Thank you for staying this hour here, we will talk about resynchronization cardiac, we have two speakers Latin American, two international. I have the pleasure of sharing this table with Dr. Fernando Vidal, who is cardiologist and electrophysiologist at the Cedimad Hospital Dominican Republic. In order not to waste more time, I would like to introduce Dr. Juan Carlos Diaz, Colombian electrophysiologist, he works in the Las Vegas Clinic in Medellín and he will present the topic Pacing Alternatives to Achieve Cardiac Resynchronization. The idea is that we are going to talk a little bit about the alternatives we have for stimulation and cardiac resynchronization. Before starting, these are my conflicts of interest, I am a speaker and proctor for Medtronic, specifically for stimulation of the left branch, I do not do more than that. When we are going to talk then of resynchronization therapy, we all have absolutely clear that this is a strategy that not only decreases the morbidity in the patient with cardiac failure, but also decreases the mortality, to improve the quality of life of patients and it is very important that that decrease in morbidity, that is, the rate of hospitalization is seen very early, however, the decrease in mortality we will see after six years in the RAFT or seven years in the MADIT, that is, a longer time is required but definitely the resynchronization therapy has a significant impact on our patients and despite that many patients are not considered for that therapy and they are still being handled with pharmacological treatment. In a traditional way, resynchronization therapy has been carried out through biventricular stimulation in which we simply try to locate a cable on the other side of the blockade line, there you can see how a left ventricle is depolarized with a left branch blockade, it is an epicardial map that we made a little while ago and we can see a blockade line, if I locate a cable beyond the blockade line, then I have the possibility of achieving a synchrony, not only auricular-ventricular, but between the two ventricles, however there will not be so much intraventricular synchrony, that is, the depolarization of that left ventricle will be given by a muscle-to-muscle depolarization and until it does not enter the conduction, it will not improve that intraventricular synchrony a little more. And it translates into that despite our best efforts, the success rate, despite the fact that it has been increasing, initially it was said that it was around 90%, a couple of years ago it was 94%, a last report a couple of weeks ago said that we are already at 96% in the possibility of placing a cable in a vein that is located on that side wall, remember that neither the anterior interventricular nor the posterior interventricular are adequate veins because they increase the mortality in these patients with cardiac failure and despite the fact that we have a very high success rate, it is very good to achieve a 96% success rate, because 30-40% of patients will not significantly improve their symptoms, it is possible that with the current pharmacological treatments this percentage is a little lower, but there will be a not negligible percentage of patients who will have complications with that left ventricular cable, for example, stimulation of the phrenic, dislocation of the cable, elevated thresholds, inability to locate it in an adequate position and that is where we are going to locate this type of therapies that can become alternatives. Traditionally we have used the epicardial approaches in a recent way and had a more fleeting step in the endocardial resynchronization, initially through the septum intraauricular introduce a cable in the left ventricle in the endocardial area in a more recent way, the device totally lipless for endocardial resynchronization and the alternatives that are appearing right now in fashion around the world, which are the stimulation of the conduction system, either stimulation of the hysterectomy or stimulation of the area of ​​the left branch. I believe that the epicardial cables do not require much introduction through a minitorachotomy, a cable is implanted in the lateral wall of the left ventricle and will produce a sequence of depolarization that will start from the epicardium to the endocardium and are quite effective. It has some links that are very similar to what we are going to achieve with a conventional resynchronization therapy, with a decrease in hospitalization, improvement in the functional class, improvement in the symptoms and a reduction of QRS. It has a low rate of complications for the procedure, that is, a minitorachotomy, but it is a low rate of complications. However, it is still a surgery, I do not stop having to open the patient's thorax, leave him hospitalized for several days to be able to locate that cable. And the position of that cable and the way to locate it in contact with the epicardium will have a significant impact on how well that cable behaves. One of the last epicardial cables that we sent to place in our group of surgeons asked us, well, then I put it near the apex, and they say no, no, no, no, no, please, not near the apex, try to locate it as basal and lateral as possible. But if that surgeon had not asked me, he would have put the cable in the apex and guess what the patient's response would have been. So the position of the cable is going to have a significant impact on how we are going to go, but not only that, but how well that cable is dosed to the epicardium. Although modern cables have a great ability to stick and stick very well, it depends a lot on the surgeon's ability to stick it so that there is no air interface that can later be filled with blood and fibrin reform, and that will act as an insulator. That is to say that the epicardial cable continues to be useful, but we have to be aware of it. I told you that we had also talked about endocardial resynchronization and animal studies and observational studies in humans said, look, endocardial resynchronization is superior to the epicardial from the point of acute hemodynamic improvement, with a greater capacity, a significant improvement in the QRS, but in addition to that, a significant improvement in the pressure-volume curves that will reach that left ventricle from many places of the endocardium, and possibly be in relation to the fact that being in the endocardium, going through a heart wall takes more or less 40 milliseconds. If I am from the endocardium, then from the outset I am giving the ease of that electric impulse that does not have to go through from the epicardium to the endocardium, but from the outset goes, looks for the Purkinje system, distributes by that and achieves a slightly greater intraventricular synchrony. Right now they are going to talk to us a little about the importance of accommodating the intervals and programming the devices to achieve a good auriculo-ventricular and interventricular synchrony, but intraventricular synchrony, that is, how that left ventricle is going to contract, if it is going to be synchronic or if it is going to go first one wall or the other inside that left ventricle, has a significant impact, and we use many