVR) thereby restricting blood flow through the pulmonary circulation [1, 2]. To maintain blood flow, pulmonary artery pressure (PAP) increases . Disease progression leads to right ventricular dysfunction and right heart failure [3, 4]. The physiologic response of the pulmonary vasculature to exercise is markedly different from normal in individuals with PAH [1, 5]. The pulmonary arteries and arterioles have an impaired capacity to vasodilate and distend, and the increase in cardiac output required to accommodate the metabolic requirements of exercise is limited . As a result, oxygen delivery to the peripheral muscles is impaired , contributing to the symptoms of muscle fatigue and dyspnoea [1, 5]. Whilst the impairment in cardiac output to meet peripheral oxygen demands during exercise largely contributes to the reduction in exercise capacity , skeletal muscle dysfunction may also be implicated in the exercise limitation experienced by individuals with PAH [7–10]. Several studies have demonstrated significant morphological and functional changes in skeletal musculature [8–13], which may be related to the decrease in systemic oxygen transport . Changes such as muscle atrophy, decreased oxidative enzymes and increased proportion of type II muscle fibres lead to the early onset of lactic acidosis and a reduced aerobic capacity [7, 9, 10]
Despite advances in pharmaceutical therapies, which have resulted in improvements in exercise capacity, haemodynamics and outcome in patients with PAH , exertional dyspnoea and fatigue continue to result in difficulty performing activities of daily living, lead to the avoidance of physical activity and adversely impact on health-related quality of life (HRQoL) . This inactivity and the resultant physical deconditioning are likely to further exacerbate the functional limitations associated with PAH .
Whilst there is a paucity of studies in the PAH population, the benefits of exercise training in individuals with other cardiopulmonary conditions are well established. Specifically, improvements in symptoms, exercise capacity, peripheral muscle function and HRQoL are well documented following exercise training in chronic left-sided heart failure [16–19] and in chronic obstructive pulmonary disease (COPD) [20–23], populations that both report exertional symptoms similar to PAH. These benefits have been achieved following supervised exercise training, 2 to 3 times per week for a period of 6 to 12 weeks, which comprised endurance exercise at a target intensity of between 40 and 80% of peak exercise capacity (peak oxygen uptake [VO2] or maximum heart rate [HR]) [16, 17, 19–21]. In COPD, programs of 12 weeks duration have been shown to produce greater and more sustained improvements in exercise outcomes when compared to programs of shorter duration [20, 21].
Historically, exercise training has been discouraged as a therapy for patients with PAH due to the perceived risk that exercise could lead to sudden cardiac death or worsening pulmonary vascular haemodynamics, acceleration of vascular remodelling and deterioration in right heart function . Some evidence exists to suggest that exercise training can be performed without adverse events or detriment to cardiac function or pulmonary haemodynamics [10, 15, 24, 25], however, the efficacy of exercise training in PAH warrants further investigation . To date, only three prospective studies of exercise training in PAH populations have been published [10, 15, 25]. These studies recruited subjects with idiopathic PAH or chronic thromboembolic pulmonary hypertension, who were stable on medical therapy and were in WHO functional classes II to IV. The exercise training regimen varied in these studies in terms of the frequency of sessions each week (ranging from 3 to 7), duration (7 to 15 weeks) and the exercise modalities [10, 15, 25]. The types of exercises performed included cycle ergometry [10, 15, 25], walking [15, 25], peripheral muscle training (i.e. quadriceps) , breathing exercises [15, 25], upper limb exercises [15, 25], yoga  and mental conditioning . All three studies demonstrated significant improvements (p < 0.001) in exercise tolerance as measured by an increase in 6-minute walk distance (6MWD) [15, 25] or endurance time on a cycle ergometer , one study reporting improvements in muscle strength and endurance . Improvements in HRQoL (SF-36 component summary scores) were also reported in one study (p < 0.05) . No adverse events were reported in any of the studies.
The studies to date have demonstrated improvements in exercise capacity in this patient population [10, 15, 25], however these studies have some limitations in the application of exercise training in Australia. Uchi et al  recruited subjects who had recently commenced intravenous PAH therapy and thus it is not possible to differentiate between the benefits of exercise and those attributed to the medication. The training programs have included a variety of modalities such as mental training and yoga , interventions that do not form part of most cardiopulmonary rehabilitation programs. Within Australia, most rehabilitation programs designed for cardiac or respiratory populations consist of whole body exercise training and take place in hospital outpatient departments or in community settings [26, 27]. This contrasts with the study by Mereles et al  in which subjects were admitted for a 3 week inpatient training program prior to performing a 12 week home exercise program. In Australia, the resources for providing inpatient exercise training to individuals who are stable on medical therapy are limited . The study by de Man et al  evaluated a 12 week outpatient exercise training program which comprised cycling and quadriceps training. The specificity of lower limb exercise training in this study is likely to account for the large increase in endurance cycle time and may explain the non-significant improvement in 6MWD.
To date, the studies have only reported the immediate effects of exercise training and thus it remains unknown whether the benefits are maintained following cessation of supervised training. It is also unknown whether an outpatient-based, whole body exercise training program is beneficial in patients with PAH and whether this type of program is capable of producing sustained benefits in exercise capacity and HRQoL.
This study aims to investigate the benefits of a 12 week hospital outpatient-based, individualised exercise training program involving supervised exercise sessions, followed by a 12 week home exercise program, for a cohort of subjects with PAH.
We hypothesise that:
A 12 week individualised, whole body exercise training program will improve:
Exercise training is safe and improvements in exercise capacity will be achieved without evidence of clinical worsening
An additional 12 week home exercise program will maintain or further improve the benefits gained during the 12 week, supervised, outpatient program.