Hello and welcome to Core Concepts in EP. I'm Ed Gerstenfeld from University of California San Francisco and for this session we're going to be discussing the biophysics of catheter ablation. Again, this seems like maybe a nerdy topic but it's one that's not often covered and really important since we spend a lot of our time ablating things to understand biophysics and how ablation works and what some of the limitations and the various tools that we have available to us to try and optimize lesion formation. These are my disclosures, nothing super relevant. So we're going to talk about obviously radiofrequency ablation and we'll talk about variations using large tip catheters, using irrigated RF ablation, we'll talk about cryo ablation, and then we'll talk about some of the newer energy sources including electroporation, new kid, on the ablation block. So this is the electromagnetic wave spectrum and you have to remember that at higher frequencies electromagnetic waves tend to pass through things. So things like cosmic rays, gamma rays, very high frequency pass through things and don't heat up tissue. It's actually the lower frequency signals that heat tissue and if you look at the bottom here where we talk about RF, we're talking about 500 kilohertz and you know although that sounds fast, it's at the EM spectrum it's actually relatively low frequency below visible light, below microwaves, and somewhere between FM and AM radio. That used to make sense but many of you may not listen to the radio anymore but it's around that wavelength. So when we talk about RF use of radiofrequency energy to ablate, you know there's two ways the heat is actually delivered to the tissue. The first is resistive heating and that is transfer of energy basically directly from the energy, directly sorry from the electrode to the tissue under the electrode, so the electrode tissue interface and that's affected you know directly by the current going to the catheter tip. And then from there there's conductive heating right, that central hot core basically conducts outward and that's what can what creates the majority of our lesion size with standard RF ablation, that zone of conducting heating. And in this picture you know the orange shows the resistive heating and then the red is the outward radiation that makes our lesion. The resistive heating falls off very quickly with distance one over r to the fourth so that really orange focuses just at the at the majorities at the catheter tissue interface and then the majority of our lesion you know with standard RF powers and heating. We'll talk about variations but standard most of the lesions created by conductive heating as opposed to resistive heating. This is just an example of an animal heart and an RF lesion. You see the typical RF lesion which is a necrotic core surrounded by a hyperemic zone and I would encourage everyone whether you're a fellow out in practice if you haven't done it to go you know to an animal lab and do some ablating and then look at the tissue afterwards because we're just very you know protected. We're in the lab looking at you know our proteoscreens and electrograms and saying on on on and I tell you when you see afterwards the kind of damage you can create with RF ablation it just humbles you into realizing especially when you're ablating in normal tissue. It's one thing in scar you know sometimes the lesions may not penetrate as much but when you're in normal tissue ablating a pathway ablating an ATAC you're creating you know five six eight millimeter deep lesions in someone's heart and I think it just really gives you perspective to go and and watch and see what that looks like after ablation. Now this is data from David Haynes and you know in terms of how much heating do we need to irreversibly damage cells so we know if we heat the tissue to 45 to 50 degrees we can get reversible loss of excitability so the cells look like they're not conducting you know your ATAC has stopped your pulmonary veins isolated but then that's going to recover that you have to heat cells above 50 degrees to get irreversible cell death and loss of excitability so that is a sort of temperature cut off for non-irrigated ablation or you know whatever ablation we're using the tissue temperature has to exceed 50 degrees to lead to a reversible loss of excitability. And again initially here I'm talking about standard non-irrigated RF ablation some of us still use that although most of us are used to irrigated ablation but with non-irrigated ablation what this graph is showing is distance from the catheter tissue interface on the y-axis is the temperature that we're heating the tissue to okay and then on the x-axis is the is the depth of the lesion and so measuring temperature at the at the catheter tissue interface is actually helpful because if we heat up to 80 degrees then we radiate outwards with our conductive heating and by the time we get down to 50 degrees you know we may have a two and a half centimeter lesion. If we're only heating to 70 or 60 degrees we're going to get a smaller lesion so for non-irrigated ablation we used to look you know closely at the temperature of the electrode what we're heating it to because that's a surrogate for lesion size higher temperature bigger lesion. So again just to emphasize that myocardial tissue temperatures that's what you know the actual tissue is being heated to greater than 50 degrees is required for irreversible myocardial injury and that for non-irrigated ablation lesion size is proportional to the temperature at the electrode tissue interface. Now how much heating is too much? Well two problems with heating above 100 degrees heating the tissue to above 100 degrees celsius one is you know you're essentially burning the tissue and you get coagulum on the electrode at the tissue interface and that'll impede further lesion formation and can impede the ability to deliver subsequent lesions because you've got char on the electrode interface. In fact if you're