Transcript
Speaker: Welcome to Critical Matters, a sound podcast covering a broad range of topics related to the practice of intensive care medicine.
Speaker: Sound provides comprehensive critical care programs to hospitals across the country.
Speaker: To learn more about our programs and career opportunities, visit www.soundphysicians.com.
Speaker: And now, your host, Dr. Sergio Zanotti.
Speaker: In today's episode of the podcast, we will discuss right ventricular failure.
Speaker: Right ventricular failure is a frequent occurrence in critically ill patients, and in many circumstances, it is underdiagnosed and mismanaged.
Speaker: Our guest is Dr. Ryan Tedford, a practicing cardiologist with a focus on heart failure.
Speaker: Dr. Tedford is Dr. Peter C. Gaze Endowed Chair in Heart Failure, a professor of medicine and cardiology.
Speaker: He's the section chief for heart failure, medical director of cardiac transplantation, and director of the Advanced Heart Failure and Transplant Fellowship Training Program at the Medical University of South Carolina.
Speaker: He's a recognized expert in the topic.
Speaker: It is a true honor and pleasure to have him today as our guest.
Speaker: Ryan, welcome to Critical Matters.
Speaker: Sergio, thank you very much for having me.
Speaker: Look forward to the discussion today.
Speaker: Well, it seems that the left ventricle gets a lot of attention all the time, and somehow the right ventricle is a little bit forgotten in the mind of many clinicians.
Speaker: So I thought this would be a great topic for our audience to hear from you and maybe explore right ventricular failure within the context of acute illness in the ICU.
Speaker: For sure.
Speaker: Yeah, the right ventricle has only recently gotten its due, so I look forward to any time I can talk about my favorite ventricle.
Speaker: Awesome.
Speaker: So maybe we can start with a little bit of a historical context.
Speaker: Just tell us, I mean, how initially a lot of people really disregarded the right ventricle's importance, and then why do you think today we should be paying attention to the right ventricle as critical care clinicians?
Speaker: Yeah.
Speaker: Sure.
Speaker: Well, you know, some of this goes back to early animal studies.
Speaker: One that I talk about in our recent review in the New England Journal was done by Isaac Starr, where they essentially ablated the right ventricle.
Speaker: And when they saw that there was not much change in pressures or cardiac output, you know, they really concluded that the right ventricle was less and less important.
Speaker: And then on top of that, we have the development of Fontance, which have been lifesaving therapies.
Speaker: And
Speaker: You know, it showed that people could live without a right ventricle.
Speaker: Yet, you know, what was missing there is that these folks did not have normal functional capacity.
Speaker: And those individuals do okay until the other ventricle starts to fail, and then they get into real trouble.
Speaker: And so, you know, I think because of observations like that, the right ventricle has been less well studied.
Speaker: But now we know that it is a critical determinative outcome in many different ways.
Speaker: diseases, not just pulmonary arterial hypertension, but certainly left heart failure and even COVID-19.
Speaker: So it really now is getting its due.
Speaker: And in terms of acute critical illness, you did mention COVID-19.
Speaker: You mentioned, obviously, left heart failure, which is the most common cause of right ventricular failure.
Speaker: But there's also, I mean, a growing recognition that isolated or predominant right heart failure in different situations also has significant clinical implications.
Speaker: Why do you think it's so important for us as critical care clinicians to pay more attention to this today?
Speaker: Well, I think it's for the reason that you mentioned that we know it's a major, if not the most, certainly a major determinative outcome in a bunch of different conditions.
Speaker: You know, we can think about it as both acute and chronic, and there's a differential diagnosis for both of those.
Speaker: Certainly the one that we think about with acute right heart failure, the most common would be a pulmonary embolism.
Speaker: And we know the right heart doesn't tolerate acute increases in afterload well compared to its counterpart across the septum, which can tolerate increases in load much better.
Speaker: And there's a number of different reasons for that.
Speaker: But those individuals really struggle and require, you know, certainly anticoagulation and sometimes additional therapies to alleviate that clot burden so that the right ventricle doesn't fail.
Speaker: But even in the chronic setting, the RV remains afterload sensitive.
Speaker: And so there's a number of different ways we can think about that and target that when we're thinking about treating the right heart.
Speaker: And I guess the other category that we'll maybe talk a little bit about also is acute and chronic, right?
Speaker: I mean, we see...
Speaker: This and a lot of chronic diseases in the ICU where small changes can really decompensate patients with chronic problems, but understanding how to manage them, in particular with the right ventricular failure, is going to be important for critical care physicians.
Speaker: That's exactly right.
Speaker: You know, on a chronic basis, the RV is able to compensate up to a point where it lacks reserve.
Speaker: And at that point, any further increases in afterload or decreases in contractility really push you over the edge.
Speaker: And those patients obviously become very critically ill.
Speaker: And so it's, you know, how do we recognize that?
Speaker: How do we prevent that tipping point when we're going to manage those patients?
Speaker: Excellent.
Speaker: Well, let's dive into the topic.
Speaker: And I was mentioning before we started recording how much I appreciated your recent review article in the New England Journal of Medicine and the fact that you added a lot of pathophysiology in the appendix.
Speaker: And it just reminded me of my medical student days reading Gaitan and really enjoying Gaitan.
Speaker: learning about how the heart works and the hemodynamic factors that determine function.
Speaker: So why don't we start with pathophysiology, Ryan, and maybe we could start with the hemodynamic determinants of right ventricular function.
Speaker: Sure.
Speaker: You know, when we were writing this review, we initially got a little bit of pushback as we started talking about physiology.
Speaker: And, you know, they wanted it to be a very clinically approachable review.
Speaker: But the argument, of course, is that if you don't understand the physiology, you can't treat these patients because it's all about the physiology.
Speaker: And so we actually use that framework throughout the review when it comes to diagnosis as well as treatment.
Speaker: And so really understanding the physiology is key.
