3 echocardiographic evaluation of coronary artery...

811

Echocardiographic Evaluation of Coronary

Artery DiseaseStephanie A. Coulter

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 uti-lized cardiac testing modality. The diagnosis of CAD by echocardiography is based on the concept that acute myocar-dial ischemia or infarction produces a detectable impairment in regional left ventricular (LV) mechanical function. Identi-fi cation of patients with suspected CAD and acute coronary syndrome is one of the primary indications for echocardiog-raphy. Assessment of global LV systolic function and detec-tion of the presence and extent of regional myocardial dysfunction are routine clinical indications for echocardiog-raphy. This method also has an important prognostic value in patients with acute and chronic CAD. When combined with exercise or pharmacologic stress testing, echocardiog-raphy can identify patients with myocardial ischemia and viability. Because echocardiography can provide a compre-hensive assessment of cardiac structure, function and possi-bly 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 wall-motion 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 specifi c for myocardial ischemia than is the detection of a resting RWMA2–5 because cardiac rotation, translational motion during contraction of border-ing segments, and loading conditions affect the latter fi nding. An RWMA is not specifi c for coronary ischemia and also occurs with a previous MI, a previous sternotomy, myocar-ditis, cardiomyopathies, left bundle branch block, and preexcitation.

The American Association of Echocardiography rec-ommends 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 state-ment 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 end-diastole. 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 myocar-dium not bordered by the ventricular cavity.

35

Measurement of Regional Myocardial Function . . . . . . 811Assessment of Coronary Ischemia/Acute Myocardial

Infarction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 813Location of Acute Myocardial Infarction . . . . . . . . . . . . 814Extent of Acute Myocardial Infarction . . . . . . . . . . . . . . 815Acute Complications of Acute Myocardial

Infarction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 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

C

CAR035.indd 811CAR035.indd 811 11/29/2006 3:33:06 PM11/29/2006 3:33:06 PM

812 c h a p t e r 35

Four chamberApical cap

Apicallateral

Midanterolateral

Basalanterolateral

Basalinferoseptum

ApicalseptumMid

inferoseptum

Two chamberApical cap

ApicalinferiorMid

inferior

Basalinferior

Apicalanterior

Midanterior

Basalanterior

Long axisApical cap

Apicallateral

Midinferolateral

Basalinferolateral Basal

anteroseptum

Midanteroseptum

Apicalanterior

Anterior AnteriorAnterior

Base Mid Apex

Antero-septum

Antero-septum

Infero-septum

Infero-septum

Interior InteriorInterior

Infero-lateral

Infero-lateral

Antero-lateral

Antero-lateral

LateralSeptal

1 2

45

6

2

1

3

3

4 5 6

1. basal anterior 7. mid anterior

Left ventricular segmentation

8. mid anteroseptal2. basal anteroseptal3. basal inferoseptal 9. mid inferoseptal4. basal inferior5. basal inferolateral6. basal anterolateral

10. mid inferior11. mid inferolateral12. mid anterolateral

17. apex16. apical lateral15. apical anferior

13. apical anterior

4

5

11

10

1593

28

14 17 16

13 126

7

1

14. apical septal

ommended a four-point wall-motion scoring system,8,9 but the American Society of Echocardiography (ASE) recently continued to advocate a fi ve-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) echocardiogra-phy, 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.

Regional Myocardial Doppler Velocities

Differentiation of passive motion from active myocardial shortening or thickening is limited by the temporal resolu-tion (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 ex-cludes the high-frequency velocities of the rapidly moving blood. Assessment of peak regional myocardial velocities with TDI techniques can be achieved in simultaneous seg-ments 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 attrib-uted to the complexity of myofi ber orientation, which creates motion in three dimensions: longitudinal shortening (base > middle > apex), radial thickening (all segments), and circum-ferential 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 myocar-dial function from TDI velocity data, which theoretically is

FIGURE 35.1. Analysis of wall motion. The left ventricle (LV) can be divided into 17 segments and identifi ed 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 leafl ets); 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 opacifi cation 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.

FIGURE 35.2. Display, on a circumferential polar plot, of the 17 myocardial segments and the recommended nomenclature for tomographic imaging of the heart.

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; hypo-kinesis, 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 evalu-ation of regional wall motion.5,7 Previous authors have rec-


e c ho c a r dio g r a p h ic e va luat ion of c oron a ry a rt e ry di s e a s e 813

not confounded by translational movement or tethering.17 Strain rates refl ect the speed of regional myocardial longitu-dinal 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 circumferen-tial 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 quantifi ed.13

Myocardial Performance Index

The myocardial performance index (MPI) provides a nonin-vasive, 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 mea-surements.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 relax-ation 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

size and reduced baseline LV systolic function. The MPI was also identifi ed 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 refl ected the LV contractile state during low-dose DSE.23 The MPI may refl ect the overall LV functional reserve.

