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Discussion
Bruce R. Brodie, MD: I agree. Blush is a very soft endpoint, and some of the discrepancy in ST resolution between one study and another may be related to patient composition of the trials. For example, patients with right coronary artery (RCA) infarctions have better ST resolution. We have been somewhat disappointed with the use of infarct size measured by sestamibi scans as an endpoint. It does not appear to be very sensitive. However, the observation that time to treatment does impact infarct size indicates that infarct size measured by sestamibi scans does have some discriminatory power.
Dr. Baim: So that is why the Cooling as an Adjunctive Therapy to Percutaneous Intervention in Patients With Acute Myocardial Infarction (COOL MI II) Trial looks at anterior infarcts less than 6 hours from the onset of symptoms to try to find more of those reversible patients.
Dr. Brodie: We all think that magnetic resonance imaging (MRI) is going to be a much better tool for measuring infarct size. If we think distal protection or thrombectomy will prevent distal embolization and prevent infarct expansion, our hope is that MRI may be able to detect differences in infarct size.
Dr. Baim: I guess what I would say is if 20% of the left ventricle (LV) is infarcted, then no matter what you do, if you re-open that artery, that 20% is there as a background. If your strategy to prevent distal embolization is protecting another 2% of the ventricle in terms of infarctions, it is going to be difficult to show that against the background.
Dr. Brodie: You might argue, though, that if you have an infarction and you preserve the microvasculature, you may have less remodeling and better long-term outcomes. So I think there still may be potential for long-term benefit independent of a reduction in infarct size, and we saw that, for example, with some of the early studies with fibrinolytic therapy.
Dr. Baim: Are these the wrong patients, the wrong technique, wrong endpoint?
David Antoniucci, MD: We should look at the result of the AngioJet in Acute Myocardial Infarction (AiMI) trial with a critical and proper perspective. The first point is the higher 30-day mortality of the Jet arm that cannot be explained by the characteristics of the enrolled population. It is difficult to explain how a patient with an infarct size of only 10% of the ventricle can die. As a consequence, we should clarify the causes of the 11 deaths of the Jet arm. Were these deaths related to the device, the operator or other technical concerns? Dr. Brodie, do you know the cause of death for each patient?
Dr. Brodie: It is been a long time since I reviewed those deaths. Some of them were non-cardiac. There were a few re-occlusions that resulted in death and there were a couple of bleeding deaths.
Dr. Antoniucci: Fatal bleeding is not a common cause of death. Were these bleedings related exclusively to the anti-thrombotic treatment or due to procedural aspects such as temporary pacemaker, which is a well-known risk factor for right ventricular perforation and cardiac tamponade and was frequently used in this study?
Dr. Baim: There were only a few cases that were dissections or perforations or other issues that could be theoretically mechanically related to the AngioJet. And 4.8% mortality at 30 days is very good for a primary angioplasty trial in general. Dr. Brodie: The AiMI Trial targeted high-risk patients.
Dr. Baim: But 0.8% mortality in the control group is way too low. Dr. Antoniucci: The expected mortality for this high-risk population should be closer to 4–5% than 1%.
Dr. Brodie: The deaths in some patients were related to co-morbidities. If a patient does not have a smooth course, complications may develop that result in death. For example, a patient may have a groin bleed that results in hypotension, which may cause renal failure in a patient with pre-existing renal insufficiency and the patient may not survive it. I do not remember the details of the deaths. Nobody expected a difference in mortality, so they may have been due to chance. I am less concerned about the mortality differences than the infarct size differences. Do we think that the difference in infarct size is related to technique and the statistical differences in baseline TIMI flow? Or is there something inherent in the device that it has led to larger infarct size?
Dr. Antoniucci: We should consider that the potential for a clinical benefit cannot be seen at 1-month follow-up. If you have a technique that may decrease the infarct size, it is possible you can reveal a decrease in early mortality, but more likely, the clinical impact will be revealed during a longer follow-up, perhaps 1 or 2 years, as a decrease in mortality and a decrease in hospital admission for congestive failure. Thus, I think that the clinical benefit of a decreased embolism resulting in more myocardial salvage may have a clinical impact only in the mid-term follow-up.
