Prognostic implications of an initial loss of cardiac metaiodobenzylguanidine uptake and diabetes mellitus in patients with left ventricular dysfunction

Background: Although altered cardiac sympathetic innervation is related to fatal outcome, the mechanisms and prognostic value of an initial cardiac metaiodobenzylguanidine (MIBG) defect are not known. Methods and Results: After quantitative cardiac MIBG imaging, 205 patients with left ventricular ejection fraction <50% were prospectively followed up with a primary end-point of cardiac death for 35 months. In regard to 38 cardiac deaths, consisting of 25 pump failure deaths, 11 sudden deaths, and 2 fatal acute myocardial infarctions, multivariate analysis identified diabetes mellitus as a significant independent predictor as well as reduced cardiac MIBG activity, use of nitrate, and New York Heart Association functional status. Independent of washout kinetics and cardiac function, patients with profound loss of initial MIBG uptake and those with late-phase MIBG activity of 1.74 or less had significantly greater mortality rates than did their counterparts. Initial cardiac MIBG activity closely correlated inversely with annual cardiac death rate. Conclusions: An initial cardiac MIBG defect and presence of diabetes mellitus indicate a low probability of long-term survival. The profound loss of initial MIBG activity is likely to be due to structural deficit of sympathetic neurons themselves, rather than accelerated sympathetic function, suggesting that denervation is one of mechanisms of cardiac sympathetic dysfunction leading to lethal clinical outcomes.