Continuing Education Activity

Coronary artery disease is the leading cause of ischemic cardiomyopathy. Approximately half of the patients with coronary artery disease can have dysfunctional hibernating myocardium that is potentially reversible with restoration of blood flow. Earlier identification of these areas can have profound prognostic implications. This activity reviews the role of both invasive and noninvasive imaging techniques in the evaluation of coronary artery disease.

Objectives:

• Identify the role of infarct-avid imaging techniques in the evaluation of coronary artery disease.
• Review the indications of both invasive and noninvasive imaging techniques in the evaluation of coronary artery disease.
• Describe additional information that can be obtained from infarct-avid imaging techniques that can further guide diagnostic testing and therapeutic strategy.
• Outline and explain different characteristics and limitations of individual infarct-avid imaging techniques.

Introduction

Coronary artery disease is the leading cause of ischemic cardiomyopathy. Impairment in left ventricular dysfunction can result from a spectrum of myocardial injury, including ischemia and myocardial necrosis, causing progressive tissue remodeling.[1] Approximately half of the patients with coronary artery disease can have dysfunctional hibernating myocardium that is potentially reversible with restoration of blood flow. Earlier identification of these areas can have profound prognostic implications.[2] The majority of noninvasive imaging techniques such as an echocardiogram, coronary computed tomography angiography (CCTA), magnetic resonance imaging (MRI), and nuclear studies can assess wall motion abnormalities and function. However, each of these techniques has their distinct characteristics that can help decide which study should be performed based on the clinical indication.An echocardiogram is often the initial study of choice for assessing cardiac function in critically ill or unstable patients as it can be conveniently performed at the bedside and is not associated with radiation. Thus it can be safely used in pregnant and pediatric patients. CCTA is the best non-invasive technique to evaluate anomalous vessels, luminal irregularities, and stenosis of the coronary vasculature.[3] Cardiac magnetic resonance (CMR) and nuclear studies can better characterize abnormalities within myocardial tissue, such as scar formation or infiltrative processes. Additionally, myocardial perfusion imaging (MPI) with single-photon emission computed tomography (SPECT) and positron emission tomography (PET) provide information regarding tissue viability and perfusion defects and can further guide treatment. Invasive coronary angiography serves as both a diagnostic and therapeutic assessment tool to potentially restore vascularization and improve ventricular dysfunction.

Procedures

Compromise in myocardial blood flow results in ischemia, which subsequently activates inflammatory pathways that cause a spectrum of myocardial injury. This injury can be reversible in the case of myocardial stunning or hibernation, but chronic or severe ischemia results in apoptosis and necrosis at the cellular level resulting in irreversible fibrosis. Based on their severity, these changes manifest as regional wall motion abnormalities on echocardiography, CCTA or MRI, and/or perfusion defects on myocardial perfusion imaging. 

Infarct-avid imaging has an increasing role in the noninvasive evaluation of coronary artery disease. Unlike echocardiography or CCTA, cardiac SPECT imaging utilizes the difference in the redistribution of radioactive tracer uptake by myocardium both at rest and with exercise or vasodilator stress to identify areas of potentially reversible ischemia.[4][5] The most commonly used radiotracers are technetium-labeled radiotracers, which include Tc-99m sestamibi, Tc-99m pyrophosphate, Tc-99m tetrofosmin, and thallium-201.[6] Technetium-labeled radiotracers rely on passive diffusion across viable sarcolemmal and mitochondrial membranes, whereas thallium-201 requires active transport via Na/K ATPase within sarcomeric membranes for tracer uptake.[7][8] Damaged myocardial cells with compromised permeability or hypoperfusion from stenotic lesions result in decreased radiotracer uptake, which may indicate obstructive coronary artery disease. Findings of new wall motion abnormalities, ventricular dilatation, and lack of improvement in post-stress ejection fraction on SPECT imaging may have poor prognostic value. An advantage of technetium-based radiotracers over thallium is exposure to less radiation as well as better soft-tissue attenuation resulting in better image quality, which can be particularly helpful in female patients.

