Usefulness of myocardial contrast echocardiography using low-power continuous imaging early after acute myocardial infarction to predict late functional left ventricular recovery

Microvascular perfusion is a prerequisite for ensuring viability early after acute myocardial infarction (AMI). For adequate assessment of myocardial perfusion, both myocardial blood volume and velocity need to be evaluated. Due to its high frame rate, low-power continuous myocardial contrast echocardiography (MCE) can rapidly assess these parameters of myocardial perfusion. We hypothesized that the technique can accurately differentiate necrotic from viable myocardium after reperfusion therapy in AMI. Accordingly, 50 patients underwent low-power continuous MCE using intravenous Optison (Amersham Health, Amersham, Middlesex, United Kingdom) 7 to 10 days after AMI. Myocardial perfusion (contrast opacification assessed over 15 cardiac cycles after the destruction of microbubbles with high energy pulses) and wall thickening were assessed at baseline. Regional and global left ventricular (LV) function was reassessed after 12 weeks. Out of the 297 dysfunctional segments, MCE detected no contrast enhancement during 15 cardiac cycles in 172 segments, of which 160 (93%) failed to show improvement. MCE demonstrated contrast opacification during 15 cardiac cycles in 77 segments, of which 65 (84%) showed recovery of function. The greater the extent and intensity of contrast opacification, the better the LV function at 3 months (p <0.001, r = -0.91). Almost all patients (94%) with <20% perfusion in dysfunctional myocardium (assessing various cut-offs) failed to demonstrate an improvement in LV function. MCE and peak creatine kinase proved to be independent predictors of functional recovery (p <0.001). In conclusion, low-power continuous MCE is an accurate and rapid bedside technique to identify microvascular perfusion after AMI. This technique may be utilized to reliably predict late recovery of function in dysfunctional myocardium after AMI.     

Myocardial contrast echography. History, methodology and clinical applications

Recent studies have demonstrated the usefulness of myocardial contrast echocardiography (MCE) in studying myocardial perfusion. Several first and second generation contrast agent such as Levovist, Sonovue, Optison, Definity and Imagent are commercially available or close to be introduced into the market. Use of MCE allowed the clinical demonstration of no-reflow phenomenon in patients with acute myocardial infarction (AMI) after recanalization of the infarct related artery (IRA). Coronary angiography is unable to assess the microvascular damage as showed by the poor correlation between TIMI grading and perfusion score evaluated by MCE. Furthermore, the use of MCE is important to determine coronary stenosis, to identify microvascular damage during ischaemia-reperfusion and to evaluate the presence of collateral circulation in the area at risk. MCE seems to be the most effective technique for assessing microvascular integrity after reperfusion as compared to TIMI myocardial perfusion grade, nuclear myocardial perfusion imaging and magnetic resonance imaging. These techniques are expensive, invasive and not available in most of the hospitals. Furthermore, as compared to nuclear medicine and echo-dobutamine, MCE has greater specificity and higher accuracy in detecting coronary artery disease. Recent studies showed that not only primary percutaneous coronary intervention (PCI) but also rescue and delayed PCI reduced microvascular damage and that MCE play a key role in assessing myocardial salvage after reperfusion. The most exciting aspect of MCE is the independent role in predicting left ventricular (LV) remodelling and functional recovery. The extent on no-reflow is an important predictor of LV dysfunction and remodelling at follow-up. Several studies have demonstrated that the extent of infarct-zone viability is a powerful independent predictor of LV dilation. There is a close relationship between the extent of microvascular damage, the extension of necrosis, the site of AMI and LV remodelling. We demonstrated that MCE performed 24 hours after reperfusion, at 1 week and 6 months appears to provide important prognostic information. These data support the daily use of MCE in coronary care unit and could establish a strategy for clinical decision making in patients with AMI.     