Speaker: And, you know, honestly, just like the left ventricle, the right ventricle has four main determinants of function.
Speaker: Preload.
Speaker: or essentially how much the ventricle is stretched, contractility or inotropy, afterload, the pressure or the impedance against the right ventricle must overcome to eject, and then something called lucidotropy or active relaxation.
Speaker: And it's really those four determinants of function that dictate how the right ventricle is going to do.
Speaker: You can either have too much or too little preload.
Speaker: You certainly can have a decrease in contractility.
Speaker: You can have too much afterload and then impaired lucidrophy.
Speaker: All of those will cause worsening RV function.
Speaker: And it's interesting, I mean, that obviously I think most of us have always thought at the bedside in terms of preload, afterload, and contractility, but lucitrophy is a function that really over more recent, let's say, years in research have really become more interesting for clinicians in general, both on the left and the right.
Speaker: And just as an anecdote,
Speaker: Back in the day when I was doing research, Ryan, I had an animal model of septic shock, and we did a serial echocardiography on septic mice.
Speaker: And what was super interesting is that the main determinant of survival was diastolic function, which I guess is a correlate of lucid trope.
Speaker: So the animals that could dilate their ventricles with fluid load were the ones who were survivors.
Speaker: Yeah.
Speaker: Yeah, you know, I think that makes a lot of sense, and you're right.
Speaker: You know, we talk about contractility and after a little lot in RVPA coupling, but there's increasing work and data from the groups in the Netherlands as well as Germany that suggest RV diastolic function may be, you know, just as important, if not more important.
Speaker: Now, a lot of times, you know, all of these factors coexist, right?
Speaker: If you have RV contractile deficits, you're likely going to have diastolic dysfunction as well.
Speaker: But there are certainly cases where you may have diastolic dysfunction and contractility may be normal.
Speaker: For example, in early heart failure with preserved ejection fraction, and both on the LV and RV side, there's some data to support that.
Speaker: So I think it's something that we're learning a lot more about.
Speaker: We don't have great ways to target that yet, but maybe we will in the future.
Speaker: And I agree with you 100%, especially as intensivist at the bedside.
Speaker: I think that having very firm understanding of basic physiology is going to be critical as we implement, obviously, evidence-based therapies, but in terms of trying to figure out how our patient, individual patient, is responding.
Speaker: And you're right.
Speaker: I mean, I don't see how we could talk about therapy later if we don't focus on preload, afterload, and contractility.
Speaker: I agree with you.
Speaker: Now,
Speaker: Before we go into more of the clinical aspect, I do think that, at least for me, it was a lot of interest, and obviously you are deep into this topic, so this is what you live every day, but you did talk a little bit more about cellular and molecular mechanisms, and I found that all very interesting because it's not something that I have read recently, and without nerding out too much, could you just give us maybe an overview of some of those mechanisms?
Speaker: And I believe those are going to be more important for chronic right ventricular failure, correct?
Speaker: That's right.
Speaker: You know, and I have to, one, give a shout out to my colleague, Evan Britton at Vanderbilt, who is really a leading expert in this and was really this section and the review was his focus and he was very helpful.
Speaker: But it is, you know, very interesting to look at the different aspects.
Speaker: cellular and molecular mechanisms that may contribute to right heart failure.
Speaker: You know, we think about hypertrophy that occurs, fibrosis that occurs, ischemia that occurs due to a number of different factors.
Speaker: When the right heart fails, the neurohormonal system gets activated.
Speaker: We see inflammation and there's shifts in the metabolic substrate from using fatty acid oxidization, the switch over to using glucose.
Speaker: So a lot of different mechanisms play a role.
Speaker: I think some of the other kind of fascinating and more recent findings is insulin resistance that may occur in these individuals and also the impacts of obesity.
Speaker: One of my former colleagues, Kavita Sharma, has shown us that in obese HEPP patients, for example, they have intrinsic ventricular dysfunction compared
Speaker: to their non-obese counterparts.
Speaker: So if you develop pulmonary hypertension, you're just not going to be able to tolerate that as well if you have a contractile deficit.
Speaker: So these are all very important factors when we think about the different mechanisms that are contributing to right heart failure.
Speaker: Many of these patients will have a sleep disorder of breathing, and that can cause hypoxia and also change the molecular phenotype that may be happening in the right ventricle.
Speaker: Excellent.
Speaker: And as we mentioned, these are probably very critical to understand in terms of chronic development, but also I would imagine that in terms of long-term therapy, these are all going to be targets of research of new maybe drugs in the future and of current drugs.
Speaker: So I feel that it's something that worthwhile discussing even if briefly.
Speaker: Yeah, we certainly, right now, a major element of need is a drug that targets the RV myocardial function, both systolic and diastolic.
Speaker: Most of our therapies are aimed at amelioration of afterloads.
Speaker: But, you know, that's only part of the story, as we've talked about.
Speaker: So the more we understand the pathophysiology here, the more we understand these molecular mechanisms, the more we should be able to target the myocardium itself and make advances forward.
Speaker: Absolutely.
Speaker: So let's talk a little bit about diagnosis and evaluation in terms of, like we mentioned, there's chronic right heart failure, which is something that you encounter in the outpatient setting.
Speaker: But considering our audience, I want to focus on when should we be thinking and how should we work up a suspected right ventricular failure in acute situations or acute and chronic situations in the ICU?
Speaker: Okay.
Speaker: Well, you know, it starts, of course, with a thorough history and physical exam.
Speaker: Nothing really replaces that.
Speaker: You know, in history, in the ICU, it's going to be a little bit more apparent, but, you know, we're looking for signs that they've had, you know, exertional dyspnea for a period of time.
Speaker: They have abdominal fullness.
Speaker: They may be tachycardic.
Speaker: They may have early satiety.
Speaker: A lot of those type of symptoms can give you a hint that the right ventricle may be impaired.
Speaker: Your physical exam, though, is going to be very helpful, of course.
