CARDIAC SYMPATHETIC DYSINNERVATION IN DIABETES - IMPLICATIONS FOR ENHANCED CARDIOVASCULAR RISK

Background-Regional cardiac sympathetic hyperactivity predisposes to m alignant arrhythmias in nondiabetic cardiac disease. Conversely, howev er, cardiac sympathetic denervation predicts increased morbidity and m ortality in severe diabetic autonomic neuropathy (DAN), To unite these divergent observations, we propose that in diabetes regional cardiac denervation may elsewhere induce regional sympathetic hyperactivity, w hich may in turn act as a focus for chemical and electrical instabilit y. Therefore, the aim of this study was to explore regional changes in sympathetic neuronal density and tone in diabetic patients with and w ithout DAN. Methods and Results-PET using the sympathetic neurotransmi tter analogue C-11-labeled hydroxyephedrine ([C-11]-HED) was used to c haracterize left ventricular sympathetic innervation in diabetic patie nts by assessing regional disturbances in myocardial tracer retention and washout. The subject groups comprised 10 diabetic subjects without DAN, 10 diabetic subjects with mild DAN, 9 diabetic subjects with sev ere DAN, and 10 healthy subjects. Abnormalities of cardiac [C-11]-HED retention were detected in 40% of DAN-free diabetic subjects. In subje cts with mild neuropathy, tracer defects were observed only in the dis tal inferior wall of the left ventricle, whereas with more severe neur opathy, defects extended to involve the distal and proximal anterolate ral and inferior walls. Absolute [C-11]-HED retention was found to be increased by 33% (P<0.01) in the proximal segments of the severe DAN s ubjects compared with the same regions in the DAN-free subjects (30%; P<0.01 greater than the proximal segments of the mild DAN subjects). D espite the increased tracer retention, no appreciable washout of trace r was observed in the proximal segments, consistent with normal region al tone but increased sympathetic innervation. Distally, [C-11]-HED re tention was decreased in severe DAN by 33% (P<0.01) compared with the DAN-free diabetic subjects (21%; P<0.05 lower than the distal segments of the mild DAN subjects). Conclusions-Diabetes may result in left ve ntricular sympathetic dysinnervation with proximal hyperinnervation co mplicating distal denervation. This combination could result in potent ially life-threatening myocardial electrical instability and explain t he enhanced cardioprotection from beta-blockade in these subjects.