Pulmonary gas exchange in relation to exercise pulmonary hypertension in patients with heart failure with preserved ejection fraction.

Background: Exercise pulmonary hypertension, defined as a mean pulmonary arterial pressure (mPAP)/cardiac output (Q̇c) slope >3 WU during exercise, is common in patients with heart failure with preserved ejection fraction (HFpEF). However, the pulmonary gas exchange-related effects of an exaggerated exercise pulmonary hypertension (EePH) response are not well defined, especially in relation to dyspnoea on exertion and exercise intolerance.

Methods: 48 HFpEF patients underwent invasive (pulmonary and radial artery catheters) constant-load (20 W) and maximal incremental cycle testing. Haemodynamic measurements (mPAP and Q̇c), arterial blood and expired gases, and ratings of perceived breathlessness (Borg 0-10 scale) were obtained. The mPAP/Q̇c slope was calculated from rest to 20 W. Those with a mPAP/Q̇c slope ≥4.2 (median) were classified as HFpEF+EePH (n=24) and those with a mPAP/Q̇c slope <4.2 were classified as HFpEF (without EePH) (n=24). The alveolar-arterial oxygen tension difference, dead space to tidal volume ratio (Bohr equation) and the minute ventilation to carbon dioxide production slope (from rest to 20 W) were calculated.

Results: Arterial oxygen tension was lower (p=0.03) and dead space to tidal volume ratio was higher (p=0.03) at peak exercise in HFpEF+EePH than in HFpEF. The alveolar-arterial oxygen tension difference was similar at peak exercise between groups (p=0.14); however, patients with HFpEF+EePH achieved the peak alveolar-arterial oxygen tension difference at a lower peak work rate (p<0.01). The minute ventilation to carbon dioxide production slope was higher in HFpEF+EePH than in HFpEF (p=0.01). Perceived breathlessness was ≥1 unit higher at 20 W and peak oxygen uptake was lower (p<0.01) in HFpEF+EePH than in HFpEF.

Conclusions: These data suggest that EePH contributes to pulmonary gas exchange impairments during exercise by causing a ventilation/perfusion mismatch that provokes both ventilatory inefficiency and hypoxaemia, both of which seem to contribute to dyspnoea on exertion and exercise intolerance in patients with HFpEF.