Cardiology

Noninvasive Risk Stratification: How Does a Clinician Decide Test Selection and Appropriateness

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I. Assessment of the symptomatic patient with no known coronary artery disease

Patients without a history of coronary artery disease but with symptoms of chest pain who present to the hospital, clinic or office are one of the more common presentations in which the clinician is required to assess and risk stratify. The first necessity is to determine the patients pretest probability of coronary artery disease (CAD). Although there are many existing and well validated models for this, we feel that the most practical risk tool is the model put forth by the American College of Cardiology (ACC) and its most recent guidelines (Table 1).

Table 1.

Clinical risk assessment for patient with chest pain

In this model, the likelihood that the signs and symptoms that the patients present with are related to CAD are broken into low, intermediate, and high likelihood for CAD. This model is based on the presenting symptoms, age and gender. We will focus on those patients that present with intermediate or high likelihood of CAD. The low likelihood patients generally can effectively be managed with no testing procedures.

Those patients with an intermediate to high likelihood of CAD should be planned for further risk stratification based on the patient’s ability to perform routine activities of daily living without difficulty as well as the baseline ECG being normal. The following are the minimum requirements to accurately and reliably conduct an exercise stress test. Testing is listed in order of preference.

Exercise tolerance testing (ETT) without imaging

Functional or exercise stress testing represents the “gold standard” for eliciting inducible ischemia in symptomatic patients with no known CAD according to ACC/AHA guidelines.

The production of ischemia, however, depends on the degree of stress load and also the severity of flow disturbance. Coronary artery stenosis less than 70% is often undetectable by functional testing. In addition to ischemia, this testing modality can also provide information about the long-term risk. Exercise capacity remains one of the strongest indicators of long-term risk (including death) for men and women with suspected or known coronary heart disease. Additionally, the application of a scoring system, such as the Duke treadmill score, provides additional incremental prognostic information.

Indications: indications for ETT include evaluating patients with intermediate or high pretest probability of coronary artery disease. This evaluation includes both diagnosis and risk stratification. The test is also indicated to assess exercise capacity in response to therapy in patients with heart failure.

Contraindications: conditions such as acute myocardial infarction, unstable angina, uncontrolled arrhythmia, uncontrolled symptomatic heart failure, active endocarditis, acute pulmonary or systemic embolism, hemodynamic significant aortic stenosis, resting ECG changes that impair the diagnostic accuracy during exercise or those patients who are unable to exercise due to orthopedic or other conditions.

Testing procedure: The more common modality for clinical exercise testing is using a treadmill or a stationary bicycle ergometer. The treadmill is the more popular modality in the U.S.

Testing requires a protocol that progresses from a low workload to progressively higher workloads to induce a potentially ischemic state. The Bruce protocol is a well validated and the preferred office-based testing protocol. This protocol is divided into stages with 3-minute increments. Each of these stages requires the patient to walk faster and on steeper grades.

The patient starts at stage one, which is a low grade with a 10% incline, at a speed of 1.7 mph. The patient must be able to achieve at least 85% of maximally predicted heart rate (220 minus age of patient). The patients taking an exercise stress test undergo a baseline assessment, including cardiac auscultation, blood pressure, and ECG.

Interpretation and results: The goal of exercise testing in patients suspected of having coronary artery disease is to achieve a high level of exercise (i.e., maximal exertion) in the setting of a negative ECG.

The identification of an ischemic ECG is done by observing ≥ 1 mm horizontal or down sloping ST segment depression at 80 msec after the J point and during peak exercise. The absence of this, generally and reliably excludes obstructive CAD.

Performance characteristics: the diagnostic accuracy of exertional ST segment depression has been studied extensively in several meta-analyses, systematic reviews, large observational registries, and randomized controlled trials. From this, the composite diagnostic sensitivity is 61% while the specificity ranges from 65% to 75%.

Importantly the accuracy is lower in women.

The prognostic accuracy is improved with the addition of other factors, such as exercise duration, chronotropic incompetence, angina, ventricular arrhythmias, heart rate recovery, and hemodynamic response to exercise.

Other Testing Considerations

Stress cardiac single-photon emission computed tomography (SPECT)/positron emission tomography (PET) myocardial perfusion imaging

Indications: evaluating patients with intermediate or high pretest probability of coronary artery disease in which ETT is inappropriate (abnormal ECG at rest, inability to exercise)

Secondarily, patients with ETT results that are inconclusive or need further evaluation such as positive ECG, or a negative result in a patient with strong evidence of CAD

Contraindications: Recent myocardial infarction (MI), acute coronary syndrome, respiratory distress, hypotension

Test performance: Both SPECT and PET rely upon provocation of potential ischemia in the form of exercise (generally with a treadmill) or pharmacologic stress

Patient preparation: Patients must be clinically stable and without symptoms at the time of testing.

