Linking To And Excerpting From The American Society Of Echocardiography’s “Non-Invasive Imaging in Coronary Syndromes”

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Today, I link to and excerpt from The American Society Of Echocardiography’s Non-Invasive Imaging in Coronary Syndromes: Recommendations of The European Association of Cardiovascular Imaging and the American Society of
Echocardiography, in Collaboration with The American Society of Nuclear Cardiology, Society of Cardiovascular Computed Tomography, and Society for Cardiovascular Magnetic Resonance [No abstract available] [Full-Text HTML] [Full-Text PDF]. J Am Soc Echocardiogr. 2022 Apr;35(4):329-354. doi: 10.1016/j.echo.2021.12.012

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OUTLINE

Preamble
Background
+ Definition and pathophysiology of coronary artery disease— basic concepts relevant to non-invasive imaging
+ Epidemiology—focused towards the pre-test probability of CAD and Bayesian predictive models
+ Clinical role of imaging and current guidelines for chronic coronary syndromes
+ Clinical role of imaging and current guidelines for acute coronary syndromes
Overview of imaging methods in CAD
+ Anatomical vs. functional imaging
+ Echocardiography
+ Computed tomography
+ SPECT and PET nuclear imaging
+ Cardiovascular magnetic resonance
Diagnosis of acute coronary syndromes and the role of imaging
+ Left ventricular function assessment
+ Myocardial perfusion imaging
+ Coronary artery anatomy
+ Myocardial scar and Edema assessment
+ Differential diagnosis in acute chest pain
+ Risk stratification after revascularization
Diagnosis of chronic coronary syndromes—the role of imaging
+ Left ventricular function assessment
+ Myocardial ischemia assessment
+ Assessment of coronary artery stenosis
+ Myocardial viability and scar assessment
+ Risk stratification in chronic coronary syndromes
Conclusions and future directions

Preamble

Coronary artery disease (CAD) is one of the major causes of mortality and morbidity worldwide, with a high socioeconomic impact.¹ Non-invasive imaging modalities play a fundamental role in the evaluation and management of patients with known or suspected CAD. Imaging endpoints have served as surrogate markers in many observational studies and randomized clinical trials that evaluated the benefits of specific therapies for CAD.² A number of guidelines and recommendations have been published about coronary syndromes by cardiology societies and associations but have not focused on the excellent opportunities with cardiac imaging. The recent European Society of Cardiology (ESC) 2019 guideline on chronic coronary syndromes (CCS) and 2020 guideline on acute coronary syndromes (ACS) in patients presenting with non-ST-segment elevation (NSTE-ACS) highlight the importance of non-invasive imaging in the diagnosis, treatment, and risk assessment of the disease.^3,4 The purpose of the current recommendations is to present the significant role of non-invasive imaging in coronary syndromes in more detail.

These recommendations have been developed by the European Association of Cardiovascular Imaging (EACVI) and the American Society of Echocardiography (ASE), in collaboration with the American Society of Nuclear Cardiology, the Society of Cardiovascular Computed Tomography, and the Society for Cardiovascular Magnetic Resonance, all of which have approved the final document.

The experts of the writing panel provided declarations of interest forms for all relationships that might be perceived as real or potential sources of conflicts of interest.

Background

Definition and Pathophysiology of Coronary Artery Disease—Basic Concepts Relevant to Non-Invasive Imaging

Myocardial ischemia and infarction caused by epicardial coronary atherosclerosis are the main manifestations of CAD. Stenotic or occluded coronary arteries impair downstream blood flow, reduce myocardial perfusion, cause contractile dysfunction, and ultimately lead to angina or, in acute syndromes, myocardial infarction. Coronary syndromes may have stable periods, but can suddenly lead to an unstable event caused by plaque rupture or erosion. The nature of the disease is progressive, resulting in various clinical presentations—from subclinical to CCS and ACS, all of which are covered in this recommendations paper.