using non-irrigated ablation and for some reason it seems after a while that your ablations aren't having an effect one thing we still always do is to take the catheter out look at the electrode and make sure it doesn't have any char on the tip. The other is again you're heating tissue and tissue is full of water right saline and if you heat the water inside the tissue above 100 degrees it's going to boil it's going to create steam and if it's inside the tissue that has nowhere to go and that's where you can lead to a steam pop right a mini explosion that can lead to a perforation or tamponade and this is in an animal lab to actually borrow this video from Will Stower so you can see the catheter on intergalactic echo here we're heating at 50 degrees and you can just watch and listen and do that one more time because there's two things one is you'll you see this explosion of bubbles and hopefully if you're listening and have your volume turned up you'll also hear a pop and again if you haven't heard this you'll hear it standing at the side of the bed you'll hear that pop and when you hear that that's a sign that you're you're and when you hear that that's a sign that you're you're eating too much first thing I always do is you know step on LAO and look at fluoro look at intracardiac echo because if you're on the free wall for example within structure that explosion can lead to a perforation bleeding around the heart and tamponade if you're on the septum it may not that's why we like to watch our lesion formation with intracardiac echo because you can often see the harbinger of a steam pop with bubble formation as you see here and I always tell a story where I was doing an ablation and we got a steam pop and the patient was actually under conscious sedation and he said you know what's that popping sound and I said oh don't worry this you know it's normal during ablation and then I looked on fluoro so you will hear that but again it tells you you're really being too aggressive in terms of how much energy you're giving so again ideally especially with non-irrigated ablation we'd like to monitor that temperature in the tissue just under the electrode a good surrogate for that is impedance so looking at the impedance drop as a surrogate for our lesion formation so this slide from this is an older paper 2006 but they did multiple ablations in an animal model and you can see the different colors steam pop thrombus no complications in blue so in this non-irrigated ablation study as long as they kept the impedance drop to less than 12 ohms they did not get a steam pop or thrombus that's kind of a good rule of thumb you know in the atrium what kind of impedance dropped you'd like to see it might be c5 to 8 ohms in the ventricle you know 10 to 12 maybe if you're pushing at 15 but we always monitor that impedance drop as a as a surrogate for one how big a lesion we're making and two that we're not running into problems with safety so when you come on and your impedance starts dropping rapidly that's where you might back off on the power on the other hand you have a not much change in impedance you might go up on the power so there you might see you're attending you think about it yourself you're trying to make a certain size lesion you can titrate the power based on the impedance drop and those are the loose guidelines we use this was just a case of someone obviously we're doing a lesion about 28 seconds in you see impedance in green coming down you see the temperature coming up and you see the power also gradually being increased and then all of a sudden there's this this jump in impedance and drop off automatically in power and that's kind of what you might see from the power impedance curves when you have a steam pop and a explosion that abruptly changes the impedance because the temperature goes up then the power it automatically comes down this is old slide from Hiroshi Nakagawa just again talking about how we non-irrigated you know how we titrated non-irrigated ablation which is temperature controlled ablation so this is a four millimeter electrode and we're setting the max temperature to 75 degrees and then the system is regulating the power to keep that temperature at 75 degrees so you can see from the power you can see over this lesion we have about a 10 ohm impedance drop pretty good the power is relatively low right it starts at 10 and the system is automatically ramping down to 4 watts because it just wants to keep that temperature at the electrode to 75 degrees again remember the temperature we're measuring is not exactly the temperature of the tissue right the thermistor in standard catheters is proximal to the proximal electrode so we usually set it lower than where we want to to heat because the tissue at the electrode is going to be a little bit higher and then fall off a little bit by the thermistor but we're heating this at 74 degrees so at that tissue interface in this uh you know animal experiment we're heating that to 75 degrees at three millimeters we have conductive heating that's heating that tissue at 58 and then at seven millimeters it's 41 they had plunge electrodes measuring tissue temperature at depth in this study so here we're going to get roughly a three millimeter lesion because we're heating tissue at three millimeters to over 50 degrees right this tissue at seven millimeters might be heated a little bit but that's going to be reversible injury and this highlights also you know one of the limitations of standard ablation that standard non-irrigated ablation that if you're in a low flow area a little power is going to heat the electrode up and then you're only you're limited in terms of how much power you're giving and how big a lesion you can make because um if you heat more then you'll heat that make that temperature too high and that's when you get charring or get a steam pop but this is non-irrigated temperature controlled ablation important to understand that concept another concept i wanted to emphasize is