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Persistent Atrial Fibrillation: Time to Stop Comparing Apples With Oranges: Atrial Fibrillation: Beyond the Pulmonary Veins

We thank Drs. Providencia and Lambiase and Dr. Schricker and colleagues for their important comments on our paper. We agree with them that choosing the optimal ablation strategy based on the currently existing classification of atrial fibrillation (AF) according to the latest European Heart Rhythm Association/European Society of Cardiology definition based on AF “phenotype” only is critical and of limited value. The cutoff value to distinguish between paroxysmal, persistent, long-standing persistent, and permanent AF is arbitrary and does not reflect the pathophysiology of AF, especially not of persistent AF. Selecting patients with persistent AF according to that definition does not result in a homogenous collective of persistent AF patients. Up to a quarter of patients (potentially even more) in a study by Tilz et al. (1) and approximately 60% in the CHASE-AF (CatHeter Ablation of perSistEnt Atrial Fibrillation trial turned out to benefit from pulmonary vein (PV) isolation (PVI) (“PV-dependent persAF”) alone after a follow-up of 12 months and even after a follow-up of up to 5 years. These patients remained in sinus rhythm after direct current cardioversion following PVI. It is even more remarkable — as stated by Dr. Schricker — that AF terminated in 25% of the study patients prior to or at the completion of PVI (which occurred in either case). We agree with Dr. Schricker that these patients are an interesting population and deserve focused further research for improvement of patient selection.

We will obviously not be able to demonstrate a benefit of additional ablation strategies like the stepwise approach or newer techniques in persistent AF as long as a significant amount of our so-called persistent AF patients are suffering from a “PV-dependent form of AF” and as long as we do not completely understand the underlying pathophysiology. This might be a reason why we failed to demonstrate a benefit of the stepwise approach, although we tried to overcome that problem by excluding patients with termination of AF during PVI. Patient selection prior to the procedure based on AF duration, the type of persistent AF (primary persistent AF versus secondary persistent AF [2]), left atrial size, function, and fibrosis, risk factors of AF and potentially electrophysiological criteria will be crucial in the future. International registries—as proposed by Dr. Providencia and Dr. Lambiase—as well as multicenter randomized trials would offer the chance to develop new definitions of AF and better selection criteria for choosing the optimal ablation approach tailored for the individual patient. However, such a registry requires standardization of risk factors and especially of ablation protocols, but it offers the opportunity of a more rapid evaluation of new ablation techniques. Therefore, as of today, it is sometimes challenging to discern apples from oranges in the first place since our understanding of AF pathophysiology remains incomplete.

• American College of Cardiology Foundation