Unfortunately, systolic wall motion and thickening is often diffi cult to detect and quantify. Doppler techniques lack clinical applicability, and determining the myocardial performance index is time-consuming. Therefore, 2D gray-scale 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 fl ows.25 Regional wall-motion 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

TABLE 35.1. 1. Wall motion score

Score Wall motion Defi nition

1 Normal/hyperkinesis Normal systolic motion and thickening2 Hypokinesis Reduced systolic motion or thickening3 Akinesis Absent inward systolic motion or thickening4 Dyskinesis Paradoxic (“bulging”) or outward motion5 Aneurysmal Diastolic deformation

Each segment should be analyzed and individually scored according to its systolic motion and thickening. Confi rma-tion should be made with multiple views.

Four chamber1

Base

RCALAD

Cx

RCA or Cx

LAD or Cx

RCA or LAD

4 Mid5 Apex6

Two chamber2 Long axis3

FIGURE 35.3. Typical distri-butions of the right coronary artery (RCA), the left anterior descending (LAD), and the circumfl ex (Cx) coronary arteries. The arterial distribu-tion varies between patients. Some segments have variable coronary perfusion.


814 c h a p t e r 35

by balloon infl ation during angioplasty and may last for up to several days with prolonged ischemia.26,27 These abnor-malities precede the development of electrocardiographic irregularities and the onset of cardiac symptoms. Figure 35.4 illustrates the cascade from myocardial ischemia to infarc-tion. 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 suffi -ciently 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 thin-ning suggests a previous ischemic event. For diagnosing acute coronary ischemia, echocardiography has a high sensi-tivity but a low specifi city.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 speci-fi city 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 signifi cantly 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 co-ronary 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)

risk score and the ability of RWMAs to predict cardiac events (Fig. 35.5).32

Because early detection of RWMAs adds signifi cant diag-nostic and prognostic value to the routine evaluation of patients who present to the emergency department with sus-pected 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 ven-tricular 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 accu-rately detects and identifi es the anatomic location of MIs.36–39 Two-dimensional echocardiography is less precise (sensitiv-ity, 60% to 75%) in detecting nontransmural MIs, presum-ably 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 coro-nary artery, especially if the obstruction involves the left anterior descending (LAD) or posterior descending coronary arteries.42

Perfusiondeficits

Metabolicabnormalities

Wall motionabnormalities

ECG changes

Global LV dysfunction

Stunning/Hibernation

Necrosis MI

Chest pain

Elevation ofLVEDP (SOB)

Resting flow reduction

Rest

Exercise time

Wor

kloa

d (H

RxB

P)

FIGURE 35.4. Ischemic cascade. Schematic representation of the clinical, electrocardiographic, and echocardiographic manifesta-tions of myocardial ischemia as the workload (rate-pressure product) and duration of stress is increased. SOB, shortness of breath.

1.0

0.8

0.6

0.4

0.2

0.0

0 2 4 6 8 10 12Months of follow-up

Eve

nt-

free

su

rviv

al

14 16 18 20

Abnormal RF,Abnormal MP

Abnormal RF,Normal MP

Normal RF,Normal MP

22 24

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 mod-ifi ed Thrombolysis in Myocardial Infarction (TIMI) score (3 or 4). MP, myocardial perfusion; RF, regional left ventricular function.



Left anterior descending artery obstruction creates severe wall-motion abnormalities (akinesis with complete obstruc-tion) of the septum, anterior wall, and apex. These segments are best visualized from the parasternal long-axis (anterosep-tum), and apical four- (septum and apex) and two-chamber (anterior wall and apex) views. The location of the obstruc-tion 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 circumfl ex 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 fl ow 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, infarc-tion of the right ventricle may result (see below). The poste-rior descending artery, a branch of the RCA (right dominant system) in 80% of patients, supplies the bulk of coronary fl ow to the inferior wall. Right coronary artery occlusion usually spares the apex. Two-dimensional imaging in the short-axis, basal, and midventricular views, confi rmed by the apical two-chamber view, best reveals inferior wall-motion abnormalities resulting from RCA occlusion. Careful attention to right ventricle (RV) size and function are impor-tant with acute inferior wall infarction.

Bypass grafts and collateral blood fl ow will blur these generalizations. A common post-bypass RWMA pattern in-cludes 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).

Extent of Acute Myocardial Infarction

Cardiac enzymes and electrocardiography are crude indica-tors of infarct size and location.42 Validation studies with thallium-201 scintigraphy, pyrophosphate (99mTc-PYP) scin-tigraphy, serum creatine kinase–MB levels, and coronary arteriography have shown that 2D echocardiography accu-rately detects and identifi es the anatomic location of MIs.36,37,43,44 The location of RWMAs correlates with the dis-tribution of the occluded coronary artery, especially if the obstruction involves the LAD or posterior descending coro-nary arteries.42

In postinfarct patients, LV systolic function is routinely measured by the LV ejection fraction (LVEF) on 2D echocar-diography. The extent of the infarction can be quantifi ed with the wall-motion score index. Echocardiography overes-timates the infarct size in the presence of a previous infarc-tion 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

patients following revascularization for MI serial echocar-diographic studies in 58% showed complete or partial recov-ery 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 sen-sitivity 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/effi cacy) 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 com-plication 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 echocardiogra-phy and pulsed-wave and color-fl ow Doppler imaging provide a comprehensive assessment of the anatomic and hemody-namic status at the bedside and therefore are recommended for patients with hemodynamic deterioration.

