Influence of ejection fraction on the prognostic value of sympathetic innervation imaging with iodine-123 MIBG in heart failure.

OBJECTIVES The aim of this study was to determine whether left ventricular ejection fraction (LVEF) influences the relationship between abnormal myocardial sympathetic innervation imaging by iodine 123 meta-iodobenzylguanidine ((123)I-mIBG) and outcomes in patients with heart failure (HF). BACKGROUND In systolic HF, both abnormal (123)I-mIBG imaging and reduced LVEF are associated with higher risk of cardiovascular events. Whether (123)I-mIBG imaging has the same predictive value across the LVEF spectrum is unclear. METHODS Among 985 patients in the ADMIRE-HF (AdreView Myocardial Imaging for Risk Evaluation in Heart Failure) trial with New York Heart Association functional class II or III HF and site-reported LVEF ≤35%, the core laboratory-determined LVEFs were available for 901 subjects, ranging from 20% to 58% (mean LVEF 34 ± 7%), and was >35% in 386 subjects. RESULTS The mean age of the study population was 62 ± 12 years, 80% were male, and the majority had New York Heart Association functional class II symptoms and HF of nonischemic etiology. At all levels of LVEF, the (123)I-mIBG heart-to-mediastinum ratio of <1.6 was associated with a higher risk of death or potentially lethal arrhythmic event and of the composite of cardiovascular death, arrhythmic event, and HF progression. Comparing subjects with LVEF ≤35% and >35%, there was no evidence of effect modification of LVEF on the risk associated with low heart-to-mediastinum ratio for death or arrhythmic event (adjusted hazard ratio: 2.39 [95% confidence interval (CI): 1.03 to 5.55] vs. 5.28 [95% CI: 1.21 to 23.02]; interaction p = 0.48) and for the composite (adjusted hazard ratio: 1.80 [95% CI: 1.01 to 3.23] vs. 2.41 [95% CI: 1.11 to 5.23]; interaction; p = 0.86). For death or arrhythmic event, the heart-to-mediastinum ratio appeared to improve the risk discrimination beyond clinical and biomarker data among both LVEF groups, with improvement in the model C-statistic (0.67 vs. 0.69, p = 0.03) and integrated discrimination improvement (p = 0.0008). CONCLUSIONS (123)I-mIBG imaging has prognostic value across a spectrum of LVEFs. Further studies may be warranted to prospectively test the prognostic value of (123)I-mIBG imaging in patients with HF and an LVEF >35%.