Gregg W. Stone, MD: Hello. I'm Gregg Stone, and we're at the annual scientific sessions of the American College of Cardiology in New Orleans where we're going to discuss prevention of sudden cardiac death (SCD) in high-risk patients after angioplasty, specifically those with acute myocardial infarction (MI). Over the last 2 decades we've made tremendous advances in managing patients with acute MI with primary angioplasty, significantly reducing mortality, reinfarction, recurrent ischemia, and improvement of quality of life. However, there are significant numbers of high-risk patients who present with left ventricular dysfunction who still have a high incidence of SCD and mortality even after successful primary angioplasty. I'm here with my esteemed colleagues, Jim Hermiller from the Care Group in Indianapolis, Alan Kadish from Northwestern, and Sunil Rao from Duke. We're going to discuss this topic, specifically looking at electrical therapies to prevent SCD.

Let me start the discussion by making some observations about acute MI from the CADILLAC trial. This was one of the largest primary percutaneous coronary intervention (PCI) trials. It was a study of over 2000 patients who were randomized to different antithrombotic regimens and angioplasty vs stents. When we looked at the overall outcomes, patients did very well.

We were able to identify high-risk groups and we came up with a CADILLAC risk score that we published in the Journal of the American College of Cardiology. There were 4 clinical and 3 angiographic variables that predicted high-risk patients: advanced age, presentation with Killip class 2/3, renal insufficiency, anemia; and then in the cath lab: multivessel disease, depressed left ventricular ejection fraction, and the inability to restore TIMI-III flow. We could stratify patients into low-, intermediate-, and high-risk groups.

Some patients were high risk even though we enrolled a relatively low-risk population, 95% of whom had a successful primary angioplasty. Fifteen percent of the patients died within a year in the high-risk group, most patients died within 30 days, and about 60% of these died suddenly. We know that with primary angioplasty when you have big infarcts what we don't do a great job of is salvaging myocardium. That's because patients often come in too late for us to help them. In these patients with big infarcts by getting the artery open, by treating them carefully, and putting them on good medical therapy we can prolong their lives, but we still have a high-risk group that we've got some great opportunities to intervene.

When we've identified a high-risk patient group for sudden cardiac arrest, what can we do? We know that implantable cardioverter-defibrillators or ICDs significantly prolong life in patients with left ventricular dysfunction but not necessarily in the group early after angioplasty. Alan, can you review what the current indications for ICDs are in general and then focus specifically on the post-MI population.

Alan Kadish, MD: Patients who have had a cardiac arrest or an episode of sustained ventricular tachycardia are indicated for defibrillator therapy unless it happens immediately in the setting of an acute MI. The larger group, and the group that's more complicated, particularly post PCI, are patients who have not yet had a cardiac arrest or sustained VT, so-called primary prevention of sudden death. We know in patients with chronic coronary disease, patients who have an ejection fraction < 30% or < 35% in the presence of heart failure have an indication for ICD therapy. It has been shown that ICD prolongs life in those groups of patients.

In contrast, a study that attempted to implant ICDs in the subacute phase of MI, say 7 days after MI, was unable to show that ICDs decrease mortality.

Dr. Stone: This is the DINAMIT study?

Dr. Kadish: This is the DINAMIT trial. The reasons that the ICD did not prolong life when put in immediately or soon after MI are still not completely understood, but they seem to relate to 2 factors. One is that the patients who die suddenly also have a high incidence of dying for other reasons. The other reason may be that defibrillator implantation soon after MI actually has deleterious effects. Therefore, because of the results of the DINAMIT trial, the official indications for ICD implantation exclude patients within 40 days of MI, which was the enrollment period in the DINAMIT trial. Within the first 40 days, there's pretty good evidence that an implantable defibrillator won't prolong life. In contrast, after 40 days if the ejection fraction is still down below 30 or 35, there's good evidence that the ICD will prolong life.

Dr. Stone: But aren't those first 40 days or that first month the highest risk period for SCD?

Dr. Kadish: It is, and that really gets to the question you asked before: what do we do with those patients? We don't really have great risk stratification techniques other than the CADILLAC score that you described, and in terms of arrhythmias we know from other studies that the most important risk factor for arrhythmia is left ventricular dysfunction. We have a temporary therapy that we can use aside from best medical therapy in the first 40 days after MI. That's the wearable cardioverter-defibrillator (WCD).

