Global and Regional Myocardial Innervation Before and After Ablation of Drug-Refractory Ventricular Tachycardia Assessed with 123I-MIBG

Cardiac innervation is a critical component of ventricular arrhythmogenesis that can be noninvasively assessed with I-123-MIBG. However, the effect of ventricular tachycardia (VT) ablation on global and regional left ventricular sympathetic innervation and clinical outcomes has not been previously assessed. Methods: In this prospective, single-center feasibility study, 13 patients with cardiomyopathy (n = 9 ischemic, n = 4 nonischemic) who were scheduled to undergo ablation of drug-refractory VT underwent 15-min and 4-h I-123-MIBG scans before and 6 mo after the ablation procedure. Planar and arrhythmia-specific 757-segment analysis of short-axis SPECT images was performed in all datasets. Results: Global innervation assessed with heart-to-mediastinal ratio and washout rates was preserved in all patients at baseline (1.8 [continuous variables are expressed as median and quartile: Q1-Q3, 1.7-2.4] and 54% [Q1-Q3, 47%-67%]) and did not change significantly at the 6-mo follow-up (1.9 [Q1-Q3, 1.6- 2.2], P = 0.9; and 56% [Q1-Q3, 41%-62%], P = 0.6). However, segmental analysis demonstrated that ischemic patients had larger areas of abnormal innervation at baseline (52.1% vs. 19.6%, P = 0.011) and at the 6-mo follow-up (56.7% vs. 27.5%, P = 0.011) than the nonischemic patients. Innervation defects affected 40% of the inferior segments in all ischemic cardiomyopathy patients, whereas they affected only 10% of inferior segments in 75% of nonischemic patients. When segmental data were further analyzed in denervated (DZ), transition (TZ), and normal (NZ) zones, there were changes in these designated innervation categories from baseline to the 6-mo follow-up for ischemic (19% DZ, 59% TZ, 22% NZ) and nonischemic (6% DZ, 45% TZ, 15% NZ) patients. In ischemic patients, relative changes were significantly greater in the TZ segments than in the DZ, which demonstrated the second highest proportional changes (P = 0.028). Receiver operating characteristic curves defined best cutoffs of DZ, TZ, and NZ as less than 30.5%, 30.6%-47.1%, and more than 47.1%, respectively. Conclusion: Patients with ischemic cardiomyopathy have larger areas of abnormal innervation than those with nonischemic cardiomyopathy. Although VT ablation did not change global innervation, a novel arrhythmia-specific segmental analysis demonstrated significant dynamic changes in innervation categories and allowed quantitative definitions of DZ, TZ, and NZ. These findings provide novel insights into the mechanics of sympathetic innervation in patients undergoing VT ablation and may have diagnostic and therapeutic implications.