techniques. We even got to the point of breaking the interventricular septum and putting cables to the left ventricle to try to achieve intraventricular synchrony in patients who told us surgeons, look, we can't take him to surgery, it is very high risk, and the patient accepted that we did this grace, and the electrical results were quite good. We achieved a significant reduction of the QRS and the patients were doing quite well, or that is what one wants to believe. However, when we evaluate how the outlays are, the response rate in the AllSync was around 60%, that is, 60% of the patients improved at least one functional class, that means that we continue with the 40% that do not improve. And in addition to that, the biochemical acid rate shot up, and when taking all the studies, that biochemical acid rate was approaching 6%, despite the fact that most of the studies were done with anticoagulant therapy, with cumarine, and it has to do with the fact that we have some cables located in left cavities of low flow, such as the left auricle, or in a left ventricle, in a patient with cardiac failure, and that therefore the flow is going to be lower and the possibility of forming thrombosis is going to be greater. And that was reflected in the high rate of chemical acids that the patients had, and that is why this therapy, despite the fact that it was used, everyone had a lot of concerns. More recently, the endocardial resynchronization with WISE appears, which is a device that is simply a receptor and will stimulate, again, the clinical response is around 63% when we use and do a meta-analysis of the different publications made. Whether it is going to be superior or not superior to resynchronization has not yet been demonstrated, but if you ask me what do you think the future is going to be in 10 years, how do you think cardiac resynchronization is going to be? If you ask me, I am sure that in 10 years we are going to be using these devices, which are wireless, and we are going to be placing them in the area of ​​the left branch, and the problem is over, because we are going to have the possibility of doing a synchronization specifically in the site where we need, for example, in indeterminate conduction disorders, we can go and look for the site later and locate that device there, and by leaving it in that place, we will be able to improve the synchronization of that heart, simply with an endocardial activation map made previously, and being leadless, we are not going to have the problem of the thrombi, which has been the great defect of these devices. However, it is still in the early stages of development, we are still far from, for example, us in Latin America having access to this technology, and then we have to look for other alternatives and other things that we can use. And that is where the Purkinje system appears, which I think you have heard a lot about that throughout the day, and by using the cardiac conduction system, we are going to improve the depolarization and repolarization sequences of that ventricle, it may be that it decreases the probarythmic effect, it is very interesting that some studies say, look, when you stimulate from two sites, it increases the possibility of arrhythmias, there are other studies that say, no, look, when you stimulate from two sites, you decrease the possibility of arrhythmias. So, by stimulating from several points, because I am using the conduction system, it would be possible to decrease the possibility of arrhythmias. It is known that the acute hemodynamic response is also quite good with the stimulation of the conduction system, and by randomized studies we know that it improves the fraction of ejection in a way, small randomized studies, greater than what is achieved with biventricular stimulation, which achieves a greater reduction of QRS by randomized studies, and based only on observational studies, and remember that all observational studies have inherent bias, I have no way with an observational study to eliminate all biases, however, it is what we have so far, it goes quite well with a decrease in morbidity, and right now I show you another data. The first that came out of this was the stimulation of the HYS, we have been doing HYS stimulation for many years, but it has never taken off very well, because despite the fact that it achieves very beautiful synchronies, look at the graph, see the one in the middle, how I can go from a branch block on the left to the left, and we see the very clear block line where we are green, depolarization all simultaneous, to blue, late depolarization, I can with the HYS achieve a homogenization of the depolarization sequence of that left ventricle, compared to a biventricular stimulation in which, look that where the cable is located, I will have a very early depolarization, but then I will have a block line because I am depolarizing muscle to muscle, that is, I will have intraventricular dyssynchrony, no matter how well I try to improve this. And when we compare HYS against standard resynchronization, that is, biventricular stimulation, we know that the improvement in the ejection fraction can be a little greater, and that in addition to that, the cutting of the QRS, which is what we can see in the room of electrophysiologists, is greater than what is done with biventricular. Disadvantages of the HYS, technically complex, require a large learning curve, a longer procedure time, longer fluoroscopy times, and very high dislocation rates for that cable, with thresholds that over time do not try to remain stable, but many times they increase, and in fact at 5 years, 1 in 10 patients will require a change of the generator, which is a very short time. And that is why, in the last study that was published, which was the HOT CRT, barely 4 of the 50 patients alienated to HYS stimulation, were effectively taken to HYS stimulation, because everyone is already saying, this is very good, it gives much more beautiful QRS than all the others, but we have a problem, we are not able to do it. That little problem is what has made it difficult to adopt the HYS, and only 4 patients received HYS in the arm that authorized HYS, and the vast majority received some form of stimulation of the left branch. That we have already known, this is stimulation of the left branch, it achieves very narrow QRS, a very beautiful rectification, of what we are going to see in the electrophysiology room, with an almost normalization of the QRS. If I remove the threshold, many here would say, it is a fairly normal QRS, it has some rare and ugly waves, it is not totally clear to me that that heart is totally normal, but anyone would say that it is a pretty nice QRS, and if I tell you, look, it is a patient who has 7 centimeters of diastolic diameter, it is a pretty nice QRS, right? We know that by observational studies, the outcome composed of mortality and hospitalization due to failure is lower in this group of patients in prospective records, given mainly by a lower rate of hospitalization, that is, patients are hospitalized less, but mortality is exactly the same, and it is very difficult to achieve a difference in mortality in studies that have been followed for 2 or 3 years, because