New Research Using the Cryoballoon Technique: Interview with Thomas Neumann, MD

In this feature interview, we speak with Dr. Thomas Neumann from the Kerckhoff Heart Center in Bad Nauheim, Germany, about a recent three-center trial to study the effectiveness and safety of the Arctic Front.

How long have you been using the Arctic Front catheter and why do you use it for pulmonary vein isolation? We’ve been using CryoCath’s Arctic Front since 2004 at our clinic. We were one of the first two centers in the world to use the original cryoballoon prototypes in a clinical trial. We wanted to see if a cryoballoon could simplify pulmonary vein isolation, which is now widely accepted as the foundation for catheter ablation of atrial fibrillation. We were looking for new tools that could simplify the ablation process, reduce procedural times, and help establish a reproducible anatomical procedure. We believed that these new catheters would be both safe and effective based on strong evidence that cryoablation is associated with less thrombus, less stenosis, and less damage to other structures such as the esophagus. Tell us about the Arctic Front cryoballoon, including size options, diameter, etc. The Arctic Front catheter is an over-the-wire system, compatible with a 0.035-inch guidewire. The balloon is available in two diameters: 23 and 28 millimeters. It’s a double-walled cryoballoon, which provides an added measure of safety. The left atrium can be accessed via the transseptal route from the right femoral vein with a steerable 12 French sheath. Before it can be advanced toward the vein, the balloon has to be inflated — then it can be advanced to the ostium of the PV. At this point, contrast agents are injected through the guidewire lumen to assess vein occlusion via fluoroscopy.

Are balloon catheters more effective for circumferential ablation? They can be more effective for circumferential ablation because there is nearly complete tissue contact with the balloon, producing complete occlusion of the vein. It’s also possible to get very stable catheter positioning during the freezing process because of tissue adhesion as the temperature of the catheter drops. Remember that originally only focal-tipped catheters, which were initially designed to ablate foci or create small lines of block, were available for PV isolation. However, for PVI, you need to create much larger contiguous lines in a very challenging anatomical environment — hence the advantage of a balloon approach.

What prompted you to conduct the study? There were three centers in Germany that were the first in the world to use this new technology. However, there was no data on the technology’s performance at the time. We decided to pool all data in a study and share our experience with others. What we produced, as a result, is the largest published series — showing favorable and reproducible outcomes — that supports a shift from focal-RF to cryoballoon PVI.

You mentioned three centers were involved in this study. Which three centers were they? The three centers that participated were the Kerckhoff Heart Center in Bad Nauheim, the Heart and Diabetes Center of North Rhine-Westphalia at Ruhr University Bochum in Bad Oeynhausen, and the Center of Cardiovascular Medicine.

What was the therapeutic aim of this study, and what were the primary endpoints? The therapeutic aim of the study was catheter ablation, that is, antral pulmonary vein isolation of symptomatic atrial fibrillation. The primary endpoints were the acute isolation rate of targeted PVs and the first ECG-documented recurrence of AF after a blanking period of three months in the absence of any antiarrhythmic drug therapy. The secondary endpoint was the occurrence of PV stenosis or atrio-esophageal fistula and peri-interventional safety.

How many patients were treated in this study? Our study enrolled 346 consecutive patients with symptomatic and drug-refractory paroxysmal or persistent atrial fibrillation. Explain your ablation technique. After angiography or AP projections, we mapped each pulmonary vein. We mapped inside the PVs with a 15-mm LASSO catheter (Biosense Webster Inc., a Johnson & Johnson company, Diamond Bar, CA), and outside at the level of the PV antrum with 20- and 25-mm LASSO catheters. We verified complete isolation when all signals were equal to or below 0.2 mV. In all patients, we paced at the location of bipolar signals within the PV ostium to confirm exit block. After mapping the areas of interest distal to the antrum, we performed cryoballoon ablation during sinus rhythm. As you know, the cryoballoon itself is not equipped with electrodes to record local electrical signals, so during AF, the transition zone was defined primarily by anatomical orientation. We aimed for at least one cryoballoon ablation with complete (Grade 4) occlusion on every targeted pulmonary vein. We delivered additional cryo energy after the guidewire was placed in different branches of the pulmonary veins with early branching, which usually resulted in better contact of the balloon in different areas of the PV antrum.

How did you assess occlusion? We placed a guidewire in one of the PV branches, with the deflated balloon catheter inside the sheath. Then we advanced the balloon toward the PV ostium and inflated it. We used a scale of semi-quantitative grading to gauge the degree of balloon occlusion, which was achieved by injecting a 50% diluted contrast medium into the PV. Our grading scale ranged from Grade 4, which is excellent, meaning full retention of the contrast medium without visible outflow, to Grade 1, which is very poor, that is, immediate rapid outflow from the PV. At least one cryoenergy application with Grade 4 occlusion in every targeted PV could be achieved in 90% of cases.

What was the application time per freeze? Our therapeutic aim in all patients was to isolate all targeted PVs with a cryoballoon-only approach. We set the post-isolation observation period — to check for conduction recurrence — at 20 minutes. If a cryoballoon could not reach a particular PV or if no isolation could be achieved after five balloon applications, an 8-mm cryoablation catheter was used to complete the PVI, with the LASSO catheter ensuring signal control. The application time per freeze was 300 seconds (with a range of 28 to 480 seconds). The median number of applications per patient was 11 (with a range of 9 to 13). Finally, the average number of cryoballoon applications per PV was 2.8.

