In the US, coronary artery disease (CAD) is the leading cause of death in both men and women. Its diagnosis and risk stratification are an important aspect of medical care of any specialty.
Coronary catheterization has been the technical standard for the diagnosis of CAD and is the recommended route for patients who are at high risk or who present with an acute coronary syndrome. However, because chest pain and equivalent anginal symptoms are common in patients presenting in community clinics and inpatient and emergency rooms, many physicians need skills and knowledge to assess cardiac risk.
Categorizing patients with obstructive CAD and differentiating them from others with lower risk or non-cardiac conditions may require invasive coronary testing, which may improve evaluation or decide on intervention. CAD tests can be functional or anatomical.
| Coronary artery disease |
It is an inflammatory pathological process, which begins as fatty streaks in the intimate layers of the coronary arteries and then progresses to non-obstructive atherosclerotic lesion and subsequently to obstructive plaques. There are facilitating genetic and environmental cardiovascular risk factors.
Ischemia occurs when coronary atherosclerotic plaque becomes severely stenotic or obstructive (generally, if the stenosis is ≥50% in the left main coronary artery and ≥70% in the other epicardial coronary arteries) and may be associated with symptoms of angina . or dyspnea.
Moderate stenosis (50%-70%) can also cause ischemia and equivalent anginal symptoms, due to the characteristics of the lesion (location, plaque length, presence of endothelial dysfunction and microvascular disease.
Both obstructive CAD and non-obstructive coronary stenosis can be complicated by acute plaque rupture and thrombosis, leading to acute loss of myocardial blood flow and myocardial infarction.
Clinical scores incorporate variables such as age, sex, cardiovascular risk factors (hypertension, hyperlipidemia, diabetes, smoking history, family history of CAD), electrocardiogram (ECG) changes, cardiac enzyme levels, and symptoms. These scores help determine whether patients have a low, intermediate, or high pretest probability of CAD.
Chest pain can be classified as non-cardiac, atypical angina, and typical angina. Women and patients with diabetes may present without chest pain, but with equivalent anginal symptoms such as shortness of breath with exercise or pain in the arm, or they may also have silent ischemia.
Patients who present with an acute coronary syndrome, a high probability of pretest CAD, or related clinical manifestations are strong candidates to proceed directly to invasive coronary angiography. Noninvasive imaging (stress testing or anatomical evaluation) is warranted in those with suspicious cardiac symptoms, especially if they have a high pretest probability of CAD.
| Stress electrocardiogram with exercise |
> Test characteristics
ECG stress testing is the most common practice in community and hospital settings, as a first-line functional test to evaluate chest pain and suspected CAD. Patients with a low or intermediate pretest probability of CAD are ideal candidates for stress ECG.
The Bruce protocol is the most commonly used format. The patient is placed on the treadmill at a speed of 2.7 km/min and an incline of 10%. Every 3 minutes, the speed and inclination angle are increased.
A standard 12-lead ECG is used. If movement or artifact occurs, it may help to swap the electrodes on the extremities with those on the torso and ensure that they have good contact with the skin (shaving if necessary).
Before starting, a baseline ECG is done. The stress test continues until the patient feels fatigued and asks to stop, or develops cardiac symptoms, significant ECG changes, or other high-risk characteristics.
The stress ECG test is considered diagnostic if the patient reaches at least 85% of the maximum heart rate predicted by age. If the test is terminated before reaching this threshold due to the presence of these findings, but the ECG results meet the criteria for ischemia, the test is considered positive for ischemia.
However, if a test is completed before 85% of the predicted heart rate is achieved and there are no changes in the ECG, the test is considered non-diagnostic, since it is not known whether ischemia would have occurred if the patient had continued with the test. the required workload.
> Diagnostic and prognostic features
ST segment depression and functional capacity (exercise duration) are the 2 most prognostic markers
A stress ECG test is considered positive for ischemia if there is at least 1 mm horizontal ST segment depression or in the descending branch. Ascending depression of the ST segment is not considered a positive finding. ST segment elevation >1 mm is highly suggestive of significant ischemia.
