bitter end of Saturday. I know everyone's got things to do, but this promises to be a really excellent session on ECGs, on AV block, old and new observations. I'm Evan Cronin from Temple, and I'll hand you over to my co-chair, Dr. Emily Ong from Yale, to introduce our speakers. Good afternoon, everyone. I'm Emily Ong from Yale, and it's my great pleasure to introduce our speakers for the afternoon. First, we have Dr. Behzad Bhavri from Thomas Jefferson University Hospital, and he's gonna be speaking to us about vaguely-induced and adenosine-sensitive paroxysmal heart block identification and treatment. Chairpersons, ladies and gentlemen, thank you so much. It's an honor to be here, and I thank HRS for inviting me. My task is to talk about vaguely-induced adenosine-sensitive paroxysmal heart block identification and treatment, and I have no disclosures related to this talk. Here's what I'd like to cover with you today. I'll first describe what is adenosine. I'll tell you briefly about the power of this vagus nerve, an amazing evolutionary achievement. Then we'll go over types of paroxysmal AV block, which is the meat of the matter, and then some summary, controversy, and take-home points. So let's get started. Adenosine is a nucleoside first discovered in 1929 by Drury and Zandt-Georgi, and it has been in clinical use since the 1940s. It was first used to treat SVT in 1984 and was granted FDA approval in 1989. Adenosine stimulates the same outward potassium current that is stimulated by acetylcholine via the K-adenosine receptor channels with a very short half-life. Adenosine effects are competitively antagonized by methylxanthines like aminophilin and theophylline, but are not antagonized by atropine. Adenosine has multiple properties, which we all know in clinical medicine and use. It is a vasodilator, hence it is used in myocardial perfusion scintigraphy. It slows sinoatrial and AV nodal conduction, and hence it is used for SVT termination. We all know that. It hyperpolarizes the pulmonary veins by increasing the adenosine current, and hence it is used for uncovering dormant PV connections after pulmonary vein isolation. It acts via four evolutionary, very well-conserved receptor subtypes, A1, A2A, A2B, and A3, and it is distributed in multiple locations in the body. The A1 receptors are mainly chronotropic and dromatropic effects, and they are in the sinus node and the AV node. The A2 receptors are mainly vasodilatory and antithrombotic, and they are mostly in the vasculature. A3 is in the lungs and the liver, in addition to a whole host of other tissues in the body, and activation of adenosine receptors leads to the production of cyclic AMP via G protein, and that drives potassium ions out of the cell that repolarizes or hyperpolarizes the cell membrane. It has roles in the central nervous system, in inflammatory and immune response, endocrine system, lung function, kidney function, is antithrombotic, and an endogenous modulator of pain, so it's a really important molecule in the body. That brings us to the power of the vagus nerve. In Latin, the word vagus means wandering, and that's also the origin of the word vagaries, and it is the 10th cranial nerve. It is the second largest nerve in the body after the sciatic nerve, and it has far-reaching afferent and efferent innervation, extending all the way from your eyeballs and the meninges all the way down to the end of the GI tract, and cardiac innervation is very extensive, especially in the left atrium, the sinus node, the AV node, and it extends also into infernodal and ventricular tissues, although to a lesser extent, so this nerve is very powerfully responsible for homeostasis and internal organ function and bodily function, and that brings us to types of paroxysmal AV block, which is what we are here to discuss today. So in 2017, doctors Este and Brignole from Italy suggested three types of paroxysmal AV block, intrinsic paroxysmal AV block, extrinsic vagal paroxysmal AV block, and extrinsic idiopathic paroxysmal AV block. Intrinsic paroxysmal AV block is something that is well-known to everybody. It is a manifestation of conduction system disease, cardiac syncope, also called a Stokes-Adams attack, progression of atrioventricular conduction system disease and causing syncope. Extrinsic vagal AV block is also very common. It is associated with high levels of endogenous adenosine. Syncope is due to the parasympathetic effects of vagal activation on the AV node and on the sinus node, and it is what we call reflex syncope, classic vasovagal fainting, sight of blood, trumpet player syncope, laugh syncope, cough syncope, et cetera. And then there is extrinsic idiopathic paroxysmal AV block, which is a little bit harder to recognize. It is associated with low levels of endogenous adenosine, and it's also called low adenosine syncope. So we're gonna dive into the extrinsic types of paroxysmal AV block in some greater detail. First, let's go over conduction system disease or cardiac syncope. That is well-known to everybody. It's typically an older patient who presents with an abrupt episode of usually injury-related syncopal event, recent onset of symptoms, and ECG show evidence for conduction system disease, either fascicular blocks or bundle branch blocks, except if the block is intra-his, in which case the QRS can look completely narrow. AV block is sometimes initiated by an APD or a VPD. PR interval is unchanged prior to block, Mobitz II behavior, and the sinusoid rate actually increases during the block from reflex sympathetic activation to compensate for the drop in blood pressure that occurs with asystole. AV block may begin or end with a PAC or a PVC. Here is an example of two PVCs initiating block. Note the acceleration of the heart rate that occurs as block progresses. Here is an example of an atrial premature beat that causes a compensatory pause and causes what we call phase four block, intra-his block, most likely because the QRS is narrow. Once again, the sinus rate accelerates. It can progress to complete heart block, except when it's intra-his, which is unlikely to progress to complete heart block, and there's often underlying structural heart disease. The treatment is a pacemaker, and plasma adenosine levels are usually normal. Adenosine challenge is usually negative, not required. It's a clear-cut diagnosis. Head up tilts is, again, not required, but if done, is usually negative. EP study is frequently positive. You uncover either sinus node or infranodal conduction system disease, and carotid massage is usually negative. That brings us to the common vasovagal syncope kind of episode, or reflex syncope, high-adenosine syncope. It's usually a younger patient, often seen sometimes during sleep. If it occurs during awakening hours, there's a long prodrome, where patients describe progressive symptoms over the course of many minutes. Long-standing symptoms have been there since youth. They have had multiple episodes, and ECGs are quite benign. They show no evidence of conduction system disease, but they may show Mobitz 1 Winkiebach periodicity prior to block developing, and curiously, as the heart block develops, the sinus rate slows. The same vagus that's causing the AV node to block also slows down the sinus node, so this combination of AV block and sinus slowing is quite a pathognomonic of this type of syncope, and afterwards, there's rebound tachycardia, and here's an example. You note that it occurs during sleep. The heart rate slows. The PR interval prolongs, and then there is reflex rebound tachycardia that occurs at the end. This does not progress to complete heart block. It is seen in normal hearts. It requires not a pacemaker, but fluids, salt, and lifestyle changes, teaching the patient to recognize the warning symptoms and assume the supine position. Plasma adenosine levels are typically high. Adenosine challenge may or may not be positive, and head up tilt is usually