Relationship between altered sympathetic innervation, oxidative metabolism and contractile function in the cardiomyopathic human heart - A non-invasive study using positron emission tomography

Aims To identify functional and metabolic correlates of impaired presynaptic sympathetic innervation in the cardiomyopathic human heart using non-invasive correlative imaging. Methods and Results In 10 patients with idiopathic dilated cardiomyopathy, presynaptic catecholamine uptake sites were quantified by positron emission tomography with C-11 hydroxyephedrine. Oxidative metabolism was measured using C-11 acetate. Global and regional function was assessed by tomographic radionuclide angiography. Left ventricular ejection fraction in patients was 19% +/- 10%. Myocardial hydroxyephedrine retention was abnormally low in 58% +/- 38% of the left ventricles. Globally and regionally, hydroxyephedrine retention was significantly correlated with ventricular function (r = 0.67, P = 0.03 with left ventricular ejection fraction. r = 0.31. P < 0.01 with regional endocardial shortening). Multivariate analysis confirmed hydroxyephedrine retention as the closest independent determinant of left ventricular ejection fraction. Oxidative metabolism was determined by rate pressure product as a measure of workload (r = 0.78, P < 0.01) and peripheral vascular resistance as a measure of afterload (r = - 0.61. P = 0.06), but did not correlate with hydroxyephedrine retention (r = 0.08 for global, r = 0.04 for regional parameters). Conclusion Alterations of presynaptic sympathetic innervation in dilated cardiomyopathy are associated with impaired contractile function. suggesting a common pathogenetic pathway. Overall oxidative metabolism, however, was not directly correlated with these findings. Normal regulatory mechanisms for oxidative metabolism were operational. (Eur Heart J 2001, 22: 1594-1600, doi:10.1053/euhj.2000. 2556) (C) 2001 The European Society of Cardiology.