remember that the RAF took 6 years, and that the MADIT-SIDARTY took 7 years to show a difference in mortality between non-resynchronization and resynchronization. And when we compare all the studies that have been done so far, I am from a publication that will come out in a little while in Arrhythmia and Electrophysiology Reviews, in which we simply reviewed all the studies that there were, if we evaluate, the duration of the QRS is less consistently, the change in the ejection fraction is consistently less, the time of procedure, only one study says that it is longer to stimulate the left branch than to put a cable in the coronary breast, and the time of fluoroscopy, most of the studies have been less, that is, it is quite promising, but there is still the problem that they are all observational studies, and that the randomized studies are in outlets that are not so strong, improved the ejection fraction, basically. This is a meta-analysis that we are currently sending for review, and if we evaluate all these observational studies, what is observed is that it seems that there is a sign of a lower mortality, again, all this is based on observational studies, and definitely the hospitalization rate seems to be in these lower observational studies. So there are many things that tell us, look, suddenly this is going to be the way to go, we need a little more information, particularly how these cables are going to behave, because remember that the 3830 cable, which is the one that is used by more than 90% of people, was not designed to be inserted in the interventricular septum, it was designed to be located in the hysterectomy, and that mechanics of being inserted in the septum, we do not know how it is going to behave in 10 years, now we do know how failure patients behave in 10 years, in which many of them are going to be dead, so it is good that we are worrying at this moment about how a cable is going to go in 10 years, because it means that we are assuming that the patient is going to get there, and that means that suddenly our current therapies are quite good. We had already talked a little about this type of complications, but in reality they are quite low, and if we compare them with the other types of stimulation, they are not crazy. And when we talk about stimulation of the left branch, we basically have two types of stimulation, one is the septal stimulation, and the other is the stimulation of the branch per se. Septal stimulation is simply placing the cable in the left subendocardium, in such a way that it jumps to the septum and shortens the depolarization of that left ventricle by 40 milliseconds, because that septum has already passed through it, a wall has already passed through it, or to stimulate the conduction system and produce a depolarization. And we are working on an article on that, and it seems that if you manage to capture the branch, it will definitely go much better for the patient in whom you manage to capture the branch, than if you simply manage to capture the left ventricular septum, the left subendocardium, mainly due to a reduction in the hospital rate. That is, when we take all the patients that we stimulate the area of the left branch, it definitely seems that it is better if you manage to capture the conduction system, than if you only manage to stimulate the left subendocardium. So, in conclusion, synchronization therapy played a primordial role in the management of cardiac failure. Many patients are referred to in a late way, unfortunately, and we know that it is not only going to reduce costs, it is going to reduce morbidity, but in addition to that, it is going to reduce the mortality of these patients, and therefore we must consider it early. And early is the prudential time for optimal medical treatment, according to the guides, however, see that there are already studies that are coming out and say, see how it goes to the patients if we start a little earlier. All stimulation alternatives to ventricular stimulation could have a significant impact, they can have more advantages, more disadvantages, they can have some complications, major or minor, but all, if I manage to resynchronize that left ventricle, they can become useful. The problem is all the other things that go around that. The need for thoracotomy, the need for anticoagulation, the need to enter a cable through the interventricular septum, all of them are going to have disadvantages, but all, if I manage to resynchronize, it will go much better to the patient than if I do not. And all this is simply opinion, that in the part of stimulation of the conduction system, probably this will be the future, not very far, probably in the next 5 to 10 years we will be handling this as first-line therapy, and taking into account how simple it is, it will probably be the stimulation of the left ventricle, and as I was saying, my prediction for the next 10 years is that we will probably have leadless devices that we will simply locate in the activation site later, we locate it at that point, we release it there, and we resynchronize in the case of patients that have indeterminate blockages or indeterminate disorders of the conduction system, or if only the blockage of the left ventricle, I release it in the area of the left ventricle, and I manage to capture the conduction system, and I manage the resynchronization without the problems of the need to go through a septum, nor the problem of the need for anticoagulation. Thank you very much. So, the title of my presentation is Improving Standard CRT is the way to go, and this is my disclosure, and also I have to tell you that I have another disclosure, because I have implanted in my life more than 6,000 CRT devices, so I'm still a believer in CRT. So, as you know, CRT is a very important treatment in patients with YQS, low ejection fraction, and heart failure, because CRT improves symptoms, functional capacity, quality of life, CRT has a significant impact in reverse remodeling and reduces heart failure hospitalization, and improves long-term mortality, especially in patients with left ventricle block. And this was based on a very long list of trials, and I think that today, we can say that CRT has a very strong evidence, because about 25,000 patients were included in the different randomized control trial, assessing the efficacy of CRT. And I must say that I disagree a little bit with you on Carlos, because when you discuss about CRT, and if you take a paper about CRT, the introduction is always the same. It's CRT is efficient, but we have 30 to 40% of non-responders, but I think today it's not true. If you look at the MPP-MORE CRT trial, which was designed to compare multipoint pacing versus biventricular pacing, based on echocardiographic criteria, decreasing left ventricular and systolic volume, it's true that we have, after six months, about 40% of non-responders. But if you wait a little bit longer, at one year, we have only 20% of non-responders with BIV pacing. And if I look at the result of the ADAPT response trial, which was published a few days ago in the Lancet trial, you may appreciate that if you look at the clinical composite score, about 70% of patients are improved, but also 