positive. EP studies are not indicated, and if they're done, they are going to be negative. Carotid massage is often positive, and that brings us to extrinsic idiopathic paroxysmal AV block, or low adenosine syncope. Usually occurs after age 40, although it can occur at pretty much any age. They have either very short or no prodrome, so it's different from the previous type of classic vasovagal fainting where there's a long prodrome. It is recent in onset, and ECGs show no evidence of conduction system disease. There are normal ECGs at rest, and there's no change in sinus rate or PR interval prior to, during, or after the block. And this is an example. This is a patient with a loop recorder who had vomiting. It was clearly a vagal event. You can see she goes into a long period of asystole, almost fainted at the toilet while she was throwing up, but the sinus rate barely budges. It doesn't change at all appreciably. And it does not progress to complete heart block. They have normal hearts. Once again, this does not need a pacemaker, usually, but you can try theophylline. There are some people who would say that a pacemaker is indicated if the patient is having recurrent episodes, unresponsive to theophylline therapy. Plasma adenosine levels are very low, and adenosine challenge is dramatically positive. Head up tilt is usually negative, and EP study is also negative. Carotid massage is negative. So you notice I've been talking about plasma adenosine levels. Now I'm gonna tell you about what this means, that what is the hypothesis for these extrinsic varieties of paroxysmal AV block not due to conduction system disease. Adenosine, as you know, affects the AV node via stimulation of the high-affinity A1 receptors. The number of adenosine A1 receptors undergoes upregulation or downregulation depending on ambient adenosine levels in the bloodstream. When the adenosine plasma level, the constant of dissociation of the adenosine receptor is 0.6 to 0.8 millimoles, and when the adenosine plasma level is above this value, in that situation, most of the adenosine receptors in the AV node are already occupied, and they are not available for activation. In fact, the A1 receptor expression is now downregulated because there's a lot of adenosine in the circulation, and endogenous adenosine release is unlikely to create AV block. So adenosine is not going to cause heart block in this situation where there's a high adenosine level to begin with. However, if plasma adenosine levels are low, below this dissociation value, most of the adenosine receptors are open. They are available for activation, and in fact, the receptor expression is now upregulated, and as a result, even a modest release of adenosine can bind to a high number of A1 receptors and cause dramatic AV block. So that is the distinction we think. This is the hypothesis that explains the difference in these two types of syncope. So this is a graph that shows the plasma adenosine levels in these two scenarios and in between. So here's mostly free adenosine level, and here's mostly saturated adenosine receptors. So this is low APL with mostly free receptors, and this is high APL levels with saturated receptors, and you can see that, and then something in between. Now, if you do a head-up tilt in such patients with paroxysmal AV block, the patients who have mostly free adenosine receptors will develop AV block, and the treatment for that is theophylline. For the patients who have mostly high adenosine levels and saturated A1 receptors, there is no effect on the AV node, but they do have peripheral vasodilation, so they drop their blood pressure, and the treatment for that is going to be salt fluids and compression stockings, and then, of course, there's the category in between that is tilt positive and may often require a bit of both. So to summarize the types of paroxysmal AV block, the classic cardiac syncope due to conduction system disease, the extrinsic classic vasovagal syncope with high adenosine levels, and the extrinsic idiopathic AV block with low adenosine levels, let's summarize the data. Age, they're usually older for the first category, can be male or female. For classic vasovagal syncope, it's often younger, most often female, and it can be at any age, male or female, for the third category. Duration of symptoms, recent onset, long-standing recurrent, and recent onset. ECG findings in the first category, obvious conduction system disease, wide QRS, prolonged PR, Mobitz II behavior. Extrinsic, normal, but during effects, you can see vagal activation by Wenkebach periodicity and prolonging of the AV nodal conduction times. And over here, it's a normal ECG, but shows abrupt AV block, almost looks like Mobitz II behavior, but usually with a narrow QRS. Adenosine plasma levels are normal in acquired conduction system disease of aging. They are high in the middle category and low in the third category. Action occurs via the A2 receptors and the A1 receptors, the peripheral vasodilation and the AV nodal blockade that we talked about. Head up tilt is not needed for conduction system disease. It's positive for classic vasovagal fainters, and it's often negative for idiopathic extrinsic AV block. EP study is positive. You'll uncover conduction system disease, but it's negative in the other two. And the treatment is a pacemaker for the first category, salt fluids and fluorocortisone, tilt training, elevate the head of the bed, and so on, and theophylline, and possibly a pacemaker for this kind of extrinsic idiopathic AV block associated with low adenosine levels. So to summarize and to take home points and some controversy about all this, there was a study done that said, can you use the ATP challenge test to identify need for pacing in the two different types of extrinsic block? And so the methods were, it was a multicenter randomized trial of cardiac pacing guided by ATP testing. And there were 80 patients with abrupt syncope of unknown origin, and they all had an ATP challenge test, and they all were positive. They got 20 milligrams of IV ATP bolus, and they were positive if they had more than 10 seconds of asystole, pretty dramatic. In fact, the mean pause was much longer. They were 75 years of age, 56 had no structural heart disease. AV block was the predominant finding, and the average pause was 18 seconds of asystole. And all patients got a pacemaker, but they were randomized, unknown to the patient, either to DDD pacing at a base rate of 70 beats a minute or to AAI pacing at 30 beats per minute. In other words, no protection from AV block. And they followed them for up to five years. Mean follow-up was 16 months, and the results are as follows. Syncope recurred in eight out of 39, or 21% with dual-chamber pacing, but it occurred in 66% of patients who had AAI pacing, and a significant difference. And the 27 patients who had recurrent syncope with AAI were then reprogrammed to DDD, and only one patient had recurrent syncope out of those 27. So in total, 71 out of 80 patients who had a positive adenosine challenge test had freedom from recurrent syncope with dual-chamber pacing. And so, conclusion was that the ATP test can identify patients with abrupt syncope who benefit from dual-chamber pacing, who don't have overt conduction system disease as an indication for pacing. And limitations to this elegant insight into this pathology or pathophysiology are plenty. Unfortunately, by the end of this talk, I can tell you that you can pretty much forget about all of this, because it has little clinical impact, unfortunately. So the role of adenosine testing in syncope has not been advocated by the guidelines. Authorities in syncope have stated that it is now time to abandon adenosine testing. It has been described as a test looking for a home, I think pretty brutal in some cases. And if there remains a role for adenosine testing, it might be in patients with syncope of unknown origin, even after