um so uh as Jen said we're going to today we're going to talk about uh cardiogenic shock and we are going to do this through the window of the pressure volume uh loops pressure volume domain um so if we start out historically one of the most famous slides that discusses the physiology of hemodynamics of shock is this slide from Judy Hawkman from the late 90s uh and basically the essence of this physiology shows that you know there's a primary insult to the mioardium there's a primary reduction in LV RV or both ventricular contractilities that results in reduction in blood pressure and cardiac output and then there are these secondary effects that really are very important and drive a lot of the uh the pathophysiology which are related to the activation of the barceptors and these include include increases in heart rate incluses in vascular resistance and little little less recognized but extremely important is v uh veno constriction um and this results in a increase in what's referred to as the stress blood volume or the effective uh the portion of the blood volume that is in intravascular that is effectively um contributing to uh pressure generation so that is the black what what's in black and then shortly um you know as as research kind of of uh clinical research geared up in shock it was recognized that that's just what happens in the early phases but as the shock state persists uh there's an inflammatory response that ensues that really counteracts a lot of of these uh effects specifically changing from a vasoc constrictive state to a vasoddilatory date um which further exacerbates this um this kind of this kind of spiral and it's really that inflammatory response and vasoddily um state that results in the multiorgan failure um that really once that sets in it gets harder and harder for the patients to recover um so time this this really emphasizes the fact that time is really uh very important in the uh treatment uh uh pathway of these uh patients allowing the the shock state to persist for longer periods of time increases marketkedly increases the risk of uh of uh poor uh outcomes so this is the um this classic uh paradigm for shock um is very nice uh it's maybe relatively easy to to uh understand but there's a lot more details that we can get when we look uh further into uh the hemodynamic aspects and for me um you know looking at the pathophysiology of shock and especially when you get into mechanical circulatory support the really the best way and for me the only way to really understand what's going on is to look at things through the window of the ventricular pressure volume loop so this is a normal pressure volume loop and people frequently get sympathetic activation just by looking at this um there there's uh some psychological impediments for people to uh to uh you know to look at these loops um which may have not done so since medical school but they're exceedingly easy to understand and um so this shows the normal pressure volume loop um on the left ventricle starting out at end diastilly at the bottom right with the onset of cy we enter the isobalimic contraction phase um uh when ventricular pressure exceeds aortic pressure we have the ejection phase where the volume goes down um cy continues until the end of ejection um and uh and then uh aortic valve closes and you've got the isopolyic relaxation phase then mitro valve opens and you have the filling phase so the normal pressure volume loop is um basically a rectangle um the valves open and close at the corners of the loops and the four edges of the uh rectangle are the four phases of the cardiac cycle and the loop itself is constrained to exist within the end diastolic and the nsystolic pressure volume relationships um so they'll hit this line the EDPVR at endiastel which is the point when the maximum when when all of the cross bridges are um are uh uncoupled and and we're just looking at the passive properties of the muscle and the chamber and the opposite is uh at the cy the ancystolic pressure volume relationship where uh it represents the stiffness of the heart that relationship the stiffness of the heart when the maximum number of cross bridges are are um coupled during uh the uh during the contraction so that's the basics of pressure volume loops and where the loop sits how wide and how tall it is are determined by the preload and the afterload so if you uh start at a low preload and you increase preload the um uh but meaning by preload the end diastolic volume or the end diastolic pressure um the um the pressure generation the height of the loop the width of the loop which is the stroke volume the area inside of the loop which is the stroke work um those will all increase with uh increasing preload but as you see the loops hit these uh these boundaries um the state afterload resistance um if you increase afterload resistance um as indexed by these uh lines that connect from end diia through the end of cy the slope of these lines uh are these these light blue lines are reflective of the uh systemic vascular resistance as you increase resistance this uh depicts really the fundamental a fundamental property of heart contraction which is as that