Alveolar Air and O2 Uptake During Exercise in Patients With Heart Failure

Abstract

Background: Peak exercise pulmonary oxygen uptake (V̇O₂) is a primary marker of prognosis in heart failure (HF). The pathophysiology of impaired peak V̇O₂ is unclear in patients. To what extent alveolar airway function affects V̇O₂ during cardiopulmonary exercise testing (CPET) has not been fully elucidated. This study aimed to describe how changes in alveolar ventilation (V̇_A), volume (V_A), and related parameters couple with exercise V̇O₂ in HF.

Methods and results: A total of 35 patients with HF (left ventricular ejection fraction 20 ± 6%, age 53 ± 7 y) participated in CPET with breath-to-breath measurements of ventilation and gas exchange. At rest, 20 W, and peak exercise, arterial CO₂ tension was measured via radial arterial catheterization and used in alveolar equations to derive V̇_A and V_A. Resting lung diffusion capacity for carbon monoxide (DL_CO) was assessed and indexed to V_A for each time point. Resting R² between V̇O₂ and V̇_A, V_A, DL_CO, and DL_CO/V_A was 0.68, 0.18, 0.20, and 0.07, respectively (all P < .05 except DL_CO/V_A). 20 W R² between V̇O₂ and V̇_A, V_A, DL_CO, and DL_CO/V_A was 0.64, 0.32, 0.07, and 0.18 (all P < .05 except DL_CO). Peak exercise R² between V̇O₂ and V̇_A, V_A, DL_CO, and DL_CO/V_A was 0.55, 0.31, 0.34, and 0.06 (all P < .05 except DL_CO/V_A).

Conclusions: These data suggest that alveolar airway function that is not exclusively related to effects caused by localized lung diffusivity affects exercise V̇O₂ in moderate-to-severe HF.

Keywords: Aerobic exercise capacity; Exercise intolerance; HFpEF; HFrEF; Metabolic demand; O(2) transport; Oxidative capacity.

Figure 1:

Construct validity between measured $\stackrel{.}{\text{V}}{\text{O}}_{\text{2}}$ compared with $\stackrel{.}{\text{V}}{\text{O}}_{\text{2}}$ derived using ‘ideal’ alveolar air equations in patients with heart failure. Panels A to C) $\stackrel{.}{\text{V}}{\text{O}}_{\text{2}}$ measurements at rest, 20W, and peak exercise, respectively. Measured is $\stackrel{.}{\text{V}}{\text{O}}_{\text{2}}$ reported via open-circuit indirect calorimetry system; Alveolar (STPD) is $\stackrel{.}{\text{V}}{\text{O}}_{\text{2}}$ that has been derived using ‘ideal’ alveolar air equations and converted to the proper environmental measurement units for metabolic calculation of gases (standard temperature, pressure, and dry). Data presented as box plots represents q25, median, and q75. The mean of the sample is represented as (+). Panels D (rest), E (20 watts), and F (peak exercise): For all least squares univariate regressions $\stackrel{.}{\text{V}}{\text{O}}_{\text{2}}$ (alveolar STPD) (criterion) is the dependent variable to be predicted while being set on the ordinate. Solid black line is the regression line. Presented in brackets are 95% confidence limits (CL). Panels G to I: Predicted $\stackrel{.}{\text{V}}{\text{O}}_{\text{2}}$ values using respective regression (calibration, y=mx+b) equations from Panels D,E, and F versus residuals [i.e., (criterion) $\stackrel{.}{\text{V}}{\text{O}}_{\text{2}}$ (alveolar STPD) minus predicted $\stackrel{.}{\text{V}}{\text{O}}_{\text{2}}$]. Dispersion of error occuring when predicting $\stackrel{.}{\text{V}}{\text{O}}_{\text{2}}$ using respective regression equations from Panels D, E, and F are objectively quantified using the standard error of estimate (SEE) (smaller is better) with lower and upper 95% CL in brackets.

Figure 2:

Relationships between alveolar ventilation (${\stackrel{.}{\text{V}}}_{\text{A}}$) and pulmonary O₂ uptake ($\stackrel{.}{\text{V}}{\text{O}}_{\text{2}}$). Data are least squares univariate regressions. Solid black line is the regression line for each test involving observed ${\stackrel{.}{\text{V}}}_{\text{A}}$ and $\stackrel{.}{\text{V}}{\text{O}}_{\text{2}}$ as open circles. Grey circle outlined in black within each panel is at the group mean for ${\stackrel{.}{\text{V}}}_{\text{A}}$. and $\stackrel{.}{\text{V}}{\text{O}}_{\text{2}}$. To assess the effect of ${\stackrel{.}{\text{V}}}_{\text{A}}$ on $\stackrel{.}{\text{V}}{\text{O}}_{\text{2}}$ without variability in alveolar O₂ tension (PAO₂), grey solid lines in each panel are isopleths for the theoretical relationship between observed values for ${\stackrel{.}{\text{V}}}_{\text{A}}$ and $\stackrel{.}{\text{V}}{\text{O}}_{\text{2}}$ with an invariable (constrained) PAO₂ (i.e., at the group median). To assess the equivalent total ventilation (${\stackrel{.}{\text{V}}}_{\text{E}}$) required to drive $\stackrel{.}{\text{V}}{\text{O}}_{\text{2}}-{\stackrel{.}{\text{V}}}_{\text{A}}$ relationships, grey hashed lines are isopleths for the theoretical relationship between observed values for ${\stackrel{.}{\text{V}}}_{\text{E}}$ and $\stackrel{.}{\text{V}}{\text{O}}_{\text{2}}$ when PAO₂ was set for all participants at alveolar O₂ fractions equivalent to the group median at each respective measurement time point.