Dr. Baim: The problem is that we have these different trials. Some of them show a large degree of salvage and some show no salvage. If it was just bad luck in the trial design, then you do another trial or a bigger trial. If there was some mechanistic aspect, like the right patients were not selected or the procedures were not conducted correctly, you do another trial where you do select the right patients and perform the procedure correctly. But we need to understand why the AiMI trial was negative so that it can be determined how to design another trial that is positive.
Georgios Sianos, MD, PhD: I think the AiMI trial was ambitious in trying to prove that thrombectomy is useful in all comers. That means that you are trying to prove that you use a device dedicated to remove thrombus in patients that might not have thrombus. This is a paradox because it is not logical. Also, all of the results from these trials have diverging results. In the design of these trials, thrombus grade is not taken into account at all. Or there is an arbitrary cut-off. If I review all of the literature, my comment is that at the end of the day, we still do not know how much thrombus burden is important. But our results in large thrombus burden STEMI patients show the kind of long-term clinical benefit Dr. Antoniucci described, if the thrombus is removed.
The AiMI trial was aiming at something that was beyond what the device could clearly treat, and that is why it failed. We are missing a validation of thrombus burden related to clinical outcome to find out where we should apply these devices. Dr. Brodie: Do you have any thoughts on how to quantitate thrombus burden better than what has been done?
Dr. Sianos: I think the thrombus classification system that was created by the TIMI core lab has never been validated.
Dr. Brodie: Lack of validation and assessment of thrombus burden in a totally occluded artery is meaningless. The only way I know to assess thrombus burden in a totally occluded artery is to establish distal flow with Dottering or inflating a small balloon so the distal vessel can be visualized.
Dr. Sianos: That is exactly what we have to do. In our registry, we used AngioJet only in the thrombotic lesion. After the results of AiMI, we really need these kinds of trials.
Dr. Brodie: Dr. Sharma, do you routinely perform rheolytic thrombectomy in an antegrade fashion?
Samin K. Sharma, MD: Yes, we always did. When we started our Vein Graft AngioJet Study (VeGAS), we went to Boston and everybody was very adamant to go distal to proximal, but our lab never did.
Dr. Brodie: What percentage of your ST-elevation infarctions are treated with AngioJet?
Dr. Sharma: We get about 8–10 acute MIs per month, and of that, about one-third will be treated with AngioJet and two-thirds will be treated with just a balloon and stent. Four percent of the total interventions and one-third of acute MI interventions are getting AngioJet in our lab.
Dr. Brodie: Some of the AiMI sites had less experience with AngioJet. What is your perspective on the importance of experience on outcomes with AngioJet? Do you think that could possibly explain the difference between your results and AiMI’s results?
Dr. Sharma: I think experience may be less important with the 6-French (Fr) guide compatible AngioJet catheter. With the earlier catheter, using a 6 Fr or 7 Fr guiding catheter, there is more vascular bleeding and vascular complications. We now use 6 Fr — that is one issue. Secondly, if you have not used it commonly, you may be jamming it in, sometimes causing guide issues. But hopefully with the newer catheters, that issue will not be there. The key is that the preparation of the AngioJet equipment should start as soon as the acute MI patient comes to the cath lab and you decide it looks like a thrombus.
Dr. Sianos: Does any information exist in the literature regarding the frequency of large thrombus? It represents 58% of your population that you regard as a big thrombus, but can you support it by the literature?
Dr. Sharma: All of these data come from the Platelet Receptor Inhibitor for Ischemic Syndrome Management in Patients Limited by Unstable Signs and Symptoms (PRISM-PLUS) trial, where grade 3, 4 and 5 thrombus were counted as large thrombus (Zhao et al, Circulation, 1999).
Dr. Baim: But they just made that grading scale up, and I would argue that a totally occluded artery could be totally occluded by three platelets holding hands in a tight stenosis, or by 2 cm of rattail thrombus. Unless you either cross and do a distal injection with an infusion catheter or dilate with a 2-mm balloon, which would restore flow and let you see the mass of the filling defect, I do not think you can estimate the amount of thrombus. And if the key to positive AngioJet results is using it only when there is a big thrombus, we need a better way to detect that.
