Comparing Phenotypes for Acute and Long-Term Response to Atrial Fibrillation Ablation Using Machine Learning.

Background: It is difficult to identify patients with atrial fibrillation (AF) most likely to respond to ablation. While any arrhythmia patient may recur after acutely successful ablation, AF is unusual in that patients may have long-term arrhythmia freedom despite a lack of acute success. We hypothesized that acute and chronic AF ablation outcomes may reflect distinct physiology and used machine learning of multimodal data to identify their phenotypes.

Methods: We studied 561 consecutive patients in the Stanford AF ablation registry (66±10 years, 28% women, 67% nonparoxysmal), from whom we extracted 72 data features of electrograms, electrocardiogram, cardiac structure, lifestyle, and clinical variables. We compared 6 machine learning models to predict acute and long-term end points after ablation and used Shapley explainability analysis to contrast phenotypes. We validated our results in an independent external population of n=77 patients with AF.

Results: The 1-year success rate was 69.5%, and the acute termination rate was 49.6%, which correlated poorly on a patient-by-patient basis (φ coefficient=0.08). The best model for acute termination (area under the curve=0.86, Random Forest) was more predictive than for long-term outcomes (area under the curve=0.67, logistic regression; P<0.001). Phenotypes for long-term success reflected clinical and lifestyle features, while phenotypes for AF termination reflected electrical features. The need for AF induction predicted both phenotypes. The external validation cohort showed similar results (area under the curve=0.81 and 0.64, respectively) with similar phenotypes.

Conclusions: Long-term and acute responses to AF ablation reflect distinct clinical and electrical physiology, respectively. This de-linking of phenotypes raises the question of whether long-term success operates through factors such as attenuated AF progression. There remains an urgent need to develop procedural predictors of long-term AF ablation success.