Acute decompensation leading to progressive pump failure is a main cause of death in patients with congestive heart failure. To find possible metabolic defects associated with the onset of this fatal occurrence, we measured myocardial adenine nucleotides, glycogen, and Na,K-ATPase in patients with end-stage idiopathic dilated cardiomyopathy. The biopsy specimens were obtained from the right ventricle of beating hearts during implantation of a biventricular assistance device in 23 patients (group I) suffering from irreversible cardiogenic shock and during heart transplantation in 20 patients (group II) in compensated heart failure. Left ventricular ejection fraction (LVEF) was determined preoperatively by echocardiography. Left ventricular function in group I was more severely impaired than in group II (LVEF 16.8%+/-4.6% vs 22.1%+/-5.1 %; p <0.01). Myocardial adenosine triphosphate (ATP) in group I was significantly reduced in comparison with group II (119.4+/-10.2 vs 27.7+/-7.4 nmol/mg noncollagen protein; p <0.01). There was no difference in glycogen levels. Na,K-ATPase concentration in group I (n = 8) was lower than that of group II (n = 20) (425+/-80 vs 498+/-75 pmol/g wet weight; p <0.05). Linear regression analyses showed a significant correlation between adenosine triphosphate (ATP) and LVEF (r = 0.41, p <0.01) and between Na,K-ATPase and LVEF (r = 0.55, p <0.01). These results indicate that loss of myocardial ATP and Na,K-ATPase could partially contribute to the development of spontaneous deterioration of the chronically overloaded heart.