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Journal of the American College of Cardiology Vol. 48, No. 11, 2006© 2006 by the American College of Cardiology Foundation ISSN 0735-1097/06/$32.00P

yocardial Contrast Echocardiography Evolvings a Clinically Feasible Technique for Accurate,apid, and Safe Assessment of Myocardial Perfusionhe Evidence So Far

ieter A. Dijkmans, MD,* Roxy Senior, MD, PHD,† Harald Becher, MD, PHD,‡homas R. Porter, MD, PHD,§ Kevin Wei, MD,� Cees A. Visser, MD, PHD,* Otto Kamp, MD, PHD*

msterdam, the Netherlands; Harrow and Oxford, United Kingdom; Omaha, Nebraska; and Portland, Oregon

Intravenous myocardial contrast echocardiography (MCE) is a recently developed techniquefor assessment of myocardial perfusion. Up to now, many studies have demonstrated that thesensitivity and specificity of qualitative assessment of myocardial perfusion by MCE inpatients with acute and chronic ischemic heart disease are comparable with other techniquessuch as cardiac scintigraphy and dobutamine stress echocardiography. Furthermore, quanti-tative parameters of myocardial perfusion derived from MCE correlate well with the currentclinical standard for this purpose, positron emission tomography. Myocardial contrastechocardiography provides a promising and valuable tool for assessment of myocardialperfusion. Although MCE has been primarily performed for medical research, its implemen-tation in routine clinical care is evolving. This article is intended to give an overview of thecurrent status of MCE. (J Am Coll Cardiol 2006;48:2168–77) © 2006 by the American

ublished by Elsevier Inc. doi:10.1016/j.jacc.2006.05.079

College of Cardiology Foundation

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he use of ultrasound contrast agents for left ventricularpacification and myocardial perfusion in echocardiographyas significantly improved the diagnostic accuracy of stresschocardiography. In the last decade, the clinical value ofntravenous myocardial contrast echocardiography (MCE)n patients with both acute and chronic ischemic heartisease has been demonstrated. At the same time, experi-ental and clinical studies have demonstrated the physio-

ogic basis for quantification of myocardial perfusion withCE. In comparison with other imaging techniques, MCE

s a rapid, easy-to-perform, and safe bedside technique forhe assessment of myocardial perfusion. This article pro-ides a review of the current status of MCE with respect tolinical value, practical issues, and conditions that need to beulfilled for clinical implementation.

CE PROTOCOLS

ltrasound contrast agents. Since 1968, when the exis-ence of ultrasound contrast was established, the develop-ent of ultrasound contrast agents has undergone signifi-

ant advances. Initially, contrast agents were air-filledicrobubbles, that were relatively unstable in the blood and

ould not pass the pulmonary capillary bed, rendering themnsuitable for the assessment of the left side of the hearturing intravenous injection. Second-generation contrast

From the *Department of Cardiology, VU University Medical Center, Amsterdam,he Netherlands; †Department of Cardiovascular Medicine, Northwick Park Hospi-al, Harrow, United Kingdom; ‡Department of Cardiology, John Radcliffe Hospital,

eadington, Oxford, United Kingdom; §Section of Cardiology, Department ofnternal Medicine, University of Nebraska Medical Center, Omaha, Nebraska; andhe �Oregon Health and Science University, Portland, Oregon.

rManuscript received February 28, 2006; revised manuscript received April 21,

006, accepted May 15, 2006.

gents were developed for this reason, containing a gas withow solubility and diffusibility and a shell of lipids, albumin,r galactose to prolong their life span. The microbubblesave a diameter less than that of a red blood cell, resistrterial pressure, and remain intravascular in the intactirculation. These properties allow passage of the pulmonaryasculature, opacification of the left ventricular cavity, andmaging of myocardial perfusion. Currently, the most usedecond-generation contrast agents are Sonovue (Bracco,

ilan, Italy), Optison (Amersham Health AS, Oslo, Nor-ay), and Definity (Bristol-Myers Squibb, Billerica, Mas-

