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. Methods: In consecutive ICDs implanted in 60 patients, cardiac uptake of 123 Imetaiodobenzylguanidine 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-tomediastinum ratio (HMR), and impaired tetrofosmin uptake was graded as a summed score (SS) using a computerized technique with a percentage of tracer uptake. Results: 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 6 0.34 vs. 2.06 6 0.46, P 5 0.003, and 18.0 6 16.2 vs. 5.7 6 4.4, P 5 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 x 2 of 6.454 and a hazard ratio of 3.857 (P 5 0.011) when an HMR of 1.9 or less and tetrofosmin SS of 12 or greater were combined. Conclusion: 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.

Cardiac 123I-MIBG Imaging for Clinical Decision Making: 22-Year Experience in Japan

“…Thereafter, several small but important studies (22,(52)(53)(54)(55)(56)(57)(58) showed that excess activation of cardiac sympathetic nerve function and impaired cardiac sympathetic innervation, as assessed with cardiac 123 I-MIBG imaging, are associated with arrhythmogenicity-leading to lethal ventricular arrhythmias, ICD shock against lethal arrhythmia events, and SCD independent of clinical, electrophysiologic, and LVEF symptoms (59). In addition to the assessment of BNP, LVEF, and myocardial viability, cardiac 123 I-MIBG activity is used for the assessment of prognosis and the selection of therapeutic strategy at our institutes (56,57). The incremental prognostic value of this imaging technique is also supported by larger studies (60,61) and by a PET study with 11 Cmetahydroxyephedrine (62).…”

Cardiac Mortality Assessment Improved by Evaluation of Cardiac Sympathetic Nerve Activity in Combination with Hemoglobin and Kidney Function in Chronic Heart Failure Patients

“…Increased norepinephrine spillover, decreased norepinephrine content at nerve endings, and sympathetic denervation in failing hearts can be revealed as an increase in 123 I-MIBG washout rate from the heart or a decrease in 123 I-MIBG activity. Several studies have demonstrated that abnormal 123 I-MIBG kinetics are associated with lethal cardiac events in patients with moderate to severe heart failure (6)(7)(8)(9)(10)(11).…”

Cardiac autonomic imaging with SPECT tracers

“…Nishisato et al reported that a combination of H/M and the summed perfusion defect score on 99m Tc-tetrosfomin images separated patients with ICD shocks from those without, with image variables independent and superior to age, sex, SAECG, BNP, medications, inducible arrhythmias, and LVEF in predicting shocks or cardiac death. 122 Kasama et al 123 showed a correlation of abnormally high 123 I-mIBG washout with increased SCD. Tamaki et al compared ECG parameters-HRV, QT dispersion, and SAECGwith 123 I-mIBG findings in 106 patients with LVEF \ 40%, and those with SCD had a lower H/M and higher WR, with ECG variables showing no independent relationship to outcome.…”