Speaker: The best physical exam tool that we have is to look at the jugular venous pressure.
Speaker: And we can do that either just by visualization or with a direct measurement if we're in the ICU.
Speaker: Listening to the heart for a loud second heart sound may suggest pulmonary hypertension.
Speaker: You know, having a palpable and pulsatile liver would suggest, again, right ventricular dysfunction or tricuspid regurgitation.
Speaker: And, of course, things like ascites and lower extremity edema.
Speaker: All of those can be very helpful.
Speaker: Our basic diagnostic tools then, looking at electrocardiograms, and then what's really the best screening tool we have, echocardiography.
Speaker: And that's really going to help describe to us how sick the right ventricle is and if it's involved.
Speaker: Before we talk a little bit more about echocardiography in the setting of the ICU, what are some biomarkers or EKG findings that we should be attentive to when we're evaluating these patients?
Speaker: Well, the EKG, if the right ventricle is very dilated, well, first and foremost, probably the most sensitive is just sinus tachycardia, you know.
Speaker: There was a colleague of mine who used to say sinus tachycardia scares me the most of any arrhythmias because I don't know what to do with it.
Speaker: it's usually a sign of something ominous.
Speaker: And so sinus tachycardia to begin with, we certainly can see right axis deviation, right atrial dilatation, or evidence of right ventricular hypertrophy.
Speaker: All of those may suggest that the right ventricle is in trouble.
Speaker: Now, completely perhaps separate would be, you know, a right-sided myocardial infarction.
Speaker: And there are
Speaker: you know, characteristic EKG findings of that.
Speaker: But if we're talking more just identifying in the sick shock patient is the right ventricle at play, those signs that I mentioned can be helpful.
Speaker: Biomarkers, we have, you know, brain enterotic peptide is a sensitive biomarker.
Speaker: It doesn't really differentiate between left and right-sided heart failure.
Speaker: But it's also not specific because other things can contribute either to levels that are higher, for example, in sepsis.
Speaker: As you probably know, Sergio, it can be elevated.
Speaker: But also other factors like obesity can actually cause a relative lower BNP for the degree of heart dysfunction that you have.
Speaker: Absolutely.
Speaker: And I think that also, obviously, like troponin could be helpful in the right context.
Speaker: Now, it's also nonspecific for the right ventricle.
Speaker: But if you're suspecting PE, any of these biomarkers, if elevated, should make you think that there might be RV dysfunction.
Speaker: Yeah, so troponin, of course, is not specific for acute coronary syndrome, and you're exactly right, in pulmonary embolism.
Speaker: One of my former colleagues, Tom Metkiss at Johns Hopkins, has done a lot of work in RV protective strategies in ARDS, and in fact, has shown that, of course, the higher the troponin, the worse your outcomes.
Speaker: And so a lot of that, we were actually related back to the right ventricle and how stressed it was.
Speaker: So
Speaker: Certainly a troponin can be helpful in terms of prognosis.
Speaker: And the other thing I wanted to ask you, Ryan, before we dive into echocardiography is, I know that in your review, you talk a lot about MRI a lot.
Speaker: And it's kind of like the, it seems that there's a lot of amazing things you can measure with cardiac MRI these days, but I've never seen it used at the ICU.
Speaker: And that I presume is for logistical reasons.
Speaker: But is that something that you think might be coming to an ICU soon?
Speaker: Yeah.
Speaker: You know, the MRIs still take a lot of time, and they're excellent tools.
Speaker: We can certainly learn a lot from an MRI, but I think typically, you know, folks are critical in the ICU.
Speaker: They just don't tolerate, you know, the MRI problems.
Speaker: Don't tolerate being in the MRI suite that long for various reasons.
Speaker: We certainly do it, you know, thinking about in our left heart failure world for patients that are sick that we think may have, you know, active cardiac sarcoid, for example, or myocarditis will work to try to get an MRI.
Speaker: You can obviously do it when the patient's intubated, but they need to be somewhat stable.
Speaker: But, you know, some of the things we're finding on MRI is a little bit more subtle, and I think it's more useful in more of the outpatient evaluation, with a few exceptions, like I mentioned.
Speaker: But, you know, really for the inpatient, we're going to have our invasive hemodynamics, and we're going to have our echocardiography.
Speaker: We really didn't talk about the gold standard, which, of course, is pressure volume assessment, and, you know, a lot of my research has been in PV loops.
Speaker: These are really elegant,
Speaker: type of measurements that can be used to assess the right ventricle, and they can detect abnormalities that you wouldn't detect by MRI and echo.
Speaker: For example, we showed that in patients with systemic sclerosis, these individuals have RV dysfunction out of proportion to their afterload increases, and this was very different from idiopathic pulmonary arterial hypertension patients.
Speaker: We've also used these techniques to show that women tend to have better contractile function than men.
Speaker: But, you know, these are, again, a little bit more in a research setting.
Speaker: There are surrogates that are being developed, kind of less invasive approaches, single-beat approaches that might be used clinically down the road once those are a bit more standardized.
Speaker: But, you know, the question is how do we relate that gold standard then to our more clinically approachable metrics that we have with either echo MRI or invasive heme dynamics?
Speaker: And
Speaker: You know, I think the other in the ICU, typically it's not subtle, right?
Speaker: So the RV is really blown out.
Speaker: So I think some of these other metrics are better for detecting kind of subacute or kind of hidden right ventricular failure rather than if you have a huge dilated right ventricle.
Speaker: The diagnosis is not in question at that point.
Speaker: Awesome.
Speaker: From an echo perspective, what are the things that people should be paying attention to or what are the things that you're looking at in an acute setting?
Speaker: Sure.
Speaker: Well, you know, I think it is your overall gestalt when you look at the echo, right?
Speaker: So just the RV size and the overall squeeze.
Speaker: You know, we do have some limitations when it comes to imaging the right ventricle.
Speaker: You know, sometimes, especially if a patient is acutely ill on a ventilator, it may be difficult to actually visualize.
