TY - JOUR
T1 - Reducing Pulmonary Capillary Wedge Pressure During Exercise Exacerbates Exertional Dyspnea in Patients With Heart Failure With Preserved Ejection Fraction
T2 - Implications for V˙/Q˙ Mismatch
AU - Balmain, Bryce N.
AU - Tomlinson, Andrew R.
AU - MacNamara, James P.
AU - Hynan, Linda S.
AU - Wakeham, Denis J.
AU - Levine, Benjamin D.
AU - Sarma, Satyam
AU - Babb, Tony G.
N1 - Funding Information:
This study was supported by the National Institutes of Health [ 1P01HL137630 (B. D. L) and K99HL164957 (B. N. B)], the King Charitable Foundation Trust, Susan Lay Atwell Gift for Pulmonary Research, Cain Foundation, and Texas Health Presbyterian Hospital Dallas.
Publisher Copyright:
© 2023 American College of Chest Physicians
PY - 2023/9
Y1 - 2023/9
N2 - Background: The primary cause of dyspnea on exertion in heart failure with preserved ejection fraction (HFpEF) is presumed to be the marked rise in pulmonary capillary wedge pressure during exercise; however, this hypothesis has never been tested directly. Therefore, we evaluated invasive exercise hemodynamics and dyspnea on exertion in patients with HFpEF before and after acute nitroglycerin (NTG) treatment to lower pulmonary capillary wedge pressure. Research Question: Does reducing pulmonary capillary wedge pressure during exercise with NTG improve dyspnea on exertion in HFpEF? Study Design and Methods: Thirty patients with HFpEF performed two invasive 6-min constant-load cycling tests (20 W): one with placebo (PLC) and one with NTG. Ratings of perceived breathlessness (0-10 scale), pulmonary capillary wedge pressure (right side of heart catheter), and arterial blood gases (radial artery catheter) were measured. Measurements of V˙/Q˙ matching, including alveolar dead space (VDalv; Enghoff modification of the Bohr equation) and the alveolar-arterial PO2 difference (A-aDO2; alveolar gas equation), were also derived. The ventilation (V˙E)/CO2 elimination (V˙CO2) slope was also calculated as the slope of the V˙E and V˙CO2 relationship, which reflects ventilatory efficiency. Results: Ratings of perceived breathlessness increased (PLC: 3.43 ± 1.94 vs NTG: 4.03 ± 2.18; P =.009) despite a clear decrease in pulmonary capillary wedge pressure at 20 W (PLC: 19.7 ± 8.2 vs NTG: 15.9 ± 7.4 mm Hg; P <.001). Moreover, VDalv (PLC: 0.28 ± 0.07 vs NTG: 0.31 ± 0.08 L/breath; P =.01), A-aDO2 (PLC: 19.6 ± 6.7 vs NTG: 21.1 ± 6.7; P =.04), and V˙E/V˙CO2 slope (PLC: 37.6 ± 5.7 vs NTG: 40.2 ± 6.5; P <.001) all increased at 20 W after a decrease in pulmonary capillary wedge pressure. Interpretation: These findings have important clinical implications and indicate that lowering pulmonary capillary wedge pressure does not decrease dyspnea on exertion in patients with HFpEF; rather, lowering pulmonary capillary wedge pressure exacerbates dyspnea on exertion, increases V˙/Q˙ mismatch, and worsens ventilatory efficiency during exercise in these patients. This study provides compelling evidence that high pulmonary capillary wedge pressure is likely a secondary phenomenon rather than a primary cause of dyspnea on exertion in patients with HFpEF, and a new therapeutic paradigm is needed to improve symptoms of dyspnea on exertion in these patients.
AB - Background: The primary cause of dyspnea on exertion in heart failure with preserved ejection fraction (HFpEF) is presumed to be the marked rise in pulmonary capillary wedge pressure during exercise; however, this hypothesis has never been tested directly. Therefore, we evaluated invasive exercise hemodynamics and dyspnea on exertion in patients with HFpEF before and after acute nitroglycerin (NTG) treatment to lower pulmonary capillary wedge pressure. Research Question: Does reducing pulmonary capillary wedge pressure during exercise with NTG improve dyspnea on exertion in HFpEF? Study Design and Methods: Thirty patients with HFpEF performed two invasive 6-min constant-load cycling tests (20 W): one with placebo (PLC) and one with NTG. Ratings of perceived breathlessness (0-10 scale), pulmonary capillary wedge pressure (right side of heart catheter), and arterial blood gases (radial artery catheter) were measured. Measurements of V˙/Q˙ matching, including alveolar dead space (VDalv; Enghoff modification of the Bohr equation) and the alveolar-arterial PO2 difference (A-aDO2; alveolar gas equation), were also derived. The ventilation (V˙E)/CO2 elimination (V˙CO2) slope was also calculated as the slope of the V˙E and V˙CO2 relationship, which reflects ventilatory efficiency. Results: Ratings of perceived breathlessness increased (PLC: 3.43 ± 1.94 vs NTG: 4.03 ± 2.18; P =.009) despite a clear decrease in pulmonary capillary wedge pressure at 20 W (PLC: 19.7 ± 8.2 vs NTG: 15.9 ± 7.4 mm Hg; P <.001). Moreover, VDalv (PLC: 0.28 ± 0.07 vs NTG: 0.31 ± 0.08 L/breath; P =.01), A-aDO2 (PLC: 19.6 ± 6.7 vs NTG: 21.1 ± 6.7; P =.04), and V˙E/V˙CO2 slope (PLC: 37.6 ± 5.7 vs NTG: 40.2 ± 6.5; P <.001) all increased at 20 W after a decrease in pulmonary capillary wedge pressure. Interpretation: These findings have important clinical implications and indicate that lowering pulmonary capillary wedge pressure does not decrease dyspnea on exertion in patients with HFpEF; rather, lowering pulmonary capillary wedge pressure exacerbates dyspnea on exertion, increases V˙/Q˙ mismatch, and worsens ventilatory efficiency during exercise in these patients. This study provides compelling evidence that high pulmonary capillary wedge pressure is likely a secondary phenomenon rather than a primary cause of dyspnea on exertion in patients with HFpEF, and a new therapeutic paradigm is needed to improve symptoms of dyspnea on exertion in these patients.
KW - HFpEF
KW - V˙/Q˙ mismatch
KW - dead space
KW - pulmonary capillary wedge pressure
KW - shortness of breath
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U2 - 10.1016/j.chest.2023.04.003
DO - 10.1016/j.chest.2023.04.003
M3 - Article
C2 - 37030529
AN - SCOPUS:85161531136
SN - 0012-3692
VL - 164
SP - 686
EP - 699
JO - CHEST
JF - CHEST
IS - 3
ER -