Hello and welcome to Core Concepts of Electrophysiology. I'm Ed Gerstenfeld from the University of California, San Francisco. And for this lecture, we'll be talking about the biophysics of catheter ablation or EP101. Again, I find this is a topic that often isn't covered in training programs, so I think it's extremely important for anyone performing catheter ablation and hopefully you'll find it helpful. These are my disclosures. We're going to talk about radiofrequency ablation, obviously the longest-standing method for performing catheter ablation. We'll talk about large-tip catheter ablation and irrigated RF ablation. We'll talk about cryoablation, and then obviously we're all very excited about the recent advent of the field of pulsed field ablation. So for RF ablation, remember when we think about that, higher frequencies actually penetrate through tissue and we actually want to heat up tissue. So if you look at medical RF, it's about 500 kilohertz and it's somewhere between AM and FM radio. It's a relatively longer wavelength than things such as x-rays or UV or gamma rays. And when you think of applying RF ablation to tissue, there's two components. There's resistive heating, which is the area under the tip of the catheter which is directly heated, and then there's conductive heating, which is heating from that central core to the surrounding area that makes your ablation lesion. The resistive heating falls off very rapidly with distance, one over r to the fourth, so that's a relatively small area and it's mainly conductive heating typically that contributes to the majority of the lesions we're making. This is just what a lesion looks like from a slab of tissue in the animal lab after RF ablation. It's often a central necrotic core and then surrounding hyperemic zone. Now I'd encourage anyone who's in a program that has access to an animal lab to go and perform ablation and then look at the lesions you created afterwards. I think sometimes we're sort of shielded by just saying on and pressing the ablation pedal and doing that multiple times and we forget that we're actually creating quite a bit of destruction, especially in a normal heart. So I think that really just gives you some recognition that we are creating often large lesions in normal heart cells and what we're doing shouldn't be taken lightly. That's the lesion in the sub. In terms of how much heat do we need to destroy cells in this and many of the other slides have been studies performed by the late great David Haynes, who spent a lot of time teaching us about biophysics of ablation. What he found is when you heat cells at about, if you heat them into the 40 degrees Celsius range, you get a transient loss of excitability that recovers, but then above 50 degrees Celsius, that's where you get irreversible loss of excitability and that's what we're generally shooting for at the tissue level with catheter ablation. So when you think about the original catheters, the four millimeters non-irrigated ablation, we're heating the tip of the catheter up to a certain temperature as shown here with the different colors. So in the zero range where we're at the tissue electrode interface up to 60, 70 or 80, the higher we're heating that tissue that falls off over time and the distance over which we're above that 50 degrees Celsius threshold is where we'll get our lesion. So for non-irrigated catheters, the temperature at the electrode tissue interface is actually quite useful as a gauge of how big our lesion size will eventually be. The hotter the tissue at that interface, the bigger the ensuing lesion depth. So again, just to emphasize that my myocardial temperatures are greater than 50 degrees Celsius are required for irreversible myocardial injury and for non-irrigated ablation, lesion size is proportional to the temperature at the electrode tissue interface. But you don't want to heat it too high because temperatures above 100, one can result in coagulant formation at the electrode tissue interface and that leads to ineffective ablation. And finally, if you heat the water in cells above 100 degrees, that can result in boiling or a steam pop, which can result in adverse events. And this is just an example fired from William Walsauer from the animal lab. And I don't know if you can hear this, but this is heating during an ablation. I'll play that one more time. You can hear that pop. And you'll actually feel and hear this in the lab to create a steam pop. You always want to check them for an effusion because if it's in the septum or thick area muscle, it may not lead to any complication. But if you're on the free wall, you can lead to a perforation. You want to avoid this in general. And realize also that what you're measuring when you get temperature out of an ablation catheter is not the temperature at the electrode tissue interface, right? In general, other than some newer catheters, you're actually measuring the thermistor is proximal to the electrode. So what you're measuring is actually lower than the temperature at the tissue interface. And another way to follow lesion formation is actually the impedance change during the ablation. The bigger impedance drop from baseline to the end of your ablation, the larger the lesion. In terms of what to expect, this is an old study, again, with non-irrigated ablation catheters. And this is a study that was done in the United States. And expect, this is an old