Patients must be NPO for at least 6 hours, preferably 24 hours prior to testing.

It is known that certain cardiac medications affect imaging results. As it is not known until the stress is performed whether the mode will be exercise or pharmacologic, the following medications should be withheld for all stress imaging: beta-blockers (24 to 48 hours), calcium channel blockers (12 to 24 hours), nitrates (6 hours), caffeine containing products (12 hours).

Stress performance

Exercise: graded exercise is preferred. The procedure was described previously. At peak exercise, a radiopharmaceutical is injected.

Pharmacologic stress: If a patient cannot exercise to a reasonable level (85% maximally predicted heart rate), the option is to use pharmacologic stress. This occurs in approximately 40% of all stress imaging procedures.

Vasodilator stress: most common in the form of regadenoson, dipyridamole, or adenosine; all three dilate all arteries, but if a critical stenosis is present, it preferentially gets less vasodilation, which can be observed on nuclear imaging as less uptake of a radiopharmaceutical.

For vasodilator stress, an infusion or injection of the agent is performed with injection of a radiotracer at peak hyperemia (1 to 9 minutes later). Monitoring is performed similar to exercise, including a 12-lead ECG, blood pressure, and heart rate evaluation, as well as assessment of symptoms and respiratory distress.

In cases in which vasodilator stress is contraindicated, such as patients with reversible airways disease, dobutamine stress may be performed. As this depends on an increase in heart rate similar to exercise, achievement of 85% maximum predicted heart rate (MPHR) is a target for a diagnostic test. Continuation after 85% is generally not indicated.

Combined vasodilator exercise: In cases of uncertain exercise capacity, a combined vasodilator/exercise protocol may be used.

With the most widely used vasodilator, regadenoson, exercise is attempted first and if unsuccessful, regadenoson is injected followed by a radiopharmaceutical injection.

SPECT protocol

Generally, the procedure requires a separate injection of radiotracer (generally tc99m sestamibi or tetrofosmin) while the patient is at rest, followed by another injection at peak stress described previously.

The patient is imaged under a gamma camera, generally dual-headed to save time, requiring 7 to 15 minutes for each study (rest, stress). National guidelines such as from the American Society of Nuclear Cardiology (ASNC) should be strictly followed for optimal image quality.

Processing is performed at completion and provides a display of stress and rest images viewed simultaneously in various ASNC recommended views. This includes a display of ECG-gated studies to provide information on ventricular function at both rest and stress.

Interpretation of the results: In broad categories, no abnormalities suggest a normal response to stress and no CAD; fixed defects (similar abnormalities between rest and stress) are consistent with prior MI (especially in the setting of a regional wall-motion abnormality), while a reversible perfusion defect (abnormal at stress, normal at rest) is consistent with “ischemia.”

The image interpretation also provides evaluation of the size, severity, and location of the abnormality or abnormalities. This may indicate the “culprit” artery, such as left anterior descending artery in the case of anterior perfusion abnormities, circumflex artery for lateral abnormities, and right coronary artery for inferior abnormalities.

The number of abnormalities may also provide information on the number of vessels with critical stenosis. Ventricular function can be assessed globally for both the right and left ventricle, and regionally for the left ventricle.

The normal ejection fraction for nuclear is 50% to 75%.

Performance characteristics (sensitivity/specificity, accuracy advantages/disadvantages): An important performance characteristic is that every patient presenting to the stress nuclear laboratory in stable condition can undergo a successful rest/stress protocol.

The overall sensitivity for detecting critical CAD is 85% to 90%, with a more variable specificity of 60% to 90%. Using newer camera systems equipped with attenuation correction, one can expect a specificity of 90% due to compensation for attenuation artifact.

Advantages: high diagnostic accuracy, valuable risk stratification, readily available (5,000 plus laboratories in U.S.)Disadvantages: although low, there is radiation exposure (estimated 7 to 12 mSv), a longer procedure (2 to 4 hours) than comparable procedures

Stress testing with echocardiographic imaging

The purpose of exercise stress echocardiography is to identify new or worsening wall-motion abnormality and identify changes in global LV function during or immediately after exercise or pharmacologic stress. This information can be invaluable in patients who are symptomatic but with no known CAD.

For those patients that are unable to exercise, pharmacologic stress testing echocardiographic imaging may be an option. In our opinion, this is a test of third choice behind ETT or nuclear imaging, except in situations in which nuclear imaging is not available.

Indication: Failed ETT or inconclusive nuclear cardiology study.

Contraindications: Contraindications to both exercise and pharmacologic stress echocardiography are the same as those of standard exercise ECG chip testing (see above).

Testing procedure: Baseline standard echocardiographic images are obtained prior to exercise. In addition to assessing for baseline wall-motion abnormalities, there should also be assessment of ventricular function, chamber size, wall thickness, aortic root diameter, and gross valvular structure and function.

