Purkinje De-Networking for Ventricular Arrhythmias: Mechanisms, Clinical Evidence, and Future Directions

Background The Purkinje system has emerged as a central contributor to malignant ventricular arrhythmias, extending beyond its traditional role as passive conduction tissue. Purkinje fibers can initiate ventricular fibrillation through short-coupled premature ventricular complexes and, in many settings, actively participate in arrhythmia maintenance by forming part of a distributed arrhythmogenic substrate. This is particularly relevant in structural heart disease, where surviving Purkinje fibers colocalize with myocardial scar and support reentrant circuits. These insights challenge conventional trigger-focused ablation strategies and provide a rationale for substrate-based approaches. Objective This State-of-the-Art Review synthesizes current mechanistic understanding, clinical evidence, and ablation strategies for Purkinje-mediated ventricular arrhythmias, highlighting practical decision-making frameworks and future directions for personalized arrhythmia management. Methods Using PRISMA guidelines, four databases were searched from inception, and 35 studies reporting patient-level data were included. Current evidence was critically appraised using OCEBM levels. Results Across predominantly single-center small observational cohorts and case series, Purkinje De-networking achieved 88-100% acute non-inducibility and 75% - 100% arrhythmia free survival in the mid-term, with <25% conduction system injury events depending on ablated lesion site and ablation strategy. However, the evidence is low-certainty and highly vulnerable to selection, referral, and publication bias. Conclusion Purkinje de-networking has emerged as a novel therapeutic concept aimed at disrupting abnormal Purkinje connectivity and decoupling the Purkinje–myocardial interface in patients with refractory ventricular arrhythmias. Given evidence of low certainty and high vulnerability to bias, cautious interpretation of the studies' results is warranted. Standardized procedural definitions, prospective reporting of conduction safety, and randomized comparisons are needed.