CVM Grand Rounds February 11, 2026

Name: CVM Grand Rounds February 11, 2026
Uploaded: 2026-02-11T19:35:11.0233333Z
Duration: 1 h 11 min 5 s

February 11, 2026

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04:51Alright.
04:52Sorry for the delay. No
04:54worries.
04:55Hi, everyone.
04:56Welcome to, this week's cardiovascular
04:58medicine grand rounds, which is
04:59a very special occasion,
05:01for many reasons, but, not
05:03the least. Just to briefly
05:04mention, this is our annual,
05:06Forrester,
05:07Lee or Woody Lee lectureship.
05:11In years past, we've gone
05:12into great detail
05:14to,
05:15to highlight all the ways
05:17that doctor Lee represents the
05:19best of us and really
05:20had a magnificent
05:21and longstanding impact on our
05:23organization.
05:24Today, because we're getting started
05:25a little late, I might
05:26shorten that, Woody, if you
05:27don't mind. But just to
05:28highlight the fact that without
05:30doctor Lee,
05:32this, institution would be, would
05:34be nothing like itself. Now
05:36he had an immense impact
05:38at the level of the
05:39school of medicine at the
05:40university
05:41in expanding our,
05:43understanding of how to,
05:46build a more inclusive environment
05:48and to recognize the opportunities
05:50of,
05:51of of different,
05:53trainees as well as physicians
05:55and and faculty,
05:57across the spectrum of of
05:59race, ethnicity,
06:00and and, primary kinda practice
06:03origin.
06:04And that, I think continues
06:06to pay dividends for us
06:07as a university and a
06:08school of medicine.
06:10As a cardiovascular medicine community,
06:12without doctor Li, I would
06:14dare say we would not
06:15have a heart failure program,
06:17and I think he had
06:19an immense impact on initiating
06:21our transplant program, our heart
06:23failure program, and now with
06:24the faculty of a of
06:25nearly a dozen,
06:27when I think you were
06:28only
06:29one
06:30when you started.
06:32It, I I I hope
06:33he, sees the the the
06:35the great fruits of his
06:36labor. Welcome again to,
06:39all of the people,
06:41across the state.
06:43I hope you're enjoying your
06:44lunch at our watch parties,
06:45and thanks to the team
06:46who's organized this, this event.
06:48With that, I'm gonna let
06:50doctor, Davila introduce our speaker
06:52who is a really, a
06:54great testament to the investigative
06:57interests of doctor Li. And,
07:00Carlos, take it away. Thanks,
07:01Eric.
07:02Welcome.
07:03I'm very excited to introduce
07:04today's speaker and to do
07:06so on behalf of the
07:07Forrester Li lecture.
07:08As I was reading more
07:09about doctor Li's work, not
07:11only in cardiac transplant, but
07:12also long standing commitment to
07:14faculty inclusion on diversity,
07:17I was struck by how
07:18his legacy continues to shape
07:19who has a voice in
07:20forums like this.
07:22It is in that very
07:23much spirit and because of
07:24work of leaders like doctor
07:26Lee that I feel especially
07:27honored to introduce doctor Daniel
07:29Barkoff.
07:30Doctor Barkoff is the director
07:32of heart failure hemodynamics and
07:33mechanical circulatory support research at
07:35the Cardiovascular Research Foundation and
07:37an adjunct associate professor of
07:39medicine at Columbia.
07:40His training reflects,
07:42powerful blend of engineering and
07:44medicine.
07:45He earned a degree in
07:46applied engineering physics from Cornell,
07:49followed by both his MD
07:50and PhD in biomedical engineering
07:52from Hopkins, where he also
07:54completed his cardiology fellowship.
07:56He has led major academic
07:58and research programs, including founding
08:00the cardiovascular research laboratory at
08:02Columbia, and directing the Skirball
08:04Center for Cardiovascular Research at
08:05CRF.
08:07His career
08:08career uniquely bridges fundamental cardiovascular
08:10physiology,
08:11translational medicine,
08:13clinical trials, and device innovation,
08:15including servings as medical director
08:17for multiple start up companies
08:19focused on heart failure diagnosis,
08:21mechanical circulatory support, and novel
08:23therapeutics.
08:25Dan has published more than
08:26five hundred peer review articles
08:28with seminal contributions in ventricular
08:30mechanics, remodeling, and mechanical circulatory
08:32support.
08:33He also directs the CRF
08:35international recognized teach program, which
08:38I'm a proud alumni from,
08:39and the creator of Harvey.
08:41He also serves as director
08:42of the THD Conference, one
08:43of the largest global meetings
08:45focused on technology and heart
08:46failure therapeutics.
08:48We're incredibly fortunate to have
08:49him today with us speaking
08:50on cardiogenic shock, a topic
08:52that is a center of
08:53active discussion across multiple subspecialties
08:56within cardiology and within medicine.
08:58Please join me in welcoming
08:59doctor Daniel Barkoff.
09:05Thank you all very much,
09:07and, I've just really had
09:08a great a great morning
09:09so far, and I'm sure
09:10the rest of the day
09:11will be will be equally
09:12fun.
09:13And,
09:14I will try to let's
09:16see. How do we advance
09:17the slides, though?
09:22Clicker. Now we're on the
09:27doctor Li, I had the
09:28pleasure to meet doctor Li
09:29just a few minutes ago,
09:31and it was really, really
09:32fun. Okay.
09:33So, today, we're gonna talk
09:35about cardiogenic shock. It's a
09:37massive,
09:38task to talk about this
09:40because there's so much, really
09:41there's so much going on.
09:43These are some relevant disclosures,
09:45and I do wanna make
09:46a little pitch for the
09:47THT meeting, which is coming
09:48up in about two and
09:49a half weeks.
09:50And in particular, the day
09:52before on March first, Sunday,
09:54we're gonna be hosting a,
09:56for the first time, a
09:57hands on training day,
09:59that is focused for fellows
10:01and APP APPs.
10:03And,
10:04it's we're gonna cover things
10:06like ECMO, Impella,
10:07balloon pump, LVADs, total artificial
10:10heart, and PA pressure sensors,
10:12and on all the practical
10:13hands on aspects. And it's
10:14totally free,
10:16free meeting. And so please
10:18consider,
10:20you know, attending this. So
10:21let's get to cardiogenic shock.
10:24So this is an image,
10:25from, Judy Hockman,
10:27who ran the shock trial.
10:29And this was, in the
10:31late nineties kind of the
10:32model of of a cardiogenic
10:34shock. There was a myocardial
10:36insult, in this case, myocardial
10:37infarction
10:38that led to reductions in
10:40left, right, or both ventricular
10:42contractilities,
10:43reduction in blood pressure, and
10:45cardiac output.
10:46And then there are these,
10:48the secondary effects
10:50of related to the baroceptor
10:52activation
10:53with increases
10:54in heart rate, systemic vascular
10:56resistance,
10:57and also
10:58not well appreciated, but a
11:00really a lot of action
11:01happens in the venous system.
11:03Venal constriction
11:04is really what contributes
11:05to the rise in CVP
11:07and, and wedge pressure that
11:09we see.
11:10So then,
11:11this was the this is
11:12what happens in early shock
11:14and then it was, appreciated
11:16a little bit later that,
11:18as the shock state persists,
11:20there's an inflammatory response that
11:21purse that ensues
11:23and this actually counteracts a
11:25lot of the things that
11:26are that the baroceptors do
11:28and actually to vasodilatory
11:30state that
11:31exacerbate
11:32the exacerbate the situation.
11:35So that in the longer
11:36term
11:37inflammation, vasodilation,
11:39and multi organ system
11:41failure ensue.
11:43So early on shock
11:44starts as a hemodynamic problem
11:47and as time goes by
11:48it gets worse and involves
11:49more and more organs of
11:51the body becomes a hemometabolic
11:54condition.
11:55And if we look at,
11:56look at just phenotyping patients
11:58in terms of both hemodynamics
12:00and metabolics,
12:01we can see we found
12:02in the shock working group
12:04we found three relatively distinct
12:06phenotypes
12:07that start out in in
12:10phenotype one, which is mainly
12:11hemodynamic
12:12and,
12:14transitioning
12:15to a cardiorenal
12:16phenotype and then ultimately into
12:18a cardiometabolic
12:20syndrome where
12:22multiple organs of the body
12:23are affected.
12:24And as you transition from
12:26the hemodynamic
12:27towards the hemometabolic
12:29the mortality,
12:30at the time you know,
12:32the mortality,
12:34thirty day mortality worsens
12:35as a as the patient
12:37presents in a worse condition.
12:40This is highlighted
12:42in a little bit more
12:43detail in a recent
12:44review paper in New New
12:46England Journal that just appeared
12:47last month.
12:49And here you can see
12:52really, in the ultimately shock
12:54really affects almost every organ
12:55in the body and has
12:56an implication
12:58for, prognosis.
13:00Now another way to look
13:01at shock is through physio
13:03more physiological
13:04perspective.