Dr. Stone: Right and we'll come to that. Interventional cardiologists have some opportunities here. If we see a patient in the cath lab on whom we're doing an intervention or just a diagnostic cath and their left ventricular ejection fraction is less than 30%-35%, they may have a chronic cardiomyopathy but they are not in an acute MI setting. We should strongly consider those patients for an electrophysiology consultation to see if they're appropriate for ICD implantation.

On the other hand, if the patient is in an acute infarct setting and we've taken them to the cath lab for a primary angioplasty, we can identify the high-risk patient but it's not appropriate at this time to consider an implantable ICD within about 40 days. Sunil, that brings up a frustration level because we see these patients, we have an occluded LAD, we open it up, the ejection fraction is 20%. We know the patient probably has about a 5%-7% chance of SCD in the next month. Some people nonetheless put in a defibrillator in this situation. In fact, there was a recent study in JAMA that got a lot of attention from the National Cardiovascular Data Registry (NCDR) that showed that about 22% of ICD placements were "inappropriate" according to the guidelines. Can you tell us about that study?

Sunil V. Rao, MD: It certainly has been a lightning rod for a lot of controversy within the clinical community, particularly within the electrophysiology community. We need to understand why these patients receive ICDs. While it may be inappropriate according to guidelines, there may have been good clinical reasons, many of which you outlined, for these patients to receive them.

There is a quantifiable risk for SCD in the post-MI period. The problem is twofold. One is that for interventional cardiologists it's not on their radar screen and probably should be in the acute MI setting, particularly as patients are recovering from their primary angioplasty. The other issue is that it's difficult to identify who the patients are specifically. While registry data may tell us that it's "inappropriate," there may have been clinical reasons that aren't captured why this high-risk group of patients was treated in this way. You mentioned that we're going to talk about the WCD. That may be a nice middle ground while we're waiting for better risk scores and better risk identifiers to be developed.

Dr. Stone: Short of some sort of electrical interruption therapy we're going to treat these patients with angiotensin-converting enzyme inhibitors or angiotensin receptor blockers. We're going to treat them with beta-blockers. Alan, as an electrophysiologist, is there a place for prophylactic amiodarone?

Dr. Kadish: That has been well studied. Amiodarone does not improve survival in post-MI patients or in patients with chronic disease, primarily because the antiarrhythmic effect is offset by the toxicity of the drug. There's no indication for prophylactic amiodarone to prevent SCD. One thing I want to add to what you said about the study of inappropriate ICD implantation is I want to make it clear that the guidelines very clearly state that if you've got a patient who has an episode of sustained ventricular tachycardia (VT) or ventricular fibrillation (VF) or comes to the hospital with a minor enzyme leak, that does not exclude them from having an ICD within the next 40 days.

Dr. Stone: What about a large infarct with primary VT/VF?

Dr. Kadish: For a large infarct with primary VT/VF within the first 24 hours you probably don't need to worry about that patient to a major extent, but if it happens after 24 hours that's an indication for the secondary prevention of SCD with ICD implantation.

James B. Hermiller, MD: I would echo one of Sunil's comments that as interventional cardiologists we too often think we put a stent in and think the patient is fine and don't think about this risk for SCD, which is so high within the first month or 6 weeks.

Dr. Stone: Jim, you have experience with a WCD. Can you describe this for us and then tell us what your experience has been?

Dr. Hermiller: The LifeVest (ZOLL Medical Corporation, Pittsburgh, Pennsylvania) is basically a WCD for sustained VT and VF and is easy to wear. Patients tolerate it very well. Anterior and posterior defibrillator pads with gel are activated at the time patients need to be shocked. It's able to record the rhythm so you have a recording of what happened during the event. Actually, the patient gets a warning that a shock is about to occur and if they're going to be shocked and if it is an inappropriate shock (which is relatively rare and infrequent), they're warned and they can shut the vest off by pressing a button.

Dr. Stone: So it's comfortable? They sleep in it?

Dr. Hermiller: They sleep in it. On average patients wear it 22 hours a day, so it's well tolerated. For the patient who comes in with the risk factors that you talked about; a big anterior infarct, particularly when there is nonviability, or they come in late, and there isn't good reperfusion, those are patients that I'd use this on.

