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Transcript
3 5 Echocardiographic Evaluation of Coronary Artery Disease Stephanie A. Coulter Measurement of Regional Myocardial Function . . . . . . Assessment of Coronary Ischemia/Acute Myocardial Infarction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Location of Acute Myocardial Infarction . . . . . . . . . . . . Extent of Acute Myocardial Infarction . . . . . . . . . . . . . . Acute Complications of Acute Myocardial Infarction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 811 813 814 815 Chronic Complications After a Myocardial Infarction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 819 Prognosis in Acute Myocardial Infarction and Chronic Coronary Artery Disease . . . . . . . . . . . . . . . 821 Stress Echocardiography: Assessment of Ischemic and Viable Myocardium . . . . . . . . . . . . . . . . . . . . . . . 823 815 C oronary artery disease (CAD) is the most prevalent of cardiac diseases. Routine evaluation of patients with suspected or known CAD nearly always includes echocardiography. Echocardiography is a versatile, low-cost, and portable technique that is available clinically in nearly all medical centers and subsequently is the most widely utilized cardiac testing modality. The diagnosis of CAD by echocardiography is based on the concept that acute myocardial ischemia or infarction produces a detectable impairment in regional left ventricular (LV) mechanical function. Identification of patients with suspected CAD and acute coronary syndrome is one of the primary indications for echocardiography. Assessment of global LV systolic function and detection of the presence and extent of regional myocardial dysfunction are routine clinical indications for echocardiography. This method also has an important prognostic value in patients with acute and chronic CAD. When combined with exercise or pharmacologic stress testing, echocardiography can identify patients with myocardial ischemia and viability. Because echocardiography can provide a comprehensive assessment of cardiac structure, function and possibly perfusion at the bedside, it is likely to be the technique of choice for years to come. Measurement of Regional Myocardial Function Regional Wall-Motion Abnormalities Regional systolic and diastolic function can be characterized by measuring one or more of the following parameters: the timing of regional events, regional myocardial thickening and thinning, and the velocity and direction of regional myo- cardial motion.1 With echocardiography, a regional wallmotion abnormality (RWMA) is characterized as a localized decrease in the rate and amplitude of endomyocardial motion. These abnormalities are accompanied by a reduction in myocardial thickening during systolic contraction and by thinning of the myocardial segment after a transmural myocardial infarction (MI). The loss of systolic wall thickening is more specific for myocardial ischemia than is the detection of a resting RWMA 2–5 because cardiac rotation, translational motion during contraction of bordering segments, and loading conditions affect the latter fi nding. An RWMA is not specific for coronary ischemia and also occurs with a previous MI, a previous sternotomy, myocarditis, cardiomyopathies, left bundle branch block, and preexcitation. The American Association of Echocardiography recommends a 16-segment standardized format for describing RWMAs.5 To update and unify reporting of wall-motion analysis among disparate cardiac-imaging modalities, in 2002 the American Heart Association (AHA) issued a statement on myocardial segmentation and nomenclature that revised the format to include 17 segments (Figs. 35.1 and 35.2).6 In both the 16- and 17-segment formats, the ventricle is divided into roughly equal thirds perpendicular to the apical long axis of the heart (basal, midventricular, and apical on short-axis imaging). The basal segments extend from the mitral annulus to the tips of the papillary muscles at enddiastole. The midcavitary segments extend the length of the papillary muscle. The apical view begins just beyond the papillary muscles and extends to just before the end of the cavity. The 17th segment encompasses the true apex, or apical cap, which includes the portion of the apical myocardium not bordered by the ventricular cavity. 811 CAR035.indd 811 11/29/2006 3:33:06 PM 812 chapter 35 2 Two chamber 3 Long axis 1 Four chamber Apical cap Apical cap Apical cap Apical Apical Apical Apical Apical Apical lateral inferior anterior lateral anterior 4 septum Mid Mid Mid Mid Mid Mid 5 inferolateral anteroseptum anterolateral inferior anterior inferoseptum Basal 6 Basal Basal Basal Basal inferolateral anteroseptum Basal inferoseptum inferior anterior anterolateral 3 2 1 Base Anterior AnteroAnterolateral septum Anterior Anteroseptum Inferoseptum Interior InferoInferoseptum lateral Interior 4 Inferolateral 5 Mid 6 Apex Anterolateral Anterior Septal Lateral Interior FIGURE 35.1. Analysis of wall motion. The left ventricle (LV) can be divided into 17 segments and identified by a series of longitudinal views: 1, apical four chamber; 2, apical two chamber; 3, apical long axis, or a series of short-axis views; 4, base (short axis at the tips of the mitral leaflets); 5, mid-cavity (short axis at the papillary muscles); and 6, apex (short axis beyond the papillary muscles but before cavity ends). The longitudinal and short-axis views overlap and complement each other. The apical cap, the 17th segment, can be appreciated only by echocardiography with contrast opacification of the LV cavity. A 16-segment model can be used without the apical cap. long axis; apical four chamber; apical three chamber; apical two chamber. The wall-motion score index is an expression of regional LV function that is directly proportional to the severity and extent of an RWMA. Each myocardial segment is scored on a scale of 1 to 5, according to a qualitative assessment of regional function and systolic thickening (normal, 1; hypokinesis, 2; akinesis, negligible thinning, 3; dyskinesis, paradoxical systolic motion, 4; and aneurysm, diastolic deformation, 5) (Table 35.1). The composite score, divided by the number of segments, provides a semiquantitative evaluation of regional wall motion.5,7 Previous authors have rec- ommended a four-point wall-motion scoring system,8,9 but the American Society of Echocardiography (ASE) recently continued to advocate a five-point scoring system, which included the discrimination of aneurysmal segments.7 The 16-segment format is recommended for evaluating regional LV dysfunction with two-dimensional (2D) echocardiography, because the 17th apical segment does not exhibit inward motion.7 Although the coronary artery blood supply to the myocardial segments varies, the typical relationship between the three coronary arteries and the myocardial segments is illustrated in Figure 35.3. Left ventricular segmentation 1 7 2 8 14 17 9 3 6 13 15 10 12 16 11 5 4 1. basal anterior 7. mid anterior 13. apical anterior 8. mid anteroseptal 2. basal anteroseptal 14. apical septal 9. mid inferoseptal 3. basal inferoseptal 15. apical anferior 4. basal inferior 10. mid inferior 16. apical lateral 17. apex 5. basal inferolateral 11. mid inferolateral 6. basal anterolateral 12. mid anterolateral FIGURE 35.2. Display, on a circumferential polar plot, of the 17 myocardial segments and the recommended nomenclature for tomographic imaging of the heart. CAR035.indd 812 Regional Myocardial Doppler Velocities Differentiation of passive motion from active myocardial shortening or thickening is limited by the temporal resolution (about 90 ms) required to detect differences in motion with the unaided human eye.10 Measurement of the speed of motion of low-frequency myocardial tissue can be obtained with pulsed-wave tissue Doppler imaging (TDI), which excludes the high-frequency velocities of the rapidly moving blood. Assessment of peak regional myocardial velocities with TDI techniques can be achieved in simultaneous segments at high frame rates. The accuracy of tissue Doppler imaging is limited by translational motion and tethering effects.11–16 Clinical limitations of this technique are attributed to the complexity of myofiber orientation, which creates motion in three dimensions: longitudinal shortening (base > middle > apex), radial thickening (all segments), and circumferential rotation (apex). Ability to image in only one plane and misalignment of the Doppler probe with the vector of cardiac motion diminish the accuracy of Doppler velocity imaging and may limit its clinical applicability at this time.17 Strain imaging is a method for calculating regional myocardial function from TDI velocity data, which theoretically is 11/29/2006 3:33:06 PM 813 e c h o c a r d i o g r a p h i c e va l u a t i o n o f c o r o n a r y a r t e r y d i s e a s e TABLE 35.1. 1. Wall motion score Score Wall motion Defi nition 1 2 3 4 5 Normal/hyperkinesis Hypokinesis Akinesis Dyskinesis Aneurysmal Normal systolic motion and thickening Reduced systolic motion or thickening Absent inward systolic motion or thickening Paradoxic (“bulging”) or outward motion Diastolic deformation Each segment should be analyzed and individually scored according to its systolic motion and thickening. Confi rmation should be made with multiple views. not confounded by translational movement or tethering.17 Strain rates reflect the speed of regional myocardial longitudinal deformation and are calculated from myocardial TDI velocities measured at two locations separated by a given distance.7 The longitudinal segmental strain rate is uniform throughout all segments, whereas TDI is greatest at the base and deteriorates as the motion becomes more circumferential toward the apex.12,15,18 With ultrasonic strain-rate imaging, both the amount of deformation (strain) and the rate of local deformation (strain rate) can be quantified.13 Myocardial Performance Index The myocardial performance index (MPI) provides a noninvasive, semiquantitative assessment of global LV function, incorporating systolic and diastolic function. The MPI is the sum of the diastolic intervals, isovolumic relaxation time, and isovolumic contraction time, divided by the systolic LV ejection time. The MPI is reproducible and less dependent on the heart rate and preload than are traditional Doppler measurements.19,20 In the normal heart isovolumic diastolic times shorten with increasing contractility.21,22 With ischemia, the MPI has been shown to deteriorate as the isovolumic relaxation time increases relative to ejection times.23 In patients with known LV dysfunction after an acute MI who were enrolled in the Survival and Ventricular Enlargement (SAVE) trial,24 an MPI of >0.5 was associated with a larger infarct FIGURE 35.3. Typical distributions of the right coronary artery (RCA), the left anterior descending (LAD), and the circumflex (Cx) coronary arteries. The arterial distribution varies between patients. Some segments have variable coronary perfusion. CAR035.indd 813 RCA LAD RCA or Cx Cx RCA or LAD size and reduced baseline LV systolic function. The MPI was also identified as an independent predictor for cardiovascular events after an MI in patients with LV systolic dysfunction. Because diastolic abnormalities precede the development of systolic alterations in the ischemic cascade, the MPI may be more sensitive for the detection of myocardial ischemia. It has been utilized with dobutamine stress echocardiography (DSE) for the detection of ischemia after an MI. The