 Hello, I'm Dr. Raymond Steinback, chief of non-invasive cardiology at the Texas Heart Institute. Today I'll discuss non-invasive imaging in patients with chest pain. In late fall of 2021, the ACC published a new guideline on evaluation and diagnosis of chest pain, which emphasizes the role of non-invasive imaging. Almost simultaneously, the American Society of Echocardiography and the European Association of Cardiovascular Imaging jointly published the guideline, Non-Invasive Imaging in Coronary Syndrome, and I will also touch on this document, which is complementary. After this discussion, I hope that you will feel more comfortable making decisions about how to manage patients presenting with chest pain. Coronary syndromes can be divided into acute and chronic. The current guidelines divide non-invasive imaging tests into functional or physiologic stress testing and anatomic testing. Functional imaging tests include stress echo, nuclear stress, and cardiac MRI. Coronary CTA is the test for anatomic imaging. These tests may not be indicated in all patients with chest pain, particularly if there is low likelihood that this is cardiac in origin, or these tests may be used individually or in a complementary fashion. Deciding how to evaluate possible coronary syndrome patients and applying the proper non-invasive imaging study is nuanced, and recommendations have been under evolution for the past 10 to 15 years. Let's start with some historical perspective. How are the current guidelines different or additive to our thinking? Here are the related guidelines published over the past 12 years. The older documents above the dotted line make strong recommendations for when to perform non-invasive testing, but the nuance of test selection is avoided. This is due to the lack of outcomes data for imaging and a tendency to leave the how-to details of specific imaging modalities for subspecialty society documents. In 2013, the ACC published a multi-modality, appropriate use criteria document for detection and risk assessment of a stable ischemic heart disease. This is the first of a long line of appropriate use criteria documents to address a disease process, coronary artery disease, and to address whether or not any functional or anatomic stress imaging test is indicated in each of a long list of commonly encountered clinical scenarios. This exercise was designed to identify areas of potential overuse by consensus of stakeholders since outcomes data for imaging tests were not available. This is a table for the 2013 appropriate use guidelines. And we see the first six of 80 common clinical scenarios in that document. The clinical scenarios here separate symptomatic patients into low, intermediate, and high-risk pretest probability of CAD. Their ECG appearance and the ability to exercise. Consensus was reached amongst a rating panel as to whether any of the non-invasive imaging modalities were appropriate or might be appropriate, or were they in fact rarely appropriate. The rating panel was specifically guided not to rank amongst the modalities in a competitive fashion, so while this document helps to identify overuse, it is not too helpful when it comes to providing guidance on which test to use. The AUC documents remain relevant quality tools, however, for helping to reduce unnecessary use, particularly in stable outpatients, where patterns of imaging overuse have been documented. The Inter-Society Accreditation Commission requires still that labs performing non-invasive tests assess appropriate use as one component of required quality improvement programs. The 2019 European Society of Cardiovascular Imaging Guideline for the diagnosis and management of chronic coronary syndromes states that selection of initial non-invasive tests based on clinical likelihood of coronary disease and other patient characteristics that influence test performance, local expertise, and the availability of tests is indicated. This document uses chronic coronary syndrome as opposed to the ACC's stable ischemic heart disease classification. This newer guideline emphasizes the crucial role of healthy lifestyle behaviors and other preventative actions in decreasing the risk of subsequent cardiovascular events and mortality and discusses the utility of non-invasive testing for potentially influencing patient outcome. This guideline is helpful from a taxonomy standpoint. It identifies six categories of chronic coronary syndromes, two without a prior diagnosis of coronary disease, either with symptoms suspicious for CAD or a new onset heart failure with suspected coronary disease etiology. The remaining four included patients with established coronary disease, either symptomatic or symptomatic, asymptomatic, and late after diagnosis or revascularization or early. And new emphasis is placed on patients with ischemia and no epicardial coronary disease as suspected from non-invasive testing. This is also known as Enoka. And finally, number six, asymptomatic individuals with diagnosis of subclinical coronary disease detected on screening evaluations, and this would include anatomic testing using CTA. All of these are scenarios that are classified as chronic coronary syndromes, but they may involve different risk for the development of future events, and the risk may change over time and non-invasive imaging is important for both disease classification and this risk stratification. This illustration from the ESC guidelines shows why stable ischemic heart disease classification could be misleading as patients with chronic coronary syndromes could become unstable, depending on their management. In the upper right, you can see how this could happen. A patient could become unstable at any time and have an adverse outcome, even though labeled as chronic ischemic, stable ischemic heart disease in the moment. The trajectory can be uncertain depending upon revascularization status and the intensity of risk factor modification. This illustration from the ESC 2019 guideline on chronic coronary syndromes shows how we may think about the risk in these patients with known disease by incorporating symptoms, comorbidity, and echo findings including LVEF when trying to choose the best non-invasive tests. Patients with very low risk on the left side need no testing. Consideration of anatomic coronary CTA is a good consideration in lower to intermediate risk patients without known disease. CTA has a very high negative predictive value. A negative test is truly a negative test and it offers the opportunity to discover subclinical plaque which can potentially improve the trajectory of at-risk patients if preventative measures are implemented. As suggested by the Scott-Heart