extensive testing has been performed, and you haven't identified any ideology you might consider this test. So to summarize, a low plasma adenosine level is associated with paroxysmal AV block or carotid hypersensitivity. Theophylline may be a reasonable medication to try. Pacemakers potentially could be of help. A high plasma adenosine level is associated with hypotensive or vasodepressor syncope, where pacing is definitely not indicated. It's salt fluids, tilt training, compression stockings, et cetera. The ATP provocation test has been shown to demonstrate the utility to select patients for pacemaker implantation. However, low predictive value of the test does not support its routine use in selecting patients for cardiac pacing in patients with syncope. Rather, documentation of a bradycardia, either by a holter or a loop recorder during a spontaneous syncopal recurrence, remains the preferred eligibility criterion for pacing. And this comes from Dr. Brignoli himself, who originally described the different types of response to adenosine levels. So with that, I thank you for your attention. If anyone has any questions, please feel free to submit them. We'll be taking actually questions at the end of the session for all of our speakers. You can submit questions into the app, by the way, they'll come up here. Also we have a microphone in the room for the end. So next it's my great pleasure to introduce Dr. Sergio Pinsky of the Medical University of South Carolina, who is going to talk about multilevel block, benign and malignant, and I think anyone who's been following Twitter in the past will have had some previews of what we're about to see. Thank you. I want to thank the program committee for putting together this non-PFA session. Now I'm going to talk about multilevel block with the classification between benign and malignant. I have no disclosures regarding this talk. Let's start with this tracing. It's a tracing that many of us have seen. It's a typical atrial flutter with a mygeminal ventricular response. Let's start with what this is not. This is not variable block, as the computer algorithm will tell you. It's very fixed. It's not variable. If one counts the number of flutter waves and QRSs, one finds each sequence there six flutter waves and two QRSs. So one may say this is three to one block, but it's not because in three to one block should be regular, should not be by geminal. Even if one counts with more care, one sees that there's first a two to one sequence and then a four to one sequence. So one can say this is two to one alternating with four to one. That describes what we see, but does not explain it. First, why would the AV node behave in this particular mode? And second, if this were true, then the long R2R should be twice the short one, which clearly is not. And also, each of these intervals should be an exact multiple of the flutter cycle length, which is not. So we're talking about multilevel block. This has instances of what one could call a two to one block with a prolonging PR or flutter to QRS, and terminates with two or three block P or flutter waves. In the past, this has been also known as alternating Wencky-Bach periods or Wencky-Bach periods of alternate bits. The literature is very diffused, but I like to differentiate two forms of it, which have different significance and prognosis. So as usual in electrocardiography, Peck and Langdorf were right, and they deducted what this was just by looking at the electrocardiograms from this paper in 1950. So the most common form of multilevel block, of course, during regular HR tachycardia and HR flutter, as we are going to see in a second, is very common. It occurs at the level of the AV node most of the time. One can consider it physiological, can be reproduced in the EP lab with rapid HR pacing, is facilitated by AV nodal blocking drugs, digoxin in the past, calcium channel blockers these days, and is dynamic. So going back to our first EKG, that was the 6-to-2 pattern. Essentially, we have an upper level in the AV node that has 2-to-1 block, and then a lower level that has a Mobitz 1. If this level is 3-to-2, then we get these 6-to-2 sequences. And here I have two examples. If the increment in the prolongation in the second bit is very little, the rhythm appears more bigeminal. On the other hand, if the increment in conduction time of the second bit is more marked, the QRS may look more regular and may even think like it's a 3-to-1. So type A, this is how we call this multilevel block, results in 6-to-2, 8-to-3, or 10-to-4 sequences. There is an even number of cycles. The formula is n over 2 minus 1. And as we see in these examples, always ends with three flutter waves blocked in a row. Here we have the 6-to-2, the 8-to-3, the 10-to-4. And to show you that this is a real phenomenon, I'm going to show you some examples. This is an HR tachycardia with 8-to-3 conduction. So this is best explained by the 2-to-1 in the upper level and a Mobitz 1-4-2-3 in the lower level. HR flutter with 10-to-4. Again, we have 2-to-1 upper, but the lower level is a 5-to-4. Here I have another example with 2-F-to-5 conduction. There is 2-to-1 upper level and Mobitz 1-6-to-5. This is to show that this is a real phenomenon, because we see here the fluctuation between a 6-to-2, which is a bigeminal pattern, and an 8-to-3, which is a trigeminal pattern, depending on the sequence of Mobitz at the lower level, 3-to-2 versus 4-to-3. And this is what one can see clinically when the patient presents with HR flutter. Patient presents with 2-to-1 conduction. In this case, we see that there is a right bundle and left anterior hemiblock. The patient receives an avenodal blocking drug, most commonly diltiazem. And we see that in the ER, we see this change to a 6-to-2. Look now, there are divergence urnia occurs on the short R-to-R. It's a typical Ashman phenomenon. As the patient receives more avenodal blocking, it goes to 4-to-1, which now we see that, in this case, the aberrancy disappears completely, the right bundle. So why do we get 4-to-1? We get 4-to-1 because 4-to-1 is two levels of 2-to-1. So here, we have this beautiful example. The patient was in a 6-to-2 AV block, with a 3-to-2 Mobitz in the lower level. We apply carotid sinus massage. We increase the level of AV block to 2-to-1 in the bottom level. And then you get this 4-to-1. So with two-level blocks, one cannot get more block than 4-to-1. If one sees more than 4-to-1, that means that there are three levels of block. And I want to show this beautiful example that was a courtesy of Dr. Josh Cooper. We see a patient who had HR flutter and had some AV nodal blockade, which dissipated during the course of the day. And we see here the tachogram, which shows several increments in the heart rate in very marked steps. So the patient had, initially, an HR flutter with an HR rate of 320. When the patient had 4-to-1 block, the rate was 80. Then the lower level decreased from 2-to-1 to 3-to-2. And now we have 6-to-2 with 120 beats per minute. A little bit later, the lower level is reduced to 4-to-3. Now we have the 8-to-3 sequence, 133. When we have the 10-to-4, it's 140. When we have the 12-to-5, it's 144. And eventually, the lower level dissipates completely. And we have, again, 2-to-1 with 160. So this beautiful example shows that this is a real phenomenon. Now there is another form of multilevel block with HR flutter, which is different, like in this case, with 5-to-2 conduction. In this case, the upper level is a Mobitz 1, 5-to-4 here. And the lower level is 2-to-1. This generally occurs with HR arrhythmias that are a little slower than the ones we show with the A pattern. So we call this type B multilevel block, which results in 5-to-2, 7-to-3, or 9-to-4 sequences, when the number of HR cycles is odd. There is a Mobitz 1 at the upper level and 2-to-1 in the lower level. The formula is N minus 1 over 2. N is different than the other ones with