13:06And I'm gonna try to
13:06mix the clinical and the
13:08physiology together.
13:09And when I talk about
13:10physiology, I talk about things
13:12in the pressure volume domain.
13:14This is normal pressure volume
13:15loop bounded by the end
13:16systolic and end diastolic pressure
13:18volume relationship,
13:20And this is what happens
13:21when you change preload after
13:22load and contractility. This is
13:23all very basic medical school
13:25stuff,
13:26but also the one of
13:27the advantages of the pressure
13:29volume domain is that we
13:30can also understand about metabolics
13:32because there's a very tight
13:34relationship
13:35between
13:36this parameter,
13:37with the, the stroke work
13:39and what's called the potential
13:41energy which is this area
13:42inside of the pressure volume
13:44loop that relates very closely
13:46to myocardial oxygen consumption which
13:48we think plays a big
13:49role in understanding therapeutics,
13:52and prognosis in, in, in
13:54a cardiogenic shock.
13:56So if we look at
13:57it physiologically
13:58at least in the short
13:59term,
14:00this is what happens when
14:01there's biventricular
14:03involvement. You see,
14:05that both the end systolic
14:06pressure volume relationship of the
14:08right and the left ventricles,
14:10decline,
14:11then the baroceptors
14:13activate, there's increases in heart
14:14rate, increases in systemic vascular
14:16resistance,
14:17and there's that venoconstriction
14:19which increases what's called the
14:20stress blood volume, and then
14:23the pet what happens to
14:24CVP and wedge
14:26really depend on the relative
14:28contributions or the relative diminution
14:30of right and left sided,
14:32contractilities
14:33and the degree of, venal
14:35constriction.
14:36And in fact, if we
14:37look at this is registry
14:39data from the cardiogenic shock
14:40working group. This is what
14:41we call the, the congestion
14:43profile where we plot the
14:45right atrial pressure versus the
14:47wedge pressure, and we divide
14:49this,
14:50this graph into four quadrants.
14:52Upper left is when only
14:54the wedge pressure is elevated.
14:55Bottom right is when only
14:56the CVP is elevated.
14:58The upper, right quadrant is
15:00what we call bilateral congestion
15:02when both CVP
15:03and wedge are elevated. And
15:04at the bottom left is
15:06kind of a uvelemic where
15:07neither are elevated
15:09and you can see fully
15:11this is from the all
15:13comers both heart failure and
15:15AMI shock. Fifty percent of
15:17patients present with bilateral congestion,
15:20about twenty five percent present
15:22with isolated left sided congestion,
15:24and about twenty percent present
15:25in this kind of euvolemic
15:27state. And one thing that
15:28was very interesting and maybe
15:30a little bit of a
15:31surprise
15:32is that one of the
15:32things that the power the
15:34most powerful of these
15:37indexes that
15:38are prognostic
15:40is actually the central venous
15:41pressure, the CVP.
15:43If the patient present with
15:45either isolated right sided congestion
15:47or bilateral congestion,
15:48the mortality is twice that
15:51as whether, as when the
15:53central venous pressure is normal
15:54and that cut off there
15:55was only twelve millimeters of
15:57mercury for CVP, so not
15:58very elevated.
15:59The other two things that
16:00we saw,
16:01that have come true in
16:03most registries, number one, is
16:05that we divide this into
16:06AMI shock and heart failure
16:08shock. Patients with AMI shock
16:10tend to have a much
16:11higher mortality than patients with
16:13heart failure shock. That comes
16:14through in almost all registries.
16:17And so everything that we
16:18learn about shock,
16:20which is mainly from AMI
16:22shock, do not apply one
16:24to one to, patients who
16:26have heart failure shock. These
16:27are different
16:28entities, if you will. They're
16:29not completely different, but there's
16:31a lot of unique features,
16:32and we're barely scratching the
16:33surface and understanding about heart
16:35failure shock and how to
16:37treat it.
16:38And the other thing is
16:39so this this trend for
16:41CVP to be, very,
16:43modulate,
16:44prognosis is, is present in
16:46both forms of shock.
16:48Now in terms of therapies,
16:50we have drugs, you know,
16:51the drugs, you know what
16:52they do, and we have
16:54devices,
16:55you know, all the devices
16:57we have now more options
16:59now for right sided support.
17:00We have VA ECMO balloon
17:01pumping
17:02and, two two major forms
17:04of,
17:05micro axial flow, pumps.
17:08But if we start now
17:09looking at the evidence,
17:10and how to treat patients
17:12with shock, we're really,
17:13not in a really great
17:15place.
17:16So these are a list
17:17of the, the key randomized
17:19trials that have performed. Of
17:20course, the initial one was
17:22the shock trial led by
17:23Judy Hockman, a NIH study,
17:25and I'm not not a
17:26lot of people really remember,
17:28but that was a negative
17:29trial if you go by
17:30the primary endpoint.
17:32It became positive
17:34with longer term follow-up, but
17:36to the these by today's
17:37standards, this would be considered
17:38a,
17:39a, hypothesis generating,
17:42observation.
17:43From there, we've got the
17:45IBP shock two trial that
17:47killed the balloon pump in
17:48Europe, but not in the
17:49United States. We have the
17:50corporate shock trial that that
17:52said that you should only,
17:54revascularize
17:55the corporate artery in, AMI
17:57shock. We have the DO
17:59RE MI trial,
18:00which said that there was
18:01no difference between milrinone and
18:03dobutamine.
18:04We've had the ECMO shock,
18:06ECMO
18:07cardiogenic shock and the ECLS
18:09shock which said that
18:12that the use of ECMO
18:13does not impact on mortality.
18:16And
18:18most recently we have the
18:19danger shock trial which is
18:21really
18:22the study of the Impella
18:24CP,
18:25which is really the only
18:27if I can say, positive
18:28trial that from, you know,
18:30in terms of formality,
18:32that really has guided,
18:34us has provided some, some
18:36guidance.
18:38Just as a reminder, the
18:39danger shock trial was a
18:40randomized trial
18:43with Impella
18:44with a suggestion of how
18:46the patient should treat should
18:47be treated, but not really
18:48very strictly enforced
18:50versus a control
18:51group, that did not get
18:53Impella and also they did
18:54not have balloon pump.
18:56By this time the, and
18:57this was done in Germany
18:59and and, Denmark. The balloon
19:00pump was really not used
19:02in those countries anymore.
19:04And again, with the suggestion
19:06of what to do, but
19:07it was not the protocol
19:09was not really enforced. So
19:10it was really,
19:12you know, at the discretion
19:13of the treating physician how
19:14to treat the patients once
19:15they either got the Impella
19:17or were randomized.
19:19Ten years to enroll three
19:21hundred and sixty patients
19:22and, the study had a
19:24very had a p value
19:26of point o four. It
19:28was right on the borderline
19:29of being significant,
19:31with a
19:32twelve point seven percent absolute
19:34reduction at six months. At
19:36thirty days, it would have
19:37been a neutral trial,
19:39but it also had a
19:40very low fragility index meaning
19:42if four patients
19:43move from one
19:45one group to a success
19:46to a, a failure, the
19:48true the trial would have
19:49been completely negative. So this
19:51is considered I mean it
19:53is a landmark trial, but
19:54it's it really hinges hinges
19:56on a very few,
19:58observations. And in fact, if
19:59you looked at the intent,
20:00this is the intent to
20:01treat analysis. But if you
20:03look at the protocol
20:04analysis, it was actually a
20:06neutral a neutral trial.
20:08And of course use of
20:09Impella versus no device, there
20:11were adverse events or were
20:13much higher.
20:14But despite the the increase
20:15in adverse events,
20:17you know, there still was
20:18a survival benefit
20:20that,
20:21that appears to,
20:22persist over longer periods of
20:24time.
20:25This appeared late last year
20:27in New England Journal, but
20:28I really would highlight look
20:29at the small number of
20:30patients that we're dealing with
20:32as we get out past
20:33one year. So we, you
20:34know, we're still even though
20:35this is a positive trial,
20:37we'll still a little bit
20:38on,
20:39on shaky grounds.
20:41There have been about ten
20:43more papers that have been
20:44published, secondary analysis
20:46of the,
20:47of the, danger shock trial.
20:50And I won't go into
20:51all of these,
20:53in detail,
20:54other than to say that,
20:55you know, there is significant
20:56understanding,
20:57you know, interesting observations about
20:59age,
21:01about
21:01the ability to
21:04to reduce the use of
21:05inotropes
21:06during shock.
21:09That use of Impella earlier
21:11in the course is is
21:12more favorable,
21:14and that all despite the
21:15adverse events the long term
21:17effects
21:18were
21:19you know were still observed
21:21and these papers are now
21:22coming out little by little
21:24and they're readily available.
21:27So what about the guidelines?
21:29Where does that leave us
21:30now? So in terms of
21:32revascularization
21:33of course urgent revascularization
21:36is indicated
21:38also there because of the
21:39culprit shock trial, it is
21:40really,
21:42a class three
21:43indication to in to revascularize
21:46non infarct arteries.
