Dr. Uprety discusses the current role of non-invasive testing for coronary artery disease, highlighting evidence-based diagnostic strategies and the appropriate use of imaging modalities to improve early detection, risk stratification, and clinical decision-making.
Good morning everyone. I'm Ezra. I'm a cardiologist. So, so sorry for the delay. I had some technical difficulty here. So we'll, we'll promptly get into the topic today. This is one of the common things that we do in our practice almost every day. This is revisiting the non-invasive testing modalities. That we have and several things that we discussed here, it is reinforcing things that we already know and adding some perspective on what we know and what is changing over recent years. Next slide, please. So let's start with with one patient, one case. This is a 65-year-old male. He presented with exertional syncope. So the presenting complaint was whenever he start exercising, very active gentleman, a vast history of smoking, quit about two years ago, has a history of hypertension, hyperlipidemia. Coronary artery calcification noted in the CT scan done for, done for lung cancer screening. His complaint was no chest pain, but whenever he starts exercising on the treadmill, as soon as his heart rate hits 140, he passes out. He presented to the primary care physician and exercise treadmill testing was ordered and it was done in the hospital. Next slide, please. So initial EKG, except for ectopic beats, it's Nothing obvious, nothing significant, possible septal infarct, otherwise unremarkable case. Next slide, please. As he started walking, so the first EKG that you see on the left-hand side, this is at stage 2 of bruce protocol, and on the other side is, it's a stage 3, stage 3. So his functional capacity is exceptional. He exercised up to, uh, 12 minutes. He did not have angina, but here comes the point when his heart rate is approaching 140 beats per minute. Next slide, please. And he went into torso. He had frequent PVCs and subsequent to that, he went into torso, and it continued, uh, the, the, the team, the stress lab team, they give two thumbs. Next slide, please. And, and he woke up and, of course, he told the team this is what was happening at home. So he had exercise induced arrhythmia. That's what he was experiencing, otherwise highly functional gentleman with no angina. So because of this high risk finding, patient underwent coronary angiogram. It showed three vessel coronary artery disease. I could not, uh, carry you over the, uh, uh, video. So this ventriculogram on the right side is trying to show that he had hypokinesis of the basal inferior segment. Otherwise, the remaining of the LV segments were, uh, contracted. Normally, his ejection fraction was normal. So he was referred for bypass surgery, and he under uh underwent that. So, so the fundamental question about this stress testing is, number one, the exercise treadmill testing was chosen, except for arrhythmia. He did not have any other remarkable ischemic changes noted in the EKG. But what value do we have? Even though it did not show other findings suggestive of ischemia, no angina, he, this gentleman has functional capacity of more than 12 mets. Anything above 10 mets is considered excellent functional capacity. And we'll discuss more about exercise testing later. At the same time, ejection fraction was preserved. And he had known coronary artery calcification in the CT scan done for lung cancer screening. He has risk factors and, and has indications to be treated with aggressive lipid lowering therapy, given his risk factors. Even though this testing may not have. Figure out or. Showed a low sensitivity in depicting the. Significant obstructive coronary artery disease compared to imaging. For example, if stress echo was done, the sensitivity might have been in the vicinity of around 80 to 85%. Likewise, in the nuclear stress test spec, around 90%, where in stress MRI, the sensitivity would have been around the vicinity of 90%. Even though this testing may not have. Soon the obstructive CAD, it shows the sort of the functional ability. He did not have angina. So by the CRES trial and the ischemia trial, if this patient was aggressively treated. For the non atherosclerosis of the coronary calcification, I, I think this stress test still provide provided a prognostic value. And based on the data that we have, he would still have been served well by aggressive lifestyle modification and cholesterol lowering medications should he not have those arrhythmia episodes. So the point I'm trying to make is people who can exercise, even though the exercise testing may not have so the ischemia, there, there's a big prognostic value on exercising a patient on the treadmill. So what are the modalities of the non-invasive testing that we use in our day to day practice for coronary artery disease? On the top, as you can see, there's an exercise EKG, the nuclear, the PET is arriving soon in, uh, Centar Heart Hospital. Well, the stress MRI, stress echo, and, and the coronary CTA. We'll talk more about the specific modality as we go, go on. Next slide, please. So this is, this picture is taken from the chest pain guideline from 2021. On the left side, you, you can see if the patient has acute coronary syndrome with elevated troponin, uh, we frequently use the term stemia or non-steia. Our patient is high risk. He a patient presenting to the emergency room with uh a 75 year old male with