Background:
Exertional intolerance is a limiting and often crippling symptom in patients with chronic thromboembolic pulmonary hypertension (CTEPH). Traditionally the etiology has been attributed to central factors, including ventilation-perfusion mismatch, increased pulmonary vascular resistance and right heart dysfunction and uncoupling. Pulmonary endarterectomy and, balloon pulmonary angioplasty provide substantial improvement of functional status and hemodynamics. However, despite normalization of pulmonary hemodynamics, exercise capacity often does not return to age-predicted. By systematically evaluating the oxygen (O
2
) pathway we aimed to elucidate the cause/s of functional limitations in CTEPH patients before and after pulmonary vascular intervention.
Methods:
Using exercise cardiac magnetic resonance (CMR) imaging with simultaneous invasive hemodynamic monitoring, we sought to quantify the steps of the O2 transport cascade from the mouth to the mitochondria in patients with CTEPH (n=20) as compared to healthy subjects (n=10). Furthermore we evaluated the effect of pulmonary vascular intervention (pulmonary endarterectomy or balloon angioplasty) on the individual components of the cascade (n=10).
Results:
Peak VO2 was significantly reduced in CTEPH patients relative to controls (56±17 vs 112±20% of predicted, p<0.0001). The difference was due to impairments in multiple steps of the O
2
cascade, including O
2
delivery (product of cardiac output and arterial O
2
content), skeletal muscle diffusion capacity, and pulmonary diffusion. The total O
2
extracted in the periphery, i.e. ΔAVO
2
, was not different. Following pulmonary vascular intervention, peak VO
2
increased significantly (12.5±4.0 to 17.8±7.5 ml/kg/min, p=0.036) but remained below age-predicted (70±11%). The O
2
delivery was improved due to an increase in peak cardiac output and lung diffusion capacity. However, peak exercise ΔAVO2 was unchanged, as was skeletal muscle diffusion capacity.
Conclusions:
We demonstrated that CTEPH patients have significant impairment of all steps in the O
2
utilisation cascade resulting in markedly impaired exercise capacity. Pulmonary vascular intervention increased peak VO
2
, by partly correcting O
2
delivery but having no impact on abnormalities in peripheral O
2
extraction. This suggests that current interventions only partially address patients' limitations and that additional therapies may improve functional capacity.
Diffusion capacity and haemodynamics in primary and chronic thromboembolic pulmonary hypertension
