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

Rudolf K F Oliveira, Mariana Faria-Urbina, Bradley A Maron, Mario Santos, Aaron B Waxman, David M Systrom, Rudolf K F Oliveira, Mariana Faria-Urbina, Bradley A Maron, Mario Santos, Aaron B Waxman, David M Systrom

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.

Keywords: exercise; oxygen delivery; oxygen uptake; pathophysiology; pulmonary hypertension.

Figures

Fig. 1.
Fig. 1.
Study flow diagram. PH, pulmonary hypertension; iCPET, invasive cardiopulmonary exercise testing; RHC, right heart catheterization; mPAP, mean pulmonary arterial pressure; PAWP, pulmonary arterial wedge pressure; HFrEF, heart failure with reduced ejection fraction; PVR, pulmonary vascular resistance; LHD, left heart disease; non-PH, normal resting/exercise pulmonary hemodynamics; ePH, exercise pulmonary hypertension; rPH, resting precapillary pulmonary hypertension.
Fig. 2.
Fig. 2.
Prevalence of exercise pulmonary hypertension (ePH) according to the resting mean pulmonary arterial pressure (mPAP) at right heart catheterization (RHC).
Fig. 3.
Fig. 3.
Mean pulmonary arterial pressure to cardiac output (mPAP/CO) slope from rest upright to peak upright according to the right heart catheterization mPAP. mPAP P < 0.05 compared with non-PH.
Fig. 4.
Fig. 4.
Peak oxygen uptake (VO2) across different resting mean pulmonary arterial pressure (mPAP) values at right heart catheterization. Data represent the mean ± SD (error bars). non-PH, normal resting/exercise pulmonary hemodynamics; ePH, exercise pulmonary hypertension.
Fig. 5.
Fig. 5.
Minute per minute relationship between pulmonary vascular resistance (PVR) and pulmonary vascular compliance (PVC) from rest upright to peak exercise, which included rest, freewheeling and minute per minute incremental PVR and PVC until symptom-limited peak exercise (a). Minute per minute Log [PVR] – log [PVC] plot (b). n = 2129 individual data points obtained from 224 non-PH patients, n = 294 from 35 ePH, and n = 115 from 16 rPH patients. non-PH, normal resting/exercise pulmonary hemodynamics; ePH, exercise pulmonary hypertension; rPH, resting precapillary pulmonary hypertension.

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