Charles A. Simonton III, MD: That is a problem because what you are saying is that if you had more patients in the trial, maybe things would have looked differently. Should we be concerned about using the AngioJet in a vessel that does not have thrombus? I know if you are going to do a trial, you want to do it in vessels with thrombus. You can go after that target population if you can get operators who are willing to randomize patients with large thrombus burden. Some operators may not be willing to randomize those patients, since they may be randomized to no AngioJet. But why would it have an adverse effect in the patient who has three platelets holding hands in a tight lesion other than going through and dottering the lesion, unless the force of the turbulence around the catheter is doing something bad in those patients? It should not have harmed patients without clot; it should have helped the patients who truly did have clot. So if you took the TIMI Grade 5 patients who have a totally occluded artery, in whom you do not know if they have clot or not, why would it hurt the patients who did not have thrombus? I would expect not to harm the patients without thrombus and to potentially help the patients with large thrombus, so that the net effect might be beneficial.
Dr. Brodie: The obvious question is: Does it cause distal embolization in people with or without visible thrombus?
Dr. Simonton: I cannot say it would do that more than blowing up a balloon or putting a stent in that lesion. But from a trial perspective, if the benefit is confined to people with large thrombus, then allowing people with minimal thrombus who derive no benefit to be enrolled dilutes out your treatment effect and could give you a falsely negative trial. If you are worried that the AngioJet is causing distal embolization in a patient without visible thrombus, then it is probably causing some distal embolization in a patient with thrombus. You may get the thrombus out, but then maybe you are doing something else.
Dr. Brodie: It there possibly a mechanism for increased infarct size, other than distal embolization in this setting?
Dr. Baim: It could be thrombo-embolization or athero- embolization, and these are lipid rich, vulnerable plaques that may be prone to athero-embolization.
Dr. Brodie: I have looked at time and infarct size a lot. Most patients with STEMI present after the first 2 hours and are reperfused at > 4 hours. Incremental time delays do not matter much after 4 hours in terms of infarct size, and certainly 20 minutes does not matter. And it is a small percentage (< 10%) of STEMI patients that we are able to reperfuse within the first 2 hours with primary angioplasty.
Dr. Simonton: Dr. Brodie, you have done a lot of ST-elevation trials. In my clinical practice of doing these STEMIs 24 hours a day, it is totally clear to me that this is a very heterogenous population, not just anteriors versus inferiors.
Dr. Brodie: As far as anterior infarctions — I think there is a great deal of heterogenuity with anterior infarction. Some patients with anterior infarction have paradoxical wall motion when you first see them at less than 2 hours. Some of it is related to whether they have had intermittent occlusion of the infarct artery prior to presentation.
Dr. Baim: One could argue that the right endpoint for this trial is that the residual thrombus and obstruction in the artery gets better after AngioJet with no adverse sequelae. And ST resolution, blush and infarct size were secondary endpoints. To get back to my question (wrong patients, wrong technique, wrong endpoint, which of those it is), I think the mandate that we would like to give is that the AiMI-II trial be a study of the appropriate patients (moderate or large thrombi) with the optimal technique (proximal to distal aspiration) and the right endpoint (removal in thrombotic mass, safety, ST resolution). Based on everything we know, that trial will be positive.
Dr. Antoniucci: I would parallel the long time for preparing the AngioJet to the door-to-balloon time. As you know, the door-to-balloon time is a strong indicator of the quality of the procedure, and in some way, the long time to prepare the AngioJet in the AiMI trial may suggest some logistic problem in this study.
Ray Matthews, MD: Dr. Baim, you mentioned your technique for assessing thrombus burden. We will pre-dilate with a 2.0- or a 2.5-mm balloon and assess the residual clot burden, which is how we tell which patients get AngioJet.
Dr. Baim: I think this is the only way to assess thrombus burden. Dr. Brodie: You only use AngioJet in those patients (with a totally occluded artery) that you have dilated with a small balloon, visualized the distal vessel and documented a large thrombus?
Dr. Matthews: We call it the 2.5 balloon test that they have to pass to get AngioJet. Dr. Brodie: But there are people with a totally occluded artery that you dilate with a 2.5 mm balloon, their flow is great, and the artery looks good and you do not see much.
Dr. Simonton: Then we would just stent it. And that is what we need to know. If we could all refrain from performing thrombectomy in a lesion without thrombus — that is what we want to do.
Dr. Brodie: So all your operators were consistently choosing the patients in whom they used AngioJet based on this technique?