two flutter waves block in a row. And there may be different behaviors when the number of HR cycles in the 1-qubit sequence is even. So again, to show that this is a real phenomenon, we see here a fluctuation between 5-to-2 by geminal and then 7-to-3 trigeminal. Let's try to understand why this happens. One can reproduce this in the AP lab with HR pacing. Here, we are pacing first at 110, and we get Mobitz 1 block. As we increase the rate to 170, there is 2-to-1 block. And generally, we would stop here for fear of inducing arrhythmias. But as we increase the rate now to 190, we get first type B multilevel block sequences. As we increase the pacing rate farther, we go to type A sequences, first with 8-to-3, at 230 with 6-to-2, and eventually at 290, which is the flutter rate, we get the 4-to-1. And this can be explained with this model. One can assume there are three levels of block in the A-B node, A, B, and C. The upper level generally behaves 2-to-1. The middle level behaves in a winky bank fashion. And the lower level that we call here C can occur in 2-to-1. So when we have the most common type A-B block, we are having a block on the 2-to-1 and the winky bank second. When we have the level, the type B block, then the upper level is the level B. So we start with a winky bank, and the second level is the level C with 2-to-1. So this is why one pace is progressively faster. One can go from the type B to the type A, because then we create the first level at the A level. And there is some experimental studies to show that this is a real phenomenon. This is an old study with a rabid A-B nodal preparation, where they impale cells in the N region and the N-H region. And we see that there is two levels of block. So in the upper level, we see that it blocks here. But the lower level, which would be the N-H region, had the winky bank block before. So you see these two different levels of cells impaled there. Now I said that when the type B, when there is an even number of H-S cycles, can have different behaviors. So when the upper level is 7-to-6, it's easy. We have a 7-to-3. But if the upper level is 6-to-5, then the next bit may not conduct. And then you need two sequences to complete the sequences. And we end up with a 12-to-5. But on the other hand, at times, after the block mobs its one bit in the upper level, the lower level may have recovered. And you end up with this very interesting pattern of an HR tachycardia with 4-to-2 conduction with alternating PRs, a long PR, a block B, short PR, block B. And this is the explanation of the two levels of block. So after the beta blocks in the upper level, the lower level have enough time to recover. People have, at times, described this as to separate the fast and slow pathway. But that wouldn't explain why the long path, the long PR occurs after the long cycle and the short PR after the short cycle. And also doesn't explain why this often fluctuates between these 4-to-2 and the 5-to-2. And this is an example from an EPI study showing that this is a real phenomenon. But in this case, the second level of block was below the hiss. So with rapid HR pacing, we get this 4-to-2, 1, 2, 3, 4, with prolonged PR. And we see that the first bit blocks below the hiss, and the second bit blocks above the hiss. HR tachycardia with 3-to-1 conduction is a very rare phenomenon to be sustained. But most likely, it's a type B multilevel block in which there is 3-to-2 morbids, one in the upper level, and 2-to-1 in the lower level. Occasionally, one can see three levels of block. But this is rare that would occur in the AV node unless the AV node is very sick. In this case, we have here a patient who had a 9-to-2 block. And interestingly, when they do the EPI study, the third level of block was below the hiss. So multilevel block, two levels in the node, and one level below the hiss. Now I'm going to change. I'm going to talk about what I call the malignant form of wanky bacterias of alternate bits. This is an EKG that many of us may have seen. There is sinus tachycardia, not very fast. We see that there is a 2-to-1 block where the PR appears to prolong. But then there are two block P waves in a row. And this is a right bundle branch block. This is a patient who had syncope and presented with this EKG for a pacemaker implant. So this phenomenon has been best studied by my compatriots in Buenos Aires many, many decades ago, where they describe a few patients who all have infrahisian disease and present them with these sequences. And most of them progress to complete her block or need for pacemaker. And here we see seven to three sequences where you see prolongation of the PR in the conducted bit, and then two P waves that block in a row. So this malignant form of multilevel block, different than the previous one, occurs during sinus rhythm or mild sinus tachycardia. There is concomitant infranodal disease. There are at least one, but often two, levels of infranodal block. There is a high incidence of progression to heart block, and pacemaker is generally indicated. And this was relatively common during acute MI in the preperfusion era. This is an EKG I have saved for three decades. We see here a patient who presents with an anterior wall ST-segment elevation, has right bundle branch block, and left posterior hemiblock, likely acutely. And in the past, this was an indication for prophylactic temporary pacemaker. And we see here that the patient, a few hours later, progresses to high-degree AB block. But before this, he has, again, these wanky back periods of alternate beats, where we see the PR prolongation in the conduct beat and the two P waves in a row. This is also occurring. Now from that paper from Argentina, they also had some experimental models. In that model, they would cut one of the bundle branches, and they would rub the hits to create some transient injury. And at times, they were able to reproduce these wanky back periods of alternate beats. Here we see a 7-to-3, and they were able to record a potential from the left bundle. And we see that there is an upper level of progressive A-to-left bundle prolongation, and the 2-to-1 block occurs below the left bundle. So this is a good proof that, at least in this experimental model, this malignant infranodal form of multilevel block exists. In the past, one could also see alternate wanky back periods in acute inferior myocardial infarction. Generally, they were ischemic and occurring during the first 48 hours, and oftentimes were precipitated by atropine, when atropine was given for, like, for example, sinus bradycardia. And the block occurred at the level of the node, plus minus the hiss. Here we have an example. The patient is in a junctional rhythm with sinus bradycardia. It receives one milligram of atropine. That increases the heart rate, and we end up with this 8-to-3 sequence of multilevel block. Now, up to now, I made a clear distinction between the benign and malignant form, but I think there may be in-between forms where an EP study may warrant it. Here we have an HF flutter that is not very fast, that is 5-to-2 conduction, and a left bundle branch block. So before assuming that this is the benign form of multilevel avenodal block, I think an EP study warranted to see if the lower level is not below the hiss. Thank you for our attention, and these slides will be available for download in my SlideShare net feed. Thank you. Our next speaker will be Dr. Rachel Kaplan from the Medical University of South Carolina. She'll be speaking about heart block after TAVR, prediction, rapid identification, expeditious treatment. Thank you to the committee for asking me to speak today on this topic, as it loads my slides. So heart block after TAVR, prediction, rapid identification, and expeditious treatment. We'll cover the prevalence and pathophysiology of conduction injury from TAVR. We'll discuss nonarrhythmia-related risk factors for heart block after TAVR, and then focus