thermal latency so in this experiment we have temperature in the y-axis time on the x-axis and what's happening here is the catheter is being turned on for five seconds power is being turned on and then abruptly turned off and what we're measuring here is tissue temperature at different depths two millimeters four millimeters and seven millimeters so what happens when that power is turned off at five seconds what happens to the temperature two millimeters depth well you'll see it continues to go up before it comes down why is that right because we know the majority of our lesion is formed by conductive heating so even though you turn off the power that heat is continuing to conduct continuing to make a lesion before it comes back down same thing's happening at four millimeters um you know we're not having much of an effect at seven but the reason this is important is uh you know you you using rf you don't want to do a test burn i remember when i first got the ucsf and it's you know someone was ablating and they weren't sure if they were near they're bleeding at 10 watts i'm like why using 10 watts like well i want to do a test burn to make sure you know they're in the cusp of not near the right coronary artery so you don't want to do that because again if you damage something or you're near let's say the ab node you may turn off power but you're still creating more damage before that goes away um before that heat that dissipates biggest you know the best example of this is probably we see this all the time ablating the posterior wall of the atrium near the esophagus right you see the esophagus heat up you turn off power and what happens it continues to heat up before it comes down so um near the ab node near the conduction system near critical structures you want to be comfortable that you're delivering a safe lesion and a test burn is generally not a good idea for this reason another um you know biophysical limitation of ablation is that obviously we're ablating tissue and that tissue has perfusing veins and arteries and this was a study from mark wood in virginia commonwealth he's taking a wedge of tissue this is the endocardial surface the epicardial surface and ablated from the epicardial side right on top of this marginal coronary artery right and there's two challenges with that obviously one is we know with rf ablation we can occlude or damage the artery but in this case what you see is that the artery acts as a heat sink so it kind of soaks up all that rf energy and it protects the area below and you can see the the more the faster the perfusion rate he perfused this artery in this experimental setup um the more it limited the uh injury to that myocardium and that's very relevant for you know standard ablation for example when we're ablating the mitral isthmus for mitral annular flutter right we know we often can't get a full thickness block with endocardial ablation and that's because both the circumflex coronary artery and the coronary sinus can act as that heat sink and shield basically the epicardial aspect from ablation and that's why we often have to go into the coronary sinus to ablate from the epicardial side so these arteries um you know they're not our friends when it comes to ablation uh partly because we can injure arteries but even coronary large coronary veins can act as a heat sink and limit the ability to ablate underneath them and create full thickness lesions so because of some of these limitations i mentioned of non-irrigated uh four millimeter tip ablation it led to the development of two uh different type of electrodes. First, larger RF electrodes. Again, I would say these are less commonly used, but you may still see them, so important to understand how they work. And then to cooled or irrigated RF ablation, a more common type of RF ablation we use today. So, you know, this is again, study from David Haynes, looking at the diameter of the electrode on the Y-axis and the depth of the lesion on the X-axis. And that's surprisingly, the larger the diameter of the electrode, you're increasing that area of resistive heating, and you're gonna end up with a larger lesion. And so that led to development of larger tip catheters, instead of four millimeters, eight millimeters, 10 millimeter catheters. And so, you know, I have a question for you to ponder, and I'll read that to you. So when RF lesions created in the power controlled modes, and now we're delivering at a fixed power, delivering 30 Watts for 30 seconds to either a four millimeter or an eight millimeter tip catheter. The maximum temperature is 60 degrees and is not reached using either catheter, and blood flow is exactly the same. The lesion size will be, A, larger using the four millimeter tip catheter, B, larger using the eight millimeter tip catheter, C, no difference, or D, depends on the baseline impedance. So take a second to think about that. You can pause if you wanna ponder it, and then we'll continue and I'll give you the answer. Okay, so the answer is, that the lesion is actually larger in this case, using a four millimeter tip catheter compared to an eight millimeter tip catheter. And that always, people struggle to understand this very important concept, and we'll talk about why that is. So when you're, the advantage of a larger tip catheter is that you're allowing passive cooling of the electrode by the blood pool. It's kind of a poor man's, poor person's say, irrigated catheter. So because of, you know, you might be limited, you might be wedged in with a smaller electrode, with a larger electrode, you have more passive cooling of the electrode, and that allows you to give more power without reaching maximum temperature and make a bigger lesion. So that is the main advantage of a larger tip electrode, is passive cooling by the blood pool that can lead, that can let you deliver more power. If you're delivering the same power though as a four millimeter tip catheter, now there's two problems. You're averaging that power over a larger