Hi everyone, my name is Meredith Pugh, and I'm an associate professor of medicine at Vanderbilt University Medical Center in Nashville, Tennessee. And I'm going to be speaking in this talk about decompensated right heart failure and pulmonary embolism. I have no relevant financial disclosures. So this talk is divided into three chapters. In the first chapter, we'll cover the etiology treatment and complications of right heart failure. In the second chapter, we'll talk about the diagnosis and risk assessment of pulmonary embolism. And in the third chapter, we'll talk about treatment of pulmonary embolism in critically ill patients. So for the first chapter, we're going to focus on decompensated right heart failure. The learning objectives for this session are to describe the signs and symptoms and pathophysiology of decompensated right heart failure, and to review the different causes, treatment goals, and potential complications. So I'd like to begin by reviewing some of the normal right ventricular physiology because it differs a little bit from the left ventricle. First of all, the right ventricle pumps against a low pressure system. Recall that the RV has to be able to accommodate large changes in cardiac output with exercise, and that the pulmonary vascular bed typically can respond to these changes in cardiac output and increase in flow with minimal changes in blood pressure due to pulmonary vasodilation and pulmonary recruitment. And diseases like pulmonary hypertension that affect and change these variables can lead to right ventricular pathophysiology. Recall that the anatomy of the right ventricle is different. It is a free wall that's wrapped around the medial wall of the left ventricle, somewhat crescentaric in shape and much thinner than the left ventricle. And because of the reduced muscle mass relative to the LV typically has a much lower energy expenditure. Perfusion of the right ventricle from the coronary arteries, typically the right coronary artery occurs both in systole and diastole, which differs from the LV. And the right ventricle is very poorly able to adapt to sudden increases in afterload. And stroke volume typically decreases when there is an abrupt increase in RV afterload or increase in pulmonary vascular resistance. And this, the idea of interventricular dependence affects how the RV and LV interact when there's pathology on either side of the septum. We'll review quickly the signs and symptoms of right heart failure, which can be very nonspecific. So patients with RV failure can present with dyspnea, swelling, chest pain, and syncope. On physical exam, you may see signs of elevated right-sided pressures, elevated CVP, edema. You may hear a TR murmur. Patient may be tachycardic or hypotensive, and you may feel an RV heave or hear a gallop. Labs and imaging to evaluate right heart failure would include, of course, cardiac biomarkers, lactic acid, echocardiography, contrasted CT to evaluate the pulmonary vasculature, and also the right ventricle, cardiac MRI, and then, of course, pulmonary artery catheterization. In the ICU, you may see patients with right heart failure related to a variety of acute and chronic disease processes. And many times, right heart failure in the ICU is related to an established diagnosis of pulmonary vascular disease. However, there are some acute pathologies like pulmonary embolism, ARDS, or post-cardiac surgical settings where right ventricular failure may be acute. And the goal is always to optimize right ventricular function while addressing the underlying cause of right heart failure. And the four major physiologic causes of right heart failure, or the four features, can be described as excessive preload, excessive afterload, insufficient contractility, or reduced leucotropy, or impaired relaxation. And so let's talk about each of these. So what are the causes of excessive preload that may contribute to right heart failure in the ICU? Well, certainly, valvular regurgitation like tricuspid or pulmonic regurgitation, intercardiac left to right shunts, or even extracardiac arteriovenous shunts like large hemodialysis, arteriovenous grafts, or excessive fluid administration contributing to excessive preload. What about causes of right heart failure related to excessive afterload, acute pulmonary embolism, causes of the pulmonary vasculature like pulmonary hypertension, left ventricular failure, pulmonic stenosis, and then some things that we do to patients in the ICU like positive pressure ventilation, particularly with high pressures, and pathologies that we see commonly like ARDS or acute exacerbations of chronic lung disease. Right heart failure caused by insufficient contractility comprises the third category, and this would include things like myocardial infarction or RV-specific cardiomyopathies, congenital heart disease, post-operative causes of right heart failure from LVAD in particular, and then of course sepsis, which can lead to reduced contractility of the right ventricle. And then lastly, the category of diseases that result in reduced leucotropia or impaired relaxation, which would include myocardial fibrosis, constrictive and restrictive myocardial disease, and other cardiomyopathies. A brief word about pulmonary hypertension. I think that this topic in and of