By Joshua D. Moss, MD

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

Dr. Moss reports no financial relationships relevant to this field of study.

SYNOPSIS: Late-breaking findings of several important clinical trials in atrial fibrillation management were presented as part of the “Hot Line” sessions at this year’s European Society of Cardiology Congress in Barcelona, Spain. A selection particularly relevant to the general cardiology community is presented here.

SOURCE: European Society of Cardiology Congress 365. Available at: Accessed Oct. 16, 2017.

Catheter Ablation versus Standard conventional Treatment in patients with LEft ventricular dysfunction and Atrial Fibrillation (CASTLE-AF) (Marrouche NF, et al.)

In this prospective, randomized, controlled study at 31 sites in nine countries, 179 patients with left ventricular (LV) dysfunction and heart failure randomly underwent ablation for atrial fibrillation (AF), and 184 patients received conventional therapy. Ablation consisted of pulmonary vein isolation plus additional lesions at the discretion of the operator. After a standing blanking period, an additional ablation procedure also could be performed. Conventional therapy was administered based on the 2006 American College of Cardiology/American Heart Association/European Society of Cardiology guidelines. About two-thirds of patients were treated with a rate-control strategy, targeting goal heart rates of 60-80 beats per minute at rest and 90-115 beats during moderate exercise. Mean age at enrollment was 64 years, and mean ejection fraction (EF) was about 32%, with almost all patients exhibiting New York Heart Association class II or III heart failure symptoms. Arrhythmia burden was assessed via implantable cardioverter-defibrillator remote monitoring.

The burden of AF based on memory from the implanted devices was substantially lower after ablation over a median follow-up of 38 months, comprising about 25% of the time in the ablation group compared with > 50% of the time in the conventional therapy group. At both one year and five years, the mean EF improved significantly more from baseline in the ablation group than in the conventional therapy group. Patients undergoing catheter ablation were 38% less likely to experience the primary composite endpoint (mortality and worsening heart failure admissions), 47% less likely to die, and 44% less likely to require heart failure hospitalization. Reassuringly, serious complication rates were low in the ablation group, including a rate of stroke or transient ischemic attack that was lower than that of the conventional therapy group.


Several smaller trials, non-randomized studies, and anecdotal data have suggested a benefit to rhythm control via catheter ablation of AF in patients with LV dysfunction and heart failure. Improved quality of life and EF have been mostly consistent findings. This relatively large randomized trial makes a strong case for offering heart failure patients with AF an ablation procedure to significantly reduce their risk of mortality and heart failure hospitalization. Patients with paroxysmal, persistent, and long-standing persistent AF were included, and results were largely conserved across pre-specified subgroups. Patients with EF ≥ 25% demonstrated substantially better improvement with ablation, while those with EF < 25% exhibited more equivalent outcomes with ablation or conventional therapy. Ablation also appeared more favorable in younger patients, those with less severe heart failure, and men. However, there was no subgroup in which conventional therapy was significantly superior, and the potential benefits of ablation for AF should be considered early in the management of patients with heart failure.

Catheter Ablation compared with optimized Pharmacological Therapy for Atrial Fibrillation (CAPTAF) (Blomstrom-Lundqvist C, et al.)

In another prospective, multicenter, randomized trial of ablation vs. medical therapy for AF, 155 patients with symptomatic AF first received an implantable cardiac monitor for a two-month run-in period prior to therapy. The implantable monitor was used to rigorously assess arrhythmia burden. The primary endpoint was the change in general health, as measured by the 36-Item Short Form Survey, from baseline to 12 months.

In this trial, the proportion of time in AF was reduced more in the ablation group than in the group treated with antiarrhythmic drugs, but the difference was not statistically significant. Nevertheless, after 12 months of follow-up, the general health score had improved significantly more in the ablation group than in the drug group. The complication rate between treatment groups was similar.


In patients without LV dysfunction, the main indication for AF ablation is to provide symptom relief. However, this is the first trial to use change in quality of life as the primary endpoint while simultaneously monitoring arrhythmia burden with an implantable cardiac monitor. Despite a non-significant reduction in overall AF burden at one year with ablation compared with antiarrhythmic drug therapy, patient quality of life improved significantly. The evidence continues to build that the concept of choosing rate vs. rhythm control for patients with symptomatic AF is overly simplistic, as rhythm control with ablation represents a superior option to rhythm control with drugs.

Apixaban compared with parenteral heparin and/or vitamin K antagonist in patients with nonvalvular atrial fibrillation undergoing cardioversion: Rationale and design of the EMANATE trial (Ezekowitz MD, et al.)

In the large randomized trials of the novel oral anticoagulants dabigatran, rivaroxaban, apixaban, and edoxaban vs. a vitamin K antagonist (VKA), there were low event rates of stroke, systemic embolism, and major bleeding after cardioversion procedures. However, the patients in those trials typically logged longer periods of anticoagulation prior to the cardioversion.

The goal of the EMANATE trial was to compare outcomes in patients who underwent < 48 hours of anticoagulation with either apixaban or heparin/VKA prior to cardioversion. Patients with mitral stenosis or previous valve surgery, as well as those on dual antiplatelet therapy, were excluded. Overall, 753 patients were randomized to apixaban and 747 to heparin/VKA. In the apixaban arm, cardioversion could be performed as little as two hours after initiation of anticoagulation if a loading dose of 10 mg was administered (5 mg if the patient exhibited two of three standard criteria for reduced apixaban dosing). The mean CHA2DS2-VASc score was 2-3, and most patients demonstrated preserved EF.

Over 30 days follow-up after cardioversion, there were six events in the heparin/VKA group (five ischemic strokes and one hemorrhagic stroke) and none in the apixaban group (P = 0.016). There were three major bleeds and 11 clinically relevant non-major bleeds in the apixaban group, and six major bleeds and 13 clinically relevant non-major bleeds in the heparin/VKA group.

In an additional analysis, 61 of 840 patients who underwent TEE imaging prior to cardioversion had thrombus present. All except one patient remained on their assigned anticoagulant regimen. For those who underwent repeat imaging, at a mean of 37 days later, 11 of 23 patients on apixaban still had thrombus. For those on heparin/VKA, eight of 18 still had thrombus, a similar ratio.


The results of EMANATE further support the use of apixaban for thromboembolic prophylaxis prior to cardioversion, even when anticoagulation is started as little as two hours pre-procedure. The convenience of avoiding heparin/VKA is likely to be significant to both caregivers and patients, although actual differences in costs were not reported.