Hello, everyone, and welcome to the 2024th Critical Care Congress in Phoenix, Arizona. I am Dessy Yasimi. I serve as the Division Chief of the Surgical Intensive Care Unit. I'd like to take a moment and recognize my co-authors, Dr. Wendell Block and Dr. Irfan Boudani, for the amazing work they've done on developing this chapter. Today we're going to discuss an overview of acute mechanical circulatory support. I have no disclosures. Today we're going to talk about mechanical circulatory support and its application, particularly for cardiogenic shock. After finishing the discussion, we will be able to describe the importance of mechanical support in the management of cardiogenic shock, the available devices and the current guidelines, and also spend a little bit of time to understand the etiologies different than MI that precipitate cardiogenic shock and, of course, the application of mechanical support to those as well. A quick overview of what we're going to be talking about today. We're going to touch base on cardiogenic shock. Then we're going to review the available and most used devices today for temporary management. Then we're going to review the special circumstances populations that some of those devices are already being applied to. And then we're going to conclude our discussion with future directions, the establishment of shock teams, ECMO program, and what we've learned for the pandemic and the application of ECMO during a pandemic. Let's look into cardiogenic shock and what we know about it. What is cardiogenic shock? Well, if we ask 10 people, we're going to have 10 different definitions. And that's basically the state of definition of cardiogenic shock today. There isn't a single clear definition. However, we do understand that it is a vicious cycle originating with cardiac insult that precipitates decreased cardiac output and ultimately results in an organ-tissue malperfusion. The body tries to compensate by increasing systemic vascular resistance, and unfortunately, this only contributes to further increasing the work of the heart and further decreasing the cardiac output and ultimately establishing a state of low flow across organs. There is a systemic inflammatory response associated with that, and also there is a local microcirculatory dysfunction. At the cardiac level, because of the increased left ventricular ancestral volume and pressure, we experience increasing left ventricular endothelial pressure, and unfortunately, that further worsens the myocardial oxygen supply demand mismatch. And going back into the vicious cycle of the heart is not working well, the perfusion is not working well, and it's very difficult to get out of the cycle and improve perfusion and output. In 2019, the Society of Cardiovascular Angiography and Interventions proposed a classification schema for cardiogenic shock, which was very widely accepted by multiple societies. What it does is actually stratifies patients into five categories, as you can see in the table. The key point about that is, what can we do at each level? And obviously, the next step would be, can we establish guidelines what we can intervene with at each level and make recommendations, potentially improving outcomes? Bottom line, as always, not just in medicine, but in life, is we want to understand risks, we want to be able to accept the risks that are acceptable, and be able to prognosticate. Regarding the mechanical support, there are already studies that are reporting out that if we were able to intervene at class C, which is basically there's an evidence of hypoperfusion that requires intervention today, what intervention means is medical intervention, inotropic support mainly. But what if we're able to very quickly and on time implement mechanical support at that class to be able to prove that we can improve outcomes? Well, we've got to wait and see for all the studies to come out if the outcomes are going to be improved at that early level of shock. A bit over 80% cardiogenic shock is caused by myocardial infarction. Of the rest of the so-called non-MI etiology, close to 60% is heart failure, any shape and form of heart failure, acute, acute on chronic, decompensated. About 30% is structural, mainly valvular and mechanical issues. And about 10% is other cardiomyopathies, including Takotsubo's, myocarditis, post-cardiotomy, cancer, cardiac arrest. Mortality of cardiogenic shock is very, very high. It used to be as high as 50% in the last couple of decades with our improved understanding of cardiogenic shock and actually early intervention, both medical and mechanical. The mortality had gone down to about 39%, which is still unacceptable, hence the reason of the importance of improving the support we can provide interventions and guidelines. How do we manage cardiogenic shock? Well, first we need to be able to recognize it and diagnose it early. Immediate support had already proven absolutely invaluable. And then we move on to medical interventions and mechanical interventions. Since the early 60s, we've had the intra-aortic balloon pump available, and it had made the difference. And then since the early 70s, ECMO has been introduced. Not only ECMO, but then we've become better at technologically advancing, making the devices smaller and smaller. So today, if we look at the number, the types of devices that have been used, basically, we've switched over from intra-aortic balloon pump more to ECMO and ventricular assist devices that we're going to discuss further in this chapter. Ultimately, the best management of cardiogenic shock is correcting the underlying pathology, which in many instances is much easier said than done. Moving on to review the mechanical devices. The intra-aortic balloon pump is a device which is usually percutaneously placed, most commonly through the femoral artery. At the distal end of the device, there is a balloon. And the purpose of the balloon is to inflate and deflate with the cardiac cycle. It is usually aligned either with the EKG tracing or arterial blood pressure line of the patient. What it accomplishes is then during diastole, when the balloon inflates, it augments the diastolic blood pressure, which in turn improves the coronary perfusion. That of course allows for better matching of supply and demand of oxygen to the myocardium. Then during systole, when the balloon deflates, it actually decreases the afterload of the left heart and improves perfusion or cardiac output. Something that we should emphasize is that proper placement of the device is very important because the balloon has to be distal to the left subclavian. We could potentially occlude it and that could be detrimental. I do have indication sections for all of the devices that we're going to be discussing today. But bottom line is all of them are indicated for cardiogenic shock. And I have tried to emphasize something unique for each device in an attempt to explain why in certain instances we may choose one over the other. Bottom line is intra-aortic balloon pump is most commonly used as a bridge to recovery. It's a very temporary device. It is used, as you can see, for cardiogenic shock secondary to any condition in heart failure exacerbations. There's also an application of balloon pump as an adjunct in high-risk PCI. If we think about how the balloon pump works, it's very easy to understand what would be a contraindication for the placement of a balloon pump. It's very, again, femoral insurgent percutaneous of a device that has to go through the aorta seating literally just distal to the subclavian artery. So anything that's going to make