Proximal coronary hemodynamic changes evaluated by intracardiac echocardiography during myocardial ischemia and reperfusion in a canine model

BACKGROUND: The purpose of this study was to assess whether the dynamic changes in coronary flow velocity and coronary flow velocity reserve (CFVR) by intracardiac echocardiography (ICE) within proximal coronary arteries are related to myocardial perfusion status and infarct size in a myocardial ischemia-reperfusion injury model. METHODS: In 14 dogs, left anterior descending coronary artery (LAD) was ligated for 2 hours followed by 2 hours reperfusion. Coronary flow velocity was obtained by ICE within coronary arteries at baseline, and at the end of both occlusion and reperfusion period. The CFVR was calculated as the ratio of hyperemic to resting peak diastolic velocity (PDV). Myocardial perfusion was evaluated by real time myocardial contrast echocardiography (MCE). The infarct area was detected by triphenyltetrazolium chloride (TTC) staining and expressed as the percentage of the whole left ventricular (LV) area. RESULTS: CFVR significantly decreased both in proximal LAD and left circumflex (LCx) artery at the end of occlusion, and did not recover at the end of reperfusion. However, no significant difference in flow parameters was observed between dogs with myocardial perfusion defect and those without. CFVR in LAD at the end of reperfusion did not correlate with the infarct size (r =-0.182, P = NS) either. CONCLUSIONS: Decreased CFVR detected by ICE occurs both in ischemic and in nonischemic proximal arteries during myocardial ischemia and early stage of reperfusion. This change in CFVR has poor correlation with the extent of microvascular impairment and cannot be used to predict infarct size.     

Potential clinical applications of myocardial contrast echocardiography in evaluating myocardial perfusion in coronary artery disease

Myocardial contrast echocardiography (MCE) is a relatively new technique that uses microbubbles to produce myocardial opacification. Recent advances in echocardiography have resulted in improved detection of microbubbles within the myocardium allowing combined acquisition of function and perfusion data, thus making MCE suitable for bedside use. Regardless of the imaging modality chosen or the type of stress used, MCE detects changes developing in the coronary microcirculation, providing important information for the evaluation of severity of coronary artery disease and for the detection of viable myocardial tissue in acute or chronic coronary artery disease.     

Myocardial contrast echocardiography in ST elevation myocardial infarction: ready for prime time?

Acute myocardial infarction (AMI) continues to be a significant public health problem in industrialized countries and an increasingly significant problem in developing countries. ST elevation myocardial infarctions (STEMI) constitute approximately 40% of all AMIs with approximately 670,000 cases yearly in the United States alone. The risk of further cardiac complications such as re-infarction, sudden death, and heart failure for those who survive AMI is substantial. Thus, early assessment and risk stratification during the acute phase of STEMI is important. Furthermore, it is essential to assess the efficacy early after any initial therapeutic intervention, not only to facilitate further management, but also to enable development of new treatment algorithms/approaches to further improve the outcome. The aim of reperfusion therapy in AMI is not only to rapidly restore epicardial coronary blood flow but also to restore perfusion at the microcirculatory level. Myocardial contrast echocardiography (MCE) which utilizes microbubbles can assess myocardial perfusion in real time. Its ability to assess myocardial perfusion and function in one examination allows it to ascertain the extent of myocardial reperfusion achieved in the risk area. Furthermore, in stable patients after AMI, MCE allows assessment of LV function, residual myocardial viability, and ischaemia which are all powerful prognostic markers of outcome. Its portability, rapid acquisition and interpretation of data, and the absence of radiation exposure make it an ideal bedside technique.     

The use of myocardial contrast echocardiography in clinical evaluation after myocardial infarction

Because disruption of the microvasculature is a hallmark of myocyte necrosis, MCE may be able to distinguish between viable and infarcted tissue. In order to interpret images appropriately following myocardial infarction, however, one should be versed in the pathophysiology of post-ischemic reflow, and understand that reperfusion to infarcted tissue is a heterogeneous combination of hyperemia, low-reflow, no-reflow, and impaired microvascular flow reserve. Furthermore, the relative mix of these perfusion patterns changes both temporally and spatially, which has implications for the timing of MCE following reperfusion. The identification of no- and low-reflow by MCE predicts regions unlikely to demonstrate segmental functional recovery, and is associated with adverse clinical events. To date, studies documenting the utility of MCE in the AMI setting have been performed using intracoronary injections in the cardiac catheterization laboratory. With the advent of intravenous contrast agents and innovations in ultrasound imaging systems, it may be possible to make these determinations without the need for coronary instrumentation, thus expanding the role of MCE in acute infarction and reperfusion to settings such as the emergency room and intensive care unit.     