achusetts). These agents are licensed for left ventricularpacification only. These agents differ in terms of their shellonstituents and gas content, that influence shell-stiffnessnd stability of the microbubble, and determine physicalroperties. All are suitable for MCE.hysical principles. The mechanism by which micro-ubbles enhance echocardiographic images, depends onheir behavior under acoustic pressure. Low-energy ultra-ound causes microbubbles to oscillate linearly, reflectingltrasound at the insonation (fundamental or f0) frequency.ltrasound with an intermediate energy level induces non-

inear oscillations of microbubbles, resulting in generationf frequencies other than the fundamental frequency (mul-iples of the fundamental frequency) which are calledarmonic frequencies (e.g., 2f0). Finally, high-intensityltrasound (within the energy levels used for diagnosticmaging) destroys microbubbles. In contrast to micro-ubbles, cardiac tissue produces much fewer harmonicrequencies, so selective reception of harmonic echos willreferentially detect signals emanating from contrast agent

ather than the myocardium.

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2169JACC Vol. 48, No. 11, 2006 Dijkmans et al.December 5, 2006:2168–77 Contrast Echocardiography for Perfusion Imaging

maging modalities. Initial contrast imaging modalitieselied mainly on harmonic imaging techniques, where fun-amental frequencies were eliminated and harmonic fre-uencies were selectively detected. Although these methodsmproved the signal-to-noise ratio, off-line image process-ng was frequently required to evaluate myocardial perfu-ion, because tissue signals were still present. Harmonicmaging also used high acoustic powers that destroyed

icrobubbles—consequently, the imaging frame rate had toe reduced substantially with electrocardiographic trigger-ng to allow microbubbles to replenish the myocardial

icrocirculation between pulses. Recently, several novelpproaches to imaging microbubbles were developed: Thesenclude high-power modalities with superior tissue noiseuppression that allow on-line assessment of myocardialerfusion and low-power modalities that permit imagingith high frame rates. These modalities specifically take

dvantage of the nonlinear behavior of microbubbles in ancoustic field. Many techniques use multiple transmittedulses that are, e.g., full and half amplitude (power modu-

ation (Fig. 1) to distinguish nonlinear microbubble signalsrom tissue (1). Reflected echos are scaled and subtracted.ecause tissue responds linearly (especially at low acousticowers), subtraction and scaling results in zero signal.icrobubbles reflect nonlinearly, so received echos will not

e canceled out, enabling selective microbubble detection.ost of these multipulse techniques additionally use poweroppler, and the resulting signal is color coded and dis-

layed (2).Because high-power imaging destroys microbubbles, im-

ging of myocardial perfusion cannot be performed in realime. Low-power imaging (mechanical index �0.2) in-reases signal-to-noise ratio and because of minimal bubbleestruction continuous imaging may be performed. Bothigh- and low-power MCE have their advantages andisadvantages. High-power imaging precludes continuous

maging owing to destruction of contrast, and therefore wallotion cannot be assessed simultaneously. On the other

and, signal-to-noise ratio is good. Low-power imagingllows simultaneous assessment of perfusion and contractionut has a lower sensitivity for the detection of microbubbles.tress agent. The most commonly used stress agents aredenosine, dipyridamole, and dobutamine. All 3 agents haveeen used widely for pharmacologic stress during MCE.

Abbreviations and AcronymsACS � acute coronary syndromeAMI � acute myocardial infarctionCAD � coronary artery diseaseDSE � dobutamine stress echocardiographyMBF � myocardial blood flowMBV � myocardial blood volumeMCE � myocardial contrast echocardiographyVI � video intensity

lthough the working mechanism of these agents differ, all m

gents have a high diagnostic value for detection of coronaryrtery disease (CAD) (Tables 1 and 2).

SSESSMENT OF MYOCARDIAL PERFUSION

ualitative assessment. During continuous infusion oficrobubbles in a patient with intact coronary microvascu-

ature and normal myocardial blood flow (MBF), destruc-ion of microbubbles in the microcirculation by ultrasounds followed by relatively uniform contrast appearance in theoronary microcirculation, and homogenous opacification ofhe myocardium. In case of diminished epicardial flow, e.g.,n significant CAD during stress, or after AMI, when

icrovascular integrity is affected, the speed and amount ofontrast replenishment will be decreased. Earliest studiesssessing MCE mainly used qualitative analysis in whichontrast replenishment after microbubble destruction wascored as normal, reduced, or severely reduced. With such acoring system, irreversible and reversible contrast defects inatients with flow-limiting CAD could be detected. Also,n patients with acute coronary syndrome (ACS), thesecoring systems have proven their value in determiningnfarct size, viability, and prediction of functional recovery.