electrode, and you're also losing some of that energy passively to the blood pool. So what ends up happening is you're actually delivering less current and less power to the tissue as shown here, 1.8 watts compared to 4.5 watts. Again, when you're delivering 50 watts, either to a four or eight millimeter electrode. Okay, so, you know, the advantage, if you plug in your eight millimeter electrode, you'll notice that instead of the power of the generator stopping at 50 watts, you can go up to 80 watts or even a hundred watts. So you have to, you know, the advantage here is you can deliver more power. I remember when people started using eight millimeter catheters for AF, I'd often see them doing, you know, 30, 35 watts, which is making a very small lesion. So you really have to do 70 watts, you know, more power to make bigger lesions. Again, I wouldn't recommend using an eight millimeter catheter for AF ablation, but just for the concept, if you want to get a bigger lesion, you have to use higher power. Same power to a bigger electrode, smaller lesion because you're averaging over a big area and you're losing more of that energy to the blood pool. The other disadvantage, you know, the four millimeter tip catheter, the radius and length aren't so different. So whether you're perpendicular or parallel to the tissue, you're delivering similar amount of energy. The other problem with a large tip catheter is when you're parallel, you're delivering over a bigger area and a different amount of energy compared to perpendicular. And you also have edge effects where this electrode ends that can cause charring. So most people, I would say, sometimes people still use this for flutter because, you know, especially some with heart failure, we're not using irrigation because you can deliver power, yet mapping isn't as important. We know large electrodes aren't as important for mapping, but I think for most, you know, most cases of ablation, most people have gone back to irrigated, smaller electrode tip catheters. So again, major advantage of large electrode tip catheters is increased electric cooling from circulating blood. Okay, so let's get to irrigated RF ablation. So again, the challenge, one of the challenges with non-irrigated ablation is when we're in an area of low flow or wedged in because we don't have cooling of the electrode, we're limited in terms of how much power we deliver. So by cooling the electrode, we're able to maintain power in areas of low blood flow. Also because most current irrigated catheters are external irrigation, we're also like a sprinkler cooling, sprinkling the tissue locally, and that decreases the risk of thrombus formation. Important to realize, and I'm gonna say this multiple times, and, you know, in addition to the question about eight versus four is probably one of the most important lessons from this talk, is that if you're giving the same power to an irrigated versus a non-irrigated catheter, the lesion isn't necessarily greater, deeper with an irrigated ablation catheter, right? It's not like it's a more powerful catheter, it's just that you can deliver more power. So for any constant power, lesion size and depth is the same as with a non-irrigated electrode, roughly. I mean, at the surface, you'll get a little more of a teardrop shape because you are cooling the surface, but the depth and lesion volume are similar. So again, if you're, say, delivering 50 watts through a non-irrigated catheter and that accessory pathway is not going away, I've heard people say, well, I'm gonna change to an irrigated catheter because I want more power. That's not gonna work. If you're delivering 50 watts, you can't deliver any more power through an irrigated RF ablation catheter. On the other hand, if you're delivering 15 watts and your temperature is going up to 65 degrees and you wanna deliver more power because you're in maybe a crevice in atrial flutter or maybe somewhere in a pectinate muscle, that's where irrigated ablation is gonna help you give more power. The downside of irrigated ablation is remember that temperature that we said were non-irrigated ablation was useful as a surrogate for lesion size is really useless now because we're cooling the catheter tip. So we just, what temperature we measure isn't useful as a surrogate for lesion depth. It is still useful just as a sign that the catheter is working. So if you see that temperature rising with irrigated ablation, it generally is a sign that you're not irrigating well. So it could be that some of the holes in the electrode are plugged, that you're pushing up against the tissue and plugging off those holes. You know, one sign, if every time you go on, the temperature shoots up, is your line flush connected? Is it disconnected? Those are the things to think about. But in general, you know, so it's the temperature is kind of a surrogate just that it's working, but it's not really a surrogate anymore for lesion size. So again, looking at this graph, tissue temperature on the left, depth on the x-axis, tissue temperature on the y-axis. A in purple, four millimeter non-irrigated 20 watt lesion. As we said before, we're heating the temperature to a little over 70 degrees. That falls off exponentially and creates, you know, a three and a half, say centimeter lesion depth. We're irrigating now with the same 20 watts. So now the tissue temperature isn't that helpful as a lesion size, but we're still heating the tissue to that same above 50 degrees. And we ended up with a similar size lesion. The ability though now with irrigated ablation is we can crank it up to 50 watts because we're not temperature limited anymore. We're cooling the catheter. And, you know, you can see that we're now, we're getting a huge lesion, right? We're getting, you know, nine and a half centimeter lesion. What's the danger here? Well, because you're cooling the surface, you don't know as well now what's happening at depth, right? If you know you're using non-irrigated ablation, you know your tissue