The exercise procedure can be completed using a symptom limited exercise stress test according to one of the standard protocols with either a treadmill or bicycle. As previously discussed, it’s important to obtain adequate workload by achieving at least 85% of the patient’s age predicted maximal heart rate and to produce a rate–pressure product of at least 20,000.

At peak exercise, early image acquisition is important since ischemia induced wall-motion abnormalities may resolve rapidly after discontinuation of exercise. This can lead to a decrease in sensitivity of the test.

For patients that are unable to exercise, pharmacologic stress testing using dobutamine stress testing is an option. Using this protocol, there is a graded infusion of dobutamine in 5-minute stages starting at 5 µg/kg/minute, followed by 10, 20, 30, and 40 µg/kg/min.

The endpoints are to achieve new or worsening wall-motion abnormalities, significant arrhythmias, hemodynamic instability, at or before a target heart rate of 85% of the age-predicted maximum heart rate. If an inappropriate heart rate is achieved, hand exercises, as well as atropine in divided doses of 0.25 to 0.5 mg to a total of 2.0 mg, can be used to achieve the target heart rate.

Interpretation: Visual assessment of endocardial excursion and more thickening is used for analysis of a stress echocardiogram. Function in each segment (16-segment model) is created at rest and with stress as normal or hyperdynamic, hyperkinetic, akinetic, dyskinetic, or aneurysmal.

Images from the low or intermediate stages of dobutamine infusion or bicycle/treadmill exercise should be compared with peak stress images to maximize sensitivity for detection of coronary disease. Therefore, a normal stress echocardiogram result is defined as normal left ventricular (LV) wall motion at rest and with stress at appropriate workload.

In contrast, resting wall-motion abnormalities, unchanged with stress, are classified as fixed and often represent regions of prior myocardial infarction. In contrast, a new or worsening wall-motion abnormality during stress is indicative of ischemia.

Performance characteristics: In general, a stress echocardiography has 88% sensitivity and 83% specificity. However, this may be influenced by certain patient characteristics, such as left ventricle hypertrophy or high body mass index.

Importantly, the prognostic value of this testing modality also uses demonstrating and negative predictive value for MI and cardiac death of 98% over about a 3-year period for both men and women. A normal exercise echocardiogram result is associated with an annual event rate of cardiac death and nonfatal myocardial infarction of less than 1%. Therefore, these patients rarely require further diagnostic evaluation unless there’s a change in clinical status.

Moreover, patients with extensive stress-induced abnormalities in multivessel distribution are at high risk of mortality and cardiac events. In these patients, coronary angiography and subsequent myocardial revascularization may be justified. Patients with resting LV dysfunction but no inducible myocardial ischemia have an intermediate risk, whereas patients with resting LV dysfunction and new wall-motion abnormalities have the greatest risk for death and cardiac event.

Cardiac magnetic resonance (CMR) imaging

We will limit the discussion of CMR to the detection of and prognostication of CAD. Briefly, CMR detects signals from hydrogen nuclei, which are abundant within the body. By applying pulses in the form of “pulse sequences,” signals can be received and processed to produce an image of the spatial distribution of the protons within the body

Myocardial perfusion imaging by CMR is most commonly achieved with measurement at baseline (rest) and a comparative measurement during stress

The most common form of stress is achieved by using a vasodilator, which is administered to induce maximal hyperemia and to determine the coronary flow capacitance. Exercise-induced stress is currently performed in specialized academic centers

Indications: According to the appropriate use criterion, CMR may be useful for patients with an intermediate pretest probability of CAD who have an ECG that is uninterpretable or if the patients are unable to exercise. It also has usefulness in patients suspected of having an anomalous coronary artery. It is usually reserved for patients where there is a need to reduce radiation exposure, such as the pediatric population

Contraindication: Normal prior stress test and those with a high CAD risk using the Framingham risk score. Also, it is contraindicated in those patients who have had a prior stress test within a year

Testing procedure: CMR perfusion imaging is performed using a T1-weighted sequence to visualize the first passage of a gadolinium (Gd)-based contrast agent in transit through the heart at a concentration and an infusion rate of 0.075 mM/kg 4 mL/sec, respectively

Interpretation: Following peripheral injection of Gd, the contrast is detected against the background of the myocardium, with rapid enhancement during vasodilation stress. Signal intensity correlates with contrast concentration and hence the degree of stenosis. An experienced observer examines the myocardium for regions of low signal or hypoperfusion relative to normally perfused segments.

Performance characteristic: Prognostic data are now available using both vasodilator and DS CMR methods with a 3-year event-free survival, which has been reported at 99.2% for patients with normal stress perfusion CMR or DS CMR and 83.5% for those with abnormal stress perfusion or DS CMR. Importantly, evidence of ischemia by stress perfusion CMR or DS CMR is an independent predictor of cardiac events over the 3-year period with hazard ratios of 12.5.