itself is fairly complex for the board exam, but you likely will be asked to recognize pulmonary hypertension to categorize and to think about initial treatment strategies in critically ill patients. Recall that the definition of pulmonary hypertension is a hemodynamic one with a mean pulmonary pressure greater than 20 millimeters of mercury, and hemodynamically pulmonary hypertension can be categorized in either pre-capillary, post-capillary, or combined pre- and post-capillary pulmonary hypertension. In pre-capillary pulmonary hypertension, the mean pressure is greater than 20, the wedge pressure is normal by definition less than or equal to 15, and the pulmonary vascular resistance is greater than three wood units. This would be characterized as either group one or pulmonary arterial hypertension, group three or pulmonary hypertension associated with chronic lung disease or hypoxemia, or chronic thromboembolic pulmonary hypertension, which is group four pulmonary hypertension. Post-capillary pulmonary hypertension, on the other hand, is a mean pressure above 20 and a wedge greater than 15 with a vascular resistance that's near normal, less than three wood units. Most commonly, we see this related to left heart disease, either systolic or diastolic heart failure, and occasionally in pulmonary hypertension that is group five or related to miscellaneous causes. And then, of course, the mixed group of combined pre- and post-capillary pulmonary hypertension. These patients can be challenging to manage where the mean pulmonary pressure is greater than 20 and the wedge is greater than 15, but the vascular resistance is also elevated. Frequently, pulmonary hypertension that is combined pre- and post-capillary may be seen in patients with long-standing group two pulmonary hypertension with vascular remodeling, or patients with connective tissue diseases like scleroderma that can affect primary pulmonary vascular disease and then also myocardial disease, et cetera. What is an approach to management of these patients in our ICUs with decompensated right heart failure? It goes back to thinking of the four physiologic tenets or main causes of right heart failure. First is preload optimization. An optimization of preload may be different depending on the acuity of right heart failure and the afterload of the RV. For some patients, like an RV infarct, volume challenge may be appropriate to optimize preload to help in a stroke volume, whereas in patients with an elevated right ventricular afterload, an RV failure preload reduction through diuresis or ultrafiltration is oftentimes necessary to help in forward flow and augmentation of cardiac output. What about optimization of afterload? Well, we want to avoid things in the ICU that could further exacerbate RV dysfunction and raise pulmonary right ventricular afterload or raise pulmonary vascular resistance, and this would include trying to avoid hypoxemia, avoiding positive pressure or at least high pressure ventilation, avoiding hypercarbia, and to alleviate vascular obstruction like pulmonary embolism to consider thrombolytics or embolectomy, and then for a selected group of patients with precapillary pulmonary hypertension to consider pulmonary vasodilators. For patients whose RV failure is related, is caused primarily by reduced RV contractility or to improve RV contractility in the setting of acute disease, we want to optimize again metabolic derangements and reduce ischemia by maintaining adequate SVR and consider use of inotropic agents, and in severe refractory cases, consider mechanical support like veno-arterial ECMO for RV support. And then it's difficult to acutely manage reduced contractility, excuse me, reduced relaxation that can contribute to RV dysfunction, but reducing ischemia and optimizing other variables are our best tools to help in this particular derangement. So there are no gold standard inotropes or vasoactive agents to support right ventricular dysfunction. Our primary goal is to improve right ventricular contractility and blood pressure, and to avoid increasing pulmonary vascular resistance. And as shown on this slide here, there's positives and negatives about many of these different agents. Epinephrine and norepinephrine are used commonly in the support of blood pressure in patients with RV failure, and then for inotropic agents, dobutamine and milrinone are commonly used, and this may be institution specific. As I mentioned previously, you should consider whether there could be benefit to using pulmonary vasodilators with the goal of reducing RV afterload, and these agents are specifically geared towards helping patients with precapillary pulmonary hypertension, like pulmonary arterial hypertension, or in selected other groups of patients. In the ICU, we most commonly reach for inhaled or intravenous vasodilators, as these are more rapidly titratable and easier to administrator with shorter half-lives. In the inhaled agents available to us, we have nitric oxide, iverprostanol, iloprost, and triprostanil. IV agents would include iverprostanil and triprostanil. Nalsildenafil, a phosphodiesterase 5 inhibitor, is also available to give intravenously. The oral pulmonary vasodilators are oftentimes not the first choice in the intensive care unit, but may be valuable