In this episode, Andrew Perry, MD, discusses the utility of ejection fraction (EF) with John Gorcsan III, MD, an expert in echocardiography and strain imaging at Washington University School of Medicine in St. Louis.
They explore how EF came to be used in clinical practice, the importance of it in heart failure and the variation in measurement. The interview also covers strain imaging and what it adds to ejection fraction, particularly in the setting of severe mitral regurgitation.
A transcript of the podcast follows:
Perry: Thank you for meeting with me today, John. Can I have you maybe first say your name and your title so our listeners know who we’re speaking with?
Gorcsan: Hello. I’m John Gorcsan from Washington University in St. Louis. I’m a Professor of Medicine and Director of Clinical Research in the division of cardiology here.
Perry: Great, thank you. John has done a lot of work in cardiac imaging. Today we’ll be focusing a discussion about ejection fraction, kind of reviewing the historical discovery and use of ejection fraction, and maybe some of the ways that it comes up short and other markers that we can use to assess cardiac function. One of the first things I wanted to bring up with you is that many physicians in my generation just assume ejection fraction has always been present and always been used in healthcare. It can certainly seem that way. But I wanted to ask you about how ejection fraction first came to be used in cardiology.
Gorcsan: Sure, thank you. One of my favorite sayings on rounds with the trainees is that ejection fraction is to the cardiologist as serum creatinine is to the nephrologist. We’ve gone to thinking about a cardiac patient where you can’t even describe them without knowing their ejection fraction. So how did this come about? To the best of my understanding, it actually grew out of the gated radionuclide scan. This is a multi-acquisition gated scan, also known as a MUGA. I think it came out of Barry Zaret’s lab at Yale in the ’70s.
What this is is you label blood cells with an isotope and then you look at counts. You put the camera as best as you can to focus on the left ventricle, and you get a ratio of end-diastolic to end-systolic counts over end-diastolic counts. As you know, no units of volume are used in this. It’s a ratio. So it turned out if you acquire these counts over minutes, many beats average, you get a very stable signal.
Gorcsan: This was used in several clinical trials in the early ’80s. One notable one was Arthur Moss’ Multicenter Postinfarction Research Group study, and the reference is the New England Journal of Medicine in 1983. It was remarkable to show how the radionuclide ejection fraction was correlated with survival after myocardial infarction. And because this is audio only, you saw this flatline that started to curve with an increase in mortality around an EF of 40%. Then when it dropped below 35, mortality increased dramatically.
Gorcsan: So it was from this initial dataset that these numbers of, “Well, you’re sort of okay with an EF to 40, and then the risk starts increasing, and then certainly under 35, under 30, and then when you’re in the 20s, the risk of dying increases.”
Perry: Okay, and those were all nuclear scans that they had done for that?
Gorcsan: Nuclear scans in post-infarct patients, interesting.
Perry: When did, then, echos become part of that measurement? Because today, that’s where most of those measurements come from.
Gorcsan: Yeah, that’s an interesting thing. It had to do, actually, in my lifetime, it had to do with the payers because it used to be reimbursed for both a gated nuclear scan or a MUGA and an echo, and then they said, “No, you can only be reimbursed for one.” Again, to the best of my understanding what I lived through, that was the impetus for the popularity in echocardiography because you get information on valves, on right ventricular function. With Doppler, you could estimate PA [pulmonary artery] pressures, you could look at the pericardium. This really surpassed the MUGA for just the EF measurement.
Perry: Yeah, I mean next I want to address what is the physiology of the ejection fraction and what we are measuring and kind of walk us through what those measurements actually mean.
Gorcsan: Historically, it was a very stable signal. We learned that in the past few minutes. But why is it so important and I’m going to start out saying that EF is here to stay. For the rest of my career, Andrew, for the rest of your career, EF is not going away. It is so ingrained in clinical practice, in pharmacologic therapy, in device therapy, which we’re going to talk about a little more. So it’s important to think about why is it so strong? Let’s take it apart for a minute.
It’s a ratio. On the numerator is the stroke volume, so it’s a measure of function. On the denominator is end-diastolic volume, a measure of remodeling. These two things independently measure function and then a measure of size, so you could have the same stroke volume with a small heart and have a higher ejection fraction than the same stroke volume with a big heart. That measure of remodeling is a measure of disease progression, and you put them together. You combine them with an ejection fraction. Does that make sense?