21:47I can tell you that
21:48there's gonna be some, contra
21:50some contrary data that will
21:52probably come out at, at
21:54TCT this year and papers,
21:57because don't forget this was
21:58done in the setting without
22:00Impella support. So now imagine
22:02you have patients on Impella
22:04support. Does that change,
22:06the,
22:07your strategy for revascularization?
22:09Is it safer or even
22:11more beneficial to do multi
22:12multi vessel,
22:14PCI at the time of
22:15shock unanswered
22:17question?
22:18But in terms of MCS,
22:20there was a shift last
22:22year and these the guidelines
22:23that came out where,
22:25use of Impella became a
22:26two way in selected patients
22:29and balloon pump and ECMO
22:30were were downgraded to a
22:32three,
22:34not to be used in,
22:35in as routine. So the
22:37key here is the key
22:39phrases here are in selected
22:41patients to use,
22:43Impella and with regard to
22:45balloon pump and ECMO, it's
22:47don't use it in routinely.
22:49And actually, if you really
22:50dissect this, they're saying the
22:51same thing. Don't use Impella
22:53in every use Impella in
22:55selected patients and don't use
22:56balloon pump and ECMO in
22:58every patient. It's just saying
22:59the same thing. So it
23:01was really all about how
23:02the trials were designed and
23:03what the primary endpoints were
23:05and how they were interpreted
23:06that made a difference between
23:08being
23:09a a three, a class
23:10three and being a class
23:11two a.
23:12So as we know, I
23:13mean here in the United
23:14States balloon pump is still
23:16the number one device used,
23:18ECMO is widely used. In
23:20fact after most negative ECMO
23:22studies, even VV, NVA,
23:24after negatives trials,
23:26ECMO use increased not decreased,
23:29in the face of negative
23:30trials.
23:32So,
23:33what about so how selected,
23:36should we be here? This
23:37is from,
23:38the c three t n
23:39database.
23:40They did an analysis of
23:41how many patients would fit
23:43the danger shock trial criteria.
23:46And,
23:47so this, the the the,
23:49the critical care network is
23:51looking at everything in critical
23:52care cardiology,
23:53not just not just shock,
23:55but among the the twenty
23:57thousand admissions, there were seven
23:59hundred and fifty seven
24:00STEMIs in cardiogenic shock and
24:02among those
24:04about thirty two percent were
24:05eligible. But of all the
24:07cardiogenic shock only five percent
24:09of patients who present with
24:10cardiogenic shock meet the criteria
24:13that that is the selected.
24:15That's how selective it is.
24:16So we have a long
24:17way to go.
24:18Now
24:19we know that the treatment
24:21of patients with cardiogenic shock
24:23is extremely complicated, involves many
24:25many aspects
24:26and these are this is
24:28a list of things things
24:29that were, that were
24:31identified by the cardiac, cardiac
24:33safety research consort consortium think
24:35tank as unresolved
24:37issues that need to be
24:38addressed. I'm not gonna go
24:39through this list, but even
24:41not even not even on
24:42this list was what's how
24:43do you treat STEMI versus
24:45NSTEMI? And how do you
24:46treat heart failure shock?
24:48And within heart failure shock
24:49we have de novo shock
24:50and we have patients who
24:51are chronic
24:53decompensated,
24:54shock and many other questions.
24:56So these are all the
24:57things that we have to
24:59as you as as clinicians
25:00treating these patients really have
25:01to grapple with on a
25:03daily basis and
25:05obviously we're not gonna be
25:07able to answer all of
25:07these in the context of
25:09randomized trials.
25:10So ongoing now there are
25:12currently
25:14eighteen ongoing randomized trials
25:17that looking at various forms
25:19of MCS.
25:21Again
25:22about multi vessel versus
25:25you know on support,
25:28and also other
25:30mechanical interventions in patients who
25:32have for example severe tricuspid
25:34regurgitation,
25:35inotropes and vasopressors, how should
25:37they be using a platelet
25:38agents and the use of
25:40pulmonary artery catheters.
25:42And of all of these,
25:43only one of these trials
25:45is going on in the
25:46United States and it's it's
25:47a study that we're running
25:48in the, cardiogenic shock working
25:50group,
25:52on the use of whether
25:53or not we should use
25:54pulmonary artery catheters.
25:56So I'm not gonna go
25:57through this. This is is
25:58all in this review article
25:59from Holger Teals,
26:01from last month in New
26:02England Journal. These are the
26:03actual clinical trials and I'll
26:06just I'll refer back to
26:07some of these as we
26:08move forward. But with regard
26:10to the the study that
26:11we're running,
26:12we've enrolled about a hundred
26:14and five patients
26:15with a target of four
26:16hundred over three and a
26:17half years.
26:18So obviously, this is not
26:20a way a feasible way
26:22to generate evidence
26:23that is gonna help move
26:25the field forward in a
26:26very rapid way.
26:28So in the United States,
26:30in Europe they seem to
26:31be able to do
26:32trials in shock very quickly.
26:34We cannot do them almost
26:35at all and it's because
26:37they have a different form
26:39of informed consent
26:40in, in Europe than we
26:42have here in the United
26:43States. I'm not saying which
26:44is right or wrong that's
26:45an ethical question, but I'm
26:47just saying the facts. We
26:48do have here in the
26:50United States a pathway to
26:52to mimic what they do
26:53in Europe which is called
26:54Efic, which is an exemption
26:56from informed consent.
26:57This is a very arduous
26:58process to get
27:00approved to do studies in
27:02this domain
27:03and in fact in the
27:05history of the FDA which
27:07last is about forty to
27:08fifty years, there's only been
27:10forty studies that have been
27:11done under EPIC and these
27:13are generally small trials and
27:15as you can see,
27:17the the ones where they've
27:18I mean, these are numbers.
27:19Like here, this is one
27:20one two two. So we're
27:21talking very small numbers,
27:23but, with, with traumatic brain
27:25injury,
27:26hemorrhagic shock, and out of
27:28hospital cardiac arrest is the
27:30are the ones that have
27:31received,
27:31the most, success in this,
27:34in this arena.
27:35So is it really realistic
27:37to rely on randomized trials
27:39to generate results
27:40that will significantly
27:41influence clinical practice for the
27:43care of these patients? I
27:45think the answer obviously is
27:46no. We can't, you know,
27:48at the pace that we're
27:49able to enroll patients,
27:50we're not gonna be able
27:51to do to, to do
27:53that.
27:54So what are the alternatives?
27:56The alternatives
27:59is, one question is, is
28:01there a significant role of
28:02registries
28:03in advancing the care of
28:05patients with cardiogenic shock?
28:07And right now,
28:09there are five,
28:10different well known registries that
28:12are that are active.
28:15There's the NCSI,
28:16National Cardiogenic Shock Initiative which
28:18was really the first one
28:20that really kinda kicked off
28:22kicked us off
28:24to to starting to collect
28:25data systematically in cardiogenic shock
28:28and I'll talk a little
28:28bit more about this
28:30in a minute because it
28:31also
28:33proposed not only
28:37not only advocate collecting data,
28:39but it also advocated how
28:41to treat patients.
28:42And I'll talk about that
28:43in detail in a second.
28:45There's the recover three registry
28:47from that Abiomed
28:49collected,
28:50And then we started the
28:51Cardiogenic Shock Working Group,
28:53which is really a mastermind
28:55and led masterfully by Navin
28:57Kapoor.
28:58And then there's the cardiac
28:59the cardiac critical care network
29:01that was launched after that
29:02and now the American Heart
29:04Association has a, has a
29:06registry that's ongoing.
29:07And these these registries we
29:09have,
29:10the the, Recover three and
29:12NCSI are relatively small.
29:14In Cardiogenic Shock Working Group,
29:15we have about fifteen to
29:17twenty thousand patients
29:18and c three t n
29:19and also on the range
29:21of fifteen thousand patients.
29:22So there's a lot of
29:23data being collected.
29:26C three t n has
29:27started publishing.
29:28Has not published anything yet
29:30despite having about twenty thousand
29:32patients
29:33and so they're now getting,
29:35they're getting up and, and
29:36running on that front as
29:37well.
29:39So what I do wanna
29:40talk about a little about
29:41about the NCSI initiative which
29:43really did launch a lot
29:44of this
29:45And, this is the algorithm
29:47that they recommend
29:48treating patients with cardiogenic shock.
29:51And I'm not gonna go
29:51through this in detail other
29:53than to highlight three points.
29:55One, is that they advocated
29:56for early use of mechanical
29:58support specifically Impella.
30:00Two, they advocated for the
30:02use of right heart cath
30:03to guide the therapy so
30:04that you know where you
30:05are,
30:06in the therapy in in
30:07in the where the patient
30:09is in his hemodynamic status
30:11and, and lastly
30:13they,
30:13advocated for totally weaning inotropes
30:16and pressers and that may
30:18seem counterintuitive
30:19but we'll go into a
30:20little bit now of why
30:21that is. So let's look
30:22at is there any foundation
30:24for this? We don't have
30:26randomized
30:26data
30:27when this was started
30:29or any of this, but
30:30there were some theoretical foundations.