It has been proven that the sensitivity of stress tests is 68%, with a specificity of 77%. The Coronary Artery Surgery Study database suggested that ST-segment depression and functional capacity (exercise duration) are the 2 most prognostic markers.
Functional capacity is the strongest prognostic marker of exercise ECG testing, estimated by metabolic equivalents (ME), which approximate O2 consumption during exercise, (1 ME represents 3.5 ml/kg/min). Laboratories estimate functional capacity by the duration of exercise, following an exercise protocol.
Many laboratories report the Duke treadmill score, which predicts 5-year CAD risk for patients without known CAD. This score incorporates variables including the degree of ST segment changes and symptoms. Lower scores are associated with higher mortality and a significantly increased likelihood of CAD.
> Limitations
A positive exercise stress ECG for ischemia usually shows ST segment depressions, especially in the inferior and precordial leads, and may not necessarily correspond to the territory of a specific coronary artery.
Electrocardiographic stress testing should not be used if any of the following abnormalities are found on the baseline ECG: complete left bundle branch block or a ventricular rhythm, pre-excitation syndrome, or ST-segment depression >1 mm at rest.
Pronounced hypertrophy of the left ventricle (LV) or the use of digoxin can affect the results of the stress test. Patients with reduced mobility (e.g., amputees or severe arthritis) may not be able to exercise on the treadmill or walk long enough to complete a diagnostic test.
There may be false positive results, more common in women. Many of these limitations can be overcome by adding an imaging component to the stress test, or a stress test can be performed with pharmacological stress.
| Stress echocardiography |
> Test characteristics
Stress echocardiography uses ultrasound images after exercise or pharmacological stress to detect coronary abnormalities. Ischemia is identified by abnormalities in wall motion or worsening of a preexisting abnormality, which generally correlate with stenosis in the corresponding coronary territory.
Stress echocardiography is frequently used for the diagnosis of CAD in patients with contraindications to stress ECG or when stress ECG findings cannot be interpreted or are nondiagnostic or, if the risk of CAD is sufficient to justify imaging, to improve the sensitivity and specificity of the test.
The images show wall movements in each of the LV walls, before and after stress. The results are analyzed. For scoring, a 17-segment model of the LV (divided into apical, middle, and basal segments) is used and each segment is graded on a 4-grade scale for regional wall motion (normokinesia, hypokinesis, dyskinesia, and akinesia). ).
If image quality is not optimal, particularly in patients with large body habitus or lung disease, or if more than 2 contiguous segments have poor endocardial definition, visualization of the endocardium can be improved using intravenous contrast agents (echo-contrast ).
These agents do not contain iodine and improve the accuracy of assessment of ventricular volume and ejection fraction, improve recognition of wall motion abnormalities and reproducibility. Stress echocardiography can be based on exercise on a treadmill or stationary bicycle or pharmacological stimulation. This exercise accompanies the dobutamine infusion.
Treadmill stress tests most frequently use the Bruce protocol. It is important to obtain post-exercise imaging as soon as possible after stopping exercise, as regional wall motion abnormalities that persist during recovery become less pronounced and resolve as heart rate decreases.
Bicycle stress echocardiography (supine or upright), although less common, is quieter, allowing for accurate precordial measurements, with fewer motion artifacts, and allowing imaging to be obtained while the patient is exercising, at different stages of the test. . It is often used for valvular or hemodynamic evaluation.
Exercise stress echocardiography may allow hemodynamic evaluation in addition to ischemia. Doppler evaluation may be useful in patients with dyspnea and suspected exercise-induced diastolic dysfunction or pulmonary hypertension, or in those with mitral valve stenosis or regurgitation whose clinical severity is greater than that shown by resting echocardiography. Stress echocardiography can also evaluate dynamic LV outflow tract obstruction in hypertrophic cardiomyopathy.
Pharmacological stress echocardiography can evaluate ischemia in patients who cannot exercise or can help define the severity of aortic stenosis, particularly when it is low flow gradient and severe aortic stenosis is suspected.
