Pathology of Intervention

00:00 Okay, welcome. This is an interesting topic particularly in this day and age as we do more and more things to help intervene when someone has cardiac pathology. You're going to see more and more complications related to our interventions. So we're going to talk specifically about stenting and vascular replacement. Separately, we will talk about valves we'll talk about valvular replacement and some of the complications related to that.

00:28 But this is just going to be intervention within the vascular system. Okay, with that, let's look first at something that happens daily in every major medical center, happens multiple times each day. This is going to be a patient who has a stenosis, say in a coronary artery and we need to bypass it, we need to open up that vessel because there's restricted flow.

00:53 You can see that the red blood cells are just kind of trickling past the atherosclerotic plaque. We can do this with coronary artery bypass grafting, that is to say a surgeon goes in and we'll sew a vein into the aorta and then into the distal coronary artery and bypass that area of obstruction. More commonly these days, we do it as a non-surgical approach.

01:20 It's still invasive, we have to thread a catheter up through a femoral artery into the heart in most cases but what we do is we insert a catheter to the area where there is stenosis going through the coronary artery os and we advance a wire and then we advance a stent, a wire mesh stent, that will be inflated with a balloon under several atmospheric pressures to give us that stent now holding open the vessel wall. And once we do that, we deflate the balloon, pull it back out and walla beautiful flow down this vessel. This is a great way to treat coronary artery stenosis or other stenoses in other vascular beds and is, as I said, done routinely. So what are the complications of this? When we put in that stent, I just showed you working beautifully, well it doesn't always work so beautifully. When we put in the stent, it's a metallic structure and it causes endothelial cell damage. We're looking at a cross section of a vessel where we put in the metallic stent, we damage the endothelium. Remember when we have unhappy or damaged endothelium, it can thrombose. So we could have an acute vascular occlusion due to thrombosis after we inflate the stent. You can see the stent is kind of the little blue dots kind of all the way around and the thrombus there is indicated in green. We have opened up this vessel, but now it's become acutely reoccluded because of the clot and that would actually be a cause of death in this particular patient, so it's the endothelial injury.

03:00 How do we work with this? How do we prevent that? So basically when we put in stents, we know we're going to damage the endothelium. So when we do that, we put patients on an anticoagulant, an antithrombotic regimen for several days and sometimes even longer for certain kinds of stents that may give them anticoagulation for up to months later and that prevents the thrombus from forming. And then over time, the injured endothelium will regrow over the surface of the stent and we're good to go. One of the other complications of putting in a balloon and then dilating it, opening it up under several atmospheric pressures is that we can actually induce a dissection plane, we can rupture the vessel, and the dissection plane here is indicated in green. Now usually when we are doing this procedure, we put in a stent and that helps to mitigate any dissections that occur, but sometimes we can cause through and through rupture of the vessel with bleeding into the pericardial sac and that's an untoward complication. One of the more chronic long-term complications associated with stenting is you get in-stent restenosis.

04:19 This is a vessel with atherosclerotic plaque indicated there on the left hand side of the vessel that we put in a stent probably 6-12 months ago. And you can see the struts on the stent, cutting cross section is the little black dots. And you can see where they even ripped out of their holes, those are the cleared rectangular areas. Inside of that is an area of intimal hyperplasia, smooth muscle cells, matrix of few inflammatory cells.

04:46 And that's because even though we have given this patient anticoagulation for a period of time, there's still been endothelial damage. And you will recall from our discussions having to do with atherosclerosis, endothelial damage not otherwise specified will also tend to lead to a healing response which is this, this intimal hyperplasia, much like atherosclerosis. So, how do we deal with that because this can eventually completely restenose the vessel. We opened it, we spent a lot of effort opening it, now it's closing back up because the vessel wall is trying to heal itself. You can see the stent struts, you can see the atherosclerotic plaque, you can see the intimal hyperplasia. And that again is smooth muscle cell growth, proliferation, and matrix synthesis. So it's seen in a significant proportion of patients, roughly a third of those, within 6-12 months of stenting, again depending on the kind of stent that we use. How do we mitigate that? Well, increasingly we don't use just bare metal stents. That is still used, abbreviated in the chart is BMS, bare metal stent. Increasingly, we take stents that had been coated with various drug eluting polymers. In over a period of weeks to months, those drugs elute in and around the vessel. They provide a mechanism by which we can inhibit smooth muscle cell proliferation. The drugs include paclitaxel and sirolimus but there are others that are being used and those drugs limit that intimal hyperplasia. A downside of the drug eluting stents, DES, is that they also inhibit the proliferation and regrowth of the endothelial cells. So patients with drug eluting stents will need to have anticoagulation for a longer period of time until the re-endothelialization occurs over the surface of the struts on the stent. Some other complications, kind of an interesting and curious complication is that when we put in catheters, they are coated with various polymers, they have various stent coatings and they'd fragment off the tip of our catheters and they go in to the distal circulation. This can cause focal occlusion and as you see here, a foreign giant cell reaction. That can have an associated infarction in some cases.

