AIM Chronic heart failure (CHF) is a life-threatening clinical syndrome, partly due to sudden cardiac death (SCD). Implantable cardioverter defibrillators (ICD) for primary prevention of SCD have improved overall survival of CHF patients. However, a high percentage of patients never receives appropriate ICD therapy. This prospective multicentre study evaluated whether cardiac sympathetic activity assessed by 123I-mIBG scintigraphy could be helpful in selecting patients for ICD implantation. MATERIALS AND METHODS 135 stable CHF subjects (age 64.5±9.3years, 79% male, LVEF 25±6%) referred for prophylactic ICD implantation were enrolled in 13 institutions. All subjects underwent planar and SPECT 123I-mIBG scintigraphy. Early and late heart-to-mediastinum (H/M) ratio, 123I-mIBG washout (WO) and late summed scores were calculated. The primary endpoint was appropriate ICD therapy. The secondary endpoint was defined as the combined endpoint of all first cardiac events: appropriate ICD therapy, progression of heart failure (HF) and cardiac death. RESULTS During a median follow-up of 30months (6-68months), 24 subjects (17.8%) experienced a first cardiac event (appropriate ICD therapy , HF progression , cardiac death ). Late H/M ratio and defect size of 123I-mIBG SPECT were not associated with appropriate ICD therapy. However, late H/M ratio was independently associated with the combined endpoint (HR 0.135 [0.035-0.517], p=0.001). Post-hoc analysis showed that the combination of late H/M ratio (HR 0.461 [0.281-0.757]) and LVEF (HR 1.052 [1.021-1.084]) was significantly associated with freedom of appropriate ICD therapy (p<0.001). CONCLUSION 123I-mIBG scintigraphy seems to be helpful in selecting CHF subjects who might not benefit from ICD implantation.