J Interv Card Electrophysiol (2010) 29:187–190 DOI 10.1007/s10840-010-9517-1

CASE REPORT

First report of phrenic nerve injury during pulmonary vein isolation using the Ablation Frontiers pulmonary vein ablation catheter Syed Y. Ahsan & Andrew S. Flett & Pier D. Lambiase & Oliver R. Segal

Received: 26 July 2010 / Accepted: 12 September 2010 / Published online: 13 October 2010 # Springer Science+Business Media, LLC 2010

Abstract In an attempt to improve procedural outcomes and reduce time and complications, there has been particular interest in alternative technologies specifically designed for atrial fibrillation (AF) ablation. One novel technique is isolation of the pulmonary veins using an overthe-wire multielectrode catheter delivering duty-cycled bipolar and unipolar radiofrequency energy. Phrenic nerve injury is a rare but significant complication of AF ablation. This is the first report of phrenic nerve injury following catheter ablation for AF using the Pulmonary Vein Ablation Catheter (Medtronic, Minneapolis, MN, USA). Keywords Radiofrequency ablation . Atrial Fibrillation . Paroxysmal . Pulmonary vein ablation catheter . Phrenic nerve injury A 73-year-old lady was admitted for elective ablation of paroxysmal atrial fibrillation. Two years previously, she was successfully treated with radio-iodine therapy for Graves disease. She had experienced several episodes of Electronic supplementary material The online version of this article (doi:10.1007/s10840-010-9517-1) contains supplementary material, which is available to authorized users. S. Y. Ahsan : A. S. Flett : P. D. Lambiase : O. R. Segal The Heart Hospital, University College London, London, UK O. R. Segal (*) Department of Cardiovascular Electrophysiology, The Heart Hospital, 16-18 Westmoreland Street, London W1G 8PH, UK e-mail: [email protected]

atrial fibrillation since that time, each lasting several hours, despite treatment with beta-blockers. There was no other cardiac history of note. A pre-procedural transesophageal echocardiogram revealed a mildly dilated left atrium, a thin inter-atrial septum, and normal fossa ovalis anatomy. No thrombus was seen within the left atrium. A quadripolar electrode catheter (Response™, St. Jude Medical, Minnetonka, MN, USA) was placed in the coronary sinus via the left femoral vein for pacing purposes. Single transseptal puncture was performed without complication using a 98 cm Brockenbrough needle (BRK™ Transseptal needle, St Jude Medical, Minnetonka, MN, USA) and a 12.5 F steerable transseptal sheath (Channel Steerable Sheath, Lowell, Bard, MA, USA). The patient was heparinized to maintain the activated clotting time >300 s. Retrograde pulmonary venography identified separate left pulmonary veins and a single right pulmonary venous trunk. Pulmonary venous isolation was performed using a multipolar helical mapping and ablation catheter with a 25 mm diameter at the distal tip (pulmonary vein ablation catheter (PVAC), Medtronic, Minneapolis, MN, USA), deployed over a 0.032 in. guidewire placed inside each pulmonary vein (PV) sequentially. The PVAC was advanced over the wire until it was in contact with the antrum of the left atrium adjacent to the pulmonary vein ostium (Fig. 1) Optimal tissue apposition of the PVAC was confirmed using a combination of fluoroscopy and electrogram analysis prior to each energy application. Radiofrequency (RF) energy was delivered through selected electrode pairs for 60 s, to achieve a target temperature of 60°C for each electrode in the selected pair. Initial RF deliveries used a ratio of 4:1 bipolar/ unipolar energy. If target electrograms persisted, a ratio of 2:1 bipolar/unipolar energy was utilized.