Usefulness of real-time myocardial perfusion imaging to evaluate tissue level reperfusion in patients with non-ST-elevation myocardial infarction

Microvascular integrity is a prequisite for functional recovery in patients who have myocardial infarction after recanalization of the infarct-related coronary artery. In this study, we investigated whether impaired myocardial perfusion is present in patients who have non-ST-elevation myocardial infarction and whether the extent and time course of myocardial tissue reperfusion as assessed by myocardial contrast echocardiography (MCE) are related to functional recovery. Consecutive patients (n = 32) who presented with a first non-ST-elevation myocardial infarction were included in our study. MCE was performed on admission, 1 to 4 hours after angioplasty, and at 24 hours, 4 days, and 4 weeks of follow-up. Contrast images were analyzed visually and quantitatively. Myocardial blood flow was estimated by calculating the product of peak signal intensity and the slope of signal intensity increase. Improvement of wall motion on follow-up echocardiograms after 4 weeks served as a reference for functional recovery of impaired left ventricular function. Of 496 segments available for analysis, 128 (26%) were initially dysfunctional and 96 (75%) recovered at 4 weeks of follow-up. Myocardial tissue reperfusion occurred gradually, expanding over the first 24 hours after percutaneous coronary intervention (myocardial blood flow of 0.4 +/- 0.3 initially, 0.6 +/- 0.4 at 24 hours, and 1.6 +/- 0.7 dB/s at 4 weeks of follow-up, p <0.001). Extent of tissue reperfusion was closely related to grade of improvement of global ejection fraction (r2 = 0.76, p <0.001). MCE predicted functional recovery with a sensitivity of 81%, a specificity of 88%, and accuracy of 83% on a segmental level. Thus, impaired microvascular integrity is suggested by MCE in patients who present with non-ST-elevation myocardial infarction. Improvement of regional tissue perfusion after revascularization is closely related to functional recovery. This information may aid risk stratification and allow monitoring of the effectiveness of reperfusion therapy in these patients.     

Detection and quantification of coronary stenosis severity with myocardial contrast echocardiography

The development of microbubble contrast agents and new imaging modalities now allows the assessment of myocardial perfusion during echocardiography. These microbubbles are excellent tracers of red blood cell kinetics. Apart from providing a spatial assessment of myocardial perfusion, myocardial contrast echocardiography (MCE) can also be used to quantify the 2 specific components of myocardial blood flow-flow velocity and myocardial blood volume. The method to quantify myocardial blood flow velocity is based on rapid destruction of microbubbles by ultrasound, and subsequent assessment of the rate of replenishment of microbubbles into the myocardial microcirculation within the ultrasound beam elevation. Assessment of steady state myocardial video intensity (VI) provides a measure of myocardial or capillary blood volume. Perfusion defects that develop distal to a stenosis during hyperemia are therefore due to capillary derecruitment. We have shown that the degree of derecruitment (and therefore the severity of a perfusion defect) is proportional to stenosis severity. Because the capillary bed also provides the greatest resistance to hyperemic flow, decreases in capillary blood volume distal to a stenosis during hyperemia result in increases in microvascular resistance, which is the mechanism underlying the progressive decrease in flow reserve in the presence of a stenosis. Consequently, both the severity of a perfusion defect and quantification of abnormal myocardial blood flow reserve on MCE can be used to determine stenosis severity. As imaging methods with MCE continue to be refined, the optimal imaging algorithms for clinical practice still need to be determined. MCE, however, holds promise as a noninvasive, instantaneous, on-line method for the detection and quantification of coronary artery disease.     