30:32First of all, with regard
30:33to the use of right
30:34heart cath,
30:36you know, in the late
30:37two thousands,
30:39there was a bunch of
30:40data that said you should
30:41not use right heart caths
30:42in the intensive care unit
30:43and that killed the right
30:45heart cath for,
30:47for several,
30:48for for a decade.
30:50But as we started treating
30:52more and more patients with
30:53cardiogenic shock
30:54and kinda really appreciating that
30:57we didn't know what we
30:57were doing when we didn't
30:58have a right heart cath,
31:00you know, there was there
31:01was more in there was
31:03renewed interest in this and
31:04we started using it again.
31:06And this is from the
31:07cardiogenic shock working group and
31:09we characterized
31:10patients who were treated without
31:12any hemodynamic
31:13invasive monitoring,
31:15were treated with partial information,
31:17and were treated with complete
31:18information.
31:19And what you can see
31:20here, the the focus here
31:22is this is the bottom
31:23line here is in this
31:24bottom right corner,
31:25which is in patients who
31:27present with a more severe
31:29shocks stage d and e,
31:32and even to a certain
31:33extent
31:34stage c,
31:36the more information you have
31:38about hemodynamics
31:39the lower the mortality.
31:40This is registry data. This
31:42is not randomized data again,
31:43but this is the kind
31:44of level of evidence that
31:45we have.
31:46What about,
31:47the MCS? So when we
31:50started when NCSI started, we
31:52didn't have a lot of
31:53information about Impella, but we
31:54knew a lot about the
31:55physiology of this. And this
31:56is really what, and it's
31:58important I think to understand
32:00the physiology of these devices.
32:02This is what an Impella
32:03basically does. This is the
32:05the green is the shock
32:07pressure volume loop. When you
32:09initiate
32:10support with an impeller,
32:11first you unload the ventricle,
32:13the wedge pressure goes down,
32:14the end diastolic pressure goes
32:16down. The loop changes from
32:17a rectangle to more triangular
32:19because these devices are always
32:21pulling volume out of the
32:23ventricle.
32:24So the trajectory the volume
32:25trajectory is always in a
32:26negative direction.
32:28They reduce that that area
32:30of this this pressure volume
32:31area which is the oxygen
32:33consumption.
32:34So these devices reduce oxygen
32:36consumption
32:37and of course importantly they
32:39have the potential to take
32:40over for the work of
32:41the heart. Here you see
32:42this phenomenon that we call,
32:44aortic ventricular pressure uncoupling.
32:47So the aortic valve is
32:48closed the venture the ventricular
32:50pressure goes down, aortic pressure
32:52goes up, aortic valve is
32:53closed
32:54and the the impeller is
32:55doing the work. Now the
32:56degree of uncoupling that you
32:57get depends on the on
32:59the, flow of the device
33:02and the degree of of
33:03a ventricular
33:04compromise. So you don't always
33:05get this.
33:07Those of you who treat
33:08LVAD patients see this all
33:09the time. This is the
33:10identical physiology.
33:13You you see patients without
33:14a pulse. This is the
33:15same. This is exactly what's
33:16happening, with the durable durable
33:19LVAD.
33:20So that's what we knew
33:22at the time
33:23when NCSI was getting started
33:24and it made it made
33:25sense.
33:26Now here's what happens with
33:28when you use when you
33:29use inotropes and pressors.
33:31On the left side you
33:32see the pressure volume
33:34loops and the per as
33:36you give an inotrope and
33:37a pressor, you're obviously increasing
33:39pressure, you're increasing
33:40the work that the heart's
33:41doing, you're increasing the cardiac
33:43output. But you see on
33:44the right side the metabolic
33:46consequence.
33:47And this is that pressure
33:48volume area and this is
33:49the oxygen consumption.
33:51And you can see with
33:52relatively modest increases in contractility
33:55and cardiac output, you're markedly
33:57increasing the myocardial oxygen consumption.
34:00And that was what we
34:01really think is the negative,
34:03aspects of of, of inotropes.
34:07So this is a,
34:09a plot of the cardiac
34:10power output.
34:12This is from the original
34:13shock trial. This is CPO
34:14and maybe you're using this
34:16in your clinical practice in
34:17your treatment.
34:18CPO and this is in
34:19hospital mortality.
34:21Normal cardiac power output is
34:22about one watt
34:24and as the watts wattage
34:26goes below about point seven,
34:27the mortality
34:28starts really increasing dramatically.
34:30So in the NCSI what
34:32they did was they created
34:34this plot but divided the
34:36patients between whether they needed
34:38zero inotropes or one or
34:41two or more. And what
34:42you can see is
34:44the less inotropes support that
34:46the patient needs the the
34:47better the mortality. Now, they
34:49try to make the argument
34:50that this means that inotropes
34:52are bad which obviously this
34:54does not. This just means
34:55that patients who are sicker
34:57need more inotropes.
34:58But nevertheless,
35:00this does serve as an
35:02interesting prognostic
35:04bedside
35:05tool that you can use
35:06because they just created this
35:08matrix where you have the
35:09number of inotropes patients on
35:10the cardiac power output
35:12and you can see this
35:13is while on support, you
35:15can see the patients,
35:16odds of of survival.
35:18So even though it doesn't
35:20say that drugs are bad,
35:21we do think we think
35:22that drugs are bad. And
35:24in fact, there are three,
35:26there are three trials of
35:28those that I mentioned that
35:29are looking at at drugs.
35:31And in fact the one
35:32that's most relevant is the
35:34follow-up of the DO RE
35:35MI trials called the capital
35:36DO RE MI two trial,
35:38which is looking at dobutamine
35:40or milrinone versus placebo.
35:42A very brave trial.
35:44It's really we thought that
35:45it would be finished by
35:46now, but it they have
35:47not yet completed enrollment. This
35:49is being done in Canada.
35:53Now if I can just
35:54put the
35:56the NCSI
35:57algorithm
35:58into physiological terms, what you're
35:59gonna see on the next
36:01slide are the pressure volume
36:02loops
36:03and on the left and
36:05the and the oxygen consumption
36:07stuff on the right of
36:08putting that protocol into action.
36:11And you'll see really what
36:12I think what the, the,
36:15the physiological
36:16advantage of that protocol.
36:18So we're gonna start with
36:20a patient who's in shock
36:22on inotropes.
36:23So here we this patient
36:24now is on inotropes. This
36:26is obviously simulations, but the
36:28idea.
36:29And now the first thing
36:30that we're gonna do is
36:31put the Impella in and
36:32what the Impella does is
36:34unload the heart and reduce
36:36the oxygen consumption
36:38by a certain amount because
36:39of the unloading that it
36:41provides.
36:42And now the next thing
36:43that we're gonna do here
36:45is now we're gonna do
36:46the other part of the
36:47protocol which is to withdraw
36:49the inotropes and pressors.
36:51And what you're gonna see
36:52here is that the main
36:55in terms of
36:56metabolic benefit, the main benefit
36:58of this protocol
36:59is the withdrawal of the
37:01inotropes and pressors. It's not
37:02necessarily the Impella itself which
37:05does provide some unloading and
37:06some oxygen saving,
37:08but it's really
37:09the the ability to withdraw
37:10the drugs which you could
37:12not have done if you
37:13did not have the Impella.
37:15So you can think of
37:15the Impella not only as
37:17providing a direct benefit in
37:19terms of unloading, but also
37:21the secondary benefit
37:23by allowing by taking over
37:24for the work of the
37:25heart
37:26allowing you to,
37:28allowing you to, to do
37:29this withdrawal.
37:32Which may be the the
37:33major part of the, of
37:34the benefits.
37:36So this is the NCSI.
37:37They, ultimately,
37:39enrolled, about four hundred patients
37:41in their in their formal
37:43part of their study.
37:44And really the the thing
37:46that they're very proud of
37:47is that the survival to
37:48discharge is seventy percent
37:50which compared historically to about
37:52fifty percent. But we don't
37:54know what the control group
37:55is because this is also
37:56a selected, you know, this
37:57is a selected population,
37:59to begin with.
38:01But nevertheless,
38:02this,
38:03this algorithm,
38:04this effort
38:05really,
38:06spawned a lot of activity
38:08and many other, algorithms have
38:11appeared. This is the iNova,
38:13shock,
38:14initiative.
38:15Their their algorithm it's a
38:17little bit more granular
38:18than the, than the NCSI.
38:21This is their algorithm for
38:22AMI.
38:23They also developed a algorithm
38:25for treating heart failure shock
38:27and you'll see there are
38:28there are a little bit
38:29of differences.
38:31Both of them both of
38:32these algorithms do,
38:34really focus on, or really
38:37emphasize the need to focus
38:38on LV dominant, RV dominant,
38:40or BYV and really advocate
38:42for the use of of,
38:44of right sided support in,
38:46in cases.
