Excess Ventilation in Chronic Obstructive Pulmonary Disease-Heart Failure Overlap Implications for Dyspnea and Exercise Intolerance

Rationale: An increased ventilatory response to exertional metabolic demand (high V-E/V-CO2 relationship) is a common finding in patients with coexistent chronic obstructive pulmonary disease and heart failure. Objectives: We aimed to determine the mechanisms underlying high V-E/V-CO2 and its impact on operating lung volumes, dyspnea, and exercise tolerance in these patients. Methods: Twenty-two ex-smokers with combined chronic obstructive pulmonary disease and heart failure with reduced left ventricular ejection fraction undertook, after careful treatment optimization, a progressive cycle exercise test with capillary (c) blood gas collection. Measurements and Main Results: Regardless of the chosen metric (increased V-E-V-CO2 slope, V-E/V-CO2 nadir, or end-exercise V-E/V-CO2), ventilatory inefficiency was closely related to Pc-CO2 (r values from -0.80 to -0.84; P < 0.001) but not dead space/tidal volume ratio. Ten patients consistently maintained exercise Pc-CO2 less than or equal to 35 mm Hg (hypocapnia). These patients had particularly poor ventilatory efficiency compared with patients without hypocapnia (P < 0.05). Despite the lack of between-group differences in spirometry, lung volumes, and left ventricular ejection fraction, patients with hypocapnia had lower resting Pa-CO2 and lung diffusing capacity (P < 0.01). Excessive ventilatory response in this group was associated with higher exertional Pc-O2. The group with hypocapnia, however, had worse mechanical inspiratory constraints and higher dyspnea scores for a given work rate leading to poorer exercise tolerance compared with their counterparts (P < 0.05). Conclusions: Heightened neural drive promoting a ventilatory response beyond that required to overcome an increased wasted ventilation led to hypocapnia and poor exercise ventilatory efficiency in chronic obstructive pulmonary disease-heart failure overlap. Excessive ventilation led to better arterial oxygenation but at the expense of earlier critical mechanical constraints and intolerable dyspnea.