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

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Aims: Patients with heart failure (HF) with reduced (HFrEF) or preserved (HFpEF) ejection fraction demonstrate an increased ventilatory equivalent for carbon dioxide (V˙E/V˙CO2) slope. The physiological correlates of the V˙E/V˙CO2 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 V˙E/V˙CO2 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±4kg/m2 and 33±6kg/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 V˙E/V˙CO2 slope via linear regression, and VD/VT=1-[(863 × V˙CO2)/(V˙E×PaCO2)]. Resting VD/VT (0.48±0.08 vs. 0.41±0.11; P=0.04), but not PaCO2 (38±5mmHg vs. 40±3mmHg; 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±6mmHg vs. 38±4mmHg; P<0.01) differed between HFrEF and HFpEF. The V˙E/V˙CO2 slope was higher in HFrEF compared with HFpEF (44±11 vs. 35±8; P<0.01). Variance associated with the V˙E/V˙CO2 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 V˙E/V˙CO2 slope and both VD/VT and PaCO2 are robust, but differ between HFpEF and HFrEF. Increasing V˙E/V˙CO2 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.

Original languageEnglish (US)
JournalEuropean Journal of Heart Failure
StateAccepted/In press - 2017



  • Cardiopulmonary exercise testing
  • Exercise capacity
  • Exercise intolerance
  • Exercise tolerance
  • Exercise ventilatory efficiency
  • Heart failure with preserved ejection fraction

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

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