Dr. Matthews: Two of us did it and two of us did not. (There are a total of four interventionalists in our group.) The one who did it with me is my former Fellow, so we were quite consistent with our technique in the group that received AngioJet. The other two operators did not use AngioJet consistently. Also, we primarily performed rheolytic thrombectomy distal to proximal, which may change now. Following three passes with the catheter, you can usually see an exposed ulcer crater and it looks like plaque rupture.
Dr. Baim: That is the classic ruptured plaque morphology. You have a big crater in there — that was the attachment point for that rattail.
Dr. Simonton: Are you going to be able to randomize that patient? I like your idea of maybe the endpoint being improved flow, but are we are going to go in and randomize a patient like that to no thrombectomy versus thrombectomy and have some other endpoint other than improvement of flow acutely?
Dr. Baim: So you can only randomize that patient to thrombectomy or no thrombectomy if you have clinical equipoise — if the perception of risks and benefits is equal, and I would say based on AiMI, there is reason to think that maybe you would not be helping those patients. So it is fair to randomize them.
Dr. Simonton: What if it looked worse than that? What if the thrombus is more than 1.5 times the vessel diameter, maybe TIMI thrombus grade 4? What if it is really looking dye stainy, are you going to randomize that patient?
Dr. Matthews: I think another important thing would be to try to look back at those AiMI patients and find out if there is an influence on outcome based on the patient’s anatomy. For example, small or tortuous proximal vessels may have led to more AngioJet complications. If one looks more at the anatomic characteristics, that may influence randomization in these patients too. These characteristics may have had an influence, even if they just added to the procedure time.
Dr. Baim: The definition of no reflow requires that there is no epicardial obstruction, so when you say that there was no reflow at some point, is that point when the original epicardial lesion has been treated, Dr. Matthews? Dr. Matthews: At any point during the procedure, either with pre-dilatation or with stenting.
But if you pre-dilated and there was still a severe stenosis epicardially and the flow was slow, technically you really could not call that no-reflow because there is another reason for the slow flow other than microvascular obstruction.
Dr. Matthews: Exactly.
Dr. Brodie: Those are really impressive data, 3.5% mortality in patients undergoing rescue angioplasty with 20% of the patients having cardiogenic shock.
Dr. Matthews: Thank you. We worked hard with these patients.
Dr. Brodie: There is a lot of concern and not a universal consensus on the use of glycoprotein IIb/IIIa platelet inhibitors in rescue angioplasty, and in ASSENT 4-PCI it was not used because of concern about bleeding. Regardless of the time period, did you have any bleeding problems with the use of glycoprotein (GP) IIb/IIIa inhibitors after fibrinolytic therapy?
Dr. Matthews: We were operating under the notion that we may buy some additional bleeding complications. But we felt some of the lytic failures may be due to the fact that they are platelet-rich thrombi.
Dr. Brodie: Did you have any guidelines on how soon after thrombolytics you would be willing to use GP IIb/IIIa inhibitors? Or would you give it pretty much routinely? Dr. Matthews: If patients had visible thrombus and no flow in the cath lab, they all got a GP IIb/IIIa inhibitor.
Why do you think your TIMI 3 flow rates after AngioJet were better than in the AiMI Trial? You said you did not do antegrade thrombectomy, you did retrograde. In AiMI, TIMI flows at baseline were worse in the AngioJet group compared with the control group — that is one difference, but that most likely would not explain it all.
Dr. Matthews: I am concerned about whether there were many patients with small proximal vessels and maybe this catheter is too big for very small vessels, in its previous iteration. And that may account for some of the problems in AiMI.
Dr. Brodie: And possibly less experienced operators. Dr. Matthews, I was a little concerned about the ethical issues of the HMO giving thrombolytic therapy to everybody. Can you elaborate on that?
Dr. Matthews: It is interesting. This particular HMO has about 2.5 million members in the Los Angeles basin, and they did a very interesting study where they looked at outcomes (live or dead) of their patients receiving direct angioplasty at a community hospital. It turns out the results were far inferior to the published trial results. The literature results were not translating to these small-volume clinical hospitals. Based on these data, they changed their strategy, and began requesting their patients receive lytics.
Dr. Brodie: These are patients that present to non-interventional hospitals?