MPI provided added prognostic value to DSE and accurately reflected the LV contractile state during low-dose DSE.23 The MPI may reflect the overall LV functional reserve. Unfortunately, systolic wall motion and thickening is often difficult to detect and quantify. Doppler techniques lack clinical applicability, and determining the myocardial performance index is time-consuming. Therefore, 2D grayscale echocardiographic assessment remains the standard clinical modality for detecting RWMAs. Assessment of Coronary Ischemia/Acute Myocardial Infarction The echocardiographic evaluation of coronary ischemia and of regional myocardial dysfunction during an MI varies widely over a range of coronary blood flows.25 Regional wallmotion abnormalities occur with coronary artery stenosis of >85% at rest and >50% during exercise or hyperemia.7 They arise within seconds after a coronary occlusion is induced 1 Four chamber 2 Two chamber 3 Long axis 4 Base 5 Mid 6 Apex LAD or Cx 11/29/2006 3:33:06 PM 814 chapter Workload (HRxBP) Necrosis MI Stunning/Hibernation Global LV dysfunction Chest pain ECG changes Wall motion abnormalities Elevation of Perfusion Metabolic LVEDP (SOB) deficits abnormalities Resting flow reduction Rest Exercise time FIGURE 35.4. Ischemic cascade. Schematic representation of the clinical, electrocardiographic, and echocardiographic manifestations of myocardial ischemia as the workload (rate-pressure product) and duration of stress is increased. SOB, shortness of breath. CAR035.indd 814 1.0 0.8 Event-free survival by balloon inflation during angioplasty and may last for up to several days with prolonged ischemia.26,27 These abnormalities precede the development of electrocardiographic irregularities and the onset of cardiac symptoms. Figure 35.4 illustrates the cascade from myocardial ischemia to infarction. During an episode of acute ischemic chest pain, 2D imaging should show RMWAs that normalize on resolution of the ischemia unless the duration of ischemia is sufficiently long to induce myocardial stunning.28 The transient nature of the RMWA differentiates a brief episode of acute myocardial ischemia from an acute MI. The presence of an RWMA does not establish the diagnosis of acute ischemia. However, the presence of an aneurysm and myocardial thinning suggests a previous ischemic event. For diagnosing acute coronary ischemia, echocardiography has a high sensitivity but a low specificity.29,30 In a large study,29 1017 patients with suspected cardiac chest pain without ST-segment elevation were evaluated with standard clinical and electrocardiographic variables in the emergency room. The presence of RWMAs was assessed with 2D echocardiography. The sensitivity of RWMAs for detecting acute coronary syndrome was 88%, but the specificity was only 18%. Patients with RWMAs were 6.1 times more likely to experience an early cardiac event than those without RWMAs. The presence of a RWMA significantly increased the ability of clinical and electrocardiographic variables to predict early (within 48 hours) major adverse cardiac events. In patients with symptoms of an acute coronary syndrome, nondiagnostic electrocardiography, and normal biochemical markers, demonstration of normal global systolic function by handheld echocardiography had a 91% negative predictive value for acute MI.31 The addition of perfusion imaging to routine echocardiographic assessment of RWMAs and clinical variables in patients with suspected cardiac chest pain and nondiagnostic electrocardiograms improved the prediction of cardiac events. The addition of perfusion imaging in patients with suspected cardiac chest pain and nondiagnostic electrocardiograms further enhanced the clinical Thrombolysis in Myocardial Infarction (TIMI) 35 Normal RF, Normal MP 0.6 Abnormal RF, Normal MP 0.4 Abnormal RF, Abnormal MP 0.2 0.0 0 2 4 6 8 10 12 14 16 18 20 22 24 Months of follow-up FIGURE 35.5. Perfusion imaging enhances the clinical prediction of future cardiac events in patients with suspected cardiac chest pain. Event-free survival in patients with an intermediate-risk modified Thrombolysis in Myocardial Infarction (TIMI) score (3 or 4). MP, myocardial perfusion; RF, regional left ventricular function. risk score and the ability of RWMAs to predict cardiac events (Fig. 35.5).32 Because early detection of RWMAs adds significant diagnostic and prognostic value to the routine evaluation of patients who present to the emergency department with suspected cardiac chest pain, a joint task force of the American College of Cardiology (ACC), AHA, and ASE in 2003 issued a class I recommendation for the use of echocardiography in diagnosing suspected ischemia or infarction when standard means of diagnosis were inconclusive.33,34 Location of Acute Myocardial Infarction Two-dimensional and Doppler echocardiography provides assessment of the location and extent of myocardial damage, associated and preexisting valvular dysfunction, and ventricular and pulmonary artery pressures. Cardiac enzymes and the electrocardiogram are crude determinants of infarct size and location.35 Validation studies with thallium-201 scintigraphy, technetium-99m pyrophosphate (99mTc-PYP) scintigraphy, serum creatine kinase–MB levels, and coronary arteriography demonstrate that 2D echocardiography accurately detects and identifies the anatomic location of MIs.36–39 Two-dimensional echocardiography is less precise (sensitivity, 60% to 75%) in detecting nontransmural MIs, presumably because transmural muscle loss is less than 20% and preservation of the contractility of subepicardial myocardial layers can mask subendocardial dysfunction.40 With an acute MI, the uninvolved myocardium shows a compensatory hyperdynamic contractile response, the absence of which may indicate multivessel disease.41 The location of RWMAs correlates with the distribution of the occluded coronary artery, especially if the obstruction involves the left anterior descending (LAD) or posterior descending coronary arteries.42 11/29/2006 3:33:07 PM e c h o c a r d i o g r a p h i c e va l u a t i o n o f c o r o n a r y a r t e r y d i s e a s e Left anterior descending artery obstruction creates severe wall-motion abnormalities (akinesis with complete obstruction) of the septum, anterior wall, and apex. These segments are best visualized from the parasternal long-axis (anteroseptum), and apical four- (septum and apex) and two-chamber (anterior wall and apex) views. The location of the obstruction along the vessel length (proximal, middle, or distal) corresponds to the severity and extent of the resulting RWMA. The LAD may supply a variable (and often large) proportion of the LV apex. Occlusion of the LAD may lead to distal inferior and distal inferolateral wall-motion abnormalities. Left circumflex artery (LCx) occlusion typically affects perfusion of the anterolateral and inferolateral segments. Imaging in the parasternal long-axis (inferolateral wall) and the apical four- and apical long-axis views (inferolateral wall) augment the short-axis exam for visualization of the typical LCx infarction. In approximately 20% of patients, the LCx supplies the posterior descending artery (left dominant system), and interruption of the LCx blood flow can lead to an extensive RWMA that may also include the inferior septum and inferior free wall. Occlusion of the right coronary artery (RCA) results in an inferior RWMA. With proximal RCA occlusion, infarction of the right ventricle may result (see below). The posterior descending artery, a branch of the RCA (right dominant system) in 80% of patients, supplies the bulk of coronary flow to the inferior wall. Right coronary artery occlusion usually spares the apex. Two-dimensional imaging in the short-axis, basal, and midventricular views, confirmed by the apical two-chamber view, best reveals inferior wallmotion abnormalities resulting from RCA occlusion. Careful attention to right ventricle (RV) size and function are important with acute inferior wall infarction. Bypass grafts and collateral blood flow will blur these generalizations. A common post-bypass RWMA pattern includes paradoxic septal motion with marked hypokinesis to akinesis of the septum and normal motion of the anterior wall (in the absence of a previous anterior infarct). 815 patients following revascularization for MI serial echocardiographic studies in 58% showed complete or partial recovery of function. Most of those who improved had more than a 5% increase in LVEF.46 Echocardiographic assessment of the infarct size is limited by this method’s inadequate sensitivity in differentiating old versus new infarctions.43 The 2003 ACC/AHA/ASE task force issued a class I recommendation for the use of echocardiography to assess infarct size and ventricular function when the results are used to guide therapy. It gave a class IIa recommendation (weight of evidence/opinion is in favor of usefulness/efficacy) for echocardiographic assessment of ventricular function after revascularization.33,34 Acute Complications of Acute Myocardial Infarction Left Ventricular Failure/Cardiogenic Shock Cardiogenic shock, a state of inadequate tissue perfusion related to cardiac dysfunction, complicates approximately 6% to 7% of acute MIs.47–50 Left ventricular pump failure usually accounts for acute hemodynamic deterioration. In a small number of patients, however, the cause may be a complication of an acute MI such as rupture of the ventricular septum, free wall, or papillary muscle with acute severe mitral regurgitation (MR). A high index of suspicion for one of these major complications in a patient with hypotension, tachycardia, a new systolic murmur, or congestive heart failure is required for rapid diagnosis and appropriate medical and surgical intervention.51 Two-dimensional echocardiography and pulsed-wave and color-flow Doppler imaging provide a comprehensive assessment of the anatomic and hemodynamic status at the bedside and therefore are recommended for patients with hemodynamic deterioration. Cardiac Rupture Free-Wall Rupture Extent of Acute Myocardial Infarction Cardiac enzymes and electrocardiography are crude indicators of infarct size and location.42 Validation studies with thallium-201 scintigraphy, pyrophosphate (99mTc-PYP) scintigraphy, serum creatine kinase–MB levels, and coronary arteriography have shown that 2D echocardiography accurately detects and identifies the anatomic location of MIs.36,37,43,44 The location of RWMAs correlates with the distribution of the occluded coronary artery, especially if the obstruction involves the LAD or posterior descending coronary arteries.42 In postinfarct patients, LV systolic function is routinely measured by the LV ejection fraction (LVEF) on 2D echocardiography. The extent of the infarction can be quantified with the wall-motion score index. Echocardiography overestimates the infarct size in the presence of a previous infarction and after reperfusion. Reperfusion after an infarct often leads to early (usually <14 days) improvement in the LVEF as stunned myocardial segments recover.45,46 In a review of 249 CAR035.indd 815 Rupture of the free wall of the left or right ventricle is found in less than 1% of living patients with an acute MI,52 but in as many as 26% autopsied patients who died with an acute MI.53,54 The most important risk factors for free-wall rupture are large infarct size53 and delayed hospital admission with symptoms lasting for >24 hours,55 which are consequences of inadequate reperfusion. The risk of rupture is further increased by first MIs associated