temperature at depth is generally not greater than it is at the surface because it's conductive heating. It's falling off exponentially with distance. But now that you're cooling the surface, you can heat the temperature at distance. And that's why you can boil that tissue, the water in that tissue and get a steam pop. So steam pops, if you're not aware of them, can be much more problematic and more common with irrigated compared to non-irrigated ablation. Again, just in terms of, this is thermograms of the temperature profile, non-irrigated ablation on the left, irrigated ablation on the right, same power, 15 watts. Again, the lesion itself doesn't look very different, but what you'll notice is the maximal tissue heating in this case is at the tissue electrode interface and then falling off with time. White here is the hottest. Whereas with irrigated ablation, because you're cooling the surface, the maximal temperature is at depth. There's some people who advocated non-irrigated ablation in the posterior wall of the atrium because it's possible by cooling the endocardium that you're actually limiting the injury to the tissue just under the electrode. Again, I think with modern cooled electrodes, it's not the case, but it is important to realize that your maximal temperature with irrigated ablation is at depth because you're cooling that interface. And that's where you can easily imagine now if you heat that to over a hundred degrees, that's where you get a steam pop. This was a similar study to what I showed you for non-irrigated ablation, but for irrigated ablation by Bill Stevenson's group in 2008, they looked at impedance drop and when they got steam pops versus no pops. So again, when the impedance drop is less than 10 ohms, they never had a steam pop. 80% of pops occurred when the impedance drop was more than 18 ohms and 60% of ablation lesions without pops had a drop of less than 18 ohms. So again, atrium five to eight ohm drop pretty good. Ventricle, we usually shoot to make a large lesion for 10 to 12. And if you're pushing things, maybe the 15, but if you're heading out towards 20, that's where you really probably wanna limit your power because you may get a steam pop. It may happen without warning. Another thing we realized over time is that contact is actually a big deal. So this was a type of catheter that was actually allowed us to visualize ablation within the heart. This is inside the heart from another catheter, watching an ablation lesion being formed. You can see that whitening of the tissue. And this just pointed out to me is before contact for us that we don't always realize that this catheter is bouncing around so much. Obviously the heart's beating, the patient's breathing. And this really also was another limiting factor in making adequate lesions. So this was a nice study from Hiroshi Nakagawa and others looking at lesion size and how contact force between the electrode and the tissue factored into that. And it really has led to contact force monitored ablation, which I think has given us another better way to control a lesion size. Shown in these graphs on the right with 30 Watts and 50 Watts again, measuring now the contact force between the catheter tip and the tissue, it's pretty clear that it's not just being in some contact with the tissue, but the greater the contact, the larger the lesion, right? Because you're now compressing the tissue and you're pushing into these pectinates that allows you to make a larger lesion. So shown on the left here, 15 to 30 Watts from low two grams to 20 to 60 at the highest powers and contact force is where you have the highest risk of steam pops shown here in black at 20 Watts and say moderate contact force or no steam pops. So when you're really pushing it at 30 Watts, high 60 grams, you need to be nervous because many steam pops at that power. In general, you wanna be certainly above five grams, probably ideally 10 to show that you're in good contact with the tissue, and usually you try to limit and not go too far above 30. Certainly above 40 is getting high. And in one study where they looked at trying to create perforations, it took usually 70 grams to cause a perforation. So I think contact force monitoring has helped us in two ways. One is safety, so you'll see that contact force jump up and you know not to push any harder. But the second is it lets us create control or lesions a little bit better by looking at the contact force and adjusting our power. You know, the original irrigated catheters had six end holes around the tip of the catheter. More modern catheters have multiple small electrodes and that just makes more efficient cooling of the catheter tip. But these end hole electrodes, now we used to solicit the temperature come up say 35 and make them up to 40, 45. With these more efficient cooling electrodes, the temperature just stays at 28, 29 when you're ablating, doesn't really come up at all, makes it even safer. That's probably more of the standard these days. Now, what other tricks are there? Let's say you're trying to make a big lesion, but matter when you're giving 50 watts, you're irrigated and you're having trouble getting to a deep lesion. This again is off-label, I should mention, for any RF delivery systems, you realize you're operating sort of outside of guidelines here. But remembering that standard ablation is monopolar or unipolar, right? You're ablating between the electrode tip and a dispersive patch on the back, typically of the patient. So you can do here, as shown in this experiment by Dr. Reddy's group and Jacob Carruth, you can do a unipolar lesion on one side of the tissue and a unipolar on the other, but you miss this area in between. And so one way to get around that is bipolar ablation. So instead of ablation from the catheter tip to a reference patch, you're ablating between two electrodes. And that leads, because you're heating simultaneously from both sides, you're more likely to get a full thickness lesion. And in this