Increased dead space ventilation mediates reduced exercise capacity in systolic heart failure

Rationale: Patients with chronic heart failure have limited exercise capacity, which cannot be completely explained by markers of cardiac dysfunction. Reduced pulmonary diffusing capacity at rest and excessively high ventilation during exercise are common in heart failure. We hypothesized that the reduced pulmonary diffusing capacity in patients with heart failure would predict greater dead space ventilation during exercise and that this would lead to impairment in exercise capacity. Objectives: To determine the relationship between pulmonary diffusing capacity at rest and dead space ventilation during exercise, and to examine the influence of dead space ventilation on exercise in heart failure. Methods: We analyzed detailed cardiac and pulmonary data at rest and during maximal incremental cardiopulmonary exercise testing from 87 consecutive heart transplant assessment patients and 18 healthy control subjects. Dead space ventilation was calculated using the Bohr equation. Measurements and Main Results: Pulmonary diffusing capacity at rest was a significant predictor of dead space ventilation at maximal exercise (r =20.524, P,0.001) in heart failure but not in control subjects. Dead space at maximal exercise also correlated inversely with peak oxygen consumption (r =20.598, P,0.001), peak oxygen consumption per kilogram (r =20.474, P,0.001), and 6-minutewalk distance (r =20.317, P = 0.021) in the heart failure group but not in control subjects. Conclusions: Low resting pulmonary diffusing capacity in heart failure is indicative of high dead space ventilation during exercise, leading to excessive and inefficient ventilation. These findings would support the concept of pulmonary vasculopathy leading to altered ventilation perfusion matching (increased dead space) and resultant dyspnea, independent of markers of cardiac function.