Dr. Matthews: Yes, many of these patients originated from HMO-member hospitals that did not have cath or interventional capabilities. One thing we did not talk about is the quality of the thrombus. We talk about the quantity, and ways to see how much thrombus there is, but we have been impressed with use of AngioJet in the periphery and elsewhere that the duration that the clot has been present is a big predictor of outcomes too. Many of these patients have had stuttering courses, and a history of a stuttering course may be a clue that the clot has been in the artery for some time with varying degrees of organization. Sometimes these cases are much more difficult to deal with and might best be treated with the AngioJet.
Dr. Brodie: Do you handle them any differently?
Dr. Matthews: I just think that those cases would be considered high-risk cases, not just on the basis of quantity of thrombus, but on its quality or type.
Dr. Sianos: That is an interesting point. Do you have any way that you are measuring thrombus organization?
Dr. Matthews: Unfortunately, we do not have a good way to measure the degree of organization.
Dr. Sianos: In my mind it does not matter, it goes directly to the fact that there is a discrepancy in the outcomes of distal protection devices when you use them in vein grafts in comparison to when you use them in the acute MI setting. And we know that they are working in vein grafts and they are not working in acute MI. And I think that the most reasonable explanation is that both the quantity and the quality of thrombus is different in vein grafts.
Dr. Matthews: Maybe the best clinical way to measure that is to pre-dilate with a balloon. If it is organized, the thrombus is spongy and remains after dilatation with a small balloon. And if it is not organized, then it dissolves and you get TIMI 3 flow instantly.
Dr. Sianos: Do you have any clue whether you are really influencing the baseline thrombus burden when you are inflating with a 2.5 mm balloon? Is such a big balloon necessary? If you do it with a 2.0 or a 1.5 mm balloon, do you think that you will get less information?
Dr. Matthews: I think you would end up using the AngioJet a little bit less if you predilate with a 2.5 mm rather than a 2.0 mm balloon. In some patients, clearly a 2.0 mm balloon would be adequate. We do not believe that there is a great deal of difference between a 2.5 or 2.0 mm balloon in most cases, particularly those with large vessels.
Dr. Brodie: Dr. Matthews, how do you angiographically identify the thrombus as being old? Have you noticed any difference in the response to the AngioJet between old and new thrombus? Or is it sort of a retrospective thing — after you perform thrombectomy with the AngioJet, you may not get quite the same result with an old thrombus as you would if it were fresh?
Dr. Matthews: Our best experience in old versus new thrombus is in dialysis grafts, where we have a huge AngioJet experience. Patients who come in with acute occlusion of the graft are easily treated with the AngioJet. But if you get somebody who has been clotted for a week and presents to you, it is difficult to declot, even with the AngioJet and their most powerful catheter. So clearly, the age of the clot makes a difference in its ability to be removed. We did a paper a long time ago and showed that acute MI patients who had stuttering courses and had angiographic thrombus (presumably old) had a lot of trouble, even with TIMI Grade 3 flow prior to intervention. So we think that may be a clue.
Dr. Brodie: After the concern in AiMI with increased mortality in the AngioJet group, I think it is encouraging to know that there does not seem to be any harm from the device in all the registry data presented this evening.
Dr. Simonton: I think operators are using AngioJet in patients who are the sickest with the most clot and the worst clot. And that is where we will probably see clinical benefit, but we will never be able to randomize those kinds of patients.
Dr. Brodie: Dr. Simonton, tell us how you use AngioJet in your own practice.
Dr. Simonton: The biggest trend I am seeing is a shift toward using devices that have ease of use, which is such a big thing out there. Operators are switching over — even with large thrombus — to the Pronto and other aspiration devices.
Dr. Brodie: Do you choose a device based on the amount of thrombus burden? Dr. Baim showed a patient with a huge thrombus burden. Do you have situations where you just do not think you will get it done with anything but an AngioJet?
Dr. Simonton: No, our guys are convinced these catheters are aspirating large amounts of thrombus.
Dr. Baim: Do you have cases where operators used an Export and there was still a filling defect?
Dr. Simonton: Yes. A colleague had a case of a vein graft that was diffusely diseased with a large amount of thrombus. He used the Pronto multiple times and still had this filling defect sitting down at the turn of the RCA graft. I suggested using the AngioJet, and it got better. So I do think the AngioJet in vein grafts is more efficient in removing thrombus.
Dr. Brodie: Are you using distal protection with the AngioJet in those vein grafts?