study, again, with non-irrigated ablation catheters. Showing that with up to 12 ohm impedance drop, you rarely ever got a steam pop with rhombus. But when you get higher to 20 ohms or more, that's where you run into trouble. So in general, in the atrium, we sort of expect 5 ohm, 5 to 6 ohm impedance drops. In the ventricle, 10 to 12. And if you're really pushing it, you might go out to 15 ohms. But if you're getting more than a 12 ohm impedance drop, that's where you might come off or dial back the power to make it less likely that you're heating tissue and getting a steam pop. This is just an example from a case where there was a steam pop. And you can see the impedance in green. It's coming down nicely throughout the lesion. And then you have that abrupt rise with an abrupt increase in temperature. And that's sort of a classic finding on your impedance tracing that you have a steam pop and you should come off and be vigilant about any potential issue. This is just maybe a normal tracing where you have a gradual decrease in impedance and a gradual increase in temperature. I thought it's always important to mention the sort of thermal latency in RF ablation. So this is a catheter with thermistors, so measuring the temperature at the tissue interface, as well as plunge electrodes that are measuring the temperature at depth in the tissue, 2, 4, and 7 millimeters. We don't have this available in general, but this was an experimental setting from Wittkopf. And the power was turned on for five seconds and then turned off. And often, you know, still we'll hear this from people, oh, you know, I'm near the hiss, maybe near the coronary, so I'm going to do a test burn. I'm just going to turn on for 10 seconds and make sure nothing bad happens before I get a longer lesion. The important thing to realize with RF energy, at least, is when your power is turned off, because of conductive heating, the temperature at the tissue level continues to rise after you come off. This is probably best seen, you know, when we're doing esophageal temperature monitoring during ablation of the posterior wall for atrial fibrillation, where you turn your power off because the temperature is going up, but then it continues to go up before it comes down. So if you're doing this near the hiss bundle and you get heart block, you're in trouble with RF because the temperature is going to continue to rise before it comes down. So in general with RF, you know, don't do test burns if you're in a sensitive area. Obviously, with cryoablation, that's completely different. That's much more reversible. Another important thing to realize with RF is that there are coronary vessels, including things like the coronary sinus and other coronary vessels, and that blood flow can protect the tissue below it from injury, as shown here in this study by Mark Wood, where he ablated on the epicardial surface, and you have an artery here, and that protects the tissue below. And that's why it's often hard, for example, to get a complete block in the mitral isthmus during mitral flutter ablation, because you have the coronary sinus, you have the circumflex coronary arteries, and so it's difficult to get a full-thickness lesion, and sometimes you have to ablate inside the vein to get full thickness. But realize that having arteries or veins can limit your ability to achieve depth because the blood flowing acts as a heat sink, and you just don't get the heat delivered underneath the vessel. So because of, you know, some of these limitations of non-irrigated small electrodes that led initially to large RF electrodes, and then to cooled-tip RF. Let's look at large electrodes first, and this again goes back to data from David Haynes, that if you take the diameter of an electrode, shown here on the x-axis, and you look at, let's look on the right, depth of lesion, the larger the diameter, the larger the diameter, the more you're going to have a larger zone of resistive heating, and then eventually, assuming you're getting heating to the same temperature, you're going to get a larger lesion. So people thought, well, why don't we just make a larger electrode, and then you'll get bigger lesions. And so that leads to a question for you to consider. So when RF lesions created, you know, it led to the development essentially of the 8-millimeter tip catheter, and there was some 10-millimeter tip catheters as well. This is the length of the electrodes, and RF lesions created in the power control mode, delivering 30 watts per 30 seconds to a 4-millimeter and an 8-millimeter tip catheter. The maximum temperature set to 60 degrees is not reached using either catheter, and the blood flow in the surrounding tissue is the same. Will the lesion size be larger using a 4-millimeter tip catheter, an 8-millimeter tip catheter, no difference, or will it depend on the baseline impedance? It'll give you a second to think about that. And the answer in this case is the lesion size actually is larger using the 4-millimeter tip catheter, which I think is counterintuitive to many people. You know, isn't a bigger electrode tip always going to give you a bigger lesion? And the key is it's not. What a bigger electrode allows is more passive cooling of the electrode by the blood pool so that you can put in more power. So if you're giving, for example, 10 watts with a 4-millimeter catheter and you're achieving your 60-degree temperature, you're going to get a relatively small