It is performed primarily with a dobutamine infusion, although dipyridamole or adenosine can be used to test for ischemia. Dobutamine is a synthetic catecholamine that stimulates ß1 adrenergic receptors, with chronotropic (increased heart rate) and inotropic (increased myocardial contractility) effects, resulting in an increase in O2 demand.
> The typical dobutamine stress protocol
It consists of a continuous intravenous infusion of dobutamine in increments every 3 minutes, starting with 5 mg/kg/min and up to a maximum of 40 mg/kg/min. Dobutamine may have an arrhythmogenic or hypertensive effect, and requires monitoring at all times. Patients with severe or advanced conduction disorders, asthma or airway disease are not affected by dobutamine.
> Diagnostic and prognostic features
The results of stress echocardiography are reported by the description of wall motion as normal, ischemic, viable myocardium, or scarred. Normal myocardium has normal motion of the segments at rest and after stress, all segments demonstrate normal motion or hyperkinesia, with a general increase in ejection fraction.
When the myocardium is ischemic, contractile function after stress changes from normal to hypokinetic, akinetic, or dyskinetic, in at least 2 adjacent segments.
If the myocardium shows scarring (due to a history of myocardial infarction), the dysfunction at rest (hypokinesia or akinesia) remains fixed after stress.
The myocardium is considered viable when segments with resting hypokinesia show sustained improvement during stress (indicating the presence of "stunning" ) or improvement during an early phase of stress with subsequent deterioration of peak contractility (i.e., biphasic response). ), which portends possible improvement with revascularization .
Another feature that may suggest ischemia is a decrease in LV ejection fraction after exercise (rather than an increase) or an increase in LV cavity size after stress (expected to decrease as a result of increased pressure). contractility).
A meta-analysis has shown that stress echocardiography with exercise, dobutamine, dipyridamole, or adenosine has a sensitivity of 83%, 81%, 72%, and 79%, respectively, and a specificity of 84%, 84%, 95%, and 91%. , respectively. In general, stress echocardiography is considered more specific than nuclear perfusion imaging, but less sensitive.
The advantage of stress echocardiography is greater diagnostic accuracy than stress ECG and no ionizing radiation, so it is often the preferred test for middle-aged women with symptoms and intermediate cardiovascular risk, or patients who have dyspnea and in which another hemodynamic evaluation can be done in the same test.
> Stress echocardiography has prognostic value . A normal test without regional parietal abnormalities predicts <1% per year of cardiac events. Increasing severity of regional wall motion abnormalities after peak stress corresponds to a higher rate of clinical events.
> Limitations
As with all images, the interpretation of a stress echocardiogram can be affected by subjectivity. Therefore, it is important to have good protocols and quality image acquisitions, along with experienced operators to interpret the images. Stress echocardiography may miss ischemia due to small, distal, or branching vessel disease and is considered somewhat less sensitive than nuclear imaging. Patients who are obese or have emphysema may have problems with the acoustic window, resulting in suboptimal images.
| Myocardial perfusion imaging with nuclear medicine |
> Test characteristics
Nuclear myocardial perfusion imaging (MPI) can be performed using single photon emission CT (SPECT) or positron emission tomography (PET). As with stress echocardiography, the stress test for MPI can be exercise or pharmacological induction.
IPM involves the intravenous administration of radioactive tracers. The gamma camera detects radiant emissions from the tracer perfusing the myocardium. Tracer uptake also depends on the flow dynamics and integrity of the myocyte membrane. Color-coded myocardial perfusion images, before and after stress, are generated in different axes, allowing the distribution of each coronary artery to be evaluated.
The most frequently used radioisotopes and cameras for PET and SPECT are different. Rubidium or ammonia radionuclides are generally used for PET perfusion imaging. Fluorodeoxyglucose (FDG) can be used to assess myocardial viability and inflammation.
Technetium 99 (sestamibi) is predominantly used for SPECT scans. Thallium has been eliminated due to the high associated radiation. PET has advantages over SPECT that include superior image quality due to more favorable tracer characteristics.