The distinctive pathophysiological characteristics of CAD can be evaluated with various imaging modalities such as echocardiography,³ single-photon emission computed tomography (SPECT), positron emission tomography (PET), cardiac magnetic resonance (CMR), or coronary computed tomography angiography (CTA).^5,6 Combining anatomical and functional imaging modalities by either sequential stand-alone tests or hybrid approaches [e.g. SPECT/computed tomography (CT), PET/CT] would allow a more comprehensive characterization of obstructive CAD.^7-11 When choosing a specific imaging test, one needs to take into consideration the multiple factors that interact in the development of ACS and chronic CAD. The preferred imaging technique to confirm the diagnosis of acute or chronic CAD and guide the treatment will depend on the clinical presentation and characteristics of the patient, the local availability and expertise at the clinical centre.

While this document provides a set of recommendations, many situations encountered in daily clinical practice may not be covered. Ultimately, understanding how each imaging modality assesses different aspects of CAD remains critical to deciding which modality would be most helpful in providing optimal care for each patient. This document aims to provide guidance on how to select the optimal imaging approach for individual patients.

Epidemiology—Focused Towards the Pre-Test Probability of CAD and Bayesian Predictive Models

Age, gender, coronary risk factors, and symptom characteristics are used in clinical practice to estimate the probability of CAD and risk for cardiac events and to identify patients who may benefit from non-invasive testing.

The European and American guidelines recommend the Duke clinical score and the revised Diamond and Forrester models as preferred clinical tools to calculate pre-test probability (PTP) of obstructive CAD in symptomatic patients without known coronary syndromes.^3,12 While other scores have been proposed for various other CAD scenarios, it is important to estimate the PTP using any of these clinical scores to optimize cost/benefit and to reduce false results in individual patients. However, all of these models might overestimate the prevalence of CAD, and several studies have suggested that the prevalence of obstructive disease among patients with suspected CAD is lower than previously reported.^13,14 The PTP has therefore recently been reconsidered in CCS.³

3. Knuuti, J. ∙ Wijns, W. ∙ Saraste, A. …

2019 ESC Guidelines for the diagnosis and management of chronic coronary syndromes: the Task Force for the diagnosis and management of chronic coronary syndromes of the European Society of Cardiology (ESC)

Eur Heart J. 2020; 41:407-477 [Link to the PDF]

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Bayes’ theorem of conditional probability applies to the interpretation of all non-invasive imaging test results, since none has 100% sensitivity or specificity to establish either the anatomical presence of obstructive CAD or the functional presence of ischemia. Based on this theorem, optimal performance of most non-invasive tests occurs when PTP is intermediate. The proportion of false positive results increases as PTP decreases. Conversely, the proportion of false negative results increases as PTP increases. Other significant factors that may affect the diagnostic performance of individual tests are the quality of the exams, acquisition protocols and technology used, adherence to protocol standards, patient compliance, heart rate, and body habitus.^3,7,15

Since imaging tests used for the diagnosis of CAD have different performance characteristics, it is common practice to preferentially select tests with high sensitivity in high disease prevalence groups and with high specificity in lower prevalence groups in order to reduce false negative and false positive results, respectively. Hemodynamic significance of coronary stenotic lesions varies according to anatomical location, degree of stenosis, extent and composition of obstructive plaque, amount of subtended myocardium, microvascular integrity, presence of collaterals, myocardial oxygen consumption, and many other factors.

Clinical Role of Imaging and Current Guidelines for Chronic Coronary Syndromes

Diagnostic testing is most useful and recommended when the likelihood of CCS is intermediate. According to current American and European clinical practice guidelines, patients with intermediate PTP of underlying CAD should undergo initial evaluation with non-invasive anatomical or functional diagnostic tests for the assessment of CAD (Figure 1).^3,5 Patients with very low PTP may not need evaluation (a positive test would be most likely false positive) and patients with high PTP may need direct coronary visualization with angiography (a negative test would most likely be false negative). The new and reconsidered PTP calculation, however, also permits anatomical or functional diagnostic testing in individual patients with a PTP of 5–15% if considered necessary in certain clinical situations.

