Evaluation of collateral blood flow by myocardial contrast enhanced echocardiography

Contrast enhanced cross sectional echocardiography is a new method for the real-time evaluation of regional myocardial perfusion. Two patients with a history of anteroseptal myocardial infarction and echocardiographically detected septal dyskinesia were examined by this new method. The first patient had two severe stenoses of the left anterior descending coronary artery and normal echocontrast opacification of the interventricular septum caused by collaterals from the right coronary artery. The second patient had good patency of left anterior descending coronary artery and no septal opacification. Thus contrast enhanced cross sectional echocardiography can be used to assess the importance of collateral blood flow in the myocardium.     

Combined assessment of reflow and collateral blood flow by myocardial contrast echocardiography after acute reperfused myocardial infarction

OBJECTIVE: To evaluate the combined assessment of reflow and collateral blood flow by myocardial contrast echocardiography after myocardial infarction. DESIGN: Myocardial contrast echocardiography was performed in patients with acute myocardial infarction shortly after successful coronary reperfusion (TIMI 3 patency) by direct angioplasty. Collateral flow was assessed before coronary angioplasty, and contrast reflow was evaluated 15 minutes after reperfusion. The presence of contractile reserve was assessed by low dose dobutamine echocardiography (5 to 15 micrograms/kg/min) at (mean (SD)) 3 (2) days after myocardial infarction. Recovery of segmental function (myocardial viability) was evaluated by resting echocardiography at a two month follow up. The study was prospective. PATIENTS: 35 consecutive patients referred for acute transmural myocardial infarction. RESULTS: Contrast reflow was observed in 20 patients (57%) and collateral flow in 14 (40%). Contrast reflow and collateral contrast flow were both correlated with reversible dysfunction on initial dobutamine echocardiography and at follow up (p < 0.05). The presence of reflow or collateral flow on myocardial contrast echocardiography was a highly sensitive (100%) but weakly specific (60%) indicator of segmental dysfunction recovery. Simultaneous presence of contrast reflow and collateral flow was more specific of reversible dysfunction than reflow alone (90% v 60%). CONCLUSIONS: Combined assessment of reflow and collateral blood flow enhanced the sensitivity of myocardial contrast echocardiography in predicting myocardial viability after acute, reperfused myocardial infarction. The simultaneous presence of reflow and collateral blood flow was highly specific of recovery of segmental dysfunction.     

Functional significance of collateral blood flow in patients with recent acute myocardial infarction. A study using myocardial contrast echocardiography.

BACKGROUND. We hypothesized that myocardial contrast echocardiography (MCE) can be used to both measure collateral blood flow as well as assess the functional significance of collaterals in patients with acute myocardial infarction (AMI). METHODS AND RESULTS. MCE was performed in 33 patients with recent AMI (12 +/- 7 days) and an occluded infarct-related artery (IRA), both before and after attempted percutaneous transluminal coronary angioplasty (PTCA). The size of the occluded bed was defined in patients with successful PTCA by injecting contrast directly into the opened IRA and expressed as a percent of the myocardium in the short-axis view. The percent of the perfusion bed supplied by collaterals before PTCA was determined. Transit rates of the microbubbles within the collateralized regions were also measured and were expressed as a percent of the transit rates in the normal adjacent beds. Regional function within the occluded bed was assessed using echocardiography and was graded as 1 (normal) to 5 (dyskinetic). Collaterals were graded on coronary angiography as 0 (none) to 3 (abundant). The perfusion bed size was larger for the left anterior descending (LAD) than for the right (RCA) and left circumflex (LCx) coronary arteries (37 +/- 6% versus 27 +/- 12% of the myocardium, p = 0.02). The percent of the occluded bed supplied by collateral flow was greater for RCA and LCx compared with the LAD (87 +/- 30% versus 72 +/- 22%, p less than 0.01). There was poor correlation between MCE-defined percent of occluded bed supplied by collaterals and angiographic collateral grade (r = 0.13). Regions supplied by collaterals were less likely to show confluent hypoperfused zones after reperfusion compared with those not supplied by collaterals. Similarly, the percent of myocardium not perfused by either anterograde or collateral flow correlated well (r = 0.67, p less than 0.01) with peak creatine kinase levels and was more likely to be associated with Q waves. Finally, although there was poor correlation between angiographic collaterals and regional function (r = 0.20), there was a significant negative correlation between MCE-defined spatial extent of collateral flow and regional function (r = -0.57, p less than 0.01). CONCLUSION. MCE can be used to measure collateral flow in patients with recent AMI and to assess the functional significance of collaterals in these patients. This technique may be ideally suited for the assessment of collateral perfusion in patients undergoing cardiac catheterization.     