Perry: That does make sense.
Gorcsan: The other thing that we’re going to talk about — load sensitivity. This comes from experience with animal experiments, are rarely done these days, an open-chest dog or an open-chest pig model where you’re measuring pressure volume loops and you’re doing acute changes in load. If we do this and we measure beat-to-beat ejection fraction and let’s say you occlude the inferior vena cava, what do you think happens to ejection fraction?
Perry: I would expect it to eventually decrease after a couple of beats because you’re eliminating the preload.
Gorcsan: Correct, so how does preload affect stroke volume?
Perry: Your preload is going to decrease your stroke volume.
Gorcsan: And how does preload affect end-diastolic volume?
Perry: It’ll also decrease your end-diastolic volume.
Perry: Then you’d probably have a preserved ejection fraction because of that.
Gorcsan: This is what, I think, again, on rounds with trainees, they don’t understand that I think one of the other reasons why ejection fraction has become so important in clinical practice is that when it comes to preload, it actually corrects for itself, because the stroke volume is a measure of the Frank-Starling relationship. The more you fill, the more you eject. If both are going down less filling, less ejection, less filling, less ejection, the EF is going to be preserved. But when you get to low volumes, then it falls apart. Then it’s exquisitely load dependent. When we’re talking about preload, I think it could be tolerant in a range, say a physiologic range, of being a stable signal of ventricular function.
Now on the other hand, if we look at afterload, that’s an amazing phenomenon, where if you do an acute increase in afterload, the ejection fraction dies. If you have a left ventricle that is not compensated for high pressure, it dilates and the LV stroke volume decreases, so you see the EF go down right away.
Perry: Yes, okay. I follow that, because now your denominator has greatly expanded and your numerator has also correspondingly shrunk, so then your ejection fraction really takes a dive.
Gorcsan: Takes a dive.
Gorcsan: You say to yourself and I’m amazed by this. We see patients in the clinic who come in the echo lab. Let’s say they’re non-compliant. They didn’t take their blood pressure pills, and their systolic blood pressure is 180 mm Hg. You look at their heart on echo and the ejection fraction is normal. How can this be? It has to do with compensatory mechanisms. The most important is you tune up the myocytes to become hypertrophied and able to sustain this high afterload, but we’re going to talk about that more.
But in summary, I think why is EF important? I think it’s twofold. One, again, to review, is that it’s a measure of both function and remodeling in the state-to-state. Two, it is relatively preload insensitive. Sounds crazy, but it’s true.
Perry: Now the next thing would be about distinguishing between patients with heart failure and how we’re currently bending them into two major groups: those with a reduced ejection fraction, HFrEF, and those with a preserved ejection fraction, HFpEF. How did we kind of end up into these two camps based on ejection fraction?
Gorcsan: That’s an excellent question. So heart failure is a very common, important problem in all of the world, really, not just the United States. When we see a patient with heart failure, we don’t know what treatment algorithm to follow until we know their ejection fraction. Why is that? Clinical trials enroll patients based on the ejection fraction, so that means that the evidence is based on patient selection by ejection fraction. We’re going to come back to this. We’re going to circle around.
If we practice evidence-based medicine as we should, someone has to go back and redo all the clinical trials selecting patients by some other means than ejection fraction in order to do away with it. Let’s go over some examples. Depends on how you define reduced ejection fraction. Let’s say the consensus is somewhere between 35% and 30%, below those cutoffs. Depending on the clinical trial, some use 35%, some use 30%. There is abundant evidence that — let’s start with pharmacologic therapy — ACE inhibitors or angiotensin receptor blockers given to patients with reduced ejection fraction have a mortality benefit. Then we move on to beta-blockers. Same. Then spironolactone.
Then what are newcomers? We have ivabradine [Corlanor], not used that much in this country, but selected by ejection fraction. There’s a mortality benefit in patients who are, perhaps, intolerant of beta-blockers. It’s a selective sinus node inhibitor, so-called “funny channel” agent. Then Entresto [sacubitril/valsartan] is a new one. You see, right now, we have, not counting individual drugs, we have five more or less classes of drugs that have mortality benefit based on ejection fraction. Very powerful collective data.
