4 Prior Evaluation

Functional Testing, Multidetector CT

• Functional tests such as stress electrocardiography, stress echocardiography, and stress nuclear perfusion imaging have limited accuracy for the detection of anatomical disease but provide important prognostic information.

• Impaired chronotropic response and heart rate recovery are powerful predictors of outcomes. However, it is unknown whether these variables are modifiable by revascularization.

• A normal exercise echocardiogram or myocardial perfusion imaging result is associated with a low risk of cardiac events. The extent of stress-induced segmental wall motion and perfusion abnormalities helps define incremental levels of risk and which populations of patients will benefit most from revascularization.

• Positron emission tomography (PET) is one of the most sensitive methods for the identification of viable myocardium. The detection of gadolinium-delayed enhancement by cardiac magnetic resonance (CMR) is the most sensitive method for identifying scarred, nonviable myocardium.

• A normal multidetector computed tomography (MDCT) coronary angiogram study virtually excludes the presence of coronary artery disease (CAD). However, given the relative overestimation of stenosis severity by MDCT, functional testing should be considered after MDCT studies that show moderate anatomical coronary stenosis.

Introduction

Noninvasive testing in patients with known or suspected CAD is conducted to establish the diagnosis of coronary atherosclerosis as the cause of symptoms and/or to determine whether a patient would benefit from medical therapy and/or myocardial revascularization. Functional tests such as stress electrocardiography, stress echocardiography, and stress scintigraphic myocardial perfusion imaging (MPI) attempt to quantify the presence of ischemia based on electrical, mechanical, and perfusion abnormalities. Over the last decade, cardiac computed tomographic angiography (CCTA) has evolved as a noninvasive alternative to invasive catheterization for the evaluation of coronary anatomy. In general, anatomical tests such as CCTA have greater sensitivity for the detection of CAD, whereas functional tests have greater ability to predict benefit from revascularization. This chapter provides an overview of the methodology and interpretation of these tests with the objectives of providing guidelines for appropiate test selection and treatment.

Stress Testing

Anginal symptoms in patients with obstructive CAD are caused by an imbalance between myocardial oxygen supply and oxygen demand. Asymptomatic patients with CAD have normal resting blood flow even in the presence of epicardial coronary artery stenosis. Myocardial perfusion pressure and blood flow are maintained by compensatory dilation of the coronary arterioles. During stress, myocardial oxygen demand increases but myocardial blood flow cannot increase proportionally, thus leading to the development of ischemia. Myocardial ischemia results in progressive metabolic and functional alterations including electrical repolarization abnormalities and abnormal regional diastolic and systolic myocardial function. On these principles, different stress testing modalities attempt to quantify the burden of obstructive CAD based on the extent of myocardial hypoperfusion, ST depression, and wall motion abnormalities. Stress may be accomplished by a number of methods, including exercise, pharmacological maneuvers, and even mental tests. Whenever possible, exercise is the preferred modality, since the information obtained may be more easily related to functional limitations. The choice between electrocardiography (ECG) versus echocardiography or MPI is often determined by local availability, costs, and patient characteristics. In general, specificity has been reported to be higher with stress echocardiography and sensitivity higher with MPI. Accordingly, many clinicians prefer stress echocardiography for individuals with a lower pretest probability of obstructive CAD and MPI for those with a higher probability. Although exercise ECG has lower sensitivity and specificity than stress imaging modalities, it is cost-effective and provides comparable prognostic information in patients who have a normal resting ECG and are able to exercise. One disadvantage of exercise ECG is that it cannot localize the ischemic region, rendering it less useful as a guide for targeting revascularization. Stress cardiac magnetic resonance (CMR) can provide both perfusion and wall motion information with accuracy comparable to stress MPI; however, both of these modalities are currently limited to pharmacologic stress in selected reference centers. Over the last two decades, the prognostic utility of stress testing has been increasingly recognized. Exercise capacity, heart rate response, and the extent of ST depression as well as wall motion and perfusion abnormalities are powerful predictors of outcome. Patients with decreased exercise tolerance and chronotropic incompetence during exercise stress testing have been shown to have increased adverse events independently of other factors. Chronotropic incompetence may be a marker of impaired autonomic dysfunction, which has been associated with cardiac events. Chronotropic response may be defined as the proportion of age-predicted maximal heart rate achieved or the proportion of heart rate reserve used. The latter is defined as follows:

It is the preferred method as it has been shown to be largely independent of age, functional capacity, or exercise protocol. It is defined as failure to use at least 80% of the heart rate reserve. Chronotropic incompetence has been shown to be associated with the angiographic severity of CAD and increased mortality.

