Talking Tall Rounds®: Pulmonary Embolism

Podcast Transcript

Announcer:

Welcome to the Talking Tall Rounds Series, brought to you by the Sydell and Arnold Miller Family Heart, Vascular and Thoracic Institute at Cleveland Clinic.

Leben Tefera, MD:

My name's Dr. Leben Tefera. I'm a physician in the Vascular Medicine department, and I'll be our moderator today. Our Tall Rounds today will be discussing pulmonary embolism. As we know, PE can be a complex disease that is best served with a multidisciplinary approach. So today we'll be talking about the latest cardiovascular innovations and forms of treatment and offering some insight. So, we'll get started with a case from our fellow, Dr. Umar Khalid, which really highlights all the forms of modality of treatment of high-risk PE that we'll be talking about today. Thank you.

Umar Khalid, MD:

Our case today is about an acute episode of pulmonary embolism, which basically covers almost all of the treatment modalities that are to be offered to the patients when they come with an acute PE episode. This timeline kind of gives an idea of the treatment options that were given to this patient, followed by a complicated post-op course, but an overall good outcome.

We have a patient who is a 66-year-old male with a history of COPD and an extensive smoking history who had presented with shortness of breath, chest discomfort for two weeks. In the ER it was found to be hypoxic initially, was given supplemental oxygen. However, decompensated requires high flow nasal canula. Initial investigations included a mildly elevated troponin, but an NT-proBNP 2000. And this is his 12-lead EKG showing evidence of right bundle branch block and RV strain with sinus tachycardia.

He underwent a CD pulmonary angiogram, which you can see over here. He has extensive thrombus burden in the right pulmonary artery and bilateral sub segmental and lobar pulmonary arteries as well. Along with that, there was dilation of the right ventricle suggesting strain, and then there was also dilation of the pulmonary artery. He underwent a bedside echocardiogram which showed a pressure and volume overload with septal deviation towards the left side of the heart.

Initially, the plan was made to treat him with conservative management including systemic anticoagulation. However, in the next 24 hours, the patient did not improve, and a PERT meeting was held, so he was taken for an aspiration thrombectomy. However, during the procedure, the pigtail catheter traversed a large PFO, and the pulmonary arteries could not be engaged. Then a right pulmonary angiogram was done through the PFO and there was an eccentric large occlusive thrombus seen and there was extension to the truncus basalis as well.

Here you can see on the left side of the image there is literally occlusion of the right lower lobe segmental arteries and non-opacification, and then the pigtail catheter crossing through the PFO. After this procedure, a recommendation was made to repeat an echo with agitated saline contrast, and then the patient did not improve further. So systemic thrombolysis the TPA was also given in the next 24 hours. Here you can see in the apical images that there is right ventricular dilation. There is bowing of the septum towards the left, and then on the right image there is almost spontaneous opacification of the contrast on the left side as well as through the PFO.

So, despite these measures, the patient did not have any significant improvement and required around 80 liters of high flow oxygenation. Then cardiologists were asked to evaluate the patient to see if PFO would be a possible cause for this hypoxia or in part causing the hypoxia. So, he underwent a right heart catheterization with occlusion of the PFO for 10 minutes and there was no change in arterial oxygenation pressures before and after the occlusion as we can see. At that time, recommendations were made to get in touch with cardiothoracic surgery to evaluate the patient for thromboembolectomy.

And these are the pictures from pulmonary thromboembolectomy. A pre-operative IVC filter was also placed in this patient because he had a left proximal DVT in the popliteal vein, and then after the thromboembolectomy, he required a VV-ECMO because of RV failure and cardiogenic shock. The difference between the pre-operative and post-operative pulmonary artery pressures were pretty significant and postop, the patient did well, however, developed a bronchial bleed requiring IR guided embolization and then ventilator acquired pneumonia requiring IV antibiotics extended spectrum.