How about devices? As you know, implantable defibrillators are based on ejection fraction. The MADIT trial used an EF of 30. The SCD-HeFT trial used a cutoff of 35 and included non-ischemic cardiomyopathy. Then CRT, if you have a wide QRS complex.
Perry: In addition to your low ejection fraction with a wide QRS, then you get CRT.
Gorcsan: Correct. So we’re talking about a list of important pharmacologic agents and devices where you can’t appropriately implement these treatments without knowing the ejection fraction.
Perry: Now what about people with preserved ejection fraction or normal EF?
Gorcsan: That’s a good question. What do we know about that? There’ve been many attempts over the years to find a pharmacologic agent that helps patients with HFpEF, heart failure with preserved ejection fraction. We know that they have a similar outcome as far as mortality. We know that there’s a very strong association with HFpEF patients with other cardiovascular risk factors such as hypertension, such as obesity, diabetes, but most of them aren’t dying from cardiovascular events, death from stroke or heart attacks, rather than heart failure or arrhythmias, which are the common mode of exodus for HFrEF patients.
Having said that, I think there’s no definitive, positive study. We could take TOPCAT, which was a randomized trial of spironolactone versus placebo, throw out the Georgian patients, and then end up with a positive study. So spironolactone, some believe is a treatment for HFpEF. I’m sorry, yeah, HFpEF. But clearly, the evidence for HFrEF or pharmacologic and device therapy is overwhelming.
Perry: Yeah, no, it’s been unfortunately all those trials have been largely negative in that setting for those patients. Now kind of speaking getting into the nuts and bolts of measuring ejection fraction. I think a useful question for someone of your experience is really how ejection fraction is measured and consistency of it, knowing that you’ve helped coordinate large multicenter trials in running the core echo labs for them. What are the considerations and the protocols you used in order to help reduce interobserver variability with an ejection fraction?
Gorcsan: Thank you, Andrew. Let me take you through that. It’s sort of been an honor and a privilege to have this intense experience with a sort of simple measurement as echo EF, so I’d love to share with you some of the nuts and bolts of how you do this. The expert consensus of guidelines, Roberto Lang is the lead author from the American Society of Echo, is to do 2D, biplane ejection fractions. What does this mean? That’s the four-chamber view and the two-chamber view.
Why not 3D echo? It turns out that 3D echo has advantages, in particular, with reproducibility. But if you go to a multicenter clinical trial, 3D echo is still not mainstream across the board. There’s many centers who lack experience doing 3D echo, so that the common clinical practice is to do 2D echo ejection fraction. It starts with acquisition. We teach our sites explicitly it’s important to include the LV apex. It is so easy with a 2D imaging sector to cut off the LV apex, and then you underestimate volumes, so you have to work with the patient and the person doing the scan, if it’s a sonographer or a physician, to get the maximal imaging planes.
After you have that acquired, it’s a very systematic approach to tracing. It’s still manually done. I do not think any auto ejection fraction program is robust enough to override the manual tracing of the EF. We do this with a very specific approach. I call it three steps to minimize the interobserver variability. One is a consistent approach to excluding trabeculations, to looking at near-field noise. That’s in the apex because the transducer itself, the proximity creates a little noise, so you see a little cloud in the apex commonly, so you have to account for that. Then uniform wall thickness as you go around. These three steps are a guide to giving you a more reproducible ejection fraction.
Perry: Now with those issues and we’re talking about multicenter trials, when you talk about comparing, so you have the same patient who undergoes multiple echos and they’re read by … say, actually, let’s start first they’ve had one echo and you have multiple cardiologists read and interpret their ejection fraction off that echo. Based off your experience, what do you think is the best interobserver variability you can get with ejection fraction?
Gorcsan: I’ve seen over the past, let’s say 10 years, a good movement in the field where it used to be physicians would only eyeball ejection fraction. In other words, visually estimate and they’d put in the report usually a range of 5 EF units. Like the EF is 40 to 45, something like that. But I think that as good labs have evolved and with the use of contrast imaging, with harmonic imaging, with the use of new beamformers where you’re actually improving image quality so much better that you can perform guideline-directed medicine and do tracing of biplane Simpson’s rule ejection fractions. I think it’s so critically important to learn how to do this well in your lab and learn how to do it reproducibly because it makes such a major impact.