Cardiac Rupture

Free-Wall Rupture

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 fi rst MIs associated with poor collateral blood fl ow,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 signifi cantly 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


816 c h a p t e r 35

reperfusion was achieved within 12 hours, 0.9% when reper-fusion 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 sud-denly, within 3 days following an acute MI in 50% of patients. In these cases, sudden chest discomfort, with rapidly progres-sive cardiogenic shock related to hemopericardium and tam-ponade, are followed by electromechanical dissociation67 and death. Rapid 2D echocardiography identifi es a pericardial effusion and confi rms 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 dis-section is more gradual or incomplete and produces the char-acteristic echocardiographic fi nding of a pseudoaneurysm, or false aneurysm. An LV pseudoaneurysm results from a local-ized rupture of the ventricular free wall, which produces a localized hemopericardium that is limited by parietal peri-cardium and by blood clot formation. There is an absence of heart muscle in the wall of a false aneurysm. Although ven-tricular 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 lac-eration.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 diffi cult. In a large series of pseudoaneurysms,69 abnormalities were present on the 2D or Doppler echocardiograms of approxi-mately 85% to 90% of patients, but a defi nitive diagnosis was made in only about 25%. In suspected cases, coronary angi-ography provides a defi nitive diagnosis in 87% of patients.69 Transesophageal echocardiography may improve the diag-nostic accuracy but has not been studied in this regard. Two-dimensional echocardiography can detect discontinuity of the ventricular free wall and confi rm 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-fl ow Doppler imaging shows characteristic bidirectional fl ow 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 com-plicate 1% to 3% of acute ST-elevation MIs.72 Ventricular

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 Arter-ies trial (GUSTO-I).74 Usually occurring within the fi rst 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 acceler-ates rupture when reperfusion fails. The median time from the onset of symptoms to the development of an interven-tricular 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 resis-tance. In this clinical setting, Doppler echocardiography is usually diagnostic, its sensitivity and specifi city 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-fl ow Doppler imaging77 has been shown to enhance the diagnostic accuracy up to 100% by defi ning the site of septal rupture as an area of turbulent transseptal fl ow or by detect-ing 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 fl ow across the pulmonary valve and the LV outfl ow tract, pro-vided that no valvular regurgitation is present. Contrast 2D echocardiography can also identify a VSD. Thus, 2D echo-cardiography and color-fl ow 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 fi ndings are not specifi c for RV infarction, and they com-monly occur with acute and chronic pulmonary hyperten-



A B

CFIGURE 35.6. Ventricular septal defect (VSD). (A) Apical VSD (arrow) is identifi ed by the dropout of interventricular septum visu-alized by two-dimensional echocardiography. Color Doppler dem-onstrates 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 migra-tion of blue color toward the base of the right ventricle (RV) (opposite

direction of RV infl ow). (C) Spectral Doppler identifi es 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 ven-tricle; 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.

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

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 fi vefold higher prevalence of thrombus formation than did patients with other infarct locations (11.5% vs. 2.3%, respec-tively). Worsening LV function and more extensive regional dysfunction are also recognized risk factors for LV throm-bus.85 Most thrombi occur within the fi rst 2 weeks (median, 5 to 6 days) after an acute MI.86,87 However, with worsening LV function, new LV thrombus is identifi ed in some patients after hospital discharge.87,88


818 c h a p t e r 35

A B

CFIGURE 35.7. Right ventricular infarction. The manifestations of right ventricular (RV) infarction can be identifi ed by echocardiogra-phy and include RV dilatation (*), hypokinesis of the RV free wall (arrows), and evidence of elevated right atrial pressure; dilated right

atrium (RA*) (A), or plethoric inferior vena cava (IVC*, arrow) (B). Left ventricular inferior wall motion abnormality (arrows) should also be present (C).

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 lami-nar 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 echocar-diography has a sensitivity of 75% to 95% and a specifi city of 87 to 90%,90,91,93 and therefore is the method of choice. When the apex is poorly visualized with transthoracic echo-cardiography, administration of a contrast agent may help identify suspected apical thrombus by demonstrating an absence of contrast in an LV cavity fi lled 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

FIGURE 35.8. Left ventricular mural thrombus. Two-dimensional imaging in the apical four-chamber view demonstrates an echolu-cency 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.



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 ven-tricular 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 com-plication 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 circum-fl ex 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 fl ail mitral leafl et with attachment of the mobile severed papil-lary 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 confi rmed cases, the partially ruptured papillary muscle cannot be observed to prolapse into the left atrium on transthoracic echocardiog-raphy 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

long-axis and mid-esophageal four-chamber views can detect the origin of the regurgitant jet and clarify the anatomic profi le 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 struc-ture 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 fl ash 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 car-diogenic shock.111 However, angiographic detection of moder-ate-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 leafl ets, 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

A BFIGURE 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

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.


8 2 0 c h a p t e r 35

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 anesthe-sia.120–122 MR is also likely underestimated by resting echo-cardiography in patients with LV dysfunction and symptoms of congestive heart failure in the absence of active isch-emia.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 orifi ce 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

Ventricular Aneurysm

After an acute, usually anterior, MI,95,126 a true LV aneurysm develops in up to 20% of patients, owing to gradual expan-sion and thinning of all three layers of the infarcted myocar-dium.127 The incidence of true LV aneurysm has decreased as reperfusion therapies have improved and become wide-spread.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.