Speaker: There's a really nice review out by Rebecca Hahn in Jack Journals where she kind of goes through imaging the right ventricle via echo.
Speaker: But just looking at the RV size, right, if the RV size is bigger than the LV, you know that you have a right ventricle that's in trouble.
Speaker: The TAPC, or the tricuspid annular plant systolic excursion, is a good measure of right ventricular function.
Speaker: We know that the right ventricle, about 80% of its function is contraction occurs in a longitudinal motion.
Speaker: And so seeing how that tricuspid annulus moves towards the apex gives us a good sense of right ventricular function.
Speaker: We can also look at the tissue Doppler velocity at the lateral tricuspid annulus.
Speaker: It's called S prime.
Speaker: It can be helpful.
Speaker: And we can't really get an RV ejection fraction when we use echo, at least 2D echo.
Speaker: So we look at the fractional area change, but all of those can be helpful.
Speaker: The metric that what I think is, well, maybe the two metrics that I think are the best, one is the ratio of TAPC to the pulmonary artery systolic pressure, that ratio, and of course the pulmonary artery systolic pressure being estimated.
Speaker: But that ratio is at least, has been shown to modestly correlate with
Speaker: the gold standard that we talked about earlier, that RVPA coupling from conductance catheters and pressure volume analysis.
Speaker: It's not a perfect surrogate.
Speaker: Certainly TAPC has some low dependence, and so to some extent you're kind of maybe overcorrecting for afterload, but this metric has been shown to be prognostic in left heart disease and pulmonary hypertension, and we actually have some cut points now that can be used clinically.
Speaker: So I think that that's a pretty good metric.
Speaker: We have a paper out in JACE just a couple days ago, and that's one of the factors that we use in a multimodality risk assessment for acute pulmonary embolism.
Speaker: The other is, you know, RV strain.
Speaker: And, you know, I do want people to realize that strain is actually not a measure of contractility.
Speaker: In fact, it's probably
Speaker: better correlated to afterload than contractility.
Speaker: Nonetheless, it's still quite prognostic and it's probably also, well, it is also more closely associated with RVPA coupling than some of our other metrics.
Speaker: And so I think that, you know, in more subtle cases, strain can be helpful.
Speaker: But as we go back to the ICU setting, usually it's not subtle, right?
Speaker: It's the ventricular size.
Speaker: It's the flattening of the intraventricular septum that can suggest either volume or pressure overload.
Speaker: We can quantify this by looking at the eccentricity index, which is essentially the ratio of the anterior-posterior dimension
Speaker: to the septolateral dimension.
Speaker: And if the value is more than one, this, you know, suggests ventricular overload.
Speaker: And these are patients that, you know, when you see this, this is obviously something we want to target when we're trying to improve these patients.
Speaker: Absolutely.
Speaker: And I think that the other thing I wanted to ask you about, obviously, the well-done echocardiogram can give you, like you said, a lot of measurements and new measurements being developed.
Speaker: So it's worth it.
Speaker: But like you said, in the acute setting, a fast POCUS exam or even a CT scan can show you that the RV is dilated.
Speaker: That's a starting point, right?
Speaker: And in the right clinical context, you can start making the story together.
Speaker: But the other thing I wanted to ask you, Brian, is the right heart catheterization, right, which in your world is going to the cath lab and doing all these fancy measurements.
Speaker: But in the critical care world, it used to be our bread and butter, a PAC catheter, which now is almost gone.
Speaker: However, this might be a population where perhaps we should reconsider that.
Speaker: You know, unfortunately, or maybe fortunately, right, there were a number of studies in the
Speaker: non-cardiology literature, critical care literature that suggested therapy guided by pulmonary artery catheters was not beneficial, and in fact, in some studies, perhaps harmful.
Speaker: You know, I think on the cardiology side, it's been more neutral, although arguably the design of those studies weren't perhaps ideal.
Speaker: You know, for most patients, though, right, PA catheter guided therapy is not necessary.
Speaker: I think it's
Speaker: It's one of those things where you don't need it until you actually need it.
Speaker: But I think, you know, sometimes people interpret those studies as suggesting that an invasive hemodynamic evaluation is not needed or useful, and I think that's wrong.
Speaker: Whether or not a PA catheter needs to be left in for days or a week to, you know, titrate therapy, I think that is a point you could argue, but I never think it's wrong to be able to understand hemodynamics.
Speaker: And, you know,
Speaker: And I think with all of our non-invasive tools, it's easy to be misled.
Speaker: You know, I think about an example is patients with left ventricular assist devices.
Speaker: And, you know, the unloading characteristics of our new devices are very different than the other devices.
Speaker: And you can't tell by echo.
Speaker: if someone has adequate LV unloading.
Speaker: You might have an eight centimeter ventricle, a very globular septum or a very globular LV and a septum that protrudes into the RV, yet their wedge pressure or their left atrial pressure could be one.
Speaker: And so again, I think it's never wrong to get a right heart catheterization because it's always gonna be, as long as you're doing it right, it's gonna give you important information.
Speaker: You know, we can estimate, of course, what preload is.
Speaker: Now, I want to be careful and remind everybody that pressure does not always equal volume, but you certainly can determine if pressure on the right side of the heart is elevated.
Speaker: You can determine if you have pulmonary hypertension, if that pulmonary hypertension also has a precapillary component with elevated pulmonary vascular resistance, and then what's happening on the left side of the heart as well.
Speaker: And so, again, I think it's always useful information to have.
Speaker: And then we do have, you know, some hemodynamic measurements that can give us a sense of how the RV is doing.
Speaker: One of the ones that we use a lot is the Pulmonary Artery Pulsitility Index, or PAPI.
Speaker: This is the pulmonary artery pulse pressure divided by the right atrial pressure.
Speaker: And we think about what determines pulmonary artery pulse pressure.
Speaker: Well, it's really two things.