trial, in this trial it was demonstrated a significant lower rate of combined endpoint of cardiovascular death or non-fatal MI in patients who had management with coronary CTA versus those managed with treadmill stress ECG testing as usual care evaluation. This is presumably due to management of detective subclinical disease, but other randomized prospective trials such as the PROMIS trial have not shown a survival advantage of CTA strategy over traditional stress imaging strategies. The intermediate risk patients, those in the center, benefit from non-invasive stress testing and it may be useful with test choice based on patient characteristics and availability. In high-risk patients, an invasive approach is often needed. Importantly, recommendations from the 2019 ESC guideline include the recommendation for resting trans thoracic echocardiogram as the initial test and the management of patients with suspected coronary disease. This is to rule in or rule out other non-CAD causes of chest pain that could be cardiac in origin, including regional wall motion abnormality detection, determining ejection fraction and diastolic dysfunction. Even functional testing for ischemia or CTA is recommended as an initial test in patients in whom coronary artery disease cannot be excluded by a clinical assessment alone. Let's now consider patients with acute coronary syndromes. We just talked about chronic, but in acute syndromes until this past fall, the most recent guidance was from, again, the European Society of Cardiology in 2020. Patients with suspected non-stemmy acute coronary syndromes, a resting echo, again, is indicated in moderate risk patients and even at patients with high risk who are going for cath, an echo is indicated to assess ejection fraction, regional wall motion abnormalities and for concomitant other cardiovascular conditions and complications of myocardial ischemia. In the moderate risk group, non-invasive imaging may be indicated after a resting echo has been performed and an acute coronary syndrome has been excluded. And now we come to the newly published American College of Cardiology chest pain guideline for evaluation and diagnosis. The document is strongly focused on the patient's overall clinical evaluation as being crucial for establishing a patient's pre-test probability of disease and other factors that dictate whether or not non-invasive cardiac testing should be performed at all. These are grouped into those with acute chest pain with and without established coronary disease and chronic chest pain with and without established diagnosis of coronary disease. An initial clinical assessment and classification of chest pain is essential. Only 10 percent of patients presenting to acute care facilities with chest pain on detailed evaluation can be said to have cardiac or possible cardiac chest pain based on their symptoms alone. The new guideline recommends that chest pain be described as cardiac, possibly cardiac and non-cardiac. If the pain is possibly cardiac it may be either ischemic or non-eschemic cardiac chest pain. Non-eschemic cardiac pain can be from pericarditis, severe valve disease, complications of prior myocardial infarction, aortic syndromes, stress cardiomyopathy, and acute RV failure. The new chest pain guidelines recommend that we abandon the use of typical and atypical chest pain because this can be confusing. Most ED patients with chest pain have nonspecific, plural or musculoskeletal chest pain and these individuals require no non-invasive testing. Only around 10 percent have suspected cardiac chest pain and notice the very low frequency of proven cardiac chest pain in patients younger than age 45. The low accuracy of non-invasive testing in this low pretest probability group of younger patients is well known. Even in older patients with chest pain though, true cardiac chest pain, the green arrows, is in the minority. However, in these older risk, high risk patients with compelling symptoms, the risk is truly high and there's a need for the resources for accurate diagnosis. The guidelines strongly recommend risk assessment guidelines be employed. Many such acceptable clinical tools are available and they are listed in the guidelines. At our institution, we have used the heart score algorithm to classify patients. Using this score based on the history, including symptoms, EKG, age, and other risk factors and troponin results, patients can be relatively consistently placed into low intermediate and high risk groups. Validation studies have shown that low risk patients have a less than 2 percent risk of major adverse clinical events at six weeks without further evaluation and they can be safely discharged and further evaluated as outpatients. For a few years, we have used a chest pain protocol shown here. It is in keeping with the new chest pain guidelines. We do an initial clinical assessment including all of the elements needed for the heart score. It is the intermediate risk patients with possible cardiac chest pain or suspected ischemic heart disease that we then consider non-invasive testing. Please notice that the routine use of resting trans thoracic echo in intermediate and high risk patients to further assess ischemic and potentially non-ischemic causes for chest pain appears in the bright green box. After the initial clinical risk assessment, the test can be further used to classify patients into low intermediate and high risk groups based on the test results and managed accordingly. This flow chart has been very helpful in managing length of stay given the number of patients presenting with chest pain. For intermediate risk results or for an equivocal test result, the cardiology team is typically on board and decides on further management and of course the high risk test results often indicate the need for an invasive strategy. The relatively simple pre-test probability tool from this guideline can also be used with risk based on age, gender, the nature of symptoms and the coronary artery calcium score by chest CT if known. Shortness of breath can be an additive symptom of ischemic heart disease particularly in older men and again non-invasive stress testing performs well in intermediate risk patients and less well in low and high risk patients. Because of the inherent test performance characteristics related to test sensitivity and specificity. We are not going to go through all of the extensive recommendations from flow charts and tables within the guidelines but we will look at a couple. Here we see the stable chest pain with no known coronary artery disease table. In this group, non-invasive testing is recommended for intermediate and high risk, intermediate