lesion. But on the other hand, because you have more cooling by the blood pool of the electrode or passive cooling, you can deliver more power into an 8-millimeter catheter and therefore get a bigger lesion. So if you notice often with a 4-millimeter catheter, your generator cuts off the power at 50 watts, but with 8 millimeters, you can go up to 80 or 100 watts. But if you're stuck at sort of 30 watts and you're using an 8-millimeter catheter, you're going to get a smaller lesion because that power is averaged over the whole electrode. So the only benefit here is you have cooling by the blood pool, and so you can put more power in and then get a better lesion. But at the same power, you're actually going to get a smaller lesion with a bigger electrode because you're averaging that power over a large distance. These longer electrodes also are subject to more sort of edge effects. So you're getting different power delivery that's parallel versus perpendicular to the tissue, whereas with a 4-millimeter catheter, you're not getting much difference. So bigger catheters were helpful in areas of low blood flow, but it's hard for you to control the amount of cooling, and it still may be limited when you're in areas where there's limited blood flow. But the major advantage of a large electrode tip is increased electrode cooling from circulating blood. That's important to realize. So then the next advance was irrigated RF electrodes. Rather than sort of relying on blood flow or areas of low blood flow, what if you control the amount of irrigation? One, since these are often externally irrigated, although you're giving the patient saline, which is a downside, but there's a low risk of thrombus formation, kind of a sprinkler effect from the fluid. But this is, you know, if I had to pick one thing to realize is that if you're delivering the same power with a non-irrigated and irrigated catheter to the same tip, so 4-millimeter non-irrigated, 4-millimeter irrigated, you're not going to get a bigger lesion using an irrigated catheter. It's just that the irrigation allows you to deliver more power without heating the tip. So you can deliver more power, but 30 watts with irrigated or non-irrigated is going to give you the same size lesion. For any constant RF power, lesion size and depth is the same with irrigated and non-irrigated. The downside of irrigation is, you know, we said with non-irrigated, the temperature at the electro-tissue interface was a useful surrogate for lesion size. Now, since we're cooling the tip, we can deliver more power, but the temperature at the tissue interface isn't really related at all to the lesion size. It's mainly useful as a marker of some problem. So if, for example, you know, you see the temperature, and the temperature should be relatively fixed, and if you see the temperature jumping up to 40 or 50, it suggests either maybe some of the holes are plugged and you're not irrigating it effectively. You want to check your catheter that the irrigation tubing is actually connected, and by rotating the catheter, you're disconnecting the tubing. So it's usually a sign of a problem if you see the tip heating up, but it's not useful in terms of gauging lesion size. And this is just, again, a graphic example where A is an example of a 4-millimeter non-irrigated lesion. At 20 watts, you're heating to say 75 degrees, and that's falling off of distance, and then at the 50-degree mark, you end up with a 3.5-centimeter depth lesion. If you have the same size catheter irrigated, now that's B in blue, and you'll see that, again, you get the same size lesion, but now you're cooling the temperature at the tissue interface, so you don't see as much of a temperature rise. On the other hand, if you crank up the power now to 50 watts, because you can, what happens is you're cooling the temperature at the interface, but now you're getting a much higher temperature at depth. And so the other downside of irrigated And so the other downside of irrigated ablation, because you're not as aware of the temperature at depth, is the possibility of steam pops, because you can imagine if this temperature at depth gets above 100 degrees, the tissue will boil and you'll get a pop. Important to realize, again, with non-irrigated ablation, the maximal temperature is at the tip tissue of the electrode tissue interface, and then you have conductive heating that forms your lesion. By cooling the surface, that hottest point is going to be deeper with irrigated ablation, but the ensuing lesion size is about the same. It's just that you're cooling this electrode tissue interface. Again, you have to be aware of steam pops with irrigated ablation. This is from Bill Stevenson's lab. When the impedance drop was less than 10 ohms, there were no steam pops. 80% of the steam pops occurred with impedance drops greater than 18 ohms. So if you're getting up to that 15, 18 ohm range, again, crank back the power, come off, because then you're headed towards a steam pop. The other thing just to think about, and I think now we do think about it more, is the importance of contact and the force of contact in terms of lesion formation. So this was a sort of experimental catheter that never got FDA approved, where you could actually see inside the heart, and so now we're looking at the heart during a catheter ablation. You can see the red tissue turning white as we're ablating, but what you can see is, while