the positioning of the device, the placement of the device is going to be a contraindication. And obviously we have absolute contraindication as something that could be considered a more relative contraindication, but the absolute contraindication is with absolutely easy understanding severe aortic insufficiency. The reason for that is our balloon deflates during diastole when actually the insufficiency occurs. So instead of augmenting cardiac output, it would increase the regurgitant fraction and it's going to make work of the heart worse and also cardiac output less. Any aortic dissection at any level in aneurysm is obviously contraindicated. Sepsis is a contraindication considering that it's a foreign body with an already septic system. So it is not the right device to choose. There are relative contraindications and we can, again, understand those because anywhere you have peripheral arterial disease and either the vessel is not going to be able to accommodate the device or there's a lot of plaque, obviously we're going to have issues with placing the device itself. Any type of severe arrhythmia would unfortunately not be beneficial as well because the balloon is altering, augmenting and decreasing outflow and augmenting the diastolic blood pressure. So depending of the arrhythmia, it's going to be either systolic or diastolic issue and it's not going to work very well with the device. Complications are usually associated with the access site and of course, one of the most feared one is limb ischemia because it could potentially occlude distal flow if it is temporarily placed to the rest of the leg. There is also potential of creation of hematoma, pseudoaneurysm. Of course, there's always a potential for infection being a foreign body inserted. There's also unfortunately a possibility for neurological injuries, particularly distal peripheral nerve injury. The most feared complication is a balloon rupture because first of all, we lose all the augmenting power of the device contributing to better cardiac output and also this is a malfunctioning body, foreign body within the system. Also another concern is of course, the balloon malfunctions if it deflates or inflates off the cycle and another very major complication would be malpositioning of the balloon. I will repeat myself again, but if it is occluding the left subclavian artery, then potentially devastating consequences of occluding blood flow distally. What is the evidence behind using a balloon pump? One of the first trials named shock that was published in 1999 with good number of patients compared balloon pump with thrombolysis in one arm to thrombolysis alone in patients with acute coronary syndromes and cardiogenic shock. It actually had a significance in lowering mortality using the mechanical device. Unfortunately it also had a significance in higher procedural revascularization in the arm with the balloon pump. More recent studies, however, weren't able to replicate the results of the original shock trial and unfortunately had showed that there is no difference in patients that we use balloon pump versus standard therapy. Tactic trials published in 2005 compared balloon pump with thrombolysis versus thrombolysis alone in patients with myocardial infarction complicated by hypertension and cardiogenic shock and they showed no difference in mortality. Later intra-aortic balloon pump shock trial two published in 2019 compared balloon pump versus standard which is the non-supported therapy in patients with acute MI complicated by cardiogenic shock and the data was collected over the period of 2009-2012. They also showed no difference in all-cause 30-day mortality. And furthermore they looked into their secondary analysis and they noticed that there's no difference in time to hemodynamic stabilization. There's no change in length of study in the ICU. So it actually compared that there's no change in the concentration of lactate, catecholamine therapy used and unfortunately the newer studies were not able to show what the original shock trial showed that there is an improved survival or lower mortality with the balloon pump. Complication rates of balloon pump use have been reported as high as 8% with 2.7% of major complications including death. Meaning that we today don't have evidence of either improved survival or decreased mortality. The 2023 guidelines actually recommend against the routine use of balloon pump in acute myocardial infarction complicated by cardiogenic shock. The next device we're going to be discussing is the Impella. It is an actual axial pump. It is also a percutaneously inserted device and it crosses the aortic valve. It completely unloads the left ventricle. It gets the blood from the left ventricle, circulates it through the pump of the device and then unloads it into the aorta. There are multiple devices. There is actually an Impella RP which supports the right heart and the devices depend on the maximum flow rate that it can generate. The larger the flow rate it can generate, the larger the diameter of the device. This matters for insertion purposes. What is the Impella used for? For cardiogenic shock. It is very similar to the balloon pump. It is a temporary device so the general recommendations are to be used less than 14 days. It could offer potential benefit for patients with severe aortic insufficiency that are awaiting their valvular surgery and it was approved as an emergency option in COVID patients on ACMO who are experiencing complications or decompensating. Unique contraindications to Impella placement are basically mechanical issues with the aortic valve. For instance, severe aortic stenosis, something that is not going to allow us to have the device easily cross the aortic valve area, mechanical aortic valve. There's a specific unique contraindication to Impella if there's a left ventricular thrombus because potentially this could be sucked into the device and could precipitate malfunctioning of the device. If there's a ventricular septal defect, we're not going to be able to use the Impella prior to correcting the defect because it will create, it will generate, it will exacerbate the right to left shunt further and obviously there's a left ventricular rupture. There is a relative contraindication in patients with moderate to severe aortic insufficiency even though on my prior slide I mentioned that potentially those are good population to use. If you are awaiting the surgery, this is certainly not a permanent solution. Again, percutaneously placed device, so anything that would prevent the pathway from the most frequently asserted site, the femoral artery, through the aorta, through the aortic valve is if you have an aneurysm or a dissection and if there is a left ventricular outflow obstruction, there is a relative contraindication to that because it can precipitate worsening of the obstruction basically by quickly and efficiently unloading the left ventricle. Complications associated with the Impella are similar, usually related to insurgent site and also very similar to the balloon pump. The unique component of the complication is it can precipitate hemolysis and coagulopathy because the blood actually is traveling through the device, through the axial pump, and there is a possibility of damaging the cells. Of course, it could also cause hemorrhage and anemia, and in very, very rare instances it can cause cardiac tamponade. In the last two decades, we have evidence that the use of Impella, especially over balloon pump, had significantly increased. One of the earlier studies comparing the Impella to the balloon