Roundtable Discussion on Cryoablation Procedures

PETER J. WELLS, MD: In this webcast, we will talk about what role cryoablation can play in the practice of interventional electrophysiology. I am joined by Dr. George Van Hare, who is a professor of pediatrics at the University of California San Francisco and Stanford, and by my colleague Dr. Rajjit Abrol. Raj was a fellow here with us in EP and has now moved on to be an attending and is one of the EP faculty here at Baylor. We re going to spend the first part of this webcast covering some of the basic information about cryoablation. In order to really understand this, it s important to know the history of ablation. The first ablations performed were actually epicardial surgical ablations done in the operating room, initially under cardiopulmonary bypass where the arrhythmia target was mapped and then cryoprobes using nitrous oxide were utilized to make discrete lesions to try to cure people of their arrhythmia. Much of the basic cryobiology that we ll talk about today comes from this epicardial operating room data. Obviously, with the morbidity and expense of an open-heart approach, there was a tremendous push in the early 1980s to develop some sort of percutaneous cardiovascular access that could result in intracardiac ablation. The first research was direct-current ablation, which involved putting the full output of a defibrillator through a braided Dacron catheter this created tremendous barotraumas and excitement in the EP lab. GEORGE F. VAN HARE, MD: Those were literally exciting days. PETER J. WELLS, MD: Sometimes that shock would overwhelm the insulation of the catheter, and you d even have beautiful arcing lightning in the lab. From there we learned from our surgical colleagues that you could use radiofrequency (RF) energy. They ve used RF for decades in the operating room, in the form of electrocautery devices. Catheters were developed in the early 1980s, and the first successful human RF ablation using a catheter was performed in 1985. It s a very effective energy source. However, the history of cardiac ablation doesn t stop with any one modality, and in 2007, you can see that we ve advanced quite a bit. We can now deliver cryothermic energy through catheters and balloons. We can also deliver ultrasound energy through balloons, laser energy through fibers, and microwave energy through antennae. We can also deliver ethanol either directly into the target of an arrhythmia or interrupt its blood supply. Even more recently, we are now able to make bigger RF lesions by using catheters that have needles in them. GEORGE F. VAN HARE, MD: I should point out that many of these forms of energy delivery or catheter ablation techniques are not yet in clinical use, but they are in development. I think we ll all be seeing these technologies in clinical practice at some point in the future. PETER J. WELLS, MD: Correct. Cryo, of course, is one approach that is now available for use in clinical practice. Other advantages such as three-dimensional (3D) mapping technologies, in which we build a geometric model of a cardiac chamber in which we want to ablate, facilitate identifying the site of origin. In addition, there is intracardiac imaging with ultrasound catheters, which is very important in order to see normal cardiac structures. Of course we haven t yet mentioned magnetic navigation and robotic arm type devices, in which we don t even have to be in the EP lab to use! So quite a bit has happened in the field of EP. Now we want to spend some time focusing on cryoablation. Cryoablation catheters come in 7 and 9 French (Fr) sizes. There is a wire that is connected to each electrode as well as a deflection wire, which makes the catheters steerable. There is also a thermocouple that is connected to the distal electrode so the temperature can be monitored. To create a lesion, high pressure liquid nitrous oxide is pumped down the injection tube and when it changes into the gaseous phase, absorbs heat and lowers temperature. Typically the temperatures that we reach with nitrous oxide are on the order of about -80 degrees Centigrade. To set up for a case, we hook up the electrical connection, much like you would with an RF catheter. After that we connect the coaxial cable, which transports and vacuums the nitrous oxide back. These are connected to the CryoCath console. Once the coaxial cable is connected, the console will recognize the catheter and know how much nitrous oxide can be delivered. You will see a digital readout of the temperature on the left side of the screen with timing right below it, in blue numbers. Once we ve come on with cryo, you will see a very steep descent of the temperature/time curve down to a minimum value typically of -70 to -80 degrees Centigrade. GEORGE F. VAN HARE, MD: Remember, the larger the tip, the lower the temperature goes. PETER J. WELLS, MD: The 4mm catheter can be operated in a temperature control mode where the refrigerant is adjusted to maintain the temperature at -30 º C in the cryomapping mode. However, the two larger catheters operate in flow mode only, where they drive the temperature all the way down. Unlike RF ablation, cryoablation extracts heat from the tissue. When the electrode is in contact with the endocardium, it is absorbing heat, and that produces a wavefront of cooling. The coldest temperatures are in direct contact to the electrodes. Therefore, in contrast to RF, where you can get very hot temperatures deep in the tissue, this tends to be a more controllable energy source. If the energy is delivered for a short period of time with temperatures that are -30 degrees or warmer, then that is considered the mapping mode, and we don t typically create a lesion when we do that. If we get cold enough for long enough (i.e., -70 degrees Centigrade for more than 60 seconds), then we are out of the hypothermia cryomapping mode and are producing lesions. GEORGE F. VAN HARE, MD: The other important feature at -30 or -35 degrees is cryoadhesion, in which the catheter actually sticks to the myocardium very tightly; this is a very important feature that does not happen with any other energy source. RAJJIT ABROL, MD: It is important to point out the mapping features available on the 4mm, 6mm and 8mm catheters; we may not necessarily refer to it as ‘mapping , since what we are doing is freezing the tissue in the range at which it is still reversible. With the 4mm catheter, it doesn t get below 30 degrees if you re in the mapping mode. We ll talk about this later with the different catheters. PETER J. WELLS, MD: Cryomapping is a very important feature that unfortunately we do not really have available to us with RF. What happens when we decide to create a lesion? When discussing how a typical cryolesion compares to a typical RF lesion, we ve come up with a crude rating scale to assess several different aspects