Assessment of regional myocardial blood flow with myocardial contrast two-dimensional echocardiography

It was hypothesized that regional myocardial blood flow could be measured using myocardial contrast echocardiography. Accordingly, arterial blood was perfused into the coronary circulation in 16 dogs. In Group 1 dogs (n = 8), blood flow to the cannulated left circumflex artery was controlled with use of a roller pump, whereas in Group 2 dogs (n = 8) blood flow to the left anterior descending coronary artery was controlled by a hydraulic occluder placed around it. Sonicated microbubbles (mean size 4 microns) were used as the contrast agent. In Group 1 dogs the microbubbles were injected subselectively into the left circumflex artery, whereas in Group 2 dogs they were injected selectively into the left main coronary artery and two-dimensional echocardiographic images were recorded. Computer-generated time-intensity curves were derived from these images and variables of these curves correlated with transmural blood flow measured with radiolabeled microspheres. A gamma-variate function (y = Ate-alpha t) best described the curves, and alpha (a variable of curve width) correlated well with transmural blood flow at different flow rates in all Group 1 and Group 2 dogs (mean r = 0.81 and 0.97, respectively). Other variables of the curve width also correlated well with myocardial blood flow, but peak intensity had a poor correlation with myocardial blood flow in both groups of dogs (r = 0.39 and r = 0.63, respectively). When data from all dogs were pooled, Group 1 dogs still showed good correlation between variables of curve width and myocardial blood flow (r = 0.81); Group 2 dogs did not (r = 0.45). The difference between the two sets of dogs was related to the site of contrast agent injection. It is concluded that measurement of the transit time of microbubbles through the myocardium with two-dimensional echocardiography accurately reflects regional myocardial blood flow. Although injection of contrast agent selectively into the left main coronary artery only allows measurement of relative flow, it may be feasible to measure absolute flow by injecting contrast agent subselectively into a coronary artery. Myocardial contrast echocardiography may, therefore, offer the unique opportunity of simultaneously assessing regional myocardial perfusion and function in vivo.     

Evaluation of function of human collateral coronary arteries using myocardial contrast echocardiography

The morphology of collateral vessels can be imaged by coronary angiography, but no method has been available for evaluating their function. This is a report of the use of regional myocardial perfusion to visualize collateral flow by means of myocardial contrast echocardiography in 28 patients with old myocardial infarction. Myocardial contrast echocardiography was accomplished by the intracoronary injection of two ml agitated amidotrizoate sodium meglumine. Short-axis images of the left ventricle were recorded on video tape. Those images were digitized off-line into a 512 x 512 pixel matrix. Using coronary angiography, the morphology and function of the collateral vessels were evaluated, then classified as poor, moderate or good. Myocardial perfusion was evaluated using the enhanced gray level after contrast injection, and the level was compared with the morphology and degree of collateral development. The enhanced gray level was evaluated arbitrarily as 3 +/- 2 U (mean +/- S.D.) in the "poor" group; 13 +/- 6 U in the "moderate" group; and 20 +/- 11 U in the "good" group (p less than 0.01 vs the "poor" group; NS vs the "moderate" group). Regional myocardial perfusion via the collateral vessels was generally proportional to the morphology. However, there were a few discrepancies between these two parameters.     