Dr. Stone: One of the reasons for waiting 40 days is that some patients improve their left ventricular function over time. You'd like to avoid a permanent implantable device if 1 month later their ejection fraction goes from 30% up to 50%. That happens with primary angioplasty, especially when you get them early. In this setting there have been studies with the WCD. Alan, can you tell us about those?

Dr. Kadish: The largest study was a 3500-patient study that included different categories of patients who got the WCD. Some patients had infected ICDs that were extracted, but a significant number of patients were post MI who were within the period where ICDs weren't indicated because of exactly the factors you just mentioned. In those patients, the WCD was highly effective at converting VT and VF.

It was well tolerated in most patients but not all because some patients refused to wear the device. There are improvements we can make, and I don't want anyone to feel that everybody can tolerate the device. Most patients can. Most patients wear it, and it's highly effective.

The one weakness it has is, unlike an ICD, it doesn't serve as a pacemaker. There was a significant incidence in that series of 3500 patients of asystole causing SCD, which of course was not helped by the WCD. Except for that caveat, it's a very effective device. What you can do is re-evaluate the patient 40 days after the primary angioplasty and see if the ejection fraction is still depressed or if you've been successful at salvaging myocardium. If the ejection fraction is still down, you can then convert the WCD to an ICD. The WCD is not a 6- to 12-month device, but it's very good for 30-60 days.

Dr. Stone: And it is compatible with pacemakers, so a patient who has a permanent pacemaker can still wear this vest. Is it covered by insurance?

Dr. Hermiller: Sometimes we need to argue a little bit with insurance companies to get it covered, but it has been covered in most of the patients for whom we've used it.

Dr. Kadish: That has been my experience as well. Most insurance companies now will pay for it, particularly when you juxtapose the cost of the WCD to a permanent ICD and tell the company you may be able to save implantation of a permanent ICD in people who don't really need it by using the WCD.

Dr. Stone: How common are inappropriate shocks with this device, and how uncomfortable are the shocks compared with an ICD shock?

Dr. Hermiller: They're very uncommon. In the series we just talked about, there was a very low incidence of 1%-2 %. Remember, the patient can inactivate the device. Patients are alerted if a shock is coming, and if it's going to be inappropriate then they can hold it off, so it's quite infrequent.

Dr. Stone: I can imagine other situations where the WCD may be useful. As interventionalists we need to think about this for our patients at high risk for SCD in the early phase after acute MI. There haven't been any randomized trials yet and while it would be nice to have that, it seems like a low-risk alternative that is reasonable to consider in this very high-risk group of patients.

Other patients -- for example, those who have had a recent lead extraction, let's say for lead sepsis or other indications, and who for a month or two may not be able to get an ICD placed back in -- those patients are at very high risk. Patients post surgery with poor left ventricular function have to wait 3 months according to guidelines before an ICD is put in. Patients with a new diagnosis of idiopathic dilated cardiomyopathy or class IV heart failure who don't have CRT therapy. There are a lot of other indications for ICDs that aren't currently supported by the guidelines that we might consider for this.

Dr. Rao: We probably should be using it more at our center. You brought up the patients who are probably really good candidates, but there's also a group of patients we probably should be studying more, patients who undergo high-risk PCI for ischemic cardiomyopathy and poor left ventricular function who have not had a recent MI using the vest as a bridge to ICD placement. In the era of everyone looking over our shoulder and papers coming out saying that certain things that we're doing are inappropriate, to have an option like this is very valuable.

Dr. Kadish: Almost all of the "inappropriate" ICD implantations were a timing issue. The largest group was not post-PCI patients, although it was a significant group, it was patients with recently diagnosed cardiomyopathy. Unlike the post-MI patients where at least we have 1 or 2 randomized studies that show that the ICD is not helpful in patients with recently diagnosed cardiomyopathy, either ischemic or nonischemic, in this case there are no data. The guidelines don't say you should put an ICD in because there are no data from randomized trials that are helpful.

We published a retrospective analysis of a trial in nonischemic cardiomyopathy that showed that ICDs are helpful within the first 90 days because there was a very high incidence of SCD in patients with recently diagnosed cardiomyopathy.

