Summary
Background
Radiofrequency ablation (RFA) of paroxysmal atrial fibrillation (PAF) has focused on pulmonary vein isolation (PVI). However, despite initial positive results, significant recurrences have occurred, partly because of pulmonary vein (PV) reconnection or non-PV ectopic foci, including the superior vena cava (SVC).
Objectives
This prospective, randomized study sought to investigate the efficacy of additional SVCI combined with PVI in symptomatic PAF patients referred for ablation.
Methods
From November 2011 to May 2013, RFA was performed remotely using a CARTO ® 3 System in patients randomized to undergo PVI for symptomatic drug-refractory PAF, with (PVI + SVCI group) or without (PVI alone group) SVCI. PVI and SVCI were confirmed by spiral catheter recording during ablation. Procedural data, complications and freedom from atrial tachycardia (AT) and atrial fibrillation (AF) were assessed.
Results
Over an 18-month period, 100 consecutive patients (56 ± 9 years; 17 women) with symptomatic PAF were included in the study (PVI + SVCI, n = 51; PVI, n = 49); the CHA 2 DS 2 -VASc score was 0.9 ± 1. Median duration of procedure (± interquartile), 2.5 ± 1 hours; total X-ray exposure, 13.3 ± 8 minutes; transseptal puncture and catheter positioning, 8 ± 5 minutes; left atrium electroanatomical reconstruction, 3 ± 2 minutes; and catheter ablation, 3.7 ± 3 minutes. After a median follow-up of 15 ± 8 months, and having undergone a single procedure, 84% of patients were symptom free, while 86% remained asymptomatic after undergoing two procedures. The cumulative risks of atrial arrhythmias (AT or AF) were interpreted using Kaplan-Meier curves and compared using the log-rank test. Long-term follow-up revealed no significant difference between groups, with atrial arrhythmias occurring in six (12%) patients in the PVI + SVCI group and nine (18%) patients in the PVI alone group ( P = 0.6). One transient phrenic nerve palsy and one phrenic nerve injury with partial recovery occurred in the PVI + SVCI group.
Conclusions
SVCI combined with PVI did not reduce the risk of subsequent AF recurrence, and was responsible for two phrenic nerve injuries. Accordingly, the benefit-to-risk ratio argues against systematic SVCI.
Résumé
Contexte
L’ablation par radiofréquence (RFA) de la fibrillation atriale paroxystique (FAP) repose sur l’isolement des veines pulmonaires (VPs). Malgré les bons résultats de la technique, il existe un taux d’échec et de récidives non négligeables qui peuvent être dus soit à des reconnections de VPs, soit à d’autre sources dont l’origine peut-être la veine cave supérieure (VCS). Les données de la littérature sont controversées sur l’intérêt de l’isolement systématique de la VCS en combinaison avec l’isolement des VPs dans le traitement de la FAP.
Objectifs
Cette étude randomisée a cherché à évaluer l’efficacité de l’isolement systématique de la VCS en complément de l’isolement des VPs chez les patients avec FA paroxystique symptomatique par la technique de robot magnétique.
Méthodes
De novembre 2011 à mai 2013, les patients devant bénéficier d’un traitement par RFA pour FAP étaient randomisés soit dans un groupe avec isolement des VPs couplé à un isolement de la VCS soit dans un groupe sans isolement de la VCS. Le critère principal de jugement était basé sur les récidives de FA ou d’autres arythmies atriales.
Résultats
Sur une période de 18 mois, 100 patients consécutifs avec FAP (56 ± 9 ans ; 17 femmes) ont été inclus, 51 pts dans le groupe 1 et 49 pts dans le groupe 2. Au cours d’un suivi de 15 ± 8 mois après une seule procédure, 84 % étaient asymptomatiques avec absence de récidives, alors que 86 % étaient asymptomatiques après 2 procédures. Les récidives d’arythmies étaient les suivantes : 1 tachycardie atriale (1 %), 8 FAP (14 %), 1 FA persistante (1 %). Le suivi à long-terme n’a pas montré de différence significative entre les 2 groupes, avec 6/51 récidives (12 %) dans le VCS + VP groupe (FAP, n = 5 ; TA, n = 1) contre 9/49 patients (18 %) dans le VCS groupe (FAP, n = 9 ; p = 0,6). Deux paralysies phréniques ont été observées dans le groupe 1 avec récupération totale dans un cas.