therapies for managing these patients upon recovery and outside the ICU. And then lastly, mechanical circulatory support for severe refractory patients. And a reminder that circulatory support for the RV is typically a bridge to a more definitive management strategy, either medical optimization, RV recovery, or potentially transplantation. And VA ECMO is generally preferred, as it can improve and support RV function and be used potentially in awake patients. At this present time, a right ventricular assist device is not helpful, particularly in patients with severe pulmonary hypertension, but may be helpful in some patients with post-operative right ventricular dysfunction or in the management of patients with left ventricular dysfunction. And there are complications, of course, of mechanical circulatory support, including bleeding, pulmonary hemorrhage, stroke, and VTE that have to be weighed against the potential benefit for patients. And lastly, one word of caution regarding endotracheal intubation in patients with decompensated right heart failure. Recall that many of the aspects of endotracheal intubation, including induction, positioning of patients, application of positive pressure, and then, of course, periods of apnea or hypoventilation that may occur in the peri-intubation period can be very dangerous for patients who already have right ventricular dysfunction. And this slide summarizes some of the ways that these aspects of endotracheal intubation can affect physiology and further impair RV function, including induction therapies that may decrease cardiac output or drop blood pressure, which can set off a spiral of worsening right ventricular dysfunction. Positioning, apnea, and hypoventilation can contribute to hypoxemia and atelectasis, raising pulmonary vascular resistance, and lowering cardiac output. And then, of course, positive pressure ventilation can decrease right ventricular preload and raise afterload that could further impair RV function. And so it's right to have a high sphincter tone if you're called to think about intubation in a patient with severe right ventricular dysfunction. And most sources call to avoid intubation if possible. So you want to make sure that you're maximizing use of non-invasive respiratory support measures like high flow nasal cannula and to potentially cautiously consider non-invasive ventilation before moving toward mechanical ventilation. You want to utilize your hemodynamic monitoring tools and do all that you can to avoid systemic hypotension and these other factors on the previous slide. Heavily weigh the risks and benefits of rapid sequence intubation versus awake intubation and definitely have a backup plan and experienced operators in the room to help manage these complex patients. Okay, we'll move in this next chapter to the diagnosis and risk assessment in pulmonary embolism. So in this chapter, we'll focus in specifically on diagnosis of pulmonary embolism in critically ill patients and how to assess risk of poor outcome in patients with pulmonary embolism. So as you all know, a pulmonary embolism is defined as an obstruction of the pulmonary artery or one of its branches, most commonly by thrombus. But keep in mind that the boards may ask you about some other more unusual causes including embolism of tumor, air, or fat. And pulmonary embolism can be acute or it can be chronic as we've already talked a little bit about chronic thromboembolic disease that can lead to pulmonary hypertension. The focus of this talk is primarily acute pulmonary embolism. And the first step to diagnosing pulmonary embolism is to have either a gestalt or to use a validated tool to determine the pretest probability of pulmonary embolism. The well score is a validated tool that I've shown on this slide. I don't think the boards would ask you specifically to calculate a well score for a patient. But the signs and symptoms shown here correspond to a point total and a moderate probability of pulmonary embolism is a score of two to six with a high probability of PE being a score greater than six and a low probability of PE being a score less than two. And for patients with a low pretest probability of pulmonary embolism, in many cases these are not the patients that we're seeing in our ICU. But recall that it is that population of patients where testing like a D-dimer could be helpful whereas patients with a moderate or high probability for pulmonary embolism you may need to move more quickly toward more definitive assessment or even treatment in the case of a high probability patient. As I mentioned for critically ill patients the D-dimer is not a particularly helpful test. I think if you saw D-dimer on the list of options in a board exam question about a critically ill patient with pulmonary embolism it would likely not be the correct answer. But D-dimer does have its utility and a good negative predictive value in patients with a low pretest probability where the prevalence of pulmonary embolism is low. However in a critically ill patient particularly if they have other pathology like sepsis or hemorrhage it in of itself is not a very helpful test. In terms of making the diagnosis of pulmonary embolism for many of our patients cross-sectional imaging with CT angiography is the test of choice. This slide