with poor collateral blood flow,55 undue in-hospital physical activity,55 age >70 years, and female sex.56,57 In the National Registry of Myocardial Infarction database, thrombolytic therapy accelerates the time course of cardiac rupture (often to within 24 hours) and increases the risk of rupture-related death (from 7.3% without thrombolytic treatment to 12.1% with such treatment).52 The risk of myocardial rupture was significantly decreased by successful reperfusion with thrombolytic agents in acute MI patients <75 years of age58–62 or by angioplasty in all age groups studied.63,64 In a retrospective review of 2209 acute MI patients treated with percutaneous coronary intervention,64 the risk of cardiac rupture was 0.7% when successful 11/29/2006 3:33:07 PM 816 chapter reperfusion was achieved within 12 hours, 0.9% when reperfusion occurred within 12 to 24 hours, and 3.8% after failed reperfusion. Infarcts of the lateral and anterior LV walls, subtended by the LCx or LAD coronary artery, are the most common infarcts associated with free-wall rupture.55 Myocardial rupture rarely involves the RV or the atria.65,66 The rupture site is typically located between infarcted and contractile myocardium. Myocardial rupture originates as an abrupt slit-like tear, usually in the anterior myocardium. It occurs early and suddenly, within 3 days following an acute MI in 50% of patients. In these cases, sudden chest discomfort, with rapidly progressive cardiogenic shock related to hemopericardium and tamponade, are followed by electromechanical dissociation67 and death. Rapid 2D echocardiography identifies a pericardial effusion and confirms the diagnosis.68 Contained Free-Wall Rupture: Ventricular Pseudoaneurysm Late rupture, more than 5 days after an acute MI, with infarct expansion, occurs mainly in patients who have had unsuccessful reperfusion. Late rupture with intramural dissection is more gradual or incomplete and produces the characteristic echocardiographic fi nding of a pseudoaneurysm, or false aneurysm. An LV pseudoaneurysm results from a localized rupture of the ventricular free wall, which produces a localized hemopericardium that is limited by parietal pericardium and by blood clot formation. There is an absence of heart muscle in the wall of a false aneurysm. Although ventricular pseudoaneurysms are usually the consequence of an acute MI (inferior infarctions being twice as common as anterior ones), they may also result from cardiac surgery (most commonly mitral valve replacement), trauma, or laceration.69 A pericardial effusion with organizing thrombus may help the pericardium seal the ventricular perforation temporarily, but progression to frank rupture and cardiac tamponade may occur without warning.70 Echocardiographic recognition of a pseudoaneurysm associated with a subacute or late LV rupture is difficult. In a large series of pseudoaneurysms,69 abnormalities were present on the 2D or Doppler echocardiograms of approximately 85% to 90% of patients, but a defi nitive diagnosis was made in only about 25%. In suspected cases, coronary angiography provides a defi nitive diagnosis in 87% of patients.69 Transesophageal echocardiography may improve the diagnostic accuracy but has not been studied in this regard. Twodimensional echocardiography can detect discontinuity of the ventricular free wall and confirm the presence or absence of pericardial tamponade.71 In most cases, a narrow neck abruptly connects the LV cavity to the large aneurysmal sac, which is located outside the LV cavity, is usually pulsatile, and may contain thrombus. Color-flow Doppler imaging shows characteristic bidirectional flow in both systole and diastole, resulting from a communication between the false aneurysm and the ventricular cavity. Ventricular Septal Defect Rupture of the interventricular septum is reported to complicate 1% to 3% of acute ST-elevation MIs.72 Ventricular CAR035.indd 816 35 septal defects (VSDs) accounted for 10% of total cardiac deaths73 before the reperfusion era but only 0.2% of those observed in the Global Utilization of Streptokinase and Tissue Plasminogen Activator for Occluded Coronary Arteries trial (GUSTO-I).74 Usually occurring within the first week, VSDs are more common after large infarctions of the anterior wall,75 after poorly reperfused infarcts, in the elderly, and in women.72 Although thrombolytic therapy prevents septal rupture in many patients who undergo successful coronary reperfusion, thrombolytic treatment likely accelerates rupture when reperfusion fails. The median time from the onset of symptoms to the development of an interventricular septal rupture was 1 day in the GUSTO-I trial.74 Septal rupture leads to a sudden left-to-right shunt, whose magnitude is proportional to the size of the septal defect and to the ratio of the systemic and peripheral vascular resistance. In this clinical setting, Doppler echocardiography is usually diagnostic, its sensitivity and specificity reportedly being as high as 100%.76 Rarely, when the transthoracic image quality is challenged by mechanical ventilation or obesity, transesophageal echocardiography is required for diagnosis. In up to 40% of patients, 2D echocardiography alone may show a dropout of echoes in the interventricular septum, in the region of abnormal wall motion (Fig. 35.6A).65 Color-flow Doppler imaging77 has been shown to enhance the diagnostic accuracy up to 100% by defining the site of septal rupture as an area of turbulent transseptal flow or by detecting a high-velocity jet on the right side of the ventricular septum (Fig. 35.6B). Color Doppler examination may show a single rupture site (typically seen with anteroapical defects) or multiple rupture sites (characteristically seen with inferior and inferobasal defects).78,79 Pulsed-wave Doppler imaging, undertaken on the right side of the interventricular septum (at the site of the defect), usually characterizes a high-velocity jet directed from the left ventricle to the right ventricle (Fig. 35.6C). Right ventricular systolic pressure can be estimated by subtracting the peak gradient obtained across the interventricular septum from the systolic (systemic) blood pressure, provided that no aortic stenosis is present. A semiquantitative estimate of the size of the left-to-right shunt can be obtained by measuring the volumetric flow across the pulmonary valve and the LV outflow tract, provided that no valvular regurgitation is present. Contrast 2D echocardiography can also identify a VSD. Thus, 2D echocardiography and color-flow Doppler imaging can rapidly and reliably provide an anatomic diagnosis and estimation of the hemodynamic status at the bedside. Because the prognosis depends on early surgical intervention, echocardiography has become invaluable for the rapid evaluation of this complication. Right Ventricular Infarction Right ventricular infarction, usually caused by proximal occlusion of the RCA, may complicate up to 40% of inferior MIs. The echocardiographic manifestations of RV infarction include RV dilatation, hypokinesis of the RV free wall,80–83 and manifestations of right atrial hypertension48 (dilated right atrium, plethoric systemic veins) (Fig. 35.7A,B). These findings are not specific for RV infarction, and they commonly occur with acute and chronic pulmonary hyperten- 11/29/2006 3:33:07 PM e c h o c a r d i o g r a p h i c e va l u a t i o n o f c o r o n a r y a r t e r y d i s e a s e A 817 B C FIGURE 35.6. Ventricular septal defect (VSD). (A) Apical VSD (arrow) is identified by the dropout of interventricular septum visualized by two-dimensional echocardiography. Color Doppler demonstrates an area of turbulence at the site of the VSD rupture in the apical septum. (B) Color Doppler demonstrates a high-velocity jet of mosaic color directed into the apex of the right ventricle with migration of blue color toward the base of the right ventricle (RV) (opposite direction of RV inflow). (C) Spectral Doppler identifies the direction of the shunt and the magnitude of the pressure gradient from the left to the right ventricle. The RV systolic pressure can and should be estimated as the systolic blood pressure (SBP)-4 (peak VSD jet).2 RA, right atrium; LA, left atrium; PK, peak gradient; LV, left ventricle; RV, right ventricle. sion (pulmonary embolism). An RV infarction almost always accompanies an infarction of the inferior LV wall (Fig. 35.7C). Thus, RV dysfunction with akinesis of the inferior LV wall is characteristic of an RV infarction, having a sensitivity of more than 80% to 85%.84 Prompt diagnosis of RV infarctions will differentiate these lesions from other reversible causes of cardiogenic shock such as cardiac tamponade. thrombolytic therapy for an acute MI, the Gruppo Italiano per lo Studio della Sopravvivenza nell’Infarto Miocardio III (GISSI-3) study85 reported visualization of LV thrombus on the predischarge echocardiogram of 5.1% of patients (9 ± 5 days after symptom onset). Patients with an anterior MI had a fivefold higher prevalence of thrombus formation than did patients with other infarct locations (11.5% vs. 2.3%, respectively). Worsening LV function and more extensive regional dysfunction are also recognized risk factors for LV thrombus.85 Most thrombi occur within the first 2 weeks (median, 5 to 6 days) after an acute MI.86,87 However, with worsening LV function, new LV thrombus is identified in some patients after hospital discharge.87,88 Mural Thrombus Mural thrombus is a common complication of an acute MI and had an incidence of up to 40% in patients with anterior and apical infarctions in the prethrombolytic era. After CAR035.indd 817 11/29/2006 3:33:07 PM 818 chapter A 35 B C FIGURE 35.7. Right ventricular infarction. The manifestations of right ventricular (RV) infarction can be identified by echocardiography and include RV dilatation (*), hypokinesis of the RV free wall (arrows), and evidence of elevated right atrial pressure; dilated right Thrombus, observed at the site of abnormal wall motion or within an aneurysm, appears as a mobile or an immobile opaque intracavity mass (Fig. 35.8), which may be laminar or pedunculated or may protrude into the ventricular cavity.85,89–91 Thrombi are usually located at the apex and, less frequently, along the septum and the inferior regions of the heart.92 In detecting LV thrombus, 2D transthoracic echocardiography has a sensitivity of 75% to 95% and a specificity of 87 to 90%,90,91,93 and therefore is the method of choice. When the apex is poorly visualized with transthoracic echocardiography, administration of a contrast agent may help identify suspected apical thrombus by demonstrating an absence of contrast in an LV cavity filled with contrast. In transesophageal echocardiography, the posterior position of the ultrasound probe limits visualization of the apex and thus detection of apical thrombus. The 2003 ACC/AHA/ASE task force gave a class I recommendation to the use of echocardiography for assessing mural thrombus after an acute MI.33,34 CAR035.indd 818 atrium (RA*) (A), or plethoric inferior vena cava (IVC*, arrow) (B). Left ventricular inferior wall motion abnormality (arrows) should also be present (C). FIGURE 35.8. Left ventricular mural thrombus. Two-dimensional imaging in the apical four-chamber view demonstrates an echolucency in the LV apex of a patient with a large apical infarct (arrow). RV, right ventricle; RA, right atrium; LV, left ventricle; LA, left atrium. 