you're looking at fluoro, it may look great, but that catheter is not super stable, right? It's hopping sometimes on and off the lesion, and that will lead to ineffective lesions. So that led to the development of contact force catheters, where you could actually measure the force of the contact up against the tissue, and through nice studies by some, including Hiroshi Nakagawa, it was shown that the more force you apply, you will actually ensue in a larger lesion, right? Two grams, 20 grams, 60 grams, probably need at least five grams to have stable contact with the myocardium. But if you push harder, because you're compressing the tissue, and more of the tissue surrounding the electrode, you'll get a larger lesion. So it's a combination of high power and high force, where you're most likely to get a steam pump. But again, it's shown on these graphs, whether it's 30 watts or 50 watts, at any given power, the more force will lead to a bigger lesion. Now sometimes you may have thick tissue, you may have a mid myocardial circuit or deep septal circuit, you can get to that even with high force and high power. And so, while not commercially approved, should mention that, you know, standard ablation is unipolar, it's between the tip of the electrode and the reference patch, usually on the patient's back or side. Bipolar ablation, on the other hand, is ablation between two opposing catheters. And that has an advantage because as opposed to sample A here, where you're doing two sequential unipolar lesions on the epi and endosurface, when you're heating from both surfaces simultaneously, you're more likely to heat the tissue in the middle and get a transmural lesion. And in this study from Jacob Carruth at Vivek Reddy's lab, they showed that with bipolar ablation, you were able to achieve transmural lesions 82% of the time, versus only 33% with sequential unipolar. So, that can be a trick with lesions, for example, in the LV summit or septal lesions. This is just a case where we had a VT from deep in the septum, and we have two catheters, one from the RV endocardium and one retrograde aortic from the LV opposing each other. You can see the two kissing catheters on fluoroscopy to make a bipolar lesion. Will Sauer and Alain Anter also have looked at different combinations of catheters. If you're going to do bipolar catheters, you use two 4mm catheters, technically a 3.5, or a 4 and 8 perpendicular, or 4 and 8 parallel. And for what it's worth, they found a 4mm with a parallel 8mm catheter, as your reference, led to the biggest lesion size. So, you generally need custom cables to perform bipolar lesions. Perhaps a simpler way of increasing the lesion size is to change the arrogance. So, instead of normal saline if you use half normal saline. Why does that work? Because if you look at the electrode tip and you're now with a shower head washing half normal saline around the electrode, it means the saline in the myocardium has a lower impedance and that's gonna preferentially channel RF energy into the tissue. So in this study, again by Will Sauer that we collaborated on, by changing the irrigant from normal saline to half normal saline, again not commercially approved, you get about a 30% increase in lesion size and that's something any lab can easily do. So we often will have half normal saline in case and we always start with normal saline but if we're having trouble with a deep VT or septal PVC or summit PVC, we'll have the option to change to half normal saline to try and increase our lesion depth a bit. You are more likely to get steampops with half normal saline and even more steampops with, people always ask, well what about D5W with no saline? Much higher incidence of steampop. So I wouldn't use D5W but half normal can be used. Another I think change in our thoughts about ablation was this idea of high power short duration ablation. So we know for AFib ablation, we're getting multiple lesions around the pulmonary veins and a lot of answer to this nice study where he looked at, rather than giving low power, longer duration lesions, a high power short duration lesion. What that does is the majority of your lesion is then formed by resistive heating as opposed to conductive heating. And as shown here, normally we're getting more resistive heating and less conductive. With high power short duration, it's more conductive, less resistive. What you end up with is these lesions shown here on the right. So it's a wider, shallower lesion. Now in the atrium, shallow may be fine, right? We don't wanna necessarily need dramatic depth. We don't wanna hit the esophagus in deep structures. What we want is a wide, fast lesion. And he showed compared to standard ablation parameters of like 30 to 40 watts, giving 50 watt lesions of a shorter duration actually led to more contiguous linear ablation. Also a much shorter procedure. We looked at this with a study where we randomized patients at UCSF to either high power short duration or standard power. Not surprisingly, the high power short duration led to a shorter procedure time, but actually a better freedom from AF at a year compared to standard power. Although there were a few more asymptomatic cerebral lesions seen on MRI. So that's maybe a downside of delivering high power that you're more likely to get some char. But this pretty much changed a lot of work, I would say changed the paradigm of AFib ablation as well as others like Jay