hypertension, diabetes, hyperlipidemia, coming with very typical symptoms. So in that scenario, presenting to the emergency room, the guidelines suggest proceeding to the invasive coronary angiography. The reason is. The tests are sensitive, but at the same time, when the pretest probability is very high of the obstructive coronary artery disease, guidelines do recommend proceeding with invasive coronary artery, angiography. That's the heart catheterization. Whereas on the right side of the table, you can see that it's a stable chest pain evaluation in outpatient setting. So the high risk intermediate risk here is based on the pretest probability, which we will talk in the subsequent slide. Whereas for patient, asymptomatic patient and the low-risk patient, low risk patient means patient with pre-test probability of less than 5%. So the guidelines recommend no testing. So you can see the mention of the coronary artery cal calcium score. The coronary artery calcification is for risk stratification for asymptomatic patients. So there is no role in acute chest pain. It is, however, listed in the guideline lower in the chart so that we understand that the problem with testing low pretest probability patient is, uh, we may get a false positive results, and that will lead to downstream invasive coronary artery assessment, invasive testing, and downstream further testing, which does come in with a risk. Next slide, please. So this is a ischemia cascade. Ischemic cascade, as you can see, this is taken from the article published a long time ago back in 1987. So the patient with a normal function as things go by, the perfusion abnormality in the nuclear spectrate and the nuclear pit, it shows up way earlier. Then any of the symptoms arises. Likewise, if the metabolic changes happens, that shows up, uh, in the perfusion abnormalities, and, and as it affects the contractile function, the initial diastolic dysfunction, subsequent to that, we may start seeing wall motion abnormalities in the echocardiogram, and then comes the ischemic changes in the EKG and comes, and comes the angina, chest pain. So if we wait for the chest pain, for the diagnosis of the coronary artery disease or obstructive coronary artery disease, it comes late, late in the ischemic cascade. Even though it's a sequence of events, uh, we now know that on several scenarios, the ischemic cascade does not come step by step all the time. But this is a historical background and the testing that we do, we, we think, the way we think. We do put these things into consideration and and it it has been relevant for a while and it's still relevant in our current practice. Next slide, please. So this article is from 1979. It is Diamond and Forester. So the concept of atypical chest pain, typical chest pain, and non-anginal chest pain comes from 1979 back in the day. So, This criteria, this previous probability model at that time, did not take into consideration any risk factors. The only thing it took into consideration was the type of the chest pain, whether it results with nitroglycerin or uh race. And it categorized chest pain as atypical, typical, typical if it meets all the three criteria, atypical if two criteria, and non-anginal if it is one or does not meet any of the any of the criteria. As you can see that it will see abo above 60%, uh, see above 60 year old female or male, the typical enzyme, uh, the pretest probability is already high. Whereas, as you go by on the different age group, with the chance of having significant obstructive coronary artery disease is low. It's a historical perspective, historical background, and we may hear the comment that this is not 1979, and it is often, Criticize being overestimating, overestimating the obstructive coronary artery disease than we really see in the present day data. But this is history and it is still relevant on our day to day practice. As we go over the note, we see the description of the chest pain described as atypical, typical, or non-anginal chest pain. It, it comes from these days. Next slide, please. So different model of pretest probability has been tested. So European guideline has a different recommendation, which I have the calculator online in the next slide. But the point I'm trying to make here is, as we think about ordering any test, we should keep into consideration the pretest probability. And the current guideline, current day pretest probability model increasingly takes Risk factors into consideration and some of the pretest pro pro probability testing model does take into consideration the coronary calcium score if it has been done in the past. Next slide please. So this is one of the, uh, calculator. I, it is easily available in the, uh, uh, online in the Quantity IMD website. It it is more, it is a validated test and recommended mostly in the European study. The reason why I brought up the pretest probability, like I discussed in the chest pain guideline, if the patient is very low risk, less than 5% chance of obstructive coronary artery disease, based on the pretest probability score, then the patient should not be going for any testing. Whereas a patient landing to the emergency room with very high pretest probability, Uh, invasive coronary artery assessment. We, we lean towards invasive coronary artery assessment just to, just not to miss obstructive coronary artery disease, uh, uh, that is missed due to the sensitivity of the specific testing. So when we, when we discuss about the ischemic evaluation, uh, diagnostic