My echo core lab consists of post docs who are usually international physicians, fully-trained cardiologists, and we do ejection fractions every day on many patients, and our goal is to reach the standard, set the bar high that we’re doing ejection fraction the same way, all of us, the whole team. Over the years, I’ve come to the realization that the best we could do is 5 EF units. What that means, Andrew, if you trace an EF and get 30 and I trace an EF and I get 35, it’s going to be very difficult to do better than that across the board. Maybe someone else can, but…
Perry: So plus or minus 5 EF units.
Gorcsan: That would be a range of 10.
Perry: Okay, so a range of 5 is what you mean, right?
Perry: I follow.
Gorcsan: Yeah, you’re right. That would be the end of the range of 5 EF units.
Perry: Then if we have the best we can do interobserver variability is probably 5 EF units. Then what would you say, then, is a clinically meaningful change? What is your minimal threshold of change when you’re looking at serial echos in the same patient?
Gorcsan: Right. I want to throw out there this is my personal experience and having done this over 20 years, really, in the core lab realm, perhaps. Other labs may have better tricks to do better, but I think in the clinical labs it’s really important for the practicing clinical cardiologist to accept the fact that this is the noise, the background noise in EF, and that it’s not very productive to sort of get in clinical arguments because my EF is 30 and yours is 35, and I’m right and you’re wrong. Come back, blind the observers in a month and have them do it again. You’ll be surprised with the results. I personally think you’re not going to do much better than that.
But having said all that, once you exceed these 5 EF units, I believe it’s very powerful when you’re following a patient in either direction. For example, in the EchoCRT trial, that was a trial of narrow QRS patients where we paced them with a hypothesis that we could help them. It turned out to be a negative trial, but we have this database. In the control group, there were patients who improved and some of them, their EF declined, the natural history of heart failure patients. It turned out that a change in 5 EF units, more than 5 EF units, was clinically significant, so that if you’re tracing a biplane Simpson rule and you have a patient either decrease that’s associated with increased risk — and I’m talking endpoints where heart failure, hospitalization, or death — or if it improved, it kept you out of the hospital. It decreased your risk.
Perry: Very good. Interesting stuff. Now one thing I want to bring up is I think part of my interest in this topic as being a resident and through wards, when you’re on a non-cardiology service, so much of a person’s cardiac function is just described as their ejection fraction. They might hear someone on rounds say, “Patient X, they had their echo yesterday. Their EF was 60%,” and then just move on to the next topic and realizing that really their EF is just one measurement of their left ventricle, and there’s, of course, many other parts of the heart that you could comment on. As we’ve discussed, maybe some issues with ejection fraction. I guess what are other markers that you might look at from someone’s echo to, indeed, verify that their normal ejection fraction correlates with relatively normal cardiac physiology?
Gorcsan: Thank you, Andrew. I look at assessing cardiac function in three broad strokes in the current era starting with the ejection fraction, as we talked about, then adding diastolic function, which, by the way, we could talk about for an hour, so I don’t want to spend a lot of time on that. Then the third thing is strain imaging, which I believe has really emerged as a major player as being additive to ejection fraction in the current era.
A few limited comments on diastolic function: There’s a whole literature that’s probably worthy of a separate podcast of, if you have patients with a preserved ejection fraction, what markers of diastolic dysfunction add. In particular, we’re talking about inflow velocity, pulsed Doppler of the mitral valve, and annular velocity tissue Doppler of the mitral annulus. There is systolic-diastolic coupling. You can’t take this away in the sense that I guess it’s hypothetically possible, but not very likely that you have a low-ejection-fraction patient with completely normal diastolic function. For example, their mitral annulus is reduced because, as it contracts, the relaxation, the active relaxation or the active component of early diastole, I should say, is affected.
But, again, it’s sort of interesting when you’re saying is this heart really normal? One of the things you look for after ejection fraction is the mitral annular velocity and the inflow velocity, and if that looks normal, it takes you one step up on the normal. There’s some ambiguities with abnormal diastolic function, but again, I don’t want to really get into because we don’t have time. But I think since we’re mostly focused on systolic function, why don’t we talk about strain imaging?
