Factors contributing to exercise capacity in chronic thromboembolic pulmonary hypertension with near-normal hemodynamics

Abstract

Background: Despite improved survival for patients with chronic thromboembolic pulmonary hypertension (CTEPH) due to progressive medical and interventional treatment, impaired exercise capacity remains common due to poorly understood mechanisms. We aimed to clarify the exercise capacity of CTEPH patients with near-normal pulmonary hemodynamics and evaluate its determinants among the hemodynamic, peripheral (e.g., oxygen use by the peripheral tissues), and muscular (e.g., skeletal muscle strength) factors.

Methods: Three hundred and twenty-nine patients with CTEPH (mean age, 63 ± 12 years; men/women, 73/256) with a near-normal mean pulmonary artery pressure (≤30 mm Hg) at rest were enrolled. We assessed exercise capacity by peak oxygen consumption (peak VO₂) using cardiopulmonary exercise testing with a right heart catheter. We also measured the 6-minute walk distance (6MWD) and quadriceps muscle strength.

Results: The mean pulmonary artery pressure was 19 ± 4 mmHg and mean cardiac output was 4.8 ± 1.5 L/min at rest. The mean 6MWD was 444 ± 101 m, while the mean peak VO₂ was 14.4 ± 3.9 mL/min/kg. A multivariate model that predicted 6MWD included quadriceps strength (β = 0.45, p < 0.001) and peak arterial venous oxygen difference (β = 0.29, p < 0.001). In contrast, the peak VO₂ was best correlated with mPAP-CO slope (β = -0.30, p < 0.001), followed by quadriceps strength and peak arterial venous oxygen difference.

Conclusions: The 6MWD performance may be significantly influenced by peripheral oxygen use and muscular factors, while peak VO₂ is influenced by hemodynamic and peripheral factors in CTEPH patients with near-normal hemodynamics.

Keywords: Pulmonary hypertension; exercise capacity; muscle strength.