But he was finally discharged out of the hospital on only two liters of oxygen, and on most recent evaluation in the pulmonology clinic, he was finally weaned off from the oxygen and he was able to get back to his daily life with minimal shortness of breath symptoms. That is basically what this patient covers throughout the treatment modalities of the acute PE. Thank you.

Scott Cameron, MD, PhD:

Thanks for the opportunity to present, Dr. Tefera, on three of my most precious specialties, vascular medicine, cardiology and critical care. So, this case by Dr. Khalid clearly constitutes complex decision making, which is quite typical of many of the patients, and we see in this is the whole reason behind the so-called pulmonary embolism response team concept. So, I'll show you a little bit about how this team's evolved. It's in recognition of the fact that pulmonary embolism is really a disease that's not owned by anyone's specialty. The patients will hugely benefit from input from intensivists, cardiologists, vascular medicine specialists, specialists in thrombosis, pharmacy, mechanical cardiac assistance. And because of that, the team concept was born in 2012 at the Massachusetts General Hospital. Kenny Rosenfield, who's section head of vascular medicine and interventions there, really was the individual that spearhead this and it's really, really taken off not just across the United States actually, but across the world.

And just to make the team concept a little bit clearer, I'll take an example where they looked at about 7,000 individuals and asked them to guess the weight of a cow. On the left, you're looking at all individuals on the right experts in bovine care, and what they found is that the average guess, the centroid, was actually within about 10 percent of the actual weight for both all comers and the so-called experts. So, what this highlight is even though if you're a trained expert, you actually could be wrong in decision making because it's a complex situation and that's where the team concept really comes into play. And I think Cleveland Clinic really typifies this in every area of cardiovascular medicine.

So, the PERTs around the world, as I mentioned, started off in Boston, Massachusetts. You can see that they're really taking over North America. You can see that they've branched out into Europe, into Asia and Australasia. So really this is a really fantastic thing, but does it really make a difference? The Cleveland Clinic Pulmonary Embolism Response Team is run by multiple specialties as you can see here, just some highlights. Dr. Tefara, of course, in Vascular Medicine is the lead for Cardiovascular Medicine. Dr. Ihab Haddadin in Interventional Radiology, I really credit for the decrease in mortality at the Cleveland Clinic. Dr. Joanna Ghobrial and Aravinda Najundappa from Interventional Cardiology, and then Dr. Gustavo Heresi from Pulmonary Medicine who's an expert in CTEPH and of course, Dr. Tong. So, you'll hear from some of those individuals today. We'll also show you a little bit of the quality data and some research outcomes that have been published by us and by others.

So quality assurance is of course very important. Every single case at Cleveland Clinic is carefully evaluated by about 90 variables that we keep in a HIPAA compliant database. And you can look at these things and make real time adjustments. So, for example, we know how long it takes between the diagnosis of pulmonary embolism and therapeutic anticoagulation. We know how long it takes from patient presentation to diagnosis of pulmonary embolism, and it turns out that there is mortality benefit from knowing that information as I will show you.

A good paradigm to start off with the Pulmonary Embolism Response Team is to just keep things simple. That's how I do it. So, there's low risk, intermediate risk, or high-risk pulmonary embolism. The low-risk pulmonary embolism, those are the patients that are appropriate for stratification using the pulmonary embolism PESI score severity index. Usually, those patients will have a mortality in about 30 days, no greater than about 5 percent or 7 percent. We know that if a patient has right heart dysfunction automatically, the risk for that patient for mortality is about 20 to 25 percent at 90 days. These are patients that sometimes will get treatments beyond systemic anticoagulation such as percutaneous procedures or systemic thrombolysis. We'll hear about that. And then those patients who've got cardiogenic shock from pulmonary embolism, the so-called high risk or massive pulmonary embolism, these are the patients that unless contraindicated, will require systemic thrombolysis. Sometimes surgical embolectomy with pressers, sometimes they'll go on VA-ECMO and before that happens, and we'll hear a bit about that too.