of the lesion; we ll talk in a moment about why that is clinically important. First of all, if you compare a cryolesion with an RF lesion (Figure 1), a cryolesion is much more dense and homogeneous. An RF lesion is not as homogeneous and dense a lesion as with cryo. Secondly, and this is very important, particularly for ablation on the left side of the heart, the endocardium on a cryolesion is very thin, it stains blue, and there is just a slight amount of thrombus there. However, the endocardium is largely intact, which minimizes the risk of thrombus. On an RF lesion there is fibrinoid necrosis of the endocardium and quite a bit of adherent thrombus, and so this is another advantage of cryo being relatively sparing of the endocardium. Thirdly, cryolesions tend to be less arrhythmogenic; this is predominantly related to the border of the lesion. If you were to analyze the border of these two lesions, you would see that the border of the cryo lesion is very sharply demarcated, whereas there is a relatively non-homogeneous border to the RF lesion. This is an important factor. It was found early on that this density and homogeneity tended to be non-arrhythmogenic, whereas if there were surviving strands of heart muscle and fibrotic tissue, arrhythmias (particularly late arrhythmias) could occur. RAJJIT ABROL, MD: If you think about arrhythmogenesis when we talk about cryo and the different arrhythmias that you re going to use it for (e.g., AV node reentry, atrial fibrillation, atrial tachycardia), as well as the non-arrhythmogenic factor, you need to look at previous studies that describe late recurrence of arrhythmias. A lot of times if you treat one arrhythmia with RF, there is not an inconsequential number of different arrhythmias that come about later on. Therefore, I believe the non-arrhythmogenic factor is hard to see in the short term when you are following up the patient, but when you follow up with patients five to ten years later, especially those patients with AV node reentry, it is possible that those sites that end up giving you atrial tachycardias and other dysrhythmias, that cryo would potentially give you less of that. PETER J. WELLS, MD: Lastly, preservation of myocardial tissue strength is very important. If you compare the two lesions, the structural proteins such as collagen and the cytoskeleton of the cell are denatured with RF ablation. Therefore, if you have just made an RF lesion and are continuing to push, for example, on the left atrium with the catheter, you actually have weakened it structurally, and so potentially the risk of cardiac perforation is higher. However, with cryo, the structural proteins are preserved, therefore the risk of perforation would potentially be less. What does that mean as far as clinical benefits? First of all, you can look for reversibility of the effect that you want. We ll allude to this more later and show you some examples where one can observe for both the therapeutic as well as the adverse effect before either are permanent. If you like what you see, it can be converted to a lesion; if not, you can come off. We are not afforded this luxury when we perform cases with RF. Secondly, as George alluded to a moment ago, once the cryocatheter electrode temperature reaches about -30 degrees, it becomes adherent to the endocardium so catheter stability tends to be better, particularly with right-sided accessory pathways where the tricuspid annulus is being tugged quite a bit. Next, we ve referred to the well-demarcated homogeneous lesion, and Raj made the point about late arrhythmia recurrence, which certainly is a concern with as many as 30% of people at 10 years experiencing either late heart block after ablation for AV node reentry or some new arrhythmia. Also, there is reduced patient discomfort during the procedure. We all ablate in sites that are very tender to the patient such as the area around the mouth of the coronary sinus, the isthmus, or the area around the sinus node so if patients are not fully anesthetized, they can experience significant discomfort with RF; however, this is not the case with cryo. The connective tissue matrix we referred to a moment ago is left intact and therefore we do not get burning, charring, or steam pops that can predispose to perforation. The other advantage to cryo is that there is a very precise ablative effect. I think many of us have learned over the years that the RF catheter tends to paint the endocardium during an ablation, meaning it tends to move. To some extent, that actually generates a bigger lesion, and so that may be a good thing, but on the other hand, it gives you a little bit less precise of an ablative effect. What are the implications? Obviously there is less risk of inadvertent AV block if you are working near the AV node, either with slow pathway ablation or ablation of an accessory pathway that is near the AV node. You can predict a successful ablation by the results of cryomapping: the catheter stability is better, there are probably going to be less late arrhythmias, and there is a reduced risk of embolization of thrombotic material. In addition, since it is more comfortable, you need less sedation, which can be important for COPD patients or patients that don t want to be put under. There is also potentially less risk of perforation, and there has never been, as far as I m aware, a single case of pulmonary vein stenosis with cryo. RAJJIT ABROL, MD: Clinically significant pulmonary stenosis. PETER J. WELLS, MD: Correct clinically significant pulmonary vein stenosis is another potential advantage if we are ablating in the left atrium, near the ostium of pulmonary veins. Those are all either advantages or potential advantages, but there are some concerns as well. One concern is that the efficacy of cryoablation potentially is not as great as with RF ablation. That is a concern, and we ll discuss that later and talk about what sorts of things can be done to maximize the efficacy of cryoablation. GEORGE F. VAN HARE, MD: I just want to make one point about the sedation issue. When you do a procedure that causes pain, I think the patient s autonomic state becomes a moving target. We ve all seen situations where a patient wakes up and experiences sinus tachycardia, and if you re addressing an arrhythmia that is very dependent on autonomic activity, like AV node reentry, your baseline state is no longer present. Therefore, by using something that doesn t cause pain, you get a much more steady situation autonomically. RAJJIT ABROL, MD: We ve listed a number of advantages to cryotherapy, but being a recent fellow myself, it s very often that I also talk to patients about what the risks or disadvantages of a therapy are compared to the advantages. If we can list a number of things that potentially give us the advantage of using cryotherapy, ultimately patients will say, We can t have heart block, and maybe you can t have these other tissue-related phenomenon, so what s the downside? The downside so far that we ve seen is the efficacy, meaning, whether or not the person will have to go through a repeat procedure. The second thing that we ll address is the actual time of the procedure, with four-minute lesions as opposed to shorter lesions with radiofrequency. However, looking at the clinical data that we have right now for cryo, the largest cryo trial reported was in the HeartRhythm Journal in 2004.