The Full Circle: Back into the Pulmonary Veins: A New Possibility in AF Ablation? JUSTIN M. GHOSH, M.B.B.S.∗ and MARK A. MCGUIRE, M.B.B.S.† From the ∗ Hull York Medical School, Scarborough, United Kingdom; and †The Royal Prince Alfred Hospital, Sydney, Australia
clinical: catheter ablation, atrial fibrillation Editorial Comment Ablation of atrial fibrillation (AF) is one of the most frequently performed electrophysiological procedures, and a number of techniques have been developed. These include: point by point radio frequency (RF) ablation,1 duty cycled RF ablation,2 cryoballoon ablation,3 open irrigated multipolar ablation,4 and laser balloon ablation.5 Even within the point by point method, multiple approaches exist, including ostial segmental ablation,6 wide area circumferential ablation,7 ablation of complex fractionated electrograms,8 Focal Impulse and Rotor Modulation (FIRM) ablation9 and a stepwise ablation strategy,10 with each technique having data to support its use. The fact that so many techniques exist highlights our incomplete understanding of AF. In 1998, Haissaguerre demonstrated that paroxysmal AF is frequently triggered by impulses arising in the pulmonary veins and that ablation of these sources within the pulmonary veins resulted in a reduction of AF.11 The next iteration of the ablation techniques gave us segmental ostial ablation to electrically disconnect the veins from the atrium,6 and a purely anatomical circumferential ostial strategy.12 Both of these techniques were associated with some risk of pulmonary vein stenosis, and antral ablation with a wide area encirclement was developed to decrease the risk of this complication.7,13 Pulmonary vein stenosis is the result of neo-intimal proliferation of the pulmonary vein. Many cases result in little or no symptoms, but some can be highly symptomatic or even fatal. To make the situation worse, the condition is irreversible, and treatment strategies are often ineffective. Venous narrowing results in obstruction to flow from the lobe involved and pulmonary hypertension. Exertional dyspnea is the most common manifestation. Treatment with balloon dilation and stenting is often only temporarily successful.14 In this issue of the Journal, Di Simione et al. bring us the full circle in the history of catheter ablation for AF by returning to ablation within the pulmonary veins.15 However, J Cardiovasc Electrophysiol, Vol. 26, pp. 1007-1008, September 2015. JG and MM have received honoraria from Medtronic and for presentations relating to cryoballoon ablation. Address for correspondence: Justin M. Ghosh, M.B.B.S., York Teaching Hospital NHS Foundation Trust, Scarborough Hospital, Woodlands Drive, Scarborough, YO12 6QL, UK. Fax: +447092840058; E-mail: [email protected]
Manuscript received 9 June 2015; Accepted for publication 11 June 2015. doi: 10.1111/jce.12733
they aimed to prevent pulmonary vein stenosis by the delivery of the antiproliferative drugs paclitaxel or everolimus, on a drug coated balloon (DCB). The studies were performed in a canine model. In each dog, 2 pulmonary veins underwent ablation and treatment with the DCB, 1 underwent ablation with no DCB treatment (positive control) and 1 was left untouched (negative control). The operator was able to select which veins received which treatment based on preference and ease of delivery of the DCB, and hence the treatment allocation was unrandomized. After 3 months the veins were checked for persistent isolation, and the pulmonary vein diameter and flow velocity within the veins were remeasured. Histological examination was performed postmortem. While the study assessed only a small number of veins and was nonrandomized, the effect of the treatment seems clear. The DCB effectively prevented pulmonary vein stenosis and did not adversely the effect the electrophysiological outcome. The fact that antiproliferative drugs prevent pulmonary vein stenosis should come as no surprise given that coronary interventionalists have been using drug coated stents in the coronary arteries for 10 years, for just this reason. Both paclitaxel and everolimus have robust data to support their use in the context of preventing coronary arterial stent stenosis,16,17 a condition also caused by neo-intimal proliferation. More recently, drug coated balloons have also found a place in the treatment of coronary and peripheral arterial stenosis, being a useful adjunct when stenosis has recurred within a previously stented area. So what next? The authors present this work as a “proofof-concept.” As they suggest, further research is needed to confirm their findings with a larger numbers and longer follow up. But to take the procedure forward as a clinical strategy we would need to see potential benefits to this approach. Why would we want to go back into the vein after coming out into the atrium (where we have substantial experience)? There are a few possible reasons:
(1) Recurrence of AF is commonly associated with electrical reconnection of the pulmonary veins. This technique might be associated with a lower rate of recurrence, as reliance on maintaining a line of block with a large circumferential lesion set is not required. (2) Wide area circumferential ablation, the most common ablation strategy, is associated with a significant occurrence of left atrial tachycardia, which can be more symptomatic and persistent than the original symptoms. A more distal ablation strategy would likely reduce this, although the possibility of micro reentry remains.