Positron-emitting radiotracers used in PET can produce higher energy photons than those produced by SPECT radiotracers, resulting in fewer attenuation artifacts. PET can also detect smaller, more subtle perfusion defects (typically 4-7 mm) due to its greater spatial resolution relative to SPECT (typically 12-15 mm). Other advantages of PET over SPECT are a lower radiation load and shorter scan time.
Stress for MPI can be exercise-induced (using the Bruce treadmill protocol, which has the added value of providing predictive data for functional capacity) or pharmacological, for those unable to exercise. The most commonly used stress agents are vasodilators, mainly regadenoson (which has a more favorable benefit) or dipyridamole and adenosine.
Vasodilators increase coronary blood flow through their effect on the adenosine A2A receptor, which increases blood flow and flow rate in vessels under normal conditions, compared with a lesser response in stenotic vessels that are already dilated when maximum, thus decreasing the subendocardial flow to regions supplied by diseased vessels. Dobutamine infusion can also be used, although it is rarely used in PMN imaging.
> Diagnostic and prognostic features
MPIs allow evaluating the physiological importance of coronary stenosis by measuring the heterogeneity of coronary flow. The ability to maintain maximal flow ("coronary flow reserve") is impaired when coronary stenosis is >50%. Normal myocardial perfusion is manifested by a homogeneous distribution of the radiotracer on both stress and exercise imaging. repose.
In general, perfusion defects in a coronary territory that occurs after stress, with normal flow at rest, suggest inducible ischemia, whereas a fixed defect in perfusion, both at rest and after stress, a coronary distribution, suggests a scarred myocardium (previous myocardial infarction) or hibernating myocardium (which can improve its function if it is revascularized). IMP defects are usually reported with reference to:
• Size or extent of the defect: small (<10% of the LV affected), medium (10%-20% affected) or large (> 20% affected)
• Severity of perfusion defect (mild, moderate, severe)
• Degree of reversibility (reversible, irreversible)
• Location (based on the 17-segment LV model and coronary artery territory).
Tomograms, which estimate LV ejection fraction, are also produced in MPI studies. The presence of transient ischemic dilation is a sign of severe ischemia. It refers to post-stress enlargement of the LV, rather than a decrease in cavity size, as would be expected by increasing contractility.
Myocardial blood flow and myocardial flow reserve allow quantitative assessment of myocardial perfusion and, in some cases, may help identify microvascular disease. Some centers routinely include these measurements in PET clinical reports, and in the future quantitative measurements on SPECT may also be available.
The sensitivity and specificity of SPECT for the diagnosis of CAD reported by a systematic review is 82% and 76%, respectively, and 91% and 89% for PET. The explanation for the difference is the superior spatial resolution and attenuation correction of PET. SPECT is considered more sensitive than stress echocardiography, but less specific. In general, PET is accepted as the most accurate non-invasive functional test of ischemia.
MPIs provide clinically useful prognostic information. For those with normal MPI results, the clinical event rate of cardiac death or myocardial infarction at 2 years is <1%.
The presence of perfusion defects is a predictor of clinical myocardial infarction and mortality.
IPNs are useful in symptomatic patients with suspected CAD to show the presence or absence of ischemia (as well as in those with known CAD, to assess whether the stenosis is functionally significant).
Furthermore, in those with impaired LV systolic function, viability can also be simultaneously assessed, particularly with FDG-PET, which may help guide revascularization decisions. Those with left bundle branch block may be appropriate candidates for SPECT or PET with regadenoson (as exercise stress ECG would not be diagnostic). For obese patients, PET is the best modality.
> Limitations
IPM techniques involve radiation exposure and there must be sufficient clinical value to justify testing. SPECT may be more prone to artifact from diaphragmatic attenuation or intestinal interposition, potentially leading to false-positive results. It is identified in the inferior wall of the LV, particularly in obese patients. This problem is less with PET. The main limitations of PET are the higher cost and poor availability (requires the installation of a cyclotron).
