Introduction
Noninvasive testing after presentation with acute myocardial infarction (MI) plays an essential role in patient management. Noninvasive testing complements clinical assessment of risk stratification and can be used to aid management decisions. The major purposes of testing are measurement of left ventricular (LV) function in nearly all patients and assessment of ischemic burden, primarily among low-risk patients who are initially treated conservatively, to identify potential candidates for coronary angiography or nonculprit vessel revascularization. The most commonly used tests include resting echocardiography, standard stress testing with electrocardiography (ECG) alone, stress imaging with nuclear myocardial perfusion imaging (MPI) or echocardiography, and increasingly, resting and stress cardiac magnetic resonance imaging (CMR). The use of these tests is related to the temporal evolution of the MI. Early imaging (within the first 72 hours) is performed predominantly with resting echocardiography; intermediate testing (day 3 to 6 weeks) uses the standard stress test or stress imaging; and late imaging (beyond 6 weeks) is performed with any of the techniques in selected patient subsets to measure LV ejection fraction (LVEF) after stunning has resolved for assessment of implantable cardiac defibrillator (ICD) consideration and for viability assessment.
In this chapter, we discuss the role of noninvasive testing after MI, patient selection, and considerations for choosing among the alternatives for noninvasive testing. Each modality is discussed in detail elsewhere in the text. Echocardiography is reviewed in Chapter 31 , MPI in Chapter 32 , and CMR in Chapter 33 . Although computed tomographic angiography (CTA) is playing an increasingly important role in the early evaluation of the patient with acute chest pain in the emergency department (see Chapter 9 ), CTA currently is not widely used in patients with confirmed MI and is not discussed in this chapter.
Pathophysiology of Myocardial Infarction as the Basis for Noninvasive Testing
The pathophysiology of acute MI is discussed in detail in Chapter 3 , Chapter 4 . Understanding the pathophysiology establishes the foundation for appreciating the rationale behind noninvasive testing. The amount of myocardium that is jeopardized by occlusion of a coronary artery is referred to as myocardium at risk (see Chapter 24 ). This is the amount of myocardium that is expected to become scarred in the absence of spontaneous reperfusion or treatment with reperfusion therapy. The amount of myocardium that ultimately turns into scar is referred to as the final infarct size. The difference between myocardium at risk and final infarct size is labeled myocardial salvage. Both final infarct size and myocardial salvage reflect, in part, the efficacy of reperfusion therapy (see Chapter 13 ). These measurements can be quantified by nuclear MPI or CMR techniques. This type of imaging has been applied as a surrogate endpoint in numerous research studies that have compared different reperfusion strategies or have examined the efficacy of new MI therapies. Measurement of myocardial salvage is somewhat logistically demanding and has not been shown to directly affect patient management; therefore, such measurements are not commonly performed in clinical practice. MI results in worsening wall motion in the infarct zone and commonly compensatory hyperkinesia in noninfarct zones (see Chapter 36 ). After spontaneous reperfusion or reperfusion therapy, partial or complete recovery may ensue in the motion of these stunned segments. The duration for resolution of stunning and resolution of compensatory hyperkinesia in noninfarct zones is highly variable and occurs within days up to 6 weeks.
Two of the most important prognostic variables in patients with acute MI are global LV function and the extent of coronary artery disease (CAD). Measurement of these variables is a primary objective of noninvasive testing after MI. Global LV function is most commonly expressed as the LVEF. Current professional society practice guidelines recommend measurement of LVEF in all patients with ST-elevation MI (STEMI) and recognize the relationship with the prognosis among patients with non–ST-elevation MI (NSTEMI). LVEF and regional wall motion can be measured in the catheterization laboratory by contrast ventriculography or by noninvasive methods. These measurements are increasingly being obtained noninvasively. Other indices of global LV structure and/or function, including end-diastolic and end-systolic volumes, wall motion score index, and diastolic function can also be measured, but these generally do not provide any incremental knowledge for patient management beyond that provided by LVEF. Because of the effects of stunning, repeated measurement of LVEF beyond 40 days may be required in selected patients, particularly those being considered for ICDs. Some patients with reduced LVEF undergo progressive enlargement of the LV, a process termed remodeling (see Chapter 36 ). Remodeling is associated with higher mortality and greater risk of future development of heart failure. Angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockers can favorably affect remodeling. An important reason to measure LVEF early in the course of acute MI is to identify patients who are candidates for these medications and aldosterone antagonists.
