In this interview, we speak with Malte Kuniss, MD from the Kerckhoff-Klinik in Bad Nauheim, Germany, about the recent results of the CRYOTIP study. What percentage of ablation cases at the Kerckhoff-Klinik are performed with cryo energy? What percentage are done with radiofrequency (RF) energy? Why? In 2009, approximately 10-15% of ablations were performed with cryo, most of these with cryoballoon for pulmonary vein isolation in patients with symptomatic paroxysmal atrial fibrillation. Approximately 85-90% of ablations were performed with RF energy. This is the standard energy source for the great variability of ablations performed at our center. What prompted the CRYOTIP study? Recent single-center studies have shown that cryoablation and RF ablation of the tricuspid valve - inferior vena cava isthmus are comparable with regard to success rates and safety in the treatment of common atrial flutter. Some data was available showing evidence of persistence of bidirectional conduction block (BCB) in the inferior isthmus of the right atrium as an accepted indicator for clinical long-term success during an invasive reinvestigation three or more months after initial ablation. No data existed regarding invasive reinvestigation of the durability of bidirectional conduction block after initial RF ablation of the inferior isthmus, even in asymptomatic patients. Comparison of the persistence of conduction block achieved with either cryo or RF energy as a strong predictor for clinical long-term success gives information about the efficiency of ablation source used, and also gives certain insights on durability of lesions produced with cryo in comparison to RF energy. Because the ablation target is anatomically well defined, we selected common atrial flutter as a model for the comparison of the durability of linear lesions created using different energy sources. Tell us about the study methods. How many patients were enrolled? A total of 191 patients were randomized to RF ablation or cryoablation in our multicenter trial. A maximum of 30 RF applications or cryoablations was allowed to achieve the ablation endpoint, which was defined as complete bidirectional conduction block in the inferior isthmus. Invasive electrophysiological reinvestigation three months after initial ablation was available in 60 patients in the RF group and 64 patients in the cryoablation group. The primary endpoint of our study was nonpersistence of BCB and/or ECG-documented relapse of common atrial flutter within three-month follow-up. How was bidirectional conduction block verified? BCB was verified in an accepted standardized way. A 20-polar steerable catheter was inserted into the proximal coronary sinus crossing the intended ablation line in the inferior isthmus region. BCB was confirmed by demonstrating a fully descending wavefront of activation in the contralateral atrial wall during pacing at sites immediately adjacent to the line of block. Secondly, the assumed line of block was mapped for lack of any potential and/or typically well-separated double potentials. Describe the initial results. How did the two ablation methods (cryo and RF) compare? Ten patients were excluded from the analysis due to various reasons. Successful ablation was performed in 83 (91%) of 91 patients in the RF group, with achievement of the ablation endpoint (bidirectional conduction block) within 30 energy applications, and in 80 (89%) of 90 patients in the cryo group. This difference did not reach statistical significance. However, there was a difference in procedure duration, with cryoablation lasting significantly longer (120 min. vs. 99 min. in median; p<.01>How did lesion durability differ between the cryoablation and RF groups? All patients with initial successful ablation were scheduled for a repeat EP study three months after the index procedure. Because of a clinical asymptomatic status at follow up, 23 (27.7%) of 83 patients in the RF group and 16 (20%) of 80 patients in the cryo arm refused invasive follow-up. None of the 60 patients in the RF group available for analysis of the primary endpoint showed early symptomatic ECG-documented relapse of common atrial flutter, but an asymptomatic conduction recurrence in the inferior isthmus was verified in nine patients (15%). In the cryoablation group, in 22 (34.4%) of 64 patients available for analysis, conduction recurrence in the inferior isthmus was verified. This included seven patients (10.9%) with symptomatic ECG-documented relapse of common atrial flutter. Thus, 15 patients (23.4%) showed asymptomatic conduction recurrence. We also observed a significant difference of 19.4% (p=.014) in conduction recurrences between the cryoablation and RF groups. These results are indicating a lower durability of lesions achieved with cryo. What complications were observed in the cryoablation and RF groups? During the index procedure in one patient, AV block occurred during cryoablation at the septal inferior isthmus with necessary pacemaker implantation. Three days after cryoablation, one patient was observed with a clinically manifest stroke despite sufficient anticoagulation; intracardiac thrombus formation was excluded by transesophageal echo. Due to a larger sheath diameter (8F vs. 7F) for cryoablation, two patients developed groin hematoma, and one RF patient had arterial pseudoaneurysm with conservative management. Thus, the total rate of complications was 2.6%, and the rate of severe complications was 1%. The source of the stroke remained unclear. Why was the endpoint of pain perception considered significant? Cryoablation is known to be an almost painless ablation technique, which is one of the major advantages in comparison to RF ablation. As we reported previously in