25% are stabilized. And I think that this could be also a definition of responders, because we know that heart failure is a progressive disease, but if you stabilize the patient, for me, it's already a way of response. So I think that we have to be very careful with this 30% to 40%. So how to improve CRT? First, I think we have to select the right patient. We know that CRT is much more efficient in patients with very wide QRS, over 150 milliseconds. It's also, for me, there is no issue that CRT is very efficient in LBB patients, especially if they are very wide QRS. For non-LBB pacing, I think that we have to be cautious, especially in patients with right bundle branch block, and probably CSP will be more efficient in these patients. Of course, we have to assess if the patient has scar or no scar in the left ventricle. Also look at the right ventricle on the echocardiography, it's very important. If your patient has a very large right ventricular dysfunction, your patient will never be a responder to CRT. It's like if you want to implant a NILVAD with a patient with no more right ventricle, this will not work. And also, we have to look up to other cardiac causes. And this is an example, what is in gray, that means scar. If you look at the top of the slide, you have some blue, so you have some viable myocardium. But in the bottom one, you have only gray, so you can implant many leads. You can do what you want, even with CSP, this patient have a larger scar and will never respond to CRT. I like this paper from Pacolevia published in Europe this year, which compared the outcome of the patient according to the timing of implantation to CRT. The purple curve is patient without previous hospitalization. The dark blue, just below, is patient implanting during the first hospitalization, and after you have read, during the first year of hospitalization, and then the green, one to two years, and after two years. And you may appreciate that if you implant very soon a patient with CRT device, you will significantly improve the outcome of this patient. So if you have a patient with an indication to CRT, don't wait too much, but implant the patient as quick as possible. We know also that it's very important when you implant a CRT device to have a good idea about the presence of scar. Because in this trial, also from Pacolevia, if you implant a lead in the scar, you will not have a good response to CRT. But if you implant the lead out of the scar, it's a blue line, the red line, you will have a very good outcome. So I think that for implanters, it's very important to have a good idea where is the scar on the CMO. During the implantation, we don't have many, many tools. We have a simple one, which is a delay between the onset of the QRF and the 11-tricular activation. And we know from a different study from Michael Gold that if you have a QLD below 100 milliseconds, you significantly decrease the chance of response to CRT. I think also that the follow-up of a patient with CRT is very, very important. You have to select the right patient. You have to perform a good implantation. But after, you still have a lot of work to do, because the follow-up of a CRT patient is very important. First, we have to keep in mind that it's a patient with heart failure, so you need to optimize the management of heart failure, medical treatment, lifestyle, exercise, but also patient education. And also, you have to manage the risk factor and the comorbidities. And we know that now, if you use a multidisciplinary approach, you significantly improve the outcome of the patient. So, a CRT patient should not be followed only by electrophysiologists, but also by other specialists, nurses, echocardiographists, and sometimes even by surgeons in case of need of surgery. When you follow a patient, you have to look at the percentage of biventricular pacing. This is very important. This is an old study, 12 years ago, published by David Hayes in patients with sinus rhythm or atrial fibrillation. And if you compare the outcome of the patient, if you split the population between patients with a biventricular pacing rate over 98% and below 98%, you may appreciate that you have a significant improvement in survival in patients with atrial fibrillation or sinus rhythm when you achieve a pacing rate over 98%. So, during the follow-up, you have to look if your patient is continuously paced in the left ventricle. And remote monitoring in some devices could be very helpful because this is an example of a patient without the dislodgement of the left ventricular lead. And in fact, by remote monitoring, we got an alert that we have a loss of left ventricular pacing. So, I think the follow-up of the patient by remote monitoring may be also helpful to detect left ventricular lead dislodgement. Another cause of non-responsive CRT is premature ventricular beat. And you know that we have patients with ischemic heart disease, very low ejection fraction. And usually, this patient has a lot of premature ventricular beat. And the medical treatment in this patient is very, very limited. It's amiodarone. And personally, I don't like to give amiodarone for the long term. So, this is an example of a patient who was a non-responder. He was still in New York Heart Association class 3 with a left ventricular ejection fraction of 30%. And the biventricular pacing rate was low, around 80%. And this was related to frequent PVC. We decided to perform an ablation in this patient. And six months later, he has 0.04% of PVC, so almost no PVC. He was in New York Heart Association class 2. And he has a significant improvement in the left ventricular ejection fraction. So, in patients with CRT, frequent PVC, low biventricular pacing rate, think about PV ablation. We know that atrial arrhythmias also are very common in patients with CRT. And this can lead to a decrease in biventricular pacing rate. And I think that for this patient also, you have to consider heavy node ablation, but also AF ablation. We have the result of the CASTLE-AF and CASTLE transplantation were very impressive. And for our patient with heart failure with atrial fibrillation, we have to think also to AF ablation. Something I like to do with my patient is to perform systematically every year an exocytest. Because with the exocytest, you can have a lot of information. First, when you program your patient, the device of your patient at rest, that's good. But you don't know how the patient will react during exercise. And you can have a lot of reason of loss of biventricular capture. I just put a little there, upper limit rate too low, atrial chronotropic incompetence. Sometimes during exercise, you have loss of atrial sensing, you can have T-wave over-sensing, frequent PVC atrial arrhythmia, and so on and so on. But also a spontaneous AV conduction quicker than the program AV delay. Just want to show you some examples. This is a patient we did an exocytest. This is the first step of the exocytest. So you can see that the heart rate is about 115 BPM. And when the patient arrive at the end of the exocytest, you can see that you have a strong modification of the ECG because the patient lost the biventricular capture. And if you look at the heart rate of