Coronary computed tomography angiogram (CTA)

The developments of multidetector row systems with electrocardiographic gating have made CT imaging of the heart and the coronary arteries feasible. To obtain coronary images noninvasively is compelling and therefore has led to a rapid evolution of multidetector CT technology. Despite this rapid growth, the use of this technology has not been as rapid.

Indications: According to the appropriateness criteria for cardiac CT angiography, CTA may be useful for evaluation of chest pain syndrome or acute chest pain in patients with an intermediate pretest probability of coronary artery disease, and an ECG that is uninterruptable or the patient is unable to exercise. In the symptomatic patient without CAD, this test is most useful as a secondary evaluation following an ETT or inconclusive stress nuclear/echo examination.

Contraindications: Contraindications to this test include the exposure to iodinated contrast agents that have the potential to produce allergic reactions and/or acute renal injury. Renal function must be assessed. It should also be recognized that CTA also involves radiation exposure to the body tissue. This is 12 mSv on average; however, it may be as high as 30 mSv in some hospital settings.

Testing procedure: Noninvasive coronary imaging requires a system capable of acquiring motion free, high-spatial resolution images; 64-channel multidetector row computed tomography allows for this requirement.

The patient is selected according to the indications outlined in this chapter. On an elective basis, the patient will receive appropriate beta blockage to achieve bradycardia at a rate of 50 to 60 beats/min. On the day of the examination, the patient is prepared by establishing intravenous access via the antecubital vein. The patient is then administered an additional beta blockade if the desired heart rate is not achieved.

Interpretation: Workstations with automated reconstruction are helpful to reduce the amount of physician time required for each study. And at present, there are no universally accepted conventions or standards for the display of cardiac or coronary images.

Performance characteristics: The average per patient sensitivity for identifying coronary artery disease with a 50% diameter stenosis is approximately 85%, with an average per patient specificity of 90%. Furthermore, adequate prognostic studies are required in this testing modality. This should include large samples and long follow-up periods. To date, this has not been adequately assessed and hence the prognostic value of this test cannot be adequately discussed.

Coronary calcium scoring

It is well known that calcium deposits within the coronary arteries occur almost exclusively in patients with atherosclerosis. The absence of calcium reduces the risk of the patient having significant coronary artery disease. Calcium scoring uses CT technology at a low dose of radiation to image for calcium deposits on the coronary arteries.

Indication: A noncontrast CT calcium scoring can be considered for use in patients with an intermediate coronary heart disease (CHD) risk, and for the specific subset of low-risk patients in whom a family history of premature CHD is present. Intermediate risk is defined as a 10-year Framingham risk between 10% and 20%.

Contraindications: Low risk Framingham score; prior calcium score within the last 5 years

Testing procedure: Using a multidetector CT scanner the patient is placed on the CT couch and undergoes a noncontrast low radiating scan.

Interpretation: Calcified lesions are identified on CT images by applying a threshold of 130 HU; therefore, tissues with densities of 130 HU or greater are considered to correspond to calcium. For each coronary artery, a region of interest (ROI) is drawn around each calcified lesion. A low calcium score corresponds to a very low cardiovascular risk, while a very high score (>400 HU) corresponds to a very high cardiovascular (CV) risk.

Performance characteristics: The Coronary Artery Calcification (CAS) score is an important independent predictor of all-cause mortality. After adjusting for risk factors such as family history, dyslipidemia, hypertension, smoking, and diabetes—in a study using the NCEP/ATP III model—5-year mortality varied according to the CAC score from 0.9% to 3.9%, 1.1% to 9.0%, and 2.0% to 12.2% in low, intermediate, and high-risk Framingham subsets.

II. Assessment of Symptomatic Patients with Known CAD

Patients with known coronary artery disease (CAD) can generally be categorized into two broad groups: those with CAD being treated medically, and those with CAD who have undergone either coronary artery bypass grafting (CABG) or percutaneous coronary intervention (PCI). These two general categories warrant different evaluation strategies.

For patients on medical therapy alone, the goal is often to reduce the patient’s risk of progression of CAD by lipid-lowering strategies, as well as provide the patient with a symptom-free lifestyle. The occurrence of symptoms, if demonstrated to be associated with ischemia by evaluation, indicates failure of current therapy and perhaps a need to consider revascularization procedures. The optimal test is that which can best assess the presence, location, and severity of the ischemia.

For patients who have undergone revascularization procedures, many are receiving medical therapies following their procedures. Thus the goal of therapy is similar to those without intervention: reduce progression of CAD and provide a symptom-free lifestyle. In addition, the purpose of the drug therapies is to prevent the procedure from failing, such as restenosis after PCI and closure of grafts, be they arterial or venous.