Ischemic mitral regurgitation:

incomplete mitral leaflet closure

Normal

LV

closing

force

Tethering

force

AOMR

LA

Ischemic

Papillary

muscle

displacement

Mitral valve

tethering

Restricted

closure

FIGURE 35.10. Mechanism of ischemic mitral regurgitation. Left: The balance of forces acting on the mitral leafl ets in systole. LA, left atrium, LV, left ventricle, AO, aorta. Right: Effect of papillary muscle displacement and mitral leafl et tethering to restrict mitral leafl et closure. MR, mitral regurgitation.

FIGURE 35.11. Illustration of ischemic mitral regurgitation. Two-dimensional imaging in the parasternal long axis view demonstrates apical tethering of the chordae tendineae (left, arrow) and the resul-tant jet of mitral regurgitation (right) caused by the incomplete mitral leafl et closure.

A BFIGURE 35.12. Left ventricular aneurysm (LVA). (A) Two-dimen-sional 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-

mal segment. (B) Two-dimensional imaging of the two-chamber view identifi es 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.


e c ho c a r dio g r a p h ic e va luat ion of c oron a ry a rt e ry di s e a s e 8 21

Two-dimensional echocardiography has a sensitivity of >93%129 and a specifi city of 94% in the detection of LV aneu-rysm. The characteristic echocardiographic fi nding is a thin LV wall that fails to thicken during systolic contrac-tion, producing a “bulge” during systole and diastole.127,130 A common fi nding is a hinge point (Fig. 35.12A), or junction, between contractile LV tissue and the akinetic, often para-doxic, 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 fl ow profi le with a “swirling” motion characteristic of low cardiac fl ow within the aneurysm. Thrombus within the aneurys-mal 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 fi brous tissue and calcium in the aneurysmal segment over time prevents rupture of a chronic LVA, unlike a pseudoaneu-rysm.134,135 Left ventricular aneurysms contribute to chronic cardiac decompensation with congestive heart failure, ven-tricular 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 effi cacy 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 associ-ated with an improved surgical outcome, whereas a frac-tional shortening of ≥17% entailed no subsequent clinical or surgical improvement.

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 dysfunc-tion (infarct size),139,140 function of the remaining segments, neurohormonal activation, and presence of coexisting valvu-lar heart disease, particularly MR, will determine the mag-nitude of LV remodeling.105 This process usually begins within the fi rst 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 expan-sion 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 refl ected in the poor survival of post-MI patients in whom both signifi cant 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,

and volume at end-diastole and end-systole and should also include Doppler estimation and quantifi cation 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 resid-ual 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 specifi city 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 complica-tions 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 car-diogenic shock. Survival at 1 year was 24% in those with an

1.0

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2/3/4 MR, LVEF <28%

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0/1 MR, LVEF ≥28%

0/1 MR, LVEF <28%

8 10 12

FIGURE 35.13. Survival following myocardial infarction is depen-dent on both left ventricular ejection fraction (LVEF) and the sever-ity 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.


8 2 2 c h a p t e r 35

LVEF of <28% versus 56% for those with a higher LVEF.111 In the setting of acute coronary syndrome, LV systolic dysfunc-tion increases the long-term mortality and increases the probability of having multivessel CAD by 50%.154

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

Left Ventricular Remodeling

Left ventricular remodeling can be characterized and quanti-fi ed 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 Sur-vival 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 inde-pendent 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 inde-pendent of treatment with angiotensin-converting-enzyme inhibitors (Fig. 35.16A). Survival correlated with the severity

0

2

4

6

8

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15

N = 630 162 355 604 835 611

No studywithin 14 days

<30%

30–39%40–49%

Total = 3197

50–59% ≥60%

30Resting ejection fraction (%)

Mor

talit

y (%

)

45 60 75

FIGURE 35.14. Left ventricular systolic function predicts mortality after myocardial infarction. Relation of rest ejection fraction to all-cause 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. Mor-tality rate is highest in patients with ejection fraction <30% (9.9%).

FIGURE 35.16. (A) Mitral regurgitation (MR) worsens survival after myocardial infarction. Kaplan-Meier curves of cardiovascular sur-vival 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 quantifi ed by effec-tive regurgitant orifi ce area (EROA); mild if EROA <20 mm2 and moderate or greater when EROA ≥20 mm2. Numbers at bottom indi-cate patients at risk each interval.

RV Dysfunction n = 79

15001000

Days

5000

0

25

50

Sur

viva

l (%

)

75

100

HR = 3.2 (2.0–5.1) p <.0001

No RV Dysfunction n = 337

FIGURE 35.15. Right ventricular dysfunction following myocar-dial 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.


e c ho c a r dio g r a p h ic e va luat ion of c oron a ry a rt e ry di s e a s e 8 2 3

of MR quantifi ed as effective regurgitant orifi ce 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.