Dr. Stone: Some of those patients might reverse if it was myocarditis or if it was caused by acute alcohol or cocaine use. So there's a reason to wait, especially given the cost and occasional complications of an ICD.

Dr. Kadish: Exactly, and that's why I said it was a timing issue. The WCD is a good choice for patients you're worried about in any of those timing categories where the indications don't yet support the use of an ICD. I don't want to overemphasize inappropriate ICD implantation in patients where it hasn't been shown to be helpful. There still ought to be a role for clinical judgment, and if you have a bridging option it really helps you exercise that clinical judgment in the best possible way.

Dr. Stone: The term "inappropriate" has been overused. The report from Al-Katib in the NCDR reviewed over 100,000 ICD implantations. The lowest rate was down at around 6% of "inappropriate use." The average rate was up at around 20%. It was less likely for inappropriate use to be performed by electrophysiologists compared with nonelectrophysiologists, but even electrophysiologists had a "20% or 21% inappropriate rate." Physicians need to be able to practice the art of medicine. They're using their best judgment in high-risk patients. There may certainly be mitigating factors.

Guidelines are just guidelines. They're not rules. Nonetheless, we also know about the high cost of ICDs. This is one of the biggest ticket items in the Medicare budget every year. Given that in some of these newly diagnosed heart failure patients, the post bypass surgery patient and the post primary PCI patient, anywhere from 30%-60% of the ventricles will improve over time and they won't have an indication 2 months or 3 months later for an ICD. This temporary external WCD is a good option for those patients.

Dr. Hermiller: The role of the interventionalist as these patients who have indications for ICDs now and out to 3 months, we are in some ways gatekeepers. Often they'll come through us, and unless we get them to an electrophysiologist or think about a WCD these patients aren't going to get it. They're going to go back to their cardiologist and be missed in the system. We need to be more aware of this SCD issue and whether it's WCD or getting them to an electrophysiology specialist, it needs to be on our radar.

Dr. Kadish: We've made a lot of progress at prevention of SCD as a society. We've done a lot of good things about limiting the size of MIs with PCI. We've changed lifestyle so that hopefully coronary disease is no longer increasing. We've put automatic external defibrillators in, but there are still several hundred thousand sudden deaths a year in the United States. Many of those are patients who do have indications for ICDs. The problem with inappropriate ICD implantation is actually much smaller than the problem with patients who have indications for ICDs who may benefit from them but don't get them. The idea of the interventional cardiologist being a gatekeeper and thinking about this issue is a very important one.

Dr. Rao: The onus on the interventional cardiologist is to not just think about reperfusion and door-to-balloon times and the kinds of things that we're obsessed with but also to start thinking about the period of time between the primary PCI and the time that they go home, including the time they may be candidates for an ICD. That's going to be probably the most important thing with respect to reducing the risk for sudden cardiac arrest.

Dr. Stone: As an interventional cardiologist it's wonderful to be thought of as a gatekeeper, but many of these patients will present in different care settings. Many are referred directly for bypass surgery. These are patients who we have to consider as well. Many will end up in heart failure clinics after an outside diagnostic workup shows clean coronary arteries. This is really a cardiology/medicine-wide issue. We need greater dissemination of these options for patients. Finally, it's very clear that we need more studies. A perfect setting would be primary angioplasty using the CADILLAC risk score to identify high-risk patients and then randomly assign those patients to either the WCD or control. (Editor’s note: Since the time of this recording, a recent study with the WCD (Zishiri ET, et al. Circ Arrhythm Electrophysiol. 2013;6:117-128) has been published in a population of revascularized patients showing a lower hazard for patients wearing the WCD). With enough patients and an appropriate trial, my hypothesis would be that we would show a reduction in SCD and/or total mortality. It seems like there is very little downside and very few side effects of this device, which of course makes it very, very attractive.

What we tried to do over the last 20 minutes is review some of the causes of SCD in some of the most common patients that we see in cardiology today. While we've made tremendous progress, we still have a way to go. On the other hand, we have new options. In particular, there is no doubt the ICD when used in appropriate patients saves lives. We now have a second option, the external WCD, for patients who are not yet indicated according to national guidelines for permanent ICD placement. We'd like all viewers of this program to at least consider this option when you're taking care of these high-risk patients. Thank you very much.