Assessment of myocardial blood flow and volume using myocardial contrast echocardiography

The development of new microbubble agents and ultrasound imaging modalities now allows the assessment of myocardial perfusion with echocardiography. Microbubbles also can be administered intravenously as constant infusions, which allows their concentration in blood to reach steady state. If the relation between microbubble concentration and video intensity is within the linear range, then myocardial video intensity will reflect the concentration of microbubbles in that region, which at steady state is the myocardial blood volume. The ability to destroy microbubbles and measure their replenishment into the ultrasound beam provides an opportunity to evaluate microbubble (or red blood cell) velocity. The product of myocardial blood volume and red blood cell velocity represents myocardial blood flow.     

Evaluation of coronary flow reserve using myocardial contrast echocardiography in humans.

To evaluate the applicability of myocardial contrast echocardiography for the assessment of coronary blood flow reserve, 21 consecutive patients undergoing coronary angiography were studied. Only patients with a single left anterior descending lesion or normal coronary angiogram were included. Intracoronary injections of sonicated albumin were performed before and after the administration of intracoronary papaverine. Good quality studies at baseline and after the administration of papaverine were obtained in 14 of 21 patients. Ten patients had a significant (greater than 75%) single left anterior descending lesion and four had normal or insignificant lesions (70% or less stenosis) in the left anterior descending coronary artery. Time-intensity curves for the left anterior descending coronary artery region of interest were generated and then the peak contrast intensity (PCI), washout half-time (T1/2) and the area under the curve (AUC) were calculated. The post-papaverine increases in PCI and in the AUC, compared to baseline, were 55 +/- 22% and 102 +/- 14% in the four patients with 70% or less left anterior descending diameter stenosis serving as a control group and 3 +/- 25% and 40 +/- 10%, respectively, in the 10 patients with significant left anterior descending coronary artery disease (mean +/- 1 SD, P less than 0.01). In patients with normal coronary arteriography T1/2 increased after intracoronary injection of papaverine. In patients with severe lesions, either an increase or a decrease in T1/2 was observed. Significant left anterior descending coronary artery stenosis associated with impaired coronary blood flow reserve can be detected by failure of myocardial contrast echocardiographic parameters to increase after injection of papaverine. Mild and transient side effects were noted in three patients.     

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.     

Usefulness of myocardial contrast echocardiography in predicting collateral blood flow in the presence of a persistently occluded acute myocardial infarction-related coronary artery

Adequate collateral blood flow at rest can sustain myocardial viability despite persistent occlusion of the infarct-related artery (IRA) in acute myocardial infarction (AMI). This has therapeutic and prognostic implications. Studies addressing the value of intravenous myocardial contrast echocardiography (MCE) to detect collateral blood flow after AMI in humans are limited. Accordingly, 70 consecutive patients with AMI underwent low-power intravenous MCE using a Sonovue infusion 7 to 10 days after thrombolysis. Myocardial perfusion detected by MCE was analyzed (qualitatively and quantitatively) in the akinetic segments in 20 patients (29%) with an occluded IRA who subsequently underwent revascularization. Contractile reserve, which is a marker of myocardial viability, was assessed with low-dose dobutamine 12 weeks after mechanical revascularization. Of the 102 akinetic segments (32%), 37 (36%) showed contractile reserve. Contractile reserve was present in 24 of the 29 segments (83%) with homogenous contrast opacification and absent in 60 of the 73 segments (82%) with reduced/absent opacification. Quantitative peak contrast intensity, microbubble velocity, and myocardial blood flow were significantly higher (p <0.0001) in the segments with contractile reserve than in those without contractile reserve. Multiple logistic regression analysis using electrocardiographic, biochemical, and myocardial contrast echocardiographic markers of collateral blood flow showed that MCE (odds ratio 26.0, 95% confidence interval 6.3 to 108.0, p <0.001) was the only independent predictor of collateral blood flow as demonstrated by the presence of contractile reserve. MCE may thus be used as a reliable bedside technique for the accurate evaluation of collateral blood flow in the presence of an occluded IRA after AMI.     

