Commentary

IAGS discussion – Supporting Patients in Shock (Part ii)

Participants: James P. Zidar, Fayaz Shawl, Alfredo Rodriguez, Luis de la Fuente, Kirk Garratt, Paul Overlie, Jeff Werner, Gian Feltrin, Howard Cohen, and Tom Linnemeier
Participants: James P. Zidar, Fayaz Shawl, Alfredo Rodriguez, Luis de la Fuente, Kirk Garratt, Paul Overlie, Jeff Werner, Gian Feltrin, Howard Cohen, and Tom Linnemeier
Part ii Continuation of discussion Supporting Patients in Shock Jeff Werner: I have a question for Dr. Shawl. I believe you said that you think patients should be completely revascularized during acute infarction using angioplasty and stenting. I have not been doing that, however. If patients who come in with lactic acidosis and arrhythmias turn around quickly when I open the target artery, I think they ought to have a breather, so I take the patient back upstairs and wait a while. Some of these patients also have multi-vessel disease for which the best outcome might be surgery, depending on the anatomy. If I’m wrong, I would like to know what you think I should be doing instead. Fayaz Shawl: Most of the data from the SHOCK trial regarding multi-vessel coronary disease patients with shock show that intervening solely on the infarct-related vessel results in a mortality rate of about 60–70%. Part of the reasoning is that if, for instance, a patient presents with acute myocardial infarction, the LAD is totally occluded, the sub-total circumflex is critical, then a non-infarct area may be important for the patient’s outcome. Given that information, I definitely try to completely revascularize patients with multi-vessel disease. If this is not possible, then I send the patient to surgery. Jeff Werner: Even if the patient improves as soon as you open up the infarct-related artery, the blood pressure is normal, the EKG normalizes, etc.? Fayaz Shawl: I think it does depend on the situation. I’m talking about complete revascularization for patients who are critical: blood pressure is 70, a balloon pump is in place, the patient is on epinephrine, etc. In those cases, I do everything in the lab that I can to revascularize the patient. However, if there are three occluded vessels, but the patient’s blood pressure and other signs normalize after just opening the infarct-related vessel, then I would not attempt complete revascularization at that time. Paul Overlie: Gregg Stone has looked at a large number of series on that particular issue. If the patients are still “shocky,” then it is recommended that you proceed to treat the other vessels. But if the patient rapidly recovers, you should stop after opening the target vessel. An even more difficult treatment category, but one we ought to explore further, is more widespread use of hemodynamic support. Dr. Magnus Ohman looked at the anterior infarct problems for the PAMI 2 trial. Those in the high-risk limb had balloon pump versus no balloon pump, and there really wasn’t any survival advantage even though patients tended to need fewer trips back to the cath lab when an intra-aortic balloon pump was used. Thus the balloon pump patients in the PAMI 2 trial were not quite in shock, but did show high-risk anatomy such as triple-vessel disease, diabetes, female gender, etc. Many of us face the problem of the patient who has a giant occluded right coronary artery with a 70% left main lesion. The patient is not shocky but when we open the RCA and perform angioplasty and stenting, I bet the majority of us will leave a balloon pump in place in these patients. I may send that patient to surgery if there is a left main lesion, but I want to give that patient “a ride on the balloon pump” to ensure he remains stable. Sometimes we can open that RCA rapidly, and the patient ends up with normal ventricular function. There are just so many variables in the use of hemodynamic support — and if the patient isn’t “shocky,” I still think IABP is valuable. In a true shock patient without revascularization, however, I don’t think IABP is very beneficial. Fayaz Shawl: We have all seen patients in extreme shock with a Swan Ganz in place, inotropes are administered, and they have reduced capillary pressure. Even if you totally revascularize these patients, they may still be “shocky.” These patients present the biggest challenge in terms of post-shock management. We may intubate them — which I think is very important — when their oxygen saturation is only 70–80%. Also, there is a subset of patients who have very poor left ventricular function; they have very high LVDP, they are intubated, and may need some type of support, even if revascularization was performed. This may involve either CPS or LVADs because these patients may need more prolonged support after the revascularization to improve their outcomes. Gian Feltrin: I would like to make a point about what can be expected in the future in the area of imaging as a support to cardiogenic shock or to possibly prevent its occurrence in the first place. Unfortunately, our institution does not have nuclear or magnetic resonance imaging equipment near the cardiac center. It is therefore difficult to gain any advantages from that type of imaging support. On the contrary, at the newer center, a nuclear medicine department devoted to this has ameliorated a large number of stroke problems. Good imaging is very important in stroke intervention because nuclear and MRI tests provide valuable information for treatment strategies. I think that in the future, these diagnostic modalities will play a valuable role, even in cardiac treatment areas. Howard Cohen: I would like to present a different approach that we have been taking with patients in cardiogenic shock. I had a patient who was referred to me at about 3:00 pm on a Friday. The patient was in cardiogenic shock with shortness of breath, moderate CK leak, and was thought to have aortic stenosis. This patient had prior bypass surgery. The referring physician asked if we could perform aortic valvuloplasty on the patient. I told him that we didn’t perform that procedure very often anymore, but said