07:09 Usually the amount of material that elutes off the surface of the catheters is very small so the size of the infarct is small, but the inflammatory response can sometimes be significant and we see this is just a complication of doing business with polymer coated structure stents. Okay, that's stenting. What about doing coronary artery bypass grafting? The traditional way that we do it and we still do this is that a cardiothoracic surgeon will harvest saphenous veins, so peripheral veins from the legs which are a little bit redundant and you can leave without. And then they will attach them to the aorta and then tuck them down into a coronary artery bypassing an area of obstruction.

07:58 Those saphenous vein grafts have been manipulated. They began life as a vein and don't like being in our arterial circulation. And as a consequence of those 2 things, they have a limited patency, so you gather all these effort, putting a saphenous vein graft and after 1 year roughly 40% of them will have occluded, they will have closed off even if the surgeon has magical hands and even if you do everything exactly right. So this is just showing here a saphenous vein that has been put into an arterial circulation as a bypass graft, you see the vein wall, you see that there is intimal hyperplasia so again if I put a vein into an arterial circulation it will have the same response to injury and try to buttress the wall with smooth muscle cells and extracellular matrix. So they'll have intimal hyperplasia, but a significant number of them, roughly 25% will thrombose and this is just showing the thrombosis of that vessel so it's no longer patent and it's useless for what it was intended to do. Is there a way to get around this? Well yes. So, it turns out the internal mammary artery which sits on the underside of the thoracic chest wall plate can be used as a bypass graft, you don't remove it. You actually just kind of peel it away from the anterior surface of the chest wall, leave it attached to the aorta where it normally would come off and then you plug it into the anterior surface of the heart.

09:31 The problem associated with internal mammary artery grafts is that you only have one internal mammary artery on the left and one internal mammary artery on the right and you therefore have a limited number of vessels that you can bypass. If your patient needs to have 5 areas of occlusion bypassed, you're not going to be able to do it with an internal mammary artery. Not only that, but the left anterior mammary reaches pretty well to the anterior and lateral surface of the heart but can't get to the posterior surface of the heart and similarly for the right internal mammary it won't reach all the way around to the posterior descending. So there are limits to what the internal mammary can do. However, this is an artery, it's an elastic artery actually and the patency after 1 year is better than 90% so this is a great solution if you only have 1 or 2 vessels that need to be bypassed. Now you're saying, well "Gee we can do synthetic grafts." That's true but synthetic grafts are only really going to work really well for large bore vascular replacement. So like aorta-sized vascular replacement, 12-18 mm. For small bore applications, less than 8 mm in diameter, the flow thru those with a totally synthetic surface is not sufficient to prevent thrombosis. So small bore grafts are not a solution if we need to bypass coronary artery obstructions. And I put it out there as a plea to you future physician, scientist of the future to work on how we can make better synthetic grafts. One of the other problems associated with synthetic grafts even if we have them of the right size. So this is showing you an aortic graft which is going to be fine, it's not going to thrombose. But where you attach it to the existing vessel, that vessel tends to grow in intimal hyperplasia. It's again a normal response to injury and the arrow indicated on the right hand side shows how that can become stenotic.

11:38 Going into the graft, the graft is patent, it works great but that anastomosis between the native aorta and the graft is becoming progressively stenotic and that is a limitation even of many of our synthetic grafts. And with that, we kind of looked at some of the pathology associated with vascular intervention.