Catheter ablation for atrial fibrillation may reduce mortality in patients with atrial fibrillation and heart failure

EBM Focus - Volume 13, Issue 7

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Reference: CASTLE-AF trial (N Engl J Med 2018 Feb 1;378(5):417) (level 2 [mid-level] evidence)

  • Limited data is available on the potential benefit of catheter ablation therapy to reduce mortality in patients who have atrial fibrillation as well as heart failure.
  • In the CASTLE-AF trial, 398 patients with heart failure and symptomatic paroxysmal or persistent atrial fibrillation were randomized to catheter ablation vs. guideline-based medical therapy.
  • At a median follow-up of 38 months, catheter ablation therapy was associated with a reduction in mortality (13.4% vs. 25% with medical therapy, p = 0.01, NNT 9). These results are tempered by multiple methodological limitations of the trial.

Catheter ablation therapy may be considered in patients with symptomatic paroxysmal atrial fibrillation who have failed antiarrhythmic drug treatment and have significant left atrial dilatation or left ventricular dysfunction (Circulation 2011) but additional studies on its efficacy are needed in this patient population. In the recent CASTLE-AF trial, 398 patients (median age 64 years, 86% men) with heart failure and symptomatic paroxysmal or persistent atrial fibrillation were randomized to catheter ablation vs. guideline-based medical therapy. All patients had New York Heart Association (NYHA) class II, III, or IV heart failure, left ventricular ejection fraction ≤ 35%, and an implanted defibrillator. Patients were also refractory to or intolerant of antiarrhythmic drugs. After randomization, medications to manage heart failure were adjusted for all patients according to guidelines during a 5-week run-in phase. Analyses excluded 34 patients (9%) who left the trial after the run-in phase, of whom only 9 with were withdrawn in accordance with the protocol.

The trial was terminated early due to lower than expected enrollment with analyses performed after 68% of the expected primary-endpoint events. Almost 16% of patients in the ablation therapy group did not receive ablation and crossed over to the medical therapy group, and 9.8% in the medical therapy group crossed over to the ablation group. Heart failure was due to ischemic causes in 40% of the patients in the ablation therapy group vs. 52% in the medical therapy group (p = 0.022). Comparing catheter ablation vs. guideline-based medical therapy at a median follow-up of 38 months, a composite of all-cause mortality and hospitalization for worsening heart failure was lower with ablation therapy (in 28.5% vs. 44.6% with medical therapy, p = 0.007, NNT 7). Consistent results were reported in an intention-to-treat analysis. In analyses not adjusted for multiple testing, the rates of both components of the primary outcome were lower with ablation therapy (mortality 13.4% vs. 25%, p = 0.01, NNT 9 and hospitalization for worsening heart failure in 20.7% vs. 35.9%, p = 0.004, NNT 7). Finally, the median increase in left ventricular ejection fraction was 8% with ablation therapy vs. 0.2% with medical therapy (p = 0.005).

The CASTLE-AF trial demonstrated a reduction in mortality and a reduction in hospitalization for worsening heart failure at a median of 3 years with ablation therapy compared to medical therapy in patients with symptomatic paroxysmal or persistent atrial fibrillation and a left ventricular ejection fraction ≤ 35%. Confidence in these findings is tempered by the multiple methodological limitations of the trial including early termination due to low enrollment, baseline differences, crossover to the other intervention, and lack of blinding of patients and physicians. Consistent results for mortality were reported in the AATAC trial which compared ablation therapy vs. amiodarone in patients with persistent atrial fibrillation and heart failure (Circulation 2016). At 5 year follow-up, the time in atrial fibrillation was 27% in the ablation group and 64% in the medical-therapy group suggesting that complete elimination of atrial fibrillation is not necessary to achieve clinical benefit. The improvement in ejection fraction associated with ablation therapy is consistent with findings from a systematic review of studies in patients with left ventricular systolic dysfunction (Circ Arrhythm Electrophysiol 2014), and may contribute to improvement in clinical outcome. In summary, the CASTLE-AF trial adds to the evidence suggesting that ablation therapy for atrial fibrillation may be more effective than medical therapy to improve survival in patients with heart failure, and also may extend these findings to include patients with paroxysmal atrial fibrillation.

For more information, see the topic Ablation therapy for atrial fibrillation in DynaMed Plus. DynaMed users click here.


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