to high risk groups. In low risk patients no testing is recommended except for select causes where the clinical assessment is inconclusive. In intermediate to high risk patients with stable chest pain and no known coronary artery disease all non-invasive modalities may be indicated as shown in the center box with the blue arrow but one test is not recommended above the others. However, imagers know that in older high risk patients some tests are likely to perform better than old others. No test is perfect and for inconclusive studies in these patients noted by the red arrows layered complementary testing is sometimes needed particularly in complex cases. In patients with stable chest pain with known coronary disease the management decision tree is more complex. This guideline does not pretend to provide the granularity of the nuanced mix of patient variables and test performance characteristics that would be needed to lead to the best test selection in all cases. The new EACVI ASC guideline provides a needed focus on not just when to select the non-invasive imaging in patients with suspected or established coronary disease, it provides a more detailed discussion on which tests should be considered based on more nuanced descriptions of patient characteristics not just when to do but what to do. This document also highlights the importance of patient pretest probability assessment before determining whether or not non-invasive testing should be utilized. Let's look at the relative accuracy of stress imaging tests based on estimates of test sensitivity and specificity. All of the tests have very good sensitivity and specificity when it comes to utility in intermediate risk patients. Let's take a look at the results when we try to perform stress imaging in a very low-risk population. Patients with a pretest probability of only 10% say young adults with possible cardiac chest pain. Let's run 100 patients with a pretest probability of 10% through a test with an 80% sensitivity and 90% specificity. And stress echo would be in this range, a nuclear not far off. In this group, 10 of 100 patients have actual coronary disease and 90 have no coronary disease. If we focus on the 90 patients with no disease and apply a specificity of 90%, the testing process would yield 9 out of 100 patients with a falsely positive test result. And although the test identifies most patients having no disease, the percentage of positive tests that are false positives is 53%. Therefore, when the test is positive in this low-risk group, the test is almost meaningless with a 53% false positive rate. Now let's look at very high pretest probability of disease populations, older patients with risk factors and compelling symptoms. Pretest probability of 80%. Let's run this high 80% pretest probability through the 80% sensitivity and 90% specificity test. Although 80% sensitivity is not bad, out of the 80 patients with real disease, the test may produce 16 of 100 results that are falsely negative. And of all negative tests, 47% than are falsely negative. And the test may miss 16 of 100 patients with real disease due to the high false negative rate. We just saw how we can get into trouble when applying non-invasive testing to very low and very high pretest probability patients. The available tests are very useful for the same reasons in intermediate risk patients. The pretest probability provides the link between test sensitivity and specificity in clinical utility. And because tests are not perfect, even when appropriately applied, the guidelines recognize the need for complementary testing or escalation to invasive testing when results are unexpected or inconclusive. The sensitivity and specificity of stress testing is determined by the physiology of the ischemic cascade as shown here. Very CT angiography, if we turn this cascade upside down, shows this test to be very sensitive in picking up atherosclerotic disease and also for excluding its presence. So it is at the very origin of the ischemic cascade. When absolutely normal, this test is a very powerful test. However, it picks up significant atheroma, so it can be non-specific. Normal flow reserve testing may be needed when this test shows disease that is intermediate or high, highly significant. Nuclear stress testing operates a bit further down the ischemic cascade, but its high sensitivity means that it's very able to predict ischemic perfusion abnormalities. Stress echo operates even a little further down the ischemic cascade with evaluation of left ventricular global systolic function and wall motion abnormalities. Let's look at this case of a 56-year-old male with diabetes and hypertension who presented with no chest pain but worsening shortness of breath on exertion and an abnormal EKG. He was unable to exercise due to foot infection. He developed slight test discomfort and augmented ST depression during debutamine infusion. And there's a suspicion for slight hypokinesis of the mid-lateral wall in this four chamber view, and you can see the nice endocardium even without an ultrasound-enhancing agent. In the apical long axis view, the infralateral wall is normal at baseline in the upper left but becomes hypokinetic rather than augmented at peak in the lower left. This is a typical ischemic response, but it can be subtle as in this case. In our lab, we sometimes acquire global longitudinal strain imaging at baseline and in recovery, so this is not an official protocol. It takes just a couple of minutes, and in this case, the abnormal strain pattern in the left circumflex territory with and without our visual assessment was confirmed with coronary angiography, which shows severe left circumflex disease. So in this case, adding the mechanical indices of global longitudinal strain moved this stress further down the ischemic earlier into the ischemic cascade, making it potentially more sensitive. So this and other non-invasive testing are continually undergoing improvements, and this is a changing environment. In choosing among the non-invasive tests, a positioning statement of patient-centered medicine was recently published. We would take a personalized approach to testing based on clinical information better than a one test for all patients' strategy. For any living clinical presentation, physician's role is to use his or her best judgment to decide on the optimum approach, factoring in the pretest likelihood of disease, patient preference, patient characteristics, equipment availability, and technical and reader expertise which can vary greatly. Thank you for your attention to this talk on non-invasive imaging in chest pain patients and attention to the new guidelines document from the ACC.