Use of echocardiography for predicting myocardial viability in patients with reperfused anterior wall myocardial infarction

Dobutamine stress echocardiography (DSE), myocardial contrast echocardiography (MCE), and ultrasonic tissue characterization with integrated backscatter are useful methods for assessing myocardial viability in acute myocardial infarction. In this study, we compared the potential of 3 methods for predicting myocardial viability in 38 patients with reperfused anterior wall acute myocardial infarction. We performed MCE shortly after coronary reperfusion with an intracoronary injection of microbubbles. We recorded 2-dimensional integrated backscatter images at rest and, then, performed low-dose (10 microg/kg/min) DSE 3 days later. In integrated backscatter images, we placed the region of interest in the midwall of the myocardial segment to reconstruct the cyclic variation of myocardial integrated backscatter. The myocardial segment was judged viable when it showed active contraction 3 months later. Among 74 segments analyzed, 34 were judged viable. Presence of contractile response during DSE predicted segmental viability with 91% sensitivity and 78% specificity. Intense and homogenous contrast enhancement with MCE predicted viability with 82% sensitivity and 73% specificity. The presence of synchronous contraction of cyclic variation predicted myocardial viability with 79% sensitivity and 83% specificity. There were no differences in sensitivity and specificity among the 3 methods. Thus, MCE and ultrasonic tissue characterization can predict myocardial viability as accurately as DSE in patients with acute myocardial infarction. The logistics of the methods may determine clinical application.     

Limitations and potential clinical application on contrast echocardiography

Myocardial contrast echocardiography (MCE) is a relatively simple myocardial perfusion imaging technique which should be used in different clinical settings. The ability of MCE to provide a comprehensive assessment of cardiac structure, function, and perfusion is likely to make it the technique of choice for non-invasive cardiac imaging.Contrast agents are encapsulated microbubbles (MB) filled with either air or high-molecular-weight gas. They are innocuous, biologically inert and when administered intravasculary, the sound backscatter from the blood poll is enhanced because MB have the enormous reflective ability due to a large acoustic impedance mismatch between the bubble gas and surrounding blood.MCE is an ideal imaging tool for the assessment of left heart contrast and the myocardial microcirculation. MCE detects contrast MB at the capillary level within the myocardium and, thus, has the potential to assess tissue viability and the duration of the contrast effect. MCE was equivalent to SPECT for the detection of CAD with a tendency toward higher sensitivity of MCE compared with SPECT in microvascular disease and CAD. MCE is also a bedside technique that can be used early in patients presenting with acute heart failure to rapidly assess LV function (regional and global) and perfusion (rest and stress).     

Acute assessment of microvascular perfusion patterns by myocardial contrast echocardiography during myocardial infarction: relation to timing and extent of functional recovery

OBJECTIVE: To examine the relation between the initial microvascular perfusion pattern, as assessed by intracoronary myocardial contrast echocardiography (MCE), immediately after restoration of TIMI (thrombolysis in myocardial infarction) (TIMI) grade 3 flow during acute myocardial infarction, and the extent and timing of functional recovery in the area at risk. SETTING: Referral centre for interventional cardiology. METHODS: Intracoronary MCE was performed 15 minutes after TIMI grade 3 recanalisation of the infarct artery in 25 patients. Segmental myocardial contrast patterns were graded semiquantitatively (0, none; 0.5, heterogeneous; 1, homogeneous). Functional recovery was assessed by echocardiography on days 9 and 42. RESULTS: Among 174 myocardial segments in the area at risk, wall motion recovery on day 9 was observed in 40% of MCE grade 1 segments but there was no significant recovery in grade 0 or 0.5 segments. On day 42, recovery had occurred in 56% of MCE grade 1 segments (p < 0. 0001 v MCE grade 0 and 0.5; p = 0.0001 v MCE grade 1 on day 9), and 22% of MCE grade 0.5 segments (p = 0.02 v MCE grade 0; p = 0.0005 v MCE grade 0.5 on day 9); MCE grade 0 segments did not recover. Negative predictive value in predicting recovery by contrast enhancement was 95% and 89% by days 9 and 42, respectively. CONCLUSIONS: Contractile recovery occurs earliest in well reperfused segments. Up to one quarter of segments with heterogeneous contrast enhancement show wall motion recovery within the first six weeks. Myocardial perfusion after recanalisation in acute myocardial infarction, even if heterogeneous, is a prerequisite for postischaemic functional recovery. Thus preservation of acute myocardial perfusion is associated with more complete and early functional recovery.     