Definitive myocardial blood flow evaluated by contrast echocardiography: experimental and A-C bypass flow studies]

We evaluated the feasibility of a new method for calculating definitive myocardial flow using contrast echocardiography in canine experiments and in patients who had undergone ACBG surgery. The principle for calculating flow was based on Kety-Schmidt method using time-intensity curve analysis between the epicardial and endocardial aspect. Inlet and outlet flows were hypothesized at the epicardium and endocardium, respectively. Analysis of time-contrast-intensity curves between the epicardium and endocardium, the difference of the area to the saturated point between epicardium and pericardium (A), and the saturated value (H) theoretically lead to the equation: Flow = 100 x (H/A) (Kety-Schmidt) in a 100-gram myocardium. No factors of intensity and time were included. Using this equation, the flow in 7 experimental canine and the flow of 9 patients who had ACBG surgery were compared to the electromagnetic flow. In the canine experiments, the left circumflex coronary artery was dissected free and was connected with contrast injector, a magnetic flowmeter and pneumatic occluder, proximal to distal in this order. Flow was controlled either by the occluder or drugs (papaverin and dipyridamole). Manually-agitated contrast media were injected rapidly (1 ml/2.5 sec), and M-mode echocardiographic recordings were densitometrically translated into time-intensity curves. Thirty-eight trials in 7 dogs showed close correlations (r = 0.901) between the electromagnetic flow and contrast echo flow. For the patients with ACBG, M-mode contrast echo recordings were made using transesophageal echo during the operations with contrast injections via the bypass grafts. Analysis of time-intensity curves was made and recorded in the same way as during the experiments.(ABSTRACT TRUNCATED AT 250 WORDS)     

Assessment of regional myocardial blood flow with myocardial contrast echocardiography: an experimental study

OBJECTIVES: The aim of this study was to verify the accuracy of using myocardial contrast echocardiography (MCE), to quantify regional myocardial blood flow (MBF), and to evaluate myocardial viability in comparison to that measured by radiolabeled microsphere and pathologic examination. METHODS: Epicardial MCE was obtained in five myocardial ischemic dogs with constant microbubble intravenous infusion. After the video intensity (VI, y) versus pulsing interval plots derived from each myocardial pixel were fitted to an exponential function: y = A(1 - e(-beta t)), the MBF was calculated as the product of A (microvascular cross-sectional area or myocardial blood volume) and beta (mean myocardial microbubble velocity). The MBF was also obtained by radiolabeled microsphere method. RESULTS: The MBF derived by radiolabeled microsphere method in the normal, ischemic, and infarcted region was 1.5 +/- 0.3, 0.7 +/- 0.3, and 0.3 +/- 0.2 ml/min per gram, respectively; P < 0.01. The product of A and beta in those regions was 52.5 +/- 15.1, 24.4 +/- 3.9, and 3.7 +/- 3.8, respectively; P < 0.01. The normalized product of A and beta correlated well with normalized MBF (r = 0.81, P = 0.001). CONCLUSION: Our initial study demonstrated that MCE has an ability to assess MBF in ischemic myocardium in the experimental model. It may provide a potential capability to detect viable myocardium noninvasively after total persistent coronary occlusion in the clinical setting.     

Evaluation of transmural myocardial perfusion by ultra-harmonic myocardial contrast echocardiography in reperfused acute myocardial infarction.

BACKGROUND: The transmural distribution of myocardial perfusion is important for predicting the contractile reverse of an infarcted wall in reperfused acute myocardial infarction (AMI). Evaluating transmural myocardial perfusion by myocardial contrast echocardiography (MCE) could predict the long-term recovery of left ventricular (LV) function. METHODS AND RESULTS: The study group comprised 20 consecutive patients with a first-episode anterior AMI with total occlusion of the proximal left anterior descending artery, who underwent successful percutaneous coronary intervention within 24 h of onset. MCE was performed on the 15th day after the onset, using ultraharmonic gray-scale imaging with intermittent end-systolic triggering every 4 beats or every 6 beats. Regions of interest were placed over both the endocardial and epicardial region at the mid-septal level. Regional wall motion (RWM) of the infarcted anterior wall and global LV function were assessed by 2-dimensional echocardiography and left ventriculography in both the acute and chronic phase. The transmural distribution of myocardial perfusion by MCE demonstrated a significant relation with RWM score index (r = 0.75, p = 0.0004). Recovery of RWM and LV ejection fraction (LVEF) at 6 months after reperfusion was significantly greater in the group with good perfusion of the epicardium according to MCE than in the poor perfusion group [RWM (SD/cord); -1.23+/-0.91 vs -3.51+/-0.84, p = 0.001, LVEF (%); 63.8+/-10.4 vs 47.0+/-3.4, p = 0.04]. CONCLUSIONS: Assessing the transmural distribution of myocardial perfusion by MCE can predict the long-term recovery of LV function after a reperfused AMI.     