pump, and it used Impella 2.5, which is the Impella that can generate up to 2.5 liters per minute flow, basically cardiac output. In patients that are undergoing high-risk BCIs show that there's an improvement in the hemodynamics in the impeller arm and also show that there is no major adverse events comparing both devices. In 2008, ISAR shock study published their data where they randomized 26 patients to impeller 2.5 comparing to balloon pump and they did find significant hemodynamic improvements. However, they had no evidence of improved mortality. Later in 2017, the IMPRESTA study got published and it's one of the largest comparing impeller versus balloon pump specifically in patients with acute MI and cardiogenic shock. Unfortunately, they weren't able to prove improved survival or decreased mortality as well. They were comparing 30 days and also six months survival. The same group in 2021 actually published their five-year review again confirming their prior findings that there is no difference in mortality comparing the impeller 2.5 to the balloon pump. In 2020, impeller stick trial was published randomizing 48 patients with acute MI and cardiogenic shock to either impeller 5.0 or balloon pump placement and they showed no difference in hemodynamics early on at 12 hours and later at one month. In a large registry of close to 50,000 patients for a period about decade and a half, comparing impeller placement prior to PCI and after PCI actually showed improved survival rate. However, the results may have been compounded by the fact that the placement of impeller post PCI was frequently used as a salvage maneuver. The guidelines of 2023 regarding impeller placement mostly address contraindications. Please do feel free to refer to the full table of guidelines in the chapter in the book. I do want to summarize a little bit that even though for the last decade plus the impeller use has significantly increased especially over and compared to balloon pump, we have no evidence that the impeller is providing better hemodynamics or improved survival or decreased mortality compared to the balloon pump. The next device is the tandem heart. It actually is an extracorporeal centrifugal pump. What it does is completely bypasses or unloads the left ventricle. It does have an inflow and outflow cannula for that reason. So the inflow cannula usually is inserted through the femoral vein. It goes to the right atrium and then crosses the intraatrial septum and it terminates into the left atrium and then the outflow cannula is usually placed near the femoral artery. So basically what it does is it unloads the left ventricle bypassing the blood flow from left atrium either to the descending aorta or to the femoral artery. It can generate a flow rate as high as five liters a minute effectively making a cardiac output as close to normal. Indications for placement of tandem heart are, you guessed it, cardiogenic shock. It is considered a third-line strategy when either the impeller or the balloon pump had either failed or there are contraindications to them. Specific contraindications to the tandem heart are closely related to the mechanism of action. If you think that percutaneously we enter the inflow cannula through the central venous system into the right atrium, through the septum, into the left atrium, basically any thrombosis on the pathway would be a contraindications to that because it could always be unloaded into the pump and can predispose malfunctioning of the whole system. Anywhere where there is a shunt either at atrial or ventricular level, the same reason, we're going to worsen the shunt and actually potentially even reverse it right to left. Aortic regurgitation is also a contraindication and the main reason for that is that if we are able to effectively unload the left ventricle we are basically counterproductively working towards improving cardiac output because we're simultaneously increasing the regurgitation fraction. Complications associated with tandem heart are very similar to the balloon pump in the impeller. Most of them are associated with the access site. However, we also have issues with coagulopathy associated with the tandem. Cardiac tamponade had very rarely been reported and the biggest, the most feared complications of the placement of the tandem heart is actually retraction of the inflow cannula from the left atrium into the right atrium because what this is going to create is exacerbated right-to-left shunt and hypoxemia. For that reason, the patients that are currently on tandem heart, they have to be at bed rest. That also is one of the limitations in a major consideration choosing which device to place. What's the data behind tandem heart? In 2005, Pio et al published their findings randomizing 41 patients with acute MI and cardiogenic shock to either tandem heart placement or a balloon pump placement. They did find that both arms showed improved hemodynamics. However, tandem heart arm had higher rate of improvement. Unfortunately, they were unable to show any benefits to either balloon pump or tandem heart in regards to mortality and also they acknowledged clinically significant bleeding and also lymph ischemia associated with the placement of the tandem heart. Later in 2006, Berko et al randomized 42 patients with cardiogenic shock of all causes even though majority of their patients were secondary to myocardial infarction to either tandem heart or a balloon pump. They were able to replicate the results of Pio and showing that there is a significant improvement in hemodynamics in both arms. The one thing that was significant and different compared to the prior studies is that there was no difference in the severe adverse events comparing both devices. In meta-analysis published in 2009 compared three trials. Basically, they looked into tandem heart versus balloon pump and they found no difference in 30-day survival and they also concluded that there is a higher incidence of major bleeding events associated with the placement of the tandem heart. The 2023 guidelines have a recommendation. Basically, the only thing that they address is that tandem should not be inserted in presence of no left atrial thrombus. Even though it's not high level of evidence, it is there. In summary, even though we appreciate that it provides good cardiac output and better hemodynamics, we cannot say tandem heart is better than the balloon pump and there's no direct comparison to the Impella. So, as so far we've reviewed the balloon pump, the Impella, and the tandem heart and I cannot tell you that one over the other has improved survival or decreased mortality. Next, we're going to discuss ECMO, specifically VA ECMO. It is a completely extracorporeal circuit. It has a centrifugal pump and also the bigger difference compared to prior devices is it has membrane oxygenators. So, besides supporting the function of the failing heart, it can actually support respiratory and ventilatory function. Candylation could be done either peripherally or centrally and it can generate flow rates as high as 8 liters per minute. Indications are obviously cardiogenic shock, left ventricular, right ventricular failure, also respiratory failure. As recently as the early 2020s, ECMO was approved for extracorporeal cardiopulmonary resuscitation with very, very specific criteria. There are very clear contra indications to both VA and VV ECMO. An extensive list is provided on this slide and the following slide for VV ECMO. I do want to take a moment and emphasize that one of the major contraindications to both VV and VA ECMO is the unlikelihood