So, in terms of the importance of cardiovascular medicine, well, it turns out that there are many things that can mimic high risk pulmonary embolism. And I always say that after a cardiac arrest, if you look at the right ventricular dilation and use that as justification for giving a systemic thrombolytic agent, that would not be the best thing to do. For patients, this has actually been studied experimentally. Post-arrest for any reason the right heart dilates, the ventricle dilates. It's a very flimsy structure. I've seen in many cases RV myocardial infarctions present like a pulmonary embolism. They have clear lung fields, hypotension, jugular venous distension. The right heart failure can do that. CTEPH can do that. Cardiac tamponade can do that. And of course, aortic dissection. We see it all here. We've seen aortic dissections present with a sub segmental pulmonary embolism, and the risk is of course anchoring bias. So, if you see a hypotensive patient, you know there's a pulmonary embolism. Is it the pulmonary embolism that's causing it or is it another concomitant disorder? And I think that's where the cardiologist really does their best work.

Does it change how people treat patients? Well, it turns out this has also been studied according to Likert scale. Residents and fellows, this was a study I was involved in a number of years ago, felt that after the institution of a per embolism response team, not only were they better educated, but they felt that the patients were getting better care. And they saw that as a very positive thing, not just extra work. If you look at metrics in the emergency department, the pulmonary embolism response teams have improved the triage to diagnosis time, the diagnosis to heparin institution time, and the triage to disposition time to either an inpatient in most cases or an intensive care unit. If you look here pre-PERT, this is the average triage to diagnosis time at a hospital in upstate New York where I used to work. And you can see that as you go 3, 6, 9, 12 months, see everything's tightening up there. So, this is the whole hospital learning the Pulmonary Embolism Response Team concept. And this is translating into decreased mortality, which is the whole point of the team.

So, what does Cleveland Clinic show? So, this is a paper published by our Dr. Pulkit Chaudhury and Dr. Jerry Bartholomew a few years ago that showed in the pre-PERT era compared to the post-PERT era by a Pulmonary Embolism Response Team decision making process, there was a decrease in mortality by about 5 percent at 30 days. There's a shorter therapeutic anticoagulation time, and there's also a decreased risk of significant bleeding. And part of that is there are obviously lots of different anticoagulants we can use, and one size doesn't fit all in, and that's where vascular medicine is most helpful. This was one of the first manuscripts I'll say that came out to really show a decrease in mortality. This was a study from my last institution at University of Rochester five years ago. If you look at the pre-PERT era and the post-PERT era, there was a sustained decrease in mortality out to six months after PERT implementation. This is the only study that's shown a sustained decrease in mortality. And if you go by multivariate regression analysis, the use of enoxaparin compared to unfractionated heparin actually has a decreased mortality signal and so does the triage to diagnosis time. I personally thought it would've been diagnosis to anticoagulation time, but it was actually the triage to diagnosis time that had a significant impact on mortality. And for every hour that there was a delay in diagnosis of intermediate or high-risk PE, mortality increased by 5 percent. So that's very, very significant there. And if you look at something like STEMI, the 90-day mortality for high-risk pulmonary embolism is eight times higher than STEMI. Not many people know that, so it's pretty serious.

So nonetheless, PERT also had a sustained decrease in mortality, relative risk reduction, 43 percent. And then interestingly, there was also a reduced length of hospital stay. So, there's cost savings there also.

Well, how does it stand up by meta-analysis? So, Dr. Konstantinides, who's run most of the clinical trials in systemic thrombolysis over the last 10 years, and most of the prominent manuscripts, took 26 studies. And I will say some PERTs use low risk PE as part of their algorithm. We don't. We use intermediate and high-risk PE. So, looking only at those hospitals that used intermediate or high-risk PE, you can see Dr. Chaudhury and Dr. Bartholomew's study from Cleveland Clinic is to the left of unity there with benefit for mortality. This is our study here at the bottom. A couple of studies on the east coast there were outliers. Overall, you can see that it doesn't quite reach a mortality benefit with meta-analysis. So why is that? And here's why. There is a wildly different algorithm that every hospital uses. I personally think that standardization as we do for STEMI should be the standard of care for pulmonary embolism. We're just not quite there yet.