38:47And as you saw what
38:48I showed you from shock
38:49working group when the CVP
38:50is elevated,
38:51that obviously has a big
38:52impact on mortality.
38:54And if if you think
38:55about practice, we're least aggressive
38:57about all the hemodynamic parameters.
38:59I think we're least aggressive
39:00about reducing the CVP. You
39:02know, we we had, you
39:03know, we use diuretics,
39:05but, you know, pulling the
39:06trigger on a right heart
39:08support device or on CVVH
39:10or dialysis
39:12takes a lot more. But
39:13that may be some low
39:14hanging fruit,
39:15in terms of, some of
39:16these, aspects.
39:19The NCSI
39:20protocol being,
39:21national also
39:25also fostered this kind of
39:26concept of how do networks
39:28of how the hospitals networks
39:30work together
39:31to triage patients and how
39:33do you know when
39:34if you're if you start
39:35out if in the ambulance,
39:37how do you know which
39:38hospital to go to? And
39:39if you're at a, peripheral
39:41hospital, how do you know
39:42when to transfer? When do
39:43you pull that trigger? So
39:44all of this was I
39:45think really, started,
39:47with
39:48with Bill O'Neil, Bob Herbis
39:50here when they when they
39:51started the NCSI
39:54initiative and it really has
39:56done I think really a
39:58great service and
39:59I think we're we're you
40:01know it's an example of
40:02advancing care I think outside
40:03of the context of a
40:05randomized trial.
40:07So let me talk a
40:07little bit about balloon pumping,
40:10and as we already mentioned,
40:12it's a three
40:14a class three recommendation
40:17again with the key being
40:18don't use it in routine,
40:19don't use it in everyone.
40:20Okay. Well, you shouldn't use
40:21anything in everyone. So that's
40:23not very helpful.
40:25And I'm sure I'm sure
40:26you still I'm gonna take
40:28a guess that you still
40:28use a lot of balloon
40:29pumps
40:30everywhere everywhere in the United
40:31States uses balloon pumps. In
40:33Germany, you can't find a
40:34balloon pump console. In Denmark,
40:36you can barely find a
40:37balloon pump console.
40:38And,
40:40I think that was a
40:40I think that was a
40:41little bit
40:42of a mistake. But nevertheless,
40:44this just shows the physiology
40:45of a balloon pump.
40:47The as a as a
40:49device to improve coronary flow,
40:51it's a very good device.
40:53It augments pressure
40:55during diastole when that's when
40:56coronary flow occurs.
40:58As a mechanical circulatory support
41:00system, it's not that powerful.
41:02There are generally very small
41:04reductions in wedge pressure and
41:06small increases in cardiac output.
41:09And that was really the
41:10basis of this study that
41:12was done in Germany, the
41:13shock one IVP shock one,
41:15which is a hemodynamic study
41:16that showed no hemodynamic benefit
41:18to all commerce. And then
41:20the shock two study which
41:21showed no benefit in terms
41:22of survival when used in
41:24everyone.
41:25But,
41:27everyone everyone has an experience
41:29where balloon pump worked. Right?
41:30Is anyone not having that
41:32that experience?
41:33So when we this was
41:35a study that we did
41:36at Columbia,
41:37led by Rishad Goran.
41:39This is AMI shock patients
41:41and this waterfall plots just
41:43show individual patients
41:44and the effect on cardiac
41:46output. And what you can
41:48see is there are responders
41:50and there are non responders.
41:51In this case, there it's
41:53very symmetrical
41:54with the zero crossing. There's
41:56a zero effect on cardiac
41:57output,
41:58being right in the middle
42:00and and also the the
42:01pattern here being very symmetrical.
42:03So if you take all
42:04these patients together
42:05and average them out, you're
42:07gonna get zero, which is
42:08almost what you get in
42:09almost all trials of balloon
42:11pump that looked at hemodynamics.
42:13The average all pooled the
42:15average increase in cardiac output
42:16is about point three to
42:17point four liters a minute.
42:19And this is basically
42:20probably the reason because there
42:22are responders and there are
42:23non responders.
42:24When you look at heart
42:25failure shock, the picture is
42:27very different.
42:29And,
42:31you see here there are
42:32many in for heart failure
42:33shock, there are many many
42:34more responders
42:35than non responders.
42:36Do we know why? No.
42:38We don't know why. There
42:39have been many many efforts
42:41to understand
42:42to identify who's gonna be
42:44a responder and who's gonna
42:45be a non responder to
42:46a balloon pump, and they've
42:47all they've all failed when
42:49they've been tested prospectively.
42:51This to me was the
42:52best review article that kind
42:53of brought all those data
42:55together
42:56and identified,
42:58phenotypes.
42:59What are the characteristics
43:00tend to be the characteristics
43:01of people who tend to
43:03respond, respond,
43:05you know, heart failure over
43:06AMI,
43:07preserved RV function,
43:09high afterload resistance,
43:11not in,
43:14not
43:14in not in severe
43:18pulmonary congestion.
43:19Also have a relatively, you
43:21know, not a very high
43:22tachycardia.
43:24But when this when all
43:25attempts to,
43:26put this into an algorithm
43:28to say this is gonna
43:29be a responder and that's
43:30not gonna be have have
43:31all failed.
43:33So what we always talk
43:34about is okay, if you're
43:36gonna use a balloon, no
43:37problem.
43:38But you know, have a
43:39right heart cath in, have
43:41a target
43:41and know if the patient's
43:43gonna respond and if they
43:44don't respond,
43:45escalate as soon as you
43:46can. Because time is really
43:49a big problem as what
43:50I already said and we'll
43:51we'll talk a little bit
43:52more about time.
43:54And that's where I think,
43:55some algorithms, some hospitals have
43:58a a, for AMI shock
44:00have a policy
44:02if they initiate
44:03a MCS,
44:04they don't leave the cath
44:06lab until they have reached
44:07a hemodynamic goal with the
44:09device that they've chosen. So
44:10if you choose
44:12balloon pump first, fifteen minutes
44:14later,
44:15not improving,
44:17escalate.
44:17Same thing for Impella. If
44:19you're if you have an
44:20Impella CP and you're not
44:21achieving your goals, escalate either
44:23to VA ECMO or get
44:24your surgeons to do a
44:25five five.
44:27So that is that makes
44:28a lot of sense.
44:29Time is is very important
44:31factor.
44:32What about VA ECMO?
44:35This is the physiology of
44:36VA ECMO which is is
44:38a little bit counterintuitive in
44:39a
44:40way because
44:41VA ECMO diverts blood away
44:43from the heart. It reduces
44:44the venous return to the
44:45heart.
44:46Yet
44:47what we what you see
44:49here on the pressure volume
44:50loops is that the VA
44:52ECMO actually loads the heart.
44:54Even though it diverts away,
44:56Venus return
44:58in the end, the unlike
45:00an impeller,
45:01the VA, the heart itself
45:02has to pump blood from
45:04the ventricle to the a
45:05r artery.
45:06So if the patient's blood
45:07pressure goes up, the heart
45:09is pumping against the higher
45:11afterload pressure and to ink
45:12to,
45:13eject
45:14the the residual venous return,
45:17it has to it will
45:18retain fluid so that it
45:20can achieve that higher pressure
45:21and eject the,
45:23eject the blood. There has
45:24to be a balance between
45:26venous return and and cardiac
45:28output.
45:29And there are many things
45:30that go along with this.
45:31Now not everyone that gets
45:33put on VAICMO
45:34responds like you see here.
45:36Probably about twenty to thirty
45:37percent of patients respond this
45:39way and that's why we
45:40need unloading strategies.
45:42But there are many things
45:43that go together with this
45:45loading and lack of aortic
45:46valve opening or reduction in
45:48aortic valve opening that I'm
45:49sure that you're all aware
45:50of. This is an aortogram
45:53of a patient on VA
45:54peripheral ECMO
45:55and you see the dye,
45:57injected into the or never
45:58gets below the diaphragm. So
46:00the superior part of the
46:01body is perfused from the
46:03heart,
46:04the inferior parts perfused from
46:05the ECMO.
46:07So if the patient is
46:07in pulmonary edema,
46:09you're perfusing the brain with
46:11deoxygenated blood and you know
46:12how that you can use
46:13near infrared spectroscopy,
46:15right radial artery oxygen saturations
46:18to really look and see
46:19if you're in this situation.
46:21But also going along with
46:22this is a more extreme
46:24example where the aortic valve
46:25is not even opening. And
46:27that then becomes in my
46:28mind kind of a medical
46:29emergency in the sense because
46:32aortic valve not opening
46:34goes along with pulmonary congestion
46:37in worsening markedly worsening
46:40or inducing
46:41pulmonary edema
46:43and then also
46:45stasis of blood in the
46:46ventricle,
46:48and development of
46:50of clots in the ventricle.