of recovery and inability to be placed on a transplant list. Also, somebody with severe neurological impairment is not going to be a good candidate because a very durable device, it is still a very temporary support. We do not have any specific requirements or guidelines as to the amount of time allowed to be on ECMO and certainly there are cases reported in the number of weeks. It is still a temporary device. So ideally, by placing somebody on ECMO, we have to have a plan and goal for a destination therapy after that. Even though respiratory failure is not within the scope of this presentation, I included the slide for contraindications for ECMO for respiratory failure for completion one and secondly, to emphasize that the conditions for contraindications for both cardiogenic shock and VA ECMO and respiratory failure and VV ECMO are quite similar. Complications of ECMO are very similar to other support devices. Lymph ischemia with ECMO, it could be offset by reperfusion cannula placed just distal to the original cannulation site. Hemolysis is also common in VA ECMO. It's a larger circuit one and secondly, it's a centrifugal pump that circulating the blood through can damage the cells. This is further associated with bleeding, anemia, coagulopathy, and even renal failure. Bleeding with ECMO is not uncommon and it's been reported that up to 35% of VA ECMO patients require intervention for their bleeding complications. Metabolic derangements have been reported. Just by the mechanism of action, the way it unloads the left ventricle, it actually increases the afterload to the left heart, which in turn increases the myocardial oxygen demand and that further decreases the native cardiac function. This is something to be considered when we're planning and strategizing about winning the patient off the support. Something that is very unique to ECMO is the phenomenon called Hurlican syndrome. What it does is that's particularly happening when you have a arterial cannula placed at the femoral artery site. It can actually precipitate differential oxygenation between the upper and the lower body. And this is important to know where when we are managing patients on ECMO, where we're sampling for arterial blood gases. 2016 meta-analysis compared VA ECMO versus supportive care in patients suffering from cardiac arrest and in cardiogenic shock. And they actually were able to prove that there is evidence of improved survival. They were also able to find that there is a higher rate of neurological outcome with patients placed on VA ECMO. They further compared VA ECMO and balloon pump and they did show better 30-day survival with the ECMO. However, they found no difference in survival rate when they compared ECMO to either tandem heart or Impella. ECMO CS trial randomized 117 patients to VA ECMO versus conservative management for cardiogenic shock and they found no difference in 30-day mortality, cardiac arrest, or implementation of another support device downstream. They also found no difference in serious adverse events. Sakamoto et al. performed an observational study published in 2014 of 454 patients comparing extracorporeal CPR versus non-extracorporeal CPR and compared performance, overall performance, in Glasgow-Pittsburgh cerebral performance scale. They found that both at one month and at six months, there was an improvement in outcome in the patients that were undergoing extracorporeal CPR. Kawakale et al. in 2022 further looked into the extracorporeal CPR and did an observational study with a good number of patients. What they wanted to accomplish was to identify if there is any benefit of shorter time to ECMO and they were able to conclude and show a favorable outcome with a shorter time to extracorporeal CPR. Later in 2022 also there was a National Repatient Sample Review of 1.6 million patients with cardiogenic shock on VA ECMO for almost a two-decade period of time. One major conclusion that they were able to find was that there was a 23-fold increase in the use of ECMO through that period of time and also there was a significant decrease in mortality throughout the years. With continuous advancement in technology, increased use and application of mechanical circulatory support and beta data available, we're actually able to provide better and more robust recommendations and guidance for the use of different devices. This year's recommendations are actually a good reflection of that. I do want to take a moment and just quickly go over a few of the significant points with a good level of evidence made during this year's recommendations. So first highlighted item is they do recommend a shock team when we approach the management of circulatory support. Development of hospitals, also called hubs, that are circulatory support capable in establishing of protocols for the management of those patients. Additionally we were able to address the timing to placement on extracorporeal support or basically any mechanical support. The other component that I particularly appreciate is that we are able to make strong recommendation in regards to the use of acute mechanical support and differentiated for durable devices, meaning that if we're planning on putting somebody on a durable device there is a recommendation that we should try temporary device prior to destining somebody to a durable device. And if you remember in the beginning of this discussion I mentioned that there is no one clear definition of cardiogenic shock and there truly isn't, but if you look at the last point in the table on the slide it actually specifies very very specific hemodynamic characteristics to choose the type of device you want to place the patient on. I'm not gonna bother you and go through that but basically if you look at them it is all about perfusion, perfusion, perfusion and based on the specifics of your patient you get to choose which device to place for support. A quick overview of right heart failure. As we all know thankfully it's rare compared to left ventricular failure. This slide has some statistics. I find them very important and it does help me when I look at those numbers to realize that even though it's super rare it is very deadly. As you can see that mortality is as high as 50% in patients with cardiogenic shock and it is very high up to 14% whether you're treating the patient medically or with mechanical support. Something to emphasize again it is the same idea as with left ventricular failure. You want to be able to recognize and diagnose early. You want to provide immediate support whether it's medical or mechanical and more importantly the goal of management should always be to correct the underlying pathology. When we consider right ventricular support we basically have the options of Impella RP, Protec Dual and of course VA ECMO. A little bit about the difference between the Impella and the Protec Dual. The Impella RP is if you can imagine a mirror image of the Impella that we've already discussed. Previously we discussed that it completely unloads the left ventricle so now we're going to do the same thing with the right ventricle. We're going to be placing the Impella device through the pulmonary valve and what it's going to do is basically it's going to get the blood from the right ventricle and it's going to bypass it and facilitate output directly into the pulmonary artery. The Protec Dual on the other hand it's extracorporeal system and it has a continuous flow pump so does a similar thing completely bypasses the right ventricle. It grabs the blood from the right atrium and it actually delivers it into the pulmonary