11/29/2006 3:33:08 PM 819 e c h o c a r d i o g r a p h i c e va l u a t i o n o f c o r o n a r y a r t e r y d i s e a s e Embolization has been reported to occur in 26 of 119 patients with documented LV thrombi after an MI.91 Thrombi that are protruding, pedunculated, or mobile within the ventricular cavity are most likely to embolize, usually within 3 months after an acute MI.91,93–95 Papillary Muscle Rupture Producing Acute Mitral Regurgitation Severe MR resulting from papillary muscle rupture is a rare and often fatal complication of an acute MI.96 In the absence of prompt surgical intervention, the mortality of this complication is as high as 50% at 24 hours,97,98 which is nearly double the mortality seen in patients with a postinfarction VSD.99 The median duration of survival is reportedly 3 days.100 The anterolateral papillary muscle is rarely affected, because it has a dual blood supply from the LAD and circumflex arteries.101 Infarction of the posterior descending artery is associated with necrosis of the posteromedial papillary muscle, which produces sudden clinical and hemodynamic deterioration and fulminant acute left-sided heart failure. It is important to recognize that severe MR with complete rupture of the papillary muscle may occur in the absence of a cardiac murmur or in the presence of a very soft murmur; therefore, this diagnosis must be considered with a high index of suspicion in the appropriate clinical setting. It is crucial that a defi nitive diagnosis be reached rapidly in these patients. Two-dimensional echocardiography shows flail mitral leaflet with attachment of the mobile severed papillary muscle head, which prolapses into the left atrium in systole, and abnormal cutoff of one papillary muscle (Fig. 35.9A).102,103 In up to 35% of surgically confirmed cases, the partially ruptured papillary muscle cannot be observed to prolapse into the left atrium on transthoracic echocardiography imaging.104 Transesophageal echocardiography has become an invaluable technique for diagnosing acute MR that complicates an MI, especially in hemodynamically compromised patients in the intensive care unit, in whom transthoracic echocardiography imaging may be limited. Transesophageal echocardiographic imaging in the gastric A FIGURE 35.9. Papillary muscle rupture. (A) Transesophageal imaging in the mid-esophageal four-chamber view demonstrates the prolapse of the severed head of the papillary muscle (arrow) into the left atrium (LA) during ventricular systole. The mitral subvalvular CAR035.indd 819 long-axis and mid-esophageal four-chamber views can detect the origin of the regurgitant jet and clarify the anatomic profile of the mitral and submitral valvular apparatus (Fig. 35.9B).89 Chronic Complications After a Myocardial Infarction Ischemic Mitral Regurgitation Mitral regurgitation caused by changes in ventricular structure and function as a consequence of coronary ischemia is best described as ischemic MR.105 Usually a consequence of a previous infarction and chronic LV remodeling, ischemic MR may also be precipitated by active ischemia, creating flash pulmonary edema or, rarely, rupture of the papillary muscle (see above). Incidence Ischemic MR occurs in 20% to 25% of patients followed after an MI106–109 and in 50% of those with congestive heart failure.110 Moderate or severe MR is found in roughly 40% of patients within 24 hours of an acute MI complicated by cardiogenic shock.111 However, angiographic detection of moderate-to-severe MR after an MI has been reported in only 3% to 4% of patients.112,113 When evaluated by echocardiography within 30 days after an MI, moderate or severe MR was present in 12%.114 Mild MR has been reported in 50% to 64% of post-MI patients undergoing echocardiography within 30 days of the MI.106–111,113–115 Mechanism Mitral regurgitation after an acute MI is due primarily to segmental and global LV dysfunction, which causes chronic papillary muscle displacement, apical tethering of the mitral leaflets, annular dilatation, and decreased systolic mitral closing forces (Fig. 35.10).105 Elegant models of MR have shown that ischemia of the papillary muscle in the absence B apparatus with rupture of the papillary muscle head (arrow) is shown by two-dimensional imaging in the deep gastric long-axis view (B). LV, left ventricle; MV, mitral valve. 11/29/2006 3:33:09 PM 820 chapter 35 Ischemic mitral regurgitation: incomplete mitral leaflet closure Normal Ischemic LV closing force Papillary muscle displacement Mitral valve tethering Tethering force LA Restricted closure AO MR FIGURE 35.10. Mechanism of ischemic mitral regurgitation. Left: The balance of forces acting on the mitral leaflets in systole. LA, left atrium, LV, left ventricle, AO, aorta. Right: Effect of papillary muscle displacement and mitral leaflet tethering to restrict mitral leaflet closure. MR, mitral regurgitation. of infarction does not cause MR.105,116–118 Ischemic MR depends on a balance of forces and LV geometry and varies with loading conditions (Fig. 35.11).119 Characteristically dynamic in nature, MR may be elusive on transesophageal echocardiography in cardiac surgical patients under anesthesia.120–122 MR is also likely underestimated by resting echocardiography in patients with LV dysfunction and symptoms of congestive heart failure in the absence of active ischemia.123–125 With semisupine bicycle exercise, Pierard and Lancellotti125 demonstrated a twofold increase in MR volume (from mild to moderate-to-severe) and a corresponding increase in orifice area (by >20 mm2) in nearly 30% of patients. Exercise-increased MR also correlated with increased pulmonary artery pressure and conferred an adverse prognosis.125 A FIGURE 35.12. Left ventricular aneurysm (LVA). (A) Two-dimensional imaging in the four-chamber apical view demonstrates a thin distal septum and apical LV segment with a hinge point (arrow) demarcating the transition from contractile tissue to the aneurys- CAR035.indd 820 FIGURE 35.11. Illustration of ischemic mitral regurgitation. Twodimensional imaging in the parasternal long axis view demonstrates apical tethering of the chordae tendineae (left, arrow) and the resultant jet of mitral regurgitation (right) caused by the incomplete mitral leaflet closure. Ventricular Aneurysm After an acute, usually anterior, MI,95,126 a true LV aneurysm develops in up to 20% of patients, owing to gradual expansion and thinning of all three layers of the infarcted myocardium.127 The incidence of true LV aneurysm has decreased as reperfusion therapies have improved and become widespread.128 The usual time of aneurysm formation is within 3 months after the onset of an MI. True LV aneurysms almost always involve the LV apex and extend into the anterior or anterolateral walls (Fig. 35.12A). Rarely, true aneurysms are found in the basal inferior or high lateral wall (Fig. 35.12B). Aneurysms are usually the consequence of left anterior artery occlusion and are rarely present with multivessel CAD and extensive collateralization. B mal segment. (B) Two-dimensional imaging of the two-chamber view identifies an aneurysm of the inferior base (arrows) and an apical thrombus (arrow), which is present in up to one third of patients with acute myocardial infarction. 11/29/2006 3:33:09 PM e c h o c a r d i o g r a p h i c e va l u a t i o n o f c o r o n a r y a r t e r y d i s e a s e Left Ventricular Remodeling After an MI, the left ventricle accommodates to the loss of regional myocardial function by increasing the contractile state of the remaining viable segments. Left ventricular remodeling is clinically characterized as a change in cardiac size, shape, and function as a result of myocardial injury or an increased load.137,138 The severity of the regional dysfunction (infarct size),139,140 function of the remaining segments, neurohormonal activation, and presence of coexisting valvular heart disease, particularly MR, will determine the magnitude of LV remodeling.105 This process usually begins within the first few hours after the infarct and progresses over time.141–143 Disproportionate thinning and dilatation of the infarcted segment after an MI is defi ned as infarct expansion and is accompanied by gross distortion of the LV shape and volume144,145 and loss of functional myocardium that initially contracted normally.146 With remodeling, the left ventricle dilates, becomes more spherical, and declines in function.147 Alterations in LV geometry lead to ischemic MR, which further increases LV volumes and diastolic wall stress, activates the neurohumoral cascade, and further decreases LV contractility, thus leading to a cycle of LV remodeling and MR.105 The important relationship between LV function and MR is reflected in the poor survival of post-MI patients in whom both significant MR and severe LV dysfunction coexist (Fig. 35.13).111 Echocardiographic assessment of LV remodeling after an acute MI includes 2D measurements of the LVEF, size, shape, CAR035.indd 821 1.0 0.9 0.8 Proportion alive Two-dimensional echocardiography has a sensitivity of >93%129 and a specificity of 94% in the detection of LV aneurysm. The characteristic echocardiographic fi nding is a thin LV wall that fails to thicken during systolic contraction, producing a “bulge” during systole and diastole.127,130 A common finding is a hinge point (Fig. 35.12A), or junction, between contractile LV tissue and the akinetic, often paradoxic, motion of the aneurysm. True LV aneurysms distort LV geometry during both systole and diastole.129 Doppler echocardiography can be used to detect a low-velocity flow profile with a “swirling” motion characteristic of low cardiac flow within the aneurysm. Thrombus within the aneurysmal segment is detected echocardiographically in at least a third of patients with LV aneurysms (Fig. 35.12B),131,132 and such thrombus may account for the increased risk of stroke in the 5 years after an acute MI.133 Deposition of fibrous tissue and calcium in the aneurysmal segment over time prevents rupture of a chronic LVA, unlike a pseudoaneurysm.134,135 Left ventricular aneurysms contribute to chronic cardiac decompensation with congestive heart failure, ventricular arrhythmias, and systemic emboli. Compared to medical therapy alone, surgical repair of LV aneurysms in selected patients improves survival, functional class, and symptoms.136 Two-dimensional echocardiography has been used to evaluate the efficacy of aneurysmectomy in patients with ventricular aneurysms. Ryan and colleagues126 found that a fractional shortening of >17% in the uninvolved myocardium (measured at the base of the heart) was associated with an improved surgical outcome, whereas a fractional shortening of ≥17% entailed no subsequent clinical or surgical improvement. 8 21 0/1 MR, LVEF ≥28% 0.7 0.6 0.5 0.4 2/3/4 MR, LVEF ≥28% 0/1 MR, LVEF <28% 0.3 0.2 0.1 2/3/4 MR, LVEF <28% 0.0 8 10 12 4 6 Time from randomization (months) FIGURE 35.13. Survival following myocardial infarction is dependent on both left ventricular ejection fraction (LVEF) and the severity of mitral regurgitation (MR). Kaplan-Meier estimates of survival up to 1 year after randomization for four combinations of LVEF and MR in the SHOCK trial. Total n = 90; MR 0/1 and LVEF >28%, n = 33; MR 0/1 and LVEF <28%, n = 20; MR 2/3/4 and LVEF >28%, n = 16; MR 2/3/4 and LVEF <28%, n = 21. 