Elevated Left Ventricular Filling Pressures

Elevated LV fi lling 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 fi lling pressures may be characterized echocardiographically as a shortened deceleration time (DT) of mitral early infl ow velocity (DT <150 ms), an increased ratio of early (E) to late (A) LV diastolic fi lling velocities (mitral infl ow E/A >2), and pulmonary venous diastolic fl ow predominance. Additionally, the LA volume, when indexed to body surface area (>28 mL/m2), refl ects the severity and duration of elevated LV fi lling pressures and is a powerful

predictor of survival after an acute MI.165 Measurements uti-lizing TDI have provided incremental prognostic informa-tion in patients with CAD or congestive heart failure.166–168 After an acute MI, the ratio of the early diastolic mitral fi lling 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 myo-cardial ischemia, to risk-stratify patients with known CAD, and to assess myocardial viability in regions of myocardial dysfunction.

Basic Principles and Defi nitions

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 identifi ed when it contracts normally. The discrimination of dysfunc-tional, but living, myocardium from necrotic tissue is the more common and clinically relevant description of viabil-ity. 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

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Follow time (months)0 10 20 30 40

Follow time (months)

6 12 18 24

E/e’ > 15

E/e’ ≤15

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 demon-strates 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 veloc-ity (B) and mitral annulus systolic velocity (C).


8 2 4 c h a p t e r 35

recovery.169 Severe regional LV dysfunction, leading to depres-sion of LV systolic function in patients with CAD, can result from myocardial necrosis, postischemic stunning, or myo-cardial hibernation. “Stunning” refers to contractile dys-function in viable myocardium as a result of transient ischemia followed by reperfusion.12 “Hibernating” myocar-dium refers to myocardial tissue that is persistently hypo-contractile 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.

Interpretation

A new RWMA provoked by stress indicates cardiac ischemia. Improved contractility of myocardial segments with abnor-mal baseline function on inotropic stimulation is character-istic 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.

Methodology

Analysis of stress echocardiograms is predominantly based on qualitative comparison of regional wall motion at base-line 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 myo-cardial 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

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 defi ne 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 wall-motion abnormalities at various stress stages. Because accu-racy of image interpretation remains subjective, physician experience is a major determinant of the accuracy of stress echocardiography.172

Treadmill Stress Echocardiography

Exercise protocols generally consist of either treadmill exer-cise 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 four-chamber, and apical two-chamber. Exercise is performed according to a standard exercise protocol, and the heart rate, blood pressure, and electrocardiogram are monitored through-out the test at each stage of exercise (Table 35.4). Only postex-ercise imaging is available with treadmill exercise. Therefore, rapid acquisition (within 60 to 90 seconds) of postexercise

TABLE 35.2. Myocardial segment response to stress

Resting Stress

Likelihood ofsegment function Exercise Low dose Peak dose Interpretation functional recovering

Normal ↑ ↑ ↑↑ Normal n/aNormal ↓ ↑ ↓ Ischemic n/aAbnormal* ↑ ↓ Ischemic and viable High “Biphasic”Abnormal ↓ ↓ ↓ Ischemic, viable ModerateAbnormal ↑ ↑ ↑↑ Nonischemic, viable LowAbnormal No change No change No change Nonviable, scar Low

* Viability assessment requires graded stress with image acquisition at multiple stages. Treadmill echo is not recommended for the assessment of viability.

TABLE 35.3. Selection of stress echocardiography protocols for clinical decision making

Stress echo protocol

Clinical indication TME Bike Dobutamine

Chest pain + + ±Post-MI + + +Viability − ± + +Dyspnea + + ± MR + + +Valve disease MS + + + AS + + + AI + +Pulmonary artery pressure − + + −Preop risk assessment ± ± +

AI, aortic insuffi ciency; AS, aortic stenosis; MI, myocardial infarction; MR, mitral regurgitation; MS, mitral stenosis; TME, treadmill stress echocardiography.



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 in-formation 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 moni-tored 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 fi nd 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

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 affi nity for the different recep-tors, 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 reach-ing 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 phar-macologic stress testing is diagnostic or prognostic. Hypo-tension during DSE may be related to (1) decreased systemic vascular resistance associated with a β2-agonist response; (2) LV outfl ow tract (LVOT) obstruction produced by systolic anterior motion of the mitral valve associated with increas-ing 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 syn-dromes (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

TABLE 35.4. Exercise echocardiography protocols

Immediate (<1 min) Baseline images postexerciseProtocols ± Doppler Exercise imaging imaging Advantages Limitations

Treadmill ✓ ✗ ✓ High workload Imaging only postexercise Widely available Exercise itself is prognostic: Duration ECG SymptomsBike ✓ ✓ ✓ Images during exercise Lower workload Diffi cult for patient

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Atropine 0.5–1 mg as needed to achieve85% MPHR at peak dobutamine dose

Hand grip exercise may also be utilized toincrease heart rate at peak dose

FIGURE 35.18. Dobutamine stress echocardiography (DSE) protocol.

TABLE 35.5. Dobutamine stress echocardiography

Indications Contraindications

Patient unable to exercise Unstable coronary syndromeGraded stress imaging Severe arrhythmiaIdentifi cation of viability Severe hypertension Severe aortic stenosis Aortic aneurysm or dissection Resting left ventricular outfl ow tract (LVOT) obstruction


8 2 6 c h a p t e r 35

develops in two or more segments. Development of a signifi -cant arrhythmia, LVOT obstruction of >4 m/s, or signifi cant 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 dobu-tamine 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.