46:51I don't know if these
46:52videos are oh yeah. So
46:53here's another patient on VA
46:55ECMA completely closed
46:57aortic valve and you can
46:58see the smoke
46:59echogenic smoke in the aortic
47:01and the and the ventricular
47:02and aorta, and then that
47:04can lead to these kinds
47:05of things that you don't
47:06wanna see.
47:07This is a thrombosis
47:09in the aortic root, here's
47:10a completely thrombosed
47:13a completely thrombosed ventricle and
47:15you if this would play,
47:16you would see this the
47:17ventricles kinda quivering around this
47:19complete, you know, thrombus of
47:20the entire the entire ventricle.
47:26So this is the, the
47:27ECLS shock the results of
47:29the ECLS shock study again
47:30run-in Germany,
47:32which was negative.
47:34But, you know, the thing
47:35about both the IBP shock
47:36trial and the ECLS shock
47:38trial is they just use
47:39these devices indiscriminately
47:41without
47:42any bailout, without any
47:44human dynamic guidance, without any
47:47algorithm for how to manage
47:48the patients. And when you
47:49do that, I think you're
47:50gonna get a negative trial.
47:52And you know, I think
47:53what we learned from danger,
47:56which could have been predicted
47:57for for these trials as
47:58well is you you have
48:00to have some guidance on
48:01on how to use how
48:03do you use these devices
48:04properly.
48:08So there are nine ways
48:10to deal with
48:11overload and aortic valve closure,
48:14in in the setting of
48:15ECMO. I'm not gonna go
48:16through this, but it is
48:18relevant to know these these
48:20different ways
48:21and also to know when
48:22they're useful and when and
48:23some of these are certain
48:24circumstances when these are actually
48:26even contra indicated
48:28and is relevant to know,
48:29when especially when they're contra
48:31indicated.
48:32And this is one, one
48:33approach which is most very
48:35popular now which is combining
48:36ECMO with Impella
48:38either as a primary strategy
48:40or going from ECMO to
48:43adding Impella or from Impella
48:45and adding ECMO.
48:47And this just shows that,
48:49from the physiology
48:50perspective you can very easily,
48:53deal with all of the
48:54consequences
48:55of ECMO loading
48:57the with, with an Impella.
49:00And just here's one actual
49:01this is actual patient example.
49:04Patient presented with profound shock
49:06and
49:07a wedge of almost forty
49:09crashed onto ECMO, wedge went
49:11up further and then Impella
49:12CP was put and then
49:14the
49:15the wedge went down markedly.
49:17You don't need a lot
49:17of unloading,
49:19a lot of flow from
49:21the Impella to achieve this
49:22because all you have to
49:23do is balance out the
49:24residual Venus return which might
49:26only be one or one
49:27or one to two liters
49:29a minute.
49:31So this can be very
49:32effective.
49:34There are two studies going
49:35on now that are looking
49:36at loading,
49:37unloading,
49:38strategies for in combination with,
49:41with ECMOBIs again are are
49:42all occurring in, in Europe.
49:45So in the, the last
49:47few minutes,
49:48I just wanna talk about,
49:50you know, what where what
49:52can we in the United
49:53States do
49:54to advance the field?
49:56If we're not gonna be
49:57able to do,
49:59to do randomized trials, what
50:01what can we do? Just
50:02sit back and let everything
50:03happen in Europe?
50:05So there are two reasons
50:06to to do,
50:08to advance the science and
50:09the and the clinical care.
50:11One is to get FDA
50:13approval of new devices
50:15and the other is to
50:16influence the guidelines which are
50:17really in the end
50:19what, you know, practicing clinicians
50:21really look to,
50:22to, you know, to to
50:24guide their what they do.
50:25That's why they're called guidelines.
50:27So,
50:28one example,
50:29that's that's being that has
50:31been initiate initiated by Abiomed
50:34is the what's called the
50:35OASIS,
50:36study registry.
50:38They are educating sites on
50:40twelve core they're actually thirty
50:42one best practices of what
50:43should be done
50:45to when you in the
50:45care of a patient on
50:47Impella.
50:48And of those, they consider
50:50twelve of them them to
50:51be core competencies.
50:53They're they're listed here.
50:56So they're going out and
50:57educating sites,
50:59intensively
51:00about these core competencies.
51:03And, and then they're gonna
51:05do a registry,
51:06to see, if if the
51:08rates of adverse events, can
51:10be reduced
51:11from historical controls.
51:13So that's one part of
51:14it, but I think that
51:15one of our efforts that
51:17we're working on, at CRF
51:19is actually to generate in
51:21parallel to this another,
51:23registry
51:24which is not being educated
51:25on these on these principles
51:27so that we'll have some
51:28kind of a a comparative
51:30group. I'll get a little
51:31bit more into that in
51:32just a minute.
51:33With regard to the development
51:35of new devices, there's a
51:36lot of activity.
51:38And really the, these are
51:40some of the these are
51:41the main ones that are
51:42being,
51:43under development. And the main
51:44reason,
51:45that's motivating
51:47the investment in these developments
51:49is,
51:50in reducing the French size
51:51for the introduction.
51:53So the the goal
51:54of of the industry now
51:56is to reduce French size
51:57and increase the flow capacity.
51:59So,
52:01five five of course is
52:02a surgical a surgical device.
52:05These devices over here are,
52:08are percutaneous
52:09devices. They go in at
52:11a French size of ten
52:12or nine French
52:13and they expand
52:15to a French size of
52:16twenty, two to twenty one
52:17French.
52:18And this the French size
52:20during the deployment
52:21here, during the while they're
52:23working
52:24that dictates their, their flow
52:26capacity.
52:27So these devices have a
52:28flow capacity the they're reported
52:31at,
52:32over five liters a minute
52:33comparable to five five. So
52:35now if these pan out
52:37these are very early,
52:38you would have the potential
52:40to
52:41to provide five five like
52:43support with a percutaneous
52:44device in the cath lab.
52:48So the the if we
52:49think about the development, the
52:51regulatory
52:52development,
52:54these p vads are used
52:55of course in high risk
52:56PCI
52:57and also for cardiogenic shock.
52:59They're used in both in
53:00both settings. In the setting
53:02of high risk PCI,
53:04the regulatory path to get
53:05these approved is relatively straightforward
53:07because they're used in elective
53:09cases. So you can go
53:10to a patient and say,
53:11look, we have a device.
53:12We think it's we think
53:13it's better. We can randomize
53:16you to either the standard
53:17or to the new device
53:18and no problem, those kind
53:20of trials will enroll relatively
53:22quickly.
53:23But for cardiogenic
53:24shock, it's really not not
53:27gonna be the case because
53:28of the urgency of the
53:29situation
53:30and the difficulty of randomizing
53:32patients in the setting of
53:33the urgent of the urgent
53:35setting.
53:36Again,
53:37we don't have this epic.
53:39It's very difficult to obtain,
53:43in in the context of
53:44a of a multicenter
53:46study.
53:47So,
53:48is there what are the
53:49what are the options? What
53:51is what can we do
53:52instead of a randomized trial?
53:54So one thing that we
53:55could do is rely on,
53:58randomized studies conduct out of
54:00the US. We can just
54:01sit back, let everything happen,
54:03but the FDA does not
54:04allow that. In in order
54:05to get devices approved in
54:07the United States, they have
54:08to be tested in patients
54:10in the United States, in
54:11our health care system because
54:13there are
54:14differences in how devices are
54:16used in medical background, medical
54:17therapy and demographics.
54:20You could develop what's called
54:22an objective performance criteria OPC.
54:25This relies completely on historical
54:27data,
54:28But the only data that
54:29we have that's almost it's
54:30not really reliable even because
54:32it was never used for
54:33regulatory purpose is the danger
54:35shock trial. But the danger
54:37shock trial span ten years
54:39during which the device evolved,
54:42practice
54:43evolved, medical therapies evolved.
54:45So we really cannot get
54:46an OPC
54:47from the danger shock trial.
54:50The other alternative is to
54:51develop is to use what's
54:52called an external database,
54:55that could be used with,
54:57for statistical matching
54:58to an industry sponsored single
55:00study, single arm study. And
55:02this is the approach that
55:03we're taking in two different
55:05domains. One
55:07is to try to develop
55:08a control group for the
55:09OASIS study, and the other
55:11is to try to develop
55:12a,
55:13a a control group for,
55:15for, new new new device
55:17development.
55:18So So what is an
55:19external database? It's a database
55:21not collected directly within the
55:23trial protocol,
55:24but used to support compare
55:25enhanced trial data. And there
55:27are many potential sources,
55:29electronic health records,
55:32they're not granular enough where
55:33we we and others have
55:35been using databases like Truveta,
55:37IQVIA, and trying to probe
55:39them
55:40for data of patients in
55:42shock. And it's extremely it's
55:44still extremely difficult to extract
55:46data even with, with with
55:48AI,
55:50natural language algorithms
55:52still very difficult to extract
55:54the granular data that we
55:55need for that.
55:57Claims databases.
