• Bryce N Balmain, Andrew R Tomlinson, James P MacNamara, Linda S Hynan, Benjamin D Levine, Satyam Sarma, and Tony G Babb.
• Institute for Exercise and Environmental Medicine, Texas Health Presbyterian Hospital, Dallas, TX; Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX.
• Chest. 2022 Dec 1; 162 (6): 134913591349-1359.

BackgroundPatients with heart failure with preserved ejection fraction (HFpEF) exhibit many cardiopulmonary abnormalities that could result in V˙/Q˙ mismatch, manifesting as an increase in alveolar dead space (VDalveolar) during exercise. Therefore, we tested the hypothesis that VDalveolar would increase during exercise to a greater extent in patients with HFpEF compared with control participants.Research QuestionDo patients with HFpEF develop VDalveolar during exercise?Study Design And MethodsTwenty-three patients with HFpEF and 12 control participants were studied. Gas exchange (ventilation [V˙E], oxygen uptake [V˙o2], and CO2 elimination [V˙co2]) and arterial blood gases were analyzed at rest, twenty watts (20W), and peak exercise. Ventilatory efficiency (evaluated as the V˙E/V˙co2 slope) also was measured from rest to 20W in patients with HFpEF. The physiologic dead space (VDphysiologic) to tidal volume (VT) ratio (VD/VT) was calculated using the Enghoff modification of the Bohr equation. VDalveolar was calculated as: (VD / VT × VT) - anatomic dead space. Data were analyzed between groups (patients with HFpEF vs control participants) across conditions (rest, 20W, and peak exercise) using a two-way repeated measures analysis of variance and relationships were analyzed using Pearson correlation coefficient.ResultsVDalveolar increased from rest (0.12 ± 0.07 L/breath) to 20W (0.22 ± 0.08 L/breath) in patients with HFpEF (P < .01), whereas VDalveolar did not change from rest (0.01 ± 0.06 L/breath) to 20W (0.06 ± 0.13 L/breath) in control participants (P = .19). Thereafter, VDalveolar increased from 20W to peak exercise in patients with HFpEF (0.37 ± 0.16 L/breath; P < .01 vs 20W) and control participants (0.19 ± 0.17 L/breath; P = .03 vs 20W). VDalveolar was greater in patients with HFpEF compared with control participants at rest, 20W, and peak exercise (main effect for group, P < .01). Moreover, the increase in VDalveolar correlated with the V˙E/V˙co2 slope (r = 0.69; P < .01), which was correlated with peak V˙o2peak (r = 0.46; P < .01) in patients with HFpEF.InterpretationThese data suggest that the increase in V˙/Q˙ mismatch may be explained by increases in VDalveolar and that increases in VDalveolar worsens ventilatory efficiency, which seems to be a key contributor to exercise intolerance in patients with HFpEF.Copyright © 2022 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.

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