BackgroundEven though implantable cardioverter defibrillator (ICD) implantation for primary prevention has shown to reduce the risk of sudden cardiac death in chronic heart failure patients with reduced left ventricular ejection fraction (LVEF), a significant portion of these patients will never receive appropriate ICD therapy. We aimed to functionally characterize the arrhythmogenic substrate using left ventricular (LV) global longitudinal strain (GLS) and heart-to-mediastinum (H/M) ratio on 123I-meta-iodobenzylguanidine (123I-MIBG) scintigraphy.MethodsWe included patients with heart failure with reduced LVEF who received an ICD for primary prevention. To functionally characterize the arrhythmogenic substrate, we measured the LV GLS with two-dimensional speckle tracking echocardiography and cardiac innervation measured as the H/M ratio on 123I-MIBG scintigraphy. An event was defined as appropriate ICD therapy.ResultsA total of 155 patients were included, 74% were male and the mean age was 72 ± 9 years. During a median follow-up of 10 (6–12) years, 43 patients (28%) experienced appropriate ICD therapy. Patients that experienced an event were more often male, had more often ischaemic cardiomyopathy and were more likely to have worse renal function. There was no difference in the left ventricular ejection fraction (LVEF) between the two groups (25 ± 6.4% vs 26 ± 6.0%, p = 0.276). However, LV GLS was significantly more impaired in the group that experienced an event compared to patients that did not (− 6.7 ± 2.1% vs − 7.6 ± 2.1%; p = 0.020). The innervation, measured as the H/M ratio on 123I-MIBG scintigraphy was also significantly more impaired in the patients that experienced and event compared to patients that did not (1.34 ± 0.2 vs 1.47 ± 0.2, p ≤ 0.001). Multivariable Cox regression analysis showed LV GLS and H/M ratio independently associated with appropriate ICD therapy with a hazard ratio of 1.24 (95% CI 1.027–1.491, p = 0.025) and 5.71 (95% CI 1.135–28.571, p = 0.034), respectively. LV GLS and H/M ratio were significantly correlated (Pearson correlation coefficient − 0.30, p < 0.001).ConclusionsFunctionally characterizing the arrhythmogenic substrate using different imaging techniques defines the risk for appropriate ICD therapy, whereas LVEF did not.