A fib ablation in HFrEF patients gains momentum



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– Results from two recent trials suggest that cardiologists may have a new way to improve outcomes in patients with heart failure with reduced ejection fraction if they also have atrial fibrillation: Cut the patient’s atrial fibrillation burden with catheter ablation.

This seemingly off-target approach to improving survival, avoiding heart failure hospitalizations, and possibly reducing other adverse events first gained attention with results from the CASTLE-AF (Catheter Ablation vs. Standard Conventional Treatment in Patients With LV Dysfunction and AF) randomized trial, first reported in 2017. The study showed in 363 patients that atrial fibrillation (AF) ablation in patients with heart failure with reduced ejection fraction (HFrEF) led to a statistically significant 38% relative reduction in the primary endpoint of mortality or heart failure hospitalization during a median 38 months of follow-up (N Engl J Med. 2018 Feb 1;378[5]:417-27).

This groundbreaking finding then received some degree of confirmation when Douglas L. Packer, MD, reported primary results from CABANA (Catheter Ablation vs Anti-arrhythmic Drug Therapy for Atrial Fibrillation Trial) at the annual scientific sessions of the Heart Rhythm Society. CABANA compared upfront ablation against first-line medical management of AF in 2,203 patients. While the primary endpoint of the cumulative rate of all-cause death, disabling stroke, serious bleeding, or cardiac arrest over a median follow-up of just over 4 years was neutral, with no statistically significant difference between the two treatment arms, a subgroup analysis showed a tantalizing suggestion of benefit in the 337 enrolled patients with a history of congestive heart failure (15% of the total study group).

In this subgroup, treatment with ablation cut the primary endpoint by 39% relative to those treated upfront with medical management, an effect that came close to statistical significance. In addition, Dr. Packer took special note of the per-protocol analysis, which censored out the crossover patients who constituted roughly a fifth of all enrolled patients. In the subgroup analysis using the per-protocol data, ablation was linked with a statistically significant 49% relative reduction in the primary endpoint among patients with a history of heart failure.

The patients for whom there may be the quickest shift to upfront ablation to treat AF based on the CABANA results will be those with heart failure and others with high underlying risk, Dr. Packer predicted at the meeting.

“The CASTLE-AF results were interesting, but in fewer than 400 patients. Now we’ve basically seen the same thing” in CABANA, said Dr. Packer, professor and a cardiac electrophysiologist at the Mayo Clinic in Rochester, Minn.

Notably however, the results Dr. Packer reported on the heart failure subgroup did not include any information on how many of these were patients who had HFrEF or heart failure with preserved ejection fraction and how the apparent benefit from AF ablation affected each of these two heart failure types. In addition, the reported CABANA results did not have an endpoint result that completely matched the mortality and heart failure hospitalization composite endpoint used in CASTLE-AF. The closest endpoint that Dr. Packer reported from CABANA was a composite of mortality and cardiovascular hospitalization that showed, for the entire CABANA cohort, a statistically significant 17% relative reduction with ablation in the intention-to-treat analysis. Dr. Packer gave no data on how this outcome shook out in the subgroup of heart failure patients.


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