testing for the non for non-invasive modality for, uh, obstructive coronary artery disease, there are anatomic and functional testing. The functional testing is exercise EKG, which is historical low cost modest sensitivity. It is pharmacological where we use dobutamine, and the dobutamine stress echo, dobutamine stress nuclear, or, or even dobutamine stress MRI. Likewise, the vasodilator, reggadeosin, popularly known as LEXA scan, and adenosine infusion, which is less frequently used these days in our current day patches and in Centera. So what do we look for when we start doing the functional diagnostic testing? When we are exercising the patient or rising the heart rate using dobutamine, we are trying to look at the EKG changes when we use. Echocardiography as the imaging modality. Likewise, CMR is the imaging modality. We are looking for one muscle assessment and myocardial perfusion in the spec that we commonly use and more widely available than the cardiac PET and, and the stress MRI. So these are the functional functional diagnostic testing modality that is commonly being used, and I, I'll go over each one of it in the next slide. Next slide, please. So this is exercise stress testing, EKG only. So, the sensitivity is modest, uh, about 70% and similar specificity as well. The key benefit of exercise stress testing is one, we look at, uh, the blood pressure response to exercise. Number two, whether angina is inducible with exercise, the functional capacity. And heart rate recovery during the recovery phases. Each has prognostic implication. And the treadmill score. This is something that we use to risk stratify. If the score is greater than 5, it is, the patient is considered to be low risk with 5-year survival at around 99%, whereas the score, if it is -10 or lower, it is considered high risk with 5-year survival to 79%. So it has a prognostic implication, benefit of assessing functional ability, inducing symptoms, and likewise, looking at the EKG with modest sensitivity in diagnosing stress test, uh, diagnosing the obstructive coronary artery disease. Several times, the testing choice we make is, Determined by us based on the patient profile and several times a known fact is, it is also determined by a payer. We are in several situations, we are dedicted on doing the exercise treadmill testing because we think that's probably the test that's covered for a patient with, Uh, a normal EKG and we should understand what we can achieve from running this test. Next slide. Next slide, please. So this is a nuclear perfusion study with LEXA scan, also popularly known as reggadenosone. So we are looking at perfusion. The nuclear spec perfusion can be done with LEXA scan and also with exercise. If we're on exercise, treadmill, nuclear stress testing, we still get the benefit of inducing symptoms, assing the functional ability that we would have achieved from exercise treadmill only. With added perfusion, which shows ejection fraction and also the perfusion defect. As you can see here from resting image on the bottom, the uh the post-stress image on the top, you can see the defect and it is suggesting possible obstructive coronary artery disease in that particular territory. The drawback of this test is, number one, cost compared to the exercise treadmill testing, and the second thing is the ionizing radiation involved. So it involved about 9 to 12 millisieverts of radiation, which is about 3 to 5 years of background radiation we receive when we are not receiving any of the testing. So that's the, that's the drawback. Next slide, please. So, is there a value of adding exercise to myocardial perfusion imaging? So this is a study done in Sweden, uh, where they looked at whether adding exercise to the nuclear perfusion added anything in the prognostication. So the letters side is small as uh so the first graph that is showing is the prognostic uh uh prognostication when the myocardial perfusion is negative and the EKG part of the testing is negative as well. Whereas on the last. Yeah, on the last, as you can see, when the perfusion imaging is abnormal, likewise, the EKG part is abnormal, uh, it, it, it makes a big difference in prognosticating the outcome, uh, uh. Over the years. And on the right side, you can see the probability of the competent outcome. On the green on the bottom, it is exercise treadmill testing is negative and the perfusion is negative, whereas on the top, you know, you have the exercise treadmill testing is positive and perfusion is positive. So, when the patient was followed for 5 years, it kept on proving the value of exercising a patient when they are getting a nuclear perfusion study, added exercise. So in between, as you can see that there are instances where perfusion study is normal, where it's exercise treadmill testing is abnormal. They attribute that to microvascular. Obstructive coronary artery disease and sometimes inducible angina. Adds the value on adding antianginal therapy in addition to the statin lipid lowering lifestyle modification when the patient has symptoms with exercise. So the benefit of functional testing has been proven for a very long time. This study is, old study from 2002, it's still relevant. So as you can see, a, a patient who can walk more than 8 minutes, Versus the subjects who cannot meet 5 minutes of the exercise capacity with or without cardiovascular disease. So over the 14 years of the follow-up, it keeps on proving beneficial that it has a prognostic implication, and