Different Strokes

DOI: 10.19102/icrm.2014.050903

^1,2TOMAS KONECNY, MD, PhD, ¹CHRISTOPHER V. DESIMONE, MD, PhD, ³NANDINI SEHAR, MD and ^1,4SAMUEL J. ASIRVATHAM, MD

¹Division of Cardiovascular Diseases and Internal Medicine, Mayo Clinic, Rochester, Minnesota

²International Clinical Research Center (ICRC) of St. Anne's University Hospital, Brno, Czech Republic
³ Cardiovascular Research Institute, University of Kansas
⁴ Department of Pediatrics and Adolescent Medicine, Mayo Clinic, Rochester, Minnesota

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Perhaps one of the most significant advances of electrophysiology was the appreciation that understanding the initiation of triggers for atrial fibrillation yields a new effective therapeutic strategy – pulmonary vein isolation.¹ Why (atrial fibrillation) AF terminates is less well-studied despite the intuitive notion that understanding the reason for AF cessation should most closely mimic effective invasive treatment strategies. Further, in the EP laboratory, significant controversy exists as to whether AF termination or non-inducibility of sustained AF represents desirable endpoints for existing ablation strategies. Termination of AF during ablation could potentially result from eliminating a trigger that served to maintain AF, ablation-based modification of the pericardiac autonomic nervous system,¹ or disruption of a relevant functional circuit – an ongoing rotor.

Drug-induced cardioversion of AF to sinus rhythm is equally less well-defined. Clearly, there may be drug-specific mechanisms as well as preferential effects on triggers, sustaining flutter circuits, autonomic modulation, or changes in tissue refractoriness.²

In this issue of Innovations, Gorev and colleagues present a retrospective analysis of 77 consecutive patients who underwent 92 AF ablation procedures between 2007 and 2012. The authors divided the study cohort into 3 groups: those who converted to sinus rhythm “spontaneously” during the ablation procedure (i.e. without ibutilide or cardioversion), those who could be chemically cardioverted during the ablation procedure with ibutilide, and those who required electrical cardioversion despite the use of ibutilide. Of note, the groups were classified according to each procedure performed rather than according to each unique patient – in other words one patient could be included in more than one sub-cohort. The authors appropriately highlighted in the table of baseline characteristics several intergroup differences which were clinically relevant despite their statistical nonsignificance, particularly that the groups differed in terms of AF type (paroxysmal vs persistent), the frequency of amiodarone use, average body mass indices, and scores on CHADS2 risk assessments.

The key comparison in this study took place between the ablation procedures in which ibutilide administration led to the resumption of sinus rhythm versus the procedures in which AF continued despite ibutilide administration, hence necessitating electrical cardioversion to achieve sinus rhythm. The patients in these two groups carried similar baseline characteristics, and despite being relatively modestly powered, the followup data displayed similar times to the first AF recurrence between these two groups and delivered a convincing message: stratification by the response to the intraprocedural ibutilide administration during AF ablation was not associated with increased freedom from AF.

What do we expect with administration of Ibutilide?

Perhaps these findings merit the proper context of what we think we would see with ibutilide administration. We should ask: on what basis would we expect ibutilide to help stratify the prognosis of AF patients after ablation? Ibutilide is a methanesulfonamide derivative with structural similarities to sotalol and is widely recognized for its ability to block the rapid component of the cardiac delayed rectifier potassium current (IKr), as well as increase the slow inward current carried by sodium ions.^3,4 In patients with paroxysmal AF, ibutilide more effectively converts those who have a shorter preconversion duration of arrhythmia and those with smaller atrial size.⁴ Therefore, the expectation that ibutilide during AF ablation would more readily cardiovert patients with a shorter AF duration and those with smaller left atrial size seems plausible, and this in turn would stipulate that such patients would theoretically carry a lower risk of AF recurrence. However, the study by Gorev and colleagues did not show such a finding.

Inspection of type of AF patients in the study and response to Ibutilide

Only a small minority of patients with paroxysmal AF was administered ibutilide, and even though ibutilide can help in cardioverting persistently atrially fibrillating patients,⁵ it remains unknown whether in such populations it retains the ability to identify this “lower risk” subgroup.^6,7 It has been previously suggested that ibutilide in the setting of persistent AF could be effectively incorporated into the ablation protocol, but rather as an agent to facilitate intra-procedural slowing and organization of atrial activity, thereby allowing for increased specificity of complex fractionated atrial electrograms ablations.⁸ It would, therefore, be enticing to know what the Kaplan-Meier plot would look like if the ibutilide had been used to prognostically stratify more patients with paroxysmal AF. In addition, it would also be interesting to determine which patients' ablations were guided towards further ablative lesions if chemical cardioversion was not achieved. Future protocols aiming to prospectively incorporate ibutilide into AF ablations should pay a consideration to how its relatively large volume of distribution and long elimination half-life (2 to 12 hours)⁴ could influence adenosine testing for pulmonary vein block, and its interference with the search for early returns of AF from sites such as the superior vena cava or coronary sinus.

In summary, we thank Gorev and colleagues for a well-communicated finding that importantly teaches us that intraprocedural ibutilide response does not uncover a favorable subset of patients in terms of postablation recurrence of arrhythmia. Although we begin to learn from studies such as these that pharmacological termination of AF may have little bearing to what we achieve with ablation, perhaps more importantly, what we are learning is that termination of AF, or for that matter lack of inducibility of persistent AF postablation, may not be the endpoints that best reflect what can possibly be achieved with existing AF ablation strategies.

References

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