you increase afterload the pressure goes up but the stroke volume goes down and that's of course obvious obviously very important for understanding the impact of uh vasopressors um in shock when contractility is changed the slope of the systolic pressure volume relationship which is the which is really the uh represents the stiffness of the heart at ancy and is related to the number of cross bridges that are formed at ancy um you know this slope changes when you increase contractility from a baseline that slope increases reflecting a stiffer heart and in ancy greater number of cross bridges and when the contractility declines as in shock the slope decreases reflecting a less stiff heart um and cy less crossbridge uh less cross bridges that are formed in diastily um uh the the line at the bottom of these curves um this the end diastolic pressure volume relationship is um nonlinear which is very important from a physiological perspective because it means uh what as the heart gets filled and is working at a higher filling pressure further increases in filling pressure uh don't allow for increases in um in the preload volume and therefore it limits the um the ability of the heart to uh to to uh increase stroke volume and and blood pressure um at these uh when you're working at a higher filling pressure um when this curve shifts leftwards that's what is referred to as diastolic dysfunction and when it shifts rightwards that is what is referred to as ventricular remodeling as occurs in patients with uh most almost all forms of systolic heart failure heart failure reduced uh ejection fraction so we can use these concepts not only in the left ventricle but in the right ventricle and as well in the atria uh but we can really use these um concepts to understand this pathophysiology of cardiogenic shock and also more importantly the effects of mechanical circulatory support um also in addition to hemodynamics we also get important information about energetics and um the first part of energetics is how much work the heart does and that is indexed by the area inside of the pressure volume loop and clinically this can be estimated by assuming the loop is a rectangle with height mean arterial pressure and the width of the stroke volume so that's the stroke work and there's a closely related index which is which is the cardiac power output which is uh work per time which for the heart is excuse me is uh stroke work times heart rate and if you substitute in map time stroke volume for stroke work and then recombine stroke volume and heart rate into what that is which is cardiac output you get the formula that is used clinically to quantify cardiac power output CPO which is MAP times cardiac output so if you do use this um in your practice um CPO is derived from pressure volume analysis this is where that comes from and the reason that is important in um in shock is that it was shown from the original shock trial that there's this inverse relationship between CPO and survival um in hospital uh mortality um the um um the um oops sorry having a little trouble here um the normal cardiac power output is about one watt and when uh watts at presentation drop below about8 or 7 the inhosp mortality has been shown to increase and this relationship has been reproduced in multiple registry studies since this time and I'll come back to that um again later um so work output the CPO or the stroke work or the CPO are one component of energetics but the other component of energetics is how much energy the heart consumes to perform that work and um it turns out that there is um a mechanical correlate to myioardial oxygen consumption which is depicted on here um stroke work is the external work that the heart does but there's also energy stored in the myofilaments at the end of cy that's that are not not expressed externally and that's quantified by the by the area to the left of the loop which is referred to as the potential energy and the sum of these two the stroke work plus the potential energy is called the pressure volume area PVA and that quantifies the total mechanical energy that the heart um liberates with each beat and it turns out that that's extremely linearly related to myioardial oxygen consumption and this uh just depicts uh that relationship between pressure volume area and myioardial oxygen consumption um even when the heart is totally unloaded that means zero external work there's still a lot of energy that's consumed because of basil metabolism and calcium cycling with each beat and it's the energy above this intercept which um is accounted for by the um by the crossbridge cycling so with the pressure volume analysis we get a huge amount of insight not only into hemodynamics ventricular physiology but also myioardial energetics and we'll use all of these concepts to um uh to um uh to uh investigate uh to describe or discuss the pathophysiology of shock and mechanical circuitry support so this depicts the kind of the pathophysiology of shock um with if if the shock is due to completely isolated left ventricular failure you see that there's the reduction in the ventricular left ventricular contractility um that results in a reduction in