Generalizability of the CASTLE-AF trial: Catheter ablation for patients with atrial fibrillation and heart failure in routine practice

Peter A. Noseworthy, Holly K. Van Houten, Bernard J. Gersh, Douglas L. Packer, Paul A. Friedman, Nilay D. Shah, Shannon M. Dunlay, Konstantinos C. Siontis, Jonathan P. Piccini, Xiaoxi Yao

Research output: Contribution to journalArticlepeer-review

15 Scopus citations


Background: In the Catheter Ablation for Atrial Fibrillation with Heart Failure (CASTLE-AF) trial, catheter ablation reduced the risk of death and heart failure (HF) hospitalization in patients with atrial fibrillation and HF by 40%. Objectives: The study aimed to assess the generalizability of CASTLE-AF to routine clinical practice. Methods: Using a large US administrative database, we identified 289,831 patients with atrial fibrillation and HF treated with ablation (n = 7465) or medical therapy alone (n = 282,366) from January 1, 2008, through August 31, 2018. Patients were divided into 3 groups on the basis of trial eligibility: (1) eligible for CASTLE-AF, (2) failing to meet the inclusion criteria, and (3) meeting at least 1 of the exclusion criteria. Propensity score overlap weighting was used to balance ablated and drug-treated patients on 90 baseline characteristics. Cox proportional hazards regression was used to compare ablation with medical therapy for the primary outcome of a composite end point of all-cause mortality and HF hospitalization. Results: Only 7.8% of patients would have been eligible for the trial; 91.0% failed to meet the trial inclusion criteria; and 15.5% met the exclusion criteria. Ablation was associated with a lower risk of the primary outcome in the overall cohort (hazard ratio [HR] 0.81; 95% confidence interval [CI] 0.76–0.87; P < .001), in the trial-eligible cohort (HR 0.82; 95% CI 0.70–0.96; P = .01), and in patients who failed to meet inclusion criteria (HR 0.79; 95% CI 0.73–0.86; P < .001) but not in patients who met the exclusion criteria (HR 0.97; 95% CI 0.81–1.17). The relative risk reduction was consistent regardless of whether patients had HF with reduced left ventricular ejection fraction. Conclusion: The benefit associated with ablation appears to be more modest in practice than that reported in the CASTLE-AF trial.

Original languageEnglish (US)
Pages (from-to)1057-1065
Number of pages9
JournalHeart rhythm
Issue number7
StatePublished - Jul 2020


  • Atrial fibrillation
  • Catheter ablation
  • Heart failure
  • Trial generalizability

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)


Dive into the research topics of 'Generalizability of the CASTLE-AF trial: Catheter ablation for patients with atrial fibrillation and heart failure in routine practice'. Together they form a unique fingerprint.

Cite this