Regional patterns of myocardial sympathetic denervation in dilated cardiomyopathy: an analysis using carbon-11 hydroxyephedrine and positron emissiontomography

Objective-To assess presynaptic function of cardiac autonomic innervation i n patients with advanced congestive heart failure using positron emission t omography (PET) and the recently developed radiolabelled catecholamine anal ogue carbon-ii hydroxyephedrine (HED) as a marker for neuronal catecholamin e uptake function. Design and patients-29 patients suffering from dilated cardiomyopathy with moderate to severe heart failure were compared with eight healthy controls. Perfusion scan was followed by HED dynamic PET imaging of cardiac sympathe tic innervation. The scintigraphic results were compared with markers of di sease severity and the degree of sympathetic dysfunction assessed by means of heart rate variability. Results-In contrast to nearly normal perfusions, mean (SD) HED retention in dilated cardiomyopathy patients was abnormal in 64 (32)% of the left ventr icle. Absolute myocardial HED retention was 10.7 (1.0)%/min in controls v 6 .2 (1.6)%/min in dilated cardiomyopathy patients (p < 0.001). Moreover, sig nificant regional reduction of HED retention was demonstrated in apical and inferoapical segments. HED retention was significantly correlated with New York Heart Association functional class (r = -0.55, p = 0.002) and ejectio n fraction (r = 0.63, p < 0.001), but not, however, with plasma noradrenali ne concentrations as well as parameters of heart rate variability. Conclusions-In this study, using PET in combination with HED in patients wi th dilated cardiomyopathy, not only global reduction but also regional abno rmalities of cardiac sympathetic tracer uptake were demonstrated. The degre e of abnormality was positively correlated to markers of severity of heart failure. The pathogenetic mechanisms leading to the regional differences of neuronal damage as well as the prognostic significance of these findings r emain to be defined.