stroke volume blood pressure there's the activation of the uh bar receptors of the of the sympathetic nervous system with increases in heart rate SVR and stress blood volume and in the case of isolated left ventricular failure you wind up with a uh a loop that is is uh has a very high end diastolic pressure the the pressure at the bottom of the loop uh bottom right corner is the end diastolic pressure and that of course links tightly with pulmonary capillary wedge pressure so you see here the um the reduction in stroke volume and blood pressure and the elevation of the uh wedge pressure on the right side um due to the increase in the wedge pressure pulmonary artery uh systolic and diastolic pressures increased dramatically even though there's no abnormality of the lung vascule or the right ventricle um but due to that increase in wedge pressure the afterload um the the hydraulic afterload on the right ventricle is marketkedly increased um and of course CVP which is tightly linked with the RVN diastolic pressure uh may not change or may actually go down in completely isolated leftsided failure in isolated right ventricular failure the pathophysiology at the onset is different um there is a reduction in RV contractility and that results in a reduction in the filling of the left ventricle and it's the reduction in the filling of the ventricle of the left side that results in the hypotension and the reduction in stroke volume but the barceptors don't know why the blood pressure is low why the stroke volume is low and the same sequence occurs uh with the activation of the receptors an increase in heart rate SVR and stress blood volume but in this case um what happens is there's a marked increase in the central venus pressure um with wedge pressure maybe being normal or being uh low so that's wasolated right ventricular failure but in reality um typically both right and left ventricles are involved um if for no other reason the fact that the septum uh contributes to both right and left ventricular contractilities uh typically with let's say with a large anterior infar proximal l infar uh where the septum is involved both right and left ventricles can be affected and then it gets a little bit more complicated in terms of figuring out u predicting the balance between right and left ventricular contractilities and what's going to happen to CVP and wedge And actually when we look at this uh this relationship between uh right atrial pressure or CBP and wedge pressure in individual patients uh we can arrive at this plot which we refer to as the congestion profile and this shows um we we we take this plot and we divide it into four quadrants um and the top left is when the wedge pressure is elevated but the CVP is normal meaning that it's basically left-sided congestion predominant leftsided failure bottom right is predominant right-sided congestion or predominant RV failure upper right side is uh when both wedge and CVP are elevated and that is what we refer to as bilateral congestion and at the bottom sometimes it can occur that uh there the wedge and CVP are are not elevated at all um and this is from the the shock working group led by Naveen Kapoor 50% of patients in this cohort um presented with um by ventricular congestion bilateral congestion about 25% present with isolated leftsided congestion and about 20% present where the wedge and the uh both the wedge and the and the right atrial pressures are normal um and um this uh congestion profile where the patient sits actually has a significant impact on prognosis so here you see the um the status which quadrant the patients were in and it turns out interestingly that uh if the CVP is elevated either due to isolated rightsided congestion or bilateral congestion mortality in those patients is twice as much as if the um as if the CVP is uh is uh is in the normal range um so that was a little bit of a surprise when we first saw this but this also has been um has been uh demonstrated in other registries um interesting point is um in the blue and and the green here we separated out patients with shock due to acute myioardial infarction and shock due to heart failure and there are two important take-home messages here one is that this uh impact of elevated CVP persists despite um independent of whether it's MI or heart failure shock but also what you can see is that the in general the mortality in patients with heart failure shock is a little bit lower than patients with AMI shock another feature that has been um um been reproduced in other registries um don't know the reason for this But it turns out that even when accounting for the severity of shock in terms of hemodynamics and lactates and other parameters u patients with heart failure or shock have a lower risk of mortality than patients with acute MI um now if we transition now into therapeutics um you know there are drugs of course and devices so this uh if we talk about drugs first this shows the hemodynamic and the metabolic implications of combined inotrope and pressor support on the left you see that as you take a patient with shock and give them an inotrope and a presser uh to increase the contractility and increase the SVR