Natale, Roger Winkle, where most of us shifted to a high power short duration approach. Now lesion indexing also came around as a way for us to get more surrogate information about our lesion depth of irrigated ablation. And these are indexes that integrate power, contact force and time to give us a sense for how big a lesion we're getting. And the different systems have different lesions but different parameters, but basically the longer you stay on, the larger this lesion index parameter gets and that can be proportional to lesion depth seen in the experimental lab. And it's a good way to get a sense of, when you're trying to push the boundaries between lesion size and complications, where you are for a superficial right atrial tachycardia, you may not need as big a lesion as for a septal ventricular tachycardia. And then again, this is now, I call this talk EP101, but this is an advanced concept, EP201, which is again, another nice study from a lot of answer that's changed a little bit how I do ablation, realizing that for any given ablation index, you know, beginning to say, in this case, an index of 800, you would think intuitively, if you were to pour in higher power, 40 or 50 Watts, you're gonna get a better lesion than at a lower power. Well, it turns out, for example, shown on the right here, 30 Watts, 15 grams, versus 40 Watts, 15 grams, for the same ablation index of 800, you actually get a smaller lesion with higher power. How can that be? You're giving more power. Shouldn't your lesion be bigger? And the answer is, it's related to duration. So to get to the same ablation index at a lower power, you spend more time, and that time allows more conductive heating and ends up making a bigger lesion. So whereas high power short duration is good for the atrium when you want a superficial lesion, when you're ablating the ventricle, it may actually make sense to have a lower power, longer duration lesion. So I, you know, whereas we used to ablate with 50 Watts, I kind of have cut back to say 35, 40 Watts in the ventricle letting the lesion take a little bit longer, and that can help in terms of your lesion depth. So I think a important biophysical principle that you really can use clinically, you're not getting the VT to go away, you're giving 50 Watts, it may be faster, but you may need a longer, lower power lesion to get that. Needle arc ablation has been described primarily by Bill Stevenson and Nusha Pedro. These are catheters that have a needle that can extend from the dome of the electrode. And this needle actually also infuses saline into the tissue and that lowers the impedance and creates very large lesions. There are no commercial catheters approved for this, and it's being looked at experimentally and thought I would mention it. So for RF ablation, again, tissue injury occurs reproducibly at a temperature of 50 degrees. For non-irrigated RF, the lesion size is proportional to electrode radius, the temperature at the tissue electrode interface and the power delivered. Larger tip electrodes allow more delivered power, generally due to greater cooling by the blood pool. And irrigated RF allows you to control the cooling, so it allows greater delivered power and therefore larger lesions by cooling the electrode tissue interface. But again, at the same power, you're not necessarily getting a bigger lesion. So if you're not getting a pathway to go away at 50 watts with a non-irrigated catheter, changing to irrigation is not gonna help. If you can't get it to go away with 10 watts though with a non-irrigated catheter because of your heating up to 60 degrees, well then changing to irrigated is gonna help because you can deliver more power by cooling the tip. So remember lesion size is no different with the same power using non-irrigated or irrigated ablation for the same power and duration. Better contact force will give you larger lesions. And if you're really trying to have a tricky case, a tricky DPVC exit, and you're trying to enhance lesion size, tricks are bipolar RF, half normal saline irrigation, for AFib, perhaps high power short duration or needle enhanced RF ablation. Again, most of these are experimental and not commercially approved. I'll just give a few words on cryoablation. Here you're, as opposed to heat destroying cells, you're creating hypothermia when you get below zero degrees that results in ice crystals that destroy the cells. Now, when you're at zero to 30 degrees Celsius, you'll have a transient loss of function, but that will recover. And that can be an advantage of cryoablation. Even if you're below zero at the electrode tissue interface, you have a leading edge, in this case, of stunned but viable cells. And so as opposed to what I mentioned with RF test burns, this could be advantage of a test freeze, or if you see an adverse event from a freeze, like AV block, if you're near the HISS bundle, and you turn the cooling off right away, you can have recovery of that tissue. And so cryoablation is gonna be safer near structures that might be at risk of injury. But again, if you stay on, you can cause heart block or injure any tissue with cryo as much as with RF. So the unique advantages of cryo, one is adhesion to cardiac tissue. When it freezes, it sticks, so you don't have to long for the catheter, you're not dependent on pushing for contact force. And it can be very stable if you're, you know, in a rapid heart rhythm or near a critical