¹ It was a prospective registry called the FROSTY trial, and it covered 14 centers three in Canada and 11 in the United States. There were 166 patients in the trial. The arrhythmias studied in the trial included AV node reentry, ORT or ART, and atrial fibrillation, of which patients underwent AV junction ablation with a 4mm catheter. The cryomapping option was available at that time with the 4mm, and was performed at -30 degrees Centigrade for less than 80 seconds. The cryoablations were then done for four minutes with no refreeze. Another point to make about what we have learned using cryotherapy is that by putting in a freeze, thaw, and refreeze, you can actually get a more permanent, more stable lesion than just doing a lesion in and of itself. It s possible to explain the results of the FROSTY trial based on the fact that they just did a freeze but no refreeze. The endpoints for the FROSTY trial, which were understandable, were not exactly the endpoints that we use clinically in the lab. They used acute success as less than 15 seconds of supraventricular tachycardia (SVT) or the development of complete heart block (which is an endpoint in the lab). If you develop complete heart block, you must quit. However, if you had less than 15 seconds of SVT, with or without isoproterenol, then chronic success was looking at no recurrence at six months. If you look at the outcomes of the FROSTY trial data, the AV node reentry group of 103 patients had an acute procedural success of 91%, with a confidence interval between 84 and 96%. Of the ORT and ART patients with accessory pathway tachycardias, there were 49 patients with acute procedural success at 69% using the 4mm catheter. The numbers here are about what people quote when referring to the success of cryo. They ll say, Well, if I m going to use cryotherapy for an accessory pathway, for instance, the best success rate I m going to get is 75%. If you look at the way the trial was set up and what we do now with cryotherapy, using larger catheter tips, doing freezes, thawing in the same spot, refreezing in the same spot, and also getting an idea of what the signal should look like on the monitor for AV node reentry, the procedure times that are reported in previous trials as well as the success rates would potentially be different. GEORGE F. VAN HARE, MD: I just want to make the point that I find it interesting from this trial that even when they set out to attempt to cause heart block, they only succeeded two-thirds of the time. PETER J. WELLS, MD: It s reassuring. RAJJIT ABROL, MD: If you look at one electrogram tracing courtesy of Dr. Friedman showing the cryo at 6.25mm per second speed, you see the cryotherapy comes off on somebody who developed a 2:1 heart block, and in a short period of time, the conduction comes back. You know, I can t emphasize enough as a young electrophysiologist going into practice that cryotherapy has really made these procedures extremely comfortable for me. It took a lot of procedures during my fellowship over 50 AV node reentry cases with cryotherapy in order to learn exactly how to use the catheter. It also took a while for the entire lab staff to learn how to use it because it is distinct from RF. Knowing that if you do inadvertently get a fast pathway in a spot where you think you re ‘safe , using cryotherapy and seeing connections come back is extremely comforting to a young electrophysiologist. You don t want to be known as the guy who is giving everybody heart block with ablations! Consenting with patients is also extremely important. When giving patients the alternative of RF versus cryotherapy, in which their chances of a repeat procedure or the possibility that they may end up with a pacemaker is higher, I think that the choice for cryotherapy for those patients becomes pretty easy for them. It s not uncommon that a patient will ask me Why would you even use radiofrequency? I use cryo for almost all of my AVNRT cases. PETER J. WELLS, MD: This efficacy issue was a problem. There have been two randomized trials, both conducted in Europe, and this is one that was published by Zrenner where patients with AV node reentry were randomized to either RF or cryo, again with the 4mm catheter. The endpoint of this study, which I think raised some concern about efficacy, was a composite endpoint. The endpoint was either no acute procedural success, development of complete irreversible heart block, or recurrence of SVT. The interesting thing is that the acute procedural success was very similar between cryo and RF although there was one case of AV block with RF and none with cryo so what really drove this endpoint was recurrent SVT. The efficacy issue is germane let s address that. GEORGE F. VAN HARE, MD: If you notice, we are still seeing recurrences beyond 180 days. What the FROSTY trial defined as success was 180 days without recurrence. Here we re still seeing them beyond a year, so if you are cautioning patients about the possibility for a recurrence, make sure that they know it could still happen beyond six months. PETER J. WELLS, MD: Excellent point. Okay, so just a summary about efficacy: the FROSTY trial in 2003 had a 91% acute procedural success. Then came the European trial, and finally, a single-site registry in Sweden where a 6mm catheter was used.² The acute procedural success is now up to 99%, and the recurrence rate, although still maybe a bit more than we would expect with RF, is certainly better. This raises the question of best practices, also in pediatric patients. GEORGE F. VAN HARE, MD: It s my turn to talk a little bit about pediatrics. We really jumped at the opportunity to use this technology when it first became available. However, it is important to remember that when we talk to our patients, we re also talking to our patients families. It s much more difficult for a parent to give permission for a procedure for their child than it is for them to give permission for a procedure on themselves. The possibility of heart block, I think, loomed very large in the parents of our patients, and so being able to offer them a procedure that perhaps would have a higher recurrence risk but would clearly have a lower risk of heart block was a major advantage. To date, in about 189 procedures at our center, our overall success rate is 93%, which is pretty good. The recurrence