Stress Echocardiography for Detection of Myocardial Ischemia

Accuracy of Exercise Stress Echocardiography

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 steno-ses >50% ranged from 71% to 97%.172,182–191 In a literature review, 44 articles met the criteria for determining the sen-sitivity and specifi city of exercise echocardiography and exercise myocardial perfusion imaging with single photon emission computed tomography (SPECT) compared to coro-nary 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 sig-nifi cantly greater specifi city (77% vs. 64%). Both tests per-formed better than standard exercise testing, for which a sensitivity of 68% and a specifi city of 77% have been reported.193 The sensitivity of exercise echocardiography was better for the detection of multivessel disease than single-vessel 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 infl uence 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-nega-tive exercise echo cardiographic results. The situations listed in Table 35.3 are appropriate indications for stress echocar-diography. This method is portable, low-cost, and free of

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 fi brillation with rapid response Supraventricular tachycardia LVOT obstruction (>4 m/s) Abnormal blood pressure ≥230/120 SBP ≤80 Intolerable dobutamine reaction Anxiety, nausea, headache

TABLE 35.7. Selected studies outlining the accuracy of exercise echocardiography

Total No. Sensitivity Sensitivity OverallReference of patients Sensitivity (%) for 1-VD (%) for MVD (%) Specifi city (%) PPV (%) NPV (%) accuracy (%)

Armstrong et al.182 123 88 81 93 86 97 61 88Crouse et al.183 228 97 92 100 64 90 87 89Marwick et al.184 150 84 79 96 86 95 63 85Quinones et al.185 112 74 59 89 88 96 51 78Hecht et al.186 180 93 84 100 86 95 79 91Beleslin et al.188 136 88 88 91 82 97 50 88Roger et al.187 127 88 — — 72 93 60 —Marwick et al.189 161 80 75 85 81 71 91 81Marwick et al.194 147 71 63 80 91 85 81 82Luotolahti et al.190 118 94 94 93 70 97 50 92Roger et al.191 340 78 — — 41 79 40 69

1-VD, single vessel disease; MVD, multivessel disease; NPV, negative predictive value; PPV, positive predictive value.



ionizing radiation. It provides additional information regard-ing valvular, structural, and hemodynamic factors that affect patient management and outcome. In a review of 1223 stress echocardiograms, a signifi cant Doppler abnormality was detected in 17% (moderate or greater MR, 5.5%; mild or greater aortic insuffi ciency, 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 risk-stratifi cation technique in patients with known or sus-pected 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 circum-fl ex 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 con-tribute to the prognostic value of exercise echocardiography. The exercise variables, exercise duration, and ischemic ST-segment 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 isch-emia.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 echo-cardiograms (LVEF <50%; wall-motion score index >1.4) had signifi cant 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 specifi c 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 ste-nosis and the extent of myocardial ischemia.206,207 Harmonic imaging and LV opacifi cation with intravenous contrast agents improve endocardial defi nition and the accuracy of DSE.208,209 In a study of 283 patients with suspected CAD, the positive predictive value of DSE increased signifi cantly as the extent and severity of induced wall-motion abnormality increased (more myocardium at risk). Furthermore, the sensi-tivity 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 specifi city for detecting CAD with DSE mirror those of exercise echocardiography in multiple studies with a range of sensitivity reported from 70% to 96% and specifi city 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 specifi city of 84%, and an accuracy of 81%. Like exercise echocardiography, DSE was more accurate in detecting multiple-vessel than single-vessel CAD (Table 35.8).210 In a review of 120 studies involv-ing 10,817 patients, DSE was more specifi c than SPECT myocardial perfusion imaging for the detection of obstruc-tive 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 iden-tifi ed in 237 of 860 patients referred for DSE either for diag-nosis of suspected CAD (55%) or for risk stratifi cation 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 incor-porates the extent of myocardial dysfunction and the amount of jeopardized myocardium, predicted a higher risk of subse-quent 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

Dobutamine dose range Total No. Sensitivity Sensitivity Sensitivity Specifi cityAuthor (Ref.) (mg/kg/min) of patients (%) for 1-VD (%) for MVD (%) (%) PPV (%) NPV (%) Accuracy (%)

Segar et al.217 5–30 88 95 — — 82 94 86 92Marcovitz et al.213 5–30 141 96 95 98 66 91 84 89McNeill et al.214 10–40 80 70 — — 88 89 67 78Marwick et al.195 5–30 217 72 66 77 83 89 61 76Previtali et al.216 5–30 80 79 63 91 83 92 61 80Takeuchi et al.218 5–30 120 85 73 97 93 95 88 88

1-VD, single vessel disease; MVD, multivessel disease; NPV, negative predictive value; PPV, positive predictive value.