artery. VA ECMO, again, the same mechanism as before, we can support the right heart only, the left heart, or biventricular support. The mechanism of action, obviously, it depends of which device you're gonna be using and if you need gas exchange or not. Indications, cardiogenic shock, secondary to either left ventricular, right ventricular, or biventricular failure. Also, the devices listed above could also be used for respiratory failure, which is out of the scope of the discussion. The data behind right ventricular support is a bit more sparse, but also a little more consistent compared to the left ventricular support devices. Perhaps part of it is that there's not as much variety of the devices. The following two studies were published in very recent years, 2015 and 18, respectively. They randomized a good number of patients. All of those patients were post either placement of a left ventricular support device, cardiac surgery, myocardial infarction, and in the second study, post-transplanted patients. They compared impeller placement versus standard medical management and they showed improved survival rate at 30 days with 73 and 72%, respectively, and both studies were consistent in significant improvement in hemodynamics. Why is it of huge importance? Because we all know that the most common cause of right ventricular failure is actually left ventricular failure. And if you notice, the population here is post-intervention and especially the ones that are dependent on devices, they really need a good right ventricular support to be able to have a good preload on the left side and, respectively, better cardiac output. So the hemodynamic improvements actually is quite significant. This is earlier study and also retrospective, but it has the same conclusions as the previously discussed two studies about right support. What they did, basically, they looked into clinical outcomes with impeller R&D or RP, both are right ventricular support devices over a period of six years. And if you notice, their survival rate is also reported to be a 72% with significant improvement in hemodynamics. Why does it matter? As I emphasized previously, we need the right ventricular output to have left ventricular preload so we can actually have a good cardiac output. The 2020 guidelines have recommendation that PROTEC or impeller RP can be considered for acute right ventricular support. Also, if you notice the second bullet specifies that in patients that have right ventricular devices without left ventricular support, we must monitor for polioedema because if the right ventricular support is not sufficient, this is where I go back to my repetitive stage of we need right ventricular output to have left ventricular preload so we can actually have good cardiac output. So the importance is emphasize that it's a good level of evidence in this year's guidelines. This is my very favorite slide of this presentation because I feel like it portraits very well the hemodynamic effects of all the devices that we've discussed so far. I will try to go slow and I hope you can follow in the colors. In the gray color, we have the normal VP loop with normal cardiac output and normal cardiac function. In dark blue or purple, I hope you can appreciate that on your screens, is the example of a VP loop of a patient in cardiogenic shock. So if you notice, there's a right shift to the whole loop and it's very much narrower. So what this signifies is basically an increase in left ventricular preload and significant decrease in stroke volume. It's basically the standard definition of cardiogenic shock or cardiac dysfunction. Then we're gonna move on to the red VP loop, which is signifying a patient with intra-aortic balloon pump. It is a narrower loop, as you notice as well, compared to the baseline normal gray color loop. It also has a little bit of leftward shift compared to the cardiogenic shock. So what does it tell us? First, it tells us that there is a small decrease in the left ventricular preload, but also a small increase in the stroke volume. How do we accomplish that? Remember that the balloon pump has two functions. One is during diastole, it augments the diastolic pressure. And during systole, it actually decreases the afterload, which facilitates easier work on the heart and also better forward flow with increased stroke volume and cardiac output. And because we were able to unload, and it's probably not the right term for balloon pump, but facilitate a forward flow, we have a little bit of decrease in the preload. The next, we're gonna talk about the impella. This is the very light blue triangular-shaped VP figure. So I'm gonna go ahead and just address the triangular shape, which is very specific to the impella. What does it indicate? So basically, we have lost the isovolumetric relaxation and isovolumetric contraction because the left ventricle is completely, completely, completely unloaded. Also, we have a little bit of a left shift, signifying basically decrease in the left ventricular preload because now we're able to pump blood through the left ventricle, and we are continuously moving forward. If you also notice, there is no physiological closing and opening of the aortic valve because the device is sitting through the aortic valve area. Then we're gonna go and discuss the green-shaped VP loop. This is the tandem heart. If you notice, it is shifted to the right, and we've already discussed that shifting to the right indicates that we are improving the preload. That's one. The second, it's a little narrower, if you notice, and we have the physiological opening of the aortic valve and closing of the aortic valve because there's no device that's crossing the valve at all. Also, if you notice, we do have a significantly reduced left ventricular and diastolic pressure, signified by the shifting of the curve to the right and also the narrowing of the loop. This indicates that we're able to unload the left ventricle okay. We also have increased left ventricular ancestral volume in a little bit of a decrease of stroke volume. That actually happens because that's the stroke volume of the heart, but the device is not allowing the heart to function because it's basically taking it, unloading it. That's the reason why it looks the way it does. We do have a little bit of an increase of aortic pressure, and this is because we have augmented systemic blood flow. Basically, we have achieved better cardiac output. Then we're gonna move on to the last curve, and this would be the yellow-shaped VP loop, which signifies the placement of peripheral cannulated VA ECMO. What do we notice? So it is completely shifted to the right. That means that we have significantly increased left ventricular preload, and we also have increased left ventricular and diastolic pressure. We do have decreased stroke volume, and if you remember when we were talking about ECMO, we acknowledged that we have an increased afterload, which decreases the negative heart stroke volume when we have to strategize how we're gonna win off patients from the ECMO. Also, if you notice, we do have an increase in the aortic pressure. That's also secondary to the increased blood flow, systemic blood flow. On the curve, we still have the physiological opening and closing of the aortic bone pump. I'm sorry, of the aortic valve. Overall, every device augments the hemodynamics a little bit differently, but the overall goal has been achieved by improving systemic cardiac output, respectively, perfusion to end organs. This table has concise list of specification for the devices we discussed. I do wanna acknowledge