the patient, it's 137 BPM. But the problem that the upper rate limit was programmed at 130. So this patient has had a loss of biventricular capture during exercise. So we just have to increase the upper rate limit in this patient. This is also another patient. It's a male with non-in ischemic cardiomyopathy, optimal medical treatment, LBBB, good candidate, LVF 30%. He was implanted with a CRT device. He was a NICOR responders. The movies are not working, but I can tell you that we have a significant improvement in the biventricular fraction, and you may appreciate also that we have a significant decrease in the dimension of the biventricle. But this patient was not a clinical responders. So we perform an exocytest. And in fact, this patient has atrial carotopic incompetence. Because the heart rate of baseline was 55 BPM, and at the peak of exercise only 80 watts for this young patient, the heart rate was 65. So we switched on the rate response algorithm, and the patient became a very good responders. AV delay is very, very important. This is an example of a patient performing a six-minute wall test, and we interrogate the device at the end of the six-minute wall test. And you may appreciate that in this interrogation, we have APs, means atrial pacing, but we have RVS and LVS, which mean right and left ventricular sensing. And the patient was not supposed to have a spontaneous conduction. So we decided to shorten the AV delay, and you can see that now we have RV pace and LV pace. And this is very important, because usually if you still perform an echo optimization for the AV delay, you do this at rest. But AV delay is a very dynamic parameter. This can change according to the activity of the patient. This can change also with the medication, if you increase, for example, beta blockers, or also related to the disease progression. And so I think that now we have automatic algorithm, and personally, I prefer the algorithm when you have a continuous monitoring of the AV delay and a continuous optimization of the AV delay, like, for example, the adaptive CRT or the SYNC-AV from Hubbard, because for adaptive CRT, it's every minute, and for the SYNC-AV Plus, it's every 256 cycles. And this is just an example of a patient performing an exercise test. With the red arrow, you can see that the QRS is not typical of CRT optimization. So with the three stars, you have a 11-branch bug, because this algorithm, every 256 cycles, increase the AV delay to allow a spontaneous conduction, and it will automatically measure the delay between the atrial sensing and ventricular sensing. And then after, we'll optimize the AV delay, and you can see on the green arrow that you have narrow QRS with the airwave in CRT1. So just to show you that the AV delay is very important, because according to the AV delay, you can have two wave of activation, three waves of activation, intrinsic RV and LV pacing, and also LV only with intrinsic conduction. Good monitoring can also help you to monitor your patient with a lot of parameters dedicated to diagnose heart failure. Cardiomyopathy is very interesting. Unfortunately, it's not reimbursed in Europe, but I have some patient with that. It's very useful, because you have a continuous monitoring of pulmonary artery pressure. Perhaps in the future, artificial intelligence will be very helpful to predict the patient who will have the best outcome. And finally, I would conclude that the rate of response to CRT in the modern area is rather 80%. CRT can be optimized during the selection of patient, implantation and follow-up. LBBA pacing are very interesting, but I think that still have to be validated. And just to remind you that LBB pacing is also not so easy in patient with very large ventricle. Thank you very much for your attention. Thank you very much, Dr. LeClerc. I would like to invite to introduce you Dr. Devi Nair. She is Director of the Cardiac Electrophysiology Division at St. Bernard's Heart and Vascular Center, Johannesburg, Arkansas, USA. Dr. Devi, thank you very much. I know that you was very busy today. I'm sure that she will answer the next question in this minute. Should the CRT-P be our routine strategy in still CRT-D? I'm sure that she answered this question. Thank you very much. Good evening, everyone. I'll keep my presentation in English as well. So the question was, should CRT-P be our routine strategy instead of CRT-D? And I'll try to bring some evidence to light. These are my disclosures. So the question is, why do we care? And this was a quotation in 2021 by Andrew Clark, that perhaps everyone is destined to develop heart failure unless they die from something else first. So we just know that the prevalence of heart failure and the incidence of heart failure is probably pretty bad. And why is it such a big problem? So it is probably one of the most common cardiology issues that we run into. Patients usually have pretty severe symptoms, multiple admissions, long admissions, very high mortality rate. And it's really expensive, not just for the patient, but also for the hospital systems. And the goal for heart failure treatment is almost always relief of symptom for the patient, avoiding admissions and readmissions. And also preventing sudden death. So let's take a train ride back to the history of treatment of heart failure. This is the pre-diuretic stage where you see these tubes that are being used to drain fluid out of the patient's legs. And we've come maybe a little long ways. And if you look at heart failure therapy from where it was in 1785 to 1985, which is two centuries, there was not really much of a difference. It was just mainly things such as digoxin. That fox glow is from my garden, and I have some, too. But since then, you can see that therapy advancements that we have had in the last 35 years is immense. The amount of clinical trials that have come in the heart failure space brought in a lot of these new medical therapies have been immense, and a lot of advancements have been made in the medical therapy regimen in heart failure management. If you look at the mortality in the heart failure clinical trials as well, over time, you can see mortality was as high as anywhere 50%, now all the way down to like 7%. So let's look at Entrestor or Sacrobitril-Valsartan combo. And there are two major modes of death in heart failure. One is sudden death, and one's death due to worsening heart failure. If you look at that effect that Entrestor has, you can see that there was a significant reduction in death, both sudden death and death due to worsening heart failure in patients treated with Entrestor. How about Farsiga or Dapaglifosin? Same thing. We see that there was at least a 21% relative risk reduction in composite of serious ventricular arrhythmias, resuscitated cardiac arrest, and sudden death. And the effect was consistent across each of these categories. And these are all the clinical trials that looked at the different medical regimens and sudden death. And you can see there was a significant, the sudden death rates are extremely low, and the reduction in sudden death that we see with these new medical therapies are immense. This is just kind of bringing back the decline in the rate of