Evaluation of dynamic changes in microvascular flow during ischemia-reperfusion by myocardial contrast echocardiography

Background. Dynamic changes of myocardial blood flow have been observed after reperfusion of an occluded coronary artery. MCE performed by intracoronary contrast injection can provide an estimate of microvascular flow. We hypothesized that MCE performed using intravenous infusion of a new generation contrast agent and electrocardiogram-gated harmonic imaging would be able to assess serial changes of microvascular perfusion.Objective. To study the potential of myocardial contrast echocardiography (MCE) to assess serial changes of microvascular flow during ischemia-reperfusion.Methods. Sixteen dogs underwent 90 or 180 min of left anterior descending coronary occlusion, followed by 180 min of reperfusion. Regional blood flow (RBF) was measured with fluorescent microspheres at baseline, during coronary occlusion, and at 5, 30, 90, and 180 min during reperfusion. At the same time points, MCE was performed with intravenous infusion of AF0150 (4 mg/min). Gated end-systolic images in short axis were acquired in harmonic mode and digitized on-line. Background-subtracted videointensity measured from MCE and RBF obtained from fluorescent microspheres were calculated for the risk area and for a control area, and were expressed as the ratio of the two areas.Results. After initial hyperemia, a progressive reduction in flow was observed during reperfusion. MCE correctly detected the time course of changes in flow during occlusion-reperfusion. Videointensity ratio significantly correlated with RBF data (r = 0.79; p < 0.0001).Conclusions. The progressive reduction in blood flow occurring within the postischemic microcirculation was accurately detected by MCE. This approach has potential application in the evaluation and management of postischemic reperfusion in humans.     

Detection of recent myocardial ischaemia by molecular imaging of P-selectin with targeted contrast echocardiography.

AIMS: We hypothesized that molecular imaging of endothelial P-selectin expression with targeted myocardial contrast echocardiography (MCE) could identify recently ischaemic myocardium without infarction. METHODS AND RESULTS: The microvascular behaviour of P-selectin-targeted (MB(p)) and control (MB(c)) microbubbles was assessed by intravital microscopy of the cremaster muscle in mice. Targeted MCE imaging with MB(p) and MB(c) was performed in mice after brief left anterior descending (LAD) occlusion and reperfusion and in open- and closed-chest controls. Regional wall motion and perfusion by MCE were assessed during occlusion and after reperfusion. On intravital microscopy, ischaemia-reperfusion produced a 10-fold increase (P < 0.01) in venular attachment for MB(p). Attachment for MB(c) was rare. With myocardial ischaemia-reperfusion, LAD occlusion produced hypoperfusion and wall motion abnormalities that resolved after 45 min of reperfusion. At 45 min, signal enhancement in the post-ischaemic region was four-fold greater (P < 0.05) for MB(p) vs. MB(c). MB(p) produced low-level enhancement in non-ischaemic myocardium in all open-chest animals, suggesting P-selectin expression from surgical cardiac exposure. CONCLUSION: Molecular imaging of P-selectin with targeted MCE can identify the presence of recently ischaemic myocardium in the absence of necrosis and after resolution of hypoperfusion and post-ischaemic stunning. This technique can potentially provide a method for risk stratifying patients with acute chest pain.     

Serial evaluation of perfusion defects in patients with a first acute myocardial infarction referred for primary PTCA using intravenous myocardial contrast echocardiography.