most of our time on arrhythmia-related risk factors for heart block, as well as risk categorization and management of each group that we can divide patients into. Studies of TAVR have compared surgical valves to the new TAVRs and have shown that TAVR is at least as good as a surgical AVR for many outcomes. TAVR is certainly much less invasive, and most patients prefer the idea of it compared to open-heart surgery. However, for us in EP, TAVR is not quite as golden as it is for interventionalists. Rates of pacemaker implantation after TAVR have consistently been higher than those after surgical AVR, as you see in the meta-analysis that need for pacemaker consistently favors a surgical valve. We can see in the histograms that the rates of pacemaker implant after surgical AVR are typically under 10 percent and pretty consistent in that, while those after TAVR have ranged in studies up to 20 to 30 percent and are really quite variable depending on the study. So why is this? So to answer that question, we have to step back and look at the anatomy of the aortic valve as it relates to the conduction system. In EP, we often focus on the parts of the conduction system that we routinely access from the right side of the heart. But it's also important to remember that when we talk about ablating parahysian atrial tachycardias, one solution is to target that from the non-coronary cusp of the aortic valve. This reminds us that the aortic valve is right there. It's right next to the hyst and the proximal left bundle. Consequently, implanting a new valve in this region can directly cause pressure on those structures and result in the conduction injuries. System EKG that we're all familiar with, however, when we see it the day after a TAVR, our approach to management is different than one day after a surgical valve replacement. That's because we know that in many surgical AVR cases, the same patient may recover and by a few days later have this EKG. In that patient, who almost certainly is going to have temporary epicardial pacing wires, we don't need to rush to make a decision about what to do as far as implanting a permanent pacemaker or not. After all, that patient's not going to be leaving the hospital anytime soon. They're going to be there for several days, continuing to recover from an invasive surgical procedure. In contrast, the TAVR patient is often ready for discharge the next day, and so the only reason they might stay in the hospital is until we as electrophysiologists decide what to do and implement a plan for their rhythm management. And so we have to manage this balance of keeping the patient in the hospital for close rhythm monitoring and the ability to have rapid response in the case that they do develop heart block, while being the service that is delaying the discharge and increasing length of stay. Additionally, pacemaker need after a TAVR is a complication, and so we have to work and communicate with our interventionalists so that we maintain some harmony with our colleagues. And this leads us to the three categories of factors to consider with regards to risk of serious conduction injury after a TAVR. Only one-third of these are really in our area of expertise as electrophysiologists. The others are related to details of the valve implant procedure, from valve selection to sizing and positioning during the case, as well as anatomic factors, and these can include degree of and location of calcifications and the size and shape of the landing zone for the valve. We'll briefly cover the nonarrhythmia aspects. Selection of the type of valve affects the risk for conduction injury with the self-expanding valves having a higher risk compared to a balloon expandable valve. However, if the interventionalist then performs additional balloon dilations of the balloon expandable valves, that step alone is a risk factor for conduction damage. It's helpful to see the procedure reports sometimes for us to get a sense of what valves were put in and what was done in the case to help estimate the patient's risk. Oversizing a valve also increases risk of injury, as does implanting it lower in the left ventricular outflow tract, where it's more likely to cause conduction injury. So we'll focus on the aspects that are in our area, pre-existing conduction defects and then the management of new ones. Right bundle branch block has consistently been shown to be a major risk factor for heart block from TABR. The reason makes sense when we remember anatomy. The TABR valve is most likely to damage the proximal left bundle branch, and if the right bundle is already weak, there may not be adequate conduction to the ventricles. These patients are at highest risk for heart block after TABR. Ideally this is something that is discussed with them beforehand by our colleagues. Although it is a major risk factor, not every patient who has a right bundle ends up in heart block, and so prophylactic pacemaker implant for all patients like that is not recommended. Many of those patients will actually not need pacing, and despite our best efforts, we still also have complications related to implanting pacemakers as well. When we look at the post-op EKG after the TABR, we can stratify patients into five groups that can help guide management, but it's also important to note that these are not completely siloed, and patients may move between groups as their EKG changes over the course of their post-op time. Group one are the luckiest patients. They have a normal EKG at baseline and a normal EKG post-operatively without any changes. For those patients, they just may need to be monitored overnight, and if there's no new changes, they can be discharged. If new changes did develop overnight to their EKG, then that patient would have to be reclassified into a higher risk group and then treated accordingly, as we'll discuss. Group two are those patients who have the preexisting right bundle branch block but do not have any new EKG changes after the TABR. Even without new changes, there is a recommendation to keep the temporary pacing wire overnight. If high-grade block develops, a pacemaker should then be implanted. If there are new EKG changes, which I mean by focusing on changes in the PR interval or QRS duration, then we'll follow the algorithm for a higher risk group. However, if no new EKG changes occur, the temporary wire can be removed and the patient monitored for a second day before discharge. In these patients, many of us also recommend that the patient go home with mobile telemetry or an event monitor in order to catch delayed onset heart block, especially if they had other non-arrhythmia risk factors for heart block after a TABR. Group three are one of the more complicated patients to risk stratify, and these are patients who have some degree of baseline conduction disease and then also have some changes in either PR or QRS durations after the TABR. These patients, the recommendation is still to keep a temporary pacing wire overnight, although actual practice on this varies and certainly not done routinely at my institution. If the EKG change is resolved, then the patient should be monitored for one more day, and if no new changes develop, they can be discharged. For those patients who have further EKG changes, we again are looking at the duration of the PR interval and the QRS, and specifically looking at cutoffs of a PR greater than 240 milliseconds and a QRS greater than 150 milliseconds as markers of higher risk injury. So where do those numbers come from? It's from this study that evaluated the post-op EKG of patients in sinus without a prior right bundle and it plots them out by the combination of their PR and QRS intervals and then what ended up happening to them. A small minority of patients had temporary pacing wires, as you can see with the circles. Those denoted by triangles develop late heart block, and specifically the red triangles show the high-risk patients, those