Figure 1 Pre-test probability (PTP) of epicardial CAD (modified Diamond and Forrester) and value of imaging testing. This simple (age, sex, and symptoms) assessment of pre-test probability can be complemented with other data for an improved PTP estimation. Complementary data include traditional risk factors for atherosclerosis (family history of early CAD, dyslipidemia, smoking, diabetes, etc.) and other biomarkers such as Q or ST abnormalities in ECG, low EF, or WMA on resting imaging, etc. The value of each diagnostic approach in each box and its variance based on complementary data is reflected in the colors and their shades.

Adapted from 2019 ESC guidelines.³

A resting transthoracic echocardiogram (TTE) is recommended in all patients with a suspicion of CCS for assessment of wall motion and structural abnormalities.³ The evidence of inducible myocardial ischemia or abnormal perfusion by functional imaging testing, coronary atherosclerosis by coronary CTA, or both, may allow the diagnosis of CAD requiring medical treatment. In cases of either failure of medical therapy to control symptoms or of imaging findings suggesting a high risk of coronary events, invasive coronary angiography (ICA) is indicated to address the possible need for revascularization.^3,5,6,16

Thus, non-invasive functional imaging tests serve not only to diagnose the presence of CAD, but also to guide clinical decision-making, and are preferable in patients with high intermediate PTP. The documentation of ischemia involving more than 10% of left ventricular (LV) myocardium or in a multivessel pattern are relevant hallmarks of high risk,³ as reducing ischemia may favorably impact symptoms and outcome.^17,18

Coronary CTA is the preferred test in patients with the lowest intermediate range of clinical likelihood of CCS, no previous diagnosis of CAD, and characteristics associated with a high likelihood of good image quality, based on its high negative predictive value (the ability to exclude significant CAD).³ Functional testing with imaging is preferred in patients with a higher likelihood of CCS, known CAD, high burden of calcified atherosclerosis on prior CT imaging, and in patients who are not ideal candidates for coronary CTA (Figure 1).

Coronary CTA may also be utilized in patients with chronic chest pain syndrome and equivocal findings with functional imaging. Conversely, functional testing with imaging may be performed in patients with intermediate stenoses on coronary CTA when the results of these tests may lead to changes in patient management (e.g. medical vs. revascularization strategy) (Figure 2).¹¹ Recently, evaluation of fractional flow reserve (FFR) by CTA has offered the potential to obtain anatomic and functional information from a single exam. Anatomic testing can be useful when a functional test is equivocal or uninterpretable, and vice versa.

Figure 2 Chronic coronary syndrome. A 49 years old lady with family history of CAD, hypercholesterolemia, and recent onset of effort angina with non-diagnostic ST-segment depression (0.1 mV in the anterior leads) at maximal exercise ECG. Her PTP of obstructive CAD is 10% but the clinical likelihood is higher. She performed CTA as the initial test which allowed the diagnosis of obstructive CAD (LAD middle third and proximal LCX) without high-risk features. Stress SPECT was sequentially performed. CTA-SPECT images demonstrated a severe reversible perfusion defect (>10% LV myocardium) in the LAD territory with preserved perfusion in the LCX territory. These high-risk findings prompted invasive coronary angiography and revascularization (PCI and stenting) of LAD was decided.