Finally, a normal MPI suggests the absence of obstructive CAD. Still, that doesn’t rule out mild to moderate atherosclerosis, which may not be contributing to symptoms, but may nevertheless warrant preventive measures. Identification of calcium on pre-MPI CT images may help identify the presence of subclinical coronary arteriosclerosis.
| Coronary computed tomography angiography |
> Test functions
Coronary CT angiography (CTA) is a non-invasive modality that can identify and assess the severity of CAD. It differs from the stress test in that it directly visualizes the coronary arteries and can quantify the degree of stenosis and evaluate plaque characteristics. In contrast, stress testing evaluates LV wall motion abnormalities or perfusion defects to determine whether obstructive CAD is present.
Adequate patient preparation is necessary to achieve high-quality images and greater accuracy. Ideally, a heart rate <60 beats/min is needed, although with more advanced scanners it can be <70 beats/min. The target heart rate can be achieved with a calcium channel blocker, either orally or intravenously. Sublingual nitroglycerin is administered just before the scan, to help dilate the coronary arteries and improve image quality. An iodinated contrast medium is then administered intravenously into the cubital fossa.
Computed tomography (CT) images are acquired with electrocardiographic guidance. To reduce radiation exposure, it is preferable to use a prospective acquisition protocol for CTCA scans, with images obtained at a point in end-diastole (or sometimes end-systole) when cardiac and coronary motion is smaller, thus reducing the artifact caused by movement.
> Diagnostic and prognostic features
The images are reconstructed and analyzed to analyze the presence, degree and location of coronary stenosis. Plaque composition (calcified, noncalcified, or mixed) and characteristics of high-risk plaque, if present, are also reported.
The Society of Cardiovascular CT recommends using the EAC data and reporting system to standardize AATC reporting. Segments are classified as no stenosis, minimal stenosis (0%-24%), mild (25%-49%), moderate (50%-69%), severe (70%-99%), or total occlusion (100 %).
High-risk plaques are classified according to attenuation, which depends on the amount of lipids and presence of calcium. These characteristics suggest that the plaque is more vulnerable to rupture and, therefore, the patient has a greater probability of clinical events such as myocardial infarction.
Numerous meta-analyses have confirmed the diagnostic accuracy of AATC, with a sensitivity of 99% and specificity of 89%. Therefore, it has excellent negative predictive value and can accurately rule out CAD. Guidelines recommend ACTC as a first-line test to evaluate stable precordialgia.
The results of the ACTC are prognostic. Patients with obstructive CAD identified on CTCA have worse outcomes than those with nonobstructive CAD, who, in turn, have a higher rate of clinical events than those without CAD. CTA is clinically useful as it can identify patients with non-obstructive CAD, which a stress test would classify as normal, as non-obstructive lesions do not limit flow. Furthermore, identification of nonobstructive CAD by CCTA offers an opportunity for aggressive risk factor modification, including statin therapy.
CTA can also be used to evaluate bypass graft patency of the coronary arteries, and is excellent in the evaluation of suspected cases of anomalous coronaries. Although CTA is predominantly used to assess coronary anatomy, techniques such as fractional flow reserve CT and stress perfusion CT (FFR-CT) imaging are now available to determine functional significance. of a moderate coronary lesion (e.g., whether or not a 50% to 70% stenosis on CT is obstructive flow limiting). FFR-CT has additional costs and images are analyzed off-site. On the other hand, CT perfusion requires higher doses of radiation and contrast and longer scanning time, limiting its widespread adoption.
Another advance in imaging studies is the use of inflammatory markers such as attenuation in coronary perivascular fat in CCTA, which can predict cardiac mortality, so may play a clinical role in prevention.
Anticipated developments in artificial intelligence open the possibility of radiomics evaluation to improve image evaluation and quantitative evaluation of ACTC, with improvements in workflow and diagnostic accuracy. They are expected to have a significant impact on clinical practice.
> Limitations
CCTA involves exposure to ionizing radiation. It requires an iodinated contrast medium, which requires premedication in patients with iodine allergy. And its use is limited in those with kidney failure. In general, CTA is less useful for evaluating coronary stents due to an artifact that limits its ability to evaluate stent restenosis unless the stent is large.