Heart rate recovery is another index that appears to be related to autonomic tone. Most evidence suggests that a rapid reactivation of vagal tone is the major determinant of a decline in heart rate during the first 30 seconds to 1 minute after exercise. Unlike chronotropic incompetence, heart rate recovery is not significantly affected by the administration of beta blockers. Heart rate recovery is calculated as the difference in heart rate at peak versus 1 minute after exercise. A value <12 beats per minute is considered abnormal. Patients evaluated for suspected or known CAD with an abnormal heart rate recovery have a markedly increased mortality rate that is independent of other risk factors.¹ Although both impaired chronotropic response and heart rate recovery are powerful predictors of outcomes, it is unknown whether these are modifiable. Moreover, their association with mortality may be independent of the presence or severity of CAD. Therefore they may have limited value in guiding therapeutic interventions.

ECG Stress Testing

Detection of ischemia by ECG stress testing relies on the development of abnormal repolarization, manifesting as ST-segment depression during and/or immediately after exercise. This is achieved by serial or continuous recordings of a 12-lead ECG, which is often aided by computer analysis. Exercise ECG testing has modest diagnostic accuracy; it is most useful when performed in patients with an intermediate pretest probability of obstructive CAD. It is now recognized that the early reported sensitivities of exercise ECG testing were affected by a verification bias (positive studies are more likely to be referred for catheterization). This bias leads to overestimation of sensitivity and underestimation of specificity. Recent data suggest that the true sensitivity of exercise testing may be as low as 50%. Despite this limitation, exercise ECG testing remains a useful prognostic test. An index derived from the exercise ECG test that incorporates exercise time, magnitude of ST-segment deviation, and angina—also known as the Duke treadmill score—has proven to be a powerful prognosticator of events. The Duke Treadmill score index is calculated as follows:

Maximum net ST-segment deviation is defined as the maximum deviation (elevation or depression) noted in any of the 12 ECG leads as compared with baseline. The treadmill anginal index is defined as having a value of 0 if no angina occurs, 1 if angina occurs during exercise but is not test-limiting, or 2 if test-limiting angina occurs. Exercise time is measured based on the Bruce protocol and appears to be the most important determinant of prognosis.² Using the Duke treadmill score, patients may be divided into categories of low (score ≥ +5), intermediate (score < 5 but ≥ −10), and high risk (score < −10). The 5-year survival rates among patients categorized as low, intermediate, and high risk were initially reported at 97%, 91%, and 72%, respectively. The prognostic information derived from the Duke treadmill score is independent of coronary angiography findings. The predictive utility of the Duke score has been validated in many different subpopulations, including women. A low score is associated with a very low risk for cardiac death (0.3%–1.2% per year).

Stress Echocardiography

The interpretation of stress echocardiography is based on the identification of regional wall motion abnormalities induced by ischemia in the presence of obstructive CAD. The test has gained increasing acceptance following the introduction of digital acquisition, harmonic imaging, and contrast agents, all of which have incrementally contributed to increased image quality, reproducibility, and accuracy. The performance and interpretation of stress echocardiography require close supervision and attention to detail. Accordingly, accuracy varies significantly between experienced and inexperienced centers. Real time three-dimensional echocardiography facilitates faster data acquisition and better image segmentation and has been shown to improve diagnostic accuracy.³ Strain imaging has also been shown to improve the accuracy for detecting stress-induced ischemia and/or viability in dysfunctional segments.⁴ In stress echocardiography, regional wall motion is assessed from parasternal long, parasternal short, and apical images using a 17-segment model of the LV.⁵ Each segment is described as either normal, hypokinetic, akinetic, or dyskinetic, and the results of the individual segments are averaged to calculate a global wall motion score. The diagnosis of CAD is based on the detection of either resting or stress-induced regional wall motion abnormalities (Figs. 4-1, 4-2, and 4-3). In most cases, resting regional wall motion abnormality implies a prior myocardial infarction while a stress-induced regional wall motion abnormality implies ischemia caused by obstructive CAD. Stress echocardiography may also be used to evaluate the severity of ischemic mitral insufficiency.