Radiation risks associated with CT or nuclear imaging with contrast agents should be considered when choosing a specific exam and weighed against alternate procedures and the risk of missing a diagnosis.¹⁹ All efforts are recommended to reduce imaging-related risks by using adequate protocols, proper technologies, and avoiding useless/redundant procedures.^19,20

In about 20% of all patients with stable symptoms and evidence of ischemia, obstructive epicardial disease will be absent (ischemia and non-obstructive coronary artery disease, INOCA); thus, the apparent ischemia may be due to microvascular disease or non-cardiac causes. Whether the endothelium, the smooth muscle cells in the microvasculature or both are the culprits of such disease is unknown. Nevertheless, both are possibly associated with cardiovascular risk factors or structural myocardial abnormalities such as hypertrophy, dilatation, or a mix of them.^21-23 Recognition of these conditions by non-invasive imaging is relevant for risk stratification even if the clinical impact of pharmacological treatment is not yet defined^23,24 (Figure 3).

Figure 3 CTA-PET imaging. CTA-PET imaging in two patients with recent onset dyspnea. Case A is a 67 years old man with multiple risk factors, LBBB, systolic LV dysfunction (LVEF 30%), and diffuse non-obstructive CAD at CTA. Case B is a 60 years old man with glucose intolerance, mild hypertension, systolic LV dysfunction (LVEF 33%), and normal coronary arteries at CTA. In both cases, quantitative hyperemic (after i.v. dipyridamole) myocardial blood flow values with N-13 ammonia PET are globally reduced (normal values > 2 mL/min/g, please note different color codes have been used in these cases) (see also Ref.²¹ Liga et al. and Ref.²⁴ Neglia et al.).

Clinical Role of Imaging and Current Guidelines for Acute Coronary Syndromes

Transthoracic echocardiography, using either fully equipped units or point-of-care ultrasound systems, should be available to all emergency rooms and should be performed and interpreted by trained expert operators, in all patients referred for chest pain, except in limited situations such as ST-elevation myocardial infarction (STEMI) where imaging would delay reperfusion.⁴ Bedside echocardiography is beneficial when complications are suspected or when an alternative diagnosis is considered (Figure 4). Alternative diagnoses include aortic dissection, pericarditis with or without pericardial effusion, hypertrophic cardiomyopathy, mitral valve prolapse, or right ventricular (RV) dilatation that could be suggestive of acute pulmonary embolism (PE).

Figure 4 Echocardiography can quickly reveal complications in ACS. Large papillary muscle rupture after acute myocardial syndrome in a 69 years old male. Left panel is a modified apical four-chamber view and the ruptured papillary muscles are easily seen (white arrow). Right panel reveals the associated severe mitral regurgitation (white arrow).

In patients presenting with acute chest pain syndromes, European guidelines and American appropriate use criteria recognize the value of coronary CTA or functional testing as an alternative to ICA to rule out ACS in patients at very low or low risk for ACS.⁴ This includes patients with indeterminate electrocardiogram (ECG) changes, negative troponins, and no recent chest pain. Functional imaging in this situation has higher accuracy and is clearly favored over a stress ECG. This strategy is, however, not recommended in STEMI or NSTE-ACS with high-risk features, where prompt ICA should be pursued [primary percutaneous coronary intervention (PCI) for STEMI, within 24 h for NSTE-ACS].^4,5,25

Collet, J.-P. ∙ Thiele, H. ∙ Barbato, E. …

ESC Scientific Document Group 2020 ESC Guidelines for the management of acute coronary syndromes in patients presenting without persistent ST-segment elevation

Eur Heart J. 2021; 42:1289-1367

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Overview of Imaging Methods in CAD

Non-invasive imaging methods used to evaluate patients with known or suspected CAD rely on assessing: (i) presence and anatomic severity of stenosis, (ii) abnormal flow in epicardial arteries, (iii) abnormal myocardial perfusion, or (iv) abnormal myocardial contractility. LV regional assessment of perfusion or systolic function is important for the detection of CAD, characterizing the spatial distribution of ischemia (i.e. coronary territories involved), and for identifying patients who are at high risk for adverse events and may benefit from revascularization. By convention, regional myocardial involvement is described using either a 16-segment model (the LV is divided into six segments at the base and mid-level, and four at the apex) or a 17-segment model (including the additional area of an ‘apical cap’), which was added to standardize reporting among imaging modalities. A wall motion score can be derived by assigning each segment a numerical value (e.g. one for normal/hyperkinesis, two for hypokinesis, three for akinesis, four for dyskinesis, and five for aneurysm) and computing a mean value for all segments.^26-28 While standards for assigning each segment to a major coronary artery perfusion territory have been developed, there is considerable inter-subject variation in coronary artery anatomy. Correlation between methods is imperfect and therefore understanding the physiology and technical aspects of each methodology is of critical importance for optimal test performance and image interpretation.