risk is about 9%, which is a little disappointing and certainly higher than is reported for the RF ablation registry that we did over approximately 15 years. Also importantly, there was not a single case of persistent AV block in any of these patients. We do worry about the coronary arteries in children using RF, but there are no incidences of coronary injury using cryoablation in this series. RAJJIT ABROL, MD: George, in terms of recurrence rates, do you know the mix between the 4mm and 6mm catheters? GEORGE F. VAN HARE, MD: Yes, most of the recurrences were with the 4mm catheters. PETER J. WELLS, MD: So how can we maximize cryo? We ve had decades to maximize RF, and hopefully that process is still ongoing, but how can we maximize the use of cryo? That involves what we call cryo best practices. The first thing is that cryoablation, just like RF ablation, is a contact-dependent energy source. If you look at making lesions, the more contact force you have with the catheter in general, the larger lesion you have not only that, but the larger electrode you have, the larger lesion you make, similar to RF. There are 4mm, 6mm, and 8mm electrode catheters; as you get a larger electrode, in general you will get a larger lesion. Also, the electrode orientation is important. If we re orienting the electrode perpendicular to the endocardium, we get a lesion of a certain depth. If we orient it parallel to the endocardium, we get the same lesion depth but typically more diameter, and therefore a larger lesion size, so in general we try to orient the electrode parallel to the endocardium rather than perpendicular. Also, the increased duration of the freeze affects the lesion size, and this is dependent on both the time that the catheter is on and how big the catheter is, but in general, the longer you freeze in some animal studies as long as eight minutes the bigger the lesion does tend to get. Therefore, we want to try to freeze for a long period of time. Also very important is that the refreeze after thaw increases lesion size. We re not exactly sure why this is, but it may have to do with interruption of the microcirculation such that the second lesion is met with less resistance from conductive heat because the capillary network has been destroyed. Thus, it s very important to consider those if we re going to maximize effectiveness. We should also discuss how the lesion sizes vary with 4mm, 6mm, and 8mm catheters. There are no dimensions on this, but I think all of us would agree that CryoCath s Freezor catheter, which has a 4mm electrode, produces a very small lesion. We have not had much luck getting this to work at least in adults, although George I understand you still do use it some in children. GEORGE F. VAN HARE, MD: Yes, for sure. PETER J. WELLS, MD: The 6mm catheter generates a lesion that is maybe not quite as big as a 4mm RF lesion, but pretty similar in size and depth. The 8mm catheter almost certainly generates a lesion that is approximately the size achieved with an irrigated RF catheter, which is quite a bit bigger that is something that is important to remember as far as lesion size. The next thing that is very important is time to effect. Cryo is a very precise technology, so you really want the catheter to be right on top of the target in order to have it work. So if the target arrhythmia disappears before -30 degrees we ll discuss examples of cryomapping in a few minutes that is considered excellent, because you are in very close proximity to the arrhythmia target. If it doesn t go away until you re down to -70 degrees having been on for about 20 seconds, that is still okay, but once we get past 20 or 30 seconds, it means that it s really kind of a marginal position, and the catheter should be repositioned and tried again. GEORGE F. VAN HARE, MD: I think also what people have found is that even when the lesion is acutely successful with time to effect beyond 20 or 30 seconds, that pathway is coming back. RAJJIT ABROL, MD: It s not unlike RF, though. We also look at RF and the time that it takes for RF to work with eliminating accessory pathways. Very often if it takes more than 5 to 8 seconds for RF to work, then the chances are that pathway may recur as well. PETER J. WELLS, MD: Right. We have an example of this phenomenon. One of the two cases we did here in preparation for this is this concealed accessory pathway. The cryo is already on, and there is a white hash across the bottom third of the screen; we ve just induced SVT, which is going down the AV node and up this left lateral pathway. Now we re out to 30 seconds, then 40 seconds, and we didn t really have an effect. So that is something that needs to be noted. GEORGE F. VAN HARE, MD: The key point to keep in mind is that when you re at a spot and you re not getting success within 20 or 30 seconds, you don t need to go the full four minutes. In fact, you should come off, reposition your catheter and try again. RAJJIT ABROL, MD: Here is the important thing to note between the 4mm and 6mm catheters: if you re doing pediatric EP, you have the mapping option available with the 4mm catheter where the temperature will go to -30 degrees; stay there, you can see time to effect, and if you re in a good spot, then put in a full lesion, which is what I m sure you do with your kids. As opposed to using the 6 or the 8, as we ve described, by doing 20- or 30-second cycles, finding an endpoint, and targeting that endpoint. If you find that endpoint in the first 30 seconds, then continue with the full four-minute lesion, and thaw and refreeze at the same spot. PETER J. WELLS, MD: Right. We should also mention the importance of single versus double freeze cycles, either for lesion depth or lesion diameter. If the time is short, then refreezing does significantly increase the lesion size, whereas if time is long, there tends to be a slight increase in lesion volume, but not dramatic. One important thing to note, which Raj discovered here at Baylor, was that if you re in the same place, the refreeze time to nadir temperature is much faster than on the initial freeze. We think that this initially tells you that you re at the same site, which is absolutely where you want to be. RAJJIT ABROL, MD: George, how long do you wait between freezes and refreezes as many people have different timeframes? GEORGE F. VAN HARE, MD: Thirty seconds. RAJJIT ABROL, MD: Thirty seconds of thawing. The concern now is during that 30 seconds of time of whether or not you stay in the same spot to refreeze. In the time to effect back to minus temperature, it s quite quick, about 14 seconds or so. We ve noticed that if the catheter is moved to a different spot, it takes longer for that to come up, even if you come back to that spot again a few minutes later, you can refreeze in the same spot and it comes down quickly. We also look at the time it takes to thaw to