REDUCED ALVEOLAR-CAPILLARY MEMBRANE DIFFUSING-CAPACITY IN CHRONIC HEART-FAILURE - ITS PATHOPHYSIOLOGICAL RELEVANCE AND RELATIONSHIP TO EXERCISE PERFORMANCE

Background The pulmonary diffusing capacity for carbon monoxide (DLCO) is reduced in chronic heart failure (CHF) and is an independent predictor of peak exercise oxygen uptake. The pathophysiological basis for this remains unknown. The aim of this study was to partition DLCO into its membrane conductance (D-M) and capillary blood volume components (Vc) and to assess if alveolar-capillary membrane function correlated with functional status, exercise capacity, and pulmonary vascular resistance. Methods and Results The classic Roughton and Forster method of measuring single-breath DLCO at varying alveolar oxygen concentrations was used to determine D-M and Vc in 15 normal subjects and 50 patients with CHF. All performed symptom-limited maximal bicycle exercise tests with respiratory gas analysis; 15 CHF patients underwent right heart catheterization. DLCO was significantly reduced in CHF patients compared with normal subjects, predominantly because of a reduction in D-M (7.0+/-2.6 versus 12.9+/-3.8 versus 20.0+/-6.1 mmol . min(-1). kPa(-1) in New York Heart Association class III, class II, and normal subjects, respectively, P<.0001), even when the reduction in lung volumes was accounted for by the division of D-M by the effective alveolar volume. The Vc component of DLCO was not impaired. D-M significantly correlated with maximal exercise oxygen uptake (r=.72, P<.0001) and inversely correlated with pulmonary vascular resistance (r=.65, P<.01) in CHF. Conclusions Reduced alveolar-capillary membrane diffusing capacity is the major component of impaired pulmonary gas transfer in CHF, correlating with maximal exercise capacity and functional status. D-M may be a useful marker for the alveolar-capillary barrier damage induced by raised pulmonary capillary pressure.