what happens is the uh blood pressure goes up of course uh stroke volume may or may not go up depending on the degree of increase in SVR um this is the thing that you know if you just use pressors in shock um you run the risk of increasing pressure uh pressure at the detriment of cardiac output in which this is why combined use of uh pressors and inotropes um you know are generally wind up being used in patients with cardiogenic shock but the consequence of of using uh inotropes and pressors really is um this marked increase in mioardial oxygen consumption here you see again this MV2 PVA relationship and with uh inotropes and pressors you have an increase in contractility you have an increase in in the pressure volume area the amount of work and you increase the heart rate all of these things increase contribute to the increase in oxygen consumption and very quickly here you could see with even modest improvements in hemodynamics you could increase uh contractility by over 50% which in the setting especially of of um AMI when um oxygen delivery is limited to the infark zone and into the border zone um this can actually have detriment and we know from preclinical ical studies that use of inotropes and pressers increases infark size that's known there's a suspicion never been proved that inotropes and pressers are bad uh for the heart in in um in cardiogenic shock and that has driven really the um the um the development um of that along with the high residual mortality when when when drugs are used that has really driven the innovation in the development of u of device devices and you know of course we have balloon pump emo uh tandem heart is really no longer available and was not really used very much we've got the Impella classes of devices and then we have combinations of devices such as ECMO and Impella and ECMO and balloon pump um so let's just look at the hemodynamics of these different devices and some of the clinical evidence um this just shows the hemodynamic effects of balloon pumping at the bottom you see the impact on uh aortic pressure well-known augmentation during diastily pressure of aortic pressure and in in cy the deflation reduces the afterload uh pressure and you can see that a little bit here on the pressure volume loop um the thing about balloon pumps are that they are very effective in increasing um coronary flow which occurs during diastily um and so as a anga treatment if you if those of you who practice in the 80s and 90s remember that you know balloon pump was like the first line mechanical support device when when patients with unstable anga uh you know failed to respond to nitroglycerin and and and uh nitro nitro and uh and calcium channel blockers and beta blockers we used to put balloons in for anga treatment um but as a mechanical support device for for um as uh in in terms of increasing pressure uh increasing cardic output and reducing wedge pressure not that effective in on average um and this shows um the average results of u this was 20 years ago now holert Teal before he did the uh IBP shock 2 study um studied the hemodynamics and in most studies you could see balloon pumping um in in an average cohort will increase cardiac output by about a half a liter little less and have minimal effect on cardiac wedge on a pulmonary capillary wedge pressure as you see uh here and I think that this really underlies um the uh IBP shock 2 study which showed no no beneficial effect of um of uh balloon pumping in the in the overall cohort um which you I'm sure you're very well aware of this result showing lack of effect of a balloon pump in AMI shock but um the thing about balloon pumping is that its response um is highly variable hemodynamic response is highly variable among patients so this is a study that we did at Colombia just uh this this waterfall plot shows individual patients um lined up from the highest response to the lowest response and you see there are there are some patients that have really a good response to balloon pump and some patients that have no response or or a bad bad response to balloon pumping and uh you could see that this uh the zero crossing is kind of right in the middle and these uh the the negative and the positives are kind of balanced so that if you average this out you'd get you know you'd see almost no you'd see no effect on cardiac output um but nevertheless it must be recognized that there are some patients that respond very well to balloon pump this is AMI shock and if you look at heart failure shock the situation is bit different um yes there is a range of response but there are far more responders than non-responders to balloon pump in heart failure shock um and uh you see the zero crossing is way shifted to the left um and uh there's also very asymmetrical in terms of the pattern above the line above the zero line and below the zero line um so uh this really uh underscores again the fact that the pathophysiology of AMI shock and heart failure shock is really different and things that we learn from one cannot be translated onetoone uh to the other form of uh of cardiogenic shock so this just emphasizes this uh this difference and of course in the US despite the