0 2 and volume at end-diastole and end-systole and should also include Doppler estimation and quantification of MR severity. Prognosis in Acute Myocardial Infarction and Chronic Coronary Artery Disease In patients with CAD, the prognosis is related to the extent of myocardial damage, the magnitude of the resultant LV remodeling, the LV fi lling pressures, and the degree of residual coronary ischemia and viability. As a cardiac imaging modality, echocardiography is uniquely suited for the routine examination of each of these important predictors of outcome. Two-dimensional echocardiography can be used to identify patients with acute MIs who are at high risk for short-term complications in the hospital and for long-term complications after hospital discharge.148–151 Horowitz and Morganroth149 found that echocardiography had a sensitivity of 83% and a specificity of 85% in identifying patients at high risk for in-hospital complications. Ventricular Systolic Function Left Ventricular Systolic Function The extent of myocardial damage can be measured globally as the ejection fraction or regionally as a wall-motion score index. Both parameters have been shown to correlate with the outcome in patients with an acute MI or chronic CAD (Fig. 35.14).28,30,152,153 Nishimura and colleagues150 found that post MI patients with a higher wall-motion score index at discharge are more likely to have cardiovascular complications at follow-up examination. The LVEF and severity of MR were the only independent echocardiographic predictors of both early and late survival for patients presenting with cardiogenic shock. Survival at 1 year was 24% in those with an 11/29/2006 3:33:10 PM 822 chapter 10 Left Ventricular Remodeling <30% Total = 3197 Mortality (%) 8 6 No study within 14 days 4 30–39% 40–49% 2 ≥60% 50–59% N = 630 0 162 35 355 604 835 611 15 30 45 60 75 Resting ejection fraction (%) FIGURE 35.14. Left ventricular systolic function predicts mortality after myocardial infarction. Relation of rest ejection fraction to allcause mortality in 3197 patients enrolled in the TIMI II study. Kaplan-Meier analysis of mortality rate related to time from study entry, with patients categorized according to ejection fraction. Mortality rate is highest in patients with ejection fraction <30% (9.9%). LVEF of <28% versus 56% for those with a higher LVEF.111 In the setting of acute coronary syndrome, LV systolic dysfunction increases the long-term mortality and increases the probability of having multivessel CAD by 50%.154 Left ventricular remodeling can be characterized and quantified by 2D echocardiographic measurements of LV size and volume. The prognosis in patients with CAD is also related to the extent of LV remodeling. After an acute MI, small increases in LV volume (particularly LV end-systolic volume)156,157 or decreases in the LVEF158 increase the risk of death and congestive heart failure.156,159 In-hospital evaluation of the postinfarct LVEF and the extent of RWMA, but not LV dilatation, predicted progressive LV remodeling.143,146 In the Beta-Blocker Evaluation of Survival Trial (BEST), however, Grayburn and colleagues160 found that LV volume and MR were the best predictors of outcome in patients with LV dysfunction. Mitral Regurgitation The presence and severity of ischemic MR has been shown to worsen survival in patients with acute MI and chronic CAD with or without LV dysfunction.107,109,111–114,161–163 Mitral regurgitation that follows an acute MI is an important independent predictor of early and late death.109,113 In the SAVE trial,24 any degree of MR detected within days after an MI was associated with a poorer outcome, which was independent of treatment with angiotensin-converting-enzyme inhibitors (Fig. 35.16A). Survival correlated with the severity Right Ventricular Systolic Function In 416 patients with LV dysfunction (LVEF <40%) after an MI, persistent RV dysfunction has been shown to decrease overall survival. The RV systolic function correlated weakly with the LV systolic function. However, RV function, measured as a fractional area change, was an independent predictor of mortality, cardiovascular mortality, and congestive heart failure. Each 5% decrease in RV fractional area change increased the odds of cardiovascular mortality by 16% (Fig. 35.15).155 100 No RV Dysfunction n = 337 HR = 3.2 (2.0–5.1) p <.0001 Survival (%) 75 RV Dysfunction n = 79 50 25 0 0 500 1000 1500 Days FIGURE 35.15. Right ventricular dysfunction following myocardial infarction decreases survival. Cumulative percent survival of patients with and those without right ventricular (RV) dysfunction measured as fractional area change (FAC). RV dysfunction = FAC <32.2%; normal RV function = FAC >32.3%; HR, hazard ratio. CAR035.indd 822 FIGURE 35.16. (A) Mitral regurgitation (MR) worsens survival after myocardial infarction. Kaplan-Meier curves of cardiovascular survival in patients with and without MR following acute myocardial infarction in the Survival and Ventricular Enlargement (SAVE) Study. MR, mitral regurgitation. (B) Decreased survival after MI with increasing severity of MR. Degree of MR quantified by effective regurgitant orifice area (EROA); mild if EROA <20 mm2 and moderate or greater when EROA ≥20 mm2. Numbers at bottom indicate patients at risk each interval. 11/29/2006 3:33:10 PM 823 e c h o c a r d i o g r a p h i c e va l u a t i o n o f c o r o n a r y a r t e r y d i s e a s e 1.0 E/e’ ≤15 Survival 0.9 0.8 0.7 0.6 0.5 0 Number at risk 250 A E/e’ > 15 6 12 18 24 195 113 49 16 Duration of follow-up (months) 1.0 0.9 Em >5 cm/s 0.8 0.7 3< Em ≤5 cm/s 0 Elevated Left Ventricular Filling Pressures Elevated LV filling pressures in patients with acute MI and chronic CAD are the consequence of LV dysfunction, MR, and ventricular loading conditions. As such, they have been shown to predict the short- and long-term outcome of patients with CAD. Elevated filling pressures may be characterized echocardiographically as a shortened deceleration time (DT) of mitral early inflow velocity (DT <150 ms), an increased ratio of early (E) to late (A) LV diastolic filling velocities (mitral inflow E/A >2), and pulmonary venous diastolic flow predominance. Additionally, the LA volume, when indexed to body surface area (>28 mL/m2), reflects the severity and duration of elevated LV filling pressures and is a powerful Sm >5 cm/s 0.8 0.7 10 20 30 40 Follow time (months) B 0.9 3< Sm ≤5 cm/s Sm ≤3 cm/s Em ≤3 cm/s of MR quantified as effective regurgitant orifice area (EROA) and regurgitant volume in the elegant studies by Grigioni and coworkers115,164 (Fig. 35.16B). In the echocardiographic substudy of the SHOCK trial (SHould we emergently revascularize Occluded Coronaries in cardiogenic shocK?),111 the only independent multivariate predictors of either 30-day or 1-year mortality in patients with cardiogenic shock after an acute MI were moderate or greater MR severity and an LVEF of <28% (Fig. 35.13). For patients with moderate or severe MR, the 1-year survival rate was 31% compared to 58% for those with mild or no MR. This outcome is comparable to the mortality of 52% at 1 year and 24% at 30 days in 50 patients with moderately severe to severe (3+ to 4+) MR on routine angiography during an acute MI (total, 1485 patients).113 In these studies, MR severity was associated with increasing LV volumes, which underlie and contribute to the mechanism of MR after an acute MI. CAR035.indd 823 Cum survival FIGURE 35.17. Elevated left ventricular fi lling pressures predict survival after myocardial infarction. (A) Ratio of early mitral diastolic velocity to diastolic annular tissue velocity (E/e’) predicts survival. Kaplan-Meier plot demonstrates improved survival for patients with E/e’ ratio of <15. (B,C) Peak LV annular velocities in both systole and diastole predict survival after MI. Cumulative cardiac death by tertiles of the early mitral annulus diastolic velocity (B) and mitral annulus systolic velocity (C). Cum survival 1.0 0 10 20 30 Follow time (months) 40 C predictor of survival after an acute MI.165 Measurements utilizing TDI have provided incremental prognostic information in patients with CAD or congestive heart failure.166–168 After an acute MI, the ratio of the early diastolic mitral filling velocity to the early diastolic tissue velocity of the mitral annulus (E/e’ > 15) (Fig. 35.17A)167 as well as the maximal peak tissue systolic velocity (Sm) (Fig. 35.17C)166 and peak early diastolic tissue velocity (Em) (Fig. 35.17B)166 when added to other echocardiographic variables, further predicts survival. Stress Echocardiography: Assessment of Ischemic and Viable Myocardium Stress echocardiography is routinely used to document the presence of CAD, to identify the location and extent of myocardial ischemia, to risk-stratify patients with known CAD, and to assess myocardial viability in regions of myocardial dysfunction. Basic Principles and Definitions Ischemia is characterized by hypoperfusion of myocardial cells and can occur at rest or after stress. Viable myocardial cells are living cells. Viable myocardium is easily identified when it contracts normally. The discrimination of dysfunctional, but living, myocardium from necrotic tissue is the more common and clinically relevant description of viability. Ischemia produces regional myocardial dysfunction within seconds. Experimental studies have shown that the duration and severity of an ischemic insult is the major determinant of both functional and metabolic myocardial 11/29/2006 3:33:11 PM 824 chapter 35 TABLE 35.2. Myocardial segment response to stress Resting segment function Stress Likelihood of functional recovering Exercise Low dose Peak dose Interpretation Normal Normal Abnormal* ↑ ↓ ↑ ↑ ↑ ↑↑ ↓ ↓ Abnormal Abnormal Abnormal ↓ ↑ No change ↓ ↑ No change ↓ ↑↑ No change Normal Ischemic Ischemic and viable “Biphasic” Ischemic, viable Nonischemic, viable Nonviable, scar n/a n/a High Moderate Low Low * Viability assessment requires graded stress with image acquisition at multiple stages. Treadmill echo is not recommended for the assessment of viability. recovery.169 Severe regional LV dysfunction, leading to depression of LV systolic function in patients with CAD, can result from myocardial necrosis, postischemic stunning, or myocardial hibernation. “Stunning” refers to contractile dysfunction in viable myocardium as a result of transient ischemia followed by reperfusion.12 “Hibernating” myocardium refers to myocardial tissue that is persistently hypocontractile secondary to chronic or repetitive low coronary perfusion.170 Hibernating myocardium has been described as an adaptation to severe and chronic ischemia that increases the risk of sudden death even in the absence of infarction.171 Recovery of hibernating myocardium is characteristically late (two of three segments recovering in >3 months) after reperfusion. is dependent on visualization of all myocardial segments and evaluation of myocardial thickening and regional wall motion. Myocardial contrast agents, which opacify the LV cavity and better define endocardial borders, enhance the detection of RWMAs. Tissue harmonic imaging and digital image acquisition, which allow comparison of side-by-side optimized images of representative cardiac cycles with reduced respiratory interference (particularly at peak stress), have further improved the discrimination of subtle wallmotion abnormalities at various stress stages. Because accuracy of image interpretation remains subjective, physician experience is a major determinant of the accuracy of stress echocardiography.172 Treadmill Stress Echocardiography Interpretation A new RWMA provoked by stress indicates cardiac ischemia. Improved contractility of myocardial segments with abnormal baseline function on inotropic stimulation is characteristic of viable but dysfunctional myocardium. A dysfunctional segment may