who went into heart block without a sufficient escape rhythm. These are the patients who we worry most about, particularly if they're outside of the hospital. The blue triangles, on the other hand, are patients who developed heart block but had an adequate escape rhythm. And when we look at this figure, we can see that of the individuals with a PR less than 200 milliseconds and a QRS less than 120, none of them developed heart block. In the intermediate range of a PR from 200 to 240, and a QRS of 120 to 150, as shown in the gray, a few patients did develop heart block, but they all had an adequate escape rhythm. The red shows the high-risk patients and those with the PR greater than 240 or QRS greater than 150. A number of those patients developed heart block, including some without a sufficient escape rhythm. However, many patients, even in that high-risk group, did not develop heart block. And so the EKG characteristics have to be considered alongside some of the non-arrhythmia risk factors when we consider which patients should undergo a pacemaker implant prior to discharge as opposed to discharging them with a monitor if they have not developed heart block yet. Group 4 are those patients who have developed a new left bundle branch block after the TABR. Again, it's recommended that they continue to have a temporary pacing wire overnight. If they progress to developing high-grade block, then a pacemaker should be implanted. If there are continued changes in their PR or QRS intervals but not reaching the point of heart block, these patients are considered to be at higher risk, and additional precautions or investigations should be considered. And these can include a range of directions from just discharging with a live monitor to implanting a pacemaker or really anything in between. And that can include an electrophysiology study to help determine what direction to choose. In the middle of the figure, we can also see those patients in whom the left bundle branch block resolves. And in those cases, we monitor the patient for another day to assess for persistent recovery or for redevelopment of conduction injury. This helps us decide what direction to go with them. So how can an EP study help us sort this out? Well, the data have been mixed in different approaches to it. One of the earliest studies on this idea looked at a change in HV interval from pre- and post-TAVR. And although they showed that a change greater than 13 milliseconds had good specificity and sensitivity, reality is that this requires having a pre-TAVR HV measurement, and that's not something that's typically performed. Additionally, subsequent studies have not been able to show this association be quite as clear. Other studies have used absolute HV cutoffs of varying degrees, ranging from greater than 100 milliseconds to greater than just 65. However, most studies have centered around greater than either 70 or 75 as a cutoff. Some studies have suggested that a static measurement can be helpful in risk stratifying patients, but they've not proven themselves to be a clear step forward in risk stratification in all patients in these middle areas. And this may be because these conduction injuries can be dynamic, especially with valves that continue to expand after implantation. So the HV measurement may be different from day to day, and HV measurement of 60 on one day isn't necessarily as reassuring as we might hope. Rapid atrial pacing was brought up in one study and considered as having the benefit of being relatively quick and simple to perform, could even be done by our colleagues at the time of TAVR by pulling the temp wire back into the atrium at the end of the case. The protocol that was used was to gradually increase the rate up to 120 beats per minute and just see if the patient conducts one-to-one at this or if they develop Wenckebach. The initial study seemed promising, with 13 percent of patients who had Wenckebach at a rate of 120 ultimately getting pacemaker, compared to 1 percent of those who could conduct one-to-one. However, subsequent studies were not able to validate this, and with the factors coming out in multivariable analysis that were predictive of pacemaker implant being the ones we are already know, having a prior right bundle, having new persistent conduction injuries, and post-dilating the valve. Lastly, group five are those patients who had intraoperative heart block. For those patients who then persist in heart block, a pacemaker will certainly be implanted, and some cases will pursue this as soon as the same day rather than having the patient wait overnight. Now, particularly in those patients who have additional risk factors for heart block, many operators will choose to move forward immediately, and that way the patient could actually be discharged the following day, and we don't even lengthen their length of stay. For those patients who have temporary heart block with the TAVR, then we have to consider what to do because it is such a brief transient event that resolved. And so they should be monitored for new conduction injuries on EKG, and subsequently either discharged with monitoring or potentially pursuing other risk stratification, like for the last group. So in conclusions, conduction injuries post-TAVR remain frequent, and there are many patient device and implanter factors that can affect risk for conduction injury, many of which we have no control over. Risk stratification based on the EKG changes can be used to allow for early discharge in some patients or even an early pacemaker in other patients as indicated. There's increasing evidence to help assist with determining the plan for these intermediate risk patients, where it's not always clear what direction they're going to go immediately. Thank you for your attention. And last but definitely not least, I'd like to ask Dr. Carlos Morillo from the Libman Cardiovascular Institute, who's going to discuss syncope and bifascicular block, do the guidelines need an update, and is empiric pacing ever justified? Thank you very much for the invitation. Okay, thank you. I think we're first going to start with the... Guidelines always need to be updated, but it depends on the evidence. I guess you can scan the QR code if you want to ask a question. So this is a case of a 74-year-old male that presents to the emergency room after having two episodes of syncope. In the previous wake, that was abrupt onset, no prodrome. Past medical history is unremarkable. He's on no medications. He actually bumped his head quite bad and had a subdural hematoma. And this is his ECG. It shows a complete left bundle branch block with a left axis deviation. So I guess that the question here would be, what do you want to do? Are you going to do an EP study, a tilt test, implantable loop recorder, or are you just going to go directly to a pacemaker? And I think people can answer the question, but I don't know if the thing is working, loading. Anybody is using that app? Just show of hands, how many would do an EP study? EP study, yeah. The Europeans and Spanish, they all do EP studies for everything. Head-up tilt test. Nobody likes tilt tests anymore. Well, actually, 50%. A loop recorder. Nobody would put a loop recorder, and no one would pace this patient. Wow, interesting. Well, this guy was in Canada, so we pace everybody. So patient had recurrent syncope. Well, we gave him a pacemaker, dual-chamber pacemaker. But he comes three months later with syncope again. Exactly the same history. No prodrome, has syncope again, but the only thing is that he didn't have a second subdural hematoma. That's good. So he gets a tilt table test, which is kind of negative, has some positive carotid sinus massage, so vasodepressor response, despite being paced at about 80 beats per minute. The pacemaker interrogation was fine. So now what? You have a midriff fluorinef, call the syncope team. So this is what happens usually with these