Latent class analysis to identify phenotype-specific treatment effects of catheter ablation vs drug therapy in patients with atrial fibrillation: A secondary analysis of the CABANA trial.

BACKGROUND

The risk profile of patients with atrial fibrillation (AF) is heterogeneous, and treatment responses to catheter ablation vs drug therapy may vary across clinical phenotypes. Latent class analysis (LCA) identifies unobserved subgroups from baseline characteristics.

OBJECTIVE

To apply LCA to CABANA data to define AF phenotypes and assess whether treatment effects differed across latent classes.

METHODS

This secondary analysis of the CABANA trial included 2204 patients randomized to catheter ablation or drug therapy. Twenty baseline variables covering demographics, comorbidities, AF history, symptom burden, and echocardiographic measures were used for LCA. The primary outcome was a composite of all-cause death, disabling stroke, serious bleeding, or cardiac arrest. Treatment effects across latent classes were evaluated under intention-to-treat (ITT) and per-protocol (PP) frameworks using Cox models with a treatment-by-class interaction term.

RESULTS

Three latent classes were identified: class 1 (n = 558), an older multi-morbid symptomatic phenotype; class 2 (n = 739), an older preserved-function lower-comorbidity phenotype; and class 3 (n = 905), a younger male metabolic-risk phenotype. In ITT, treatment-effect estimates for catheter ablation vs drug therapy were most favorable in class 2 (adjusted hazard ratio 0.56, 95% confidence interval 0.34-0.92), whereas estimates in other classes were less distinct; interaction P = .070. PP analysis showed similar patterns, with the most favorable estimates observed in class 2; interaction P = .047.

CONCLUSIONS

LCA identified 3 AF phenotypes with differential responses to catheter ablation vs drug therapy. These findings suggest treatment heterogeneity across AF phenotypes and support further evaluation of phenotype-guided rhythm-control strategies.