Noninvasive testing can approximate the extent of CAD and its functional significance. In patients with MI who are initially treated conservatively and do not undergo early coronary angiography, stress testing can be performed to identify patients who are candidates for coronary angiography and possible revascularization. Moreover, noninvasive testing may be useful for assessing the functional significance of residual CAD after an initial revascularization of the culprit artery (see Chapter 17 ).
Rational Use of Noninvasive Testing
Noninvasive testing should be viewed as an adjunct to clinical assessment for risk stratification and to aid in management decisions. Accurate risk assessment begins with clinical assessment of risk, which can be aided by calculating a clinical risk score (see Chapter 11 ). Clinical variables and the ECG can also be used to estimate LVEF. This clinical estimate can occasionally suffice for adequate risk assessment in selected patients without the need for further evaluation. In general, testing is least helpful for aiding clinical management at the two ends of the risk spectrum, in patients either at low or at high risk based on prognostic information that is already available. For instance, a young patient who presents early with first MI, and at angiography has single vessel right or circumflex CAD treated with successful PCI followed by an uncomplicated hospital course, also has a very high likelihood of a normal LVEF. Although measurement of LVEF is categorized as a class I indication in STEMI guidelines, the measurement reasonably could be avoided in this patient example, because of the high likelihood of normal LVEF on the basis of clinical assessment. At the other end of the risk spectrum, there are an increasing number of patients with end-stage CAD who are living longer and present with multiple MIs during their lifetime. If previous evaluation has demonstrated that coronary anatomy is not amenable to further revascularization, or if LVEF is severely reduced, and the patient is already taking an ACE inhibitor and has an ICD, there is little to be gained from noninvasive testing. Testing should be performed only when the results are likely to affect clinical management and in a cost-effective manner. Redundant testing should be avoided. If a patient undergoes left ventriculography as part of the early catheterization procedure, performance of echocardiography generally is not necessary.
Noninvasive Testing According to Temporal Sequence of Myocardial Infarction Evolution
The time course of recovery after MI can be separated into three general phases: early (within 72 hours); intermediate (day 3 to week 6); and late (beyond 6 weeks). These phases provide a useful framework in which to consider the goals and alternatives for noninvasive testing ( Table 30-1 ). Resting echocardiography is the most commonly performed test in the early phase ( Figure 30-1 ). The major goal is to provide information on LVEF and regional wall motion. Echocardiography (see Chapter 31 ) can also identify mechanical complications of MI (see Chapter 26 ) and aid in the recognition of conditions that mimic MI (see Chapter 6 ). Early submaximal stress testing (usually performed between days 3 and 5 and before hospital discharge) with or without imaging is performed primarily in the subset of low-risk patients who do not undergo early coronary angiography for risk stratification ( Figure 30-2 ). Delayed symptom-limited stress testing (usually between 3 and 6 weeks) can be helpful to guide additional revascularization decisions in patients who undergo early angiography and have evidence for significant CAD in vessels other than the infarct-related artery (see Figure 30-2 ). Delayed imaging (beyond 40 days) with any of the imaging techniques can be performed in selected patients primarily for two major purposes: measurement of LVEF to determine eligibility for ICD and assessment of viable myocardium ( Figure 30-3 ).
| Time | Main Modality ∗ | Goal | Impact on Management |
|---|---|---|---|
| Early (≤2 h) | Resting echo (MUGA or CMR) | Measure global and regional LV function Identify MI complications Identify conditions mimicking MI | Use of ACE inhibitor, ARB, aldosterone antagonist Selection of revascularization strategy Appropriate treatment for identified condition |
| Intermediate (days 3–5) Intermediate (weeks 3–6) | Submaximal stress test † Symptom limited stress test † | Assess residual ischemic burden Same as submax test (if not performed). Assess ischemia related to the noninfarct artery ‡ | Identify pts for cor angio Identify pts for cor angio Select pts for additional PCI/CABG |
| Late (≥40 days) | Echo (MUGA or CMR) Nuclear PET or CMR (echo) | Measure LVEF (after stunning resolves) Assess myocardial viability | Eligibility for ICD Revascularization (usually CABG) |
∗ The generally preferred and most commonly applied modality is shown first. Modalities listed in parentheses indicate secondary choices.
† Selection between a standard stress test and stress imaging is based primarily upon ability to exercise and interpretability of the electrocardiogram.
‡ If testing is performed to assess ischemia in the noninfarct vessel, stress imaging is recommended over standard stress testing.