predict how much of a consistent lesion you have. PETER J. WELLS, MD: Right, so with that information in mind as far as best practices for cryo, let s now discuss AV node reentry, which is the hallmark arrhythmia for this device. George, why don t you bring us up to speed on pediatrics? GEORGE F. VAN HARE, MD: First just a couple of comments on technical aspects about how to do this kind of work in children. We do most of our patients under general anesthesia, and this means that AV node reentry is often not inducible. Therefore, we end up having to use isoproterenol to induce it, and we get what we call the Goldilocks phenomenon, which means sometimes too much, sometimes not enough, and sometimes just right. Trying to achieve that dose of isoproterenol that will allow you to repeatedly induce sustained AV node reentry, so we test a number of different doses. We find that the strictly defined jump in AH interval a 50 msec jump in A2H2 in response to a 10 millisecond decrement is often not present in children and even teenagers, and so we actually substitute this other criterion which we call PR greater than RR (or crossover). It s an essentially consistent or persistent conduction down the slow pathway so that the conduction essentially skips an R wave. We do obviously like to make a diagnosis, and the fastest way in our lab to do that is to rule out atrial tachycardia by terminating this from the ventricle without advancing the A. I didn t make this point before, but in the large multicenter RF ablation series in children, we found that the risk of heart block was 2% for RF; we think 2% is too high in children. RAJJIT ABROL, MD: On the isoproterenol issue, I think it s extremely important to point out also that with RF cases, we try to induce and not get induction, induce them on isoproterenol, turn off their isoproterenol, come back in the baseline state, and then potentially chase targets that may or may not exist in the baseline state, then go back on and off isoproterenol. Cryotherapy is excellent because of the adherence and the controllability, especially with the 8mm tip catheter. It s not uncommon to do AVNRT cases on isoproterenol or at least even a little bit of isoproterenol so that you can look for those endpoints. GEORGE F. VAN HARE, MD: You could certainly run isoproterenol with an adhered catheter and test during the lesion. First a couple of examples: one patient did not have sustained tachycardia in a baseline state under anesthesia, but we could get two to three beats of non-sustained tachycardia. Nonetheless, we went ahead. Here we show the unusual occurrence of retrograde dual AV node pathways. This is somewhat helpful in certain cases. It allows you to map that slow pathway a little bit better. In this case, by giving isoproterenol we were able to induce sustained AV node reentry, so the last paced beat is actually not the R wave following the last stimulus artifact but is in fact the next R wave. This is PR greater than RR, or as you say, crossover. It is a very characteristic finding for induction of AV node reentry and the presence of a slow pathway. One important point that we need to make is that the electrogram morphology that we seek for a successful site is in fact different than what we were all taught to use for RF. With radiofrequency, we ve usually used an AV ratio on our ablation catheter of 1:2, hopefully with a Haissaguerre potential, a little bump between the A and the V. However, what we ve found through trial and error using cryoablation is that we get better results if we use a higher AV ratio. In other words, an AV ratio of about 1:1. One thing that we find useful to do in children and in large children and teenagers is to image the coronary sinus directly. This is an LAO view of an injection through a 7 Fr lumen decapolar catheter in the coronary sinus. This is useful in LAO view because it actually identifies where the coronary sinus really is in relation to the coronary sinus electrodes. You might have imagined that the coronary sinus was adjacent to CS 9-10, but this injection in fact shows you that it s adjacent to 7-8. It allows you to go to the septum with your catheter. To show the ablation catheter location in RAO view, we ve placed this 6mm catheter through a positioning sheath (a Daig SR0), and in this view, we are adjacent to the AV annulus. In the LAO view, we are just above the coronary sinus. This is actually a different case than I showed you with the injection in the coronary sinus, but you get the sense of how adherent the catheter is to the myocardium with that electrogram. It s not moving around too much. Or I should say, it s moving exactly with the coronary sinus, which means it s nicely adhered to the myocardium. PETER J. WELLS, MD: Why don t we stop at this point and field a question from the audience? RAJJIT ABROL, MD: Okay. The first question I have from the audience is: What catheter do you use for AV node reentry ablation, and what can you say about the stiffness of the different catheters? GEORGE F. VAN HARE, MD: I can start off. I think that as a pediatrician, I find the fact that we have multiple tip sizes to be an excellent feature. There are situations where I want to make sure I make a very small lesion, so if I have to do AV node reentry, say, in a 4-year-old who might weigh around 20 kilos, I m very happy about the availability of the 4mm catheter. But for anyone over the age of 12 or 13, I m using 6 and often 8mm catheters. The stiffness is an important feature, and you need to know about that. We will occasionally see transient AV block due simply to catheter contact. The catheter is quite a bit stiffer than the RF catheters that we re used to using, and it s changed our approach. Instead of placing the catheter, finding the His potential and then curving the catheter down, as we might do with a radiofrequency catheter, I actually teach our fellows to place the catheter in the right ventricle and then go clockwise to the slow pathway region rather than getting anywhere close to the region of the fast pathway. PETER J. WELLS, MD: Raj, do you want to speak about adults? RAJJIT ABROL, MD: For the AVNRT cases, I usually use a 6mm catheter just because I m more comfortable with using it. I think over the course of time, I m going to start using the 8mm catheter more often. I think the stiffness of the 8mm catheter has kind of scared me again, being a young electrophysiologist and I don t want to have complications with tamponade or anything with a stiffer catheter; bumping the node can obviously be an issue with that as well. I m sure it s a much bigger issue in pediatrics than it is for us, but when I use a 6mm catheter to do AV node reentry, I usually use an SRO sheath like Dr. Van Hare had. For the few cases that I ve done with an 8mm catheter we did a series of AV junction ablations with the 8mm I haven t