Conclusions
Cette étude randomisée avec la technique du robot magnétique montre que l’isolation systématique de la VCS en combinaison avec l’isolement des VPs ne réduit pas le risque d’arythmies atriales mais au contraire expose les patients à d’autres complications comme la paralysie phrénique.
Background
For several years now, radiofrequency ablation (RFA) therapy has played a decisive role in the treatment of complex arrhythmias and, particularly, atrial fibrillation (AF) . To date, RFA of paroxysmal atrial fibrillation (PAF) has focused on pulmonary vein isolation (PVI), regardless of whether the PVI approach was segmental or circumferential . However, despite initial positive results, significant recurrences occurred after the first procedure, partly because of pulmonary vein (PV) reconnection, although non-PV ectopic foci, including the superior vena cava (SVC), might also be implicated . Applying a strategy of SVC isolation (SVCI) in addition to PVI appears to improve the outcome of AF ablation solely in patients exhibiting PAF , although this is still subject to debate. There are, in fact, only two randomized studies available, which are hampered by several limitations and contradictory results . We therefore need further investigation into whether SVCI combined with PVI provides additional clinical benefits in a PAF population .
The only beneficial randomized study available, by Corrado et al., involved procedures performed with non-irrigated catheters, and clinical evaluation seems to have been obtained retrospectively . Conversely, Wang et al. did not find any additional benefits, but their study follow-up was short term, and patients were randomized before evaluation of SVC arrhythmogenicity . Moreover, no data exist concerning the feasibility of SVCI using the remote magnetic navigation system (RMNS), which was developed with the aim of improving the benefit-to-risk ratio for both patient and operator .
This study had two objectives: first, to prospectively compare the effect of PVI plus SVCI versus PVI alone on PAF patient outcome; second, to determine SVCI feasibility using the RMNS.
Methods
Catheter ablation was performed remotely via the Niobe ® II RMNS (Stereotaxis, St. Louis, MO, USA), combined with a new three-dimensional (3D) non-fluoroscopic navigation system (CARTO ® 3 System; Biosense Webster, Diamond Bar, CA, USA), in 100 consecutive patients who underwent PV disconnection for symptomatic drug-refractory paroxysmal AF. Randomization was only carried out at the time of the procedure if the circular-mapping catheter placed above the right atrium (RA)-SVC junction revealed active electrical potentials in the SVC (detected in sinus rhythm or under stimulation). Patients with persistent and permanent AF were excluded from participation, as were those with an electrically silent RA-SVC junction. All patients provided written informed consent before the procedure, but were only included if their SVC was electrically active, with all patients blinded to their group assignment.
Electrophysiological procedures
All patients received anticoagulation therapy with vitamin K antagonists (VKA) over a minimum period of at least 2 months before the procedure (target international normalized ratio, 2 to 3), and therapeutic anticoagulation was maintained with intravenous or low-molecular-weight heparin, with treatment commencing after VKA discontinuation and 3 days before the intervention. Transoesophageal echocardiography was performed within the 48 hours before the procedure, to exclude left atrial (LA) thrombus. VKA administration was resumed on the day after the procedure, and effective anticoagulation was maintained with heparin until the international normalized ratio was > 2.0. Surface electrocardiograms and bipolar endocardial electrograms (filtered from 30 to 500 Hz) were monitored continuously and recorded on a computer-based digital amplifier-recorder system. A deflectable quadripolar catheter (5 mm interelectrode spacing; Xtrem; ELA Medical, Montrouge, France) was positioned in the coronary sinus to carry out pacing and recording. The left atrium (LA) was accessed either via a patent foramen ovale, when present, or by transseptal puncture. A guidewire was inserted into the LA using an 8F sheath. Over the course of the procedure, the sheath was perfused with heparinized solution (3000 U of heparin in 500 mL of sodium chloride 0.9% at a rate of 150 mL/h). A multipolar deflectable catheter (LASSO ® ; Biosense Webster, Diamond Bar, CA, USA) was inserted through the long sheath to enable the mapping of the PV ostia required for the ablation procedures. RFA was performed using a 3.5 mm open irrigated-tip magnetic ablation catheter (NAVISTAR ® RMT ThermoCool ® ; Biosense Webster, Diamond Bar, CA, USA). The catheter was introduced into the LA through a second transseptal puncture; the venous sheath was then withdrawn into the RA and continuously perfused. After the transseptal puncture, intravenous unfractionated heparin was administered as a bolus (7500 U); additional boluses were given throughout the procedure to ensure an activated clotting time of at least 300 seconds. The activated clotting time was determined 30 minutes after the transseptal puncture and every 30 minutes thereafter. When the activated clotting time was < 300 seconds, an additional bolus of 2500 U was administered. Deep sedation was achieved using intravenous nalbuphine and midalzolam.
