Background: Pulmonary hypertension causes pulmonary artery (PA) stiffening, which overloads the right ventricle (RV). Since symptoms of pulmonary hypertension (PH) are exacerbated by exercise, exercise-induced PA stiffening is relevant to cardiopulmonary status. Here, we sought to demonstrate the feasibility of using magnetic resonance imaging (MRI) for non-invasive assessment of exercise-induced changes in PA stiffness in patients with PH. Methods: MRI was performed on 7 PH patients and 8 age-matched control subjects at rest and during exercise stress. Main pulmonary artery (MPA) relative area change (RAC) and pulse wave velocity (PWV) were measured from 2D-PC images. Invasive right heart catheterization (RHC) was performed on 5 of the PH patients in conjunction with exercise stress to measure MPA pressures and stiffness index (β). Results: Heart rate and cardiac index (CI) were significantly increased with exercise in both groups. In controls, RAC decreased from 0.27 ± 0.05 at rest to 0.22 ± 0.06 with exercise (P < 0.05); a modest increase in PWV was not significant (P = 0.06). In PH patients, RAC decreased from 0.15 ± 0.02 to 0.11 ± 0.01 (P < 0.05) and PWV and β increased from 3.9 ± 0.54 m/s and 1.86 ± 0.12 at rest to 5.75 ± 0.70 m/s and 3.25 ± 0.26 with exercise (P < 0.05 for both), respectively. These results confirm increased MPA stiffness with exercise stress in both groups and the non-invasive metrics of MPA stiffness correlated well with β. Finally, as assessed by PWV but not RAC, PA stiffness of PH patients increased more than that of controls for comparable levels of moderate exercise. Conclusion: These results demonstrate the feasibility of using MRI for non-invasive assessment of exercise-induced changes in MPA stiffness in a small, heterogeneous group of PH patients in a research context. Similar measurements in a larger cohort are required to investigate differences between PWV and RAC for estimation of MPA stiffness.

Objective

Inadequate right ventricular (RV) and pulmonary arterial (PA) functional responses to exercise are important yet poorly understood features of pulmonary arterial hypertension (PAH). This study combined invasive catheterisation with echocardiography to assess RV afterload, RV function and ventricular-vascular coupling in subjects with PAH.

Methods

Twenty-six subjects with PAH were prospectively recruited to undergo right heart catheterisation and Doppler echocardiography at rest and during incremental exercise, and cardiac MRI at rest. Measurements at rest included basic haemodynamics, RV function and coupling efficiency (η). Measurements during incremental exercise included pulmonary vascular resistance (Z₀), characteristic impedance (Z_C, a measure of proximal PA stiffness) and proximal and distal PA compliance (C_PA).

Results

In patients with PAH, the proximal PAs were significantly stiffer at maximum exercise (Z_C =2.31±0.38 vs 1.33±0.15 WU×m² at rest; p=0.003) and PA compliance was decreased (C_PA=0.88±0.10 vs 1.32±0.17 mL/mm Hg/m² at rest; p=0.0002). Z₀ did not change with exercise. As a result, the resistance-compliance (RC) time decreased with exercise (0.67±0.05 vs 1.00±0.07 s at rest; p<10^-6). When patients were grouped according to resting coupling efficiency, those with poorer η exhibited stiffer proximal PAs at rest, a lower maximum exercise level, and more limited C_PA reduction at maximum exercise.

Conclusions

In PAH, exercise causes proximal and distal PA stiffening, which combined with preserved Z₀ results in decreased RC time with exercise. Stiff PAs at rest may also contribute to poor haemodynamic coupling, reflecting reduced pulmonary vascular reserve that contributes to limit the maximum exercise level tolerated.