show one of four responses: (1) an improvement in contractility (contractile reserve) that further improves with maximum stimulation; (2) no improvement (nonviable); (3) worsening function (ischemic); or (4) improvement with low-dose inotropic stimulation that becomes dysfunctional at higher doses of inotropic stimulation.8 This biphasic response is characteristic of viable segments that become ischemic at higher levels of stress. Table 35.2 summarizes the myocardial segment responses to stress. Exercise protocols generally consist of either treadmill exercise or upright or supine bicycle exercise. Baseline images are acquired before and after exercise in four standard views: parasternal long-axis (or apical three-chamber), parasternal short-axis at the level of the papillary muscles, apical fourchamber, and apical two-chamber. Exercise is performed according to a standard exercise protocol, and the heart rate, blood pressure, and electrocardiogram are monitored throughout the test at each stage of exercise (Table 35.4). Only postexercise imaging is available with treadmill exercise. Therefore, rapid acquisition (within 60 to 90 seconds) of postexercise TABLE 35.3. Selection of stress echocardiography protocols for clinical decision making Methodology Analysis of stress echocardiograms is predominantly based on qualitative comparison of regional wall motion at baseline and during stress. Semiquantitative assessment of RWMAs by determining the wall-motion score index (described above) is recommended. Newer techniques for quantitation of regional LV systolic function include TDI and its derivative, strain-rate imaging. Because regional myocardial dysfunction occurs within seconds of acute transient ischemia, and because recovery usually occurs within 2 to 3 minutes, imaging can be done after stress if performed rapidly. Stress echocardiography can be performed using either exercise or pharmacologic stress, depending on patient ability, laboratory preference, and the reason for clinical study (Table 35.3). The accuracy of stress echocardiography CAR035.indd 824 Stress echo protocol Clinical indication Chest pain Post-MI Viability Dyspnea MR MS AS AI Pulmonary artery pressure Preop risk assessment TME Bike Dobutamine + + − + + + + ± + ++ ++ ++ ++ ++ ± ± + ++ ± Valve disease − ± + + − + AI, aortic insufficiency; AS, aortic stenosis; MI, myocardial infarction; MR, mitral regurgitation; MS, mitral stenosis; TME, treadmill stress echocardiography. 11/29/2006 3:33:11 PM 825 e c h o c a r d i o g r a p h i c e va l u a t i o n o f c o r o n a r y a r t e r y d i s e a s e TABLE 35.4. Exercise echocardiography protocols Baseline images ± Doppler Exercise imaging Immediate (<1 min) postexercise imaging Treadmill ✓ ✗ ✓ Bike ✓ ✓ ✓ Protocols images is imperative to prevent resolution of an inducible RWMA and, thus, a false-negative result. The advantages of treadmill stress testing include the widespread availability of treadmill equipment and the independent prognostic information obtained from exercise treadmill testing. Bicycle Stress Echocardiography Stationary bicycle exercise, either upright or supine, can also be used for exercise stress echocardiography. As in treadmill testing, baseline images are acquired before exercise. Patients then pedal against progressively increasing resistance; the blood pressure, heart rate, and electrocardiogram are monitored throughout the test at each stage of exercise. One advantage of supine bicycle testing is that images can be acquired during exercise. The disadvantage is that many patients find bicycling in the supine position awkward and cumbersome, so they may be unable to achieve optimal stress levels (Table 35.4). However, the onset of ischemia appears to occur sooner in the supine position, perhaps Dobutamine dose (μg/kg/min) 40** * 30 20 10 5 0 3 6 9 12 Advantages Limitations High workload Widely available Exercise itself is prognostic: Duration ECG Symptoms Images during exercise Imaging only postexercise Lower workload Difficult for patient because of the increased venous return, preload, or blood pressure associated with supine bicycling.173 Pharmacologic Stress Echocardiography When a patient is unable to exercise, stress is induced with pharmacologic agents such as dobutamine, adenosine, or dipyridamole. Dobutamine, the most commonly used agent, stimulates β1-, β2-, and α-adrenergic receptors, resulting in both inotropic and chronotropic stimulation. Because of dose-dependent differences in affinity for the different receptors, low doses produce a predominantly inotropic response, and increasing doses augment the chronotropic response. Images are acquired at baseline and after administration of graded doses of dobutamine, beginning with 5 to 10 μg/kg/ min and increasing the dose every 3 to 5 minutes until reaching a maximum dose of 40 μg/kg/min, at which 85% of the maximum age-adjusted (220 − age) heart rate is obtained. Atropine (0.5 to 2.0 mg) is frequently (in up to 25% of patients)174 used in conjunction with dobutamine to augment the heart rate response, especially in beta-blocker recipients, in whom the heart rate response may be blunted. Figure 35.18 summarizes the DSE protocol. Neither the electrocardiogram nor the hemodynamic response to pharmacologic stress testing is diagnostic or prognostic. Hypotension during DSE may be related to (1) decreased systemic vascular resistance associated with a β2-agonist response; (2) LV outflow tract (LVOT) obstruction produced by systolic anterior motion of the mitral valve associated with increasing LVOT velocity and reduction in LV systolic cavity size; (3) hypovolemia; or (4) severe (usually multivessel) ischemia. Contraindications to DSE include severe arrhythmia, marked systemic hypertension, severe aortic stenosis, resting LVOT obstruction, aortic aneurysms, and unstable coronary syndromes (Table 35.5). Testing is terminated when the patient has completed the protocol and achieved >85% of the maximal predicted heart rate (MPHR) or if a new RWMA Time in minutes TABLE 35.5. Dobutamine stress echocardiography 2D imaging 2 minutes after dose adjustment * Atropine 0.5–1 mg as needed to achieve 85% MPHR at peak dobutamine dose ** Hand grip exercise may also be utilized to increase heart rate at peak dose FIGURE 35.18. Dobutamine stress echocardiography (DSE) protocol. CAR035.indd 825 Indications Contraindications Patient unable to exercise Graded stress imaging Identification of viability Unstable coronary syndrome Severe arrhythmia Severe hypertension Severe aortic stenosis Aortic aneurysm or dissection Resting left ventricular outflow tract (LVOT) obstruction 11/29/2006 3:33:11 PM 826 chapter TABLE 35.6. Dobutamine stress echocardiography end points Completed protocol Achieved target heart rate >85% of (220—age in years) Cardiac Angina New RWMA ≥2 segments Arrhythmia Ventricular tachycardia Atrial fibrillation with rapid response Supraventricular tachycardia LVOT obstruction (>4 m/s) Abnormal blood pressure ≥230/120 SBP ≤80 Intolerable dobutamine reaction Anxiety, nausea, headache 35 Stress Echocardiography for Detection of Myocardial Ischemia Accuracy of Exercise Stress Echocardiography develops in two or more segments. Development of a significant arrhythmia, LVOT obstruction of >4 m/s, or significant hypotension or hypertension should lead to cessation of the dobutamine infusion and termination of the test (Table 35.6). In a review of 1118 patients,175 the primary reason for terminating DSE was achievement of the target heart rate (52%), completion of the protocol with the maximum dobutamine dose (23%), or development of angina (13%). In only 3% to 7% of patients was the test terminated for a noncardiac side effect (nausea, anxiety, headache, tremor, urgency). Overall, the frequency of such side effects was 26%. The most frequent side effects were arrhythmias, hypotension, nausea, and dyspnea, but these led to test termination in only 3% of cases.175 The incidence of supraventricular arrhythmia during DSE has reportedly been as low as 0.5%176 and as high as 7%.177 Sustained ventricular tachycardia occurs in up to 6% of DSE studies177,178; acute MI is rare, occurring in <0.1%.177,178 Provocation of LVOT or midcavity obstruction with DSE occurs in up to 35% of patients.179,180 Those who develop LVOT obstruction but not midcavitary obstruction may be at risk for future chest pain and syncope.181 Women, patients with diabetes, and those receiving beta-blockers, calcium channel blockers, or both, were more likely to have suboptimal stress. The accuracy of stress echocardiography for the detection of CAD has been well studied (Table 35.7). In 16 published studies including 1972 patients, the sensitivity of exercise stress echocardiography for the detection of coronary stenoses >50% ranged from 71% to 97%.172,182–191 In a literature review, 44 articles met the criteria for determining the sensitivity and specificity of exercise echocardiography and exercise myocardial perfusion imaging with single photon emission computed tomography (SPECT) compared to coronary angiography for the diagnosis of CAD.192 In pooled data, the two modalities had similar sensitivities for detecting CAD (85% vs. 87%), but exercise echocardiography had significantly greater specificity (77% vs. 64%). Both tests performed better than standard exercise testing, for which a sensitivity of 68% and a specificity of 77% have been reported.193 The sensitivity of exercise echocardiography was better for the detection of multivessel disease than singlevessel disease (average 92%, range 80% to 100%; vs. average 79%, range 59% to 94%) in nine studies involving 1355 patients.182–185,187,188,190,194 Patient characteristics also influence the accuracy of exercise stress testing. Left ventricular hypertrophy, cardiomyopathy, microvascular disease, and an acute hypertensive response to exercise diminish the accuracy of exercise echocardiography compared with the angiographic standard.8 However, stress echocardiography may be more accurate than exercise myocardial perfusion imaging in this setting.194–196 Exercise myocardial perfusion imaging is more accurate in the presence of preexisting abnormal wall motion, left bundle-branch block, ventricular pacing, a previous MI, and cardiomyopathy. The accuracy of exercise echocardiography depends on the exercise level. Failure to achieve 85% of the MPHR precludes the exclusion of CAD. Submaximal exercise, single-vessel disease, and moderate coronary stenosis (50% to 70%) lead to false-negative exercise echocardiographic results. The situations listed in Table 35.3 are appropriate indications for stress echocardiography. This method is portable, low-cost, and free of TABLE 35.7. Selected studies outlining the accuracy of exercise echocardiography Reference Armstrong et al.182 Crouse et al.183 Marwick et al.184 Quinones et al.185 Hecht et al.186 Beleslin et al.188 Roger et al.187 Marwick et al.189 Marwick et al.194 Luotolahti et al.190 Roger et al.191 Total No. of patients Sensitivity (%) Sensitivity for 1-VD (%) Sensitivity for MVD (%) Specificity (%) PPV (%) NPV (%) Overall accuracy (%) 123 228 150 112 180 136 127 161 147 118 340 88 97 84 74 93 88 88 80 71 94 78 81 92 79 59 84 88 — 75 63 94 — 93 100 96 89 100 91 — 85 80 93 — 86 64 86 88 86 82 72 81 91 70 41 97 90 95 96 95 97 93 71 85 97 79 61 87 63 51 79 50 60 91 81 50 40 88 89 85 78 91 88 — 81 82 92 69 1-VD, single vessel disease; MVD, multivessel disease; NPV, negative predictive value; PPV, positive predictive value. CAR035.indd 826 11/29/2006 3:33:11 