55:58Historically,
55:59these were used to to
56:01tell people that Impella was
56:03bad. There were two two
56:05important two studies that were
56:06published
56:07using electronic,
56:09health records
56:11and claims data.
56:12The set the third one
56:14that that concluded that Impella
56:15worsened outcomes.
56:17And,
56:18these were published in high
56:19profile journals
56:20and, and gave a lot
56:22of angst to a lot
56:23of people including the FDA.
56:25But they turned out to
56:26be wrong.
56:27Registries.
56:29So registries,
56:31disease specific or treatment specific
56:33databases
56:34that exist. So for example,
56:35could we use the cardiogenic
56:37shock working group or the
56:38working group? The answer is
56:40no. Not for regulatory purposes.
56:42These are not calc these
56:43are not these databases are
56:45not collected
56:46with the rigor,
56:48the regulatory rigor that's required
56:50to to submit to regulatory
56:52agencies.
56:53Historical controls don't work and
56:55really what all we're left
56:57with really is this real
56:58real world, evidence.
57:00So this is what we
57:01are, this is what we're,
57:03kind of pursuing now. We're
57:04in the early stages of
57:06of developing this.
57:08One of the things that
57:09we wanna do differently than
57:10all the other registries is
57:12to provide funding to the
57:13sites
57:14so that they have the
57:15appropriate resources to collect the
57:17appropriate data. That's the difference
57:18between industry led,
57:20registries
57:21and industry led studies
57:24or trials
57:25and these other registries like
57:26the the shock working group,
57:28the c three t n.
57:29Those are almost charity on
57:31parts of the, of the
57:32investigators. There's they're they're very
57:34underfunded.
57:35They have huge amounts of
57:37missing data and they're not
57:38useful. So that's the number
57:39one thing that we're gonna
57:40try to
57:42to overcome by getting sufficient
57:43funding
57:44to to reimburse sites to
57:46collect the right the proper
57:48data.
57:49We need to you know
57:49we're we're developing inclusion exclusion
57:52criteria that parallel
57:53what what they would, be
57:55required
57:56in a, in a in
57:58a regulatory trial.
57:59We're gonna use case report
58:00forms, electronic medical records, and
58:03we're also collaborating closely with
58:05the FDA
58:06to prospectively
58:07define statistical,
58:09approaches that will allow
58:11using these two databases to
58:13be, to be used. And
58:14there are various
58:15statistical approaches of propensity matching,
58:18and and Bayesian approaches,
58:21that we're working with, you
58:23know, with statisticians,
58:25and working closely with the
58:27FDA on these, on these
58:28efforts.
58:30So,
58:31can't believe that I fit
58:33in a hundred slides in
58:34less than fifty minutes.
58:36And,
58:38just wanna emphasize
58:39one more thing. This is
58:40from, again, from the Schacht
58:41working group, the issue of
58:43time.
58:44So what really what happens,
58:47the course of the patient,
58:50if you just look at
58:51these,
58:52plots,
58:54a lot of most of
58:55the action is is very
58:56early, the first six hours.
58:59And after the first six
59:01hours, the course I mean,
59:02there are there are, you
59:02know, there are some movement
59:03between
59:04between,
59:06stages here. And this is
59:07these are the sky stages
59:09and these are the phenotypes
59:10that I showed you at
59:10the beginning.
59:11But most of it is
59:13really determined,
59:14at the from the first
59:15six hours.
59:16So time is important.
59:18This really,
59:20feeds heavily into
59:22especially when you're developing,
59:23algorithms for systems of care
59:26and how you deal with
59:27patients,
59:28transfer,
59:29and and resource allocation at
59:31the peripheral sites.
59:33So
59:34and then I'll just leave
59:35you with this, this one
59:37image here of the the
59:38shock working group app,
59:40which has a lot of
59:41resources
59:42about,
59:43you know, staging, helping to
59:45stage and phenotype patients giving
59:46prognostic information.
59:48We have the congestion profile
59:50tracker which allows you to
59:51track a patient where they
59:52are in their CVP
59:54wedge
59:54profile.
59:56And
59:57this is a it's been
59:59helpful especially when sites are
01:00:01just initiating their
01:00:03their programs.
01:00:04So with that, I covered
01:00:05a a huge amount of
01:00:06ground.
01:00:07Didn't there's a lot that
01:00:08I didn't cover, of course.
01:00:09It's a huge field right
01:00:11now. A lot of lot
01:00:11of things happening and a
01:00:13lot of opportunities to, to
01:00:15be involved with advancing the
01:00:16field. Thank you.
01:00:25So,
01:00:27as I walk up to
01:00:28give the mic,
01:00:29quick question.
01:00:31You know, it really was,
01:00:32first of all, fantastic talk,
01:00:33and thank you and a
01:00:34wonderful way to celebrate
01:00:36Woody's achievements in in in
01:00:38our program.
01:00:39I I guess I wanted
01:00:40to ask you around
01:00:42this concept of the of,
01:00:45not leaving the lab
01:00:47until you have a hemodynamic
01:00:49target that's been met.
01:00:51And
01:00:51in that process, do we
01:00:53know whether we can predict
01:00:56those individuals that are going
01:00:58to fail
01:01:00CP and go to five
01:01:01point five quicker? Because we
01:01:03are seeing within our own
01:01:04organization
01:01:05a rapid increase in five
01:01:07five use.
01:01:08And and I'm just curious
01:01:09if you if anyone's evaluated
01:01:11that yet or you have
01:01:12any thoughts about what could
01:01:14be predictors.
01:01:15Yeah.
01:01:16So the five five use,
01:01:18what what I see is
01:01:20is
01:01:21is largely in the heart
01:01:22failure community as opposed to,
01:01:24let's say, the AMI.
01:01:27And, those tend to be
01:01:29more elective,
01:01:30not as urgent. Oh, wow.
01:01:32And,
01:01:34that's,
01:01:35at least
01:01:36at Columbia This morning during
01:01:37the COVID station, we bought
01:01:39a house and
01:01:40our heating went down.
01:01:42Okay. Hot water and and
01:01:44heating.
01:01:45The AMI patients tend to
01:01:47tend to be treated obviously
01:01:48in the lab, and that's
01:01:49really where this don't leave
01:01:50the lab until you're moving.
01:01:52I shouldn't maybe say reach
01:01:54the target, but moving towards
01:01:55the target that you see
01:01:56that there is a benefit.
01:01:57We don't know. There is
01:01:58no way right now to,
01:02:00to predict who's gonna need
01:02:02escalation.
01:02:04But,
01:02:05you know, if they leave
01:02:06the lab successfully, who's gonna
01:02:08need escalation later? We don't
01:02:09really have an index of
01:02:10that. People have looked at
01:02:11things like the cardiac output
01:02:13deficit. So you calculate
01:02:15you you look at the
01:02:15cardiac output.
01:02:17You say, you know, you
01:02:18say the patient needs a
01:02:20cardiac index of two point
01:02:21five, and then you subtract,
01:02:22and you say, okay. I
01:02:23need this many liters a
01:02:24minute. So that would that's
01:02:26one way
01:02:27that people have tried to
01:02:28look at, but it hasn't
01:02:29been very, hasn't been very
01:02:31helpful, has not proliferated.
01:02:34But, really, the main the
01:02:36main escalation in the lab
01:02:37is either from a CP
01:02:39to a CP plus an
01:02:40RP, so that CVP
01:02:42monitoring that or to a
01:02:44from a CP to a
01:02:45CP plus ECMA.
01:02:47Those are the usual in
01:02:48the lab.
01:02:51Thanks so much.
01:02:53You know, as an interventionalist,
01:02:55I think, or even as
01:02:56physicians, right, the do no
01:02:57harm versus benefit. And, obviously,
01:02:59you know, I think we
01:03:00will address a lot of
01:03:01those when you get to
01:03:03smaller devices. Right? A lot
01:03:04of the harm is due
01:03:05to vascular injuries or stroke
01:03:06or other things. I think
01:03:08that the challenge that that
01:03:10we face a little the
01:03:11a little bit or when
01:03:12I look at what the
01:03:13recommendations
01:03:14are
01:03:15is is the evidence
01:03:17for
01:03:19putting a large
01:03:21device
01:03:22in the femoral artery
01:03:23before you've even opened up
01:03:25the coronary.
01:03:27We know you know, I
01:03:27can tell you in our
01:03:28lab, it takes much longer
01:03:30to put in an impeller
01:03:31than it does to open
01:03:32up a coronary. And we
01:03:33also clearly have good evidence
01:03:36that, you know, the quicker
01:03:37you open up the coronary,
01:03:38it's beneficial. If you go
01:03:39radial, it's beneficial.