So, in summary, team-based management for decision-making high-risk PE appears to be clear to me. There's massive heterogeneity in PERTs across the United States and across the world. Standardization is needed. And one of the things that the PERT consortium is really trying to do, Cleveland Clinic is part of that, is figure out what that metric is. Is it the door to balloon time that we use in STEMI? Is it the door to needle time that you use in thrombotic stroke? It may be the diagnosis time, depending on that timeframe from presentation to diagnosis that makes the biggest difference. But nonetheless, we really don't know what the best metric is.

And then just as a plug, when I'm on call, everyone knows I'm going to recommend nothing less than enoxaparin. The pharmacology is predictable. It works within 90 minutes unless it's contraindicated. We should all be giving that. As I showed you in the data here, it was an independent predictor of mortality. So again, my opinion is that a cardiologist in fact should be part of the first responders and recognition of their expertise in hemodynamic management, anticoagulation management, and then also percutaneous procedures.

Karen Hurley, PhD:

Good morning. I wanted to say thank you very much to Drs. Tefera and Cameron for inviting me to speak and for referring patients to me. So, I'm a clinical psychologist by training. My primary specialty before coming to Cleveland Clinic was cancer and hereditary cancer risk. What I want to do today is to give you an overview of some of the key psychosocial issues that we see in survivors of PE, some of which is specific to PE survivors and others which come more generally out of health psychology research and combined with observations gleaned from the psychotherapy room. And most importantly, what I wanted to do is to give you a few nuggets that you can use to connect with patients to help you in the important task of building and maintaining emotional rapport in this very challenging and highly technical situation.

So, what do we know so far? There are now a handful of studies that specifically focus on quality of life after PE, and we are learning that there are a wide range of quality of life effects very specifically in the area of dyspnea and exercise intolerance, which in turn have broad effects in terms of functioning at work, at home, educational goals, and also leisure goals such as travel or involvement in exercise and sports. We know that people are psychologically distressed, but the people do over time, as we see in other patient populations, they do start to recover a sense of quality of life. For the most part, we do see a vulnerable subset of people who either maintain a poor quality of life or who get worse over time. A very recent paper by Fisher found that about 20 percent of their population had levels of anxiety and depression that were high enough on validated scales to indicate the likelihood that they had a major psychiatric diagnosis such as major depression. This is about what we see in cancer. So, it's good that we are seeing the ways in which this literature is consonant with other observations.

Currently, we have an active study designed in collaboration with Drs. Tefera and Cameron. And the core of it is that we're using five validated measures of different kinds of psychological distress to be able to describe in more detail what's happening with our patients to be able to use validated methods of intervening with the patients. This will form the basis of developing the role of psychology and mental health in PE survivorship. I want to go through each of these very briefly. We do know that there is a risk factor for depression in these patients. Of course, people who've had depressive episodes in the past are more likely to respond with depressed mood, but there are also what we refer to in psychology is the invisible losses that happen after such a major event. So, the picture in your head of what you think is going to be happening, when we lose that through a sudden change or trauma, that loss actually, we grieve those as if we had lost a person. People also lose a sense of themselves as the different impacts on quality of life are felt.

Another thing that can happen, and again, this is probably a brief, easy intervention that anyone can do even without psychology training. We know that isolation is a risk factor for depression. So, if you ask a patient, do you have at least one person to whom you can say anything without feeling judged? That gives you a quick idea about their risk for developing depression. In terms of anxiety, if loss is the breeding ground for depression, then threatened uncertainty is a breeding ground for anxiety, and we certainly have that here in this situation. Again, patients who already have a history of anxiety being perfectionists, being worriers, history of panic attacks will all be at risk to respond with anxiety. The fact that a PE can happen suddenly and catastrophically brings a great deal of uncertainty and makes people feel that they don't have a safe zone if they're just out walking around and that you can just have the sudden symptoms, that this is an overwhelming fact of life that people are now trying to accommodate within themselves. A very special challenge with this particular population group is that the symptoms of a possible recurrence overlap significantly with the experience of anxiety, so shortness of breath in particular makes people feel that they may be having a recurrence and can in and of itself result in emergency room visits.