that the third column basically tells you the flow rate achieved by the device, the maximum flow rate achieved by the device, which would be corresponding to the cardiac output that we can achieve with that. The next column has the cannulus sizes. Some of them, it could be easily inserted peripherally, and you can go down the list. You can notice that the cannulus become thicker and thicker and thicker. Obviously, insertion becomes a little more challenging, and this is where we go into more centrally inserted devices. And then the next column has the maximum number of days recommended to have the device in place. The only device that doesn't have number of days is the ECMO because there is no single recommendation for the maximum days to be on ECMO. And as I mentioned previously, there are reports of patients being on ECMO for weeks and weeks and weeks and being successfully decannulated, actually. And then the last column is gonna cover the type, the side of the heart that it's able to support. Most of the devices discussed are the left ventricular support. You have the ECMO, which could do biventricular support, and then you have the Impella and the ProtecDuo that provide right ventricular support. This is a quick table summarizing the shared complications of the devices we've discussed. Quick reference for you, we've covered all of them, and obviously, more specific and unique complications have not been listed in here, but it's very easy to go back to the device slide and you can easily find them there. Now that we're a bit more familiar with the mechanical support devices available and most commonly used today, we're gonna look into special circumstances and their application to special populations. The first pathology we're gonna discuss is peripartum cardiomyopathy. I do wanna take a step back and remind us that physiological changes during pregnancies are quite significant, and they do last up to six months postpartum, meaning that we should never lower our guards when we're investigating the potential causes for either cardiomyopathy or cardiogenic shock in patients that had already delivered. Circulatory volume significantly increases during pregnancy, and it may last, again, up to six months postpartum. What does it do? So with the significantly increased circulatory volume, obviously, we're gonna have an increase in left ventricle and diastolic volume. That can actually alter the chamber size as well. There is variety of changes associated with the systolic volume and also the ejection fraction, and it's patient-dependent, prior comorbid condition dependency, but it's something that we should always keep in the back of our mind. As we know, cardiovascular disease is the leading cause for morbidity and mortality in peripartum patients, and about 50% is secondary to cardiomyopathy. Of the causes for cardiogenic shock and acute heart failure, peripartum cardiomyopathy and PE are quite common. As we know, peripartum patients are challenging to study, and we do not have randomized controlled trials, but we do have some data available. One of those studies is registry study from 2020 that looked into almost 1,400 patients between the years of 2002 and 14, and what it acknowledged was that there is an increased use of support for peripartum cardiomyopathy. However, there was no change in mortality. They did look into secondary analysis to find if time to placement has any significance to mortality, and they did find that if the device was placed less than six days from the diagnosis, there was a significant improvement in survival. The next study that was published in 2022 followed 13 peripartum cardiomyopathy patients. One had a mortality reported secondary to unrelated pathology. Of the 12 patients, five received heart transplant and seven actually recovered. In 2012, a review of the Intermax, which is the International Registry for Mechanical Assisted Circulatory Support, identified 1,258 peripartum patients and compared the peripartum patients requiring mechanical support based on primary diagnosis. What they found was that peripartum cardiomyopathy was identified only as a primary diagnosis in 99 patients versus 1,159 patients with other pathologies. Of note here is that a large percent of the 1,159 patients is secondary to respiratory failure. The more interesting finding was that the two-year survival compared peripartum cardiomyopathy to other primary diagnosis was significantly better, 83 versus 64%. And the conclusion was that the peripartum patients were usually younger with fewer comorbidities. We also have peripartum cardiomyopathy recommendations from this year's guidelines. And it's a good level of evidence. They do recommend that patients with peripartum cardiomyopathy and cardiogenic shock should receive acute mechanical circulatory support. They also have additional comments regarding the application. First is that mostly that should be as breached to recovery. And also their recommendation is that the management of those patients should be in conjunctions with maternal fetal medicine specialists. The next population we will discuss is trauma patients. Just a history fact, the first trauma patient on ACMO was in 1972 and he was for ARDS and he was a VV ECMO. Trauma patients overall represent less than 1% of all the ECMO patients. And perhaps one of the major reasons for that is the coagulopathy associated with trauma. In the past, the trauma coagulopathy was considered a contraindication for ECMO. What data do we have about trauma patients and mechanical support? In 2018, Swell et al published a review of the Extracorporeal Life Support Organization Registry over a period of almost 30 years and identified 279 trauma patients. And that represented less than 1% of all patients on ECMO for the time period. He categorized them in three groups. One was respiratory failure. Those were patients on VV ECMO and represented 89% of all trauma patients. Then he separated the VA ECMO patients based on cardiac failure or as ECMO was used as extracorporeal CPR and those were 7% and 4% respectively. Then he looked into survival to hospital discharge. What they found was that 25% survived to hospital discharge from the extracorporeal CPR, 50% of the cardiac failure and 63% of the patients that required VV ECMO for respiratory failure. They also noticed that there is about 29% bleeding complications associated with the trauma patients put on ECMO. As I mentioned previously, coagulopathy of trauma was considered a contraindication to ECMO in the past. So obviously it is a subject worth pursuing and investigating further. And Wood et al did a single institution review published in 2020, identified 203 patients. All of them are VA ECMO patients and of all of those 35% of the patients were not anticoagulated. And what they found was that they did have a lower complication rate, 57 versus 76 and that was significant. Also, they had lower rate of heat or transfusion. There was no difference in thrombosis and there was also no difference in mortality which obviously raises a lot of questions of if we consider trauma patients to be good candidates for ECMO or how exactly are we gonna approach anticoagulations, what type of circuits are gonna be used but it certainly provides data that allows us to better understand what options we have available for this population. Badir et al in a systematic review published in 2017 identified 12 studies, total of 215 patients. Those were trauma patients on ECMO and they wanted to investigate anticoagulations patterns. So what they found was that there were four reports with