sudden death that we've seen in our heart failure population and through these major randomized clinical trials. It used to be at least 2.4% at that first 90 day from enrollment, to down to now at about 1% in the most recent clinical trial, which was Paradigm HF. So let's now take a train ride through the history of devices. So as early as 400 BC, Hippocrates mentioned that those who suffer from frequent and strong faints without any manifest cause die suddenly. So where does that go? What happened first? So the earliest that I could find was in 1775, where a Danish physicist, he put electrodes on the sides of a hen's head and applied discharge, which caused the hen to drop dead. And he applied electrodes all around the hen's different parts of the body. And finally, the hen got up when he put electrodes around the chest and walked away. How about in humans? Marie Francois was the first person that did this experiment in decapitated humans in whom he was able to make the heartbeat again using electrical current. Again, this was at the time of the French Revolution. But what about sudden death in heart failure? We all know that eventually it is sometimes the rhythm that gets you in heart failure. And we know that ICDs can prevent cardiac arrest, prevent ventricular tachyarrhythmias by delivering therapy. So nobody disagrees that defibrillators save lives. They do save lives, right? There are many ways that they save lives. This gentleman definitely was saved by his defibrillator for very various different reasons. There are defibrillators that save lives by not shocking, but by pace dominating. So here you have a beautiful example of anti-tachycardia pacing suppressing ventricular arrhythmias. So then the question is, shouldn't everyone get an ICD? Shouldn't we try to prevent sudden death in everyone? But we know that there are problems with ICDs. They don't really improve symptoms, which is what we wanted to do first. They don't really improve their functions. Patients don't feel good just because of an ICD. They're expensive. Not everyone benefits from ICD therapy. We have to worry about things like inappropriate shocks and large can and implications to lifestyle and psychological burden that comes with having an ICD. And the hardest part, at least for me sometimes, is as an older patient that comes to end of life on their device and is aging, is what do you do with that defibrillator therapy? So if you look at ICDs in heart failure and look at the clinical trials, I have ischemic cardiomyopathy trials on the left and non-ischemic cardiomyopathy trials on the right. You can see there have been significant number of trials that have been done. And if you look at the effect of ICDs in heart failure in preventing sudden death, in the ischemic cardiomyopathy population, both CABG-PATCH and DYNAMIT were neutral trials. They did not, there was no effect. In the non-ischemic arm, almost all of the clinical trials were neutral. SCUDHEFT, half of the SCUDHEFT population was non-ischemic. And in that subgroup, it was still neutral. So this is where we are. We don't have good positive data. Now how about the positive ones? There were two in the MAIDER trials and the SCUDHEFT trial in the ischemic side had some data. So let's look at those patients. META-2 had about 1,200 patients. Their EF was less than 30%. They didn't have any previous VTVF. So this was primary prevention. They post MI over a month. The mortality rate in the ICD arm was 14%. And in the medical therapy arm was about 20%. So there was a 31% relative risk reduction in this group. And we'll come back to this group. How about SCUDHEFT? SCUDHEFT was about 2,500 patients. It was 50% ischemic and 50% non-ischemic. But average age was about 60 years, with about 77% of these patients being male patients, less than or equal to 35% EF. Majority of these patients were class 2. Remember, that's 70% of these patients were class 2, and about 30% class 3. And in SCUDHEFT, we did see 23% relative risk reduction in sudden death in the ICD arm. So in 2016, the ESC guidelines for ischemic heart disease and dilated cardiomyopathy were in class 1. Ischemic heart disease was 1A, and dilated cardiomyopathy was 1B. Soon after that, we had the DANISH trial. The DANISH trial was a multicenter, randomized controlled trial, looking at ICD versus oral medical therapy. They were mainly non-ischemic patients, and these were diagnosed with non-invasive or non-invasive or CT. These patients were followed for about 5 1⁄2 years. They were mostly class 2 and class 3 patients with an EF less than or equal to 35. 58% of these patients, remember, received CRT. Now, that could have been CRTP or CRTD. If they fell in the medical therapy arm, they would get a CRTP device, and if they fell in the ICD arm, they would get a CRTD device. And 92% of these patients were on beta blockers, and 59% were on MRA agents. What did the DANISH trial show? It showed that primary prevention ICD implantation was not associated with any overall survival benefit in patients with non-ischemic systolic heart failure. So there was no cardiovascular mortality improvement or all-cause mortality improvement. How about sudden death? We did see that the risk of sudden cardiac death was halved with an ICD in this group. So this is just a subgroup analysis, and it's a very busy slide, so I'm gonna just kind of highlight where we actually saw the difference. We saw the difference in patients who were younger, so less than 59, and patients who had a proBNP that was much smaller, so less sicker in the heart failure realm patients. Those were the patients that we saw the difference. So the DANISH trial concluded that primary ICD implantation in non-ischemic cardiomyopathy did not reduce all-cause mortality or cardiac mortality. And overall mortality rate was higher in older patients. 31% of the deaths were due to non-cardiovascular causes, and device adverse events were not trivial in this trial. And it did highlight the importance of selecting ICDs in a particular group of patients, especially younger patients who might have a higher survival benefit. And the ESE guidelines actually dropped down non-ischemic ICD therapy to 2A at that point. So what was the difference between the DANISH and the SCUD-HEFT? And if you look at that, you'll see that it was mainly the drug therapy. The medical therapy in the DANISH trial versus the SCUD-HEFT trial were very different. Otherwise, they were pretty matched. So who was the patient in SCUD-HEFT? Why did we see all that difference? It was a young patient who had minimal symptoms, no other comorbidities, and on really old-fashioned therapy. And that is not the patient that we see anymore. Mortality, you know, if you look at the mortality in the control limb of ICD trials, again, that pattern which I showed earlier, both sudden death and total mortality rates have significantly come down, even in the control arms. This is looking at ICDs in non-ischemic cardiomyopathy and the different other trials that were done. And I'm not gonna go through every one of them, but you can see the pattern. There was no difference in any of these trials in reducing cardiac death or all-cause mortality. So let's look at trials versus