study, with bipolar ablation, 82% of lesions were transmemorial compared to only 30% with sequential unipolar ablation. People have described using simultaneous unipolar ablation to achieve a similar effect. This is just an example using electro-atomic mapping systems. So we have one catheter in the RV outflow tract. We have a second catheter, retrograde aortic, in the left ventricular outflow tract. And we're ablating between these two for a difficult summit VT. And you can see sort of kissing catheters on fluoroscopy here in the RAO and LAO. Here are the two catheter tips in the RVOT and LVOT. So that's one option, but it takes some finagling to wire the systems this way. A second, probably easier approach to enhancing lesion volume is changing the irrigant used to irrigate the electrode from normal saline to half normal saline. And this was shown nicely by Will Sowers' group. We participated and Dewey Wynn was the first author. Now, why does this work? So by irrigating the electrode with half normal saline, there's half normal now in the milieu around the electrode, and that causes more of the energy to be concentrated into the tissue based on the ionic current differences. And in this study, comparing normal saline irrigant at the same power and temperature to half normal saline, the lesions were about 30% bigger. So this is much easier. You have to have a bag of half normal saline available with order this ahead of time. And you just ask the nurses to change the bag from normal saline to half normal saline. And again, assuming you're using similar powers, you will get larger lesions if you're limited in terms of the lesion size. They also looked, just for interest, at D5W, and the problem is they got a lot of steampups with D5W, so I wouldn't recommend that, but half normal saline is a pretty easy option that any lab can use. Finally, I wanted to mention just a, you know, a different biophysical approach to ablation that's used, I would say, more commonly for AFib ablation, and that is high power, short duration ablation. So, you know, on the left, as we said, standard ablation, this is a nice paper by a lot of Anter's group, standard ablation where using a little bit of resistive heating, and the majority of the lesion as shown here with the weight, with the scale balance is formed by conductive heating. With high power, short duration, we're giving a high power, short duration lesion, so the majority of the lesion is now formed by resistive heating. What's the advantage of that? Well, you're getting a broader, less deep lesion, and it's much faster, for one thing, so as opposed to giving a lesion over 30 seconds, you're giving it over five to 10 seconds, so when you're delivering multiple lesions, it's a faster procedure, but for the atrium where you have two millimeters of thickness, you're not looking for a deep lesion, right? You're looking for contiguous lesions that don't have gaps, and so high power, short duration actually can work better as shown in this slide where they tried to make linear ablation compared to standard ablation where you can leave gaps. And again, in the atrium, we're only dealing with a couple of meters of thickness, it works fine, and it's much faster, and there've been studies now comparing high power, short duration to standard ablation, one of them coming from our lab should be published soon, but this, I think, is becoming more widely adapted, just ablating at 40 to 50 watts for short duration during a fib ablation. Most of the systems now have some kind of leak Most of the systems now have some kind of lesion indexing, so in the past, again, we used to sort of just gestalt it, I would say, by looking at the impedance drop and looking at the power and trying to, we knew that higher impedance drops, longer duration lesions made the lesions a little bigger, but these have now been worked into equations, so they look at the time, they look at the impedance drop change, they look at the power, look at the contact force, and there's lesion size index, ablation index, different systems have different values they use, but as you go higher on these ablation indexes, it's been shown experimentally that you're getting larger, deeper lesions, so again, that's given us better control over our lesion volume, for a deep septal VT, you might wanna make a big lesion for a fib on the posterior wall, you might wanna make a smaller lesion or a pathway, and so these lesion indexes are another way to control our lesions. So to summarize, for RF ablation, tissue injury reproducibly occurs at a temperature of about 50 degrees Celsius, RF lesion size for non-irrigated RF is proportional to electrode radius, the tip of the temperature-electrode tissue interface, sorry, the temperature at the tissue-electrode interface and the power that you're delivering. A larger tip electrode allows more delivered power because of greater cooling by the blood pool, but at the same power, again, you're actually getting a smaller lesion, so you have to give higher power. Irrigated RF allows greater delivered power and therefore larger lesions by directly actively cooling the electrode tissue interface, but again, lesion size of the irrigated RF is not different with the same delivered power, again, whether you're using irrigated or non-irrigated ablation. Greater contact force will cause a larger lesion and then tricks for making lesions even larger are bipolar RF, half normal saline irrigation, or again, for wider lesions, high power, short duration. So just to jump briefly to mention something about cryoablation. So as opposed to heating, now we're ablating tissue by freezing and by freezing the water inside the cells and causing the cells to rupture and cause cell death. So when you freeze below zero degrees, as you said, heating above 50, freezing below zero, that results in ice crystals and cell death. Important to realize that you've got that central core of freezing below zero, but then surrounding it, you've got a hypothermic