By Joshua Moss, MD

Associate Professor of Clinical Medicine, Cardiac Electrophysiology, Division of Cardiology, University of California, San Francisco

SYNOPSIS: In patients with atrial fibrillation and heart failure, definitive rate control via atrioventricular junction ablation and biventricular pacing resulted in a significant reduction in all-cause mortality vs. pharmacologic rate control.

SOURCE: Brignole M, Pentimalli F, Palmisano P, et al. AV junction ablation and cardiac resynchronization for patients with permanent atrial fibrillation and narrow QRS: The APAF-CRT mortality trial. Eur Heart J 2021;Aug 28:ehab569. doi: 10.1093/eurheartj/ehab569. [Online ahead of print].

Ideal management of atrial fibrillation (AF) in patients with heart failure remains a challenge. Rhythm control via left atrial catheter ablation in this population has been associated with a lower mortality rate compared with medical therapy. However, restoration and maintenance of sinus rhythm in patients with longstanding persistent AF can be much more difficult.

Brignole et al studied the effect of atrioventricular (AV) junction ablation plus biventricular pacing (cardiac resynchronization therapy [+CRT]) for rate control of “permanent AF” compared with pharmacologic rate control.

After exclusions, 133 heart failure patients (mean age, 73 years; 53% male) from 11 European centers were randomized 1:1 to AV junction ablation +CRT or drug therapy. Patients had to have experienced symptomatic AF for more than six months that was considered unsuitable for AF ablation or for which AF ablation had failed and QRS duration ≤ 110 msec. Randomization was stratified by ejection fraction (EF; ≤ 35% and > 35%). The mean EF was 41%. An implantable cardioverter-defibrillator (ICD) was implanted in both groups if clinically indicated.

In the ablation +CRT arm, the procedures were performed within 30 days of randomization. In the drug therapy arm, significantly more patients were on digoxin after a planned 30-day optimization period (60% vs. 32%), with therapy optimized to achieve a resting heart rate < 110 bpm. More than 80% of patients in both arms remained on beta-blocker therapy. Six patients in the ablation +CRT arm either did not undergo ablation or failed cardiac resynchronization therapy implant, and 18 patients in the drug arm crossed over to ablation +CRT. Investigators ended the trial prematurely after interim analysis met prespecified criteria for stopping. The primary outcome measured was all-cause mortality, which occurred in 11% of patients in the ablation +CRT arm and 29% of patients in the drug arm (HR, 0.26; 95% CI, 0.10-0.65; P = 0.004) using an intention-to-treat analysis.

In a prespecified subgroup analysis, the overall mortality benefit was similar in patients with EF > 35% (HR, 0.27; 95% CI, 0.08-0.84; P = 0.024) and EF ≤ 35% (HR, 0.34; 95% CI, 0.06-1.92; P = 0.22). Appropriate ICD shocks for ventricular tachyarrhythmias occurred in four patients in the ablation +CRT arm and one patient in the drug arm. Five patients experienced inappropriate ICD shocks for AF with rapid ventricular rates, all in the drug arm. Three patients required lead repositioning, and one patient required repeat AV junction ablation. A sensitivity analysis to assess the potential interaction of differential digoxin usage was consistent with the primary analysis. The authors concluded AV junction ablation +CRT was superior to pharmacologic therapy alone for preventing mortality in patients with heart failure and AF.


Several trials have demonstrated improved outcomes with catheter ablation of AF via pulmonary vein isolation (PVI) in patients with heart failure, generally attributed to superior rhythm control and less exposure to potentially toxic antiarrhythmic drugs. For example, the AATAC trial showed a 56% reduction in all-cause mortality with ablation vs. amiodarone.1 The CASTLE-AF trial showed a 47% reduction in all-cause mortality with catheter ablation vs. any medical therapy (whether rate or rhythm control).2 However, duration of AF before enrollment in those trials was relatively short overall (mean duration = 8.5 months in AATAC; 71% less than one year in CASTLE-AF).

By contrast, the APAF-CRT trial authors studied patients with “permanent” AF, with a median arrhythmia duration of 19 months in the CRT group and 18 months in the drug group. Patients were, on average, nine years older than CASTLE-AF participants and 12 years older than AATAC participants. They also likely were more ill, with 68% presenting with New York Heart Association class III or worse heart failure symptoms (vs. 29% in CASTLE-AF). In fact, mortality in the drug therapy arm of APAF-CRT was 29% through a median follow-up of 29 months vs. 25% in the medical therapy arm of CASTLE-AF through a median follow-up of 38 months. Thus, the previously demonstrated benefits of more extensive left atrial catheter ablation likely would not have been expected in the APAF-CRT population.

Long-term rhythm control via PVI generally is poor in permanent AF (particularly with only one procedure), and procedural complications likely are more frequent in older patients with less clinically stable heart failure. Ablation of the AV junction plus pacemaker implant typically is simpler and safer, with far less need for repeat procedures. Using a CRT device, even in patients with EF > 35%, alleviates the long-term risks associated with RV-only pacing. Hypothetically, conduction system pacing would produce similar or better results, but longer-term risks and benefits require further study in this population.

The APAF-CRT population was small, and medical rate control was not achieved or assessed in a standardized way. However, median resting heart rate in the drug therapy arm was 82 bpm after only 30 days of optimization, suggesting a reasonable degree of control was achieved (with digoxin in many, and amiodarone or sotalol in about 10%). The difference in outcomes was profound despite a relatively high percentage of crossovers.

Overall, the APAF-CRT trial confirms an additional tool for lowering the mortality rate in certain patients with heart failure and AF, and a powerful tool at that. For patients without longstanding arrhythmia who are reasonable candidates for PVI, catheter ablation of AF should be strongly considered based on multiple prior studies. For patients with EF ≤ 35% and left bundle branch block, CRT likely is indicated anyway, and AV node ablation clearly can improve biventricular pacing burden. However, for symptomatic heart failure patients in whom the AF is deemed more permanent, even with narrow QRS or EF > 35%, AV junction ablation and CRT implantation may win the race.


  1. Di Biase L, Mohanty P, Mohanty S, et al. Ablation versus amiodarone for treatment of persistent atrial fibrillation in patients with congestive heart failure and an implanted device: Results from the AATAC multicenter randomized trial. Circulation 2016;133:1637-1644.
  2. Marrouche NF, Brachmann J, Andresen D, et al. Catheter ablation for atrial fibrillation with heart failure. N Engl J Med 2018;378:417-427.