the, and, and the person who can do more than 8 minutes of, uh, uh, physical activity, specifically more than 10 minutes, the chance of adverse cardiovascular outcome, including, Heart rate and the death over next next year is very low, and it continues to be low in the years to come when the patient will be followed. This testing was, uh, this study was specifically for the men. Next slide, please. The and this was a different study done in the female and and the same data that was shown in the earlier testing holds true. Next slide. And in and in this recent study, this was done in the patient with peripheral arterial disease published in 2019, 2013. It holds true as the years go by, it, it keeps on changing, and as you can, you can see the graph, the benefit keeps on widening. So there's a fundamental value of exercising a patient on the treadmill. So any patient who can exercise should be given the opportunity to exercise in addition to imaging, if the imaging modality is being, uh, applied as a part of the diagnostic testing. Next slide, please. So going back to the sensitivity and the specificity of the testing. As we can see here, this is taken from one of the meta-analysis done in 2017. Uh, the different uh studies has a different number, but as you can see, stress EKG only uh. As we discussed earlier, has sensitivity in the vicinity of around 70%, whereas stress echo in this study, they say it is about 77%. In different studies, it is about 80 to 85%. Likewise, it is very specific. But when you go up and see the, uh, see, see the coronary CTA, it's a very sensitive testing, and without the FFR the specificity is modest. So the point I'm trying to make here is when the specificity is low, any testing that is positive could lead to downstream testing. And when we take into consideration, analyze the study, the report, we should take into consideration, uh, this factor, likewise, we, we choose the test. When we talk about the stress echo, the, uh, sensitivity is in the vicinity of about 80%. It involves exercise testing where we assess the functional capacity. We look at the EKG finding, and likewise, we look at the ejection fraction, uh, systolic function at rested, and the post stress. So the key benefit of a stress echo is. It uses ultrasound, so it does not involve the radiation. Likewise for the younger female, when we choose stress echo as the modality of the functional testing, we are avoiding the radiation exposure there. And the sensitivity is pretty decent. It's 80 to 85%, and it is accessible in several of the offices where they don't have a setup for nuclear, uh, nuclear stress testing or coronary CTA or other imaging modality, with a treadmill and sonographers being available, it is widely accessible even in the lower setting. But as you know, in patients who are obese or has underlying obstructive, uh, lung disease, the poor acoustic window, it reduces the sensitivity video of the study and sometimes causes difficulty in interpreting the echo part. Next slide, Liz. So it's a diastolic stress echo. So, the stress echo that we do for coronary artery disease, it looks at the wall motion abnormalities, function, the wall motion abnormality at rest and at the PEAC exercise. Whereas diastolic stress test has a value when we are looking for an answer. Several times, most of the clinicians been practicing, we see several of the patients who come in with uh. Exertional shortness of breath with no other explanation, other causes ruled out, including the possibility of. Obstructive coronary artery disease ruled out by other testing modalities. In that scenario, the diastolic stress testing is available, preferably done in the recumbent bike, but it can be done even on the treadmill, as you can assess, you have about 5 minutes window to assess the diastolic function. The fundamental benefit of using this is we are trying to look at patients who are at risk of developing heart failure. The first blue. Blue sign that you can see is as the cardiac output increased with with the activity or exercise. The pulmonary capillary wave increases some, but it does not increase a lot. This is a normal testing, whereas the red, the orange graph that you can see, even when the pulmonary capillary waves increase up to 40, the cardiac output increase is just modest. It does not increase much. So the second sign is suggesting. Exercise-induced heart failure with preserved ejection fraction diastolic function, and on the right side, what we are trying to see is these are the parameters that we look in the echo images when the patient is exercising. And the workload that you can see is in the wards because this testing that I'm showing here is done on the combined bike. So the key value of this is. Uh, uh, is giving the answer for several of our patients and also treating with diuretics if indicated to assess the symptoms. Next slide please. So that is a non-invasive modality, and Doctor Deepak T Talreza published this article back in 2007. And, and the invasive invasive assessment of the feeling pressure is definitely the gold standard, but non-invasive method, diastolic testing correlated and, and has a value. Next line. So stress MRI. So the vasodilator, regadenoso, adenosone can be used, and in our stress lab, our advanced imaging team also uses dobutamine as well when necessary. So the benefit is it looks at the perfusion sensitivity around 90% and likewise, the specificity is very high in the vicinity. So those are the