The occurrence of symptoms, if associated with ischemia, indicates a failure of the revascularization procedure, the medical arm of therapy, or both. The object of the testing procedures in these patients is to document the presence of ischemia and to reproduce the symptoms. In addition, the location and severity of the ischemia may guide the physician to either change the medical arm of treatment or perhaps entertain a failure of the revascularization procedure and proceed with catheterization. Generally, if the symptoms recur several months after the procedure, a noninvasive strategy is warranted.

Indications: patient’s postmedical therapy or post-PCI/CABG with symptoms suggestive of ischemia

Contraindications: recent MI, acute coronary syndrome, respiratory distress, hypotension

Test performance: Both SPECT and PET rely upon provocation of potential ischemia in the form of exercise (generally with a treadmill) or pharmacologic stress. This was described in Section 1.

Interpretation of the results: In broad categories, no abnormalities suggest a normal response to stress and no ischemia. Fixed defects (are consistent with prior MI (especially in the setting of a regional wall-motion abnormality), while a reversible perfusion defect (abnormal at stress, normal at rest) is consistent with “ischemia.” This was described further in Section 1.

Performance characteristics (sensitivity/specificity, accuracy advantages/disadvantages): Also described in Section 1.

Outcomes: The results of the SPECT or PET study should first be considered on the basis of previous therapies: medical vs. interventional (PCI or CABG). In general, SPECT and PET results provide assessment of both stress-induced myocardial perfusion and function. The categories of importance are: normal, mildly abnormal, and moderate to severely abnormal. The implications of each are listed below by specific therapies:

Outcomes of SPECT imaging in CAD patients receiving medical therapy alone

Normal results: A stress SPECT or PET study that is normal in symptomatic patients with CAD on medical therapy alone indicates no evidence of ischemia and success of current treatments. It also indicates that the symptoms the patient is having may be from some other cause, and a further noncardiac workup may be warranted.

The finding of normal ventricular function in this setting indicates a good prognosis and no evidence of myocardial injury from the patient’s CAD.

Abnormal results:Positive for ischemia. A result of a reversible or partially reversible perfusion abnormality indicates active ischemia, and a failure of medical therapy.

Two approaches are reasonable: if the perfusion abnormality is confined to one or less than one vascular territory, and there is room for more vigorous medical therapy, medicines can be increased and evaluation of symptoms made. If either the patient is already maximized on therapy or if the perfusion abnormalities are of sufficient size, indicating more than on vascular territory, cardiac catheterization is warranted.

Abnormal, fixed defect(s): Fixed perfusion abnormities, especially in the setting of a regional wall-motion abnormality in the same area indicate prior infarction, not ischemia. This is especially true for a patient with a history of prior MI. Thus the patient’s symptoms may not be due to ischemia, and other etiologies may be sought.

Another important part of the results is overall ejection fraction. If this has changed (worsened), especially if lower than 35%, new therapies may be warranted.

Outcomes of SPECT imaging in CAD patients who have undergone PCI/CABG

Normal results: A stress SPECT or PET study that is normal in symptomatic patients with CAD s/p PCI/CABG indicates no evidence of ischemia and success of current treatments. It also indicates that the symptoms the patient is having may be from some other cause, and further noncardiac workup may be warranted.

The finding of normal ventricular function in this setting indicates a good prognosis and no evidence of myocardial injury from the patient’s CAD.

Abnormal results: Positive for ischemia. A result of a reversible or partially reversible perfusion abnormality indicates active ischemia, and a failure of medical therapy. Two approaches are reasonable: if the perfusion abnormality is confined to one or less than one vascular territory, and there is room for more vigorous medical therapy, medicines can be increased and evaluation of symptoms made. If either the patient is already maximized on therapy or if the perfusion abnormalities are of sufficient size indicating more than on vascular territory, cardiac catheterization is warranted.

Abnormal, fixed defect(s): Fixed perfusion abnormities, especially in the setting of a regional wall-motion abnormality in the same area, indicate prior infarction, not ischemia. This is especially true for a patient with a history of prior MI. Thus the patient’s symptoms may not be due to ischemia, and other etiologies may be sought.

Another important part of the results is overall ejection fraction. If this has changed (worsened), especially if lower than 35%, new therapies may be warranted.

Alternative procedures: stress echocardiography

Either pharmacologic (in the form of dobutamine) or exercise stress can be performed in conjunction with echocardiography. Generally the same indications are operative for stress echo, although patients with high body mass index are generally excluded because of poor image quality. Further, patients with prior MI or CABG are suboptimal candidates as identifying wall-motion changes in the setting of baseline abnormalities is difficult.

The images for exercise must be obtained as soon as the patient is removed from the exercise, while dobutamine is used as pharmacologic stress, and achievement of 85% maximally predicted heart rate is the same goal as with ETT or nuclear. Thus, in the setting of symptomatic patients with known CAD, stress nuclear imaging is preferred.