Early Imaging (Within 72 Hours) After Myocardial Infarction
Resting Echocardiography
The mainstay of early imaging is resting echocardiography. Echocardiography (see also Chapter 31 ) possesses certain advantages over other imaging modalities, including its more widespread availability and portability. There are essentially no contraindications to the performance of an echocardiogram. Transthoracic echocardiography provides a comprehensive cardiac assessment that encompasses global and regional LV systolic function, global right ventricular function, chamber sizes, wall thickness, LV diastolic function, valve status, estimated right ventricular systolic pressure, and pericardial fluid and thickness. Myocardial contrast can be administered to enhance image quality in patients with technically poor images. When clinically necessary, resting echocardiography can be performed at the patient’s bedside. Transesophageal echocardiography provides an alternative to transthoracic echocardiography in critically ill patients who may have limited acoustic windows because of chest bandages or for other reasons. Performance of transesophageal echocardiography solely to assess cardiac function is an uncommon indication. Transesophageal echocardiography has particular use in the assessment of the thoracic aorta and main pulmonary arteries to diagnose conditions that can mimic MI. Myocardial strain imaging represents a newer method of assessing systolic function, but its incremental clinical value over routine measurement of LVEF and regional wall motion assessment remains to be determined. Myocardial contrast echocardiography with microbubbles has been used to assess myocardial perfusion, but this technique is not commonly performed clinically.
The major reason for performing resting echocardiography early in the course of MI is measurement of LVEF (see Figure 30-1 ). Knowledge of LVEF can influence medical decision-making. ACE inhibitors and aldosterone antagonists are class I guideline recommendations in patients with reduced LVEF (see Chapter 13 , Chapter 25 ). Knowledge of LVEF may also influence selection of a specific revascularization procedure, particularly in patients with NSTEMI (see Chapter 16 ). For NSTEMI, or stabilized patients after STEMI, coronary artery bypass grafting (CABG) is preferred instead of multivessel PCI in patients with multivessel CAD if the LVEF is reduced. Assessment of regional wall motion can also provide an estimate of infarct size. Global LV function can also be measured as a wall motion score index, which is determined as the summation of regional wall motion in multiple LV segments. Some studies suggest that this measurement is a more accurate predictor of outcome than LVEF.
A second reason to perform early echocardiography is to aid in the identification of conditions that can mimic acute MI (see Figure 30-1 ), including pulmonary embolus, aortic dissection, myocarditis and/or pericarditis, and apical ballooning syndrome (see Chapter 6 ). All of these conditions can present with chest discomfort, ischemic-appearing ECG changes, and elevated troponin. Because these conditions occur much less frequently than MI, there is a higher likelihood that they will be misdiagnosed initially. Echocardiography can provide clues to the presence of these conditions. The echocardiographic findings are not always definitive, and additional imaging procedures are commonly necessary to confirm the alternative diagnosis.
A third major reason to perform early echocardiography is to identify complications of acute MI (see Figure 30-1 ), including LV thrombus; right ventricular infarction; pericardial effusion, especially when associated with tamponade; rupture of the LV free wall, papillary muscle, or interventricular septum; and valvular heart disease, especially new ischemic mitral regurgitation (see Chapter 26 ). Prompt and accurate identification of these complications can be critical to patient management and outcome.
Cardiac Magnetic Resonance and Nuclear Imaging
CMR (see also Chapter 33 ) is being increasingly used in the MI setting and possesses certain advantages over other imaging techniques. It provides high spatial resolution and is not limited by acoustic windows as occurs with echocardiography. CMR has been shown to be superior to echocardiography in the assessment of the LV apex, which may have important clinical implications in the setting of anterior infarction, where assessment of apical thrombi may be challenging with echocardiography. CMR can more accurately characterize the anatomy of the right ventricle and provide volumetric measures of right ventricular size and function. Knowledge of these variables may have clinical implications in the care of patients presenting with inferior MI or pure right ventricular infarction. A unique property of CMR is tissue characterization, which helps delineate the presence of inflammation. This property can be very useful to correctly identify the rare patient who presents with myocarditis masquerading as MI.
MPI may be useful in the initial diagnostic evaluation of patients presenting with chest pain suspicious for MI (see Chapter 9 ). However, there is little role for nuclear MPI (see Chapter 32 ) in the early setting for patients with confirmed MI. Radionuclide angiography, commonly referred to as multigated analysis (MUGA), can be useful for evaluating LV function when echocardiographic images are limited. This technique provides an accurate quantitative assessment of LVEF. It has the theoretical advantage over other techniques of being geometrically independent and is especially useful for measuring LVEF in patients with distorted LV anatomy, such as an aneurysm. Both CMR and radionuclide angiography apply ECG gating for assessment of LV function. Because accurate measurement of LVEF and regional wall motion by gated techniques depends upon a fairly regular heart rhythm, these techniques generally are not advised in patients with atrial fibrillation or frequent cardiac ectopy.
