Sudden cardiac death from ventricular fibrillation (VF) remains a major health problem worldwide. Currently, there are limited treatment options available to patients who suffer from episodes of VF. Because Purkinje fibers have been implicated as a source of initiation of VF, we are presenting the first paper of a series highlighting the promising results of substrate modulation through "De-Networking" of the Purkinje system preventing VF in patients without an alternative ablation strategy.We studied 10 consecutive patients (two female) all but one implanted with an ICD with documented VF or fast polymorphic Ventricular tachycardia (VT) (five patients without history of structural heart disease, two with ischemic cardiomyopathy, one with hypertrophic obstructive cardiomyopathy, one with dilated cardiomyopathy, and one with aortic valve disease). After 3D electroanatomical mapping, the left bundle branch (LBB) and left ventricular Purkinje potentials were annotated creating a virtual triangle with the apex formed by the distal LBB and the base by the most distal Purkinje potentials. Linear radiofrequency catheter ablation at the base of the triangle was performed, followed by ablation within the virtual triangle sparing the LBB and both fascicles ("de-networking"). All patients were treated without complications. During 1-year follow-up, only 2/10(20%) patients experienced recurrence in form of a single episode of polymorphic VT/VF.Catheter ablation of VF through "de-networking" of the Purkinje system in patients without overt arrhythmia substrate or trigger appears safe and effective and will require further study in a larger patient cohort.