AIMS: To investigate whether myocardial contrast echocardiography using Sonazoid could be used for the serial evaluation of the presence and extent of myocardial perfusion defects in patients with a first acute myocardial infarction treated with primary PTCA, and specifically, (1) to evaluate safety and efficacy of myocardial contrast echocardiography to detect TIMI flow grade 0--2, (2) to evaluate the success of reperfusion and (3) to predict left ventricular recovery after 4 weeks follow-up. METHODS AND RESULTS: Fifty-nine patients underwent serial myocardial contrast echocardiography, immediately before primary PTCA (MCE1), 1 h (MCE2) and 12--24 h after PTCA (MCE3). A perfusion defect was observed in 21 of 24 patients (88%) with anterior acute myocardial infarction. All but one had TIMI flow grade 0--2 prior to PTCA. Nine of 31 patients (29%) with inferior acute myocardial infarction showed a perfusion defect and all had TIMI flow grade 0-2 prior to PTCA. Restoration of TIMI flow grade 3 was achieved in 73% of the patients by primary PTCA. A reduction in size of the initial perfusion defect of at least one segment (16 segment model) or no defect vs persistent defect in patients with anterior acute myocardial infarction was associated with improved global left ventricular function at 4 weeks; mean global wall motion score index 1.29+/-0.21 vs 1.66+/-0.31 (P=0.009). Multiple regression analysis in patients with an anterior acute myocardial infarction revealed that the extent of the perfusion defect at MCE3 was a significant (P=0.0005) independent predictor for left ventricular recovery at 4 weeks follow-up. The only other independent predictor was TIMI flow grade 3 post PTCA (P=0.007). CONCLUSION: Intravenous myocardial contrast echocardiography immediately prior to primary PTCA seems safe and is capable of detecting the presence of a perfusion defect and its subsequent dynamic changes, particularly in patients with a first anterior acute myocardial infarction. A significant reduction in size of the initial perfusion defect using serial myocardial contrast echocardiography predicts functional recovery after 4 weeks and these findings underscore the potential diagnostic value of intravenous myocardial contrast echocardiography.     

Correlation between ECG and myocardial perfusion after mechanical reperfusion of acute myocardial infarction

The identification of viable myocardium after myocardial infarction (MI) carries major prognostic impact. Due to myocardial stunning early after successful mechanical reperfusion of acute myocardial infarction, analysis of myocardial perfusion but not of contractile function can be used to differentiate between necrotic and viable myocardium. Although being widely regarded as an indicator of infarct transmurality, the relation between post-infarct Q-wave formation and the amount of viable myocardium has not been studied. We hypothesized that there was a correlation between the extent of Q-wave formation and the extent of perfusion abnormalities on myocardial contrast echocardiography early after successful mechanical reperfusion of first acute myocardial infarction and that the extent of post-infarct Q-wave formation might therefore be used as a simple estimate of the amount of viable myocardium. METHODS AND RESULTS: 47 patients with first MI and treated by direct PCI were enrolled. Patients were divided into 3 groups according the presence and number of abnormal Q waves (group A-no abnormal Q wave; group B-< or =2 abnormal Q waves, group C-> or =3 abnormal Q waves). Left ventricular pump function was defined by ejection fraction (EF) on ventriculography and wall motion score index (WMSI) on echocardiography. Myocardial perfusion was defined by perfusion score index (PSI) on myocardial contrast echocardiography. Patients in group A had significantly better LV function than patients in other groups [EF 57+/-5 vs. 48+/-11% (group B) and 47+/-10% (group C); p<0.05], also WMSI was the best in this group [1.34+/-0.22 vs. 1.67+/-0.39 (group B) and 1.68+/-0.31 (group C); p<0.01]. Myocardial perfusion assessed by PSI was best in group A (1.2+/-0.3, p<0.05). With respect to PSI, there was a significant difference between group B and C (1.41+/-0.21 vs. 1.56+/-0.29; p<0.05), even though EF and WMSI did not differ in these groups. The amount of perfused segments with severe wall motion abnormality was higher in group B compared to group C (47% vs. 25%; p<0.05). CONCLUSION: In patients after successful mechanical reperfusion of first MI, the extent of Q-wave formation on ECG may be regarded as a corollary of the amount of myocardial microvascular damage and may, therefore, be used to estimate the amount of viable myocardium post-infarct.     