Figure 4-1 Normal stress echo response. Images obtained at end-diastole (ED) and end-systole (ES) at rest and immediately after exercise stress from the parasternal long axis (LAX), short axis (SAX), and apical four-chamber (AP4) and two-chamber (AP2) windows. Notice the decrease in end-systolic LV cavity size after stress.

Figure 4-2 Abnormal stress echo response in a patient with severe multivessel CAD. Images obtained at end-diastole (ED) and end-systole (ES) at rest and immediately after exercise stress from the parasternal long axis (LAX) and short axis (SAX) windows. Notice the end-systolic dilatation of LV cavity.

Figure 4-3 Abnormal stress echo response in a patient with severe stenosis of the mid-left anterior descending coronary artery. Images obtained at end-diastole (ED) and end-systole (ES) at rest and immediately after exercise stress from the apical four-chamber (AP4) and two-chamber (AP2) windows. Notice the relative end-systolic dilatation of the LV apical segments (arrows).

Exercise Echocardiography

Exercise stress may be performed with a treadmill, supine or prone bicycle, and even arm ergometry. Treadmill stress echocardiography is by far the most commonly used modality in the United States. With treadmill exercise, only pre- and postexercise images are obtained. This is done while the patient lies in a supine lateral position. Postexercise images must be obtained within 1 minute of termination of exercise. Any delay can result in resolution of regional wall motion abnormalities, thus reducing the sensitivity of the test. Bicycle ergometry allows the operator to obtain images while the patient is still exercising; thus, in theory, it is capable of detecting more subtle wall motion abnormalities caused by transient ischemia. Both treadmill and bicycle ergometry allow evaluation of important functional data such as exercise capacity, blood pressure response, hemodynamic responses to exercise including the assessment of cardiac output and pulmonary pressures, as well as standard ECG ST-segment analysis. The complete interpretation of the test takes into account all of these variables. Several studies have reported sensitivities ranging from 71% to 97% and specificities ranging from 64% to over 90%. The differences in results often relate to the definition of wall motion abnormalities. If hypo- or akinesis is required, sensitivity tends to be lower and specificity higher. On the other hand, if tardokinesis (delayed contraction or postsystolic shortening) or lack of hyperkinesis is the accepted definition, sensitivity is higher and specificity tends to be lower. Reported accuracy parameters also vary according to whether obstructive CAD is defined as a >50% or >70% reduction in diameter. The sensitivity of exercise echocardiography is lower for the detection of single-vessel CAD, in particular in the circumflex coronary artery distribution. Quite often, ischemia is only detected in the territory supplied by the most stenotic vessel in those patients with multivessel disease, especially if the test is discontinued at a submaximal workload.

Resting and/or exercise-induced wall motion abnormalities may occur in patients with cardiomyopathies, microvascular disease, severe hypertension (increased afterload), or valvular disease; they are often a cause of false-positive interpretations. Several stress echocardiographic variables have been shown to have important prognostic value in patients with known or suspected CAD. A low exercise wall motion score index or a fall in exercise ejection fraction is highly predictive of an increased risk of adverse cardiac events. This prognostic value is equivalent to that of an MPI perfusion defect of >15%. Echocardiographic variables have incremental independent prognostic utility over other variables, such as the Duke Treadmill score.⁶ The rate of cardiac events in individuals with a normal exercise echocardiogram has been reported in several studies to be <1% per year.