had to use a sheath because that catheter is extremely well positioned and is able to maneuver very well in the posterior septum. In fact, there is something that you can do that I just learned recently: disconnect the coaxial cable from the catheter itself to try to get maneuverability with the catheter in the 8mm catheter this can help if you think it s going to be very stiff. So there are different things you have to learn about this technology in order to help you use it, because it s extremely different from RF. How about you, Pete? PETER J. WELLS, MD: Well, George, you may want to speak to this. We here at Baylor have never taken these catheters retrograde across the aortic valve, but I think you re braver. You ve done it with the 4mm catheter, have you not? GEORGE F. VAN HARE, MD: Yes, I did it once or twice when cryoablation first came out, before the information about the high recurrence risk with accessory pathways came along. I generally don t do that any longer. I use cryoablation for AV node reentry and for any pathway close to the AV node or close to a coronary artery where I m worried. I m not really using it for left-sided pathways any longer. There is an excellent question that has come in by email which I ll read: I would like to clarify an implication made by the presenters. Just because a cryomapping test does not show AV delay does not mean that the following freeze will be safe, i.e., will not produce AV node or His bundle damage. The sensitive tissue can be just outside the effective zone of a partial freeze but become included in the ice ball as the temperature drops and the ice ball grows to full size subsequently, damaging the sensitive tissue. I would entirely agree. I would say that one excellent habit to get into if you are using cryoablation for AV node reentry or any time you are close to the AV node is your eyes do not leave the screen during the entire four minutes of your lesion. You need to watch, because we have occasionally seen patients at three and a half minutes have their PR interval start to prolong. We use a mapping feature on the GE Prucka system that allows us to see within a beat whether the PR interval has prolonged even as much as 5 or 10 milliseconds; when that happens, we immediately come off. Often what happens then is that the PR gets a little bit longer while we re waiting for the ice ball to disappear, and then in every single case so far, the PR interval has tightened up and gone back to normal. The important point is that even though it seems like nothing is happening because you can take your hands off the catheter, you need to keep your eyes on the screen at all times because as that lesion grows, it can start to involve high-risk areas. PETER J. WELLS, MD: Yes, although the nice feature about that is as the expanding hypothermia wavefront encroaches on the tissue, it does so at about 0 degrees Centigrade, so if the PR is getting longer, then immediately when we come off we haven t yet reached -70 degrees at the AV node, we re only at 0 degrees. That is very important. Here is a question: What if you don t have clear endpoints with cryo? What do you do without junctional tachycardia? That is a great question. You know, this is one of the criticisms of cryo; the use of cryo in AV node reentry is that junctional tachycardia or accelerated junctional rhythm (AJR) is a very good indicator of where the slow pathway is. It s not as 100% as we think, but it s probably about 90% specific. That is, about 5% of the time, you can actually ablate the slow pathway without AJR, but it s pretty specific. For those of us who have been doing RF ablation for a long time, it definitely provides some comfort that we re in the right spot. Not only that, it affords us the opportunity to look at retrograde conduction, so when you have accelerated junctional rhythm, it s going up the fast pathway, and if we ever see retrograde block up the fast pathway, we come off right away. So not having AJR is a limitation, but I don t think it s an insurmountable limitation. For example, if you look at one of the cases we did here at Baylor, the second from the bottom electrogram is the distal ablation. This is a little bit different than what George was saying, although we typically do look for AV ratios of about one, but you can see the atrial electrogram is quite a bit smaller than the ventricular electrogram. This is a cryomapping case, so what we do is come on with cryo, stick the catheter to the endocardium, and usually that happens at about -30. However, if you re looking on fluoro, you can see there will always be a little discordant motion with the catheter and the endocardium until it sticks, so as soon as it s stuck, now you can see all the hash, which is artifact that is on the distal ablation signal. Then we ve already practiced pacing and putting in this single atrial extra stimulus that you can see goes down the slow, up the fast, and induces AV node reentry. We know this will happen every time we do it: so we come on with cryo and induce AV node reentry, and five beats later, it terminates. It s important to know that it terminates with an atrial electrogram, so that means that we re blocking in the slow pathway. As soon as we terminate, we don t just sit there and congratulate ourselves. We do the identical activation sequence again that induced AV node reentry. The identical PAC now blocks in the slow pathway. So cryomapping is useful. In the FROSTY trial not all investigators used it, and some of them believed that it was not all that predictive of a successful spot. We use it routinely, though. George, what about in pediatrics? GEORGE F. VAN HARE, MD: Certainly when we have a 4mm catheter, we would. PETER J. WELLS, MD: Okay. Now sometimes we don t have those kind of endpoints, and this is what George alluded to earlier, the idea of crossover. Here you can see two atrial paced events (Figure 2), and the last atrial paced event crosses over from the QRS nearest to it and goes to the next one. Now, if this is your endpoint for slow pathway ablation, then after you cryoablate the slow pathway, you pace again at the same cycle length. We re pacing at the same cycle length and we really can t generate that long AH interval anymore because the slow pathway is gone, so we don t have PR longer than pace cycle length, we don t have crossover, and that is a successful site. There is also a case we did of a patient who had already had an RF ablation for AV node reentry; we had an EKG in our hands after that procedure that showed what we thought was clear slow/fast AV node reentry, but sure enough, once we got to the lab, even with the patient wide awake, this was all we had, a single echo. You ll notice that this was a bit of a different case in that we had ablated where we thought the slow pathway should be and we really couldn t get it. Therefore, we