fact uh despite the am uh the IBP shock 2 study results balloon pump remains the number one um uh utilized device in shock and also despite it being downgraded in the guidelines um um for shock treatment it still is the number one uh used devices uh there are a number of review articles that that took a that tried to um uh explore who are the best responders to um uh to uh um uh balloon pumping and there are several features I won't go through these that that um tend to result in a better response to balloon pumping but there has never been a prospective study that used any index um uh or any kind of prognostic uh index that said these patients would be better responders has never borne out in prospective studies so the bottom line is that if you do choose to use a balloon pump as um the first line treatment it's highly suggested to you you know to really monitor the patient with a a right a right hard calf to make sure that you're getting the response that you that you want and if you don't get that in a very short period of time that uh you know you should consider um escalation now if we look at the um pathophysi or the hemodynamics of VA ECMO peripheral VACMO um it's also of course variable among patients but what I'm going to show you is the pure hemodynamic response of ECMO in a patient with shock uh assuming that nothing else in the cardiovascular system changes that you just put in this device and um and um and and you you divert blood from the heart to the arterial system from the Venus from from the the uh IVC or the right atrium to the arterial system and what you can see here is that fundamentally um VA ECMO um loads the heart why is that so you first of all you divert blood away from the from the heart um and therefore Venus return is decreased to the heart so you decrease Venus return shouldn't preload go down Well that's the simple way of thinking about it and is not really what happens um the heart um with VA ECMO the heart itself has to increase has to eject the blood that's returned to it so even though Venus return is reduced there still is Venus return and if the um initiation of ECMO is successful in increasing blood pressure which is not always the case um you the the only way for a weak heart to overcome an increased afterload pressure is to retain fluid retain blood so that um it can um by stling mechanism it can overcome that new new increased blood pressure and maintain maintain a balance between venus return and and cardiac output so fundamentally if again if nothing else changes like contractility doesn't change SVR doesn't change stress blood volume doesn't change the ECMO circuit will will increase the load and has the potential to worsen or induce pulmonary edema now this doesn't always happen because when ECMO is initiated sometimes contractility does improve sometimes SVR does decrease because ECMO also is associated with initiating an inflammatory response and sometimes the stress blood volume decreases because of bleeding and also the systemic inflammatory response can cause veno dilation as well as um arterial uh dilation but nevertheless this phenomenon of ECMO loading the heart is very important and goes along with uh other the other phenomenon uh which is the harlequinn syndrome or the north south syndrome where the heart and the emma are competing with each other um and in this case you see an aortagram with dye injected into the aorta and um the dye never goes below the uh basically go below the diaphragm because the heart and the and the ECMA are are actually completely balanced so if the patient is in pulmonary edema the um the cerebral circulation the and the superior part of the body will be perused with deoxxygenated blood whereas the inferior part of the body is perused with um with oxygenated blood and in the extreme case um here's where the heart is completely overtaken by the ECMO because here you see the aortic valve is not opening this is kind of a medical emergency in the sense that this now when the aortic valve doesn't open or is opening a limited amount goes along with induct that induction of pulmonary edema like you see here that results in stasis of blood in the atrium ventricle um and that can also then lead to thrombus and there are extreme you know examples of thrombus formation here large thrombus across the mital valve here complete thrombosis of the left ventricle here is another example where you see um completely shut aortic valve with uh with um stasis in the aortic root and here are some examples of thrombus being formed in the uh aortic root here's another example of complete thrombosis of the uh of the ventricular chamber so these can um these events can of course be avoided by monitoring for um aortic valve opening or lack of aortic valve opening and also by monitoring for the harlequin syndrome uh by multiple mechanisms looking at right radial artery o saturation and um by temporal uh near infrared spectroscopy to look at bmporal uh oxygenation oxygen saturation um so these are all the reasons why um you know monitoring patients closely on ECMO is really is really important energetically um this loading can increase the myioardial oxygen consumption