A popular 19th century fairy tale involves a young girl named Goldilocks, who ventures out into the woods. She comes across a small cottage, knocks on the door, and finding it empty, enters. On a table in the kitchen, she encounters three bowls of porridge. She tastes each and finds that the first is too hot, the second too cold, and the third just right. Throughout the tale, she encounters may things in threes, all of which test the principle of finding something that is of just the right amount. This concept has become known as the Goldilocks Principle.
When considering cryothermal balloon ablation for the treatment of atrial fibrillation (AF), applying the Goldilocks principle and finding the right amount of energy to deliver has been a challenge. Cryothermal balloon ablation is not alone in this challenge; this impacts all forms of ablation currently used. However, cryothermal ablation is unique as it can homogenize operator experiences and approaches and uses discrete time periods of energy delivery. As a favorable consequence of a more simplistic technical approach, the use of this technology can be promoted to achieve similar outcomes across a broad scope of operators. As a negative consequence, without a true understanding of the principle of too much, too little, or what is just right, untoward complications will predictably rise when excessive injury is delivered.
The first-generation cryoballoon had nonhomogeneous balloon cooling with freezing primarily along the equator. In an early experience, 35 of 71 patients that underwent cryoballoon ablation for AF had recurrences of AF or tachycardia. In those patients with recurrence, 26 underwent a repeat electrophysiology study. Of the 97 pulmonary veins that were identified as treated, 67 (69%) had recurrent conduction. Recurrences typically were found in inferior segments of the vein and were felt to reflect improper alignment of the balloon and an equatorial zone of cooling. Cryoballoon modifications including optimizing the flow of refrigerant, increasing the number of refrigerant jets within the balloon from four to eight, and positioning the jets closer to the distal balloon were made for improving thermal energy transfer to the tissue and circumferential cooling of the balloon including the tip region. The device modifications favorably impacted the pulmonary vein recurrence rate in a comparative study of 206 patients, of whom 18 underwent a repeat electrophysiology study. In those that had a repeat procedure, 77% of the veins initially isolated with the second generation balloon were still isolated compared with 32% of those treated with the first generation balloon. In another small comparative study of 56 repeat ablation patients between second generation cryoballoon ablation and force-sensing radiofrequency ablation, pulmonary vein recurrences were less in the cryoballoon group (36% vs 20%).
The Goldilocks principle is in essence a "U" shaped curve paradigm. As the pendulum swings from that of "too little" toward "just right," it is very challenging to stop and not drift into "too much." For a therapy initially touted as one that minimizes risk of esophageal injury and pulmonary vein stenosis, reports of injury began to increase with adaptation of the second generation cryoballoon. In a study of 100 patients that underwent a cryoballoon ablation with endoscopy performed afterwards, 17% had gastric hypomotility and 9% esophageal lesions. In another study of 50 patients that underwent endoscopy post cryoballoon ablation, 12% had esophageal lesions consistent with thermal lesions. The impact of the new technology on the lung injury has also been examined. In an observational study of 586 patients, 33 (5.6%) developed hemoptysis after second generation cryoballoon, felt to reflect bronchial injury. This is in addition to a number of published case reports of severe pulmonary vein stenosis.
The reports of these complications reflected an augmented scope of injury from a larger and more efficient freeze zone. This larger injury should improve pulmonary vein isolation rates and perhaps augment ablation success by treating peri-vein anatomy, which can serve as sites of arrhythmia triggering such as ganglion plexi, ligament, or vein of Marshall, and so on. In paroxysmal AF patients that have implanted cardiac devices to measure continuously arrhythmia recurrence rates, 1-year freedom from the AF rate was 64% in patients treated by the second generation device. In an observational study of 281 patients with persistent AF, long-term outcomes after second generation cryoballoon evaluation were examined. The 1-year freedom from the clinical atrial arrhythmia rate was 76%, which fell over 5 years to approximately 50%. Although these rates are similar to those achieved with radiofrequency ablation catheters because the second generation cryoballoon is a more durable tool for pulmonary vein isolation, the mechanisms behind these persistently elevated arrhythmia recurrence rates need to be better understood.
In this issue of the Journal, Chang et al evaluated the role of extrapulmonary triggers and atypical atrial flutters as mechanisms of arrhythmia recurrence of second-generation cryoballoon ablation. In a propensity-matched analysis of 138 patients (69 patients that received a prior radiofrequency ablation, 69 patients that received a prior second-generation cryoablation ablation) mechanisms of arrhythmia recurrence were examined and compared. Recurrence rates in this institution between both ablation therapies were similar at approximately 23% to 28% at 1 year. Pulmonary vein reconnection rates were nonsignificantly better in the cryoballoon group, 82% vs 94%. The cryoballoon group had a significantly larger scar burden in the left atrium and had a mean lower global voltage. The significant differences in the groups were higher nonpulmonary triggers (64% vs 13%; P = 0.009) and atypical atrial flutters (55% vs. 13%; P = 0.027) in the cryoballoon group. Atrial flutter is critically dependent on an isthmus of tissue that slows conduction. Most of the flutters in the cryoballoon group were mitral annular or left atrial roof dependent and likely reflected the large ablation lesions that left a vulnerable isthmus along the posterior wall and/or mitral annulus. An interesting finding was that the nonpulmonary vein triggers in the cryoballoon group were the vein of Marshall, superior vena cava, and coronary sinus ostium that are structures often at the periphery of the enlarged freeze zone and may have been altered, but not fully ablated.
In this study a procedural approach was performed that highlights the Goldilocks principle and the quest for "just right." The operators delivered a "bonus freeze" systematically unless phrenic nerve palsy occurred. The need for a bonus freeze is largely unknown and with a therapy trending towards "too much" can be problematic, when we consider the results of this trial. This group is not alone in applying extra freezes. Bonus freezes are frequently performed in high volume centers performing cryoballoon ablation and in reported studies are part of the protocol or used without a systematic approach up to approximately 50% of the time.[8,9]
Cryoballoon ablation is not alone in the quest to find "just right" in the treatment of AF. Parallels to this discussion can be drawn when examining the data after force-sensing catheters became available for those that use radiofrequency energy. What is clear is that when tools emerge that improve the efficacy of pulmonary vein isolation, they will drive the pendulum towards increased harm as they expand thermal injury. As researcher and physicians, we must then understand this paradigm and work towards "just right."
J Cardiovasc Electrophysiol. 2019;30(1):25-26. © 2019 Blackwell Publishing