Dynamic changes in microcirculatory blood flow during dobutamine stress assessed by quantitative myocardial contrast echocardiography

Background: Although dobutamine‐atropine stress echocardiography (DASE) has been widely used for evaluating patients with coronary artery disease (CAD), dynamic changes that occur at microcirculatory level during each stage of stress have not been demonstrated in humans. Aim: We sought to determine variations in myocardial blood flow (MBF) during DASE using quantitative real time myocardial contrast echocardiography (RTMCE). Methods: We studied 45 patients who underwent coronary angiography and RTMCE. Replenishment velocity of microbubbles in the myocardium (β) and MBF reserves were obtained at baseline, intermediate stage (70% of maximal predicted heart rate), peak stress, and recovery phase. Results: β and MBF reserves were lower in patients with than without CAD at intermediate (1.65 vs. 2.10; P = 0.001 and 2.44 vs. 3.23; P = 0.004) and peak (1.63 vs. 3.00; P < 0.001 and 2.14 vs. 3.98; P < 0.001, respectively). In patients without CAD, β, and MBF reserves increased from intermediate to peak and decreased at recovery, while in those without CAD reserves did not change significantly. Optimal cutoff values of β reserve at intermediate, peak, and recovery were 1.78, 2.09, and 1.70, with areas under the curves of 0.80 (95%CI = 0.67–0.94), 0.89 (95%CI = 0.79–0.99), and 0.69 (95%CI = 0.53–0.85). Sensitivity, specificity and accuracy for detecting CAD at intermediate stage were 68% (95%CI = 48–89), 85% (95%CI = 71–98), and 78% (95%CI = 66–90), at peak stress were 79% (95%CI = 61–97), 96% (95%CI = 89–100), and 89% (95%CI = 80–98), and at recovery were 74% (95%CI = 54–93), 65% (95%CI = 47–84), and 69% (95%CI = 55–82), respectively. Conclusion: RTMCE allows for quantification of dynamic changes in microcirculatory blood flow at each stage of DASE. The best parameter for detecting CAD in all stages was β reserve. (Echocardiography 2011;28:993‐1001)     

Is myocardial contrast echocardiography ready to assume 'gold standard' status for quantification of collateral flow in humans?

Quantification of collateral flow in humans is most importantand we recognize the valuable contribution by Vogel et al.¹towards this aim. However, some methodological issues relatedto the promising ultrasound-based method described     

Extracoronary collateral myocardial blood flow during cardioplegic arrest

Extracoronary blood flow to the myocardium was studied in 54 patients during cold cardioplegic arrest. Coronary venous return was measured with the aorta and the pulmonary artery cross-clamped, both venae cavae occlusively snared, and the heart completely drained. Cold St. Thomas' cardioplegic solution was infused into either the aortic root or the coronary ostia. Myocardial septal temperature was continuously monitored. The amount of blood in the right atrial effluent was determined by means of the hematocrit and was considered to be the extracoronary collateral myocardial blood flow (QE), originating from the systemic circulation. QE ranged from 0 to 1470 ml-100 min-1 (x = 241.1 ml-100min-1). The myocardial spontaneous rewarming rate was not significantly correlated to QE. QE was lowest in pure mitral valve stenosis (x = 39.9 ml-100 min-1) and higher in aortic valve disease (x = 165.5 ml-100 min-1). Very high QE values (greater than 800 ml-100 min-1) were only observed in patients with severe three vessel coronary artery disease. Patients with angina at rest appear to have lower QE values than patients with equally severe coronary artery disease suffering from angina under excise only. It is concluded that extracoronary collateral blood flow may unpredictably influence the efficacy of clinical cardioplegia and may to some extent compensate for severe coronary artery disease.