New imaging techniques for cardiovascular autonomic neuropathy: a window on the heart

Cardiovascular autonomic neuropathy (CAN) is a common complication of diabetes, which results in disabling clinical manifestations and may predispose to sudden cardiac death. Recently, direct scintigraphic assessment of cardiac sympathetic integrity has become possible with the introduction of radiolabeled analogues of norepinephrine, which are actively taken up by the sympathetic nerve terminals of the heart. This article reviews how these techniques have been utilized to improve understanding of CAN complicating diabetes. Quantitative scintigraphic assessment of cardiac sympathetic innervation heart is possible with either [123I]-metaiodobenzylguanidine (MIBG) and single photon emission computed tomography (SPECT) or [11C]-hydroxyephedrine (HED) and positron emission tomography (PET). Studies in diabetic patients have explored the sensitivity of these techniques to detect CAN, characterize the effects of glycemic control on the progression of CAN and evaluate the effects of CAN on myocardial electrophysiology, blood flow regulation and function. Deficits of left ventricular (LV) [123I]-MIBG and [11C]-HED retention have been identified in diabetic subjects without abnormalities on cardiovascular reflex testing consistent with increased sensitivity to detect CAN. Poor glycemic control results in the progression of LV tracer deficits, which can be prevented or reversed by the institution of near-euglycemia. Deficits begin distally in the LV and may extend proximally. Paradoxically, however, absolute HED retention is increased in the proximal segments of the severe CAN subjects consistent with regional "hyperinnervation." These regions also exhibit abnormal blood flow regulation. Impaired myocardial MIBG uptake correlates with altered LV diastolic filling and myocardial electrophysiological deficits and is predictive of sudden death. Scintigraphic studies have provided unique insights into the effects of diabetes on cardiac sympathetic integrity and the pathophysiological consequences of LV sympathetic dysinnervation. Future studies using complementary neurotransmitter analogues will allow different aspects of regional dysfunction to be characterized with the aim of developing therapeutic strategies to prevent or reverse CAN.