patients in the real world. Although he looked like he'd probably need a pacemaker, actually all you need to do is really a good history. So most of the time, people older, the good history is ask the wife or the partner, and that's what we did that day. So I asked the wife, so what's going on with John or whatever his name was? Well, you know, he's got this little carpentry in the garage, and every time he tries to reach that shelf up there, he faints. So we get him into an MRI, and we get him to try to get to the shelf, and that's what he got. He has a Stiehl's syndrome here from the subclavian. So sometimes it may look that people with a complete left bundle branch block, syncope without protome, look like a slam dunk to put a pacemaker, but all you need is actually a good history. Now, again, is program electrical simulation useful? There's where there's a discrepancy between the American-Canadian guidelines and the European guidelines. So usually the Europeans look for an HP study and look at the HP, and depending on what they find, they decide whether the patient needs a pacemaker or not. And this has, you know, evolved from the ESC guidelines in 2009 and 2001. You know, there's a Brignola study after a negative EP study. You can see that there's a proportion of patients that will have AV blocks, syncope, and the total number of events is about 40% to 50%. Now, we did a meta-analysis up there at Calgary with Bob Sheldon, Satish Raj, and myself and a bunch of fellows, and the thing is that we looked at those that had an implantable cardiac monitor and that had an ECG, looked at the value, the negative predictive value of these tests. The problem is that about 70% have an HP that will progress to complete heart block, and those that had an ECG description, and about only 30% with the implantable cardiac monitor. So really the negative predictive value of the EP study is not that good from our perspective. It's still 30% that, you know, would still have a question of that. So one would question how good is an EP study in this population. And again, the European guidelines have very strong indications for EPS-guided therapy in patients with syncope and biophysicular block. EP studies should be considered when syncope remains unexplained after non-invasive evaluation as a 2A, Class B recommendation. Patients with syncope and asymptomatic sinus bradycardia, EPS may be considered. And where did they get this information? So this is based on a couple of studies that are older studies, a press study that was a randomized study of patients with unexplained syncope and bundled branch block, and basically they saw almost a 60% relative risk reduction in recurrence of a combined endpoint of syncope, presyncope, and actional bradycardia, which seemed to indicate that DDD pacing at 60 beats per minute, pacing per minute, was much more effective than not pacing at all. And you can see here, here's the EPS IRR-guided pacemaker implant. None of those patients had syncope after going through that strategy, but empiric pacemaker did not do that well. About 30% still had syncope after 60 months, so about five years. And you can see that the total number of patients with syncope, DDD, and DDD-60 around here was not different. So really it didn't prevent syncope, which is why you want to put a pacemaker. Maybe presyncope, but that's not a very strong outcome. In symptomatic AV block, apparently there was a reduction that was about as significant. So the primary outcome was pretty much driven by preventing symptomatic AV block. So you may say, okay, it's worth doing an empiric pacemaker in that population. Now this is what the European guidelines from 2018 recommend. If you have a bifascicular block and an unexplained syncope, depending on your injection fraction, obviously it's less than 35, you go for an ICD or a shade of T, depending. And if it's greater than 35%, you can consider an EP study as a class 2A indication, and as a negative, go and implant an ILR. Some would say, well, if it's negative, why don't you just go on and put a pacemaker? And that's the other probability here. Now there's been some study. This one was published a few years ago that basically compared these guidelines, and you can see an implantable loop recorder in this population in the American ACCHA-HRS guidelines has a class 2A recommendation compared to a class 1 recommendation with some further recommendations here that patients with recurrent syncope of a known etiology, absence of high-risk criteria, and high likelihood of recurrence within the battery life of the device should probably get an implantable loop recorder or be paced. And again, you can see that there are some differences among the guidelines. Same thing with the diagnosis and management here between the EP study. Really, the American and HRS guidelines don't see any benefit in doing the EP study if there's a normal ECG and no structural heart disease. And the ESC, again, as I mentioned, there are some differences there. And this is from the pacing guidelines that are a little bit more current from 2021. Then again, in patients with unexplained syncope and bi-physical block, pacemakers indicated when the HV is greater than 70. I don't know. We don't do a lot of EP studies in this population in Canada, and I would think that in the U.S. you just go directly to a pacemaker or a loop recorder, but we can leave that for the discussion. And again, these are the predictors of pacemaker requirements in patients receiving a loop recorder for unexplained syncope, and this is in a group of systematic review and meta-analysis, not necessarily all with bi-physical block, but it shows you that most of these have sinus node dysfunction, AV block and AF, but really almost half of them really ended up getting a pacemaker. Now, the SPRIC-LEA trial was one that we ran up in Calgary, also in Canada. It's a multi-center Canadian trial. It's a post-3 trial in which we randomized patients to a pacemaker or to an implantable cardiac monitor with bi-physical block. It wasn't a very large study, about 100 patients overall, but the primary outcome was a composite outcome of recurrent syncope, presyncope, axonal bradycardia, or mortality. And you can see here that the monitor group did worse than the pacemaker group, but again, big surprise, absolutely no difference in prevention of syncope, which is the main reason why would you put a pacemaker in someone with bi-physical block and syncope. So some questions there on really which are the patients that actually benefit. Now, interestingly, all of the patients in the loop recorder arm crossed over to a pacemaker, and both strategies resulted in similar syncope outcomes, and primary pacemaker did reduce procedures at no cost to the outcome rate. Now, the thing that basically drove the main primary outcome was actionable bradycardia. So by looking at the loop recorder or even at the pacemaker when it's paced, you can see that the patients that had actionable bradycardia, so what does this mean, bradycardia less than 50 beats per minute, that was or not associated with symptoms, these patients did actually pretty well compared to those that had an implantable cardiac monitor. So for every ten patients, six bradycardias led to a pacemaker, two had vasodepressor syncope, one died, and one got demented or just withdrew from the study. So I don't think we still know exactly what are the patients that actually benefit the most, and we looked at left bundle, right bundle, and there was no difference in the outcomes here on the right between left bundle, right bundle branch, so we couldn't really identify the patients that benefit the most. We did some cost studies, and basically it is cost-attractive to just put a pacemaker in this population. So just to wrap it up, EP assessment, as far as I am concerned, has a weak sensitivity, but I know some people here in the audience that may make some questions