actually had to search for the posterior leftward AV node extension, which is about 5 to 10 millimeters inside the mouth of the coronary sinus, so you can see a much bigger atrial than ventricular electrogram. Here was our echo (Figure 3) this was all we had to map with. Here it shows the successful ablation site (Figure 4). You can see the two electrograms from the bottom and how big the atrial electrogram is twice as big as the V. This is inside the coronary sinus. Post-ablation, we put in the identical PAC and we don t go down the slow pathway. I will point out that there is after that atrial extra stimulus an HV, but you can see that if that is conducted, the AH is something on the order of 500 milliseconds, so that is actually just a junctional beat after we block in the slow pathway. RAJJIT ABROL, MD: Speaking of endpoints in AV node reentry, I ve noticed over the course of time of doing these cases that because you don t get junctional tachycardia, you actually have to come up with a number of different potential endpoints to check. With the four-minute lesion, you can check for the different types of endpoints, whether it be a change in wenckebach cycle length, induction of tachycardia, with a different cycle length, or with or without isoproterenol. That is part of the process of learning how this technology works, how you can use it. It s different than RF technology. If you really want to succeed and improve on the numbers that we talk about for AV node reentry, you have to know that you have to put in freeze, thaw and freeze cycles, and you have to know what your endpoints are. To be perfectly honest with you, as a young electrophysiologist, using cryo has helped me improve my EP knowledge of what the endpoints are for AV node reentry and so on and so forth. Of course, I can use RF and get junctional tachycardia and see that the slow pathway is gone, but with this, the precision of this technology and as you learn it, you learn that you re getting things better. GEORGE F. VAN HARE, MD: Here is a question from a pediatric cardiologist: Have there been any reported cases of late occurrence of complete heart block after AV node reentry cryoablation? I think the answer to that is not that I know of, although we ve heard a rumor from this person s institution of a patient with other major medical problems who developed a late occurrence of AV block. If it happens, I guess it s not surprising that one might occasionally have that. There is some inflammatory response that occurs with cryoablation although very little but if it does happen, I think that the incidence is going to be quite a bit lower than what we would occasionally see with RF. The second question is: What does the occurrence of transient AV block during the case mean for long-term follow-up? PETER J. WELLS, MD: We see transient AV block commonly, and I think one of the advantages of cryo is that when you use it enough, you realize that transient AV block is not anything bad. As far as the adult literature, I think there have been two pacemakers implanted in adults out of about 15,000 worldwide cases. For transient AV block, we probably see, what do you think, 10% of the time? RAJJIT ABROL, MD: Probably. PETER J. WELLS, MD: It almost always just lasts a few seconds, and as George very aptly put it, this is not a technology where you get lulled to sleep. I remember we did a four-minute freeze I think you may have done this case with me. RAJJIT ABROL, MD: Three and a half minutes in... PETER J. WELLS, MD: Yes, three and a half minutes into the refreeze in the identical location, we got heart block. So this is definitely not a technology that you go to sleep when you re using it, but a transient AV block virtually never causes permanent AV block. GEORGE F. VAN HARE, MD: The question, I think, is whether the outcomes might be better with AV node reentry if you in fact push the envelope some. I ve often wondered about that. I don t really know the right answer. PETER J. WELLS, MD: That brings up the point about if all you have are single AV node echos, then if you re using RF, your only endpoint is junctional tachycardia, which tells you that you re in the right place. The problem is that not infrequently after you get junctional tachycardia, you still have a single echo. So it s very difficult to know when you don t have very clear endpoints how aggressive you can be. Whereas with cryo, you know that you can, as George puts it, push the envelope a bit because the likelihood of complete, permanent AV block is very low, although you may see transient AV block. What happens if you ablate where you think the slow pathway is, and let s say you can t get it. Well, with cryo, the very first thing we do here at Baylor and George, you chime in as well is we tend to pull back toward the compact AV node. Now, we don t do that in any sort of cavalier fashion. We re very careful about it, but as George showed, the higher AV relationship, particularly if you ve started at more of a traditional RF site with a small A big V, is important. Therefore, the very first thing we do is pull back until that AV relationship is at least 1:1. What if that doesn t work? This is just our practice, but we tend to then go inside the mouth of the coronary sinus and look for that posterior leftward AV node extension that Anton Becker and Sonny Jackman have so elegantly described. If that doesn t work, what we typically do as a last resort or actually,as a second-to-last resort is to go north up the septum toward the compact His bundle, understanding that it is very difficult to produce complete heart block with cryo, so the technology is reasonably safe. The last thing I would say, which we ve never actually done with cryo, is to go retrograde. We do this with RF. You can go retrograde across the aortic valve and come down to just below the His bundle, which puts you right across the septum from where you ve been working for the past hour. Frequently you can get accelerated junctional rhythm there and effective slow pathway ablation there as well. GEORGE F. VAN HARE, MD: I think the issue of the left atrial extensions of the compact AV node is really interesting. Certainly some of our cryo and RF failures for that matter are probably patients who had that problem. Mapping that location is of course a challenge. If you have the advantage of having demonstrated a retrograde jump, you can then map the earliest retrograde atrial activation. If you find that a centimeter into the coronary sinus, that is your hint that that is where you re going to go. The other possible thing is if you should be fortunate enough to induce an atypical AV node reentry, where you re actually coming up the slow pathway, you can then go ahead and map that. The very few cases that I have addressed that issue knowingly have been situations like that. PETER J. WELLS, MD: Right. So