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Symposium Clinical 8
New Developments in Echocardiography: Recent Advances in Technology and Challenges to Ischemic Heart Disease
Shintaro Beppu
Osaka University, Suita, Japan
Young-Jae Lim
Kawachi General Hospital, Higashi-Osaka, Japan
Hiroyuki Watanabe
Osaka City University Graduate School of Medicine, Osaka, Japan
 
  • Myocardial Contrast Echocardiography Investigation of the Coronary Circulation
  • Coronary Tree Assessment with Contrast Harmonic Imaging
  • Non-Invasive Assessment of Coronary Flow by Transthoracic Doppler Echocardiography



  • Myocardial Contrast Echocardiography Investigation of the Coronary Circulation


    Myocardial contrast echocardiography (MCE) had been limited by the requirement for direct injection of the contrast agent into the coronary artery. However, myocardial opacification is now possible with venous injection. The use of MCE for the diagnosis of coronary stenosis and investigating the microcollaterals and coronary tree are expanding its use.


    Figure 1. Comparison of the sensitivity of detecting coronary stenosis using the slope of the replenishment curve and the wall motion abnormalities.
    Click to enlarge

    The concept of coronary flow reserve is used to diagnose coronary stenosis. Hyperemia is caused by dipyradimole or ATP and then real-time perfusion imaging using high-energy ultrasound and microbubbles allows for calculating the replenishment curve. In the basal state, the replenishment curve is nearly identical between the normal controls and the area at risk. But the curves differ greatly under ATP. The sensitivity for detecting coronary stenosis using the slope of the replenishment curve is very high in the range of 88-100%, compared to using wall motion abnormalities in the range of 11-55% (Figure 1).


    A diagnostic tool for myocardial ischemia is available for each stage of the ischemic cascade that follows reduced coronary flow: MCE for decreased myocardial perfusion; positron emission tomography (PET) for anaerobic metabolism; Doppler ultrasound for diastolic dysfunction; 2-dimensional echocardiography for wall motion abnormality; and electrocardiogram for electrical changes. However, calculation of the replenishment curve is time consuming. Hence, the difference between the area under the curve (stenosis present) and the area above the curve (stenosis absent) is informative. Thus, parametric imaging provides good demonstration of the area at risk, with images quite similar to those obtained with thallium SPECT imaging.

    Microcollaterals are essential for myocardial salvage, while the presence of angiographically-proven collaterals is not crucial. For the calculation of the microcollaterals, three regions in the area at risk are identified and the collaterals are classified into 1 of 4 categories: none, poor, fair, good. Asynergy is also classified, as normal, mild hypokinesis, severe hypokinesis, and akinesis. The total score is calculated by adding the scores for the three different regions. A good correlation between the collateral score and wall motion score has been demonstrated.

    Clinically, a mean arterial pressure (MAP) of less than 80 mmHg after nitroglycerin administration is associated with a larger area of myocardial damage, compared to a MAP greater than 80 mmHg after nitroglycerin administration. The blood pressure level effects the opacification; compared to the opacification achieved with a control blood pressure of 92 mmHg, opacification is worsened when the blood pressure is reduced with nitroglycerin to 65 mmHg but improved when the blood pressure is increased to 133 mmHg. Yet, a further increase in blood pressure to 152 mmHg worsens the opacification, similar to that seen with a blood pressure of 92 mmHg, showing the delicate nature of the effect of blood pressure on collaterals. A J-curve effect exists in relation to the blood pressure, in which a high or low blood pressure level is associated with poor collateral flow, while a blood pressure of 140 mmHg is associated with good collateral flow. In the normal coronary artery, there is a curvilinear relationship between coronary perfusion pressure and coronary flow volume. But in the collaterals, there is a reverse J curve phenomenon.

    MCE is the only tool for detection of microcollateral vessels, which are responsible for wall motion abnormality in a region of coronary occlusion. The microcollateral region is characterized by an ischemic zone with a core and border zone, slow blood filling, and blood pressure-dependency, such as a reversed J response or loss of autoregulation of coronary flow.