8 2 8 c h a p t e r 35

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 equiv-alent. 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 Stratifi cation After a Myocardial Infarction

Dobutamine stress echocardiography has been successfully used for risk stratifi cation of patients after an acute MI.223–225 In this setting, identifi cation of viable and ischemic seg-ments with DSE improves risk stratifi cation beyond tradi-tional clinical variables.226 In 123 patients with a previous MI, the diagnostic accuracy of exercise echocardiography for detecting signifi cant coronary stenoses in infarct-related arteries was determined by comparison to quantitative coro-nary angiography performed within 2 weeks of stress echo-cardiography.227 Treadmill exercise echocardiography was

highly sensitive (91%) regardless of infarct size but was less specifi c (59%) for detection of infarct-related coronary lesions.227

Assessment of Myocardial Viability

Viable myocardium has been reported in up to 60% of dys-functional myocardial segments in ischemic cardiomyopa-thy.228,229 Myocardial segments that are viable and poorly perfused should recover function after coronary revascular-ization. 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 func-tion).230 Furthermore, when performed in patients with signifi cant global LV dysfunction but little viable myocar-dium, coronary bypass does not improve global systolic function.231,232

Dobutamine Stress Echocardiography in the Identifi cation of Myocardial Viability

Dobutamine stress echocardiography is the preferred echo-cardiographic method for the assessment of myocardial via-bility 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 myo-cardial ischemia by including more images at lower dobu-tamine doses (Table 35.10). The goal is to identify any improvement in contractile reserve in patients with myocar-dial dysfunction, which may be transient in those with con-comitant ischemia. Viable segments should demonstrate contractile reserve with inotropic stimulation, normal myo-cardial thickness, and evidence of some coronary perfusion and metabolism.233 The biphasic response—initial improve-ment in contractility followed by deterioration at higher doses—indicates viable and ischemic myocardium and is a

TABLE 35.9. Weighted mean sensitivities, specifi cities of pharmacologic studies

Pharmacologic test Studies Subjects Mean age (years) CAD (%) MI (%) Men (%) Sensitivity (%) Specifi city (%)

Adenosine echocardiography 6 516 65 73 31 71 72 (62–79) 91 (88–93)Adenosine SPECT 9 1,207 63 80 17 59 90 (89–92) 75 (70–79)Dipyridamole echocardiography 20 1,835 56 67 15 72 70 (66–74) 93 (90–95)Dipyridamole SPECT 21 1,464 60 71 31 77 89 (84–93) 65 (54–74)Dobutamine echocardiography* 40 4,097 59 70 26 66 80 (77–83) 84 (80–86)Dobutamine SPECT 14 1,066 58 66 9 63 82 (77–87) 75 (70–79)

Total 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.

00

20Normal

% of segmentsabnormal at peak stress

≤25IschemiaInfarction

40

60

80

Eve

nt-f

ree

prob

abili

ty, %

100

10 20Time, months

30 40 0 10 20

51–10026–50

Time, months30 40

No. at risk 774 641 235 40 774860 641 235 40860FIGURE 35.19. Abnormalities on dobutamine stress echocardiog-raphy predict future adverse cardiac events. Left: Ischemia and fi xed wall motion abnormalities (infarction) by dobutamine stress echo-cardiography decrease cumulative cardiac event–free probability. Right: The percentage of abnormal segments at peak stress increases the risk of future cardiac events.

TABLE 35.10. Dobutamine stress protocol

Ischemia vs. Viability

Rest 10 μg Rest 5 μgPre-peak Peak > 88% 10 mcg Peak > 88% MPHR MPHR

MPHR, maximal predicted heart rate.



reliable predictor of functional recovery (Table 35.2).234 The value of DSE in the identifi cation of myocardial viability and, therefore, in the selection of patients who may benefi t from revascularization is well established. In a number of studies in which postrevascularization echocardiography has been used to assess LV functional recovery after catheter-based or surgical revascularization, the average sensitivity of DSE to predict functional recovery ranges from 74% to 88%, and the specifi city is 73% to 87%.235–242 The positive predic-tive value is 81%, and negative predictive value is 87%. Com-parative studies have shown a higher specifi city and a lower sensitivity with DSE than with radionuclide techniques for the identifi cation of functional recovery after the revas-cularization 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 diffi cult to measure and accounted for nearly all of the immeasurable but dysfunc-tional segments (17%). A myocardial thickness of >6 mm had a sensitivity of 94% and a specifi city of 48% for recovery of function. A combination of preserved wall thickness and evidence of contractile reserve during DSE improved the specifi city of DSE to 77% and, thus, is a valuable adjunct to DSE in the assessment of myocardial viability.

Prognosis: Viability and Potential Benefi ts 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-

ization compared with medical therapy when viability was present, but there was no benefi t 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 revas-cularization.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 deforma-tion can be identifi ed and quantifi ed 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 myocar-dial ischemia and viability.

Strain-Rate Imaging

Strain-rate imaging provides objective quantifi cation of seg-mental myocardial function by measuring myocardial defor-mation 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 differenti-ate 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 M-mode analysis of segmental strain and strain rate, was per-formed in 44 patients undergoing traditional DSE.16 Ischemia was defi ned by concurrent pharmacologic SPECT myocar-dial perfusion imaging and stenosis confi rmed by coronary

DE0

20

40

60

80

100

%

321090

Sensitivity p SpecificityDE vs othersothers vs TI-RIMIBI vs TI-RR

FDG vs others <.05<.05<.05

p<.05<.05<.05

TI-RI vs DE, MIBITI-RR vs DE

22557

11301

20488

20598

Studies (no.)Patients (no.)