uantitative assessment. Because the microvascular rhe-logy of microbubbles is similar to that of red blood cells,ssessment of the transit of microbubbles through theoronary microcirculation with MCE should allow quanti-cation of MBF (3). The first in vivo studies assessinguantification of MBF with MCE used bolus injections of

igure 1. Pulse cancellation techniques: principles of power modulation.A) Resulting signal of tissue reflection. (B) Resulting signal of contrasteflection.

icrobubbles (4–6). The ratio of video intensity (VI) in

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2170 Dijkmans et al. JACC Vol. 48, No. 11, 2006Contrast Echocardiography for Perfusion Imaging December 5, 2006:2168–77

iseased/nondiseased vascular territories correlated wellith radiolabeled microsphere-derived blood flow ratios.he use of bolus injections of microbubbles, however,

llows assessment of only relative differences in MBF andot absolute MBF. This limitation was overcome withontinuous microbubble infusions, which allow a steady-tate microbubble concentration to be reached in the blood.t this time, after microbubbles are destroyed by ultra-

ound, the subsequent replenishment of microbubbles intohe ultrasound beam elevation will reflect MBF. The re-lenishment of contrast can be characterized by a time-ntensity curve (Figs. 2 and 3), which can be fitted to a

onoexponential function: y � A(1 � e�t). The reappear-nce rate of microbubbles, reflected by the slope of theeplenishment curve (�), provides a measure of meanyocardial microbubble velocity, and the plateau value (A)

f the replenishment curve reflects the microvascular cross-ectional area (7). The product of A and � thereforeepresents MBF. Animal studies using a coronary stenosisodel demonstrated that the MCE estimate of MBF

orrelates very well with absolute MBF as measured withadiolabeled fluorescent microspheres (8–10). During phar-

able 1. Concordance of MCE and SPECT for Detection of Sigoronary Artery Disease

Patients (n) Imaging Mode

aul et al. (17) 30 THIeinle et al. (26) 123 HPD

himoni et al. (18) 101 AIIei et al. (23) 54 HPD

occhi et al. (21) 25 HPDlszowska et al. (19) 44 HPD

enior et al. (22) 55 IPIie et al. (31) 36 RTIorosoglou et al. (27) 120 PPI

ote: values expressed as concordance and agreement (kappa).AII � accelerated intermittent imaging; HPD � harmonic power Doppler; IPI �

ulse inversion; RTI � real-time imaging; SPECT � single-photon emission comp

able 2. Sensitivity and Specificity of MCE and SPECT/DSE tongiography

Patients(n)

DefinitionStenosis

ImagingMode S

himoni et al. (18) 44 �50% AIIlszowska et al. (19)* 44 �60% RTHIocchi et al. (21)* 25 �70% HPDlhendy et al. (29)† 169 �50% RTPIenior et al. (22) 55 �50% IPIeltier et al. (24) 35 �70% PMsutsui et al. (28)* 16 �50% RTIie et al. (31)† 27 �50% PPI

eetley et al. (30) 123 �50% TRIorosoglou et al. (27) 89 �75% PPIaravidas et al. (in press) 47 �50% TPDooled estimate 85% (

he pooled estimate is a percentage (95% confidence interval). *Analysis by territory

DSE � dobutamine stress echocardiography; PM � power modulation; RTHI � real-tim

oppler; TRI � triggered replenishment imaging; other abbreviations as in Table 1.

