Paradoxical Relationship Between N-Terminal Proatrial Natriuretic Peptide and Filling Pressure in Adults With Cyanotic Congenital Heart Disease

Abstract

Background Many adults with cyanotic congenital heart disease are characterized by reduced ventricular filling pressures and decreased systemic oxygen transport. Data from animals suggest that hypoxia can induce synthesis and secretion of atrial natriuretic peptide. Methods and Results We measured plasma N-terminal (1-98) proatrial natriuretic peptide (proANP) in 26 cyanotic adults and 28 noncyanotic control subjects. Resting arterial oxygen saturation was significantly lower and hemoglobin concentration and hematocrit significantly greater in cyanotic patients than in control subjects (82±6 versus 96±3%, 19.7±2.2 versus 14.7±2.1 g/dL, and 59.0±8.5% versus 44.3±5.2%, respectively, P <.0001 in all cases). Four cyanotic patients had evidence of iron deficiency. Plasma proANP levels were elevated in cyanotic patients compared with control subjects (1828±1147 versus 689±343 pmol/L, P <.0001). Comparison of resting arterial oxygen saturation and proANP levels demonstrated an inverse linear relationship between the two measures ( r =−.70, P <.0001). There was a significant linear relationship between both hemoglobin concentration and hematocrit and proANP levels as well ( r =.53, P =.0003 and r =.48, P =.002, respectively). Cyanotic patients had lower mean right atrial pressures than the control subjects (4±3 versus 7±2 mm Hg, P =.005), and there were inverse logarithmic relationships between proANP levels and systemic cardiac index ( r =−.82, P =.0002), systemic oxygen transport ( r =−.68, P =.005), and mixed venous oxygen saturation ( r =−.79, P <.0001). Conclusions Adults with cyanotic congenital heart disease are characterized by increased levels of plasma proANP. The increased atrial natriuretic peptide most likely results in extracellular and plasma volume depletion and reduced systemic oxygen transport. Measures designed to increase ventricular filling may improve quality of life of these patients.