TI-RR TI-RI MIBI FDG

FIGURE 35.20. Techniques for the noninvasive assessment of myo-cardial viability; comparison of weighted sensitivities and specifi ci-ties. Regional recovery of function after revascularization was the gold standard for viability. Open bars, sensitivity; solid bars, speci-fi city. DE, dobutamine echo; FDG, fl uorine-18 fl uorodeoxyglucose; MIBI, technetium-99m sestamibi; Tl-RI, thallium-201 reinjection; Tl-RR, thallium-201 rest-redistribution.

20

15

10

5 3.2

16.0

7.76.2

NonviableViable

–79.6%

p<.0001χ2 = 147

23.0%

p = .23χ2 = 1.43

Dea

th r

ate

(%/y

r)

0

FIGURE 35.21. Survival following revascularization is increased in patients with evidence of myocardial viability. Without myocardial viability, there was no signifi cant difference in survival between patients treated medically and those revascularized. Open bars, revascularization; solid bars, medical therapy.


8 3 0 c h a p t e r 35

angiography. Qualitative assessment of strain and strain-rate curves was possible in 85% of segments. In normally per-fused segments, the peak systolic strain rate increased with increasing dobutamine stimulation. Ischemic myocardial segments had signifi cantly lower strain-rate increases and strain than did nonischemic segments. Compared with tra-ditional DSE parameters, strain-rate imaging improved the sensitivity of DSE from 81% to 86% and the specifi city 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 nonspecifi c 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 identifi ed by 2D imaging because of its relatively low amplitude and short duration.10 Strain-rate imaging allows quantifi cation of postsystolic shortening, which is defi ned as the maximum change in segment length occurring between aortic valve closure and the regional onset of myocardial lengthening caused by early diastolic LV fi lling. In one study, the ratio of postsystolic shortening to maximal segment deformation was the best quantitative parameter for identifying stress-induced 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 myocar-dium.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 revasculariza-tion.254 The inclusion of regional strain-rate imaging with routine visual wall-motion scoring identifi ed patients with signifi cant myocardial viability (an improvement in more

than four myocardial segments or an overall increase of >5% in the LVEF after revascularization) and increased the sensi-tivity of DSE from 73% to 83% without changing the speci-fi city. In a separate study,255 tissue Doppler echocardiography with strain-rate imaging without DSE differentiated trans-mural from nontransmural MIs in 47 consecutive patients with a fi rst 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 specifi city (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 specifi city of 83.3% in distinguishing subendocardial infarctions. The peak strain rate was signifi cantly lower in segments with transmural infarctions identifi ed with contrast magnetic resonance imaging compared to normal myocardium or seg-ments with a nontransmural infarction (both p <.0005).255

Perfusion Imaging

Myocardial contrast echocardiography (MCE) is an evolving technique for the evaluation of myocardial perfusion. Intrave-nous injection of gas-fi lled microbubbles scatters ultrasound and can be used to defi ne LV endocardial borders and myocar-dial blood fl ow. Steady-state microbubbles within the myocar-dium can be destroyed with high-energy ultrasound pulses, and the rate of microbubble reappearance approximates myo-cardial blood fl ow. Improvements in bubble size (<10 μm to allow transcapillary migration), as well as echocardiogra-phic 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 accu-racy. Specifi cities 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 abnor-mal results in the circumfl ex territory have been reported.263

Myocardial contrast echocardiography has been shown to be accurate in detecting fl ow-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 echocar-diography 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 exer-cise improved the sensitivity, specifi city, and accuracy to 86%, 88%, and 86%, respectively, for establishing the pres-ence of CAD on angiography.267

Abnormal myocardial perfusion imaging during vasodi-lator stress (dobutamine) echocardiography in 788 patients contributed signifi cantly to the predictive value of clinical risk factors, resting systolic LV function, and RWMAs. Event-free 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

100

828186

89

SRI

sensitivity

specificity

2D-gray

80

60

40

20

0

[%]

FIGURE 35.22. Strain-rate imaging (SRI-CMM) improves the sen-sitivity and specifi city of conventional two-dimensional imaging (2D-gray) during dobutamine stress echocardiography (DSE).



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, identifi cation of CAD as the etiology was facili-tated by MCE at rest and after dipyridamole stress. Com-pared to patients without CAD and to normal control subjects, patients with CAD had a reduced myocardial blood fl ow velocity reserve in vascular territories supplied by vessels with >50% obstruction. In this population, MCE was the only independent predictor of CAD among clinical, elec-trocardiographic, biochemical, and resting echocardiographic variables (Fig. 35.23).269 Myocardial contrast echocardiogra-phy may provide an added benefi t to dobutamine echocar-diography in the evaluation of myocardial viability. The demonstration of specifi c patterns of contrast within dys-functional myocardial segments may discriminate viable from nonviable myocardium.270

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FIGURE 35.23. Perfusion imaging with myocardial contrast echo-cardiography demonstrates myocardial blood fl ow in viable myocar-dial 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 myo-cardial 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 fl ow limiting stenoses were confi rmed by coronary angiography.


8 32 c h a p t e r 35

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