acologic stress, impaired hyperemic flow in the presencef coronary stenosis was associated with decreases in both And �. Thus, abnormalities in either MBF velocity or MBVuring stress can be used to detect and quantify stenosiseverity. In dogs, quantification by triggered MCE appearedo be accurate enough to make a distinction between endo-nd epicardial flow (11). In humans, similar results wereound (12). Myocardial blood flow reserve decreased in atep-wise manner in mild, moderate, and severe stenosis.uantitative measures of MCE can not only be used to

stimate stenosis severity, they can also be used to assesserfusion defect after AMI or to predict recovery of hiber-ating myocardium (13,14).Absolute MBF in ml/min/g of tissue can be derived usingCE (14). Vogel et al. (15) have shown that myocardial

lood volume (MBV) fraction can be derived from the ratiof myocardial video intensity and that of the adjacent leftentricular cavity. This method adjusts for inhomoge-eous contrast enhancement of the myocardium due toechnical factors such as attenuation. The MBV fractionan then be used to derive absolute MBF (MBF �elative blood volume � �/tissue density, where the

ant Coronary Artery Stenosis in Patients With Suspected

Concordance, % (Kappa)

Patient Basis Territory Basis Segment Basis

86 (0.71) 90 (0.77) 92 (0.99)81 (0.60) 76 (UN) 70 (0.32)76 (0.50) 76–89 (UN) 92 (0.32)84 (0.63) 65 (0.41) UN84 (0.67) 92 (0.81) UN

UN 73–91 (0.4–0.8) 89 (0.81)UN 70 (0.37) UN

75 (0.50) 85 (0.61) UNUN 83 (0.65) 86 (0.65)

ittent pulse inversion; MCE � myocardial contrast echocardiography; PPI � powerd tomography; THI � triggered harmonic imaging; UN � unknown.

tect Stable Coronary Artery Disease: Gold Standard

MCE SPECT/DSE

ivity Specificity Sensitivity Specificity

100% 75% 81%93% 93% 84%

100% 100% 88%51% 70% 74%58% 49% 92%69% 82% 85%92% 68% 61%65% 33% 72%56% 82% 52%93% 77% 52%92% 73% 72%

–88.5%) 74% (67.7%–80.3%) 71% (66%–76%) 71% (64%–78%)

ded from meta-analysis. †Compared with DSE.

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2171JACC Vol. 48, No. 11, 2006 Dijkmans et al.December 5, 2006:2168–77 Contrast Echocardiography for Perfusion Imaging

elative blood volume is Amyocardium/Acavity). In thattudy, MCE-derived absolute MBF was compared withositron emission tomography and showed excellentorrelations.

A new application of quantitative MCE is generation ofarametric images derived from contrast-enhanced images16). These images contain information about the qualityf acquisition, the maximal intensity of contrast in theyocardium, and the speed of contrast replenishment

Fig. 4) and allows fast visual interpretation of myocardialerfusion.

CE IN DETECTING STABLEORONARY ARTERY DISEASE

n normally perfused myocardium, the rate of capillarylood flow is 1 mm/s. Saturation of the coronary microvas-ulature by microbubbles therefore takes about 5 s (becausehe thickness of the ultrasound beam is approximately 5m). When there is no flow limiting stenosis, MBF

ncreases 5 times during hyperemia (stress testing), andherefore the myocardium replenishes in 1 s. In addition, aow-limiting stenosis leads to a reduction in capillary bloodolume in the distal microvasculature, with an accompany-ng decrease in signal intensity during MCE. These 2eatures (slowed contrast appearance and decreased capillarylood volume) form the basis for detecting CAD usingCE.One of the first studies assessing MCE with triggered

igure 2. Example of adenosine stress myocardial contrast echocardiographpical 3-chamber view. (A) Baseline; (B) contrast destruction; (C to H) c

maging in stable CAD patients showed that MCE can D

efine the presence of abnormal perfusion at rest anduring pharmacologic stress, with a high concordanceetween MCE and 99mTc-sestamibi single photon emis-ion computerized tomography (SPECT) (17). Also,omparison of accelerated intermittent imaging at restnd with exercise to 99mTc-sestamibi-SPECT demon-trated a concordance of 76% to 92% (18). Several othertudies assessed the accuracy of MCE and SPECT/obutamine stress echocardiography (DSE) for detectionf stable CAD. In general, agreements are high, rangingrom 65% to 92% (19 –27) (Table 1).