and there are preclinical studies that show that use of ECMO during experimental MI can actually um um you know increase infark size we don't have clinical data to that effect um but uh you know there are multiple studies that show no improvement in survival um with the use of ECMO now this is the ECLS shock uh uh shock uh study again from Holar Teal um and uh one of the interesting things um there's been a many criticisms of this study in particular one of the interesting things though is is that the early in the early days you see that there's a trend for survival to be a little bit better with ECMO than with standard of care um whereas at 30 days there's no um you know there's no benefit but you know this this study took all comers with um with shock and put them on ECMO or treated them with medical therapy and that's not really how ECMO was used um you know ECMO was used really as a bailout when patients are really really crashing and that's not how it was studied here so the the conclusion of this study is don't use ECMO as in routine you know as as firstline um you know routine use in um in shock but it was never used that way um but it is intriguing that there is some early survival uh apparent um you know not statistically significant but at least a trend so that brings us to um transvalular pumps like uh the impella family and here you'll see a very very different hemodynamic response um and the key points are number one directly pulling blood out of the ventricle reduces the preload unloads the ventricle number two the loop changes from a rectangle to a triangle because the blood is uh always being pulled out of the ventricle the trajectory is always to negative volume a decreasing volume um because it's pulling it's pumping blood independent of the phase of the cardiac cycle and even during when the mitro valve opens during filling uh there is blood still going out of the ventricle u uh out of the ventricle through the aortic valve um so that's why the shape changes so dramatically um third is the uh pressure volume area the the ind again indicating the oxygen consumption will be reduced by this uh approach and then fourth at the bottom you see this phenomenon of LV aortic pressure uncoupling obviously normally aortic and ventricular pressures are the same during cy during ejection but if the conditions are right meaning that the contractility of the heart is low enough and the speed of the uh elvad of the pump is high enough the aortic valve can become closed and um and the pressures can become dissociated and of course unlike ECMO a closed aortic valve with a valve with a ventricular assist device that's pumping blood from the chamber and discharging it into the proximal aorta maintains turbulent flow um in both the uh ventricle and the aortic root so you don't have the same risk of uh thrombus formation as you do when the aortic valve is closed during um during ECMO support so these are some real loops measured um in patients using a conductance catheter um this was from Bill O'Neal early in the days when this was actually with a Impella 50 showing the difference between the loop without E uh without the impella and then with the impella here you see these triangular shaped loops and and again you see the enstolic and the end diastolic pressure volume relations uh that you see with the unloading of the um of the ventricle um and then I already mentioned that energetically um you know this um uh impella can unload the uh ventricle and reduce the um infar size or reduce energy consumption and unlike ECMO multiple preclinical studies starting back in the 1990s showing using devices like Impella and the predecessor of Impella the hemop uh that you can reduce infar size in experimental um experimental u inffort and of course now we've got the um the danger shock trial which showed a u at six months a 13% absolute reduction in mortality um with a number to treat of eight to save one life so this of course was the first the actual very first positive trial of a therapy in cardiogenic shock um and certainly was a very um um pivotal study um and uh obviously has resulted in an upgrade of Impella um in the guidelines from a 2B to a 2A didn't quite make it to a one class one indication um but and of course there are there are multiple limitations of this study the major one um in terms of clinical practice is that um you know of all patients presenting with shock and and AMI shock um the danger criteria the patients that that really qualify in most registries that have looked at it so far range between um 10 and 20% with an average around 15% meaning um you know 85% of patients that present with AMI shock would not would not qualify to be enrolled in the study and therefore you know there are still questions about whether or not um you know in that bulk of patients the 85% whether whether uh unloading with Impella would really uh you know provide um a benefit but nevertheless um I'm sure that you're all aware of the NCSI National Cardiogenic Shock Initiative led by Bill O'Neal and Bobber Bassier um this is the um algorithm that they had developed and tested in registry form not in randomized study form this algorithm