and maybe think that EP assessment is important in this population. The ILR had a very high crossover rate to pacemakers, so maybe an empiric pacemaker is worth it, but keep in mind that almost two-thirds of these patients are going to continue to have syncope, and most of the syncope that they're going to have is going to be narrowly mediated or reflex. So probably the type of pacemaker or the programming or algorithm that we need to use may be a little bit different. Bundle branch block had no predictive value. An empiric pacemaker may be justified as first line of therapy, particularly in those elderly, frail patients that have been presenting with syncope, with trauma, and no proteome. So I'll leave it at that, and I guess we'll open up to the discussion. Thank you. Thank you. So if anyone has questions from the audience, you haven't put them into the app yet, please also feel free to use the microphone. Just to start through, there's some great questions here. For Dr. Pavri, perhaps, what is the best time to get plasma adenosine levels? Does that matter? Well, the best time would be if the plasma adenosine levels were available anywhere. Plasma adenosine levels that had been reported by Brignola's studies in those paroxysmal AV block patients were done mostly experimentally in one lab in France. So it's not something that you can order on your Epic and get it done, unfortunately. But what we've done, and there's been some interesting studies, and actually there's randomized trials going on, and actually what I do with those patients, I just give them theophylline if they're younger. Younger is under 50. And if they respond well to theophylline, I'll leave them alone. And if they don't, then there's another randomized trial that we're doing that you could either give them placebo or theophylline or randomize them to cardio-neuroablation for functional sort of AV block. I think another question for Dr. Povery. Some types of syncope, such as cough, defecation, or laughing, are particularly difficult. They're sudden and disabling. In the U.K., they actually result in a driving ban. Would you recommend trying theophylline prior to pacing for these patients? Sorry, could you please repeat the question? Yes. So some types of syncope, particularly cough, defecation, laughing-related, are particularly difficult. They're sudden and disabling. In the U.K., they result in a driving ban. Would you recommend trying theophylline prior to pacing for these patients? Yeah, that's a good question. I think you can certainly try it. Situational syncope is very difficult to handle. The usual recommendations for things like micturition syncope is to sit down and not be standing. For, you know, trumpet player syncope, laugh syncope, is to be aware and not engage in activities that might be known to bring it on. I don't think that's an indication for banning driving in the United States, as far as I'm aware. I don't know if that's an indication to take away somebody's license. But I think a theophylline trial may be reasonable. Unless you were playing the trumpet while you were driving. That would be quite a feat, yes. No, and the Canadian guidelines do not restrict driving for people with reflex syncope. In fact, the commonest cause of motor vehicle accidents in the United States is vasovagal fainting. But they usually result in fender benders, because the classic vasovagal fainting, there's enough of a prodrome that the patient can pull over to the side and, you know, put their head down and step on the brakes, so they don't result in catastrophic accidents, as opposed to ventricular arrhythmias that can be quite lethal. This is a great question. One of the frequent kind of troublesome things that you get consulted for from the SICU in particular, what's your advice for treatment of recurrent episodes of vaguely induced asystole in intubated patients in the ICU? Yes, we get that all the time. We see that in two scenarios, especially in spinal cord injury patients and then in other intubated patients who are... So if the intubation is clearly short-lived and there's nothing that is going to be permanent, then we do nothing except, say, pre-treat with atropine before you give... do the suctioning or the stimulus. For patients with spinal cord injuries, I really try to avoid a pacemaker as much as possible. I tell them that this is not a lethal condition. It will always end on its own. Usually those patients are bed-bound anyway, so it's not likely that they're going to have a catastrophic injury from a period of asystole. They're not likely to fall. But if it's a recurring problem, it interferes with their rehabilitation, I'm loathe to put in a usual pacemaker because of risk of infection from the tracheostomy site, so that's when I may consider a leadless pacemaker. But I do everything possible to educate the staff that this is not a lethal problem. It will always self-terminate. It is more concerning to the providers than it is to the patient. Patients are usually asymptomatic during these pauses and try and avoid pacing as much as possible. We saw that one of the best things that our tamoxetine does is prevent vaguely induced breast cancer. who may or may not have a history of syncope, but specifically during adenosine or egadenosone, they have prolonged asystole. I would do nothing, just use a different modality of testing. That's clearly an hydrogenically-induced asystolic pause. They may be one of those low-adenosine patients that Brignoli described. Yeah, I remember that before the guidelines of 2018, we were recommending the adenosine test to try to identify these patients, but then we got rid of it because the sensitivity and specificity was very low. There was only one study that was done in France in which they got some patients with adenosine-positive asystole and then gave them a pacemaker and it appeared to work, but it wasn't a randomized trial. And really, there's never been any data to support pacing on those patients. I referred to that study in my talk. So caffeine and theophylline have similar effects certainly. Terbutaline can be tried as well. Sometimes patients don't tolerate theophylline, but terbutaline can be tried. You know, in my experience, theophylline, chronic theophylline is very poorly tolerated. So even when theoretically appears useful to antagonize the adenosine, I think long-term treatment with theophylline, even in a younger person, it's not very viable in my experience. But caffeine works pretty well if you ask them to take it to therapy. Another question here for Dr. Kaplan. In patients post-HAVR who are at risk for AV block, do you consider the type of valve, balloon versus self-expanding, in your telemetry monitor, a timing recommendation? if they got a self-expanding valve, we're particularly concerned that they will continue to change. And so those patients, we may keep in the hospital for another day, may send them out with a monitor, and particularly counseling the patient that just because they're going home, that may not be the end of their journey post-TAVR, that there's a possibility if they pass out or they hear from us about their heart block that they may have to come back in. I have a question actually for Dr. Kaplan as well. What about the situation, what do you do when you kind of know or strongly suspect that there's a strong avian nodal component to PR prolongation? So you have evidence from Wenckebach or from very rapid junctional escape? How often do you see a venial disease after TAVR as a result of TAVR? I think we're a little bit over time already, so we're gonna conclude our session here. Thank you everyone for coming. Thank you to our speakers for presenting today. And everyone have a good day. Thank you.

electrocardiograms

atrioventricular block

ECG

adenosine

vagus nerve

paroxysmal heart block

transcatheter aortic valve replacement

TAVR

bifascicular block

syncope

risk stratification