A number of these studies employed angiography as theold standard (Table 2). Most reported a sensitivity ofCE for CAD detection that is similar to or higher than

PECT/DSE, ranging from 64% to 97%, compared with3% to 100% for the latter (18,19,21,22,24,27–31). Fur-hermore, the addition of MCE may improve sensitivity foretection of CAD over wall motion analysis during DSE18,29,31,32). We performed a meta-analysis of thesetudies and determined that the sensitivity and specificity of

CE for detection of CAD are at least not inferior toPECT/DSE (Table 2, Fig. 5).Myocardial contrast echocardiography also provides

rognostic value in patients with stable CAD (33). Patientsith normal perfusion have a better outcome than patientsith normal wall motion. This underscores the value of

ncorporating MCE in stress echocardiography. An exam-le of a perfusion defect with real-time perfusion during

bsequent end-systolic frames) with region of interest for quantification thest replenishment.

SE is shown in Figure 6.

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2172 Dijkmans et al. JACC Vol. 48, No. 11, 2006Contrast Echocardiography for Perfusion Imaging December 5, 2006:2168–77

CE IN ACUTE CORONARY SYNDROMESurrently, the diagnosis of ACS is based on the triad of

linical history, electrocardiography, and laboratory investi-ation. These methods, although useful, can often beondiagnostic in this setting. Because MCE is the onlyechnique that permits immediate assessment of wall mo-ion and perfusion, it has a unique role in the diagnosis ofCS. Myocardial contrast echocardiography allows quick

valuation of myocardial perfusion in the emergency depart-ent and may be used to triage patients into a low- or

igh-risk category. The value of MCE in acute coronary

igure 3. Example of (A) replenishment curve with slope (�) and plateau

igure 4. Parametric image of apical 4-chamber view, containing information ayocardial blood flow, and (D) quality of data.

yndromes has been studied experimentally using coro-ary balloon occlusions in pigs. Myocardial contrastchocardiography accurately reflects the decrease in myo-ardial perfusion during balloon occlusion compared withicrosphere-derived MBF (1). Studies have also shown that

uring coronary occlusion the area at risk correlates closelyith the contrast defect early after contrast flash destruction

nd that the plateau contrast defect identifies infarct size34). Kamp et al. (35) were the first to report theensitivity of MCE to detect perfusion defects in patientsuspected of having AMI. With 1:1 end-systolic–

(A) of the replenishment curve fitted to a monoexponential function (B).

bout (A) peak intensity, (B) slope of replenishment curve, (C) estimate of

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2173JACC Vol. 48, No. 11, 2006 Dijkmans et al.December 5, 2006:2168–77 Contrast Echocardiography for Perfusion Imaging

riggered imaging, MCE perfusion defects were detectedn 19 of 32 patients (59%) with Thrombolysis In Myo-ardial Infarction (TIMI) flow grade 0 before percutane-us transluminal coronary angioplasty (35). The sensitiv-ty of MCE tended to decrease when patients had betterIMI flow and inferior infarctions (20%), whereas the

ensitivity of MCE in patients with an anterior coronaryrtery occlusion was high (88%). Other studies assessinghe potential of MCE to acute coronary syndromes alsoeported high sensitivities, comparable with those oftandard echocardiography and SPECT (35– 43) (Table). In addition, MCE appears to have important prog-

igure 5. We conducted a meta-analysis of 8 studies (PubMed referencpecificity of myocardial contrast echocardiography (MCE) and single-phgraphy (DSE) for detection of significant coronary artery disease (CAD)ontrast echocardiography,” “single-photon emission computerized tomogtudies were included when coronary angiography was used as gold standaochrane Collaboration Group was used to calculate variance-weighted petween MCE and SPECT/DSE according to a random effect meta-analys95% confidence interval [CI] 0.09 to 0.20) and 0.03 (95% CI �0.14 to 0.2o difference was found for the specificity. n/N � number of patients with Cith CAD; RD � risk difference. * indicates DSE.

igure 6. Example of dobutamine stress contrast echocardiography. Rever

erfusion defect during peak stress (arrows). Coronary angiography (angio) demo

eft circumflex (posteroapical defect), and right coronary arteries (inferoapical d

ostic value in patients presenting to the emergencyepartment with acute chest pain (38 – 43).Besides detection of acute ischemic heart disease, MCEay play a pivotal role in prediction of functional recovery

n patients after ST-segment elevation myocardial infarc-ion. The severity of myocardial damage is currently mainlystimated by enzymatic damage and wall motion score,hereas recovery of myocardial function is importantlyependent on reflow of blood to the risk area. The presencef reflow after coronary angioplasty is suggested by resolu-ion of chest pain and the degree of resolution of ST-egment elevation but can be visualized by MCE (Fig. 7).