PM 827 e c h o c a r d i o g r a p h i c e va l u a t i o n o f c o r o n a r y a r t e r y d i s e a s e ionizing radiation. It provides additional information regarding valvular, structural, and hemodynamic factors that affect patient management and outcome. In a review of 1223 stress echocardiograms, a significant Doppler abnormality was detected in 17% (moderate or greater MR, 5.5%; mild or greater aortic insufficiency, 13%).197 For patients able to exercise, the 2003 ACC/AHA task force on chronic stable angina gave a class I recommendation for the use of exercise echocardiography as an initial diagnostic test or riskstratification technique in patients with known or suspected CAD.34 The accuracy of stress echocardiography in identifying stenosis has consistently been greater in the LAD territory than in the RCA and LCx. The reported average sensitivity of exercise echocardiography for detecting coronary stenosis is 77% in the LAD, 75% in the RCA, and 49% in the circumflex artery.182,184,198,199 This may be related to the greater extent of the LAD circulation and the ease with which it may be imaged. Overlap of the RCA and LCx territories further limits discrimination between the two. Prognosis After Exercise Stress Echocardiography Electrocardiographic and echocardiographic variables contribute to the prognostic value of exercise echocardiography. The exercise variables, exercise duration, and ischemic STsegment depression remain important independent predictors of outcome when modeled with ventricular function at peak exercise.189 The extent and severity of exercise-induced LV dysfunction is the most important prognostic echocardiographic variable associated with ischemia.200–202 Patients with negative stress echocardiograms have low rates of cardiac events at 1 (1%) and 3 (3%) years of follow-up. Conversely, patients with abnormal stress echocardiograms (LVEF <50%; wall-motion score index >1.4) had significant adverse events.203 The negative predictive value of a normal exercise echocardiogram in patients with normal exercise tolerance is >99%.201,203–205 The ACC has reported that stress echocardiography is a useful adjunct to standard exercise testing and provides a more sensitive and specific means of detecting myocardial ischemia; the diagnostic accuracy is similar to that of nuclear technologies, but stress echocardiography can be performed at a considerably lower cost. Accuracy of Dobutamine Stress Echocardiography The accuracy of DSE depends on the degree of coronary stenosis and the extent of myocardial ischemia.206,207 Harmonic imaging and LV opacification with intravenous contrast agents improve endocardial definition and the accuracy of DSE.208,209 In a study of 283 patients with suspected CAD, the positive predictive value of DSE increased significantly as the extent and severity of induced wall-motion abnormality increased (more myocardium at risk). Furthermore, the sensitivity increased as a faster maximal heart rate was achieved (sensitivity: 67% with an MPHR of <75%, 71% with an MPHR of 75% to 85%, and 86% with an MPHR of >85%; p <.05).207 The sensitivity and specificity for detecting CAD with DSE mirror those of exercise echocardiography in multiple studies with a range of sensitivity reported from 70% to 96% and specificity range from 66% to 93% (Table 35.8).193,195,210–219 A review of 28 studies involving 2246 patients who underwent both DSE and coronary angiography reported that DSE had an overall sensitivity of 80%, a specificity of 84%, and an accuracy of 81%. Like exercise echocardiography, DSE was more accurate in detecting multiple-vessel than singlevessel CAD (Table 35.8).210 In a review of 120 studies involving 10,817 patients, DSE was more specific than SPECT myocardial perfusion imaging for the detection of obstructive coronary disease (Table 35.9).212 Prognosis with Dobutamine Stress Echocardiography Dobutamine stress echocardiography predicts the prognosis in patients with CAD. Development of a new or worsening wall-motion abnormality (ischemic response) occurred in 321 patients, and a fi xed wall-motion abnormality was identified in 237 of 860 patients referred for DSE either for diagnosis of suspected CAD (55%) or for risk stratification in patients with known CAD (45%).220 Adverse cardiac events (cardiac death and MI) occurred equally in both groups (14% and 13%, respectively) within 52 months of follow-up. The percentage of abnormal segments at peak stress, which incorporates the extent of myocardial dysfunction and the amount of jeopardized myocardium, predicted a higher risk of subsequent cardiac events (Fig. 35.19). Left ventricular dilatation at peak stress and a low ischemic threshold also increase TABLE 35.8. Selected studies outlining the accuracy of dobutamine echocardiography Author (Ref.) 217 Segar et al. Marcovitz et al.213 McNeill et al.214 Marwick et al.195 Previtali et al.216 Takeuchi et al.218 Dobutamine dose range (mg/kg/min) Total No. of patients Sensitivity (%) Sensitivity for 1-VD (%) Sensitivity for MVD (%) Specificity (%) PPV (%) NPV (%) Accuracy (%) 5–30 5–30 10–40 5–30 5–30 5–30 88 141 80 217 80 120 95 96 70 72 79 85 — 95 — 66 63 73 — 98 — 77 91 97 82 66 88 83 83 93 94 91 89 89 92 95 86 84 67 61 61 88 92 89 78 76 80 88 1-VD, single vessel disease; MVD, multivessel disease; NPV, negative predictive value; PPV, positive predictive value. CAR035.indd 827 11/29/2006 3:33:12 PM 828 chapter 35 TABLE 35.9. Weighted mean sensitivities, specificities of pharmacologic studies Pharmacologic test Adenosine echocardiography Adenosine SPECT Dipyridamole echocardiography Dipyridamole SPECT Dobutamine echocardiography* Dobutamine SPECT Total Studies Subjects Mean age (years) CAD (%) MI (%) Men (%) Sensitivity (%) Specificity (%) 6 9 20 21 40 14 516 1,207 1,835 1,464 4,097 1,066 65 63 56 60 59 58 73 80 67 71 70 66 31 17 15 31 26 9 71 59 72 77 66 63 72 (62–79) 90 (89–92) 70 (66–74) 89 (84–93) 80 (77–83) 82 (77–87) 91 (88–93) 75 (70–79) 93 (90–95) 65 (54–74) 84 (80–86) 75 (70–79) 120† 10,817† CAD, coronary artery disease; MI, myocardial infarction; SPECT, single photon emission computed tomography. * One dobutamine echocardiographic study not included here because only multivessel disease was examined. † Total number of tests and subjects exceeds the number of studies reviewed because some studies examined more than one pharmacologic test. adverse cardiac events.220 Conversely, patients with normal DSE results have low annual cardiovascular event rates. In a report of 1737 patients with known or suspected coronary heart disease (CHD),221 the annual event rate (cardiac death or MI) at 5-year follow-up was 1.2% when the study was normal. In a study of 301 patients unable to exercise, both DSE and dobutamine SPECT myocardial perfusion imaging were performed and outcomes were determined after 7 years of follow-up. The predictive value of both methods was equivalent. The annual cardiac mortality was 0.6% and 0.7%, and the annual cardiac event rates (death, MI, revascularization) were 3.3% and 3.6%, respectively, when the test was normal. With an abnormal test, the annual cardiac mortality was 2.8% and 2.6%, and the annual cardiac event rates were 6.9% and 6.5%, respectively.222 Risk Stratification After a Myocardial Infarction Dobutamine stress echocardiography has been successfully used for risk stratification of patients after an acute MI.223–225 In this setting, identification of viable and ischemic segments with DSE improves risk stratification beyond traditional clinical variables.226 In 123 patients with a previous MI, the diagnostic accuracy of exercise echocardiography for detecting significant coronary stenoses in infarct-related arteries was determined by comparison to quantitative coronary angiography performed within 2 weeks of stress echocardiography.227 Treadmill exercise echocardiography was Event-free probability, % 100 80 60 40 Normal Ischemia Infarction 20 0 % of segments abnormal at peak stress ≤25 26–50 51–100 0 10 20 30 40 20 30 40 Time, months Time, months No. at risk 860 774 641 235 40 860 774 641 235 40 FIGURE 35.19. Abnormalities on dobutamine stress echocardiography predict future adverse cardiac events. Left: Ischemia and fi xed wall motion abnormalities (infarction) by dobutamine stress echocardiography decrease cumulative cardiac event–free probability. Right: The percentage of abnormal segments at peak stress increases the risk of future cardiac events. CAR035.indd 828 0 highly sensitive (91%) regardless of infarct size but was less specific (59%) for detection of infarct-related coronary lesions.227 Assessment of Myocardial Viability Viable myocardium has been reported in up to 60% of dysfunctional myocardial segments in ischemic cardiomyopathy.228,229 Myocardial segments that are viable and poorly perfused should recover function after coronary revascularization. Careful selection of patients for revascularization is imperative, as the operative mortality for coronary artery bypass in patients with LV systolic dysfunction varies from 5% to 30% (increasing with age and worsening LV function).230 Furthermore, when performed in patients with significant global LV dysfunction but little viable myocardium, coronary bypass does not improve global systolic function.231,232 Dobutamine Stress Echocardiography in the Identification of Myocardial Viability Dobutamine stress echocardiography is the preferred echocardiographic method for the assessment of myocardial viability because inotropic stimulation is graded and imaging can be performed frequently. The DSE protocol for viability assessment differs from that used for the assessment of myocardial ischemia by including more images at lower dobutamine doses (Table 35.10). The goal is to identify any improvement in contractile reserve in patients with myocardial dysfunction, which may be transient in those with concomitant ischemia. Viable segments should demonstrate contractile reserve with inotropic stimulation, normal myocardial thickness, and evidence of some coronary perfusion and metabolism.233 The biphasic response—initial improvement in contractility followed by deterioration at higher doses—indicates viable and ischemic myocardium and is a 10 TABLE 35.10. Dobutamine stress protocol Ischemia Rest Pre-peak vs. 10 μg Peak > 88% MPHR Viability Rest 10 mcg 5 μg Peak > 88% MPHR MPHR, maximal predicted heart rate. 11/29/2006 3:33:12 PM 829 e c h o c a r d i o g r a p h i c e va l u a t i o n o f c o r o n a r y a r t e r y d i s e a s e 100 80 60 % 40 20 0 DE TI-RR TI-RI MIBI FDG 32 Studies (no.) 22 11 20 20 Patients (no.) 1090 557 301 488 598 Sensitivity p Specificity p FDG vs others <.05 DE vs others <.05 TI-RI vs DE, MIBI <.05 others vs TI-RI <.05 TI-RR vs DE <.05 MIBI vs TI-RR <.05 FIGURE 35.20. Techniques for the noninvasive assessment of myocardial viability; comparison of weighted sensitivities and specificities. Regional recovery of function after revascularization was the gold standard for viability. Open bars, sensitivity; solid bars, specificity. DE, dobutamine echo; FDG, fluorine-18 fluorodeoxyglucose; MIBI, technetium-99m sestamibi; Tl-RI, thallium-201 reinjection; Tl-RR, thallium-201 rest-redistribution. ization compared with medical therapy when viability was present, but there was no benefit when viability was absent (7.7% vs. 6.2%) (Fig. 35.21).246 Viability testing also predicts improvement in regional and global LV function after revascularization.246 However, the extent of viable myocardium required in order to expect improvement in the LVEF after