    Visualization of the coronary tree is possible, and the acoustic power used determines which vessels can be imaged, since the video intensity depends on flow speed and acoustic power. 3-D imaging allows visualization of the arteriolar plexus. Doppler should be used for imaging the stem and branches of the coronary tree, and contrast echo with changes in the acoustic power for the fine branches of the tree. Clearly, beyond myocardial opacification, MCE is a powerful tool for investigating the coronary circulation.

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    Coronary Tree Assessment with Contrast Harmonic Imaging


    Harmonic imaging (HI) represents one of the recent revolutions in echocardiography. Myocardial contrast echocardiography (MCE) is performed intravenously using intermittent imaging. Third-generation harmonic imaging has provided real-time MCE. Determining the degree of myocardial blood flow in each level of the coronary tree is the goal of MCE.

    Young-Jae Lim and colleagues at Kawachi General Hospital in Higashi-Osaka, Japan investigated the use of different frame rates in MCE to visualize the coronary tree, with the hypothesis that a higher frame rate to increase the destruction of microbubbles would image only faster flow. Other investigators have used higher acoustic power to visualize the coronary tree.

    In 20 patients with ischemic heart disease (IHD) the three different frame rates for visualizing the coronary tree were: 1) intermittent, slow frame rate; 2) semi-real time, intermediate frame rate; 3) real time, fast frame rate. Levovist was used in the third-generation HI.

    Intermittent imaging consisted of a pulse interval of 1:1 to 1:8 to detect slow flow. Clear visualization of the infarct area was achieved with intermittent imaging. Third-generation HI was very sensitive to the signal from the microbubbles, compared to second generation HI. Blood volume and blood velocity could be calculated from the replenishment curve by changing the pulse interval. Using intermittent imaging, curve fitting was possible in 76.5% of the targeted region of interest. Blood volume was 5.3 ±3.8 and the blood velocity was 1.0± 1.0. Capillary circulation could be assessed with slow frame rate MCE.


    Figure 2. 3rd Harmonic semi-real time imaging in a patient with an anterior septal myocardial infarction showed rapid filling in the normal areas and delayed filling via collateral channels in the infarcted areas.
    Click to enlarge
    Semi-real time imaging at 5 frames per second detected intermediate speed flow. A representative case, in a patient with an anterior septal myocardial infarction (MI), showed rapid filling in the normal areas and delayed filling via collateral channels in the infarcted areas (Figure 2). Moreover, a cyclic variation could be seen, in which myocardial staining increased in diastole and decreased in systole.

    The visual score for myocardial staining was only 1.0 ± 0.6 in the infarct region, compared to 1.5 ± 0.55 in the normal region (p<0.05). Moreover, analysis of cyclic variation in normal and infarcted regions showed a greater change in cyclic variation in the normal areas (50dB peak intensity (PI) at end diastole, 30 db PI at end systole; p<0.05) compared to the infracted areas (25 dB PI at end diastole, 12 dB at end systole). In summary, semi-real time perfusion imaging at 5 Hz showed more rapid flow in the capillaries; compression of arterioles may result in cyclic variation; pre-capillary circulation may be damaged during infarction. Pre-capillary circulation could be visualized with semi-real time perfusion imaging.

    Real-time imaging at 26 frames per second was used to detect fast flow, with the goal of visualizing intramyocardial small vessels. The septal perforator was visualized. Real-time imaging at this speed resulted in vascular, not perfusion, imaging. Line-form small artery flows were detected in 80% of viable areas. Doppler evaluation could be possible for small arteries. Thus, a high frame rate vascular image could assess small artery flow.

    The investigators concluded that MCE at different frame rates visualizes coronary flow at different flow velocities. Intermittent imaging using a low frame rate visualized coronary circulation and no cycle variation. Semi-real time imaging using an intermediate frame rate visualized pre-capillary circulation, including arterioles and venules. Real-time imaging using a high frame rate visualized small artery circulation. Hence, echocardiography can non-invasively assess all rates of flow of the coronary tree. They suggest real-time imaging for small arteries, semi-real time for pre-capillary vessels, intermittent imaging for capillaries, and Pulse Doppler transthoracic echocardiography for epicardial coronary arteries.