Alternative procedures: Stress magnetic resonance imaging

This procedure can be performed, but is rarely used in this situation and generally performed in hospitals due to equipment and operational costs. The study is performed under the MR camera with no personnel in the room. Dobutamine is generally used as the stress. This is a difficult procedure with safety concerns for patients with known CAD, as the possibility for a stress-induced event is higher than in a population with no CAD. This test is not recommended for this population, especially those symptomatic.

Alternative procedures: coronary CTA

Coronary CTA can be performed by injection of contrast dye and a short acquisition phase for the CT data. It is generally not recommended for patients with known CAD, as the question is not the presence of CAD, but rather ischemia. Determining the percent stenosis precisely is difficult with CTA and further, even if abnormal, the physiologic consequence would still not be known.

Alternative procedures: calcium scoring

This procedure is not recommended either in symptomatic patients or those with known CAD.

Alternative procedures: exercise tolerance testing (ETT)

Exercise tolerance testing is valuable primarily in patients with no known CAD. In a vulnerable population of symptomatic patients with CAD, a negative ETT may not provide the diagnostic accuracy desired.

III. Assessment of Asymptomatic Patients with No Known CAD

Patients with no symptoms and no history of CAD can often pose a challenge for the provider, especially in the setting of multiple cardiac risk factors providing a greater risk for CAD.

It is well known from epidemiologic studies that readily measured and often modifiable risk factors are associated with development of CAD. It is therefore advisable to apply global risk scores, such as the Framingham risk score, to assess risk in all asymptomatic adults without a clinical history of CAD. Although the Framingham risk score provides a continuous range from 0% to 100%, it can also be used to categorize patients in broad terms as “low risk,” intermediate risk,” and “high risk.”

Resting electrocardiogram

Several studies have demonstrated that abnormal 12-lead electrocardiograms are predictive of subsequent mortality in cardiovascular events among asymptomatic adults.

Indications and patient selection: A resting electrocardiogram is reasonable for cardiovascular risk assessment in asymptomatic adults with hypertension or diabetes. It may also be considered in patients without hypertension and diabetes.

Contraindications: none

Details of how the procedure is performed: this procedure is performed by the application of 12 separate leads on the patient’s limbs and chest. Electrical impulses are then measured at the level of each lead in a continuous manner.

Interpretation of results: The identification of abnormalities, such as hypertensive left ventricular hypertrophy, QRS prolongation, ST segment depression, T-wave inversion, and pathologic Q waves, have important implications and are therefore useful for risk assessment.

Performance characteristics of the procedure: a number of classifications seem to have been identified to risk stratify ECG abnormalities. One is the normal code criteria, which subdivides electrocardiographic abnormalities into major and minor types.

Major abnormalities include a trooper bleaching or flutter, high-grade atrioventricular block, baby dissociation, complete bundle branch block, pathologic keyways, isolated ischemic abnormalities, left ventricular hypertrophy with accompanying repolarization abnormalities, and arrhythmias, such as supraventricular tachycardia or ventricular tachycardia.

Minor abnormalities include first- and second-degree AV block, borderline prolongation of the QRS interval, prolonged repolarization, isolated minor Q waves, and ST-T LVH high-voltage only, left atrial enlargement, frequent atrial or ventricular premature beats, or secular blocks.

Outcomes: both Q-wave abnormalities, as well as left ventricular hypertrophy, and associated repolarization abnormalities have been predictive of subsequent cardiovascular risk.

Alternative and/or additional procedures to consider

Computed tomography for coronary calcium scoring: the acquisition of thin slices of the coronary arteries is a noninvasive, sensitive test for the detection and quantification of coronary calcium, and therefore coronary atherosclerosis. Data suggest it performs better in risk stratification.

Contraindications: Persons at low risk should not undergo coronary artery calcification scoring to measure cardiovascular risk.

Details of how the procedure is performed: the test is typically performed using 2.5 to 3.0 mm thick axial images obtained through the heart. The calcium then is quantified within the coronary arteries as the area affected on the scan multiplied by a weighting factor, depending on the Hounsfield unit density of the calcium deposits.

Interpretation of results: a calcium score of zero has a low risk of cardiac events for 3 to 5 years (0.4% annually). A calcium score between 100 and 400 indicates an increased risk, with the risk ratio of 4.3. Furthermore, a calcium score range of 400 to 1,000 indicates a risk ratio of 4.6%, while a score greater than 1,000 indicates a risk of 7.1%.

Performance characteristics of the procedure: the relationship between coronary artery calcification and cardiac outcomes in both men and woman, and different ethnic groups are similar based on score.

Exercise electrocardiography: Generally, in asymptomatic patients without CAD, and ETT is not recommended. However, it is recommended in patients with intermediate to high pretest risk who have a strong family history of premature CAD and wish to increase their exercise regimen.

