Alveolar-capillary membrane gas conductance:: a novel prognostic indicator in chronic heart failure

Aims. Lung dysfunction occurring in chronic heart failure worsens clinical status and exercise performance. The prognostic value of airway and alveolar function measurements in chronic heart failure has not been explored. We aimed to evaluate the prognostic value of lung function tests in a population of patients with stable chronic heart failure. Methods and Results One hundred and six stable chronic heart failure patients (whose left ventricular ejection fraction averaged 33 +/- 1%) underwent echocardiography, metabolic stress testing, assessment of pulmonary function at rest (by spirometry), of alveolar diffusing capacity (DLeo) (with carbon monoxide technique) and of its membrane (D-M) and capillary blood volume (Vc) components. Prognostic relevance of pulmonary variables was assessed by the Kaplan-Meier approach with log-rank testing and by Cox regression analysis. Cut-off values of lung parameters were based on the 33rd and 66th centiles. Seventeen patients died for cardiac reasons. Non-survivors compared to survivors showed lower forced expiratory volume in 1 s (2(.)1 +/- 0(.)1 vs 2(.)4 +/- 0(.)11; P<0(.)01), forced vital capacity (2(.)6 +/- 0(.)1 vs 2(.)9 +/- 0(.)11; P<0(.)01), maximal voluntary ventilation (80(.)7 +/- 2(.)5 vs 95(.)4 +/- 2(.)71; P<0-01), DLeo (16(.)5 +/- 1(.)1 vs 19(.)3 +/- 0(.)6 ml. min(-1) . mmHg P<0(.)01) and D-M (25(.)1 +/- 1(.)8 vs 31(.)9 +/- 1(.)5 ml . min(-1) mmHg(-1); P<0(.)01). They also exhibited a smaller peak VO2 (14(.)6 +/- 0(.)7 vs 15(.)9 +/- 0(.)6 ml . min(-1) . kg(-1); P<0(.)05) and a steeper VE/ VCO2 slope (45(.)0 +/- 1(.)7 vs 41(.)9 +/- 1(.)5; P<0(.)01). Multivariate analysis revealed that D-M was the only independent predictor of cardiac death, Cases at high risk for adverse outcome were identified by a D-M<24(.)7 ml . min(-1) . mmHg(-1). Patients receiving ACE-inhibitors presented with a higher D-M (32(.)1 +/- 1(.)7 vs 27(.)9 +/- 1(.)7 ml . min(-1) . mmHg(-1) P<0(.)05) as well as a better Cox estimated survival rate. Conclusions. Impaired D-M is a powerful independent predictor of worse prognosis in stable chronic heart failure and may be considered an additional index of disease severity, as well as a specific therapeutic target.