area where the cells are being stunned, but not damaged, as we said, for thermal ablation where you're heating to 45 to 50 degrees. So it's one of the reasons cryoablation can be more forgiving. You do not have that thermal latency with cryo. So in fact, if you see a bad effect, you're ablating near the conduction system and you see block and come off, this leading wave of hypothermic tissue will recover and you can avoid AV block. Again, if you stay on long enough, absolutely. You can create AV block and damage anything, but if you recognize that and come off right away, it's much more forgiving than RF. So the advantages of cryo, adhesion to the cardiac tissue. When you freeze, the catheter sticks to the tissue. You don't even have to long to it. And as opposed to RF where you have to worry about contact, this can be helpful, particularly around like the papillary muscles where the motion makes it very, and the angulation makes it hard to keep in contact with RF. The reversibility of electrical effects. So if you're near a critical structure, you can come off and see electrical activity return. And then third, the preservation of tissue architecture. This was just a study where they compared a four millimeter RF and a four millimeter cryo lesion. And you do get smaller lesions with cryo compared to RF. So it's got to be a little more accurate when you're targeting pathways. It's also why most people will use a six millimeter cryo catheters. They come in four, six or eight. Eight is nine frames, so it has to go through a bigger sheath than we're used to. But most people, initially with four millimeters, say for AVNRT found a higher recurrence rate, but at six millimeters, you're making a bigger lesion as shown with this thermal imaging. And most people are using six millimeters these days for clinical applications. Again, compared to RF shown here on the right, we can often get charring thrombus, necrotic core and tissue disruption. The cryo lesions tend to be cleaner, less thrombus, less destruction of the tissue architecture. So again, many people use focal cryo. Occasionally, again, maybe for a parahystic inaccessory pathway, a difficult AVNRT, or again, by papillary muscle, a papillary muscle PVC, where you'd be having difficulty with contact. But probably the majority of cryo is used for pulmonary vein isolation. And that is one of the cryo balloon tools. This is the cryo, the Arctic front cryo balloon, comes in two sizes. Most people just stick with the bigger size, and it's basically a double latex balloon with infused freon that creates cooling. You know, this, again, the same way we had conductive heating, we have conductive cooling. So you're cooling to less than zero at the core. It's radiating outwards, takes about 160 seconds roughly to get to five millimeters depth below zero degrees, and get a five millimeter lesion. And that's why typically, you know, deliver 180 second or three minute lesions with cryo. You do need to stay on a little bit longer to get a lesion at depth. The lesion you're, the temperature you're measuring at inside the balloon, remember, is much colder than what's actually happening at the left atrial pulmonary vein junction. So you may be measuring, you know, minus 50 degrees that you're delivering, but keep in mind that at the pulmonary vein junction, it may be just under zero. So you're not quite cooling the tissue as low as you're freezing, but as long as you're getting under zero, then you're getting a thermal effect. So again, cryoablation kills cells via ice crystal formation. The volume in general, the four millimeter tip catheter is gonna be smaller than RF lesions, but similar depth. Most operators use six millimeter tip for focal clinical cryo applications. Cryo balloon is widely used for pulmonary vein insulation. It has the advantage of reversibility of electrical effect if you come off before the tissue gets below zero, less thrombus and preservation of tissue architecture. Just gonna briefly also mention the laser balloon. You may, this also is a commercially approved system for RF ablation. You may encounter it in the lab or hear about it. This is a compliant balloon. So as opposed to the cryo balloon, which is a fixed diameter, this is an adjustable balloon. It has an endoscope down the middle of the balloon. So it actually allows you to visualize the pulmonary veins as you're ablating them. And it uses laser energy again to create a thermal based ablation. The balloon itself, the laser ablation is actually filled with deuterium oxide, D2O. This is heavy water, which was the same substance used by the Germans in the early atomic bomb experiments. And the reason it's used for a laser ablation interestingly is for water shown here in blue with this absorption spectrum, the peak absorption is 980 nanometers, which is the exact frequency the laser uses to heat tissue. Well, D2O, it's a nadir of its absorption. So it allows the light energy to pass through the balloon without heating and then maximally heat the water in the tissue. This is just an example where you're looking, you know, it started with 360 degree laser and then went to 90, and now it's a 30 degree laser. At this point, it was manually directed around the pulmonary veins, the pulmonary vein with blood in the center. Now it's automatically rotated around the pulmonary vein. And in this animal, you can actually see the whitening. You can see the lesion forming, although unfortunately you don't see it as clearly in humans, but this is an approved approach for pulmonary vein isolation under direct visualization as shown here on the right. You know, the hope was that direct visualization would approve outcome, but in a pivotal study that compared laser balloon to RF, the freedom from AF at a year was basically exactly the same with very stringent, you know, 100% freedom from AF after blanking period off drugs, 60, basically 62% versus 61%, no difference. So it does work, but no different compared to RF in terms of outcome. Finally, the