Predictive value of markers of myocardial reperfusion in acute myocardial infarction for follow-up left ventricular function

This study evaluated recently suggested invasive and noninvasive parameters of myocardial reperfusion after acute myocardial infarction (AMI), assessing their predictive value for left ventricular function 4 weeks after AMI and reperfusion defined by myocardial contrast echocardiography (MCE). In 38 patients, angiographic myocardial blush grade, corrected Thrombolysis In Myocardial Infarction frame count, ST-segment elevation index, and coronary flow reserve (n = 25) were determined immediately after primary percutaneous transluminal coronary angioplasty (PTCA) for first AMI, and intravenous MCE was determined before, and at 1 and 24 hours after PTCA to evaluate myocardial reperfusion. Results were related to global wall motion index (GWMI) at 4 weeks. MCE 1 hour after PTCA showed good correlation with GWMI at 4 weeks (r = 0.684, p <0.001) and was in an analysis of variance the best parameter to predict GWMI 4 weeks after AMI. The ST-segment elevation index was close in its predictive value. Considering only invasive parameters of reperfusion myocardial blush grade was the best predictor of GWMI at 4 weeks (R² = 0.3107, p <0.001). A MCE perfusion defect size at 24 hours of ≥50% of the MCE perfusion defect size before PTCA was used to define myocardial nonreperfusion. In a multivariate analysis, low myocardial blush grade class was the best predictor of nonreperfusion defined by MCE. Thus, intravenous MCE allows better prediction of left ventricular function 4 weeks after AMI than other evaluated parameters of myocardial reperfusion. Myocardial blush grade is the best predictor of nonreperfusion defined by MCE and is the invasive parameter with the greatest predictive value for left ventricular function after AMI. Coronary flow parameters are less predictive.     

Detection of Viability of Dysfunctional Myocardium in Coronary Heart Disease. II. Echocardiography

The detection of viable myocardium in patients with severe left ventricular (LV) dysfunction is important because these patients benefit most from revascularization. Three echocardiographic techniques can be used for the noninvasive assessment of functional correlates of viable myocardium. Two-dimensional echocardiography (2DE) is well suited for quantifying resting LV regional and global systolic function and dysfunction before and after revascularization, in addition to providing data on chamber size, shape, and wall thicknesses. The presence of hypokinesis on a resting 2DE indicates that viable myocardium is definitely present, but presence of dykinesis does not exclude viability. Dobutamine stress echocardiography (DSE) before revascularization unmasks viability by demonstrating augmentation of systolic function. Several clinical studies have shown that improvement of regional function during DSE indicates contractile reserve and predicts improvement of function after revascularization. A biphasic response on DSE appears to predict residual coronary artery stenosis and is a reliable marker of viability. DSE also appears to be useful after revascularization for unmasking contractile reserve. Myocardial contrast echocardiography (MCE) detects viability by defining microvascular perfusion, the extent of myocardium at risk, and coronary flow reserve. The clinical utility of MCE is undergoing evaluation. The combination of DSE and MCE might provide an improved estimate of the extent of viable myocardium based on assessment of function and perfusion. Meanwhile, echocardiographic and nuclear techniques can be used to complement each other in the assessment of myocardial viability.     

Detection of viable myocardium by transvenous myocardial contrast echocardiography using harmonic power Doppler: canine model of acute coronary occlusion and reperfusion

