By Cara Pellegrini, MD

Assistant Professor of Medicine, University of California, San Francisco; Cardiology Division, Electrophysiology Section, San Francisco VA Medical Center

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

SYNOPSIS: Addition of left atrial appendage ablation to pulmonary vein isolation, and extensive other ablation, improved freedom from atrial arrhythmias in patients with long-standing persistent atrial fibrillation without increasing complications.

SOURCE: Di Biase L, Burkhardt JD, Mohanty P, et al. Left atrial appendage isolation in patients with longstanding persistent AF undergoing catheter ablation: BELIEF Trial. J Am Coll Cardiol 2016;68:1929-1940.

The most efficacious management of patients presenting with long-standing persistent atrial fibrillation (LSPAF) is unclear. Many patients desire sinus rhythm for symptomatic improvement or other reasons. Unfortunately, pulmonary vein isolation (PVI), the standard of care for paroxysmal atrial fibrillation (AF), is insufficient for the vast majority of LSPAF patients. Yet, results of Substrate and Trigger Ablation for Reduction of Atrial Fibrillation Trial Part II (STAR AF II) suggested that additional ablation lines or focal ablation of areas of complex fractionated atrial electrograms (CFAEs) did not augment the results of simple PVI ablation. What to do?

Experts in the field are of mixed opinion, with advocates for multiple techniques — identification and ablation of rotors, identification and ablation of non-pulmonary vein triggers, ablation of autonomic innervation areas, epicardial surgical ablation, scar homogenization, and others — battling it out. From the fray comes this study by Di Biase et al, with impressive results. Noting that many LSPAF patients demonstrate triggers emanating from the left atrial appendage (LAA), the authors randomized 173 such subjects who had been refractory to a mean of two antiarrhythmic medications to empirical electrical LAA isolation (EEI-LAA) plus standard ablation vs. standard ablation alone. The primary outcome was freedom from atrial arrhythmia recurrence off antiarrhythmic drugs, excluding a 12-week post-procedure blanking period. Incidence of stroke, death, and cardiovascular-related rehospitalization were secondary endpoints.

The study population primarily was comprised of obese men in their 60s; 20% had heart failure, mean CHA2DS2-VASc score was 2.25, and the groups were well-balanced overall. At 12-month follow-up, 56% of those with the addition of EEI-LAA were arrhythmia-free off antiarrhythmics compared to 28% in the standard ablation group. After adjusting for age, sex, and left atrial size, those with the more limited ablation demonstrated more than two-fold rate of recurrence. With repeated procedures, average 1.3/patient, those in the more aggressive group achieved an impressive 76% arrhythmia freedom. There were no deaths in either group, no strokes in the EEI-LAA group and four in the standard group, and hospitalization rates were similar between groups. Although the majority of patients who underwent ablation of the LAA demonstrated impaired LAA mechanical function at transesophageal follow-up, there only was one patient with a LAA thrombus and one with spontaneous echocardiographic contrast. The authors concluded that EEI-LAA improved long-term freedom from atrial arrhythmias without increasing complications.

COMMENTARY

These results are remarkable for several reasons. The incremental benefit of ablation of the LAA appears large, despite an already extensive ablation in the control group. Notably, standard ablation in this study involved isolation of the posterior wall of the left atrium (LA), ablation of the anterior LA septum, ablation of the LA roof, isolation of the superior vena cava (in vast majority), and ablation of any other sites that appeared to be arrhythmia triggers. In fact, eight patients in the control arm underwent LAA ablation due to the ability to elicit sustained arrhythmia with isoproterenol that mapped to this area; conversely, isolation of the LAA was unsuccessful in 11 patients in the EEI-LAA group. Whether ablation of the LAA would be more or less beneficial on the background of a more typical, less extensive AF ablation is unclear, as is the generalizability of this technically challenging technique to the larger community.

Yet, an ultimate success rate of 76% with patients off antiarrhythmic medications rivals that which is achievable for those with paroxysmal AF and begs attention. There is biologic plausibility that ablation of the LAA could be important. With its complex architecture and highly heterogeneous fiber orientation, the LAA may promote slow conduction and block, factors that make induction and maintenance of AF more likely. Despite the high impact of the addition of LAA ablation on ultimate procedural success, isoproterenol challenge during the procedure did not identify the LAA as a significant source of non-PV arrhythmia triggers in this study, nor most others. While this is puzzling, the authors noted that it is standard practice to isolate all PVs, even those which do not appear to exhibit a high degree of electrical firing, thus the importance of isolation of the LAA should not be underestimated for this reason alone. This may be true, but it isn’t a completely satisfying explanation.

Of concern is the somewhat unknown implications of the loss of normal mechanical appendage activity. Many of these patients would be advised to remain on anticoagulation long-term, given their CHA2DS2-VASc scores, the majority are gaining sinus rhythm in the process, and for those who cannot or do not wish to tolerate long-term anticoagulation to prevent stroke given this finding, there is the option of LAA ligation or exclusion. Notably, comparison of endocardial ablation of the LAA with LAA ligation with the Lariat or exclusion with the Watchman or other devices was beyond the scope of this study and remains an open question. How any of these procedures affect overall atrial function long term also is unanswered. Given past experiences of new techniques appearing to be paradigm shifting, only to falter with attempted adoption, it is too soon to try to apply this technique broadly. Nonetheless, it brings welcome hope to many with LSPAF and those who care for them.