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1 Discussion

Fig. 1 The distal array portion of the pulmonary vein ablation catheter (PVAC) with ten 3-mm electrodes and 3-mm spacing

All local potentials at the antrum, adjacent to the ostia of the left PVs, were abolished. PV isolation was confirmed by positioning the PVAC inside the vein to confirm electrical silence during coronary sinus pacing or sinus rhythm. RF energy application to the right pulmonary vein was performed under continuous fluoroscopy to ensure normal diaphragmatic movement. Three RF energy applications were delivered to the antrum adjacent to the upper branch of the right pulmonary vein using a 4:1 bipolar/ unipolar energy setting. Despite this, local electrograms were still recordable. A further energy application was delivered using a 2:1 bipolar/unipolar energy ratio without moving the catheter, during which the patient noticed an abrupt change in her breathing pattern. Energy delivery was terminated within 2 s and the catheter withdrawn in to the body of the left atrium. It was immediately evident that the right hemi-diaphragm was paralyzed on fluoroscopy (Fig. 2 and supplemental video). Fluoroscopic acquisition of diaphragmatic movement was recorded immediately and 20 min later, at which time there was no discernable improvement in diaphragmatic function. Catheters and sheaths were subsequently withdrawn after reversal of anti-coagulation with 50 mg of Protamine. The patient experienced no immediate symptoms related to diaphragmatic paralysis and oxygen saturations and respiratory rate remained normal. Ultrasound imaging of the diaphragm performed 1 h later demonstrated paradoxical movement in keeping with a diagnosis of right phrenic injury secondary to ablation. The patient was discharged the following day. She experienced marked difficulty in breathing in the first week at home, but subsequently her symptoms improved dramatically with no limitation in exercise tolerance. Despite this, thoracic MRI demonstrated an elevated right hemidiaphragm which was partly paralyzed. The anterior portion was hypokinetic and the posterior portion akinetic. There was no paradoxical movement (see Fig. 2 and supplemental video)

Radiofrequency catheter ablation has become first line treatment for drug refractory atrial fibrillation (AF) [1, 2]. A recent worldwide survey on the methods and safety of conventional catheter ablation for AF reported an incidence of major complications of 6% [2]. The potential complications of catheter ablation for AF include stroke, pericardial effusion, pulmonary vein stenosis, and atrio-oesophageal fistula. Extracardiac penetration of ablative energy can lead to phenic nerve injury (PNI), as the anatomical course of this nerve may predispose it to damage during ablation. The right phrenic nerve descends through the mediastinum, parietal pleura, and pericardial sac to pass along the superior vena cava and right atrium (Fig. 3). In up to 79% of cases, this nerve passes in close proximity to the right superior pulmonary vein [3]. In a recent retrospective analysis of 3,755 patients referred for catheter ablation of AF, the incidence of phrenic nerve damage was 0.48% [4]. Ablation at the infero-anterior portion of the right superior pulmonary vein ostium and the postero-septal portion of the superior vena cava are more likely to be associated with PNI [4]. The most frequent symptom of PNI is dyspnoea, although up to 31% of patients remain asymptomatic [4–6]. Although complete or partial recovery is observed in the majority of patients between 1 day and 28 months, up to 17% do not regain diaphragmatic function [4]. Several mechanisms have been proposed to explain PNI after catheter ablation and include direct heat transfer from the ablation site to the nerve, the electromagnetic field generated at the catheter tip, and generation of a resonance current around the heart [7–9]. Experimental data from canine models demonstrate early transient nerve effects prior to permanent nerve injury [10]. PNI has been reported with a variety of energy sources, including cryothermy [4, 6, 11], laser energy [6, 12], ultrasound [11, 13, 14], and radiofrequency catheters (4 mm, 8 mm and irrigated tip). In an attempt to improve procedural outcomes and reduce time and complications, there has been particular interest in alternative technologies specifically designed for AF ablation. One novel technique is isolation of the pulmonary veins using an over-the-wire multielectrode catheter delivering duty-cycled bipolar and unipolar RF energy at relatively low power [15]. 1.1 The Ablation Frontiers Pulmonary Vein Ablation Catheter The PVAC is a 9-French, helical, decapolar mapping, and ablation catheter with a 25-mm diameter at the distal tip (Fig. 1). The catheter has bidirectional movement and the distal array can be manipulated into a spiral configuration through controls on the handle. Catheter placement and stability to map and ablate the PVs is facilitated by use of a