new kid on the block, which everyone's excited about is electroporation. So this is, you know, I'd say one of the first non-thermal ablation approaches. So it involves delivering a high voltage, short duration electric field to cells. It's been described for many years that if you deliver a certain voltage and duration, you actually form holes in the cell membrane and that can lead to reversible electroporation. So you form pores and you can use that to target viral vectors or drugs into the cells and then it'll heal. But if you give a high enough voltage, you get irreversible electroporation where these pores form and the cell contents drain out and the cell dies either through necrosis or apoptosis. So you're actually not heating the tissue, but creating cell death. This view paper shows the slide on the right. Again, two of the important variables are the field strength, so the volts that you're applying and then the pulse duration, which typically is in the microsecond duration. But you can see that if you give, you know, a lower field strength, you will get reversible electroporation. As you get to a higher field strength, longer pulse duration, you'll lead to irreversible electroporation. And if you get high enough on your amplitude and pulse duration, you will end up with a thermal effect. So you can heat tissue even with electroporation if you're giving a high enough strength current. But it's important to realize similar to cryo that you'll have, you know, even when you're creating a lesion with irreversible electroporation, there'll be a surrounding area because of the lower field strength that's not directly encountered of reversible electroporation and that you have to get used to that. There is tissue that will seem electrically inactive, but that will recover. And so typically we're giving a train of multiple pulses to try and, you know, create a broad area of irreversible electroporation. You know, this is just showing some of the differences in pulse waveforms that can be used. So you can, this is a 500 volts per centimeter amplitude. This is the same at, you know, 100 microsecond duration, which is typical. You can go up to 1,000 volts with the same monophasic waveform. This is now a biphasic waveform. You can shorten the pulse duration or you can have a decaying pulse duration. Most commercial applications, which are used for AFib ablation are using bipolar, biphasic waveforms. And, you know, you can vary all these things now with pulse field ablation. The number of pulses, pulse duration, the orientation, the pulse strength, the shape, the frequency, and the polarity. An advantage of electroporation is, as with cryo preservation of tissue architecture. So here you can see this ablation has been performed. You can see that the myocardium has been totally eliminated with this histologic stain, but the tissue architecture is preserved. So less destructive lesions and more likely for the healing to occur with fibrosis shown here in blue. This was a preliminary pilot study done by the McReady and colleagues. This is a catheter that's delivering electroporation. It's a basket catheter that can form either a basket or a flower. Again, there'll be several different companies and catheters that have become apparent, but at least in the initial trial, they were able to isolate pulmonary veins 100% of the time with only a 90 minute procedure and 30 minutes of left atrial dwell time. So this shows here the signals in the pulmonary vein, basically a two and a half second delivery, and then you have pulmonary vein isolation. So a couple of advantages of electroporation. One seems to be tissue selectivity. So through good fortune, myocardial cells seem to be sensitive to electroporation, but non-myocardial cells, including nerve, blood vessels, other tissues are more or less sensitive so that you're actually able to get lesions in the myocardium but people have shown that ablating directly on, for example, the esophagus or nerve does not create any damage. So most studies have shown, as shown here, no esophageal damage, no pulmonary vein stenosis, and no phrenic nerve injury. So improved safety, very fast, again, two seconds to isolate a vein, although again, typically six to eight applications per pulmonary vein to maximize irreversible electroporation but still much faster than RF or even cryo. And the hope will be better, longer lasting pulmonary vein isolation. So at least in this initial feasibility, when they remapped veins using the latest waveform, they found 100% of the veins were durably isolated, which has really been, as we know, the Achilles heel of afib ablation. So this new approach seems very promising. This is just from our lab, showing this back to catheter, how it's situated. This is after pulmonary vein isolation. So you have really nice proximal isolation of the pulmonary veins. And this is the electrical signal in the pulmonary vein. And you'll see when we come on. That's it. Really rapid destruction of those signals. So this, I think will really, I don't think I'm over hyping it to say it's likely to change the way many of us are doing. Certainly afib ablation is being investigated for other chambers in the future. So again, to summarize, today, radiofrequency energy remains the mainstay of catheter ablation understanding these concepts of resistive and conductive heating electrode size and configuration, irrigation and contact force, extremely important. Cryo ablations used mainly for pulmonary vein isolation. Focal cryo for parahystia and some other arrhythmias that I've mentioned. Laser ablation only approved for PVI. Electroporation trials for afib ablation are underway and may have broad applications in the future, including VT and focal arrhythmias. So I hope this is helpful. Thank you for attending this Core Concepts in EP lecture.

biophysics

catheter ablation

radiofrequency ablation

RF waves

lesion formation

tissue temperature

irreversible cell death

cryoablation

electroporation