represents a patient with a very large burden of central or saddle pulmonary embolism by the filling defects on both the left and the right and then crossing the main pulmonary artery here. Some patients that we see may be too sick or too unstable to travel to the CT scanner and bedside echocardiography has utility in this instance. And some of the signs that may support a pulmonary embolism diagnosis on echo would include dilation of the RA or RV, right ventricular dysfunction, in particular hypokinesis of the right ventricular free wall with preservation of apical contraction known as McConnell sign may be seen. And then the 60-60 sign, which is a shortened pulmonary ejection acceleration time less than 60 milliseconds with a mid systolic velocity deceleration or notch in the RVOT and peak systolic gradient of less than 60 is another useful sign with a bit more advanced bedside echocardiography that can support a pulmonary embolism diagnosis. And then of course the finding of thrombus in the right atrium or right ventricle or clot in transit sign, along with lower extremity evaluation showing thrombus all are worrisome and would support a diagnosis of acute pulmonary embolism. Recall that PE can be classified into low intermediate and high risk on the basis of clinical factors. In the ICU, we are likely seeing patients who more likely will fall into the intermediate and high risk, but a low risk pulmonary embolism patient is a patient who for that pathology alone likely does not need the intensive care unit. These are patients who are hemodynamically stable and have no evidence of right ventricular strain biochemically or by imaging, whereas a high risk patient with pulmonary embolism would be a patient who has hemodynamic instability defined in most sources as a systolic blood pressure less than 90 or a drop in more than 40 millimeters from baseline or a requirement for vasopressors. And these high risk patients with pulmonary embolism are the group that carry the highest risk for death or poor outcome, should likely be managed in an intensive care unit setting until they are stabilized and where therapies like thrombolysis or embolectomy should be considered. And then this intermediate risk group of patients are patients who are hemodynamically stable but have evidence biochemically through troponin BNP or imaging evidence of right ventricular dysfunction, including evidence of RV dysfunction on echo or through CT findings like a dilated RV or an RV to LV ratio greater than one. What are the predictors of mortality in pulmonary embolism? Well, the big ones are RV dysfunction and RV thrombus. Studies have shown that the presence of right ventricular dysfunction defined either by echo or CT scan increases mortality twofold in all comers. And of course, development to overt hemodynamic instability or hypotension increases the risk substantially. The finding of a right ventricular thrombus increases both 14 day and three month mortality quite considerably as well. And laboratory assessment that predict poor risk or predict high risk in pulmonary embolism include elevations in BNP and troponin. And of course, the finding of both of these things together increases mortality in an additive fashion. There are validated scores to predict mortality. A commonly utilized one is the simplified pulmonary embolism severity index or S-PESI that is shown that consists of six variables here, including age, history of malignancy, history of chronic lung or heart disease, tachycardia, the heart rate greater than 110, hypotension with a systolic blood pressure less than 100, and hypoxemia with a saturation less than 90. And scoring one or more of these points denotes a high risk of 30 day mortality. And if overt shock is present, it's associated with 30 to 50% risk of death. So when thinking about risk stratification of patients and who should come to the intensive care unit, assessing the cardiac biomarkers, early assessment of imaging, and then considering calculation of an S-PESI are all things that can help predict the highest risk patients that should land in the intensive care unit setting. And you're familiar with the complications of pulmonary embolism that can be divided into early complications like RV failure, hypoxemia, pulmonary infarction, hemothorax, and then of course death, typically related to hemodynamic deterioration. And late complications, which would include recurrent venous thromboembolism or development of pulmonary hypertension related to chronic pulmonary embolism. And so again, if we summarize this section of the talk, diagnosis of pulmonary embolism is typically done by CT angiography or echocardiography or the combination of those two tests together through analysis of clinical parameters, either gestalt or use of a well score to calculate a pretest probability. High risk patients are those patients that have evidence for right ventricular dysfunction biochemically through echo or CT, and then treatment relies on risk stratification of patients into low, intermediate, or high risk. So now in the final portion of this talk, we'll move on to talking about treatment of pulmonary embolism with a focus on intermediate and high risk patients. Our learning objectives for this portion are to talk about the guideline directed