Mechanistic Insights From Trials of Atrial Fibrillation Ablation: Charting a Course for the Future

Success rates for catheter ablation of atrial fibrillation (AF), particularly persistent AF, remain suboptimal. Pulmonary vein isolation has been the cornerstone for catheter ablation of AF for over a decade. While successful for most patients, pulmonary vein isolation alone is still insufficient for a substantial minority. Frustratingly, multiple clinical trials testing a diverse array of additional ablation approaches have led to mixed results, with no current strategy that improves AF outcomes beyond pulmonary vein isolation in all patients. Nevertheless, this large collection of data could be used to extract important insights regarding AF mechanisms and the diversity of the AF syndrome. Mechanistically, the general model for arrhythmogenesis prompts the need for tools to individually assess triggers, drivers, and substrates in individual patients. A key goal is to identify those who will not respond to pulmonary vein isolation, with novel approaches to phenotyping that may include mapping to identify alternative drivers or critical substrates. This, in turn, can allow for the implementation of phenotype-based, targeted approaches that may categorize patients into groups who would or would not be likely to respond to catheter ablation, pharmacological therapy, and risk factor modification programs. One major goal is to predict individuals in whom additional empirical ablation, while feasible, may be futile or lead to atrial scarring or proarrhythmia. This work attempts to integrate key lessons from successful and failed trials of catheter ablation, as well as models of AF, to suggest future paradigms for AF treatment.