Impaired Cardiac Sympathetic Innervation and Myocardial Perfusion Are Related to Lethal Arrhythmia: Quantification of Cardiac Tracers in Patients with ICDs

Abstract

Despite widespread prophylactic use of implantable cardioverter defibrillator (ICD) therapy, sudden cardiac death and refractory arrhythmia events are still important clinical issues to be overcome. We examined whether the impairment of cardiac sympathetic innervation and myocardial perfusion is responsible for lethal arrhythmic events and has prognostic value by comparing conventional clinical indices. In consecutive ICDs implanted in 60 patients, cardiac uptake of (123)I-metaiodobenzylguanidine and (99m)Tc-tetrofosmin at rest was quantified, and then patients were prospectively followed with endpoints of appropriate ICD shocks or cardiac death. Cardiac metaiodobenzylguanidine activity was quantified as a heart-to-mediastinum ratio (HMR), and impaired tetrofosmin uptake was graded as a summed score (SS) using a computerized technique with a percentage of tracer uptake. During a mean 29-mo interval, ICD shock was documented in 30 patients (50%); 3 cardiac deaths were also observed in this group of patients. Patients with ICD shocks had a significantly smaller HMR and a greater SS than did those without (1.73 +/- 0.34 vs. 2.06 +/- 0.46, P = 0.003, and 18.0 +/- 16.2 vs. 5.7 +/- 4.4, P = 0.001, respectively). Kaplan-Meier analysis showed that patients who had both an HMR of 1.90 or less and an SS of 12 or greater had a significantly greater ICD discharge rate than did those who had both an HMR greater than 1.90 and an SS less than 12 (94% vs. 18%, P < 0.005) (log rank, 15.14; P < 0.0005). Multivariate analysis with a Cox model identified the greatest Wald chi(2) of 6.454 and a hazard ratio of 3.857 (P = 0.011) when an HMR of 1.9 or less and tetrofosmin SS of 12 or greater were combined. Impairment of cardiac sympathetic innervation and myocardial perfusion is related to lethal arrhythmic events leading to sudden death, and the combined assessment of these can identify patients for whom prophylactic ICD use has the greatest potential.