Positron emission tomography (PET) imaging assesses uptake of F-fluorodeoxyglucose (F-FDG), a glucose analog. Under ischemic conditions, myocytes convert to glucose-based metabolism over fatty acids; new areas with FDG uptake suggest regional ischemia. Various comparative studies have found PET imaging with slightly better sensitivity (92%) than SPECT imaging (85%) with better spatial resolution and lower radiation. Despite these small differences, a randomized trial suggested similar results outcomes with the clinical decision using SPECT versus PET-based techniques.[9]

Cardiac magnetic resonance (CMR) is another noninvasive technique that can detect areas of ischemia and infarction but is commonly utilized in evaluating inflammatory and infiltrative processes affecting myocardium and pericardium. Furthermore, concurrent cardiac gating allows the measurement of right and left ventricular function. A cardinal feature of CMR is the late gadolinium enhancement (LGE) percentage of wall thickness, which has >90% specificity of predicting myocardial viability.[10] LGE detects the increase in extracellular space following myocardial necrosis as a consequence of ischemia. Less than 25% of the involved region reflects a higher likelihood of recovery following revascularization in contrast to less likelihood if LGE is >50%.[11]

Both invasive coronary angiography with cardiac catheterization and coronary CT angiography (CCTA) evaluate anatomic defects of the coronary vessels such as anomalous coronaries or coronary atherosclerosis. Both techniques require the injection of iodinated contrast to characterize the lumen of coronary vessels. Although coronary CTA can offer detailed plaque characterization and identify culprit lesions, ultimately, coronary angiography is the gold standard technique that offers both diagnostic and therapeutic intervention.[3]

Indications

Noninvasive infarct-avid myocardial perfusion imaging can be particularly useful in the evaluation of acute myocardial infarction and coronary artery disease when diagnosis by conventional methods is limited. A late presentation of suspected acute myocardial infarction after approximately 7 days in the context of equivocal clinical history, absent or uninterpretable diagnostic EKG findings, and negative cardiac biomarkers can be challenging to diagnose. Tissue characterization, including new areas with reversible ischemia, old infarcts, or viable myocardium, can be identified using myocardial perfusion imaging.

Exercise stress testing is the most commonly utilized means of risk stratification in patients with low to intermediate pretest probability of coronary artery disease. However, in the presence of baseline EKG abnormalities such as a left bundle branch block, left ventricular hypertrophy, preexcitation, paced rhythm, or baseline ST-segment depression, results of exercise stress testing may be uninterpretable. An allergic reaction to iodine/ iodinated contrast is a contraindication for CCTA, while a morbidly obese patient may have poor windows for visualization with echocardiography. In such scenarios, including pregnancy, CMR can be a useful diagnostic modality in the evaluation of coronary artery disease. In patients who are suspected to have new ischemia after recently having undergone coronary artery bypass grafting or other major surgical procedures, SPECT and PET can also help identify areas of new periprocedural infarcts.

Coronary CTA can be utilized in the ischemic evaluation of a patient with an intermediate pretest probability of having coronary artery disease and evaluating coronary artery defects such as anomalous coronaries. Coronary angiography and catheterization offer both diagnostic and therapeutic interventions. Techniques such as fractional flow reserve (FFR) utilized during coronary catheterization evaluate blood flow under conditions of maximal hyperemia help to identify clinically significant stenosis and potentially offer appropriate revascularization strategy, including percutaneous coronary intervention, bypass grafting, or medical management.[3]

Normal and Critical Findings

Abnormal imaging findings vary depending upon the type of imaging study utilized in the evaluation of coronary artery disease. For example, regional wall motion abnormalities on echocardiography, CCTA or MRI, and/or perfusion defects on myocardial perfusion imaging are indicative of ischemia or infarction. Furthermore, a global reduction in wall motion, ventricular dilatation, and lack of improvement in post-stress ejection fraction on SPECT imaging may portend a poor prognosis.

