Background: Patients with heart failure (HF) are at increased risk for left ventricular (LV) dyssynchrony which is associated with sudden cardiac death (SCD). This study examined the association of LV mechanical dyssynchrony and cardiac sympathetic denervation with potential SCD events in symptomatic patients with HF and reduced ejection fraction (HFrEF). Methods: Of the 917 HFrEF patients in ADMIRE-HF, 92 experienced adjudicated potential SCD events during a 17 months median follow-up. Propensity scores were used to assemble a matched cohort of 85 pairs of patients with and without potential SCD events. ADMIRE-HF subjects had rest gated SPECT Tc-99m and I-123 MIBG imaging. Perfusion images were processed using phase analysis software to derive phase standard deviation (SD), an index of mechanical dyssynchrony. Results: Of the 92 patients who experienced adjudicated potential SCD events 23 had SCD, 5 fatal myocardial infarction, 7 resuscitated cardiac arrest, 46 had appropriate ICD therapy, and 11 had sustained ventricular tachycardia. Patients who experienced potential SCD events had significantly wider phase SD than matched control patients (62.3 ± 2.4° vs 55.5 ± 2.3°, P =.03) and were more likely to have a phase SD ≥ 60°(53 % vs 35 %, P =.03). Fewer patients with potential SCD events (6 % vs 15 % of the controls, P =.08) had an MIBG heart/mediastinum uptake-ratio ≥1.6. Conclusions: Among symptomatic HFrEF patients, LV mechanical dyssynchrony is independently associated with potential SCD events. Phase analysis may provide incremental prognostic information on top of current indicators of SCD risk in HFrEF. © 2013 American Society of Nuclear Cardiology.