    The assessment of absolute myocardial blood volume (MBV) in the coronary tree may be possible. Yamada and colleagues reported a novel method for estimating MBV using the ratio of the signal intensity in the myocardium versus blood. Relative amplitude can be measured as the brightness of the myocardium minus the brightness of the blood. Thus, the absolute MBV can be calculated using this equation: 10RelAmp/10X100 (ml/100cm3). Tanaka and colleagues reported that the triggering method in MCE gives the absolute MBV in capillary flow, while semi-real time imaging at 5 Hz provides absolute MBV in pre-capillary flow.

    Clinically, 3-staged intravenous MCE provides non-invasive imaging from the small artery to the capillary bed. Thus, the entire flow of the coronary tree can be assessed. Yet, some limitations must be addressed for this to be an established clinical tool, including stronger myocardial opacification, better reproducibility, lesser attenuation and shadow, elimination of LV opacification, and true-real time imaging. On the horizon, real-time imaging with a newly available 1.5 HI appears to allow visualization of defects despite coronary reflow.

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    Non-Invasive Assessment of Coronary Flow by Transthoracic Doppler Echocardiography


    Coronary flow assessment is useful in the evaluation of ischemic heart disease (IHD) and variation in coronary microcirculation. Images obtained by transthoracic Doppler echocardiography (TDE) allow for visualization of the colored Doppler signal throughout diastole and the flow signal in the left anterior coronary artery. TDE is real-time, easy, accurate and cost effective. Pulse Doppler provides for measurement of flow velocity.

    Hiroyuki Watanabe, MD, reviewed research by investigators at Osaka City University Graduate School of Medicine with TDE for the diagnosis of coronary artery disease (CAD) and assessment of the coronary microcirculation. These data, with that from other investigators worldwide, show TDE to be an important clinical tool for the noninvasive and physiological evaluation of the coronary circulation.

    These investigators compared coronary flow reserve (CFR) measures as obtained by TDE and the validated measures obtained with 201-TI SPECT imaging. Of 12 patients who were SPECT-positive, 11 were CFR positive on TDE, with a threshold of 2.0. Of 21 SPECT-negative patients, 19 were CFR negative on TDE. The sensitivity and specificity of TDE, compared to SPECT imaging, was 92% and 90% respectively. The positive predictive value was 85% and the negative predictive value was 95%.

    In patients with angina, Doppler guide wire measurement for severe stenosis (>85% diameter stenosis) was shown to have a specificity of 77.9% and sensitivity of 77% for a cut-of value of 1.5. Despite the somewhat limited values, the advantage is that stress is not required.

    In a study of 296 patients, TDE showed reverse flow in 22 patients and forward flow in 274 patients. In the patients with reverse flow, coronary angiography revealed occlusion in the left anterior descending (LAD) in 16 patients and in the septal branch in 6 patients, and occlusion in one patient with forward flow. For the LAD, TDE compared to coronary angiography for the assessment of flow direction has a sensitivity of 70% and only 26% for the septal branch. However, combining the LAD and septal branch yields a sensitivity of 96%. CFR measurement by TDE accurately reflects the physiological severity of the coronary narrowing as well as anatomical severity.

    Flow estimation and coronary flow visualization in the right coronary artery and left circumflex by TDE was successful in the hands of these investigators, showing TDE to be a promising technique to diagnose significant stenosis in the three major coronary arteries.

    In their research in assessing the coronary microcirculation with TTDE, they showed that passive smoke decreased CFR to about 3.4 in non-smokers, which was about the same level seen in smokers after exposure to passive smoke. The smokers had a lower baseline CFR compared to non-smokers (3.6 versus 4.4, respectively). The investigators say this provides direct evidence that passive smoke is harmful for the coronary microcirculation in nonsmokers. CFR was decreased at 5 hours after a single high fat meal to 3.3 from 4.0 at baseline. Estrogen had no effect on CFR in men, while it increased CFR in both pre- and post-menopausal women. Additional studies showed that vodka and white wine had no effect on CFR in 15 volunteers, however, CFR was significantly increased from 3.0 to about 5.0 after consumption of red wine, which may be one of its important cardioprotective effects. These studies show that coronary flow assessment by TDE can be used for the assessment of the coronary microcirculation in subjects without coronary narrowing.

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