algorithm for treatment and to describe the indications and contraindications for thrombolytic therapy in pulmonary embolism. So the highest risk patients are the patients that present with hemodynamic instability, and the tenets of management for these patients include anticoagulation or thrombolysis, respiratory support, hemodynamic support, and then as I mentioned, definitive acute management with either thrombolytic therapy or embolectomy. What is the best anticoagulation strategy? It really, again, depends on risk. For highest risk or hemodynamically unstable patients, most studies and data support the use of unfractionated heparin. However, low molecular weight heparin could also be considered in patients with low bleeding risk. For low risk patients, again, patients not likely to arrive in our ICU for that diagnosis, a direct oral anticoagulants are now the preferred agent based on the guidelines. And then hemodynamically stable or these intermediate risk patients, the choice of anticoagulation may be center and intensivist or procedural specific, but would include low molecular weight heparin for many patients or unfractionated heparin for some patients as well. What about respiratory support? So all patients should have their hypoxemia supported with supplemental oxygen, and in some cases, high flow nasal cannula may be needed. And as we discussed previously, when considering RV failure, non-invasive ventilation may carry some risks because of reduced preload in the setting of positive pressure, and definitely approach mechanical ventilation, which may be indicated with caution, particularly in patients who have intermediate risk or evidence of right ventricular dysfunction. Those patients are at particular risk, as we previously discussed, around the time of intubation. And for hemodynamic support of these patients, a lot of the tenants that we discussed in RV failure apply. We want to have caution with IV fluids. We want to consider a vasopressor and inotropes in patients. And then there is a growing body of evidence supporting the use of extracorporeal life support, primarily VA ECMO, in managing patients with hemodynamic instability in acute pulmonary embolism. So let's talk now about the role of thrombolytics. I think for the board exam, because this is an area with a lot of gray zone, the board exam is likely only to ask you about situations where the guidelines are fairly clear. And for pulmonary embolism, the guidelines are clear that thrombolytics should be avoided for low-risk patients, and thrombolytics should be considered for patients with low risk of bleeding who are hemodynamically unstable. And then there's a lot of gray zone in between. The pros of thrombolytic therapy, we know that thrombolytics improve short-term RV function and pulmonary perfusion. And several meta-analyses have shown that in the setting of massive pulmonary embolism, thrombolytics improve composite outcome of death and recurrent pulmonary embolism. But the cons or the main risks of thrombolytics relate to bleeding risk, and that numerous studies have not shown conclusive evidence of a long-term mortality benefit to thrombolytic therapy, and there is a clear signal for increased risk of bleeding, both intracranial and extracranial significant bleeding episodes. This slide lists several of the potential indications for thrombolytics, with hypotension, the systolic blood pressure of less than 90, and then of course cardiac arrest or CPR being the two clearest indications in the current guidelines for thrombolytic therapy. And then several others, at least in our U.S. guidelines, that are not quite as clear, but times where intensivists may consider thrombolytics include severe RV dysfunction, severe hypoxemia, an extensive clot burden, or a clot in transit or free-floating clot. Contraindications to thrombolytic therapy should be known, and this is testable, and would include the risk of CNS bleeding, so intracranial neoplasm, or recent CNS surgery or trauma, a history of hemorrhagic stroke at any point, a recent non-hemorrhagic stroke, or uncontrolled systemic hypertension, and then of course the risk of internal bleeding if a patient has had a recent internal bleeding, has a bleeding disorder, recent surgery at a non-compressible site, or severe thrombocytopenia. I am going to review a few of the guideline statements which I think are important for clinical practice, and these arise from the guidelines in CHEST 2021. In patients with acute pulmonary embolism associated with hypotension, so this high-risk PE group who do not have a bleeding risk, we suggest systemically administered thrombolytic therapy over no thrombolytic therapy. What about the patients in this intermediate risk, or submassive pulmonary embolism group? So as a reminder, these are patients who have biochemical or imaging findings of right ventricular dysfunction who are normotensive. This has been evaluated through several studies, and this slide summarizes the PYTHO study from New England Journal of Medicine in 2014 that looked at 1,000 patients who were randomized to either receive tenecteplase or placebo in addition to anticoagulation. This study showed a reduction in the primary outcome of death or hemodynamic instability in the group treated with thrombolytic