largely formed the basis for the danger shock trial um because danger was built on on um you know best practices at the time and evolved over time of course Danger enrolled over a 10-year period uh which was another issue with the study um and you know clinical practice changed but in the end you know this protocol this algorithm did underly um the concept of what was being tested in danger in addition to the um the device itself and there are three points that I want to make from this study uh from this algorithm one is that they strongly advocate using a right heart calf um early immediately a patient presents with shock put in a right heart cast so that you can guide your therapy number two is early initiation of MCS so that was also done in danger so early initiation of MCS and number three was uh complete weaning ofotropes and pressors this is all predicated on the concept that inotropes and pressors are bad for the patient for the heart um again that's an assumption a hypothesis that we don't really have perfect data we don't have you know data to prove that in the clinical setting there's plenty of data in preclinical but not in the clinical setting so these are the um the principles that underlied the um the danger shock trial and the NCSI protocol and what I'm going to do in the next slide is show you in the pressure volume domain and the MV2 PVA domain this algorithm so we're going to start out with a patient who is in shock on inotropes and pressors we're going to then put in an impella and then we're going to wean the inotropes so here is the patient um we're going to now put in the impella and you see the changes in the um the pressure volume loop and you see on the um on the MV2 PVA relationship that there's the reduction in oxygen consumption due to the unloading it's a relatively modest amount um but now what we're going to do is um is wean the anotropes and pressors and what you see is in this case um you know we've got now the ventricular aortic pressure uncoupling but now um due to the weaning of the anotropes and pressors we have a marked a much more a much greater um reduction in myioardial oxygen consumption due to the increase uh the decrease in contractility the decrease in the pre the work of the heart and the decrease of heart rate uh that that could be achieved by um withdrawing the um the inotropes and pressors so in my mind the value of the um impella is not only to do primary unloading which of course will have benefit to the wedge pressure uh again when the EDP goes down that means the wedge pressure goes down so there's a primary benefit of that but also um it it it permits um the uh weaning of inotropes and pressors and that may that fact itself may have a uh a substantial benefit to the patients as well in terms of reducing infark size again this is all hypothesis uh but but uh something that um you know would be very intriguing um you may know that there is a study going on now in Canada uh called the dome 2 uh study that is actually um randomizing patients to inotropes versus no inotropes versus placebo um in in cardiogenic shock um and uh that that study is I think about uh I'm not 100% sure i know it's not fully enrolled yet but I think it's nearing uh nearing enrollment and um and we'll hoping to see the results this uh coming year um what was done in the cardiogenic shock uh the NCSI uh registry they basically um reproduced this graph from the shock uh study and divided patients into the number of pressors that they were receiving zero pressors here one pressor uh orotrope and and two or more and what you can see is that um if a patient was able to achieve a certain watts um with no pressors then they had a better survival than if they needed two one or two or more um and the argument that they're trying to build is that inotropes are bad but I mean obviously the main conclusion here is that you know the sicker a patient is the more treatment they get the more inotropes and pressors they get so from a mechanism point of view you know this is not you know hugely hugely helpful but still from a prognostic perspective practically and when you're treating a patient um you know this is useful information um you know if you look at the number of of um the the cardiac power output that you're able to achieve um this table is um is not un unhelpful uh so it it it gives you a good target that you know if you're able to achieve a cardiac power output over you know 6.7 with one or no inotropes then that the um odds of survival um of the patient is um is uh pretty pretty high um other information and this just shows that that you know that indeed in the danger trial um where um inotrope use was not protocolized and pressor use it was not protocolized it does show that inotrope and pressor use was reduced um in the in the patients who received the microaxial flow pump that's in orange here and it was uh it was the case for both the um the pressers and for the uh for the inotropes interestingly this this difference only persisted for the first 24 hours and um and then there was kind of a catchup uh after 24 hours and um that the reason for that has been speculated but but again it was not the