Exercise-induced Pulmonary Arterial Hypertension Is Associated With An Attenuated Increase In Cardiac Output During Exercise

Abstract

Pulmonary arterial hypertension (PAH) can be diagnosed at rest (rPAH) or in response to exercise (EIPAH), however the clinical significance of EIPAH is unclear. rPAH is associated with reduced pulmonary artery capacitance (PAC), an attenuated increase in cardiac output (CO) and a rise in pulmonary vascular resistance (PVC) during exercise. The presence of these abnormalities in subjects with EIPAH may reflect early pulmonary vasculopathy. PURPOSE: To determine whether clinically significant hemodynamic and ventilatory abnormalities exist in patients with EIPAH, despite normal mean pulmonary artery pressure (mPAP) at rest, and their impact on aerobic capacity and health related quality of life (HRQoL). METHODS: 39 symptomatic patients, NYHA class II (n = 27) or III (n = 12), at risk for PAH, underwent a cardiopulmonary exercise test (CPET) with a right heart catheter in situ. 21 healthy controls (C), matched for age, gender and BMI with EIPAH subjects, underwent CPET for comparison of aerobic capacity and ventilatory response. HRQoL (SF-36) was assessed in all subjects. RESULTS: Following CPET, patient subjects were stratified using World Health Organization PAH diagnostic criteria: resting PAH (mPAP ≥ 25 mmHg at rest, n = 7), EIPAH (mPAP ≤25 mmHg at rest, ≥30mmHg on exercise, n = 22) or no evidence of PAH (nonPAH) (n = 10). Compared with nonPAH, both rPAH and EIPAH were associated with lower CO (7.4±0.7, 8.6±0.5 vs 11.0±0.8 L/min, p<0.05, mean±SEM), higher PVC (4.6±0.7, 2.5±0.3 vs 1.4±0.2 Woods units, p<0.05) and lower PAC (1.2±0.3, 1.8±0.1 vs 2.4±0.2 ml/mmHg, p<0.05) at peak exercise. Compared with C, subjects with rPAH and EIPAH had lower peak oxygen consumption (12.8±1.8, 18.0±0.8 vs 25.6±1.7 ml/kg/min, p<0.01), lower end tidal carbon dioxide at anaerobic threshold (AT) (30.3±3.1, 34.0±0.8 vs 39.4±0.6 mmHg, p<0.01) and a higher ventilatory equivalent for carbon dioxide at AT (49.0±5.4, 39.2±1.7 vs 30.9±0.7, p<0.01). rPAH and EIPAH subjects had impaired HRQoL compared with C (p<0.05). CONCLUSIONS: EIPAH is associated with hemodynamic and ventilatory abnormalities typical of rPAH and is suggestive of a clinically important pulmonary vasculopathy linked to reduced exercise capacity and HRQoL.