What were the acute results? Out of 1,403 pulmonary veins, a total of 1,360 (or 97%) could be isolated with one or two balloons. CryoCath’s Freezor MAX focal catheter was used in combination with balloon ablation in 58 patients.

Why could you not achieve 100% PVI, and why did you use Freezor MAX? There are many anatomical challenges in the left atrium, including the common ostia. In the case of the common ostia, these were a little more challenging, and we had to go a little more distal and ablate the branches. In some of these cases, it was necessary to use an additional focal cryocatheter (i.e., Freezor MAX) to help us complete the isolation.

What was the average length of these procedures? How does it compare with PV ablation using radiofrequency (RF) energy? The total procedure time was approximately 170 minutes, and the median fluoroscopy time was 40 minutes (ranging from 30-57 minutes). Both results compare favorably with RF procedures. All three centers have seen their procedure times and fluoroscopy times decrease as they gained experience.

What were the differences between using the 23- and 28-mm balloon? The smaller, 23-mm balloon was selected for 116 patients. In the rest of the patients studied, the procedure was started using the 28-mm balloon. Comparing the 23- and 28-mm balloons, we observed no significant differences in the number of applications, total cryo time per pulmonary vein, procedure time, incidence of acute PV isolation, and long-term success. The fluoroscopy time was significantly higher with the 28-mm balloon, with a median fluoroscopy time of 46, compared to 33 minutes for the 23-mm balloon. This was probably because it takes a little more time to position the larger balloon.

What was your method for follow-up? How long was the follow-up period? Post procedure, patients were scheduled for quarterly follow-ups. Late follow-up visits (i.e., over a year post intervention) were also performed. At each follow-up visit, we obtained seven-day Holter recordings. The median follow-up time for patients was 12 months (ranging from 7-16 months). In 264 patients, the follow-up time was equal to or greater than six months, while in 133 patients, it was over 12 months.

What were the results of the trial? We found that circumferential PVI using the cryoballoon technique resulted in the maintenance of sinus rhythm without the use of antiarrhythmic drug therapy in 159 patients (or 74%) with paroxysmal atrial fibrillation. In patients with persistent AF, the maintenance of sinus rhythm without the need for antiarrhythmic drug therapy was observed in only 13 (or 42%) out of 31 patients. What stands out in our multi-center results is that the procedure is achievable in the same manner across all centers, and produces positive and reproducible results.

Why was the cryoballoon more effective in paroxysmal AF than in persistent AF patients? PVI has established itself as the foundation for treating AF and is well suited for patients with paroxysmal AF. Our study shows that PVI with the cryoballoon technique is effective in PAF. Patients remained AF-free AF throughout follow-up, which we documented with serial Holter ECG recordings and the use of seven-day event recorders. As for patients with persistent AF, it’s known that the disease progresses and the atria remodels. As a result, as multiple studies have suggested, more extensive ablation strategies beyond PVI may be required. In our multi-center study, Arctic Front was used exclusively for PVI, and additional ablations were not performed. Comparable RF ablation studies have demonstrated single-procedure efficacy ranging from 42–88%. In studies with more favorable outcomes, physicians used an ablation strategy that combined PVI and additional substrate modification techniques such as the ablation of complex electrograms, the mitral isthmus line, and the posterior left atrial line.

Were there complications? We observed two pericardial tamponades, which we treated with pericardial drainage — both resolved without the need for surgery. There were five patients with groin hematoma, two patients with femoral arterial pseudoaneurysm, and one patient with femoral arteriovenous fistula. All of these cases of vascular complications could be managed in a conservative manner. Right phrenic nerve palsy (PNP) was observed in 26 patients (out of a total of 346 patients) during cryoablation of the RSPV. In 24 of these 26 patients, PNP occurred with the 23-mm balloon; PNP was observed in only two patients treated with the 28-mm balloon. Two of these 26 PNP cases resolved during the procedure. Early termination of cryoenergy application during right phrenic pacing did not prevent the subsequent occurrence of PNP. Full recovery of right phrenic function was observed in all patients during follow-up of less than one year. In two patients, transient ST-segment elevation due to bubbles in the sheath occurred in the inferior leads without hemodynamic complication. It resolved within two minutes in both patients. In two patients (or 0.8%), left atrial flutter occurred within three months post intervention. However, these two patients were not included in the subsequent analysis of long-term successful ablation, since both cases were successfully resolved with an additional left atrial ablation procedure. There were no other atrial tachycardias or atrial flutters reported during follow-up.

Did you observe any pulmonary vein stenosis? As you know, this is a concern for many electrophysiologists when ablating with RF energy. From the literature and past experience with cryoablation, we didn’t expect PV stenosis with Arctic Front. In our study, procedure-related vein narrowing was set at 30% and up. MRIs were performed in 310 patients prior to ablation to measure PV diameters, and data for 1,222 pulmonary veins were available. During follow-up, the PV measurements of 239 patients were available, and no stenosis or a diameter reduction of over 30% was observed.

Did you observe any atrial esophageal fistula? No, we had no incidence of esophageal fistula.

What advantages does the Arctic Front balloon offer? Arctic Front provided several advantages, including easy system handling, no need for three-dimensional mapping, a reassuring safety profile, and an easy learning curve. It really offers a simplified PVI procedure compared to other systems.