01:03:41And I've struggled to find
01:03:43sort of good data that
01:03:46has said
01:03:47it is clearly
01:03:48better to go
01:03:51upfront
01:03:52and put this in and,
01:03:53you know, we you you
01:03:54know, your patient comes in
01:03:55Sure. Chest pain, ST elevations,
01:03:57arrests,
01:03:59gets gets shocked, is on
01:04:01some epi, comes up to
01:04:02the lab. My read of
01:04:03it is you should put
01:04:04an Impella in first of
01:04:06of a lot of what
01:04:07it is. But I can't
01:04:08find anything that said we've
01:04:10looked at just opening up
01:04:11this coronary, which will take
01:04:13five, ten minutes. And then
01:04:15Yeah. And then evaluating. And
01:04:16I'm and I'm that's where
01:04:17I think a lot of
01:04:18interventionalists
01:04:20have the the challenge of
01:04:21telling us to sort of
01:04:22do that other piece different.
01:04:24And I wonder if you
01:04:24could help us there as
01:04:26we work towards that. Yeah.
01:04:26I don't think I don't
01:04:27the the algorithms,
01:04:31are
01:04:32are less specific
01:04:34about Impella first or artery
01:04:35first.
01:04:36Obviously, we're gonna have the
01:04:38DTU, the door to unload
01:04:39is gonna be presented at
01:04:40ACC.
01:04:42So maybe that's it's a
01:04:43different population.
01:04:45It's, you know, who knows,
01:04:47what what that will show
01:04:48and and what its implications
01:04:50would be for, for cardiogenic
01:04:52shock.
01:04:54In danger,
01:04:55I don't know the numbers
01:04:56off the top of my
01:04:56head. There were a certain
01:04:57number of patients that were
01:04:59that were Impella was put
01:05:00in first, and there was
01:05:01a certain percentage that were
01:05:03where it,
01:05:05it, was put in after.
01:05:07I think
01:05:08if I I I really
01:05:09don't wanna misquote it, but
01:05:10I don't think the numbers
01:05:12are small, but I don't
01:05:13think there was a difference
01:05:14in the outcomes if it
01:05:16was put in before or
01:05:17after.
01:05:17That paper either is should
01:05:19be coming out or is
01:05:21out. I don't I don't
01:05:22remember that. Maybe someone else
01:05:23is it out already? I
01:05:24don't even know.
01:05:28Yeah.
01:05:29Similar. Disparison out. Yeah. And
01:05:32it didn't if you look
01:05:33at the forest plots in
01:05:34the, in the appendix, they
01:05:35they didn't matter. They formed
01:05:37the forest.
01:05:42Yeah. Yeah. Also,
01:05:45I don't think if I'm
01:05:46not mistaken, correct me, if
01:05:47if you if you go
01:05:48below nine if you could
01:05:49get your artery open in
01:05:50less than ninety minutes, that
01:05:52doesn't matter either. So ninety
01:05:54minutes, you know, was that
01:05:55cutoff that was established, like,
01:05:56ten years ago or whatever.
01:05:58And all the data show
01:05:59it doesn't matter if it's
01:06:00sixty minutes or ninety minutes,
01:06:01didn't really make a difference.
01:06:03So it's not the that
01:06:04that delay doesn't really,
01:06:07you know,
01:06:09concern me. Also,
01:06:10the other thing that I've
01:06:11that I think that these
01:06:12are a little bit anecdotal,
01:06:13but I think if you
01:06:14have a patient with, like,
01:06:15refractory VF,
01:06:16if they're unloaded,
01:06:17they seem that seems to
01:06:19reduce the the the fibrillation
01:06:21threshold.
01:06:22And that also makes a
01:06:23physiological
01:06:24sense, less stress on the
01:06:25myocardium
01:06:26that, you know, they can
01:06:27they can be defibrillated. So
01:06:28there's all sorts of scenarios.
01:06:31Dan, one last question. Perhaps
01:06:32maybe two last questions. Tara
01:06:34and then Al, then we'll
01:06:35close it up with the
01:06:36last time. Doctor. Bercow, thank
01:06:37you so much for excellent
01:06:39talk. I have two quick
01:06:40questions. So you had alluded
01:06:41to the fact that
01:06:43inotropes,
01:06:44they improve hemodynamics, but they
01:06:47increase myocardial oxygen
01:06:49demand.
01:06:50So should we be
01:06:53telling people to use less
01:06:54inotropes
01:06:56even if they're improving hemodynamics?
01:06:59And the second question is
01:07:01that why have inotropes
01:07:02like
01:07:03Omacamta, for example, that do
01:07:06improve hemodynamics and they don't
01:07:08have,
01:07:09you know, they don't really,
01:07:10as far as we've been
01:07:11told, increase oxygen requirement.
01:07:14Why have the clinical,
01:07:16outcome studies been so,
01:07:19disappointing?
01:07:22So two
01:07:24should we should we I
01:07:25think that from a physiological
01:07:27perspective,
01:07:29you should reduce inotropes and
01:07:30pressors. I mean, think about
01:07:32AMI.
01:07:33Beta blockers are class one
01:07:34indication in AMI
01:07:36because
01:07:37they reduce infarct size, they
01:07:38reduce oxygen consumption, they reduce
01:07:40heart rate, they reduce mortality,
01:07:43they reduce,
01:07:45incident heart failure,
01:07:46beta blockers.
01:07:47So now we're talking about
01:07:49AMI, and we're we're doing
01:07:50AMI shock, and we're doing
01:07:51the opposite. We're doing so
01:07:53it does does not make
01:07:54sense to use inotropes in
01:07:55that setting. We know that
01:07:57inotropes increase in farc size.
01:07:59So it makes it makes
01:08:01indirect sense, let's
01:08:03say, that we we should
01:08:04not be using inotropes, but
01:08:05you have to. You have
01:08:06no choice. Right? Because you
01:08:07you've gotta get the blood
01:08:08pressure up until you have
01:08:09an alternative,
01:08:10which is what MCS mechanical
01:08:12support devices give you an
01:08:13alternative.
01:08:14So I think that is
01:08:15the right thing.
01:08:17Now why do inotropes increase,
01:08:19oxygen consumption? It's mainly because
01:08:21of their impact on calcium.
01:08:24It's the SR ATPase.
01:08:27The way inotropes work is
01:08:29number one, by increasing calcium,
01:08:31and that has to be
01:08:32sequestered by the,
01:08:34circuit two a, which ATP
01:08:36requirement. That's the major part.
01:08:38It's the there's additional
01:08:39work that is being done,
01:08:40but the main thing is
01:08:41really the the, the circuit
01:08:43two a. So if you
01:08:44have a a drug that
01:08:46does not increase that increases
01:08:48contractility
01:08:49without increasing,
01:08:51calcium,
01:08:52then that would be theoretically
01:08:53beneficial,
01:08:54but that has not been
01:08:55tested yet.
01:08:59So question. You showed just
01:09:00CVP is an important predictor
01:09:02of outcome, and then you
01:09:04talked about pressure volume loops
01:09:06looking at sort of work
01:09:07and demand.
01:09:09So how do you
01:09:11see pressure volume loops coming
01:09:12to play
01:09:13in the sort of adjustment
01:09:15or management
01:09:16of unloading?
01:09:19Well, I think I think
01:09:21that pressure volume loops can
01:09:22be helpful at the bedside.
01:09:25And,
01:09:28but there's a long way
01:09:29to go to get there.
01:09:30First, we have to develop
01:09:32techniques where we can actually
01:09:33display them at the bedside
01:09:34in the intensive care unit,
01:09:36and there are many people
01:09:37working on that. Paul here
01:09:38is here working on that.
01:09:39We're working on it, and
01:09:40there are other people that
01:09:41are working on that.
01:09:43The next thing that the
01:09:44next hurdle we have to
01:09:45overcome is education.
01:09:47So we don't teach we
01:09:48stop teaching physiology
01:09:50overall,
01:09:51but in specific, we stop
01:09:52teaching PV loops. We don't
01:09:54teach them because they're not
01:09:54used clinically,
01:09:56and we don't use them
01:09:56clinically because no one understands
01:09:58them. So we've gotta break
01:09:59that cycle.
01:10:01And I think that the
01:10:02efforts that we're doing,
01:10:04I hope, and all the
01:10:05papers we're writing, the efforts
01:10:07we're doing are are to
01:10:08reintroduce,
01:10:09this education into the the
01:10:11curriculum,
01:10:12hopefully, will go there. But
01:10:13I think what PV loops
01:10:14can do is, number one,
01:10:17in comparison to just looking
01:10:18at signals
01:10:20streaming across the screen, which
01:10:22are gone
01:10:23every thirty
01:10:24seconds, you can put a
01:10:25PV loop on the screen
01:10:26and it could stay there.
01:10:28You can see where you
01:10:29started. You could put a
01:10:30target, and you can see
01:10:31where you are compared to
01:10:32where you wanna be. It's
01:10:34it yet the p d
01:10:35loop, if you really understand
01:10:37it, has all the information
01:10:38from all the numbers that
01:10:40are that are around
01:10:41the the perimeter of the
01:10:43those,
01:10:44those, of those squiggles that
01:10:45are going across the the
01:10:46line. So we have a
01:10:47lot of work to do,
01:10:49but we're trying. I think
01:10:50many people are trying.