I would take a look at the patient. The patient obviously had very severe mitral regurgitation and also had fairly significant aortic valve disease and aortic stenosis. When in cardiogenic shock, the patient’s PA saturation was about 45% and his Ph about 7.07, so he was really in the tank. The question was: What should we do? The surgeons obviously were not anxious to take this patient, given his condition and history of bypass surgery. By the way, the patient’s coronary arteries showed that he had severe three-vessel disease, but did have a patent LIMA. The first question was: What advantage would an intra-aortic balloon pump provide in this case? In my estimation, IABP would offer little benefit because the patient had a fixed obstruction at the aortic valve and a balloon pump wouldn’t do much for mitral regurgitation. We placed a large transseptal catheter in the patient’s left atrium and took the flow from the left atrium and reinfused it with a centrifugal pump that sits on the leg (about half the size of a coffee cup), with approximately 4 liters of flow. Thus, it is taking all the left atrial flow, all that mitral regurgitation, and now making it forward cardiac output. In the cath lab, the patient’s PA saturation rose to 68% and really turned around. We put the patient in the coronary care unit, tuned him up and ultimately sent him on to surgery. Paul Overlie: That’s a good point, Howard, in cases where there is potential for recovery. In earlier years, we would rescue patients from cardiac arrest and find out there was nothing to rescue. But if the patient can rest and improve, I think that approach offers a definite advantage. Howard Cohen: We use a large 21 Fr cannula placed over an Inoue wire. This transseptal catheter will take the blood from the left atrium through the pump and reinfuse the femoral artery. We looked at flow in the descending aorta to see how much the pump contributed to systemic blood flow. Many people said: “This thing is in the femoral artery, really perfusing the brain.” We looked at retrograde and antegrade flow. With the pump turned on at one liter per minute, there is not much retrograde flow — it’s mostly antegrade flow. When the tandem heart was turned on to 2 liters of flow, we achieved more retrograde flow. There is also a very narrow spike of systolic flow in the aorta. But as we increase to 3.5 liters per minute, a broad continuous antegrade flow is evident. There is continuous flow in the descending aorta and good reperfusion in the systemic circulation. When the flow is increased; there is more continuous flow, more diastolic flow in the carotid artery, so the brain is definitely perfused. Very interestingly, the patient I am describing here went to surgery, had aortic valve replacement, mitral valve repair and triple-vessel bypass. The assist device was in place during the surgery; it was turned on at low flow and was left in place afterwards which helped to recover the left ventricle. The patient was then weaned from the device by turning it down and cardiac output was monitored. Next, the device was withdrawn and the patient survived and did well. Thus, this represents a different approach to handling a patient with cardiogenic shock. Unlike CPS, this approach does not require a membrane oxygenator because it uses the lungs; it takes the left atrial flow and allows the heart to rest so that it can recover some of its function when it is supported in this fashion. James P. Zidar: That is a unique approach. Are you able to leave the assist device on for several days without incurring any red cell trauma? Is there much hemolysis taking place? Howard Cohen: It’s an interesting point, Jim. I believe the device was in this patient for eight days. Initially, it was used as an implantable device in about 30 patients. It’s a good left ventricular assist device that doesn’t produce much in the way of hemolysis or red cell trauma. Also, as opposed to CPS, which you can only leave in for a few hours, this device can remain in place for several days with no apparent problem. Obviously, the longer the device is in place, the more likely infection will be, just as with the balloon pump, but it is a very powerful device. Unlike the balloon pump in patients with coronary disease, this device does allow for improved microvascular flow because the heart shrinks and the transmyocardial pressure gradient is significantly reduced. Fayaz Shawl: As we discussed earlier, this would be a great device to use in patients who are in severe cardiogenic shock, are still “shocky” after revascularization, and have high LVDP. James Zidar: Another problem we encounter involves intervening solely on the infarct-related vessel in “shocky” patients, as Jeff mentioned. We try to assess the condition of the patient’s ventricle — because patients like these often have mitral regurgitation. The question often boils down to: If these patients have multi-vessel disease, will the mitral regurgitation improve if you open up that vessel, or do these patients have at least moderate mitral regurgitation anyway? Thus, we are faced with left ventricular dysfunction, multi-vessel disease, and moderate mitral regurgitation for which the best course of treatment would be mitral valve repair and CABG. Our approach has typically been to treat the infarct-related artery — usually with a balloon pump — stabilize the patient over a period of 24–48 hours, perform a good echocardiogram at that point, and reassess mitral valve function. Does anyone here have a different treatment algorithm on how to handle mitral regurgitation in the setting of “shocky” patients? Fayaz Shawl: In the mid-1980s we reported approximately ten cases which were published in the Journal of American College of Cardiology. These cases featured acute mitral regurgitation and acute infarction. It was interesting to note that there was no regurgitation on the echocardiogram. And in early intervention, the majority of patients had mitral regurgitation post-intervention. Thus, we open the vessel in the cath lab, then perform an echocardiogram. If