Contraindications: as above

Details of how the procedure is performed: as above

Interpretation of results: as above

Performance characteristics of the procedure: Although the measurement of ST segment changes are important markers of ischemia during an exercise stress test, a more important prognostic marker includes exercise capacity, where a decreased exercise capacity is associated with increased risk of cardiovascular events. Additionally, markers reflective of autonomic nervous system function can also predict cardiovascular events. The heart rate recovery after exercise cessation is an important marker of parasympathetic tone and a delayed heart rate recovery is associated with death and cardiac events, including in patients who are asymptomatic.

Stress echocardiography: this test is not indicated for cardiovascular risk assessment in asymptomatic patients with low or intermediate risk.

Stress myocardial perfusion imaging: This test has been described previously and may be considered in the assessment of the asymptomatic adult patient with diabetes or a strong family history of coronary artery disease or if previous risk assessment testing suggests high risk for coronary artery disease, such as a calcium score greater or equal to 400.

Coronary computed tomography angiography: Assessment of asymptomatic patients without CAD is not recommended for this indication.

Magnetic resonance imaging of plaque: coronary magnetic resonance imaging of plaque is not recommended for cardiovascular risk assessment in asymptomatic adults.

IV. Assessment of Asymptomatic Patients with Known CAD

Patients with known CAD can generally be categorized into two broad categories: those with CAD being treated medically, and those with CAD who have undergone interventional procedures, either coronary artery bypass grafting (CABG), or percutaneous coronary intervention (PCI). These general categories warrant different evaluation strategies for the asymptomatic patient.

For CAD patients on medical therapy alone, the goals are often to reduce the patient’s risk of progression of CAD by lipid-lowering strategies, as well as provide the patient with a symptom-free lifestyle. The occurrence of symptoms, if demonstrated to be associated with ischemia by evaluation, indicates failure of current therapy and perhaps a need to consider revascularization procedures. In the absence of symptoms, the goal of testing is to evaluate progression of disease, which would represent a failure of medical therapy alone.

For patients who have undergone revascularization procedures, many are also receiving medical therapies following their procedures. Thus the goal of this group of patients is similar: reduce progression of CAD and provide a symptom-free lifestyle.

The occurrence of symptoms, if associated with ischemia, indicates a failure of the revascularization procedure, the medical arm of therapy, or both. In asymptomatic patients, the objective to the testing procedures is still to document the presence of ischemia. Testing in asymptomatic patients has a much lower yield and needs to be approached with caution. However, in patients with CAD, the testing procedure of choice is cardiac nuclear imaging with either PET or SPECT.

Stress cardiac SPECT/PET myocardial perfusion imaging

Stress SPECT or PET imaging has a primary role in the assessment of asymptomatic patients with known CAD. The procedure can be performed with either exercise or pharmacologic stress. Every patient who presents to a nuclear cardiology lab can have the study performed, unless he or she is clinically unstable. Most data relates to SPECT, but in some circumstances cardiac PET may be performed instead.

Indications:indications for each group are listed below:

CAD patients receiving medical therapy: In CAD patients receiving medical therapy alone, there are no clear guidelines for assessment. However, data suggests that CAD proceeds with significant progression in approximately 3 years. Thus, medical therapy could be assessed after initiation of therapy beyond 3 years.

Asymptomatic following PCI: The therapies for PCI have improved vastly over the past few years, thus appropriate use criteria (ACC/ASNC) recommend testing procedures not sooner than 2 years postprocedure.

Asymptomatic patients post-CABG: The recommendation is at least 5 years after the procedure.

Repeat testing after initial posttreatment test: No clear guidance, but a normal test indicates a very good prognosis and short of symptoms developing, no further testing is warranted for several years.

Contraindications: Recent MI, acute coronary syndrome, respiratory distress, hypotension

Test performance: Testing procedures have been described in the symptomatic CAD section previously.

Interpretation of the results: Interpretation of results has been described in Section 2, symptomatic CAD patients.

Performance characteristics: previously described.

Outcomes: The results of the SPECT or PET study should first be considered on the basis of previous therapies: medical vs. interventional (PCI or CABG). The categories have been previously described in the “symptomatic CAD” section.

Outcomes of SPECT imaging in asymptomatic CAD patients receiving medical therapy alone

Normal results: A stress SPECT or PET study that is normal indicates no evidence of ischemia and success of current treatments. The finding of normal ventricular function in this setting indicates a good prognosis. Although no formal guidelines exist, retesting in this patient group is unwarranted unless symptoms develop.

Abnormal results: Positive for ischemia. A result of a reversible or partially reversible perfusion abnormality indicates active ischemia and a failure of medical therapy.

Two approaches are reasonable: if the perfusion abnormality is confined to one or less than one vascular territory, and there is room for more vigorous medical therapy, medicines should be increased without catheterization. In the asymptomatic patient, only those with severe perfusion abnormalities indicating multivessel ischemia should be considered for cardiac catheterization as minimal data demonstrate benefit to revascularization.