area and you don't wanna move. Again, this reversibility of the electrical effect when you're cool, but not frozen, and the lesions seem to have better preservation of tissue architecture. This is just a case I did with RF. It was from a moderator band PVC. You can see ice here, and I'm gonna play this video. So you can see with the ice, the problem for this moderator band is we're just hopping on and off it, and we just could not get stable enough to get this PVC to go away. So we switched to cryo on the right, and now look at ice. I mean, we're stuck to that moderator band. You can let go of the catheter, and PVC went right away. So on mobile structures like the moderator band or the papillary muscles, can't get good stability with RF. Cryo is a good option because of that adherence freezing. In general, with a four millimeter RF catheter and four millimeter cryo, you are gonna get a smaller lesion volume with cryo. And so cryo comes in four, six, and eight millimeters. Most people for commercial use will use a six millimeter cryo catheter because of higher recurrence rates with four millimeter catheter. Eight is also available, but requires a larger sheath. And again, if you look at tissue architecture after RF, you may have more disruption of endothelial boundary and perhaps some char or thrombus formation, whereas you tend to get cleaner lesions with cryo. So for cryo, cryo ablation kills cells via ice crystals. Volume of ablation lesions with four millimeter tip are generally smaller than RF lesions with similar depth. So most operators will use a six millimeter tip for focal applications. I didn't talk much about cryo balloon, but that is a widely used, I would say, for pulmonary vein isolation. Although not competing with pulse field ablations, why they spend a lot of time on it, but the same biophysical principles apply. And cryo ablation in general has the advantage of reversibility, less thrombus and preservation of tissue architecture. So moving on to the new kid in the block, pulse field ablation. So pulse field ablation is a non-thermal ablation modality, does not use heat or freezing. What it uses is a high voltage electric field. And as shown on the right, that high voltage electric field causes electroporation, or it forms holes in the cell membrane. And if it's at a low electric field, you will get recovery of the cells as shown in the bottom, and that can be used to transfect drugs for chemotherapy. But if you give a high enough electric field, the cell contents spill out and the cell dies. So as shown on the left here, electric field applied. Again, often we're using about 2000 volts. And at any particular duration, you can get at a lower electric field reversible electroporation, but obviously what we want for catheter ablation is irreversible electroporation. And if you crank the energy up high enough, you will get thermal effects. It's important to realize that in generally, again, we're operating around the 1500 to 2000 volt per centimeter range for irreversible electroporation. Thinking about pulse field ablation, it's really completely different than RF. There are a lot of parameters that can be varied. A lot of it is done by the companies and we have a limited ability to make adjustments. You can adjust the strength of the field. So here, 500 versus 1000 volts, most of the waveforms now are not monophasic, but biphasic. You can have trailing waveforms. You can change the duration of these pulses. They're typically in the microsecond range for most companies, although some companies are looking at nanosecond range. You can change the number. Again, the companies change the number of packets, the orientation of the field. But in general, we can change the voltage, things are pre-programmed and part of sort of the secret sauce of proprietary company information, which is the number of packets delivered and the pulse width of each packets. But in general, you're getting a biphasic. And in this case, typically bipolar between electrode ablation modality, but there are some monopolar applications and catheters coming. Pulse field ablation, myocardial cells, it turns out, are just much more sensitive to the electric field than vascular smooth muscle or nerve cells. So why do we care about that? Obviously, when we're ablating tissue in the heart, we want to kill the myocardium, but spare, for example, the esophagus or nerve. So pulse field ablation, very difficult. From the endocardium, probably nearly impossible to cause esophageal or phrenic nerve injury. And that has certain safety advantages and has led to its adoption pretty rapidly for treatment of atrial fibrillation. Now, there's a big controversy about whether contact force matters or not for pulse field ablation as it does for RF. And it turns out it does matter. It's not as critical. But if you're not in contact, even though you're generating electric field, you just have poor tissue coupling and you will not get much of a lesion. And if you increase the contact up to a degree, up to 10 grams here, you will get bigger lesions as shown in these studies from Hiroshi Nakagawa. So probably, again, for different biophysical reasons, but probably because you're just embedding the electrode deeper into the tissue and compressing the tissue. So needing some contact is still important for pulse field ablation. You can't just wave the catheter near the area you're trying to ablate. This is from a study