Infarct Avid Imaging Study

Procedures

Compromise of myocardial blood flow results in ischemia, which activates inflammatory pathways that lead to a spectrum of myocardial injury. This injury can be reversible in myocardial stunning or hibernation, but chronic or severe ischemia leads to 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 uses the redistribution of radioactive tracer uptake in the 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 poststress ejection fraction on SPECT imaging may have poor prognostic value. An advantage of technetium-based radiotracers over thallium is lower radiation exposure and improved soft-tissue attenuation, resulting in better image quality, which can be particularly helpful in female patients.

Positron emission tomography (PET) imaging assesses the uptake of F-fluorodeoxyglucose (F-FDG), a glucose analog. Under ischemic conditions, myocytes switch from fatty acid-based to glucose-based metabolism; new FDG-positive areas suggest regional ischemia. Comparative studies have found PET imaging to have slightly better sensitivity (92%) than SPECT imaging (85%), with better spatial resolution and lower radiation exposure. Despite these small differences, a randomized trial suggested similar results for clinical decision-making 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 used to evaluate inflammatory and infiltrative processes affecting the 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 greater than 90% specificity in predicting myocardial viability.[10] LGE detects the increase in the extracellular space following myocardial necrosis due to ischemia. An involved region of less than 25% indicates a higher likelihood of recovery following revascularization, whereas an involved region greater than 50% indicates a lower likelihood.[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 iodinated contrast injection to characterize the lumen of coronary vessels. Although coronary CTA can provide detailed plaque characterization and identify culprit lesions, coronary angiography remains the gold-standard technique for both diagnosis and therapeutic intervention.[3]

Indications

Noninvasive infarct-avid myocardial perfusion imaging can be particularly useful in evaluating acute myocardial infarction and coronary artery disease when conventional diagnostic methods are limited. A late presentation of suspected acute myocardial infarction after approximately 7 days in the context of equivocal clinical history, absent or uninterpretable diagnostic electrocardiogram (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 evaluating coronary artery disease. In patients who are suspected of having 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 used to evaluate a patient with an intermediate pretest probability of coronary artery disease and to assess coronary artery defects, such as anomalous coronaries. Coronary angiography and catheterization offer both diagnostic and therapeutic interventions. Techniques such as fractional flow reserve (FFR), used during coronary catheterization, evaluate blood flow under conditions of maximal hyperemia to help identify clinically significant stenosis and potentially guide revascularization strategies, including percutaneous coronary intervention, bypass grafting, or medical management.[3]

Normal and Critical Findings

Abnormal imaging findings vary depending on the imaging study utilized to evaluate coronary artery disease. For example, regional wall motion abnormalities on echocardiography, CCTA, or MRI, and/or perfusion defects on myocardial perfusion imaging indicate 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 on cardiac magnetic resonance helps identify inflammatory and infiltrative processes affecting the myocardium and pericardium, as well as 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 relative to the presumed onset of infarction, as maximum deposition in infarcted areas occurs approximately 48 to 72 hours after the ischemic event, with subsequent clearance. 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, so repeating a study about 4 to 5 days later may help improve diagnostic yield. Decreased myocardial mass in the inferior and posterior walls, compared with the anterior and lateral walls, or in smaller infarction territories, may decrease sensitivity. However, 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] Due to the short half-life of PET radiotracers, cardiac PET requires concurrent administration of vasodilators. 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 to cardiac MRI include metal devices or implants, such as cardiac implanted electronic devices, wires, clips, and foreign bodies. A comprehensive patient screening is mandatory to assess potential risks before the MRI. CMR requires longer image acquisition times 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 gadolinium, the theoretical risk of nephrogenic systemic fibrosis remains a concern, especially in patients with poor kidney function. 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 on the imaging study a patient is undergoing, patients are encouraged to follow specific instructions to optimize results. Patients are usually required to avoid oral intake after midnight before a myocardial perfusion imaging study to minimize the risk of increased gastric metabolic activity interfering with the evaluation of the inferior wall. Additionally, caffeine, other sympathomimetic medications, nitroglycerin, or beta-blockers should be held to optimize evaluation for coronary artery disease. Jewelry and other metal objects should not be worn to avoid potential imaging artifacts. Patients are encouraged to wear comfortable clothing and shoes for exercise stress testing.[15]

Clinical Significance

Noninvasive imaging modalities such as SPECT, PET, and CMR are increasingly important in assessing tissue characterization, cardiac function, and areas of infarction to further guide patient management and therapeutic strategy. In addition to functional and anatomic information, the pattern and extent of radiotracer uptake, as well as the duration of a positive study, provide prognostic information. Using this information allows the clinician to develop a therapeutic approach that optimizes medical therapy or revascularization via 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. As discussed above, various imaging modalities are key components in evaluating and managing coronary artery disease. It is important to consider the study indication, costs, contraindications, and procedural risks, tailored to each patient's unique characteristics, to determine the best study to perform. Consultation should be considered to ensure that appropriate studies are ordered to obtain the intended information.