STUDY OBJECTIVE: To assess whether myocardial contrast echocardiography (MCE) using harmonic power Doppler (HPD) in conjunction with the transvenous contrast agent SHU 563A would be useful in detecting stunned but viable myocardium. DESIGN: Acute coronary occlusion (2 to 3 h) followed by 1 h of reperfusion was created in 10 dogs in an open-chest model. Measurements and results: Continuous harmonic B-mode for wall motion analysis and ECG triggered HPD for assessment of myocardial perfusion was employed during coronary occlusion and after reperfusion. Postmortem 2,3,5-triphenyltetrazolium chloride (TTC) staining was performed to verify infarction. Extent of wall motion abnormality (WMA), perfusion defect size, and anatomic infarct size (myocardial infarction [MI]) were analyzed in a 5-segment model. All 10 dogs showed WMA in 23 of 50 segments during coronary occlusion. In eight dogs, HPD detected perfusion defects in 18 of 50 segments. The concordance rate between WMA and perfusion defect was 86%. Mean linearized power (MLP) in segments with WMA was significantly lower compared to normal segments (60.7 +/- 38.9 vs 110.5 +/- 108.8, p < 0.05). After reperfusion, the extent of WMA was larger than the area of perfusion defect (percentage of left ventricular slice area): 30 +/- 13% vs 9 +/- 8%, p < 0.01. Eventual infarct size was 6 +/- 7%. WMAs were seen in 18 of 50 segments. TTC confirmed MI in 7 of 18 segments. MLP in segments with WMA but no MI was significantly higher compared to segments with WMA and MI (84.5 +/- 67.3 vs 13.2 +/- 9.6, p < 0.01). Thus, the extent of WMA after reperfusion was greater than the size of perfusion defect and eventual MI, indicating the presence of stunned but viable myocardium. CONCLUSION: MCE using HPD and the contrast agent SHU 563A can demonstrate the efficacy of reperfusion, identify necrotic regions, and aid in the recognition of stunned but viable myocardium. This approach could be useful clinically in patients with acute MI undergoing reperfusion therapy.     

Microvascular integrity and the time course of myocardial sodium accumulation after acute infarction

Loss of membrane permeability caused by ischemia leads to cellular sodium accumulation and myocardial edema. This phenomenon has important implications to left ventricular structure and function in the first hours after myocardial infarction. We hypothesized that during this period of time, after prolonged coronary occlusion and complete reflow, the rate of myocardial sodium accumulation is governed by microvascular integrity. We used 3-dimensional (23)Na MRI to monitor myocardial sodium content changes over time in an in vivo closed-chest canine model (n=13) of myocardial infarction and reperfusion. Infarcts with microvascular obstruction (MO) defined by both radioactive microspheres and contrast-enhanced (1)H MRI showed a slower rate of sodium accumulation as well as lower blood flow at 20 minutes and 6 hours after reperfusion. Conversely, the absence of MO was associated with faster rates of sodium accumulation and greater blood flow restoration. In addition, infarct size by (23)Na MRI correlated best with infarct size by triphenyltetrazolium chloride and contrast-enhanced (1)H MRI at 9 hours after reperfusion. We conclude that in reperfused myocardial infarction, sodium accumulation is dependent on microvascular integrity and is slower in regions of MO compared with those with patent microvasculature. Finally, (23)Na MRI can be a useful tool for monitoring in vivo myocardial sodium content in acute myocardial infarction.     

Treatment strategies for microvascular dysfunction following acute myocardial infarction

Successful reperfusion following acute myocardial infarction is considered to be restoration of epicardial infarct vessel patency, but recent studies suggest that disrupted microvascular function and inadequate myocardial tissue perfusion are often present despite epicardial patency. New angiographic techniques, including the corrected Thrombolysis in Myocardial Infarction (TIMI) frame count and myocardial blush grade, have been used to demonstrate that restoration of downstream coronary flow and tissue perfusion may be the key links to improved clinical outcomes. Additionally, other diagnostic techniques, including infarct size measurement with cardiac marker release patterns, or ^99m Tc-sestamibi single photon emission computed tomography imaging, and analysis of ST-segment resolution have also been used to assess microvascular function and tissue perfusion. Promising adjunctive therapies that target microvascular dysfunction, including platelet glycoprotein IIb/IIIa inhibitors, anti-inflammatory agents, vasodilators, glucose-insulin-potassium, and embolization protection devices, may ameliorate microvascular dysfunction following epicardial reperfusion. However, these therapies have not yet been shown to improve clinical outcomes and are thus currently being studied together with fibrinolytics and primary angioplasty in clinical trials. Therefore, shifting the focus of reperfusion therapy to the microcirculation offers the potential to further improve myocardial salvage and clinical outcomes following acute myocardial infarction.