Intermediate Term Testing (Day 3 to Week 6) After Myocardial Infarction
Traditional Role of Stress Testing
The two most common reasons to perform stress testing are to aid in the diagnosis and prognosis of CAD. In the setting of acute chest pain, stress testing plays a major role as a diagnostic aid to help confirm the presence or absence of underlying CAD when the diagnosis of acute MI has been ruled out by standard emergency department evaluation (see Chapter 6 , Chapter 12 ). Because most patients with confirmed MI have obstructive CAD, stress testing has no value for diagnostic purposes.
The major goal of stress testing in the setting of acute MI is risk stratification (see Figure 30-2 ). In contrast to testing for diagnostic purposes, in which medications with antianginal properties are commonly held before testing to enhance test sensitivity, patients with MI are tested on medical therapy. In the pre-reperfusion era, few patients underwent early angiography, because studies demonstrating the benefit of primary PCI and an early invasive strategy had not yet been performed. Stress testing was performed late in the hospital course in most of the population for prognostic purposes to guide decisions regarding the value of coronary angiography. The most important prognostic variables using the standard treadmill test were limited exercise duration and abnormal blood pressure response. ST-segment depression on the exercise ECG was useful to identify increased risk primarily in patients with inferior MI. Studies of MPI reported that delayed redistribution, perfusion defects in more than one vascular region, or increased thallium lung uptake identified high-risk patients. Based on these studies, the clinical paradigm that evolved in the pre-reperfusion era was to perform standard exercise testing or stress imaging to identify patients with poor exercise performance and/or significant ischemia who were candidates for coronary angiography and revascularization.
Stress Testing in the Current Era
Coronary angiography is now performed in most patients with MI as part of primary PCI (see Chapter 17 ) or delayed invasive management (see Chapter 14 ) in those with STEMI or as part of an early invasive strategy in those with non-STEMI (see Chapter 16 ). As a result, the traditional role of performing stress testing to identify high-risk patients who are candidates for coronary angiography does not apply to patients who undergo immediate or early angiography as part of their treatment. American College of Cardiology Foundation/American Heart Association (ACCF/AHA) guidelines for patients in whom stress testing is recommended are similar for STEMI and non-STEMI, with some minor differences.
Stress Testing in ST-Elevation Myocardial Infarction
Primary PCI or delayed invasive evaluation after fibrinolysis are indicated for most patients with STEMI (see Chapter 13 ). The sole class I indication for stress testing in the ACCF/AHA STEMI guideline is limited to the subset of patients without high-risk clinical features who have not undergone early coronary angiography. In addition, it may be reasonable to consider (class IIb indication) stress testing (1) to guide the post-discharge exercise prescription or (2) to evaluate the functional significance of a noninfarcted artery noted on coronary angiography. If stress testing is performed for this purpose, stress imaging is preferred because the exercise ECG cannot localize ischemia.
Stress Testing in ST-Elevation Myocardial Infarction
For patients presenting with NSTEMI, an early invasive approach (between 2 and 72 hours of presentation) is recommended for most patients with ongoing symptoms or indicators of high risk (see Chapter 16 ). Nevertheless, there are circumstances in which patient preferences are for a noninvasive course of evaluation or the risks of the comorbid conditions and/or the revascularization procedure outweigh the benefits of revascularization. Similar to STEMI, stress testing in patients with NSTEMI is performed primarily in the small subset who are at low to intermediate risk on the basis of clinical risk score (Thrombolysis In Myocardial Infarction [TIMI] score 0 or 1 or Global Registry of Acute Coronary Events [GRACE] score <109), with a stable clinical course, or in whom a noninvasive management strategy is selected for the previously identified reasons. Initial noninvasive evaluation with stress testing may also be preferable in patients with troponin elevation that is suspected to be on the basis of demand ischemia (type 2 MI; see Chapter 1 and Chapter 6 ) in the clinical setting of other significant comorbidities, such as sepsis or acute renal failure. This approach mitigates against the immediate performance of coronary angiography in such patients. After recovery from the acute illness, stress testing can help guide the decision to proceed with coronary angiography.
