Differential contribution of dead space ventilation and low arterial pCO2 to exercise hyperpnea in patients with chronic heart failure secondary to ischemic or idiopathic dilated cardiomyopathy

In chronic heart failure (CHF), the abnormally large ventilatory response to exercise (VE/VCO2 slope) has 2 conceptual elements: the requirement of restraining arterial partial pressure of carbon dioxide (pCO2) from increasing (because of an increased ratio between increased physiologic dead space and tidal volume [VD/VT]) and the depression of arterial pCO2 by further increased ventilation, which necessarily implies an important non-carbon dioxide stimulus to ventilation. We aimed to assess the contribution of these 2 factors in determining the elevated VE/VCO2 slope in CHF. Thirty patients with CHF underwent cardiopulmonary exercise testing (age 65 ± 11 years, left ventricular ejection fraction 34 ± 15%, peak oxygen uptake 15.2 ± 4 ml/kg/min, VE/VCO2 slope 36.4). At rest and during exercise, arterial pCO2 was measured and VD was calculated and separated into serial and alveolar components. VD/VT decreased from 0.57 at rest to 0.44 at peak exercise (p <0.01). VE/VCO2 slope was correlated with peak exercise VD/VT (r = 0.67), the serial VD/VT ratio (r = 0.64), and alveolar VD/VT ratio (r = 0.51) at peak exercise (all p <0.01). VE/VCO2 slope was also correlated with arterial pCO2 (r = −0.75, p <0.001). Despite this, arterial pCO2 was not related to peak oxygen uptake (r = 0.2) or to arterial lactate (r = −0.25) and only weakly to New York Heart Association functional class (F = 3.7). First, the increased VE/VCO2 slope was caused by both the high VD/VT ratio and by other mechanisms, as shown by low arterial pCO2 during exercise. Second, this latter component (depression of arterial pCO2) was not related to conventional measures of heart failure severity.