Radiofrequency catheter ablation procedures
For both study groups, the endpoint of ablation was the isolation of the PVs, defined by complete elimination or dissociation of pulmonary potentials, confirmed in all cases with a circumferential mapping catheter. Radiofrequency was applied using an open irrigated-tip catheter, with a power output not exceeding 35 W when positioned close to the PV ostia, and not exceeding 25 W when in the posterior part of the PV ostia or the SVC ostia. Tip irrigation was achieved by using sodium chloride 0.9% at a rate of 20–35 mL/min to maintain a tip temperature of < 43 °C. SVCI was performed by segmental ablation in all cases.
CARTO ® 3 System features
This study used the CARTO ® 3 System, which allows for real-time advanced catheter location and visualization of both ablation and circular-mapping catheters (NAVISTAR and LASSO). The catheter location display was identical to that of the fluoroscopic view. The CARTO ® 3 System combines electromagnetic technology (as in the CARTO XP System) with new Advanced Catheter Location™ technology that enables visualization of multiple catheters without requiring fluoroscopy. Briefly, Advanced Catheter Location is an impedance-based catheter localization system that enables precise cardiac mapping and navigation with multiple electrodes. Six electrode patches were attached to the body surface, constantly monitoring the current, which was emitted at a frequency unique to each individual catheter electrode. In addition, each electrode patch was equipped with a magnetic sensor, enabling 3D localization. The currents detected at the patches were associated with the 3D positioning of the electrode inside the human body. The ability of the CARTO ® 3 System to visualize the manipulation and placement of circular-mapping catheters in each vein could further reduce the duration of fluoroscopy procedures. This system also improved catheter stability during ablation and facilitated the identification of each catheter electrode pair position. The visualization of catheters and electrode pairs was provided via a real-time on-screen display of a geometrically-reliable icon representing the distal part of the LASSO catheter along with the electrode positions. LA reconstruction was obtained using a fast anatomical map algorithm. This method produced a continuous (non-gated) record of the movements of the magnetic NAVISTAR catheter. Based on this volume sampling, surface reconstruction was built in accordance with the set resolution level. On completion of the map, a 3D computed tomography scan was performed to optimize LA reconstruction.
Remote magnetic navigation system
The Niobe II RMNS is a technological platform that employs a steerable magnetic field to remotely guide a supple catheter inside the heart . The steerable magnetic field contains two giant computer-controlled 1.8 tonne magnets positioned on opposite sides of the fluoroscopy table. A magnetic field of 0.08 to 0.1 Tesla was generated (according to the initial choice) so that the three small magnets incorporated in parallel into the tip of the radiofrequency catheter could enable 3D navigation. The magnetic field was applied to a theoretical cardiac volume of 20 cm × 20 cm. By means of a vector-based computer system (Navigant 2.1; Stereotaxis Inc., St. Louis, MO, USA), precision guiding of the catheter tip was possible. This system operated by aligning the catheter to the generated magnetic field, making the movements of the catheter dependent on the changes in direction of the two magnets, each in relation to the other. A computerized motor drive system (Cardiodrive ® ; Stereotaxis Inc., St. Louis, MO, USA) advanced or retracted the catheters, whereas the computerized work station (Navigant 2.1) was required to guide their orientation in space. Using a keypad (arrows) or joystick, the catheter could be continuously advanced, retracted or even adjusted (from 1 mm to 9 mm). Use of the second-generation Niobe II enabled us to tilt the magnets at angles ranging from 40° left anterior oblique to 30° right anterior oblique. The magnetic field was constantly generated during the ablation procedure, thus keeping the catheter tip in permanent contact with the endocardial tissue throughout the cardiac cycle, and therefore improving the delivery of the radiofrequency currents. Given that the magnetic field exerted a weak force (15–20 gm) and the catheter was very flexible, navigation inside the heart was highly reliable, with nearly zero risk of perforation . The system was able to store certain data, such as the position of veins, and these vectors could then be reapplied during examination to facilitate catheter navigation or reduce procedure time.
