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. 2017 Dec;19(12):1675-1685.
doi: 10.1002/ejhf.913. Epub 2017 Oct 8.

Physiological dead space and arterial carbon dioxide contributions to exercise ventilatory inefficiency in patients with reduced or preserved ejection fraction heart failure

Erik H Van Iterson  1 , Bruce D Johnson  1 , Barry A Borlaug  1 , Thomas P Olson  1
Affiliations

Physiological dead space and arterial carbon dioxide contributions to exercise ventilatory inefficiency in patients with reduced or preserved ejection fraction heart failure

Erik H Van Iterson et al. Eur J Heart Fail. 2017 Dec.

Abstract

Aims: Patients with heart failure (HF) with reduced (HFrEF) or preserved (HFpEF) ejection fraction demonstrate an increased ventilatory equivalent for carbon dioxide (V̇E /V̇CO2 ) slope. The physiological correlates of the V̇E /V̇CO2 slope remain unclear in the two HF phenotypes. We hypothesized that changes in the physiological dead space to tidal volume ratio (VD /VT ) and arterial CO2 tension (PaCO2 ) differentially contribute to the V̇E /V̇CO2 slope in HFrEF vs. HFpEF.

Methods and results: Adults with HFrEF (n = 32) and HFpEF (n = 27) [mean ± standard deviation (SD) left ventricular ejection fraction: 22 ± 7% and 61 ± 9%, respectively; mean ± SD body mass index: 28 ± 4 kg/m2 and 33 ± 6 kg/m2 , respectively; P < 0.01] performed cardiopulmonary exercise testing with breath-by-breath ventilation and gas exchange measurements. PaCO2 was measured via radial arterial catheterization. We calculated the V̇E /V̇CO2 slope via linear regression, and VD /VT = 1 - [(863 × V̇CO2 )/(V̇E × PaCO2 )]. Resting VD /VT (0.48 ± 0.08 vs. 0.41 ± 0.11; P = 0.04), but not PaCO2 (38 ± 5 mmHg vs. 40 ± 3 mmHg; P = 0.21) differed between HFrEF and HFpEF. Peak exercise VD /VT (0.39 ± 0.08 vs. 0.32 ± 0.12; P = 0.02) and PaCO2 (33 ± 6 mmHg vs. 38 ± 4 mmHg; P < 0.01) differed between HFrEF and HFpEF. The V̇E /V̇CO2 slope was higher in HFrEF compared with HFpEF (44 ± 11 vs. 35 ± 8; P < 0.01). Variance associated with the V̇E /V̇CO2 slope in HFrEF and HFpEF was explained by peak exercise VD /VT (R2 = 0.30 and R2 = 0.50, respectively) and PaCO2 (R2 = 0.64 and R2 = 0.28, respectively), but the relative contributions of each differed (all P < 0.01).

Conclusions: Relationships between the V̇E /V̇CO2 slope and both VD /VT and PaCO2 are robust, but differ between HFpEF and HFrEF. Increasing V̇E /V̇CO2 slope appears to be strongly explained by mechanisms influential in regulating PaCO2 in HFrEF, which contrasts with the strong role of increased VD /VT in HFpEF.

Keywords: Cardiopulmonary exercise testing; Exercise capacity; Exercise intolerance; Exercise tolerance; Exercise ventilatory efficiency; Heart failure with preserved ejection fraction.

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Conflict of interest statement

Conflicts of Interest: none declared.

Figures

Figure 1
Figure 1
Measurements or univariate linear regressions involving the ventilatory equivalent for carbon dioxide (V̇E/V̇CO2) slope, physiologic dead space to tidal volume ratio (VD/VT), or arterial carbon dioxide tension (PaCO2). Data presented in panels A to C are interquartile range with mean represented as (+). Variables presented on the abscissa in panels D to F are at rest, peak exercise, and peak exercise, respectively. For panels D to F representative of all participants: filled circle is mean ± SD of V̇E/V̇CO2 slope at the mean of the variable set on the abscissa, solid line is goodness of fit line of the model fit equation, dotted lines are 95% prediction bands of the model fit equation, and grey bands are isopleths representing linked changes in observed V̇E/V̇CO2 slope and PaCO2 or VD/VT when either PaCO2 or VD/VT are theoretically constrained values. Interpretation of R2: modest=0.02; moderate=0.15; or strong≥0.25. The Y-intercept in panels D to F differed from 0.0 (P<0.01). Differences in R2: panel D vs. E or F, P<0.001; panel E vs. F, P=0.16. Heart failure with reduced (HFrEF, N=32) or preserved (HFpEF, N=27) ejection fraction. *Following post-hoc Tukey-Kramer testing, different within group for both HFrEF and HFpEF or all HF, rest to peak exercise, P<0.05.
Figure 2
Figure 2
Univariate linear regressions involving the ventilatory equivalent for carbon dioxide (V̇E/V̇CO2) slope (dependent, ordinate), peak exercise physiologic dead space to tidal volume ratio (VD/VT) (independent, abscissa), or peak exercise arterial CO2 tension (PaCO2) (independent, abscissa). For all panels: filled circle is mean ± SD of V̇E/V̇CO2 slope at the mean of the variable set on the abscissa, solid line is goodness of fit line of the model fit equation, dotted lines are 95% prediction bands of the model fit equation, and grey bands are isopleths representing linked changes in observed V̇E/V̇CO2 slope and PaCO2 or VD/VT when either PaCO2 or VD/VT are theoretically constrained values. Interpretation of R2: modest=0.02; moderate=0.15; or strong≥0.25. The Y-intercept in panel A did not differ from 0.0 (P=0.14), whereas the Y-intercept in panels B to D differed from 0.0 (P<0.01). Differences in R2: panel A vs. B, P=0.06; panel A vs. C, P=0.33; panel B vs. D, P=0.06; panel C vs. D, P=0.30. Heart failure with reduced (HFrEF, N=32) or preserved (HFpEF, N=27) ejection fraction.
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