Perry: Yeah, that would be great. I know you have a lot of experience yourself in studying strain imaging. Maybe first some of our listeners won’t probably be too familiar with what strain imaging is, so I guess what is strain imaging conceptually?
Gorcsan: The left ventricle is a 3-dimensional object, so we have to think about, as it displaces blood, it does this in a way by shortening, thickening, and twisting. Echocardiographic technology has evolved that we can measure these vectors of wall deformation, which is another way of saying strain. The current technology, I can see in the future we just do a 3D scan of the entire heart and you get one number that combines the shortening, thickening, and twisting, but currently we do this in two dimensions, and we look at shortening separately in the long-axis views and the thickening, well, there’s circumferential and radial, so there’s different ways to look at thickening in the short axis view. In the twisting, you need to do serial short-axis views.
I can make this simple because over 90% of the literature today is focused on the longitudinal component of strain. In other words, you scan the patient in the apical views, typically three views, four chamber, two chamber, long-axis views. Software uses a technology known as speckle tracking on the B-mode imaging dataset to look at the speckles as they shorten or come together in systole and then lengthen as they come apart in diastole. That is reported as the global longitudinal strain, or the GLS.
Perry: Okay. That’s usually what people are talking about nowadays because that’s what most of the literature is about.
Gorcsan: I think so. For those who are new to strain, I think that would be where you start and where you measure and where you get comfortable with is the GLS, global longitudinal strain.
Perry: Now how has strain been additive to ejection fraction? I’m sure that’s a whole conversation in itself, but maybe you could highlight a couple specific clinical scenarios.
Gorcsan: Thank you. There’s a couple questions in there. Let me start with how is it additive. I want everyone to think about if strain is measuring how the wall is changing its shape and we talked about ejection fraction being the change in volume, the stroke volume, over the original volume end-diastolic volume. Strain is the change in length over the original length. It’s a similar process you could say intellectually of looking at a measure of change or a measure of how the left ventricle is performing, but strain is focused on the wall and EF is focused on the blood inside the chamber. You say to yourself, “They have to be related, right?”
Gorcsan: You change the wall a little bit, the blood displacement must be a little bit. You change the wall a lot, the blood displacement must be a lot. If they’re measuring exactly the same thing, then why bother? It turns out, indeed, you could do a mathematical modeling and they’re linearly related, GLS and EF. It’s actually three times the GLS is the EF. Then you could argue on what the intercept is. But it turns out and I want our audience to review a paper that I found to be particularly landmark and interesting. It’s by Park, et al. JACC 2018, volume 71 and this is looking at over 4,000 patients with acute heart failure. It turned out to be a multicenter study conducted in Korea, but it’s large-sample volume, I mean a large sample of patients, over 4,000. They nicely plotted ejection fraction versus GLS, and it’s linear related. No surprise. But a lot of scatter. The dots are not nicely aligned along the line of identity. There’s a lot of factors.
The human reality is that there’s related but different information. To just stay on time, I’m going to rush to the punchline. I believe the wall properties that are additive to ejection fraction are mostly three. One is fibrosis, that’s very important. Two is hypertrophy. You can have myocyte dysfunction from hypertrophy such as hypertensive heart disease, aortic stenosis is another one, without fibrosis being the major one. The third one is infiltration, such as amyloid heart disease. To review: fibrosis, hypertrophy, infiltration. These are wall properties with the identical EF that will affect your strain, and that’s why I think there’s additive prognostic value.
Perry: I see. Great. Thank you for that reference. I’ll make sure I have that in the show notes for this episode. What is a normal strain?
Gorcsan: That’s a good question. I could tell you my opinion and it may change with time. It’s important for our listeners to understand that this speckle tracking algorithm differed a little bit between companies. It’s proprietary, and in a competitive sense, they’re not going to share all their secrets. If you look at strain measurements on the same patient using different echo machines and different software, the numbers will be slightly different.