Speaker: One is stroke volume.
Speaker: and the other is the compliance of the pulmonary artery.
Speaker: And so this can be a good surrogate of right ventricular function.
Speaker: And in fact, one of my colleagues, Stephen Su, was able to isolate individual myocytes from patients with heart failure and reduced ejection fraction and RV dysfunction.
Speaker: And when he compared the different hemodynamic measurements to isolated myocyte function, he found PAPI
Speaker: was really the most closely associated with that individual myocyte function.
Speaker: So PAPI can be very helpful.
Speaker: I do want to point out, because the denominator of PAPI is right atrial pressure, there is a point where it may be less useful.
Speaker: For example, if your right atrial pressure is two versus four, that ventricle probably is about the same in terms of their filling pressures, yet this could lead to very different PAPI
Speaker: calculations.
Speaker: But if your right atrial pressure is elevated, I think PAPI is a good one that can help determine how sick the right ventricle is.
Speaker: You can also look at more simple things, just stroke volume, stroke volume index.
Speaker: We know both of those are very prognostic in pulmonary arterial hypertension.
Speaker: The ratio of right atrial pressure to wedge pressure may also be useful.
Speaker: So again, I think it's always helpful to have a hemodynamic assessment.
Speaker: It doesn't mean that a catheter has to be left in place for a week to get infected, but I think it'll give the physician taking care of the patients more information.
Speaker: Excellent.
Speaker: And one more question I had before we move on to a different area is what are some signs that help differentiate between truly acute right ventricular failure versus acute on chronic?
Speaker: It's a good question.
Speaker: You know, I think it goes back to the history and
Speaker: you know, what was the time course?
Speaker: Was this something that, you know, developed all of a sudden, or was it, you know, something that was a little bit more progressive?
Speaker: And that can be somewhat difficult to tease out, and particularly in young patients.
Speaker: You know, I think that when you look at
Speaker: The echocardiogram, if you see signs of, you know, left heart failure, for example, valvular abnormalities, this would suggest, you know, some chronicity to the right-sided failure usually.
Speaker: But it can be difficult to determine.
Speaker: I think the main thing goes back to your history to determine timing there.
Speaker: Perfect.
Speaker: Let's talk a little bit about causes of right ventricular affair in the setting of the ICU.
Speaker: And I really think that a great framework to talk about this is through preload, afterload, and contractility.
Speaker: Sure.
Speaker: Yeah, so we can start by talking about disorders of excessive preload.
Speaker: And then again, I kind of always break this down into acute versus chronic preloads.
Speaker: And so excessive preload acutely, the one that we think about, although it's not very common, would be tricuspid regurgitation.
Speaker: That could occur if you have endocarditis and a valvular involvement there, or if you had some damage to that tricuspid valve during an intervention.
Speaker: Usually that is tolerated well, as long as you have
Speaker: normal right ventricular function and you have a normal left ventricular function.
Speaker: And so, you know, again, normally that's going to be tolerated well.
Speaker: When you have another condition and you develop worsening TR, that's a separate issue.
Speaker: When we think about more chronic RV preload abnormalities,
Speaker: You know, again, we think about worsening tricuspid insufficiency.
Speaker: We think about shunts, intracardiac left to right shunts, or extracardiac shunts.
Speaker: Extracardiac shunts, for example, being AV fistulas, right?
Speaker: So if we think back many decades ago, these AV fistulas for dialysis patients were put in the forearm, and that was...
Speaker: problematic a bit for our renal colleagues because they tended to close more often.
Speaker: They were more difficult to dialyze patients with, and so they moved them up to the upper extremities, and it works great for dialysis.
Speaker: Unfortunately, these fistulas can grow, and we've seen some of these grow to an excessive stint where there is liters and liters of flow going through these fistulas,
Speaker: And there's been elegant work from Barry Borlaug and Yogesh Reddy that have shown us that over time, the right heart dilates and becomes dysfunctional in these patients with very large fistulas.
Speaker: And so one of my favorite quotes or one of the things I always tell my colleagues and fellows is that I've never met a fistula.
Speaker: I didn't want to revise or close.
Speaker: Now, I do realize that they're a necessary evil for patients who have incision renal disease, but
Speaker: They do have a decrement.
Speaker: They can lead to problems with the right ventricle, particularly if they're high flow.
Speaker: And if they have underlying cardiac dysfunction, you know, I think that's going to be exacerbated.
Speaker: So that's something that I'm always kind of looking out for there.
Speaker: Not to mention that, as we talked earlier, a lot of now recognized risk factors for RV dysfunction, obesity, insulin resistance, are probably going to be more prevalent in some of these populations with fistulas.
Speaker: You bet.
Speaker: Absolutely.
Speaker: What about... Go ahead.
Speaker: Yeah, so then if we think about excessive afterload, again, breaking it down to acute and chronic, so acute...
Speaker: The classic example, of course, is the pulmonary embolism.
Speaker: Patients don't tolerate these big increases in afterload acutely because of the thin-walled nature of the RV that's used to ejecting into a low afterload circuit.
Speaker: And so that obviously is not tolerated well.
Speaker: Chronic increases in afterload, we really think about the development of pulmonary hypertension.
Speaker: And when we think about pulmonary hypertension, we really have five categories, right?
Speaker: We have group one pulmonary arterial hypertension, which is either idiopathic or connective tissue disease related or a couple of other causes.
Speaker: We have group two or pulmonary hypertension due to left heart disease, which is by far the most common cause of pulmonary hypertension in the world.
Speaker: We have group three, which is pulmonary hypertension due to lung disease or hypoxia.
Speaker: We have group four, which is pulmonary hypertension due to arterial obstructions, the most common there being chronic lung block disease.
Speaker: And then we have group five, which is multifactorial conditions like sarcoid, for example.
Speaker: And so those are going to be your more chronic disorders of excessive afterload.
Speaker: And then, you know, moving on to contractility, acutely, the big one is myocardial infarction.