therapy, but no significant difference in the death from any cause outcome. Patients treated with thrombolytic therapy have a significantly higher increased risk of stroke and extracranial bleeding, and the take-home from this study is that fibrolytic therapy decreased the risk of hemodynamic deterioration in these intermediate risk PE patients, but increased the risk of bleeding and did not change mortality at 30 days. And this is reflected in the current guideline statements that in patients with acute PE not associated with hypotension, we recommend against systemically administered thrombolytic therapy. However, the guidelines support considering systemic thrombolytics in patients with acute PE who initially may be hemodynamically stable but then deteriorate with anticoagulation alone. And another meta-analysis published in JAMA in 2014 looked at 16 trials of patients, the majority of whom had this intermediate risk, and found that thrombolytics decreased mortality but increased risk of bleeding, and the patients at greatest risk for adverse outcome related to thrombolytics appeared to be patients over the age of 65. So I think the response to evaluation of a intermediate high risk, intermediate to high risk patient is a challenging topic, likely not to be covered on the board exam because there is a need for ongoing study, and it's a very individualized approach to managing these patients. What alternatives exist to systemic thrombolytics? Of course, there are catheter-directed thrombolytic treatment options with current data being small studies but a potential benefit for patients who may be at higher risk of bleeding. And then, of course, catheter-directed clot removal or retrieval devices or catheter-directed embolectomy oftentimes combined with thrombolytic therapy. There are no large randomized controlled trials to date. And then, of course, surgical embolectomy requires availability and an experienced surgeon but is to be considered when a patient has a high risk of bleeding or contraindication to thrombolytic therapy. What do the guidelines say about catheter-directed options? Well, for catheter-directed thrombus removal, the guidelines suggest that it should be considered in patients with acute pulmonary embolism with hypotension who also have a high bleeding risk in whom thrombolytic therapy may be contraindicated or in patients who fail systemic thrombolytics or in patients who have shock that is likely to cause death before thrombolytic therapy can take effect. And in these groups of patients, catheter-assisted thrombus removal may be recommended over anticoagulation alone. And in patients with acute pulmonary embolism who are treated with thrombolysis, the guidelines currently suggest systemic administration of thrombolytics rather than catheter-directed thrombolytics. And then lastly, let's talk about IVC filters. Currently, the guidelines do not support placement of IVC filters in patients with an acute DVT who are on anticoagulation. However, in patients with a DVT that is proximal who cannot be anticoagulated, an IVC filter should be considered. And the placement of retrievable IVC filters and whether they reduce long-term risks, and in particular, recurrent VTE has been evaluated in several studies, and one that I've summarized here that looked at patients who had intermediate risk and high risk for recurrent PE with risk factors shown here. All patients received anticoagulation, and in most patients, filters were removed. But this study showed that the placement of retrievable filters did not reduce the risk of recurrent pulmonary embolism at three months. And lastly, many of our institutions have created a PE response team because this is such a complex management decision that oftentimes crosses multiple disciplines where decisions need to be made very quickly. The role of the PE response team or PERT team is to help provide an institutional framework and an organization to be able to rapidly manage these patients. And there have been several publications that have looked at potential benefits including reduction in mortality, less bleeding, lower rate of IVC filter or off-guideline treatment decisions, and I think many of our institutions have adopted a multidisciplinary PE response team to help us support these patients. However, overall, to date there has been inconsistent mortality benefits seen with the creation and utilization of a PERT team. So I'll end with some summaries and some pearls for the board exams about pulmonary embolism. I think you will likely be asked and need to identify factors associated with high risk, including elevated biochemical markers like BNP troponin and findings of right ventricular dysfunction by CT or echocardiography. I think you should be familiar with when the guidelines would recommend administration of thrombolytics. I think you're likely not to be asked on the board exam about intermediate risk patients because there is a lot of gray zone here and that PE response teams may provide some benefit but at least right now have not uniformly been shown to decrease PE mortality. Thank you very much for your time and good luck on the boards.

decompensated right heart failure

pulmonary embolism

etiology

treatment

diagnosis

risk assessment

individualized patient management