we looked at, and I think important just to realize that, we talked about the autonomic triggers in the atrial fibrillation lecture and the importance of autonomic changes. And with thermal ablation, we're getting a lot of sort of incidental autonomic de-innervation by ablating nerves around the heart. But when we looked at heart rate and heart rate variability changes in the ADVENT trial, which compared pulse field and thermal ablation, you'll see that there's a much less of an increase in heart rate and much less of a decrease in heart rate variability after pulse field compared to thermal ablation with either cryo or RF. So you are getting less adjunctive autonomic de-innervation and whether that plays into the long-term outcome after arrhythmia treatment of either AFib or VT remains to be determined. So again, for single-shot AFib, pulmonary vein ablation technologies, we've talked about some studies in the AFib lecture. This pentaspline catheter has been FDA approved as well as the circular catheter. But there'll be other catheters from multiple companies coming, and again, remember the waveforms that are delivered are really up to the companies and they don't tell us. So it's up to us to really make sure all of these are equivalent. Not every pulse field ablation catheter will be the same as opposed to RF where the technology is quite similar. Some new potential adverse events to be aware of with pulse field ablation. Again, we've said much lower incidence of esophageal injury or nerve injury. But one thing that's been recognized is when you apply pulse field, for example, with this pentaspline catheter near a coronary artery shown here, you will get spasm of the coronary artery. That's a direct effect of pulse field energy on the coronary artery. The spasm itself could be reduced by pre-treating with IV nitroglycerin. But in our preclinical studies, we also have seen chronic injury to the coronary arteries, mild, but characterized by neodymial hyperplasia and tunic-medial fibrosis. So in general, we want to avoid using pulse field ablation directly on coronary arteries, the same as we want to avoid it with RF energy. Just in terms of covering other ablation modalities biophysically, non-invasive ablation of ET has been described by Phil Kucelich using radiation therapy. So this uses non-invasive imaging to plan a region of the heart that you're trying to ablate for refractory VTs that are not amenable to catheter ablation. This is now being evaluated in clinical trials and is used at many centers. Interestingly, while one would think the primary effect of radiation, shown on the right here is the amount, the drop in voltage on a map after radiation at different energy levels seems about 25 greater than myocardium's enough to ablate tissue. So that's what most systems are delivering or trying to deliver about 25 gray locally. Interestingly, while you would think the electrical endpoint loss of voltage and removal of arrhythmias is due to fibrosis and loss of electrical conduction, in this one study, what they showed is actually that low doses of radiation from myocardium led to up-regulation of sodium channels and improved conduction. So you see a shorter PR interval and narrower QRS after radiation therapy, implying that there might be some beneficial effects due to improvement in the conductive properties of the heart as opposed to just fibrosis. And then there are some studies showing that while there's an acute benefit, some patients can have later VT recurrences. So the long-term outcome after non-invasive radiation therapy, I think, is still open and being learned. And again, there's a prospective randomized trial going on comparing radiation to catheter ablation after repeat, after a failed initial catheter ablation and an eoderone. So I think there's a lot more we'll learn about non-invasive ablation, but, you know, in the future, I'm sure we'll get better different energy sources. Now we're using, you know, LINAC or linear radiation, but people are looking at proton beams and carbon beams, and probably eventually we'll be, like the radiation oncologists, where we plan the therapy at home and don't need to play with different catheters, but we'll see, that's probably far away. So to summarize in terms of the biophysics of ablation, radiofrequency energy has been the standard for catheter ablation for the past several decades. Important to know the concepts of resistive versus conductive heating, electrocytes and configuration, irrigation and contact force. Focal cryoablation is, I would say, most useful for arrhythmias near the conduction system, but sometimes also for arrhythmias near mobile structures like moderator band or papillary muscles. Pulse field ablation is quickly becoming the standard for AF ablation. There's newer catheters being developed that may also be useful for VT, and those studies are underway, and important to understand the unique benefits as well as the new risks of pulse field ablation. And then stereotactic body radiation therapy or non-invasive SBRT is undergoing a prospective investigation for non-invasive VT substrate ablation and maybe have applications for other arrhythmias in the future as well. So thanks for your attention. I hope this was helpful and enjoy your day.

catheter ablation

radiofrequency ablation

cryoablation

pulsed field ablation

myocardial injury

electroporation

contact force

non-invasive ablation