don t miss the opportunity with AV node reentry just because it s a nodal pathway to map earliest retrograde atrial activation. That is somewhat of a lost art, I think. We have another question: What is the role of cryoablation for accessory pathways? You know, one of the real benefits of cryoablation is in the area of pathways that are right on the His bundle, the so-called parahisian pathways, which we here would define as at least a 100 microvolt His deflection when the catheter electrode is at a site that is recording the accessory pathway potential. Traditionally those have not fared well with RF, and this is for a couple reasons. One is that efficacy and safety are linked in that procedure. In other words, you can get the pathway with RF, but you ll probably also produce complete heart block. It s this balancing act of Well, how close can I get? How many watts, what s the temperature? that leads to low efficacy rates and higher recurrence rates. With cryo, that is a good use of the tool. As far as other accessory pathways, this is a summary of the Atakr Registry database, published in 1999 in Circulation;³ this was a multicenter study mainly of academic centers and very experienced physicians. They looked at different pathway locations and what the success was with RF ablation. With left free-wall pathways, which at least in adults are probably 55% of all the pathways, there was 92% initial success. On a second procedure, they got another 3%, so with one or two procedures, there was 95% success. The recurrence rate was on the order of 3%, and there obviously was no heart block. So do we need cryoablation for left free-wall pathways? Almost certainly not, unless they are in unusual locations, as George alluded to. If they are within the coronary sinus, particularly within 5 millimeters of an epicardial coronary artery, then we know that the risk of coronary artery damage is high with RF. However, for the usual endocardial pathways, we really don t need cryo for the left free-wall pathways. With septal pathways, it s a different story, though. If you look at the Atakr Registry database, there was only 84% initial success with RF ablation of septal pathways, and these are right anteroseptal, intermediate septal, and posterior septal pathways with an 11% arrhythmia recurrence rate. Arrhythmia recurrence was only defined in the group that initially had a successful RF ablation. So you re looking at a nearly 3% incidence of heart block. So that is nearly a 30% incidence of suboptimal outcome that I think we would say we need a different tool for that. Lastly, as far as right-sided pathways, as many of you know that when you read echo, you can see how the tricuspid annulus is really yanked during right ventricular systole, so catheter stability is a real issue on the right side. Initial success was only 83% with right free-wall pathways with a 14% incidence of recurrent arrhythmias, and of course, no heart block. So I think for septal and right-sided pathways, which make up at least in the adult population about 45% of the cases, cryo can have some advantages. GEORGE F. VAN HARE, MD: We ll do two more questions and then we ll be done. RAJJIT ABROL, MD: Some of the questions that we re getting in deal with other arrhythmias, so I ll just do a summary. Here are two questions: Please compare cryoablation with RF ablation, and then perhaps you can address the issue of cryotherapy with esophageal injury. I know that we have been talking for some time about arrhythmias that we can treat with cryo, and the bulk of it that we ve been talking about is AV node reentry because that happens to be what we use on almost a daily basis. In terms of other arrhythmias and the use of cryo I ll just briefly mention ventricular tachycardia. You can potentially safely ablate areas of the outflow tract. As we all know, the coronary arteries run near the right and left ventricular outflow track, and I ve heard of cases with RF, you ve had either spasm or coronary artery injury. So the use of cryo in the outflow tract is something that should not be underestimated. Regarding atrial tachycardias, we have done live cases that we were going to show you; there were two young patients with tachycardia that both terminated with vagals and adenosine, and one ended up being an atrial tachycardia. One was a left-lateral pathway, so we spent the majority of our time talking about AV node reentry, but we don t have examples to show you. In general, I would suspect that with atrial tachycardias, as easy as it is to RF-ablate, it s hard to find the spot, but when you get to the spot, it s easy to get rid of it. It is a kind of endocardial tissue that is causing the arrhythmia, and cryo would be effective if you can find the spot. However, a big advantage to cryo is when working near the right phrenic nerve. We did this case where we paced the phrenic nerve and then froze below the place that we were pacing from, to make sure that we could freeze the tachycardia site, which we were effectively able to do. Unfortunately, the patient had four or five different tachycardias, but we were effectively able to in at least three of them eliminate her tachycardia without damaging the phrenic nerve. I think that is an important tool for cryotherapy. As far as atrial fibrillation, we would probably have to have a separate webcast. The cryoballoon is right now under an FDA study, which our hospital is involved with. My personal feeling with the balloon again, this is biased by the limited experience I ve had with cryo is that it potentially gives you good lesions that will dissociate the pulmonary veins from the atrium without having the risks of pulmonary vein stenosis. There is preservation of the endothelium with the cryoballoon. The structural integrity is similar to all the things we talked about non-arrhythmogenic with cryo, less risk of esophageal injury, the data for all that. If you want to find a treatment or a therapy that is going to provide patients with a safe way of treating their tachycardia in the left atrium, I think cryo is potentially a therapy that we are going to be able to use with the balloon system. We have had very good results here at our institution so far, but the data is not available yet. We haven t done enough patients to be able to say that this is definitively one way or the other. However, I think in terms of covering the arrhythmias, you probably have to have a webcast covering each different arrhythmia, because we have spent a lot of time talking primarily about AV node reentry today. PETER J. WELLS, MD: George, thank you very much. Raj, I appreciate your help. We re glad that you joined us. We hope that this has given you some initial information for how cryoablation might fit into your current practice. Thank you very much. For more information, please visit: www.cryocath.com www.or-live.com