Abnormal enhancement noted on cardiac magnetic resonance helps to identify inflammatory and infiltrative processes affecting myocardium and pericardium in addition to ischemic or infarcted regions. CT angiography can detect anomalous vessels and luminal stenosis of the coronary vasculature. Furthermore, interventional techniques such as measuring fractional flow reserve can further characterize areas of critical stenosis that may benefit from therapeutic intervention.[3]

Interfering Factors

An important consideration in myocardial perfusion imaging is the timing of radiotracer administration from the onset of presumed infarction as maximum deposition with infarcted areas occurs at approximately 48 to 72 hours following the ischemic event with a decremental clearance after about 7 days. Hence, studies performed within 24 hours or past 7 days have higher rates of false-negative results. Obtaining serial scans at 48 to 72-hour intervals can increase diagnostic yield.[6] 

False-negative results may arise when a heavy burden of diffuse coronary artery disease with poor collateral circulation causes “balanced ischemia” from global hypoperfusion. There may also be a significant delay in radiotracer penetrance within myocardial tissue, in which case repeating a study about 4 to 5 days later may help improve diagnostic yield. The decreased myocardial mass within inferior and posterior walls compared to anterior and lateral walls or smaller territories of infarction may decrease sensitivity, though serial scans can significantly improve the detection of small infarcts.[12] 

The presence of intracardiac or valvular calcifications, ventricular aneurysm, infiltrative diseases such as amyloidosis, anthracycline toxicity, radiation therapy, and scarring from prior myocardial infarction can cause false-positive results when technetium pyrophosphate tracer is used in SPECT imaging.[13] 

Cardiac PET requires concurrent administration of vasodilators due to the short half-life of PET radiotracers. Other limitations include limited anatomic detail of coronary calcification due to attenuation correction. Many studies have shown high rates of false-negative results in patients with insulin resistance and low cardiac output.

Potential contraindications of cardiac MRI include the presence of metal devices or implants, including cardiac implanted electronic devices, wires, and clips, and foreign bodies. A comprehensive patient screening is mandatory to assess potential risks prior to the MRI. CMR entails longer times for image acquisition in a still position, which may be difficult for certain patients to tolerate.[10] 

Heavy coronary calcifications on CTA may cause artifacts that may impact the interpretation of results, and smaller, distal vessels may be poorly visualized.

Complications

Complications are typically associated with invasive techniques and the use of contrast material. Although rarely seen with the use of gadolinium, the theoretical risk of nephrogenic systemic fibrosis, especially in patients with poor kidney function, remains a concern. Both CCTA and coronary angiography with catheterization must be done with caution in patients with severely reduced renal function, given the use of contrast, and both imaging techniques involve radiation exposure. Despite cardiac catheterization being the gold standard imaging modality in the evaluation of coronary artery disease, risks include bleeding, infection, retroperitoneal hemorrhage, dysrhythmias, pseudoaneurysms, coronary artery dissection, tamponade, pneumothorax, and death.[14]

Patient Safety and Education

Depending upon the type of imaging study a patient is undergoing, patients are encouraged to follow specific instructions to optimize results. Patients are usually required to avoid any consumption by mouth after midnight before myocardial perfusion imaging study to minimize the possibility of increased gastric metabolic activity interfering with the evaluation of the inferior wall. Additionally, caffeine, other sympathomimetic medications, nitroglycerine, or beta-blockers should be held to optimize evaluation for coronary artery disease. Jewelry and other metal objects should not be worn to avoid any potential imaging artifacts. For exercise stress testing, patients are encouraged to wear comfortable clothing and shoes.[15]

Clinical Significance

Noninvasive imaging modalities such as SPECT, PET, and CMR are playing an increasing role in the assessment of tissue characterization, cardiac function, and area of infarction to further guide patient management and therapeutic strategy. In addition to functional and anatomic information, the pattern and extent of radiotracer uptake, along with the duration of a positive study, provide prognostic information. Using this information allows the clinician to strategize a therapeutic approach with the optimization of medical therapy or revascularization with invasive techniques to improve cardiac dysfunction.

The spectrum of ischemic heart disease can encompass temporary impairment in cardiac function that’s often reversible with restoration of blood flow to infarcted areas from myocyte necrosis, rendering them irreversible. As rates of obesity increase in the United States, the rates of coronary artery disease are also expected to increase concurrently. Various imaging modalities, as discussed above, serve as a key component in the evaluation and management of coronary artery disease. It is important to consider the indication of the study, costs, contraindications, and procedural risks based on the unique characteristics of each patient to decide which is the best study to perform. Appropriate consultation should be considered to ensure appropriate studies are ordered to obtain the intended information.