Also, the catastrophic nature of pulmonary embolism meets the stressor criterion for post-traumatic stress disorder that the person was exposed to death, threatened death or serious threat. You don't have to have a previous history of PTSD to be at risk, but someone who has had prior traumas, even if they didn't develop PTSD in the past, there seems to be kind of a potentiating factor that then can push them towards having symptoms of PTSD. These would be things like thinking about an event when you don't mean to, getting pictures flashing in your head, flashbacks to the traumatic time and avoidance of situations that function as reminders. One way I explain this to patients is a medical trauma is like the earthquake that shakes the building. Anything that's strong that stays standing, but any crack on the wall or anything that's not held solid can fall down. And patients do relate to this as a way to understand why they are reacting so strongly.

Sitting in the psychotherapy room with patients, I'm observing a few things. Some patients will develop a fear of being left alone, especially if they have a prior history of abandonment in their childhood. For example, a parent who was using substances. I've seen people develop an obsessive-compulsive type of behavior of constantly checking their pulse, checking their breathing over and over again. I also see people becoming very sensitive to their own body sensations as they're trying to figure out, how can I tell if I'm okay? Things like lying in bed and being able to hear their own pulse.

This is an important thing to understand, and this goes back to the case that we saw at the top of the hour, the gentleman who was described was in the hospital for 30 days. So, if you can imagine the level of disruption caused by such an unplanned interruption result in important life goals that either are thwarted in some way, delayed, or even have to be given up or altered depending on the medical course. And then sometimes it's not clear right away what the full impacts are going to be. So, supporting patients during this uncertain time where they're seeing what's going to be the fallout, what am I going to be able to do as I start feeling better?

This illustration is intended to show the dynamics of coping and stress. So, most people in adulthood have developed a pretty balanced match between their stress level and coping skills that they use to get through their levels of stress. However, under the pressure of this medical challenge, you see that PE affects, in particular, people who cope with exercise as a way to relieve stress. People who keep busy, all of a sudden, they're flat on their backs in the hospital. Then on the other hand, you have people who are suddenly going to lots of appointments, taking new medications, facing significant disruption. So that upsets the balance. As coping resources go down, stress level goes up and the person starts falling through the cracks. This actually helps to destigmatize those feelings of anxiety and depression that people are getting, and it starts to give a narrative of how you put the pieces back together.

So just to wrap up, going through a medical challenge such as a PE forces people to think about things that most of us prefer not to think about, that we're all subject to random events, we're all subject to hard times, but going through this makes that knowledge very personal.

So, in helping patients be resilient in the face of this, there are two important points. One is that resilience is something that we do. It's not a special magical power. It's the ability to create a good outcome in the face of challenge and it's always the case now. What is one thing that a person can be doing to start to help them get back on track? It's also a process. In changing circumstances, you still have to have a good day, to have that possibility be within reach. So, if somebody can't run anymore, but they've made it down the hallway and back, that becomes their new measure of a good day. Another really important process is refocusing shifting from what you can't do to what you can. If you recognize this figure from Psych 101, it either looked first to you like a vase or two faces looking at each other. That process happens naturally, and that's the foundation of our ability to make that shift.

So lastly, one of my favorite definitions of quality of life is a phrase that we are so used to hearing that maybe we don't really appreciate what we're actively talking about. Quality of life is not just what people have in their life, but also how to be in that life. So, our task truly is to help our patients figure out how to be themselves in a world that has catastrophically changed for them. Thank you very much for your attention.

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