trials are managed very particularly. How about reality? This is the UK National Heart Failure Audit that's shown all the way to the right. You get a large patient population, also the Conrad Registry, and you can see these are large patient populations. They're much sicker patients. You can look at the trial ages. The patients in real registries are much older. They're mostly of a mixed gender and much more sicker patients, whether it is AFib or other comorbidities. Let's talk about age. The question comes as to, you know, how appropriate is it for us to put an ICD in someone who has exceeded their average life expectancy, right? Many elderly patients, when you see them, they just want to feel better. You know, more likely they're gonna die from another comorbidity that they have. And does an ICD have the same effect on these elderly folks? And does age actually matter? If you think about the life expectancy of an average male, it's about 78, and about a female, it's about 82. An average age of a heart failure patient is about 78 years. Look at the age in all these heart failure studies. They're much younger patients. This is not the patients that we're seeing in some of our heart failure. And not all six-year-olds are the same either. So you have to treat the patient as they come. If you look at the heart failure class, if you look at who benefited out of ICDs, it is those in VIHC class two, the not-so-sick patients, the patients that are earlier in their heart failure regime. And also, that's a scud heft, if looking at the six-minute walk test, and patients who actually could get up and walk and do things. Those are the patients that had a better expectancy of life and who benefited from ICD. So should patients not then get a device? I mean, I'm talking about people not needing devices. Well, should they get a CRT? Well, you'd have two talks about why this is important. And these are all trials, and I'm not going to go into details because our previous speakers did an excellent job on telling you why CRT is important. It does improve six-minute walk tests, improves quality of life, and improves mortality. This was just a CRTP study, okay? So about 800 patients showing 37% relative risk reduction in cardiovascular hospitalization and death. This is from just CRTP. This is from just resynchronization therapy with improved EF and quality of life and reduction in LV and systolic volume. You're not going to get that from CRT. That's not what you get from CRTD. This is companion look, having both CRTD and CRTP versus OMT. In VIHC class three, four patients, there was at least 20% relative risk reduction in all-course mortality and hospitalization. So sometimes you get a mixed bag, and it's really hard to know whether it's a D or whether it's a P that actually did it in these patients. So there's really a very high level of increasing uncertainty on the benefits of the defibrillator part of this therapy. And our first oath that we take is do no harm. And if you're saying do no harm, then we have to think about things like inappropriate shocks. This is looking at inappropriate shock rates in a patient population. And what you see is 13% of these patients experience at least one inappropriate shock. And the cumulative incidence of inappropriate shocks continues to rise over up to 18% in five years. And if you follow these patients for about 45 months or so, what you see is that most of these patients, you know, not just have appropriate shocks. They might have a combination of appropriate and inappropriate shocks. And 11% of patients who had an appropriate shock will die within 24 hours. So the defibrillator really did not save their life. They died within 24 hours. And those surviving more than one day will more than likely die within a year. So just keep, you know, keep all that in mind as you think about it. I see these come with their own risks. I'm not going to go over each one of the complications. But if you look at the different, whether it's single-chamber, dual-chamber, or CRTD, those complication rates are as high as 10%, 16%, and 22% respectively. How about real-world data? This is looking at UK. Sorry, we are out of time. Okay, yep, absolutely. I'll come up to the summary real quick. So when we look at therapy, CRT is a fantastic treatment. Hearts do get better with our devices. It is important to choose the correct patient. CRTD is ideal for younger patients with class 2 heart failure who have genotype and who are in secondary prevention. And it is good practice to reconsider. We don't have as much evidence in non-ISKIMICS. We should probably consider evidence on ISKIMICS as well. Thank you very much. Well, thank you, doctor. And right now, and as fast as we can, I have an enormous pleasure to present one very good friend of mine, Dr. Néstor López-Cabanillas, coming from Argentina, a very dedicated electrophysiologist traveling all around Latin America. He works in Adventist Cardiovascular Institute of Buenos Aires, Buenos Aires, Argentina. He'll talk about how to deal with difficult CRT cases through the coronary sinus, which is his speciality, always. And we will try to make it... Thank you. Well, thanks a lot for the invitation. I think to continue in Spanish, I don't know. Well, I'm going to present the experience I've had throughout Latin America in resynchronizing implants, doing advanced devices implantation courses. So, it's very important to know that we have problems in the access site. There are problems for the coronary sinus cannulation, to get the desired vein. And we also have problems with the electrodes, because we often don't get the right location, have high thresholds, have nerve stimulation, and the problem of displacement. So, how to achieve success in the implantation of resynchronizers through the coronary sinus? Well, first, optimize the ergonomics of the implant, use contrast, have the right tools, and be able to know, control, and perform, in our daily practice, interventionist cardiology techniques. So, the first thing is to optimize the ergonomics. What is ergonomics? It's the science that studies the interaction of the operator with the environment, the tools, our colleagues, the electrodes and catheters. So, first, it's important to have the monitor in front of our eyes. Second, to have an assistant with us, to our right. The table has to be perpendicular to the patient. And also, if the table has a central column to be able to perform the obliques without disturbing the table interaction with the X-ray system, it's excellent. And it's very important to have a contrast administration system that will allow the main operator to be free from the injection of it. The use of contrast has to be done both in the site of the puncture, it also has to be used for the location of the coronary sinus. It has to be used selectively through the use of subselectors. But we can also use contrast through the electrode itself. The electrode itself can be used, connected to the syringe, and inject contrast through it and be able to see the anatomy beyond the tip. The tools have to be correct anatomical shirts. I always recommend the Extended Hook format that almost all commercial houses have. Use subselectors, use