Anatomical vs. Functional Imaging

Both anatomical and functional non-invasive imaging play important roles in the diagnosis and management of CAD. Non-invasive anatomical imaging is today almost exclusively performed using CT, while multiple functional tests are available including echocardiography, nuclear imaging, CMR, and dynamic CT. Recommendations for the use of anatomical and functional imaging in CAD are specific to clinical scenarios and local expertise. In the initial assessment of patients with suspected stable CAD, current European and American practice guidelines recommend either coronary CTA or functional imaging in patients with intermediate PTP, as outlined below.^3,12 These recommendations are supported by the results of the Scottish Computed Tomography of the HEART (SCOT-HEART) and Prospective Multicenter Imaging Study for Evaluation of Chest Pain (PROMISE) trials, in which a strategy of initial coronary CTA was generally shown to be equivalent to functional testing in patients with stable chest pain syndromes.^29-31

Echocardiography

Echocardiography, both at rest and during stress induced by exercise or administration of an inotrope or vasodilator, is used to detect several aspects of CAD, including resting wall motion abnormalities (WMA), impaired contractile response, microvascular perfusion, or flow in the epicardial arteries. In addition, resting echocardiography is useful in the identification of other causes of chest pain, such as pericardial effusion, aortic dissection, PE, etc.

Echocardiography is most frequently used in patients with CAD to assess global and regional systolic function at rest or during stress. Global systolic function is commonly evaluated by measurement of the LV ejection fraction (LVEF), which can be quantified by two-dimensional (2D) or three-dimensional (3D) echocardiography. The recommended 2D method is the biplane method of disks (modified Simpson’s rule). In patients with regional WMA, 3D assessment of LV volumes and ejection fraction (EF) is preferred as it is not dependent on geometric assumptions, and if image quality is good, is more accurate and reproducible. Compared to 2D, however, 3D echocardiography has a few limitations: lower temporal resolution, limited availability, and requirement of a higher level of expertise in echocardiography.^26,27,32 Because LVEF is entirely dependent on proportional volumetric change, it may not accurately reflect mechanical contractile function of the myocardium, particularly in situations where the LV chamber size is abnormally enlarged or reduced, or in increased wall thickness.

Strain echocardiography is more sensitive in detecting LV dysfunction than LVEF in a variety of myocardial diseases, including ischemia (Figures 5 and 16).^33-35 The subendocardial longitudinally oriented muscle fibers are most vulnerable to ischemia, and assessment of global longitudinal strain (GLS) at rest has therefore shown superiority to wall motion analysis in ACS.³⁶ The speckle tracking technique is the method of choice for assessment of LV strain and is particularly useful in the acute setting when LVEF is normal or WMA are not visible.^37,38

Myocardial Strain Imaging: Theory, Current Practice, and the Future [PubMed Abstract] [Full-Text HTML] [Full-Text PDF]. JACC Cardiovasc Imaging. 2025 Mar;18(3):340-381. doi: 10.1016/j.jcmg.2024.07.011. Epub 2024 Sep 11.

Speckle-Tracking Strain Echocardiography for the Assessment of Left Ventricular Structure and Function: A Scientific Statement From the American Heart Association [PubMed Abstract] [Full-Text HTML] [Full-Text PDF]. Circulation. 2025 Sep 9;152(10):e96-e109. doi: 10.1161/CIR.0000000000001354. Epub 2025 Aug 6.