Pharmacological Stress Echocardiography

Intravenous dobutamine, dipyridamole, or adenosine may be used as pharmacological stressors with echocardiography. Dobutamine is the most commonly used stressor in the United States. It is administered by continuous infusion at incremental rates starting from 5 and up to 50 mcg/kg per minute. It is often complemented by handgrip exercise and/or intravenous atropine (0.5–2.0 mg) to increase heart rate. Dobutamine increases myocardial oxygen demand by increasing contractility and heart rate. Adenosine and dipyridamole are used in many centers in Europe and South America. These agents induce ischemia by coronary steal. In order to induce regional wall motion abnormalities, the required doses are typically much higher than those used to provoke vasodilation during pharmacological MPI studies. The reported sensitivity and specificity of dobutamine echocardiography for the detection of obstructive CAD are equivalent to those reported for exercise echocardiography. The sensitivity is reduced in patients with concentric hypertrophy who experience cavity obliteration early during the test as well as in those who do not reach the target heart rate. Echocardiographic variables obtained during pharmacological stress have also been shown to have significant prognostic value.⁷ A normal dobutamine stress echocardiogram is associated with a low cardiac event rate in patients with suspected CAD and in those at clinically determined intermediate or high cardiac risk undergoing noncardiac surgery. The presence of stress-induced regional wall motion abnormalities, particularly when detected at low heart rates, is a strong predictor of cardiac events. Dobutamine stress echocardiography allows further risk stratification even in patients at intermediate or high risk who are receiving perioperative beta blockers.⁸ Dobutamine echocardiography may be performed for risk assessment in patients after myocardial infarction. In this setting, extensive resting regional wall motion abnormalities, stress-induced ischemia, absence of viability, and worsening left ventricular (LV) function with stress are associated with an increased risk of adverse events. In patients with ischemic heart disease and chronic LV dysfunction, dobutamine echocardiography is useful to identify myocardial viability. Improvement in regional contractility at lower rates of dobutamine (5–10 mcg/kg per minute) in segments that are akinetic or hypokinetic at rest predicts functional recovery after revascularization, particularly when those same segments exhibit a reduction in contractility at high dobutamine rates (biphasic response). Patients with ischemic LV dysfunction and viable myocardium who undergo revascularization have better outcomes than those who are not revascularized or have no evidence of viability regardless of revascularization. The sensitivity with which dobutamine echocardiography predicts recovery of function ranges between 74% and 88%; the specificity is between 73% and 87%. Compared with MPI, dobutamine stress echocardiography has higher specificity but lower sensitivity and overall similar accuracy for predicting functional recovery.⁹

Contrast Perfusion Imaging

Echocardiographic contrast agents consist of inert perfluorocarbon gases encapsulated in a biodegradable shell. Contrast microbubbles have a small diameter (<10 microns) that allows them to cross the pulmonary capillary bed. These agents are commercially available and approved for endocardial border definition in patients with suboptimal echocardiographic images. When they are exposed to ultrasound, these microbubbles act as strong reflectors owing to their liquid-gas interface. Contrast echocardiography may be used to evaluate myocardial perfusion. Since the LV myocardium has a dense capillary bed, the injection of contrast microbubbles results in myocardial enhancement proportional to the myocardial blood volume. During vasodilator stress in the presence of a flow-limiting stenosis, there is a reduction in capillary blood flow and myocardial blood volume in the segments supplied by the stenotic vessel. This may be detected as either a delay in myocardial enhancement following contrast injection or a relative reduction in enhancement in ischemic compared with normal segments (Fig. 4-4). Studies have shown relatively good agreement between myocardial contrast echocardiography and MPI for the detection of ischemia.^10,¹¹ An earlier study performed in high-risk patients but with normal wall motion at rest reported a sensitivity of 85% by myocardial contrast echocardiography versus 74% by MPI for the detection of obstructive CAD.¹² The high spatial and temporal resolution of myocardial contrast echocardiography makes it suitable for the detection of nontransmural ischemia and milder ischemia where blood flow may be reduced but blood volume is preserved (late enhancement). However, data have been limited to a few reports and, in some studies where the sensitivity has been reported to be high, the specificity has been low. A previously published multicenter trial performed in 123 patients reported a sensitivity of 84% but a specificity of only 56%.¹³ Protocols for image acquisition and interpretation are considerably more technically demanding than those required for scintigraphic MPI. Thus, at present the use of contrast echocardiography for myocardial perfusion assessment is not an approved clinical indication in the United States.

Figure 4-4 Myocardial contrast perfusion study showing a stress-induced (adenosine) perfusion defect not present at rest in the mid- and apical anteroseptal region (arrows) in a patient with severe stenosis of the mid-left anterior descending coronary artery.