talks about the functional testing. So now, uh, over the past decade. The concept of anatomy testing is being more frequent, and the chest pain guideline in 2021 made it a class one indication to proceed with coronary CTA for, for the patient to rule out coronary artery disease. So that has been more relevant. So anatomy testing, obviously, calcium, coronary calcium score in asymptomatic patient for risk stratification, coronary CTA. In the diagnostic heart catheterization, which is invasive coronary artery assessment, so going more, uh, more to the coronary CTA, next line, please. Next line, please. So here, I'm just showing a coronary calcium score, and, and based on what, uh, what guideline data that you look at, by using coronary calcium score, the patient can be oppressed about the future risk of the cardiovascular event. And based on what guideline you use, uh, the up risk trend may be different. Likewise, there's a recent lipid guideline change. Uh, and we are yet to see how what difference does the coronary artery calcification or coronary calcity score will make on that aspect. But this is for asymptomatic patients. It is not for. Patient presenting with acute chest pain or stable chest pain. Going to the coronary CTA. So from 20, since it has been used over the past couple of decades, in 2021, the chest pain committee guideline writing committee made it a class one indication to proceed with coronary CTA. So the key benefit is anatomical benefit. As you can see on the right side, there's a soft plaque with some calcification there. And and with with some recent trials showing which has classified the high-risk plaque based on the intravascular imaging, the soft plaque is considered to be high risk to rupture, cause acute coronary syndrome, and likewise should be aggressively treated. By medication lifestyle modification and if indicated by invasive coronary artery assessment and the PCI. So the key benefit is, as you can see, we can see the anomalous coronary artery, if there is present. We can look at the plaque burden. And it has a prognostic implication. So the drawback is it cannot be done in patients with arrhythmia. If the rhythm is irregular with atrial fibrillation, if the calcification is high in older patients who have been a smoker and diabetic, likewise, patients who have known coronary artery disease, established with PCI, CIS, Uh, so it, it, it is not the right test in those scenario. Likewise, the contrast is used, so it may not be ideal in patient with advanced stage of the CKD chronic kidney disease. And it uses radiation as well. There's ionizing radiation involved. So these are the drawbacks. So these are the pictures, uh, that discuss about the vulnerable plaque, which has caught, uh, uh, attention after the publication of the uh prophylactic PCI trial in patients with vulnerable plaque, and this can be described in the coronary CTA. It can be explained more in the coronary CTA. Next slide please. So now, after discussing all this, so what is the ideal test for a patient? So the test that is available to you, that the peer allows, and if a patient can exercise, these factors should be considered first. If, if one of the uh facility does not have the stress MRI, then there's no benefit of discussing more about the stress MRI or ordering the stress MRI. Likewise, in the, as we can discuss in the stress MRI, there's a claustrophobia factor, the time factor. And, and the reader reader constraint and the resource consent. So whatever is available to, to you, that's probably the preferred test or the best test. Uh, having said that. The stress testing, the functional testing or anatomic testing with non-invasive modality is done in the intermediate risk patient. If an acute chest pain patient present to the emergency room with high risk feature, even though it is not acute coronary syndrome, we should lean towards invasive coronary artery assessment. Whereas we should avoid testing in people who are considered to be low risk or very, very low risk. So these modalities are predominantly focused to the intermediate risk patient. If a patient is young, less than 65 years old. And does not have known coronary artery disease. Normal kidney function, or close to normal kidney function, then I think the coronary CTS should be preferred if that is available. Whereas if the patient is older, has known coronary artery disease, or significant coronary calcification in other imaging available in the back, like lung cancer screening. And then in that, in that scenario, stress testing of, uh, functional testing is preferred. So going back again, stressing again the value of exercise. If a patient can exercise in any modality, we should always lean towards adding exercise. To the imaging, including echo and the nuclear. As you can see that the goal availability expert is likelihood and the prior testing results and other compelling indication. For example, even if we have a young patient, if we are strongly suspecting. It could be potential anomalous coronary artery. Then at that time, even in a much younger patient, coronary CTA may be preferred. At the same time, we should take into consideration the beta-blocker use, the contrast that we use, and the radiation that we use. Next line, please. So So, these are the testing that we have available here in Centara. PET, PET scan is in the pipeline. And, and I welcome any questions or comments on the presentation.
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