Multipolar ablation for atrial fibrillation: are we going in circles?

This editorial refers to ‘Low rate of asymptomatic cerebral embolism and improved procedural efficiency with the novel pulmonary vein ablation catheter GOLD: results of the PRECISION GOLD trial’ by Y. De Greef et al., on pages 687–695. It seems hard to believe that it has been more than 8 years since the first patient was enrolled in the pivotal tailored treatment of persistent atrial fibrillation (TTOP-AF) study which initially evaluated the performance of a multipolar, duty-cycled, phased radiofrequency (PhRF) catheter ablation technology (Ablation Frontiers, Medtronic, Inc.).1 The efficacy of the technology was quite promising showing that nearly 56% of patients experienced substantial improvement in atrial fibrillation (AF) burden at 6 months. In smaller studies, the technology has also consistently shown the ability to achieve outcomes comparable with traditional, single-point RF technology while significantly reducing procedural time.2 In fact, during the United States Food and Drug Administration (FDA) panel hearing in 2011, there was unanimity that the technology was effective in the treatment of persistent AF. The technology was not granted approval, however, because of safety concerns. In particular, the peri-procedural stroke rate in the TTOP-AF study was 2.9%. There were also two studies in 2011 showing that the incidence of asymptomatic cerebral emboli (ACE) post-ablation was significantly higher with PhRF technology compared with open-irrigated, single-point RF and cryoablation.3–5 Since that time, there has been a substantial amount of research performed to assess the root causes of ACE and advancements to improve the PhRF technology. It is in this context that the study by De Greef et al.6 in this issue of Europace is of particular interest. The authors performed a multicentre, single-arm study in which the incidence of ACE and procedural efficiency of newly designed PhRF technology were evaluated. The specific technology enhancements to the circular mapping catheter (PVAC GOLD, Medtronic, Inc.) were replacement of the platinum electrodes with gold to enhance thermal conductivity and perhaps reduce coagulum formation; reduction of the number of electrodes from 10 to 9 to avoid a potential electrical interaction caused by overlapping of the first and tenth electrodes; and introduction of a 20° forward tilt to enhance catheter–tissue contact. As has been demonstrated with the older technology, there was a low peri-procedural ACE rate with only 1 patient (2.1%) experiencing one single post-ablation ACE lesion which resolved by 1 month. There were no clinical strokes. The PVAC GOLD also demonstrated a lower number of RF applications and higher effective contact and energy delivery compared with historical data from the older-generation PVAC catheter. Interestingly, the rate of ACE in the current study is no different than that reported in the ERACE (Evaluation and Reduction of Asymptomatic Cerebral Embolism) study evaluating the older version of the catheter (1.7%).7 This is perhaps not surprising since ERACE and other studies have shown that most of the factors related to development of ACE with multipolar ablation are dependent on the operator and not the technology. Uninterrupted peri-procedural oral anticoagulation (OAC), maintenance of an activated clotting time (ACT) of >350 s, minimization of air introduction into the left atrium during catheter exchanges, and maintenance of good catheter–tissue contact have all been shown to reduce ACE formation.7,8 Although the electrical short circuit between overlapping first and tenth electrodes has also been shown to be a major source of ACE experimentally,8 the elimination of the tenth electrode on the new PVAC GOLD did not result in any clinical differences when other operator-dependent factors were controlled. When another company manufactured a multipolar RF ablation catheter with open irrigation, the irrigation was supposed to mitigate against ACE formation.9 However, an ACE rate similar to that of PhRF was demonstrated, which was avoided in patients with uninterrupted OAC and maintenance of a high procedural ACT. Furthermore, it is unclear what relationship such small peri-procedural ACE rates have on incidence of stroke and long-term cognitive functioning. Gross cognitive functioning in the current study did not change from pre- to post-ablation. No clinical strokes resulted in this study and neither in the 2011 studies showing very high rates of ACE.3,4 Studies have also demonstrated a very high incidence of pre-existing silent cerebral lesions (73% in the current study) due to chronic AF which likely have much more significance on long-term cognitive functioning.7 These chronic lesions may be reduced by elimination of AF and may have much more clinical relevance for our patients. If this can be accomplished through catheter ablation, the long-term benefit may dwarf the relatively small trade off of a very low incidence of small and transient ACE. Yet, we continue to see small, single-arm studies (such as the current one) which report a low incidence of ACE in the absence of a proper comparator with no longer-term outcome data.10,11 While very promising, these data fail to tell us how this new gold technology would perform from a safety point of view in a large number of patients in comparison with standard technologies being used today. Neither are we much further ahead from an efficacy standpoint. The current study reports that the gold catheters provided better effective contact and energy delivery than the older platinum version, but this was based on retrospective data from an older study. It is therefore unclear how this would affect long-term clinical outcomes such as freedom from AF. Furthermore, FDA mandated another single-arm study (which is now ongoing) to evaluate the safety of the PhRF system before granting market approval called VICTORY AF (Evaluation of Multielectrode Phased RF Technology in Persistent AF; clinicaltrials.gov NCT01693120). The primary endpoint of this trial is clinical stroke at 30 days with a sub-study evaluating ACE. There is no comparator arm, and the study will provide very limited procedural outcome data. Assuming this study meets its safety threshold, how does it help operators to gauge the efficacy and safety of the technology against what is currently available? There is considerable reason to believe that multipolar technology will result in similar outcomes to currently available technology while enhancing procedural efficiency and likely reducing procedural time.2,12,13 These are good things for both patients and operators. But the existing data are largely non-randomized, retrospective, or limited to only a few centres worldwide. To move forward in our assessment how PhRF or other multipolar technologies will fit in our armamentarium of catheters for AF ablation, we need proper prospective, comparative, randomized trials. Fortunately, some of these data are just starting to be collected [CAPCOST (Efficiency Study Evaluating the Use of the PVAC Catheter Technology for Performing Ablation in Patients with Atrial Fibrillation) study NCT01562912 and GOLD FORCE (PVAC GOLD Versus Irrigated RF Single Tip Catheter with Contact FORCE Ablation of the Pulmonary Veins for Treatment of Drug Refractory Symptomatic Paroxysmal and Persistent Atrial Fibrillation) study NCT02463851], but results are still far off. Until we can start to see the results of these and future well-designed investigations, the role of multipolar ablation continues to remain unclear. I would therefore propose that further single-arm studies looking at indirect or direct acute safety endpoints in the absence of longer-term outcome data will only keep us moving in circles. Conflict of interest: Research grants—Medtronic, Bayer, and Biosense Webster. Advisory boards—Medtronic, Biosense Webster, and Bayer. Speaker honoraria—Medtronic, Bayer, and Boehringer Ingelheim.

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