vein selectors, have all the necessary guides. Use this injection system and always link it to a Y-key to be able to inject contrast and at the same time be able to mobilize guides. It is important that electrophysiologists know how to perform a venoplasty and use laces. Let's go quickly to the different techniques that we can use. In the case that there is a total occlusion of the vein and that we cannot advance a guide, it is important to use a dilator linked to the contrast injection system and a hydrophilic guide to advance in anatomy and be able to find the desired vein. And many times to recanalize. If we use a hydrophilic catheter, a contrast injection and a hydrophilic guide and we are always advancing guided by the different radiological projections, we can recanalize. It is very important to know the upsizing technique, how, if we manage to advance a finite 0.14 guide in some way, we can advance a hydrophilic catheter over that 0.14 guide, remove the 0.14 guide and advance a rigid 0.35 guide amplates, which will give us support to be able to do, for example, a venoplasty. In this case, we see a vein electrode that moved, we can advance a guide beyond the electrode, do a simple retraction, remove that electrode that we have to reposition and without doing any puncture, we are already in place. We do the upsizing, we exchange the 0.14 guide for a 0.35 and venoplasty and we are ready to implant a new electrode. This technique of the electrode of the guide under the insulator is important. If there is an electrode that does not work, we can disuse it advancing the guide below, we move, we displace the electrode guide, we remove the electrode that is malfunctioning and we do the upsizing of that guide from 0.14 to 0.35 and without doing any puncture, we are already inside when we had an occluded vein and it did not allow us to advance. The balloon system as an anchor is also something very important. If we have a siphon coronary sinus that does not allow us to advance the catheter, we can advance a 0.14 guide digitally or a venoplasty balloon or the same balloon digitally, perform traction and advance the catheter above it. Here we can also use the telescopic system. In this case, the shirt did not allow us to reach the ostium, which was very high. Then, using a very fine vein selector, we can project the guide higher and in this way advance in a coronary sinus that is in a very high position and that was difficult to cancel. You will see that I do not use a decapolar catheter. I am like an interventionist cardiologist. A hemodynamic cardiologist will never use a reflectable catheter to cancel the coronary trunk. Always use contrast. So, I am guided by the principles of interventionist cardiology. Here we are using, we will see that it is the way that many people want to do in Latin America, only a guide in the vein and the electrode. And sometimes the electrode does not want to advance. If it cannot advance, the way is to use a telescopic system with two sections, the coronary sinus vein, the coronary sinus shirt and the subselector. In this way, we can easily, with support, advance. Other times, the telescopic system to use has three sections. So, what do we do? We locate, we see here a vein in omega, we can advance the three sections, the three sections of the telescopic system, the vein selector, the subselector and the coronary sinus shirt, locate the vein, advance a guide, advance a second guide, advance the vein selector and on this rigid guide, advance above these three elements, the subselector and that's it. There we will advance yes or yes. The technique of the tie is very important. If there is a vein that is not high embryonic or has phrenic stimulation, we can advance through the collaterals a guide, digitally through the middle cardiac vein, pass it through a tie, close the tie and already with the guide, the digital end caught, we remove the vein selector, and already with the digital end caught, we can advance with total security through an electrode, through a vein with stenosis, tortuosity, without problem. So, this system of the SNER is very important to take into account. Sometimes the desired vein is in the ostium. So, it is very important to know the technique of the wide support guide. If we advance a wide digitally, we can advance and remove the shirt without losing cannulation. So, we can inject contrast, find a very proximal vein and once we are there, advance a guide, wide to have a lot of support, and there we can remove the wide that was not giving support in the coronary breast. And once this happens, we can advance the subselector and once with the subselector in the vein, release the electrode. Sometimes the existing vein has high threshold or we have problems and we can make a veinogram of the proximal veins and we will see in this case that there is a vein that we had not seen in the veinogram and we can make a retrograde electrode advance from the mid-cardiac vein to the desired vein. Very useful if there is proximal stenosis. We can enter the other way around. In this case, with a persistent upper left vein that we did in Lima, in Peru, it was a case that could not be located, they had failed, they called me to help in this case. I inflated a large diameter balloon, 4 cm in diameter, very carefully, I did not completely inflate it because I was afraid, but I was able to locate with this occlusive technique the system and with a telescopic system advance in that complex anatomy. The implants on the right side are also difficult, it is very important to have two elements, the shirt and the selector, always use an implant because it is very difficult from the right to advance in the coronary vein shirt, we do the veinogram, we locate the desired vein and it is always important to have a large diameter shirt because we can work in parallel. Here in this case I used a Worley system and always to remove the coronary vein shirt you have to remove it on the implant and the electrode with a mandrel, a rigid stylus. To finish, sometimes in very complex cases we can put two electrodes in the same vein and use an adapter to avoid nerve stimulation, putting two poles very close together and making the stimulation field small. In conclusion, we have to use contrast and make a correct veinogram to see more anatomy, it is necessary to know the tools and electrodes and to be able to master the interventionist cardiology techniques of our hemodynamic masters to optimize the chances of success and reduce the time of the implant and also avoid positions that are not good for the patient. For the impossible case, as we have already seen, there is the stimulation technique in the hysterectomy area, in the area of ​​the left branch, the endocardial stimulation system, either through the physiological or direct system with the promise of new systems without leadless electrodes. Thank you very much. Unfortunately, we don't have time for questions.

Cardiac resynchronization therapy

CRT implantations

Coronary sinus

Ergonomics optimization

Contrast for vein location

Interventional cardiology techniques

Challenging cases navigation

Electrode displacement

Dual electrode placement

Stimulation techniques