Speaker: And so you can either have a, you can have an isolated right ventricular infarction or a more global involvement of LV and RV myocardium with a myocardial infarction.
Speaker: These patients are typically very, very sick.
Speaker: They can be bradycardic.
Speaker: They can go into complete heart block.
Speaker: and they can be very difficult to manage, often requiring additional support.
Speaker: And then more chronic disorders of contractility, you know, if we think about left heart failure, for example, the same entities that impact the left heart can also impact the right heart.
Speaker: So, for example, cardiac sarcoid or amyloid, all of these things can impact right heart.
Speaker: myocardial function in the right heart.
Speaker: The other one that we think about is after cardiac surgery.
Speaker: Patients can come, have difficulty weaning from bypass.
Speaker: After a left ventricular assist device, these individuals lose a lot of their RV function for various reasons, and they can be indeed very sick and lose that function.
Speaker: So those are, you know, the kind of the big categories that I think about when it comes to the causes of right ventricular failure.
Speaker: With that framework, then I move into how we best treat those individuals.
Speaker: Absolutely.
Speaker: And before we jump into treatment, just a comment.
Speaker: Obviously, acute contractility issues, post-cardiac surgery is a growing challenge, I think, in many ICUs as we continue to expand.
Speaker: indications and procedures and we're taking care of sicker and sicker patients like you said even the increased use of assist devices in the left ventricle has now created new new paradigms right or new problems on the on the right so clearly something that a lot of our intensivists probably interact with in their daily day the last thing i wanted to ask you about causes just because it's not something that i have seen or very familiar with but it caught my eye just out of interest
Speaker: was ARVC, or Arrhythmogenic Right Ventricular Cardiomyopathy.
Speaker: Is that something that we're seeing more now?
Speaker: You know, I think we are increasingly recognizing it.
Speaker: It's actually not specific to the RV anymore.
Speaker: A lot of people now just call it AVC, arrhythmogenic ventricular cardiomyopathy, because biventricular involvement certainly is common.
Speaker: But it is certainly becoming more recognized as an important cause of heart failure and certainly a sudden cardiac death and ventricular arrhythmias.
Speaker: But when I think about somebody who has isolated RV failure, particularly in the absence of pressure overload,
Speaker: Right.
Speaker: That that differential is somewhat narrow.
Speaker: And so ARVC is certainly one of them.
Speaker: There's the 2010 revised task force criteria that provides a framework for diagnosis.
Speaker: There are ARVC centers.
Speaker: One of my former centers in Johns Hopkins is one of the leaders in this regard.
Speaker: You know, you think about, I still remember one of my favorite patients that got a transplant for isolated RV failure, and he had cardiac sarcoid that was really isolated to the right ventricle.
Speaker: Myocarditis can be isolated to the right ventricle, although it's more common to have biventricular involvement.
Speaker: But those are the three things that I think about when I see kind of isolated right ventricular failure, yet no pulmonary hypertension or pressure overload.
Speaker: Perfect.
Speaker: Thanks.
Speaker: Can we now talk about treatment?
Speaker: And I guess you would take probably a very similar approach, right?
Speaker: You have to kind of break it up into obviously different clinical conditions, but what are the things that you can do for preload, afterload, and contractility?
Speaker: Sure.
Speaker: Well, preload.
Speaker: And, you know, I think we go back a couple decades when
Speaker: people had RV failure.
Speaker: The answer was, well, they're preload dependent.
Speaker: We need to give them volume.
Speaker: And if you remember nothing else from the podcast today, please remember that that is almost always not true.
Speaker: There are rare instances, for example, in an acute RV infarct, if you have a relatively preload, a low preload state due to kind of distributive shock, then in those situations, small fluid challenges might be very reasonable.
Speaker: But in almost every other situation, either acute or chronic, volume loading is almost never the answer and will make patients worse.
Speaker: There was a study that was out recently that I really liked in acute PE where they actually randomized patients to receive a single dose of furosemide versus placebo in those who had an intermediate risk pulmonary embolism.
Speaker: And those who actually got Lasix were more likely to meet the combined endpoint.
Speaker: And so, which was a positive endpoint.
Speaker: And so, you know, very few situations would volume loading be the right answer.
Speaker: In fact, many times it may be harmful because we know as the RV gets volume overloaded, it becomes more dysfunctional.
Speaker: The septum flattens.
Speaker: We know that the septum is responsible for the lion's share of right ventricular function.
Speaker: We can develop pericardial restraint, which further reduces LV preload.
Speaker: And so most of the time, particularly and certainly in chronic RV failure, the answer is actually volume removal to optimize preload.
Speaker: And we do that through diuretics.
Speaker: Some situations may call for ultrafiltration or dialysis.
Speaker: There's even some novel therapies now that are looking at ways to reduce LV preload through devices or, for example, splintening nerve deinnervation.
Speaker: So maybe that's something that's coming down the pike.
Speaker: But normalization of preload is something that's really key to managing patients with right ventricular failure.
Speaker: And I think it's worth reemphasizing, as you mentioned, there's one thing people should take home today is this old dogma of preload augmentation to help these patients is really not based on evidence and probably more harmful.
Speaker: We want to optimize preload, but like you said, in most clinical circumstances, that's probably preload reduction and removal of fluid.
Speaker: Right, and you hear all the time, well, the patient's hypotensive.
Speaker: How could I possibly give them Lasix or diurese them?
Speaker: And, of course, we have to.
Speaker: We've got to support their blood pressure with other means, but certainly giving fluid is not the answer, and it's just going to start this RV death cycle that is occurring if you give them fluid.
Speaker: So do everything you can not to forget that age-old adage of preload dependence of the RV.
Speaker: Perfect.
Speaker: Let's talk about contractility.
Speaker: Sure.
Speaker: So, you know, as we think about optimizing contractility, I think of a few things.
Speaker: So one, and again, I'm going to take you back to preload is, is as we normalize preload, the RV is actually going to contract better, right?