Justification for an Ischemia-Guided Approach in Patients with Acute Myocardial Infarction
The rationale supporting current recommendations for stress testing in acute MI is based in large part upon the results of studies from the pre-reperfusion era and the results of studies of stress testing performed in the setting of chronic CAD. The evidence base addressing stress testing in these domains is much more extensive than the relatively small number of studies performed in acute MI in the reperfusion era. The goal of the stress test is to identify potentially high-risk patients among a generally low-risk population on the basis of significant ischemia that develops at a low workload. These patients are then referred for angiography, based upon the assumption that revascularization will result in improved clinical outcome. Although this approach appears logical and is a class I guideline recommendation, there is little evidence to indicate that this approach results in lower mortality or lower risk of re-infarction.
Studies from the pre-reperfusion era upon which this paradigm is partially based involved performing stress testing in most of the acute MI population, which generally was a “sicker” population at high risk. The current subset of MI patients for whom stress testing is recommended represents a very different population. In the setting of chronic CAD, the presence of ischemia has long been regarded as an important variable that influences patient management. However, three stress imaging substudies that were performed as part of recent large randomized trials comparing medical therapy with revascularization, COURAGE (Clinical Outcomes Using Revascularization), BARI-2D (Bypass Angioplasty Revascularization Investigation 2 Diabetes), and STICH (Surgical Treatment for Ischemic Heart Failure), reported that ischemia had no value as a prognostic variable and failed to identify patients who experienced better outcomes if treated with revascularization. A common explanation for this observation is that optimal medical therapy is associated with such a low event rate that the rate cannot be lowered further with revascularization. This issue is continuing to be evaluated in the ongoing International Study of Comparative Health Effectiveness with Medical and Invasive Approaches (ISCHEMIA) trial.
There are even less data that address this issue in patients with acute MI. In a subset of the GISSI-2 (Gruppo Italiano per lo Studio della Sopravvivenza nell’Infarto Miocardico 2) trial, the prognostic value of three exercise test scores that incorporated multiple variables was demonstrated in 6251 patients who presented with STEMI and who were treated with thrombolysis. Six-month mortality rates calculated from a modified version of the Duke treadmill score, the most widely applied score, were low risk 0.6%, moderate risk 1.8%, and high risk 3.4% ( P <.0001). The SWISSI II (Swiss International Study on Silent Ischemia Type II) trial studied a selected population of patients with recent (<3 months) MI; silent ischemia demonstrated by exercise ECG, which was confirmed by nuclear or echocardiographic imaging; and one- or two-vessel CAD at coronary angiography. Patients were randomized to PCI (n = 96) or medical therapy (n = 105). At a mean follow-up of 10.2 years, the primary endpoint (a composite of cardiac death, nonfatal recurrent MI, or symptom-driven revascularization) was significantly lower in the PCI group (adjusted hazard ratio, 0.33; P <.001). The main limitation of applying the results of this study to broader patient populations relates to the restricted entry criteria (performance of early coronary angiography, one- or two-vessel CAD, and silent ischemia). At the present time, stress testing in the MI setting is performed primarily in low-risk patients who are treated with optimal medical therapy. The ability of stress testing to accurately further risk stratify this generally low-risk patient subset and to identify those who benefit from revascularization remains to be demonstrated.
Types of Stress Testing
Standard Treadmill Testing
Exercise testing can be performed using a treadmill or cycle ergometer. In the United States, the most common modality is the treadmill. Other exercise modalities such as hand crank ergometry are not widely available and are rarely used. The hallmark of an ischemic response is ST-segment depression, defined as ≥1.0 mm horizontal or downsloping ST-segment depression 60 to 80 msec after the J point. ST-segment depression most commonly occurs in the lateral precordial leads. ST-segment depression does not localize the site of myocardial ischemia. ST-segment elevation in leads without Q waves occurs infrequently, but, when it does occur, it can identify the site of myocardial ischemia and usually indicates a high-grade stenosis in the coronary artery that supplies the myocardium in those leads where the ST-segment elevation occurs. In the post-MI patient, ST-segment elevation can occur in leads with Q waves and is considered a nonspecific response. In the pre-reperfusion era, exercise duration and abnormal blood pressure response (defined in various studies as a failure of systolic blood pressure to increase or a decrease with exercise) were the most important prognostic variables. Exercise scores that combine variables can be applied for risk stratification. The most commonly used score is the Duke treadmill score, which can be calculated as:
exercise duration ( estimated metabolic equivalents ) − maximum ST depression ( in millimeters ) − angina index
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