Journal of Cardiovascular Electrophysiology
Vol. 26, No. 9, September 2015
(3) Posterior atrial ablation can cause esophageal ulceration and, rarely, one of the most feared complications of AF ablation, atrial-esophageal fistula formation. This usually fatal complication is directly related to more midline posterior ablation strategies, and would be unlikely adopting a distal pulmonary vein (PV) strategy. It is likely that distal PV treatment is best suited to patients with paroxysmal AF, where there is less diseased atrial substrate. However, disease progression in AF is incompletely understood, with some retaining the same paroxysmal pattern for decades, while some transition rapidly toward a persisting pattern of arrhythmia. An ideal strategy would include methods of identifying the patient’s pattern of initiation and maintenance of fibrillation in order to provide treatment to the required areas, i.e., the PV triggers for purely triggered PAF, more toward the antrum for AF where early substrate disease has been identified, and more extensive atrial modification or FIRM ablation in cases of longstanding persistent AF, or in those with significant structural abnormality. However, this type of tailored strategy remains purely speculative, and would require a major advance in noninvasive testing and identification of patient subgroups. Tests such as MRI scar characterization18 and high density noninvasive monitoring may be helpful in this respect.19,20 The drug coated balloon may also be useful in treating previously acquired or even congenital pulmonary vein stenosis. The DCB may reduce the requirement for initial stent placement, or may be used to dilate a pulmonary vein stent which has developed restenosis. There are a myriad of different approaches to catheter ablation for AF, with differing results in different patient populations. One of the limitations in delivering results is that we still incompletely understand the spectrum of disease, and hence the potential targets in individual patients. When we are able to make progress with this, then treatments like distal PV ablation will more naturally find their place in our toolkit of ablation techniques. References 1. Calkins H, Kuck KH, Cappato R, Brugada J, Camm AJ, Chen SA, Crijns HJ, Damiano RJ Jr, Davies DW, DiMarco J, Edgerton J, Ellenbogen K, Ezekowitz MD, Haines DE, Haissaguerre M, Hindricks G, Iesaka Y, Jackman W, Jalife J, Jais P, Kalman J, Keane D, Kim YH, Kirchhof P, Klein G, Kottkamp H, Kumagai K, Lindsay BD, Mansour M, Marchlinski FE, McCarthy PM, Mont JL, Morady F, Nademanee K, Nakagawa H, Natale A, Nattel S, Packer DL, Pappone C, Prystowsky E, Raviele A, Reddy V, Ruskin JN, Shemin RJ, Tsao HM, Wilber D: 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. 2. Boersma LV, Wijffels MC, Oral H, Wever EF, Morady F: Pulmonary vein isolation by duty-cycled bipolar and unipolar radiofrequency energy with a multielectrode ablation catheter. Heart Rhythm 2008;5:1635-1642. 3. Van Belle Y, Janse P, Rivero-Ayerza MJ, Thornton AS, Jessurun ER, Theuns D, Jordaens L: Pulmonary vein isolation using an occluding cryoballoon for circumferential ablation: Feasibility, complications, and short-term outcome. Eur Heart J 2007;28:2231-2237. 4. Deneke T, Schade A, M¨uller P, Schmitt R, Christopoulos G, Krug J, Sz¨oll¨osi G, M¨ugge A, Kerber S, Nentwich K: Acute safety and