That feeds into the answer to the question what is a normal strain, because it’s a little different and you can look at these head-to-head comparisons. Having said all that, I think as clinicians it’s important for us to remember a couple numbers. The average normal strain and it’s reported with a minus sign which is confusing to a lot of people, so I’ll just speak in absolute values, it’s between 19% and 20%. The threshold for abnormal, how low do you go till you draw the line and start to think about this being abnormal? Let’s say the equivalent would be if 55% EF is normal and 50% EF is borderline, where do you draw the line for abnormal?
I think normal GLS is greater than or equal to 17% or -17 if you insist on using the minus sign. Clearly abnormal is when the GLS is below 15% or -15% and then the borderline abnormal is between 15% and 17%. That’s just my snapshot of looking at a lot of studies and outcome.
Perry: Okay, very useful. Are most labs across the country now reporting strain or is this also a bit of a niche measurement that’s in only selected labs?
Gorcsan: I don’t have data. I just have anecdotal reports from friends in other labs, and I think that it is the minority today that is doing strain on every patient. I’m delighted to see that is happening here at Wash. U. in St. Louis, but I think most labs are doing strain on a subset of patients. Perhaps the most popular application right now is to look for apical sparing with patients with selected amyloid heart disease. What we didn’t talk about is valvular heart disease as an added risk, and I think that would be, perhaps, the second most-popular application, would be the patient with severe mitral regurgitation.
Perry: Yeah, it was a topic I wanted to ask you about. How ejection fraction can be interpreted in those settings and then the added benefit of strain in severe mitral regurgitation.
Gorcsan: We talked about the afterload dependence of EF.
Gorcsan: I think no one is going to argue that. If you think about a certain level of contractility and during ejection you make it a lot easier. In other words, you decrease afterload tremendously. How could that happen? Severe mitral regurgitation, right? What that does is it can mask LV dysfunction in the normal range. Does that make sense to you?
Perry: It does, yes, because you’re preserving your stroke volume because a lot of your stroke volume is now going retrograde through the mitral valve, so then your ejection fraction can then be preserved as we discussed earlier from those changes.
Gorcsan: You think about blood inside a pressurized left ventricle, and you give it two choices to escape. One out the aorta, which is high pressure and one backwards into the left atrium, which is low pressure. You’re creating a scenario where it’s giving the left ventricle an easy way out. And it’s one of, I think, the most important things for the clinical cardiologist to remember is that your ejection fraction is not telling you the whole story in the setting of severe MR.
Perry: So knowing that it’s not telling us the whole story, how does strain add on top of it in that study?
Gorcsan: I think it adds a lot. I think strain has the ability, in addition to the heart failure patients we talked about, in a setting of patients with severe mitral regurgitation. I think still today there’s controversy with what to do with the asymptomatic patient with preserved ventricular function and then clearly severe mitral regurgitation. We’re not talking about moderate, moderate to severe. We’re talking about…
Perry: Wide open.
Gorcsan: Wide open MR. But the patients feel fine. They insist they feel fine, and you have to decide to send them for a mitral valve operation, mitral valve repair. Let me ask you this. In your patients, are you entertaining the idea of watchful waiting at all or are you sending these patients directly to surgery?
Perry: I’m thinking fast and I don’t know that I’ve come across a patient yet in my training who’s asymptomatic with severe MR.
Gorcsan: I don’t think it’s completely uncommon because they’re maybe, perhaps, seen in the outpatient cardiology clinic, so that if they’re admitted to the hospital, you’re seeing the symptomatic ones in your training.
Gorcsan: But anyhow, my observations are that some centers, for example, like the Cleveland Clinic and the Mayo Clinic, they’re very enthusiastic to operate on these patients early. The shift is to operate on them earlier and earlier. But still you have some patients, perhaps because of age, perhaps because of comorbidity, perhaps because of patient selection, meaning the patient doesn’t want to have surgery unless you convince them some more, you have this scenario and you’re looking for more information. I’d like to direct you to this article. It was in JACC 2016, volume 68. The first author is Mentias, and the title is, “Strain Echocardiography and Functional Capacity in Asymptomatic Primary Mitral Regurgitation With Preserved Ejection Fraction.”
It’s sort of a mouthful of a title, but it was from the Cleveland Clinic. The senior author was Milind Desai, and retrospectively they collected data on 737 patients with severe MR. All of these patients had a normal EF defined as greater than 60%. Again, in the severe MR patients, we’re not using any ones with EFs in the 50s. If you have a 50-some EF with severe MR, it’s an abnormal ventricle, so it’s over 60. Also, non-dilated left ventricles defined as a systolic volume less than 4 centimeters. You’re taking out the horrible remodeled ventricles.
