Functional impact of exercise pulmonary hypertension in patients with borderline resting pulmonary arterial pressure

Abstract

Borderline resting mean pulmonary arterial pressure (mPAP) is associated with adverse outcomes and affects the exercise pulmonary vascular response. However, the pathophysiological mechanisms underlying exertional intolerance in borderline mPAP remain incompletely characterized. In the current study, we sought to evaluate the prevalence and functional impact of exercise pulmonary hypertension (ePH) across a spectrum of resting mPAP’s in consecutive patients with contemporary resting right heart catheterization (RHC) and invasive cardiopulmonary exercise testing. Patients with resting mPAP <25 mmHg and pulmonary arterial wedge pressure ≤15 mmHg (n = 312) were stratified by mPAP < 13, 13–16, 17–20, and 21–24 mmHg. Those with ePH (n = 35) were compared with resting precapillary pulmonary hypertension (rPH; n = 16) and to those with normal hemodynamics (non-PH; n = 224). ePH prevalence was 6%, 8%, and 27% for resting mPAP 13–16, 17–20, and 21–24 mmHg, respectively. Within each of these resting mPAP epochs, ePH negatively impacted exercise capacity compared with non-PH (peak oxygen uptake 70 ± 16% versus 92 ± 19% predicted, P < 0.01; 72 ± 13% versus 86 ± 17% predicted, P < 0.05; and 64 ± 15% versus 82 ± 19% predicted, P < 0.001, respectively). Overall, ePH and rPH had similar functional limitation (peak oxygen uptake 67 ± 15% versus 68 ± 17% predicted, P > 0.05) and similar underlying mechanisms of exercise intolerance compared with non-PH (peak oxygen delivery 1868 ± 599 mL/min versus 1756 ± 720 mL/min versus 2482 ± 875 mL/min, respectively; P < 0.05), associated with chronotropic incompetence, increased right ventricular afterload and signs of right ventricular/pulmonary vascular uncoupling. In conclusion, ePH is most frequently found in borderline mPAP, reducing exercise capacity in a manner similar to rPH. When borderline mPAP is identified at RHC, evaluation of the pulmonary circulation under the stress of exercise is warranted.

Reduced Right Ventricular Output Reserve in Patients With Systemic Sclerosis and Mildly Elevated Pulmonary Artery Pressure

“…Oliveira et al found that exercise‐induced PH was most frequently seen in patients with a mean PAP of 21–24 mm Hg, who have a reduction in exercise capacity similar to that in patients with resting PH . In the present study, 22 (30.6%) of 72 patients with a mean PAP of <21 mm Hg at rest fulfilled the criteria for exercise‐induced PH versus 11 (78.6%) of 14 patients with a mean PAP of 21–24 mm Hg, consistent with the observations of Oliveira et al . However, in our study, regression and correlation analysis revealed a significant correlation of PAC at rest with 6‐minute walking distance (R = 0.448, P < 0.001) (Figure ) and ΔCO (R = 0.227, P = 0.018) and a trend toward correlation of PAC at rest with ΔCI (R = 0.178, P = 0.064).…”

“…The combination of a mean PAP of 21–24 mm Hg and exercise‐induced PH in that population was associated with worse functional capacity , increased progression to resting PH , and worse survival . Oliveira et al found that exercise‐induced PH was most frequently seen in patients with a mean PAP of 21–24 mm Hg, who have a reduction in exercise capacity similar to that in patients with resting PH . In the present study, 22 (30.6%) of 72 patients with a mean PAP of <21 mm Hg at rest fulfilled the criteria for exercise‐induced PH versus 11 (78.6%) of 14 patients with a mean PAP of 21–24 mm Hg, consistent with the observations of Oliveira et al .…”

Transition from post‐capillary pulmonary hypertension to combined pre‐ and post‐capillary pulmonary hypertension in swine: a key role for endothelin

“…; Oliveira et al . ). Clinically, group II PH comprises a variety of different aetiologies, including left HF, valvular disease, inflow‐/outflow‐tract obstructions, and congenital or acquired pulmonary vein stenosis.…”

“…The additional chronic instrumentation, and subsequent exercise testing unmasked a mild chronotropic incompetence that has also been shown in PH (Oliveira et al . ), and has been ascribed to impaired autonomic control (Bristow et al . ; Wensel et al .…”

Metabolomics of exercise pulmonary hypertension are intermediate between controls and patients with pulmonary arterial hypertension

“…5 Twenty five percent to 86% of patients with resting mPAP 21-24 mmHg have ePH. 6,7 ePH itself is associated with overt symptoms, reduced exercise capacity, and poorer clinical outcomes. 3,[8][9][10][11][12][13] Exercise PH may represent an early and clinically relevant stage of pulmonary arterial hypertension (PAH).…”