heparin-free ECMO. There were five reports with ACT less than 180 seconds goals. And the overall conclusion was that of those nine reports, there was no reported complication secondary to systemic opioid thromboembolism. The morbidity secondary to unexplained circuit changes or secondary to clotting also was not different between the not anti-coagulated patients and the less goal of less than 180 ACT. More importantly, the bleeding-related mortality of those was 15%, especially after 1995. Just to remind you that in our original review of the ELSO registry, the reported bleeding complication rate was close to 30%. Again, foot for thought, can we approach trauma patients and offer mechanical support when needed, considering that we could not anti-coagulate with higher goals of ACT or maybe special circuits? Next, we'll move on to chemotherapy-induced cardiomyopathy. A little bit of background. Incident has been reported anywhere between one to 5%. Also, there is about 20% of asymptomatic ventricular dysfunction in patients undergoing chemotherapy. The most commonly accused agent is the intracyclines. It has a bimodal presentation, either early or late onset. Also, it could be temporary stunning or it could be a permanent cardiomyopathy. Unfortunately, those patients rarely qualify for transplantation, knowing that transplantation is going to be indicated within three to five years from remission. This is where ability to offer mechanical support becomes extremely valuable in not only acute mechanical support, but also durable devices. Data is very limited regarding chemotherapy-induced cardiomyopathy and mechanical support. We do have a study from 2014, which reviewed the registry intermax and identified 3,812 patients on mechanical support between the years of 2006 and 11. And of those, only 75 were patients with chemotherapy-induced cardiomyopathy. What the authors did, they compared chemotherapy-induced cardiomyopathy to ischemic cardiomyopathy and non-ischemic cardiomyopathy. And they found that the chemotherapy-induced cardiomyopathy patients were the ones with the higher need for right ventricular support. Also, they did have a higher risk for bleeding. However, there was no difference in mortality. And that was a statistically significant finding. Another pathology deserving its own category for consideration for mechanical support is congenital heart disease. It is a very challenging population because there is a complex anatomical and physiological pathology. It's also a very heterogeneous group, and it's very difficult to combine together. Adults with congenital heart disease now live longer and longer, and very, very likely, they have undergone multiple procedures. So for that reason, there's a high likelihood that they would require more than just single ventricle support. They would probably qualify for biventricular support or artificial heart. And unfortunately, they would also very likely have generally worse outcomes just because of the predisposition and comorbidities associated with the original disease. We were able to identify the same review published in 2013 and published in 2014 from Intermax and the conclusion that there are similar outcomes for adults with congenital heart disease when left ventricular assist device was used versus biventricular support. And also, this year guidelines actually have a special section for adults with congenital heart disease. I have it included here, and the full table is in the book for your references. Temporary mechanical circulatory support can have a huge impact on patients awaiting heart transplant. Before 2018, patients that were not qualified for durable devices actually had very long times and a high mortality rate associated with that. In 2018, NUNUS introduced new allocation schema, and perhaps in conjunction with advancement in temporary support and also the ease of placement, the number of patients in Category 1a for transplant significantly increased. Also, the number of patients with temporary support significantly increased from 10% prior to 2018 to 41% after the introduction of the new allocations schema. Of the patients that were breached with temporary support, 33% were breached with a balloon pump and received transplant and 12.4% were breached with ECMO and other temporary devices. Those were the successfully breached patients, percentage of patients to heart transplant. And we can appreciate this is significant because basically 41% to receive a transplant needed a temporary support device, and we were able to get them to transplant. Not a lot of data is available to compare bridging patients with durable devices versus temporary devices. However, in reviews of the United Network for Organ Sharing and National Repatient Sample Database from three years of 14, 16, and 18, comparing balloon pump breached transplanted patients and durable support devices breached transplant patients, there were similar rates of length of stay, acute renal failure, acute rejection, and perioperative mortality. Perhaps even though this is not a randomized controlled trial, it still opens up the door for the acute and temporary support devices for the patients awaiting heart transplants. Now that we have that understanding of mechanical circulatory support, what can we do in the future to improve outcomes? Similar to organ transplants, STEMI, and stroke teams, shock team is a multidisciplinary team. Once activated, the team cohesively direct the multidisciplinary care of the patient. And we already have evidence that such teams improve outcomes. Data supports the benefit of establishing a shock team. University of Utah had their cardiac recovery shock team established and compared patients prior to creation of the team and immediately after, and they did show improve in-hospital 30-day survival independent of the device that was used for either groups. Later in 2021, Propolis also looked into cardiogenic shock admissions in presence of a shock team and also concluded that there is a decreased mortality. Interesting finding in their study was that the presence of a shock team actually used less mechanical circulatory support. And when the mechanical circulatory support was utilized for the care of those patients, it was actually more advanced types of devices. What does it take to establish an ECMO program? With every new initiative, it obviously needs to be very well-researched prior to delving into the project. ECMO is a very heavy, resource-intensive endeavor. And having the expertise of physicians and providers is always a wonderful first step, but it's not enough. We need financial support, we need a system with appropriate infrastructure, and very importantly, we need to have a need within the community. The most commonly pathologies that we usually provide ECMO services for are ARDS and cardiogenic shock. We also have to be able to provide the care that is needed for that. So we need the departments within the system to support that. We need to be able to establish very good and protocols and evidence-based approach to the care of those patients. And very importantly, the system must be able to support the overall care of those patients. It's not just the emergent patient that needs to come in and be placed on ECMO. We need to be able to follow up those patients throughout their hospital stay, and then even outside of the hospital. Then, probably one of the biggest hurdles to face is basically being able to convince the institution that this would be something investing in. Obviously, the primary goal of establishing a new initiative is better patient