Abnormal, fixed defect(s): Fixed perfusion abnormities, especially in the setting of a regional wall-motion abnormality in the same area, indicate prior infarction, not ischemia. No change in therapy is recommended, unless ventricular function has worsened, especially if the EF has fallen below 35%.

Outcomes of SPECT imaging in CAD patients who have undergone PCI/CABG

Normal results: A stress SPECT or PET study that is normal in symptomatic patients with CAD s/p PCI/CABG indicates no evidence of ischemia and the success of current treatments. These results suggest continuation of current therapies. Retesting of such patients unless symptoms develop is discouraged.

Abnormal results: Positive for ischemia. A result of a reversible or partially reversible perfusion abnormality indicates active ischemia and a failure of therapy. Several studies have demonstrated that even asymptomatic patients following intervention with ischemia on nuclear imaging have a worse prognosis than those with a normal study. For those patients following PCI, ischemia that is suspicious for the vessel(s) revascularized, catheterization is warranted. In patients post-CABG, only those with moderate to severe perfusion abnormalities should be considered for catheterization.

Abnormal, fixed defect(s): Fixed perfusion abnormities, especially in the setting of a regional wall-motion abnormality in the same area, indicate prior infarction, not ischemia. Another important part of the results is overall ejection fraction. If this has changed (worsened), especially if lower than 35%, new therapies may be warranted.

Alternative procedures: exercise tolerance testing (ETT)

Exercise tolerance testing is valuable primarily in patients with no known CAD. However, in this setting, an ETT may be reassuring for the patient, especially if the patient has good exercise tolerance and the test is normal for ECG changes or symptoms. It does not have the accuracy of assessing ischemia as does nuclear imaging.

Alternative procedures: stress echocardiography

Either pharmacologic (in the form of dobutamine) or exercise stress can be performed in conjunction with echocardiography. Patients with prior MI or CABG are lesser candidates, as identifying wall-motion changes in the setting of baseline abnormalities is difficult. The real disadvantage to this test in the setting of known CAD is the limited abilities with prior MI and also determination of multivessel disease. Thus in the setting of asymptomatic patients with known CAD, stress nuclear imaging is preferred.

Alternative procedures: stress magnetic resonance imaging

This testing procedure is rarely performed in the setting of asymptomatic patients, with or without CAD.

Alternative procedures: coronary computerized tomographic angiography (CTA)

It is generally not recommended for patients with known CAD, as the question is not the presence of CAD, but rather ischemia.

Alternative procedures: calcium scoring

This procedure is not recommended either in asymptomatic patients with known CAD.

What's the evidence?

Heller, GV, Hendel, R. Handbook of nuclear cardiology: Cardiac SPECT and cardiac PET. New York. 2013.

(This reference outlines some of the technical and practical components of cardiac SPECT and cardiac PET.)

Heller, GV, Hendel, R. Nuclear cardiology: Practical applications. McGraw-Hill. 2010.

(This reference also addresses the practical applications of nuclear cardiology. It’s useful to get some of the technical background on the testing modalities addressed in this chapter.)

Hendel, RC, Patel, MR, Kramer, CM. "Computed tomography and cardiac magnetic resonance imaging". J Am Coll Cardiol. vol. 48. 2006. pp. 1475-497.

(This reference outlines the appropriateness criteria of cardiac computed tomography and cardiovascular magnetic resonance imaging. It clearly outlines when tests can be used and when not to use it.)

Jneid, H, Anderson, JL, Wright, R. "2012 ACCF/AHA focused update incorporated into the ACCF/AHA 2007 guidelines for the management of patients with unstable angina/non–ST-elevation myocardial infarction: A report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. Table 6: Likelihood that signs and symptoms represent an ACS secondary to CAD". J Am Coll Cardiol. 2013.

(This reference has an important recommendation for the evaluation of the patient with chest pain. Additionally, Table 6 is referenced in this chapter for determining likelihood that chest pain represents acute coronary syndrome.)

Fihn, SD, Gardin, JM, Abrams, J. "2012 ACCF/AHA;ACP/AATS/PCNA/SCAI/STS guideline for the diagnosis and management of patients with stable ischemic heart disease". J Am Coll Cardiol. vol. 60. 2012. pp. e44-e164.

(This reference outlines the management and evaluation of patients with chest pain and chronic ischemic heart disease.)

Douglas, PS, Garcia, MJ, Haines, DE. "ACCF/ASE/AHA/ASNC/HFSA/HRS/SCAI/SCCM/SCCT/SCMR 2011 Appropriate use criteria for echocardiography". J Am Coll Cardiol. vol. 59. 2011. pp. 1126-66.

(This reference outlines the appropriateness for using echocardiographic images to assess for ischemic heart disease.)

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