Regression and progression of cardiac sympathetic dysinnervation complicating diabetes: An assessment by C-11 hydroxyephedrine and positron emission tomography

Cardiovascular denervation complicating diabetes has been implicated in sud den cardiac death potentially by altering myocardial electrical stability a nd impairing myocardial blood flow. Scintigraphic evaluation of cardiac sym pathetic integrity has frequently demonstrated deficits in distal left vent ricular (LV) sympathetic innervation in asymptomatic diabetic subjects with out abnormalities on cardiovascular reflex testing. However, the clinical s ignificance and subsequent fate of these small regional defects is unknown. This study reports the results of a prospective observational study in whi ch positron emission tomography (PET) with (-)-[C-11]-meta-hydroxyephedrine ([C-11]-HED) was used to evaluate the effects of glycemic control on the p rogression of small regional LV [C-11]-HED retention deficits in 11 insulin -dependent diabetic subjects over a period of 3 years. The subjects were di vided into two groups based on attained glycemic control during this period : group A contained six subjects with good glycemic control (individual mea n HbA1c < 8%), and group B contained five subjects with poor glycemic contr ol (individual mean HbA1c greater than or equal to 8%). Changes in regional [C-11]-HED retention were compared with reference values obtained from 10 healthy aged-matched nondiabetic subjects. At baseline, abnormalities of [C -11]-HED retention affected 7.3% +/- 1.4% and 9.9% +/- 6.6% of the LV in gr oup A and B subjects, respectively, with maximal deficits of LV [C-11]-HED retention involving the distal myocardial segments. At the final assessment in group A, the extent of the deficits in [11C]-HED retention decreased to involve only 1.7% +/- 0.7% of LV (P <.05 v baseline scan), with significan t increases in [C-11]-HED retention occurring in both the distal and proxim al myocardial segments. In contrast, in group B with poor glycemic control, the extent of [C-11]-HED deficits increased to involve 34% +/- 3.5% of the LV (P <.01 v baseline), with retention of [C-11]-HED significantly decreas ing in the distal segments ([C-11]-HED retention index, 0.066 +/- 0.003 v 0 .057 +/- 0.002, P <.05, at baseline and final assessment, respectively). Po or glycemic control was associated with increased heterogeneity of LV [C-11 ]-HED retention, since three of five group B subjects developed abnormally increased [C-11]-HED retention in the proximal myocardial segments. In conc lusion, defects in LV sympathetic innervation can regress or progress in di abetic subjects achieving good or poor glycemic control, respectively. In d iabetic subjects with early cardiovascular denervation, institution of good glycemic control may prevent the development of myocardial sympathetic dys innervation and enhanced cardiac risk. Copyright (C) 1999 by W.B. Saunders Company.