CLINICAL INVESTIGATIONS Cardiac Adrenergic Innervation Is Affected in Asymptomatic Subjects with Very Early Stage of Coronary Artery Disease

The aim of this study was to investigate whether, in subjects with a very early stage of coronary artery disease without hemodynamically significant coronary artery stenoses, cardiac adrenergic innervation is already affected. Methods: Quantitative coronary angiography and dual-isotope SPECT with 123I-metaiodobenzylguanidine (MIBG) and 99mTc-sestamibi (MIBI) were conducted to assess the function of cardiac adrenergic innervation and myocardial perfusion, respectively, in 30 asymptomatic volunteers with a high familial risk for coronary artery disease. Regional quantitative analysis of MIBG uptake and washout rates was performed using the SPECT data from the anteroseptal, lateral, and inferior myocardial regions, which represented vascular supply by the left anterior descending coronary artery (LAD), left circumflex coronary artery (LCX), and right coronary artery (RCA), respectively. Results: The average severity of stenoses was 33% 11% in the LAD, 29% 14% in the LCX, and 26% 19% in the RCA. The severity of stenosis was not related to MIBI uptake in any corresponding myocardial region at rest or during exercise. However, the degree of LAD stenosis correlated directly with delayed MIBG uptake (r 0.43; P 0.05) and inversely with MIBG washout (r 0.34; P 0.06) of the anteroseptal myocardium. When subjects were divided into tertiles according to the separate severity of stenosis for each coronary artery, delayed MIBG uptake in the anteroseptal region was significantly lower in the lowest LAD tertile (0.34 0.05) than in the middle (0.41 0.06; P 0.01) or highest (0.43 0.05; P 0.001) LAD tertile. Correspondingly, delayed MIBG uptake in the lateral region was also lower in the lowest LCX tertile than in the middle tertile (0.34 0.04 vs. 0.41 0.06, respectively; P 0.01). Washout rate was also higher in the lowest LAD tertile (44% 7%) than in the middle (36% 10%; P 0.05) or highest LAD tertile (34% 8%; P 0.01). Conclusion: The degree of coronary artery stenosis was associated directly with MIBG uptake and inversely with MIBG washout. This finding suggests that the function of cardiac adrenergic nerve endings is modified even in mild coronary artery disease before denervation occurs.