Editor's Note: Based on Pokushalov E, Romanov A, De Melis M, et al. Progression of Atrial Fibrillation After a Failed Initial Ablation Procedure in Patients With Paroxysmal Atrial Fibrillation: A Randomized Comparison of Drug Therapy Versus Reablation. Circ Arrhythm Electrophysiol 2013;6:754-60..

Introduction

Catheter ablation of atrial fibrillation (AF) via pulmonary vein isolation (PVI) is an effective treatment and is more effective than antiarrhythmic drugs (AAD).^1,2 The single procedure success rate of PVI for paroxysmal AF is ~50-75%.^2,3 The treating physician must then choose how to manage the ongoing arrhythmia in patients who suffer a recurrence of AF. This study assessed control and progression of AF after initial failed PVI by using an ILR to monitor the heart rhythm. The aim of the study was to assess whether early reablation was superior to AAD therapy.

Methods

Patients undergoing PVI for paroxysmal AF had an ILR implanted. Following a three-month blanking period, they were assessed for recurrence. Patients with symptomatic AF were randomized to repeat ablation (PVI with flutter ablation if needed) or AAD (according to the 2006 ACC/AHA/ESC guidelines⁴).

The primary endpoint was progression to persistent AF or increased AF burden. Secondary endpoints were occurrence of atrial arrhythmia, number of additional ablations, predictors of AF progression and complications.

Results

From 742 patients, 23% had recurrent AF. AF burden at randomization was similar in both groups at ~15%. After three months of study therapy AF burden reduced to 3.3% (AAD) and 1.9% (reablation). During follow up there was a significant increase in AF burden in the AAD group compared to reablation (18.8% vs. 5.6% respectively). A marked increase in AF burden was seen around 15 months in the AAD group. Progression to persistent AF was reduced in the reablation group (4% vs. 23% AAD).

Predictors of AF burden progression were reablation strategy, age >60, AF duration >5 years, hypertension, diabetes, HATCH score ≥2. Predictors of progression to persistent AF were reablation and diabetes.

Freedom from any atrial tachycardia was improved with reablation (58% vs 12% AAD group). There were large crossovers; 43 (56%) patients from the AAD group were ablated due to sustained AF. In the reablation group 21 (27%) needed AAD therapy. No significant differences were reported between the groups with respect to left atrial tachycardias, complications or number of ablations.

Conclusion

After a first failed ablation for paroxysmal AF reablation is better than AAD at controlling AF progression and recurrence.

Perspective

It has long been recognized that "atrial fibrillation begets atrial fibrillation." We now understand this phenomenon to be indicative of atrial remodeling. Loss of atrial contractility during AF leads to atrial stretch and myocyte calcium overload, which activates an ill-defined genetic program leading to electrical and structural remodeling of the atria.⁴ The observed remodeling is diverse and includes promotion of AF circuit re-entry and increased triggers via ectopic activity.

Conditions for re-entry are enhanced by conduction slowing (from remodeling of Na⁺ channels and connexins, accumulation of extracellular matrix and fibrosis), shortening of the atrial refractory period (through remodeling of the L-Type Ca²⁺ current and outward K⁺ and currents), and gross anatomical atrial dilatation.⁵ Increased ectopic activity occurs as a result of ion channel remodeling in atrial myocytes; Ca²⁺ overload during AF leads to widespread changes in cellular Ca²⁺ handling and consequent triggered activity via delayed after depolarizations. In addition increased expression of the pacemaker current I_f (the "funny current") is seen, possibly promoting automatic activity.⁵

Rhythm control in AF has been a subject of intense investigation for many years but a reliable solution has been elusive. Awareness of the importance, and rapid onset, of atrial remodeling in the progression of AF has focused efforts on preventive strategies. Many pharmacological 'secondary prevention' strategies have been proposed including ACE-inhibitors, angiotensin receptor blockers, aldosterone blockade, statins and polyunsaturated fatty acids. However, in clinical trials the initial promise from animal data have not been realized.⁶ Therefore in the absence of pharmacological agents that can prevent or retard atrial remodeling in AF we are necessarily left with the requirement to control the arrhythmia to control the long term disease progression. This study by Pokushalov et al.⁷ aids our decision-making process, having demonstrated that, after an initial failed PVI, a strategy of early reablation is superior to AAD in controlling AF. Furthermore, this strategy may prevent progression to persistent AF.

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References

1. Calkins H, Kuck KH, Cappato R, et al. 2012 hrs/ehra/ecas expert consensus statement on catheter and surgical ablation of atrial fibrillation: Recommendations for patient selection, procedural techniques, patient management and follow-up, definitions, endpoints, and research trial design. Heart rhythm 2012;9:632-696 e621.
2. Calkins H, Reynolds MR, Spector P, et al. Treatment of atrial fibrillation with antiarrhythmic drugs or radiofrequency ablation: Two systematic literature reviews and meta-analyses. Circ Arrhythm Electrophysiol. 2009;2:349-361.
3. Cappato R, Calkins H, Chen SA, et al. Updated worldwide survey on the methods, efficacy, and safety of catheter ablation for human atrial fibrillation. Circ Arrhythm Electrophysiol 2010;3:32-38.
4. Fuster V, Rydén LE, Cannom DS, et al. ACC/AHA/ESC 2006 guidelines for the management of patients with atrial fibrillation--executive summary: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines and the European Society of Cardiology Committee for Practice Guidelines (Writing Committee to Revise the 2001 Guidelines for the Management of Patients With Atrial Fibrillation). J Am Coll Cardiol 2006;48:854-906.
5. Nattel S, Burstein B, Dobrev D. Atrial remodeling and atrial fibrillation: Mechanisms and implications. Circ Arrhythm Electrophysiol 2008;1:62-73.
6. Savelieva I, Kakouros N, Kourliouros A, Camm AJ. Upstream therapies for management of atrial fibrillation: Review of clinical evidence and implications for european society of cardiology guidelines. Part ii: Secondary prevention. Europace 2011;13:610-625.
7. Pokushalov E, Romanov A, De Melis M, Artyomenko S, Baranova V, Losik D, Bairamova S, Karaskov A, Mittal S, Steinberg JS. Progression of atrial fibrillation after a failed initial ablation procedure in patients with paroxysmal atrial fibrillation: A randomized comparison of drug therapy versus reablation. Circ Arrhythm Electrophysiol 2013;6:754-760.

Keywords: Aldosterone, Atrial Fibrillation, Calcium, Catheter Ablation, Connexins, Hypertension, Tachycardia

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