reasons I think are related to the fact that that um it was not protocolized and actually also the number of patients that contribute at each of these time points um differs which I think was a little bit of a mistake take and how they analyze this uh but nevertheless in the early stage when the number of patients is the same um you do see this reduction in in the use ofotropes and also maybe more importantly lactate clearance was increased in the um in the treatment group compared to the standard of care um and that also obviously is another um um kind of negative consequence of pressors is the vasoc constriction um you know in the periphery uh you know although blood pressure may be increased you know it it has the potential to uh to reduce the profusion and that's why um you know I think this is really more important than the uninrup score but just shows that that the consequence of um or the benefit benefits of of reducing pressor support and um swapping that uh for uh the uh the use of the mechanical circulatory support uh on a physiological basis there are multiple you know algorithms that are now developed they're very they're all pretty similar this is the ANOVA score um the ANOVA algorithm I'm sorry they have two algorithms one for AMI shock and one for heart failure shock this is their heart failure shock algorithm uh again this has never been tested prospectively um and probably won't but one of the things about the um the ANOVA algorithm um and subsequently uh papers like this one from uh a scientific statement um really also in addition to talking about the initiation of of uh MCS talk about deescalation um you know how do you wean the weaning weaning part uh so both escalation and deescalation are more emphasized in um you know in uh in this statement and in the ANOVA protocols so here's an example of a patient who is on ECMO and now getting escalated to ECella or combined uh uh um ECMO plus adding Impella um PA the patient that's being simulated here was a patient who indeed you know had elevation of wedge pressure due to ECMO um and what you can see is addition of impella to ECMO will completely counter counteract that um that um increase in wedge pressure um and also obiate the concern about stasis in the chamber and in the um the aortic root and this is um an example from um an actual patient um very limited data have been published hemodynamic data like this but this patient uh presented with shock with a wedge of 40 was put on ECMO wedge went up further and then impella CP was placed and you see this mark reduction in um in uh wedge pressure um and then there's a this is kind of a systematic uh study of about I think it's around 30 patients uh that got ECMO first and Then impella was added and in terms of wedge pressure you see an average 10 mm reduction in um in wedge pressure which is pretty uh pretty substantial um so that is a very very quick uh overview review of of um of how I look at the hemodynamics of shock and circulatory support of course we went through this extremely quickly um the teach uh programs that we that we go through especially for fellows we spend between three and five hours uh depending on the the depth of uh of of where of how you want to go because you know we go into the differences between bentricular failure left isolated right ventricular failure um all the ways of counteracting ECMO unloading there are at least nine different ways to counteract um uh um a patient who's loaded on ECMO um um there and then we also talk about the uses of MCS in high-risisk PCI and the whole uh physiology of um of coronary coronary physiology what happens when you uh olude and unaclude vessels during PCI and the implications uh for mechanical circulatory support in those settings uh but I think really one of the take-home messages that I like to really um leave with is that really understanding the physiology in the framework of the ventricular pressure volume domain really helps explain the human of shock and all forms of therapy drugs and devices and I think that it really gives you a the the only way to really really deeply understand what these devices are doing uh not only to blood pressure and cardiac output but to the ventricles and how they um you know and also by by ventricular you know what's happening on the right when you do when you do something on the left side there's also an implication on the right side as well um uh so I think really we're really trying to advocate for you know educating people in on understanding hemodynamics in pressure volume domain um the other thing is uh uh as we emphasized with balloon pumping but it's true with all the devices the response to device therapy and drugs vary very significantly among patients and that is why it's I think very important to monitor the patients um from the beginning with pulmonary artery catheters um also perccutaneous devices unload the ventricle while um ECMO really has the potential to increase the load on the heart um and cause stasis um in the chambers uh due to reduced uh opening of aortic uh valve um and uh so um anyway that is uh that's an overview of again a very quick overview of a huge huge amount of physiology