Perry: Yeah, okay.
Gorcsan: These should be pretty healthy ventricles, right?
Perry: These are primary valve problems and not functional MR.
Gorcsan: Right. These patients went on to have mitral valve surgery. I think almost all of them. I forget the percentage. I think the vast majority, almost all had mitral valve repair at a good center with good surgeons. Then they followed these patients for several years, like an average, I think, of follow up was something like six years. The Kaplan Meier plot goes out to 12 years. They took the baseline echos before surgery, and they measured global longitudinal strain using software that you can measure this using the DICOM digital echo. They, in this large sample, again, 737, they looked at them and it’s a common statistical way. Let’s take the group and cut it in half. Based on the median value, you have the low strain and the high strain. Again, this minus sign confuses a lot of people, so we’re going to say the good strain and the bad strain, the better strain and the worse strain. The median value in the severe MR population was 21.7% or -21.7. You could say, “Well, that’s high.”
Perry: Yeah, from what you said earlier, that’s a normal strain.
Gorcsan: But it’s on the high end. If you recall exactly what I said, it was 19 to 20. This is almost 22 if we round the 21.7 to 22. It’s the same thing, because strain is load dependent. Same thing that’s going on with EF. A normal left ventricle should have a higher strain than normal because it’s unloaded. Take a minute or two to have that sink in.
Gorcsan: Then they did the statistical analysis and I applaud this group, again, because it was such a important study, where they looked at the probability of death over 5 years. And they plotted strain versus probability of death. Again, if you’re starting with strain at 25, 24, 21, the probability of death is very low. This is after mitral valve surgery, and we’re starting with patients who were asymptomatic. But once you cross this 20% or -20% again, the probability starts going up, and then 19%, which is a normal strain value with normal human dynamics, the probability really goes up of death after surgery below 19.
What this implies retrospective, need prospective validation, that the strain is showing us some concealed left ventricular dysfunction in these patients, certainly something going on that puts them at risk for a less-favorable outcome. In heart disease, left ventricular function many times turns out to be the most important factor. We don’t know for sure. This is a retrospective analysis. But I think it teaches us something important, that strain can add to ejection fraction in a specific clinical scenario such as severe mitral regurgitation.
Perry: Wow. Thank you for that interesting discussion around severe MR, very interesting. We’ve covered a lot of different areas and topics. What do you, maybe, see coming down the line as far as next assessments or areas of growth in assessing LV function?
Gorcsan: That’s a good question. I always, as researchers do, we like to gaze into the stars or think about the future or something like that. What I think is that it should be part of a clinical trial design for future agents. There’s going to be new therapies, new pharmacologic agents, new things to be tested, new devices that this measure, GLS, becomes part of the baseline data collection. So that the evolution will be, if we’re going to establish GLS into everyday clinical practice, we have to prove it means something. That’s only going to be with a clinical trial design where you’re testing a new therapy, be it a pharmacologic agent or a device.
That’s one thing. Also in the valve story, we’re in the new era thinking about valve disease with great advances in TAVR for the aortic valve and also with the MitraClip, the COAPT study just completely changed everyone’s thinking about functional mitral regurgitation, reducing heart failure hospitalizations by half with the MitraClip. Maybe in this kind of clinical trial scenario, that if you look at strain, it will be a feature of patient selection above and beyond ejection fraction. That’s my dream in the future.
Perry: Gotcha. Great. Thank you for your time. I really appreciate you visiting with me and sharing a lot of your expertise with us.
Gorcsan: This is John Gorcsan signing off from Washington University in St. Louis, and thank you, Dr. Perry, for inviting me to speak with you.
Perry: Thank you, again. We’ll talk to you again hopefully another time.
Perry: Thank you for listening to this episode of AP Cardiology. This series is cosponsored by MedPage Today and by the Division of Medical Education at Washington University in St. Louis School of Medicine.
Andrew Perry, MD, is a resident physician at Barnes-Jewish Hospital and Washington University School of Medicine in St. Louis.