Measurements: procedural and fluoroscopy variables
The following variables were recorded for all patients and were compared between study groups: total duration time (skin to skin); total X-ray procedure time, from needle insertion to ultimate catheter removal; skin to catheter positioning X-ray time, from femoral access to the final catheter positioning in the LA, including transseptal access; LA electroanatomical mapping X-ray time, from catheter positioning in the LA to satisfactory electroanatomical reconstruction compared with LA computed tomography scan; ablation X-ray time from first to last radiofrequency delivery.
Endpoints
The procedure endpoint was PVI, confirmed in all patients by spiral catheter recording during ablation. PVI was defined as abolition or dissociation of activities in all PVs. PV potentials and far-field potentials were distinguished by means of a pacing technique from the LA, LA appendage or coronary sinus, using the ablation or quadripolar catheter. Segmental ablation was defined as targeting the earliest RA-SVC conduction in cases where the RA-SVC conduction sequence could be detected in the sinus rhythm or by RA or proximal coronary sinus pacing. SVCI was characterized as the disappearance of SVC potentials or dissociation of SVC potentials with RA activity. Phrenic nerve injury prevention was achieved by avoiding the posterolateral wall or by high-output pacing stimulation (30 mA). Procedural data was collected, including X-ray exposure and complications.
Follow-up
Patients were hospitalized for 3 days post-procedure, as standard, with a 2-month blanking period. The blanking period was defined as the interval during which early recurrences were considered a transient phenomenon rather than a procedure failure. Antiarrhythmic medication was continued for at least 3 months and then stopped. VKA administration was continued, taking into account the CHA 2 DS 2 -VASc score. Success was defined as the absence of any documented arrhythmia or symptoms suggestive of arrhythmia recurrences (atrial tachycardia [AT], atrial flutter and AF). We performed 24-hour Holter monitoring each time a patient experienced palpitations. Patients were followed-up clinically every 6 months, and a redo procedure was permitted > 6 months after the index procedure, at the request of the patient. We systematically performed 24-hour Holter monitoring at the end of follow-up, and assessed long-term complications. The patient and the medical practitioner who carried out the follow-up were blinded to the patient’s group assignment.
Statistical analysis
The baseline characteristics of the patients were examined using Fisher’s exact test for categorical variables or a t -test. The differences between groups were analysed by analysis of variance. Summary values are expressed as means ± standard deviations. All reported levels of significance were two-sided. A probability value of P < 0.05 was considered statistically significant. We estimated that the enrolment of 100 patients with symptomatic paroxysmal AF would be necessary to detect a 20% reduction in AF recurrence in the PVI plus SVCI group versus in the PVI alone group, with 80% power and a two-sided α level of 0.05. The primary endpoint was time to symptomatic AF recurrence, confirmed by electrocardiogram or Holter monitoring. The secondary endpoint was symptom evaluation and occurrence of other atrial arrhythmias. The primary analysis was an intention-to-treat comparison of time to AF recurrence. For all time-to-event analyses, rates were estimated by means of the Kaplan-Meier method and were compared using the log-rank test. Patient data were censored at time of last contact, withdrawal from the study or death. Symptomatic and asymptomatic episodes of AF were recorded. The authors had full access to the data and assume complete responsibility for its integrity. All authors have read and agreed to the manuscript as written. All analyses were performed using StatView ® 5.0 (StatView IV; Abacus Concept, Berkeley, CA, USA).
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