Speaker: Because the septal function will be better.
Speaker: So first and foremost, again, to augment contractility, we've got to optimize a preload in situations where,
Speaker: where you have ischemia, obviously large vessel ischemia from an acute infarct, we're going to want to try to open that artery and reperfuse the right ventricle.
Speaker: But then, you know, the rest of contractility augmentation is going to occur via two, really two mechanisms.
Speaker: One is to adequately support the systemic blood pressure.
Speaker: So as we get hypotensive, a couple of different things occur.
Speaker: One is the LV actually becomes less contractile as you become hypotensive.
Speaker: And we know that the RV depends on the LV for a significant amount of its contractile function.
Speaker: somewhere between 30 to 50%, and probably even more in pathologic states.
Speaker: And so as that LV becomes less contractile, we know the RV is also going to contract less.
Speaker: As the patient becomes hypotensive, there's also going to be more decreased blood flow down the right coronary artery, and the RV is going to become more ischemic as well, and that's going to further decrease contractility.
Speaker: So we want to support the systemic blood pressure.
Speaker: And then, of course, we can use direct inotropic medications like dobutamine, like epinephrine, perhaps milarnone, although we have to be careful with milarnone because of the systemic vasodilatation.
Speaker: I use milarnone a lot in patients with left heart failure, but certainly in patients with pulmonary arterial hypertension, you're probably just going to get a lot of systemic vasodilatation, and that may worsen RV function.
Speaker: So we can use those medications at least temporarily,
Speaker: to support the right heart, to optimize preload, to optimize afterload, like we're going to talk about in a minute, and support you through that acute state.
Speaker: But that's really, you know, how we're going to think about automating contractility.
Speaker: Perfect.
Speaker: And I guess last but not least would be afterload reduction, which is going to be something that we're going to be thinking, I think, in a lot of our patients in the ICU.
Speaker: Absolutely.
Speaker: And, you know, so...
Speaker: Again, going back to the construct of acute versus chronic in patients with acute pulmonary embolism, right, we have to make a decision.
Speaker: Is anticoagulation going to be enough?
Speaker: Do we need some type of either catheter-directed or systemic thrombolysis?
Speaker: And, you know, that's still a topic that has a lot of debate.
Speaker: But certainly in critically ill patients with significant pressure overload, it's something that needs to be carefully considered.
Speaker: And then, you know, in more chronic afterload states, for example, and the easier one is pulmonary arterial hypertension,
Speaker: we are going to want to try to reduce afterload, right?
Speaker: And we have a number of different medications that can do that, both oral and IV, and that's really going to be in collaboration with your PH colleagues to how best to do that.
Speaker: In the ICU, many times that's going to be IV prostacycline in our critically ill patients.
Speaker: There is also sometimes an indication for inhaled
Speaker: therapies like inhaled nitric oxide, particularly in short term, which may help reduce RV afterload.
Speaker: In patients with left heart failure, it's a little bit less simple.
Speaker: Many of our drugs that we use to treat pulmonary hypertension have not shown to be helpful in pH to left heart disease, and in fact, there's some suggestion that they can be harmful.
Speaker: So in those individuals, we're going to try to reduce RV afterload by optimizing LV function, optimizing LV preload, and eventually work on getting these patients on the guideline-directed medical therapy with our four drug pillars.
Speaker: But they're a little bit more difficult to afterload reduce outside of optimizing LV preload.
Speaker: Perfect.
Speaker: The other question I had, Ryan, in terms of the use of inhaled basal dieters like nitric oxide in the acute setting, any thoughts on that?
Speaker: I think it's still an area of a lot of mismanagement in the ICU.
Speaker: And obviously, I'm talking about a mixed bag here.
Speaker: Sometimes it's utilized for pulmonary hypertension issues, other times just for hypoxemia.
Speaker: But any comments from your perspective?
Speaker: Yeah, you know, the data with nitric oxide is mixed at best.
Speaker: But, you know, the argument, of course, is, well, you can't really study the patients who need it.
Speaker: So that's a bit of a challenge.
Speaker: I think the thing that I always go back to is, well, what is the physiology?
Speaker: You know, if somebody has an elevated pulmonary vascular resistance and they're hypoxic, I think it's reasonable if the RV is struggling to,
Speaker: The nice thing about it is you can turn it on acutely and turn it off acutely, and it goes away.
Speaker: So it's, you know, each patient can kind of be their own.
Speaker: You can look at the response in the individual patients, but I do agree with you.
Speaker: I think it can be misused.
Speaker: I think it can be overused.
Speaker: And if somebody doesn't have, you know, elevated RV afterload, it probably isn't going to do very much.
Speaker: The other area I wanted to ask about, Ryan, is in terms of afterload in the context of PE, we're seeing a rapid increase in the utilization of catheter-directed therapies for acute pulmonary embolism with RV dysfunction.
Speaker: And obviously, there's really no good mortality data that I have seen, but a lot of the arguments are hemodynamic and afterload reduction arguments.
Speaker: whether that be catheter-directed TPA or catheter-directed thrombectomy.
Speaker: Any comments on this?
Speaker: Yeah, you know, and this is not my area of expertise, but physiologically, right, you would think that it would make sense, whether that translates into
Speaker: real improvements in clinical outcomes, I think is less clear.
Speaker: And, you know, all of these have some complication rates associated with them as well.
Speaker: So I think, thankfully, there are a number of clinical trials that should be coming out that will help give us that answer and define that population better.
Speaker: You know, I think one of the major advances, though, when it comes to dealing with the QPEs is the development of the PERT team, which many hospitals have, including ours.
Speaker: And I think
Speaker: You know, they're having a multidisciplinary approach from critical care doctors, cardiologists, interventional radiologists, pulmonologists, anesthesia critical care, just like a cardiogenic shock team, can really improve patient outcomes.
