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

Abstract

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.