efficacy of a novel multipolar irrigated radiofrequency ablation catheter for pulmonary vein isolation. J Cardiovasc Electrophysiol 2014;25: 339-345. Reddy VY, Neuzil P, Themistoclakis S, Danik SB, Bonso A, Rossillo A, Raviele A, Schweikert R, Ernst S, Kuck K-H, Natale A: Visuallyguided balloon catheter ablation of atrial fibrillation: Experimental feasibility and first-in-human multicenter clinical outcome. Circulation 2009;120:12-20. Haissaguerre M, Shah DC, Ja¨ıs P, Hocini M, Yamane T, Deisenhofer I, Chauvin M, Garrigue S, Clementy J: Electrophysiological breakthroughs from the left atrium to the pulmonary veins. Circulation 2000;102:2463-2465. Oral H, Scharf C, Chugh A, Hall B, Cheung P, Good E, Veerareddy S, Pelosi F, Morady F: Catheter ablation for paroxysmal atrial fibrillation: Segmental pulmonary vein ostial ablation versus left atrial ablation. Circulation 2003;108:2355-2360. Nademanee K, McKenzie J, Kosar E, Schwab M, Sunsaneewitayakul B, Vasavakul T, Khunnawat C, Ngarmukos T: A new approach for catheter ablation of atrial fibrillation: Mapping of the electrophysiologic substrate. J Am Coll Cardiol 2004;43:2044-2053. Narayan SM, Krummen DE, Shivkumar K, Clopton P, Rappel WJ, Miller JM: Treatment of atrial fibrillationby the ablation of localized sources. J Am Coll Cardiol 2012;60:628-636. O’Neill MD, Ja¨ıs P, Takahashi Y, J¨onsson A, Sacher F, Hocini M, Sanders P, Rostock T, Rotter M, Pernat A, Cl´ementy J, Ha¨ıssaguerre M: The stepwise ablation approach for chronic atrial fibrillation– evidence for a cumulative effect. J Interv Card Electrophysiol. 2006;16: 153-167. Haissaguerre M, Jais PP, Shah DC, Takahashi A, Hocini M, Quiniou G, Garrigue S, LeMouroux A, LeM´etayer P, Clementy J: Spontaneous initiation of atrial fibrillation by ectopic beats originating in the pulmonary veins. N Engl J Med 1998;339:659-666. Pappone C, Rosanio S, Oreto G, Tocchi M, Gugliotta F, Vicedomini G, Salvati A, Dicandia C, Mazzone P, Santinelli V, Gulletta S, Chierchia S: Circumferential radiofrequency ablation of pulmonary vein ostia: A new anatomic approach for curing atrial fibrillation. Circulation 2000;102:2619-2628. Dong J, Vasamreddy CR, Jayam V, Dalal D, Dickfeld T, Eldadah Z, Meininger G, Halperin HR, Berger R, Bluemke DA, Calkins H: Incidence and predictors of pulmonary vein stenosis following catheter ablation of atrial fibrillation using the anatomic pulmonary vein ablation approach: Results from paired magnetic resonance imaging. J Cardiovasc Electrophysiol 2005;16:845-852. Packer DL, Keelan P, Munger TM, Breen JF, Asirvatham S, Peterson LA, Monahan KH, Hauser MF, Chandrasekaran K, Sinak LJ, Holmes DR: Clinical presentation, investigation, and management of pulmonary vein stenosis complicating ablation for atrial fibrillation. Circulation 2005;111:546-554. DiSimone CV, Holmes DR, Ebrille E, Syed FF, Ladewig DJ, Mikell SB, Powers J, Suddendorf SH, Gilles EJ, Danielsen AJ, Hodge DO, Kapa S, Asirvatham SJ: Direct pulmonary vein ablation with stenosis prevention therapy. J Cardiovasc Electrophysiol 2015;26:10011007. Silber S, Colombo A, Banning AP, Hauptmann K, Drzewiecki J, Grube E, Dudek D, Baim DS: Final 5-year results of the TAXUS II trial: A randomized study to assess the effectiveness of slow- and moderaterelease polymer-based paclitaxel-eluting stents for de novo coronary artery lesions. Circulation 2009;120:1498-1504. Valgimigli M, Sabat´e M, Kaiser C, Brugaletta S, la Torre Hernandez de JM, Galatius S, Cequier A, Eberli F, deBelder A, Serruys PW, Ferrante G: Effects of cobalt-chromium everolimus eluting stents or bare metal stent on fatal and non-fatal cardiovascular events: Patient level meta-analysis. BMJ 2014; 349:g6427. Vergara GR, Marrouche NF: Tailored management of atrial fibrillation using a LGE-MRI based model: From the clinic to the electrophysiology laboratory. J Cardiovasc Electrophysiol 2011;22:481-487. Ha¨ıssaguerre M, Hocini M, Shah AJ, Derval N, Sacher F, Ja¨ıs P, Dubois R: Noninvasive panoramic mapping of human atrial fibrillation mechanisms: A feasibility report. J Cardiovasc Electrophysiol 2013;24: 711-717. Di Marco LY, Raine D, Bourke JP, Langley P: Characteristics of atrial fibrillation cycle length predict restoration of sinus rhythm by catheter ablation. Heart Rhythm 2013;10:1303-1310.