another trial, RF ablation was associated with an intensive pain perception during energy delivery when compared to cryo. In 89% of patients in the RF group, pharmacologic sedation and/or analgesia was necessary. For assessment of pain perception we used an evaluated visual pain scale on a scale from 0 to 100, with 0 indicating “no pain at all” and 100 indicating “the worst imaginable pain.” The median score in the RF group was 60 versus 0 in the cryoablation group, a highly significant difference (p<.01>Tell us about the differences in short-term follow-up results between cryoablation and RF. Why do you believe there was such a stark difference in symptomatic relapse rates between the cryoablation and RF groups? Significantly more patients randomized to cryoablation developed a clinical relapse; none of the patients in the RF group experienced relapse. The overall persistence of bidirectional conduction block and therefore the durability of achieved lesions in the cryoablation arm three months after ablation was significantly inferior to RF. We speculate that the low symptomatic recurrence rate after RF ablation is the result of the significantly lower rate of overall conduction recovery compared to cryo. There were no significant differences between the two groups in terms of placement of ablation lines in the inferior isthmus, which would be a possible explanation. Also, the achieved conduction delays measured during pacing at either sides of the ablation line after achievement of bidirectional conduction block did not differ between the two groups. How do you explain differences in the conduction recovery in the cavotricuspid isthmus (CTI)? Differences in conduction recovery in the CTI may be related to the differences in the two energy types applied or to differences in ablation techniques employed by the investigators. Here we can only speculate about what the specific intra-tissue reasons for conduction recovery are. Cryoablation is applied only point by point, while dragging of the catheter during energy delivery is most commonly used with RF ablation. Herewith consistent ablation lines can be created with likely reduction of late occurrence of gaps. However, the mechanism of lesion development in cryoablation depends on more factors than in tissue heating with RF. The combination of pronounced hyperemia and edema in the borderline zones of the intra-tissue ice ball, in combination with point-by-point ablation, may represent a logical explanation for the observation of a higher rate of conduction recovery in the CTI after cryoablation in comparison to RF lesions. A very late recovery of the electrical properties of stunning cells near to apoptosis and cell death may also be a factor in comparison to RF lesions. What were some of the unique attributes of this trial? Our trial is the first demonstrating conduction recovery in the inferior isthmus by invasive reinvestigation three months after cryo and also RF ablation. Clearly it is the case that a certain number of patients, even after RF ablation of the inferior isthmus, might develop reconduction in the inferior isthmus without showing clinical recurrence of common atrial flutter. Will you continue to utilize cryoablation to treat atrial flutter? With knowledge of the results of the published trials, we use cooled-tip RF energy as standard ablation strategy for the treatment of common atrial flutter for daily routine and as standard patient care. In patients in whom RF ablation can be performed only under deepest sedation or even general anesthesia because of intolerable pain perception during energy delivery, cryoablation as an alternative energy source is a very good treatment option. What advancements have been made recently in cryoablation? Have you seen a decrease in the use of cryoablation? What improvements regarding this technology do you hope to see in the near future? Published data for the ablation treatment of AV nodal re-entrant tachycardia and common atrial flutter is showing a lower long-term success rate compared to RF ablation strategies. There is new promising data published for cryoablation of left ventricular tachycardia in addition to already published data reporting good results after cryoablation of ventricular tachycardias arising from the right ventricular outflow tract. Although cryoablation might have certain advantages concerning safety and complication rates, we certainly have seen a decrease in the use of cryoablation for these arrhythmias in our center. In the future we perhaps need an increase in freezing power and some modifications in catheter design using linear tipped cryo catheters to achieve similar success rates. However, in the treatment of paroxysmal atrial fibrillation (AF), a revolutionary increase of cryoablation used for pulmonary vein isolation can be seen since the development of a cryoballoon catheter. With this anatomically guided ablation strategy for PVI, a success rate of approximately 70-75% can be achieved regarding AF-free survival. To date, no atrio-esophageal fistulas are reported after cryo-balloon ablation, and the occurrence of significant PV stenosis seems to be nearly zero, which are both clear safety advantages compared to RF energy. Is there anything else you would like to add? I’m convinced of cryo technology, its advantages compared to RF energy and its safety. However, I believe that to date the only arrhythmia that can be treated with cryo as effectively as with RF energy is paroxysmal atrial fibrillation. The cryoballoon technology will facilitate the PVI procedure because of its anatomical approach. For patients who are suffering from intense pain during ablation (e.g., for the treatment of atrial flutter), cryo is still a very good option.