s, restricted to English-language literature) assessing the sensitivity andemission computed tomography (SPECT)/dobutamine stress echocardi-ere published before January 2006. The text words used were “myocardial,” “dobutamine stress echocardiography,” and “stress echocardiography.”d if results were analyzed on a patient-based analysis. RevMan 4.2 of thedifference of proportions for the differences in sensitivity and specificity

e pooled estimates of the differences in sensitivity and specificity were 0.14spectively, indicating a higher sensitivity for MCE than for SPECT/DSE.detected by MCE or SPECT/DSE divided by the total number of patients

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2174 Dijkmans et al. JACC Vol. 48, No. 11, 2006Contrast Echocardiography for Perfusion Imaging December 5, 2006:2168–77

loner (44) was the first to demonstrate the deleteriousffect of no-reflow on clinical outcome. Later, it was shownhat the presence of no-reflow on MCE after AMI relatedo absence of pre-infarction angina, number of Q waves,all motion score at presentation, TIMI flow grade 0, the

ize of the area at risk, and the occlusion status of the culpritrtery (45). Conversely, intact microvasculature after AMIreflow), is a positive predictor of functional recovery (46).atients without microvascular dysfunction on MCE have

ess enzymatic elevation, better functional performance,etter recovery of global and regional wall motion, lessemodeling, and better survival independent of other pre-ictors (47–49). The ability of MCE to predict functionalecovery is summarized in Table 4 (50–63) and is compa-able to that of cardiovascular magnetic resonance imaging64,65) (Fig. 8). Thus the existing literature suggests that

CE has important additional value for diagnosis and risktratification in patients with acute ischemic heart disease.

ARGETED IMAGING WITH ULTRASOUND CONTRAST

ecently, “targeted microbubbles” have been developed byncorporating ligands in the microbubble shell. Experimen-al studies demonstrated that specific ligands to intercellulardhesion molecule 1 (ICAM-1) and glycoprotein IIb/IIIanabled these targeted agents to bind selectively to ICAM-–expressing tissue and thrombus, respectively (66,67).

igure 7. No-reflow after primary percutaneous transluminal coronary

able 3. Sensitivity and Specificity of MCE for Detection of Imp

Patients (n) ACS Type

amp et al. (35) 59 STEMIocchi et al. (43) 30 AMIoir et al. (36) 34 STEMIagendorf et al. (42) 100 ACSinter et al. (37) 35 ACS

ooled estimate 258

CC � American College of Cardiology; ACS � acute coronary syndrome; AHAontrast echocardiography; NA � not applicable; STEMI � ST-segment elevation

ungioplasty for acute myocardial infarction (real-time myocardial contrastchocardiography).

ecause expression of ICAM-1 is associated with earlytherosclerosis, targeted imaging could possibly play a rolen diagnosis of preclinical atherosclerosis. Imaging ofhrombus enables us to localize vascular clots in humansoninvasively. Furthermore, lipid microbubbles with phos-hatidylserine in the microbubble shell appear to attach tonflamed tissue (68). Localized attachment of targetedltrasound contrast to specific tissue creates great opportu-ities for development of new diagnostic tools and treat-ent modalities (targeted drug delivery).

AFETY

he most important study assessing the safety of MCE waserformed by Tsutsui et al. (69). More than 1,500 patientsnderwent dobutamine stress MCE with low-mechanical-ndex real-time perfusion, during which no major adversevents were seen. Myocardial contrast echocardiography hassimilar safety profile as dobutamine stress echocardiog-

aphy. In patients with heart failure, intravenous contrastid not show any deleterious hemodynamic effects com-ared with placebo (70). The occurrence of prematureentricular contractions, especially during end-systolicigh-mechanical-index imaging, has been a matter of con-ern. However, data regarding this aspect are conflicting,nd, because significant arrhythmias during MCE are ob-erved rarely, the clinical significance is doubtful (71).