care. And even though we haven't been able to prove that it decreases mortality, we certainly have evidence that being able to place mechanical support in a timely manner improves outcomes. So getting the financial support of the institution, obviously it's gonna be challenging. It's always challenging to talk about money, but it is one of the best rainbursts, DRGs, quotes by the CMS. So potentially this could be an easy proposal to the institution for financial support. Then we certainly have to have the resources. And very likely we're not gonna have the resources immediately available, but there's also opportunities to develop and advance the resources that were currently existing. It does require very intensive ICU care as we have experienced that, but it also provides opportunity to taking the institutional services to the next level to advance not just the care that we're providing, but also the provider satisfaction, because it would require a multidisciplinary team. It would require, if we don't have all the services needed for providing the care from the beginning to discharge from the hospital, then that gives an opportunity for opening new departments. We also have to be able to evaluate the available resources. We have to be able to clearly understand the shortcomings that we may potentially face and ideally address them prior to initiating the program. It's always beneficial to reach out and collaborate with an ECMO Experience Center because they can share their experiences. We can learn from their mistakes. And of course their expertise is gonna be invaluable. Education is an absolutely priceless component of the establishing of the program. And it's not just the initial education, but also a continuous education because establishing the program is basically the very beginning. Maintaining it is gonna come along with its own challenges. ELSO has anything education was available and it's absolutely an amazing resource for any institution that is even considering to start the process. And then the next step would be after we have set up all the systems in place, that we have the infrastructure in place, that we have the resources in place, becoming an ELSO member. We have our, the institution gets registered, individual providers get registered, and then we start tracking the process. And this is also invaluable because the support that's available, not just from the ELSO organization, but partnering institutions would be able to further guide the advancement of the already established program. Well, I guess nowadays, 21st century, it's difficult to have a presentation on any medical topic without discussing COVID-19 pandemic. Same thing applies to us in mechanical support. It is fascinating that today I sit in front of you and I'm actually discussing a pandemic that would happen only in a lifetime. And many of us had to experience it with all the unfortunate challenges that we had to face. But I sure hope that something good is gonna come out of it. First, I do wanna emphasize that the pandemic didn't just stress the overall system. The whole world, as we all have experienced it, changed the way we live life and practice medicine. But it certainly stressed the ECMO infrastructure and shock teams, not just in the United States, but around the globe. As I am talking to you today, there have been more than 17,000 patients put on ECMO worldwide since the beginning of the pandemic. What it did, it actually, of course, it stressed the system but also it offered an opportune time for rapid innovation and access to mechanical support. And I am certainly hopeful that shortly we're gonna be having more and more data available with the experiences of different institutions, centers, countries, and continents that we can basically improve, learn what we have learned and actually improve on the processes that we already have in place. One such thing was we did change the guidelines for ECMO to accommodate for the support needed during the pandemic. It did broaden the application for indications for ECMO. And of course, even though it was a very horrific time, it was an experience that all of us learned from and we can apply everything learned towards future direction of mechanical support. Review and summarize. I am not sure that I am capable of summarizing mechanical circulatory support in three slides and a couple of minutes of discussion, but I will attempt to do that and try to bring the important points to light one more time. What we've learned is that cardiogenic shock, it is a very heterogeneous and complex syndrome. And even though we have mechanical support and even the medical interventions that we have available today, and we have safe therapies available, we still have very high mortality even with improved hemodynamics and mechanical support, something that would be there for us to keep improving, improving, improving with the hope that we're gonna be successful one day to say, by intervening early on, not only we have improved outcomes, but we decreased mortality. We do know that we have multiple devices. We also know that they're very safe and more data and more data is needed for us to be able to base decisions of how we're gonna change and where are we gonna go from here on. We already have evidence that shock teams and ECMO hubs or centers save lives and improve outcomes. We should continue to advance and develop not just the existing centers and teams, but spread it in geographic areas where access currently is not available. Ultimately, everything in medicine is being able to risk stratify and be able to prognosticate so you can develop and maximize the benefits of the goals and the plan of care for every patient. Opportunities certainly exist at a device level where ideally we can work on decreasing or resizing the devices, having the battery lives last longer, improving the safety of the devices itself. Vascular access side, if you remember, is always an issue with complications with most of our devices. Cannula size, the materials that are being used for the devices itself, basically we should be looking forward and trying to achieve a device that doesn't require any anticoagulation. And as surgical techniques or implantation get better and better, we may be able to have everything implanted minimally invasively, something that is not gonna require a couple of hours of oral time. Certainly opportunities to improve the process, not just by having a better device, by having less anticoagulation needed, but imagine how cath lab procedures were 20 years ago and how we can do it today in a matter of 30 minutes from the door. That could be the ECMO program of the future. If I were asked to move the mechanical circulatory support to the future, I will concentrate on the three major components for a successful endeavor, the human factor. I will propose wide adoption of shock teams because it does improve outcomes. I will propose the technology to continue improving. Imagine what artificial intelligence can do and possibility of a smart pump that can adjust to the hemodynamics needs of the patient. And of course, I will concentrate on the data. Larger trials, more data collection, more data reporting. It will certainly facilitate improving our, not only care, but also recommendations and guidelines. Thank you for your time and please email me any questions you may have.

acute mechanical circulatory support

cardiogenic shock

mechanical support

etiologies

application

available devices

guidelines

special populations

trauma patients

chemotherapy-induced cardiomyopathy

congenital heart disease