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Fig. 2 The upper panels show fluoroscopy during ablation during inspiration (INSP) and expiration (EXP). The bottom panel shows real-time coronal cardiac magnetic resonance images. During inspiration, right hemidiaphragmatic paralysis is seen consistent with phrenic nerve injury. There is no movement of the right hemidiaphragm during inspiration or expiration (dashed arrows) whereas the left hemi-diaphragm moves normally (bold arrows; see supplemental videos)

0.032-in. guidewire, positioned into different side branches to modify the tissue–electrode interface around the PV circumference. The generator used in conjunction with the PVAC can deliver alternating cycles of unipolar and bipolar energy in various ratios. When using the generator in a 4:1 setting, the maximum power delivered per electrode is 8 W, increasing to 10 W with other settings. In a recent study by Boersma et al. of 97 patients undergoing ablation for paroxysmal AF using the PVAC, 83% of patients remained free of AF at 6 months with no acute or short-term complications [15]. The authors concluded that using alternating unipolar/bipolar energy to a maximum of 8 W per electrode, lesion depth was limited to 2–4 mm, minimizing the risk of collateral damage to the esophagus or phrenic nerve. The authors also noticed that double the number of ablation lesions were required when using the PVAC in a single common PV ostium [15]. This point is particularly relevant to the present case. Wijfells et al. [16] recently performed in vitro and in vivo studies on a porcine SVC model using the PVAC to characterize ablation lesions, using varying ratios of bipolar: unipolar energy. Lesion depth was significantly decreased with more bipolar energy modes. Phrenic nerve stimulation was noted in two out of six animals during ablation at the SVC, near the intersection with the right

atrium, with a 2:1 energy mode. However, it is important to remember that the anatomical relations in a pig heart remain different to that in humans. PNI is a rare but significant complication of catheter ablation for AF. Although the prognosis is good, a small

Fig. 3 A picture of the heart demonstrating the relative proximity of the phrenic nerve to the right superior pulmonary vein as it exits behind the superior vena cava through the pericardium that contains the nerve. Wiley-Blackwell publishing

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proportion of patients do not regain diaphragmatic function. In this case, PNI occurred with ablation at the ostium of a common right pulmonary vein using the Ablation Frontiers system. Unfortunately, images showing catheter position during ablation are not available and therefore one could speculate ablation was actually delivered inside the vein. Even if this was true, we believe this case highlights the potential to cause extra-cardiac injury using a new technology with a completely new ablation delivery system. One of the principal advantages of the Ablation Frontiers system is its ability to treat AF without a three-dimensional mapping system. However, this also means the venous ostia can only be defined using two-dimensional fluoroscopic imaging and this can be difficult, especially at common venous ostia where the anatomy is complex. High output pacing from each electrode prior to ablation to try to capture the phrenic nerve energy delivery may have prevented PNI in this case. We recommend this should be performed at the SVC, RPV ostia, and left atrial appendage-roof region prior to each energy delivery in all cases. If phrenic nerve capture is observed, ablation should be avoided. In addition, use of the 2:1 bipolar/unipolar energy setting with the PVAC should probably be avoided if at all possible. While the PVAC isolation technique uses lower power outputs and compares favorably to current techniques in terms of procedure times, short-term outcomes and the ability to perform the procedure without additional 3D electroanatomical mapping, complications can still occur, including extracardiac damage.

2 Conclusion This is the first report of phrenic nerve injury following catheter ablation for AF using the PVAC. This complication may still occur despite the use of much lower power settings than with traditional single-pole ablation catheters. High output pacing and operator vigilance is still mandatory, and accurately defining the pulmonary venous ostia is critical.

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