Dr. Simonton: No. We have done it a couple of times just because we felt like maybe we should have a filter wire down while we are doing it. We do for the stenting portion, but a lot of times we just put a wire down, perform thrombectomy with the AngioJet, and then put a filter down prior to stent deployment as part of the procedure.
Dr. Brodie: You are not concerned about embolizing when you are using the AngioJet?
Dr. Simonton: Maybe we should be. If there is diffuse disease and a large thrombus and atheroma burden, I do put a filter down.
Dr. Brodie: If you are going to put a filter down anyway, why not do that first?
Dr. Simonton: We did that, and we filmed cases like that for the course to show how you can use thrombectomy and distal protection together. I like to do it because I think there is too much thrombus burden not to have a filter wire down when you are AngioJetting some of them. But I do not think it is common practice.
Dr. Brodie: Dr. Sianos, your classification is a huge improvement.
Dr. Sianos: Thank you. Our results have no evidence that TIMI Grade 5 thrombus (total occlusion) really means there is a large thrombus burden. G3 is not that much different from G2, but is definitely different from G4. So that finding is what we are missing from the literature. Of course, all of these were visual estimations, so you have to trust me — I will have to trust my eyes because I have done these 900 films. But when you have a thrombus that is 7 times or 4 times bigger than the reference vessel diameter, is that thrombus the same as the thrombus that is two times the reference vessel diameter? That is a question that we are busy working on answering. I did not show any data, but the number of the patients with large thrombus burden is going down. This is because we are better at determining which patients truly have large thrombus burden.
Dr. Baim: Probably what I would do is look at a cross-section area of the filling defect on the angiogram, rather than these discrete grades.
Dr. Sianos: We are trying to remain clinical and practical. For the academic part we have time and can perform quantitative coronary angiography (QCA) and measure thrombus volumes.
Dr. Brodie: Why do you think patients with TIMI Grade 0 thrombus had poor survival similar to patients with Grade 4 thrombus?
Dr. Sianos: That really puzzled us. Patients with very big thrombus were younger, while patients with no thrombus were older, had more multi-vessel disease and more multi-vessel PCI during the index procedure. So it was a completely different clinical picture between patients with large thrombus and no thrombus.
Dr. Brodie: Dr. Dixon, in your presentation, patients treated with AngioJet had slightly lower MACE rates that those not treated with AngioJet.
Dr. Dixon: We found that patients who were treated with the AngioJet had a larger infarct size based on the peak creatine kinase (CK), yet the overall in-hospital mortality and MACE tended to be lower in this group. The explanation for this discordance is not readily apparent, but we are looking into this further.
Dr. Antoniucci: From all presentations, it’s clear that the mortality rate for acute MI in the real world is higher compared to the randomized trials, including the AiMI trial, confirming that exclusion criteria from enrollment used in these trials play a crucial role in population bias.
Dr. Brodie: The main difference, Dr. Antoniucci, between your upcoming JETSTENT Trial and the AiMI Trial is going to be the technique in performing thrombectomy with the AngioJet and direct stenting.
Dr. Antoniucci: Direct stenting and, very importantly, the broad inclusion criteria that will allow the enrollment of patients with high-risk coronary anatomy, cardiogenic shock and multi-vessel disease. Moreover, only patients with evidence of grade 3 to 5 thrombus will be considered eligible for the study.
Dr. Brodie: You will be enrolling TIMI Grade 5 thrombus (total occlusion)?
Dr. Antoniucci: Yes, and this criterion makes a very important difference.
Dr. Brodie: I am concerned about the lack of use of temporary pacemakers.
Dr. Antoniucci: Dr. Baim may testify that 20 years ago, temporary pacemakers were used routinely in patients undergoing balloon angioplasty, but this practice was promptly stopped because it was clear that there was a very high risk of right ventricle perforation and subsequent cardiac tamponade. Moreover, I think that in patients receiving heparin plus platelet GP IIb/IIIa inhibitors, the risk of cardiac tamponade due to temporary pacemaker is not low.
Dr. Brodie: So how do you manage the bradycardia? Dr. Antoniucci: Bradycardia is very temporary. If the patient is able to cooperate, it is sufficient that the patient coughs. Otherwise, you can administer atropine before activating the device, or you can activate the device for very short times. With multiple short device activation steps, you can avoid bradycardia as well as the need for a temporary pacemaker.
