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

Background: Exercise pulmonary hypertension (ePH), defined as a mean pulmonary artery pressure (mPAP)/cardiac output (Qc) 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 ePH (EePH) response are not well-defined, especially in relation to dyspnea on exertion (DOE) and exercise intolerance.

Methods: 48 HFpEF patients underwent invasive (pulmonary and radial artery catheters) constant-load (20W) and maximal incremental cycle testing. Hemodynamic measurements (mPAP and Qc), arterial blood and expired gases, and ratings of breathlessness (RPB, Borg 0-10) were obtained. The mPAP/Qc slope was calculated from rest-to-20W. Those with a mPAP/Qc slope >4.2 (median) were classified as HFpEF+EePH (n=24) and those with a mPAP/Qc slope <4.2 were classified as HFpEF (without EePH) (n=24). The A-aDO₂, V_D/V_T (Bohr equation), and the V_E/VCO₂ slope (from rest-to-20W) were calculated.

Results: PaO₂ was lower (p=0.03), and V_D/V_T was higher (p=0.03) at peak exercise in HFpEF+EePH compared with HFpEF. A-aDO₂ was similar at peak exercise between groups (p=0.14); however, HFpEF+EePH achieved the peak A-aDO₂ at a lower peak work rate (p<0.01). The V_E/VCO₂ slope was higher in HFpEF+EePH compared with HFpEF (p=0.01). RPB was ≥1-unit higher at 20W and VO_2peak was lower (p<0.01) in HFpEF+EePH compared with HFpEF.

Conclusions: These data suggest that EePH contributes to pulmonary gas exchange impairments during exercise by causing a V/Q mismatch that provokes both ventilatory inefficiency and hypoxemia, both of which seem to contribute to DOE and exercise intolerance in patients with HFpEF.