Both central and peripheral factors contribute to low exercise tolerance in patients with pulmonary arterial hypertension (PAH), according to a study published in the Journal of the American Heart Association. 

Exercise intolerance is a characteristic clinical feature of PAH, regardless of disease severity. Scientists have thus sought to identify factors that cause this; studies indicate that reduced oxygenation to the muscles, respiratory muscular dysfunction, and deteriorating skeletal muscle strength may drive a reduction in exercise capacity among patients with PAH. 

The authors of this study sought to further investigate exercise intolerance in the context of PAH. They used various functional tests and parameters to assess exercise capacity, such as the 6-minute walk distance test, peak oxygen consumption, and ventilatory efficiency. The goal of the study was to identify potential targets that can be used to therapeutically improve exercise capacity among individuals with PAH. 

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The research team recruited patients with PAH who underwent cardiopulmonary exercise testing with right heart catheterization between May 2013 and March 2021. Selected participants must have demonstrated near-normal pulmonary arterial pressure at rest (≤30 mm Hg). Individuals who had collagen tissue disease or a high pulmonary artery wedge pressure at rest were excluded. 

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Eighty-two patients were included in the study. The authors reported 3 key findings: first, 6-minute walk distance test performance was highly associated with muscular oxygen extraction; second, peak peak oxygen consumption was associated with both peripheral and hemodynamic parameters; and third; the minute ventilation vs carbon dioxide output slope was mainly associated with hemodynamic function in patients with hemodynamically normalized PAH (low-risk individuals), showing a weak but negative correlation with peripheral muscle strength. 

The research team also discovered that exercise training reverses exercise intolerance and improves quality of life, making it an “important adjunctive medical therapy.” Exercise training improves and strengthens skeletal muscle function and increases the expression of muscular enzymes. 


Tobita K, Goda A, Teruya K, et al. Exercise capacity and ventilatory efficiency in patients with pulmonary arterial hypertensionJ Am Heart Assoc. Published online June 6, 2023. doi:10.1161/JAHA.122.026890