Background: The mechanisms of ventricular fibrillation (VF) are classically distinguished in triggers versus substrate. However, their respective location in patients with structural heart disease (SHD) has not been investigated.Objective: To precisely locate trigger and substrate in patients presenting spontaneous VFMethods: Within a 5 year inclusion period, we investigated 14 patients (57±10 years) presenting a documented spontaneous episode of VF (lasting 16± 8s before cardioversion) associated with ischemic heart disease in 8, cardiomyopathy in 4 , and Brugada syndrome in 2. VF mapping was performed using multielectrode intracardiac and body-surface recordings. The VF trigger was located at the site of earliest ventricular activation. Reentrant drivers were identified during VF using phase mapping and confirmed by the demonstration of sequential circular activation of local electrograms. We performed endocardial and epicardial mapping during sinus rhythm. The abnormal substrate was identified as areas of low voltage (≤1mV) and fragmented electrograms (≥70ms).Results:The first beat of VF originated from Purkinje network in 8 and ventricular myocardium in 6; with the earliest endocardial electrogram preceding the QRS onset by 54 ±12ms . While myocardial triggers showed a single breakthrough on body surface mapping, Purkinje triggers were associated with simultaneous emergence of multiple breakthroughs. The transition from a focal trigger to a reentrant activity occurred at a median of 4 VF cycles [range: 2-7 cycles]. Mapping at the trigger sites showed low voltage fragmented electrograms during sinus rhythm in 12/14 patients.During VF, a driver region was consistently found to colocalize with the site of triggers in 12 patients, accounting for 34±10% of the total driver activities Catheter ablation was performed at these “trigger-driver” regions resulting in abolition of abnormal electrograms and arrhythmia-free outcome in 10 of 12 patients at 18±15 months follow up.Conclusion: Purkinje focal activity may show several ventricular exit sites. In most patients with SHD, the sites of VF triggers are intertwined with the maintaining substrate, providing a dual mechanistic target for interventional treatment.Read less <