revascularization may range from 25% to 30% of the left ventricle.247 Survival is lowest for patients with severe LV dysfunction and no evidence of viability (mortality, 20% at 18 months), which is independent of revascularization.234 New Echocardiographic Quantitative Parameters Abnormalities of radial wall thickening are visualized subjectively by traditional 2D echocardiography as new or induced RWMAs. Abnormalities of longitudinal deformation can be identified and quantified by TDI and can be assessed by tissue velocity and displacement, strain and strain rate imaging, and postsystolic shortening. Tissue Doppler imaging parameters have been shown to improve the accuracy of stress echocardiography in detecting myocardial ischemia and viability. Strain-Rate Imaging reliable predictor of functional recovery (Table 35.2). The value of DSE in the identification of myocardial viability and, therefore, in the selection of patients who may benefit from revascularization is well established. In a number of studies in which postrevascularization echocardiography has been used to assess LV functional recovery after catheterbased or surgical revascularization, the average sensitivity of DSE to predict functional recovery ranges from 74% to 88%, and the specificity is 73% to 87%.235–242 The positive predictive value is 81%, and negative predictive value is 87%. Comparative studies have shown a higher specificity and a lower sensitivity with DSE than with radionuclide techniques for the identification of functional recovery after the revascularization of dysfunctional myocardial segments (Fig. 35.20).242–244 The end-diastolic myocardial wall thickness obtained by routine echocardiography is a simple and valuable marker of viability.245 In a study of 45 patients with stable CAD and ventricular dysfunction, a myocardial thickness of ≤6 mm predicted poor recovery of function after revascularization. Apical segments were the most difficult to measure and accounted for nearly all of the immeasurable but dysfunctional segments (17%). A myocardial thickness of >6 mm had a sensitivity of 94% and a specificity of 48% for recovery of function. A combination of preserved wall thickness and evidence of contractile reserve during DSE improved the specificity of DSE to 77% and, thus, is a valuable adjunct to DSE in the assessment of myocardial viability. Prognosis: Viability and Potential Benefits of Revascularization Patients with viability and LV dysfunction have improved survival with revascularization compared to medical therapy. A meta-analysis of 24 nonrandomized studies involving 3088 patients (mean LVEF 32% ± 8%) revealed an 80% relative reduction in death (3.2% vs. 16%; p <.0001) with revascular- CAR035.indd 829 Strain-rate imaging provides objective quantification of segmental myocardial function by measuring myocardial deformation or the change in regional myocardial thickening and is relatively unaffected by adjacent tissue tethering or overall motion of the heart.248–250 Strain-rate imaging can enhance echocardiographic detection of ischemia and can differentiate viable from infarcted myocardium.12,15,18,251,252 Ischemia produces a delayed onset and termination of systolic shortening that is detectable with longitudinal strain and strain-rate imaging but not by 2D imaging. Evaluation of regional LV function by TDI velocities, using color Mmode analysis of segmental strain and strain rate, was performed in 44 patients undergoing traditional DSE.16 Ischemia was defined by concurrent pharmacologic SPECT myocardial perfusion imaging and stenosis confirmed by coronary –79.6% χ2 = 147 p<.0001 20 16.0 Death rate (%/yr) 234 15 23.0% χ2 = 1.43 p = .23 10 7.7 6.2 5 3.2 0 Viable Nonviable FIGURE 35.21. Survival following revascularization is increased in patients with evidence of myocardial viability. Without myocardial viability, there was no significant difference in survival between patients treated medically and those revascularized. Open bars, revascularization; solid bars, medical therapy. 11/29/2006 3:33:12 PM 830 chapter angiography. Qualitative assessment of strain and strain-rate curves was possible in 85% of segments. In normally perfused segments, the peak systolic strain rate increased with increasing dobutamine stimulation. Ischemic myocardial segments had significantly lower strain-rate increases and strain than did nonischemic segments. Compared with traditional DSE parameters, strain-rate imaging improved the sensitivity of DSE from 81% to 86% and the specificity from 82% to 90% (Fig. 35.22).16 With ischemia, the myocardium continues to thicken during the isovolumic relaxation period.251 This postsystolic shortening is a sensitive but nonspecific marker of ischemia that was found in 100% of ischemic segments but also in 47% of nonischemic segments in the study by Voight and coworkers.16 Postsystolic shortening is not easily identified by 2D imaging because of its relatively low amplitude and short duration.10 Strain-rate imaging allows quantification of postsystolic shortening, which is defined as the maximum change in segment length occurring between aortic valve closure and the regional onset of myocardial lengthening caused by early diastolic LV filling. In one study, the ratio of postsystolic shortening to maximal segment deformation was the best quantitative parameter for identifying stressinduced ischemia with DSE.16 Peak myocardial deformation detected by strain-rate imaging can differentiate active myocardial motion from passive or translational cardiac motion in both animals and humans with nontransmural (viable) and transmural infarcted (scarred) myocardium. This method also allows noninvasive determination of the extent of nonviable infarcted myocardium.252,253 Myocardial viability assessment with DSE was improved by the addition of strain-rate imaging in 55 patients with MIs followed by percutaneous or surgical revascularization.254 The inclusion of regional strain-rate imaging with routine visual wall-motion scoring identified patients with significant myocardial viability (an improvement in more 100 sensitivity [%] 89 80 81 82 specificity 86 60 40 20 0 2D-gray SRI FIGURE 35.22. Strain-rate imaging (SRI-CMM) improves the sensitivity and specificity of conventional two-dimensional imaging (2D-gray) during dobutamine stress echocardiography (DSE). CAR035.indd 830 35 than four myocardial segments or an overall increase of >5% in the LVEF after revascularization) and increased the sensitivity of DSE from 73% to 83% without changing the specificity. In a separate study,255 tissue Doppler echocardiography with strain-rate imaging without DSE differentiated transmural from nontransmural MIs in 47 consecutive patients with a first acute MI compared to 60 age-matched healthy volunteers. The peak systolic strain rate (>−0.59 s−1) had a high sensitivity (90.9%) and specificity (96.4%) in identifying transmural infarctions. A peak strain rate between −0.98 s−1 and −1.26 s−1 had a sensitivity of 81.3% and a specificity of 83.3% in distinguishing subendocardial infarctions. The peak strain rate was significantly lower in segments with transmural infarctions identified with contrast magnetic resonance imaging compared to normal myocardium or segments with a nontransmural infarction (both p <.0005).255 Perfusion Imaging Myocardial contrast echocardiography (MCE) is an evolving technique for the evaluation of myocardial perfusion. Intravenous injection of gas-filled microbubbles scatters ultrasound and can be used to define LV endocardial borders and myocardial blood flow. Steady-state microbubbles within the myocardium can be destroyed with high-energy ultrasound pulses, and the rate of microbubble reappearance approximates myocardial blood flow. Improvements in bubble size (<10 μm to allow transcapillary migration), as well as echocardiographic imaging techniques to enhance detection (harmonic imaging)256 and enhance the durability of the microbubbles (triggered imaging)257 with a low mechanical index258 have greatly improved the potential clinical applicability of this technique.259,260 Compared to other modalities of coronary perfusion, MCE has shown progressive improvements in accuracy. Specificities range from 78% to 95%, but sensitivities for the detection of moderate to severe perfusion defects have been low (14% to 65%).261,262 A higher number of falsely abnormal results in the circumflex territory have been reported.263 Myocardial contrast echocardiography has been shown to be accurate in detecting flow-limiting CAD in patients with suspected CAD and in those undergoing vasodilator stress testing after an acute MI.264–266 This method may enhance the predictive value of standard, exercise, and dobutamine echocardiography. The addition of perfusion imaging has been shown to improve the sensitivity of routine echocardiography for diagnosing myocardial ischemia in patients with suspected cardiac chest discomfort and nondiagnostic electrocardiographic abnormalities.256 The combination of perfusion defects and wall-motion abnormalities with exercise improved the sensitivity, specificity, and accuracy to 86%, 88%, and 86%, respectively, for establishing the presence of CAD on angiography.267 Abnormal myocardial perfusion imaging during vasodilator stress (dobutamine) echocardiography in 788 patients contributed significantly to the predictive value of clinical risk factors, resting systolic LV function, and RWMAs. Eventfree survival at 3 years decreased from 95% with normal wall motion and normal perfusion to 82% when perfusion was abnormal and 68% when both wall motion and perfusion were abnormal. Multivessel perfusion defects predicted the worst outcomes.268 11/29/2006 3:33:12 PM e c h o c a r d i o g r a p h i c e va l u a t i o n o f c o r o n a r y a r t e r y d i s e a s e FIGURE 35.23. Perfusion imaging with myocardial contrast echocardiography demonstrates myocardial blood flow in viable myocardial segments and may be useful to discriminate coronary arterial obstruction as a cause of congestive heart failure. Apical four– chamber view at rest (left) in a patient with acute congestive heart failure and LV dysfunction (LVEF, 42%) demonstrating normal myocardial perfusion at rest (5 seconds after myocardial contrast destruction). Right: After dipyridamole stress, four-chamber view displayed 3 seconds after myocardial contrast destruction. Note perfusion defect in the septum, apex, and lateral wall. LAD and LCx flow limiting stenoses were confi rmed by coronary angiography. Perfusion imaging may help differentiate CAD from other etiologies in patients with congestive heart failure and severe LV dysfunction. In 55 patients with acute congestive heart failure, identification of CAD as the etiology was facilitated by MCE at rest and after dipyridamole stress. Compared to patients without CAD and to normal control subjects, patients with CAD had a reduced myocardial blood flow velocity reserve in vascular territories supplied by vessels with >50% obstruction. In this population, MCE was the only independent predictor of CAD among clinical, electrocardiographic, biochemical, and resting echocardiographic variables (Fig. 35.23).269 Myocardial contrast echocardiography may provide an added benefit to dobutamine echocardiography in the evaluation of myocardial viability. The demonstration of specific patterns of contrast within dysfunctional myocardial segments may discriminate viable from nonviable myocardium.270 References 1. Hatle L, Sutherland GR. 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