Stress Scintigraphic Myocardial Perfusion Imaging

The assessment of myocardial perfusion imaging (MPI) by nuclear scintigraphic methods relies on the administration of a radionuclide isotope that is accumulated by the myocardium in proportion to blood flow. MPI is performed with either single-photon-emitting or dual-photon-emitting isotopes using single photon emission computed tomography (SPECT) or positron emission tomography (PET) imaging systems, respectively. Thallium-201, technetium-99m sestamibi, and technetium-99m tetrofosmin are isotopes commercially available for SPECT imaging. Currently, technetium-99m-based isotopes are preferred for their higher photon energy, which results in higher image quality, and their shorter half-life, which results in lower radiation exposure. These isotopes emit single photons that travel through tissues and must be detected on a photon-sensitive detector. The direction of the traveling photon is determined by adding a lead collimator, which acts as an x-ray filter between the source and the detector. This collimator rejects most of the photons not traveling along certain directions; therefore only a percentage of the emitted photons are used for imaging. Spatial resolution is given by the space between the bars in the collimator. Increasing spatial resolution improves image quality but requires higher rejection of photons, thus reducing efficiency and increasing radiation exposure to the patient. Most dual-photon-emitting isotopes are produced using a cyclotron and have a very short half-life. These isotopes decay with the emission of a positron; after a series of collisions with atomic electrons from the tissues, it annihilates with a nearby electron and produces two high-energy photons emitted in opposite directions. A PET system relies on the simultaneous detection of the photons. These photons travel toward detectors positioned around the subject, where they interact, becoming absorbed and producing an electrical signal. The detector signals are processed by specialized coincidence circuitry. If the difference in the time of arrival of these photons is smaller than a predetermined value (typically <10 ns) a signal is recorded. Unlike SPECT imaging, PET does not require collimation, since the position of the emitting target is determined by the simultaneous registration of the two photons traveling at 180 degrees. Thus, the efficiency of PET is several magnitudes greater, providing higher resolution, lower noise, and lower radiation exposure. The signals recorded are used to reconstruct a three-dimensional image. The spatial resolution of PET images is closely related to the physical size of the detector elements and has dramatically increased in recent times with the introduction of time-of-flight (TOF) technology (Fig. 4-5). With either SPECT or PET cardiac perfusion studies, images are obtained after stress and at rest. For segmentation of the LV, a 17-segment model is applied. Images are interpreted visually or by using automated quantification based on normalized data. Myocardial scar is determined by the presence of a relative perfusion defect (compared with the segment with highest counts), which persists on both stress and resting images. Ischemia is determined by the presence of a perfusion defect on stress images that improves or resolves on the resting images (Figs. 4-6, 4-7, 4-8, and 4-9).

Figure 4-5 Example of a PET-FDG study obtained with time-of-flight (TOF) imaging. The high spatial resolution allows visualization of the papillary muscles in the transverse (A), sagittal oblique (B), short-axis (C), and horizontal long-axis (D) planes.

Figure 4-6 SPECT technetium-99m sestamibi exercise stress study showing normal myocardial perfusion during stress and at rest.

Figure 4-7 SPECT technetium-99m sestamibi exercise stress study showing a large myocardial perfusion defect in the posterolateral walls during stress (white arrows) with complete reversibility on the resting study, indicating ischemia.

Figure 4-8 SPECT technetium-99m sestamibi exercise stress study showing a mid-size myocardial perfusion defect in the anteroseptal and apical walls during stress (white arrows) without reversibility on the resting study, indicating scar.

Figure 4-9 SPECT technetium-99m sestamibi exercise stress study showing a large myocardial perfusion defect in the anteroseptal, anterior, and inferior walls during stress (white arrows), with partial reversibility (inferior and septal walls, green arrows) on the resting study, indicating both scar and ischemia.

Exercise Scintigraphic MPI

Exercise stress is well suited for SPECT MPI. At peak exercise, either on a treadmill or bicycle ergometer, patients are injected with the radioisotope. Acquisition of the stress images is performed after a few minutes to up to 1 hour after exercise, depending on the radioisotope used. Resting images are obtained before or after the exercise images following the administration of a separate dose of the isotope at rest. Different isotopes may be used for resting and for stress imaging—for example, thallium-201 injected at rest and technetium-99m sestamibi injected at peak stress.

The mean reported sensitivity and specificity for exercise SPECT is 86% and 74%, respectively.¹⁴

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Tags: Textbook of Interventional Cardiology

Jun 18, 2016 | Posted by admin in CARDIOLOGY | Comments Off

Thoracic Key

Fastest Thoracic Insight Engine

Prior Evaluation: Functional Testing, Multidetector CT

Introduction

Stress Testing

ECG Stress Testing

Stress Echocardiography

Exercise Echocardiography

Pharmacological Stress Echocardiography

Contrast Perfusion Imaging

Stress Scintigraphic Myocardial Perfusion Imaging

Exercise Scintigraphic MPI

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Prior Evaluation: Functional Testing, Multidetector CT

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