RACTICAL ISSUES

yocardial contrast echocardiography is a relatively simpleechnique for imaging of myocardial perfusion. However,here is a learning curve as with all noninvasive techniques.ecause perfusion of the myocardium is assessed in 1

pecific region, it is important to keep the transducer still toinimize movement of the heart. In contrast to real-time

maging, triggered imaging does not allow continuousisualization of the heart (unless the system is equipped withonitoring mode). Especially with this technique, the

uality of the images improves with more experience.raining is also required for interpretation.When performing MCE, infusion pump, blood pressure,

nd heart rate monitoring must be available. Stress testingith the stressors mentioned in the preceding is safe, and

he excellent safety profile is not expected to change when

Perfusion in Patients With Suspected ACS

Sensitivity Specificity Gold Standard

59% NA Angiography84% 94% Angiography79% 50% Angiography84% 93% ACC/AHA guidelines81% 67% Angiography82% 63%

erican Heart Association; AMI � acute myocardial infarction; MCE � myocardialrdial infarction.

aired

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2175JACC Vol. 48, No. 11, 2006 Dijkmans et al.December 5, 2006:2168–77 Contrast Echocardiography for Perfusion Imaging

eeds to be present to monitor the well-being of the patient72). Emergency medication and facilities should be presentn case of adverse events, which occur rarely.

UTURE PERSPECTIVES

eal-time 3-dimensional myocardial perfusion echocar-iography. A promising tool within MCE is the develop-ent of real-time 3-dimensional perfusion echocardiogra-

hy (73). The current matrix transducers use a moreomogeneous ultrasound field, which improves image qual-

ty, and acquire a full volume instead of 1 scanning plane.mage interpretation is favored by slicing the myocardium inhe appropriate view, by which perfusion defects can beisualized in any chosen myocardial region.

able 4. Prediction of Recovery of Regional and Global Functionyocardial Infarction

Regional FunctionPatients

(n)FU

(months) Sensitivit

olognese et al. (53) 30 1 96%gati et al. (59)* 23 2 100%winbum et al. (58)* 96 3–6 59%ain et al. (60) 34 2 77%illis et al. (55) 37 2 80%

anardhanan et al. (56) 50 3 87%orosoglou et al. (57) 32 1 81%uang et al. (63) 34 4 83%unes Sbano et al. (61) 50 6 95%be et al. (41) 21 6 98%ooled estimate 407 81%

Global Function and EventsPatients

(n)

Reflow

EF Baseline EF FU

to et al. (51) 39 42 � 11 56 � 13orter et al. (52) 45 59 � 10 63 � 9akuma et al. (48) 50 44 � 9 56 � 12olognese et al. (47) 124 40 � 7 51 � 11

ote: data are presented as percentage. *Patients partly revascularized.EF � ejection fraction; FU � follow-up; NPV � negative predictive value; PPV

igure 8. Fixed septal/apical perfusion defect (arrows) with myocardial contrasmiddle), and delayed enhancement with magnetic resonance imaging (right) a

ONCLUSIONS

n the past 10 years, MCE has developed from a researchool to a clinically valuable technique in patients withnown or suspected CAD. It is a rapid, safe, and accurateethod for imaging of myocardial perfusion and can be

sed for qualitative and quantitative assessment of MBF.arge prospective multicenter trials would probably fa-ilitate formal approval and more widespread acceptancef MCE.

eprint requests and correspondence: Dr. Pieter A. Dijkmans,epartment of Cardiology 6D-120, VU University Medical Cen-

er, P.O. Box 7057, 1007 MB Amsterdam, the Netherlands.-mail: pa.dijkmans@vumc.nl.

Prediction of Events by MCE in Patients After Acute

Specificity PPV NPV Accuracy

18% 41% 89% 47%90% 81% 100% 93%76% 47% 84% UN83% 90% 63% 79%67% 66% 81% 73%78% 65% 93% 81%88% 95% 61% 83%82% 92% 66% 83%52% 55% 94% 68%32% 43% 96% 55%69% 64% 83% 74%

p No-Reflow Group

FU(% Cardiac Death) EF Baseline EF FU

FU(% Cardiac Death)

35 � 9 43 � 955 � 13 46 � 5

4% 35 � 18 45 � 14 12%3% 33 � 8 NA 25%

sitive predictive value; UN � unknown.

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