the echo doesn’t reveal any regurgitation or frank rupture, a majority of the patients will show mitral regurgitation improvement. Tom Linnemeier: Yes, that is a problem. The practitioners who are using t-PA or t-NK in the local emergency rooms are often not cardiologists; they are either E.R. physicians, family practice physicians or interns, and they are being sold lytics by local sales representatives. Although the lytic sales representatives are not telling these physicians that giving patients lytics will cure them, the immediate results greatly impress these practitioners who often see, after a lytic is given, that the patient’s terrible ST-segments are down to normal. So they think the patient is cured. But we all know what can happen: the patient returns to the emergency room and there are all these coagulation cascades which often make the procedure more difficult to perform. I really don’t know what the solution is — better education, perhaps. But I don’t think that the solution is a second dose of a lytic agent. It is incumbent upon all of us in our respective communities to educate our local doctors about what they should do with these patients. Paul Overlie: Jim, you asked if we had a strategy for dealing with mitral regurgitation patients who present with acute infarction. A strategy we strongly reinforce is when local physicians give these patients t-PA or t-NK, we have the patients sent to us so we can cath and treat them. That goes back to Bill O’Neill’s plea: Let us risk-stratify these patients and determine what their exact condition is so we can better guide our therapies. Luis de la Fuente: Favaloro has operated on over 100 patients with acute myocardial infarction complicated by severe mitral regurgitation. He did come across a couple of patients in whom there was no rupture of the papillary muscle — they had significant acute mitral insufficiency from severe ischemia in the papillary muscle because the irrigation of the papillary muscles is not identical in all the patients. Since then, when we see a patient with acute mitral insufficiency in acute infarction, and the artery is occluded — usually the circumflex — we try to open the artery. If the patient does not improve immediately we send him to surgery. The mortality rate with this approach is much lower. James Zidar: In reference to what Kirk Garrett said about an area that needs further study, I’m not sure that randomized trials are good in cases of cardiogenic shock. However, a registry that studies a new mechanical device — perhaps the one Howard Cohen discussed — would be ideal for this situation. We need devices that are smaller and more user-friendly. That is one of the balloon pump’s advantages: you can use it in your everyday practice. CPS, on the other hand, is more invasive and uses bigger cannulas, which makes it difficult in patients with peripheral vascular disease. If the size of the cannulas is reduced and the device can be made more user-friendly — not that doing a transseptal would be an easy feat in shock cases — the technique would translate more easily into our everyday practices. Is there anything different we can think of in the area of pharmacology for shock patients? I have been talking with Aventis about a sodium-potassium ion exchange and anti-inflammatory agent that the company is first testing in the controlled setting of bypass surgery. The agent aims to reduce inflammation, but you need the drug on board at the time of the injury, so their first foray into this to have the drug on board six hours before the patient is put on bypass. Perhaps acute myocardial infarction would also be a setting that could be studied. I don’t know much about this drug — it doesn’t have a name yet, just a series of numbers — but Aventis has shown some interesting animal work on this agent. Any other comments, Tom? Tom Linnemeier: There are some companies involved in research that are toying with the idea of using stem cells at the time of acute myocardial infarction. They are working on the development of different types of delivery methods, whether it be an intra-myocardial delivery within the myocardium, a coronary sinus retroperfusion, or a direct intracoronary injection of the stem cells. I attended a thought leaders conference on the future of this technology. It seems like the biggest “bang for the buck” you get with stem cells is the more acute the injury, the more the cells want to go there. We also came to a solid consensus at this conference that the time of acute myocardial infarction is probably not ideal to deliver stem cells because of all the factors we’ve been discussing today — especially if it’s an intra-myocardial injection. The consensus among both the scientists and the clinicians was that two to four weeks post-myocardial infarction would be the appropriate time to deliver stem cells. Thus, in the area of biologics, stem cells represent another treatment modality that I think will be very significant in the coming years. James Zidar: Doris Taylor, PhD, at Duke University, has been doing some myoblast work using an ameroid constrictor infarct in the LAD in pigs. At the time of the injury, a soleus muscle biopsy is taken, myoblasts are grown, and are then reinjected four to six weeks later. As we move from animal studies to humans — at least in the U.S. — it is a challenge to make it practical and not exorbidantly expensive to grow these myoblast cells in closed chambers under the rigors of good clinical practice guidelines, as is being done in the area of bone marrow transplantation. We have had meetings with our hematologists, oncologists, and our bone marrow group about how we could do this in a practical setting. I know they are starting to do this in Europe as well. Stem cells may be the treatment of choice in patients with large anterior myocardial infarctions. The patients would be given a soleus muscle biopsy at the time their LAD is reperfused, then return four to six weeks later to have myoblasts reinjected. Perhaps in a few years, this will be the standard of practice, who knows?