Arrhythmias, including atrial fibrillation and ectopic rhythms, make it more difficult to obtain a quality image, requiring adjustment of protocols. The faster heart rate also reduces image quality. Intense calcification may result in segments that make the stenosis difficult to interpret and potentially limit the usefulness of AACTC in elderly or dialyzed patients. Patients who cannot hold their breath would not be suitable for ACTC.
| Coronary artery calcium score |
> Test characteristics
Coronary artery calcium cation (CAC) scoring is widely accepted and used to stratify the risk of CAD in asymptomatic patients. It is a surrogate marker for the presence and burden of CAD as it quantifies coronary calcification and therefore the extent of atherosclerotic disease. It involves the acquisition of a rapid non-contrast CT scan, with the field of view focused on the heart. Axial slices with 3 mm thickness are acquired prospectively with a synchronized ECG in mid-to-late diastole. The calcium score.
> Diagnostic and prognostic features
There are strong data to support the prognostic value of ACTC, and improve cardiovascular risk stratification. In absolute terms, an Agatston CAC = 0 is associated with an excellent prognosis; 1 to 99, 100 to 299, and ≥300 are associated with increased risks of mortality, respectively. However, risk prediction is often reported as a percentile with adjustments for age, sex, and ethnicity.
The CAC may be useful in decision making for asymptomatic patients with 10-year risk coding, according to the Atherosclerotic Cardiovascular Disease Risk Calculator system, and for whom the benefit of a statin is in question. Based on this estimate, in 2019, the American College Cardiology and the American Heart Association recommended starting a statin in patients with diabetes or those aged 40 to 75 years with risk >7.5% and continuing for 10 years. In the latter group, CAC can be used to make adjustments in risk stratification and guide initiation of statins.
> Limitations
It should be noted that although CAC has prognostic use in asymptomatic patients, if symptoms equivalent to angina are being evaluated, then CAC has no role as it cannot determine whether a calcified coronary plaque is stenotic.
| Cardiac magnetic resonance imaging under stress |
> Test characteristics
Cardiac stress magnetic resonance imaging (MRI) is a promising modality, with advantages such as good spatial and temporal resolution, wide field of view, and the ability to acquire images in different planes. The contrast medium used is gadolinium, which does not emit ionizing radiation. To detect perfusion defects, MR perfusion images can be taken before and after stress.
Furthermore, cine MR images allow evaluation of regional wall motion abnormalities. MRIs also provide information, including quantification of ventricular function. However, current technology limits anatomical evaluation of the coronary arteries in adults using MRI and only the proximal coronary portions can be visualized.
> Diagnostic and prognostic features
Stress cardiac MRI compares favorably with established noninvasive modalities in terms of accuracy in detecting CAD. MRI images of stress-induced ventricular wall motion abnormalities have a sensitivity and specification of 83% and 86%, respectively.
MR perfusion imaging has a sensitivity of 91% and a specificity of 81%. The absence of ischemia on MR images has prognostic value and is associated with very low risk of cardiovascular death and myocardial infarction (<1% combined annual rate).
> Limitations
Stress cardiac MRI is relatively new and is, at least, the most frequently used technique compared to the other modalities. Its availability and access may be limited and with practical experience still incipient and limited in most centers. Other potential limitations include the cost and long duration of the scan, which may be intolerable for people with significant claustrophobia or inability to hold their breath. It may also be contraindicated in those with metallic devices or prostheses or patients with severe renal dysfunction, due to the risk of nephrogenic systemic fibrosis.
| Appropriate use criteria |
For each imaging modality there are criteria guides for appropriate use. Guidelines announced by various medical societies are helpful in improving the understanding of test selection. However, medical judgment is always required.
| Conclusions |
Anatomical evaluation with coronary CT provides details to evaluate CAD in patients at risk. The results can help in risk stratification and prognosis. Appropriate test selection is based on the patient’s clinical picture, imaging, nature of symptoms, risk profile, clinical questions, and strengths and limitations of the tests. Other factors that may influence test selection are local experience, availability and access to a particular modality, cost, and patient preference.