Speaker: So,
Speaker: Whether those devices need to be used more or less, I think that remains to be seen.
Speaker: But I think what we have learned is a multidisciplinary approach when it comes to treating these sick patients and determining how best to care for them is a clear winner.
Speaker: Perfect.
Speaker: The last question I have regarding treatment as we wrap up is any comments on mechanical support?
Speaker: Sure.
Speaker: Sure.
Speaker: Thankfully, we do have more mechanical support options than we used to for the right heart.
Speaker: There's a couple of temporary MCS devices that are axial flow devices that are available now, although usually these are used in patients with concomitant left heart failure or in postcardotomy shock.
Speaker: These devices, again,
Speaker: or not without complications, so they shouldn't be used unless they're truly indicated, but they certainly can restore blood flow, improve LB filling, and provide RV support.
Speaker: You know, I think that what we still really don't have a good sense of is what to do if these devices
Speaker: can safely be used in pulmonary arterial hypertension.
Speaker: One nice thing about them is you can adjust the flow, right?
Speaker: So I think traditionally when you've thought about support devices for the RV and pulmonary arterial hypertension, we worry about pulmonary hemorrhage and that's still a worry, but if you have a device that could give you a liter, liter and a half of flow, maybe that's enough in the acute setting to allow someone to get more compensated to better treat the cause of their RV dysfunction.
Speaker: ECMO certainly is a mechanical support platform that can be used to bridge patients if there is a destination.
Speaker: So I think whenever we're going to use these devices, whether it's a temporary MCS device or ECMO, we need to make sure that we have a destination.
Speaker: And maybe that's just a bridging to a decision, but we want to make sure what is the long-term outcome here?
Speaker: Are we going to try to
Speaker: recover the patient?
Speaker: Are we going to move on to a lung, heart or heart lung transplant?
Speaker: You know, we always have to have these in mind when we use these, you know, very expensive therapies.
Speaker: And it becomes very difficult if we don't have a destination in the patient, then we have to have the conversation with the patient and the family, you know, now what do you want us to do?
Speaker: We're going to have to stop using the device.
Speaker: And that can be very difficult.
Speaker: So I think it's, again, speaks the importance of a multidisciplinary team,
Speaker: that can help make those decisions when these devices may be used.
Speaker: But again, the good news is we do have some potential devices now that may help with these complicated issues.
Speaker: Absolutely.
Speaker: And I think that clearly a lot that we've learned over the last, I would say, couple decades and a lot still ahead that we don't know.
Speaker: But definitely, I think, a very relevant clinical topic.
Speaker: And thanks again for sharing your expertise.
Speaker: Obviously, this is something that you live every day and you see it from every angle.
Speaker: But I do believe it's something our critical care audience needs to be more aware of and
Speaker: With that, we usually like to close the podcast, Ryan, with a couple of questions unrelated to the clinical topic.
Speaker: Would that be okay?
Speaker: You bet.
Speaker: So the first question relates to books.
Speaker: Are there any books or book that has influenced you significantly or that you have gifted often to others?
Speaker: Well, you know, I guess I would start by saying a book called The Right Ventricle in Health and Disease.
Speaker: That's one that I typically...
Speaker: like to gift to my mentees and colleagues.
Speaker: I've been fortunate enough to participate in the writing of several of those editions.
Speaker: And, you know, it really goes back to a lot of the physiology, even more sophisticated physiology than we talked about in ventricular assessment.
Speaker: And I just find we can learn so much by the history of medicine and understanding physiology.
Speaker: Um,
Speaker: you know, kind of maybe outside my expertise, I recently read The Codebreaker, which was the story of Jennifer Adudna, who helped develop CRISPR-Case9 and gene editing, and I found that to be a really nice read, and her journey as a woman in science, and I really enjoyed that book.
Speaker: Excellent.
Speaker: And we'll definitely link both of these in the show notes.
Speaker: The second question relates to something you believe to be true in medicine or life that most other people don't believe, or at least they don't act as if they believe it.
Speaker: Um,
Speaker: Yeah, that's a good question.
Speaker: The one that immediately comes to mind is that medicine is the easy part.
Speaker: One of my former mentors, Charlie Weiner, used to say that all the time, and I found that to be more and more true.
Speaker: It's more, the difficult part can be managing personalities, managing patients, managing patients' families, managing your colleagues, getting everyone on the same page.
Speaker: But typically when, you know, the actual physiology, the actual knowing what to do is the easy part.
Speaker: It's making that plan happen in a complex environment that can be more challenging.
Speaker: I agree.
Speaker: And I've heard a similar thought in the terms of managing, right?
Speaker: Because management is easy.
Speaker: It's the people part that's hard.
Speaker: But I think at the end of the day, that's exactly what's happening at the bedside.
Speaker: That's exactly right.
Speaker: It's important to have a great team, right?
Speaker: For sure.
Speaker: I agree.
Speaker: And the last question relates to what would you want every listener, all our critical care clinicians listening to us to know could be a quote, a fact, or just a thought?
Speaker: Don't forget the RV.
Speaker: Hopefully it's clear now that the RV is critically important in almost every disease.
Speaker: And so we need better ways to assess it.
Speaker: We need better ways to identify dysfunction and then certainly better ways to treat it.
Speaker: So don't forget the RV and the RV is rarely preload dependent.
Speaker: So don't give fluid.
Speaker: I love that.
Speaker: Well, Ryan, thank you so much for sharing your expertise and for giving us your time.
Speaker: I hope to have you back on the podcast to talk about more about the RV or maybe some other topics related to heart failure.
Speaker: Very good, Sergio.
Speaker: Thank you for having me.
Speaker: Thank you.
Speaker: Thank you for listening to Critical Matters, a sound podcast.
Speaker: Make sure to subscribe to Critical Matters on Apple or Google Podcasts and share with your network.
Speaker: Sound's transforming the way critical care is provided in hospitals across the country.
Speaker: To learn more, visit www.soundphysicians.com.
