Experts who spoke at this panel discussion agreed that myocardial contrast echocardiography (MCE) is a promising technique for assessment of myocardial viability because it provides direct visual assessment of regional myocardial perfusion. “MCE is the most powerful method of assessing myocardial perfusion and should be used at the first sign of ischemia,” said Fuminobu Ishikura, MD, of Osaka University.

MCE provides the real-time information about which areas of the myocardium are ischemic that is not gained with intermittent myocardial imaging, which is currently used in Japan. The advantages of real-time imaging with MCE are the more precise identification of the areas of ischemia and the information about wall motion and myocardial perfusion that is simultaneously provided. At present, real-time MCE is used in the US, mainly in the research setting. This method should be available in Japan in the near future.

“Real-time imaging can provide images of the opacified myocardium in multiple cross sections. Stress MCE will be a useful method to assess a myocardial infarction and to detect the area jeopardized by coronary stenosis,” stated Ishikura.

Studies of continuous intravenous infusion using Levovist, the only contrast media agent available in Japan, to assess myocardial perfusion was presented by Takashi Muro, MD, of Osaka City University. Muro noted that this is a rather weak contrast agent, making imaging studies a challenge.

Intravenous MCE has the potential for predicting myocardial viability in both the acute and subacute phases of myocardial infarction, said Muro. MCE assessment of myocardial viability depends on an intact microcirculation. Myocyte loss occurring as a result of myocardial infarction results in a loss of microvasculature, according to various studies. Therefore, the absence of myocardial opacification on MCE may reflect a lack of myocardial viability.

A study in 10 healthy volunteers demonstrated the feasibility of the technique. “A quantitative assessment of myocardial perfusion can be performed with intravenous MCE, particularly using harmonic power Doppler imaging with a continuous infusion of Levovist,” Muro said.

Another study assessed myocardial perfusion in 15 patients with myocardial infarction using intravenous MCE and compared it to positron emission tomography (PET) in the same patients. PET is considered the “gold standard” for myocardial imaging in Japan. All the study patients had anteroseptal myocardial infarction, indicating their lesions were well opacified in four chambers.

The concordance between MCE and PET was good in normal and severely reduced segments of the myocardium, but discordance between these two imaging modalities was observed in the mildly reduced segments (Figure 1). Many of the segments that were mildly reduced on PET imaging appeared normal on MCE, suggesting that MCE is not as sensitive as PET to mild perfusion abnormalities (Figure 2).

“The concordance between MCE and PET is not ideal, particularly when the focus is on the segments around the left ventricle. Although intravenous MCE has several limitations for identifying myocardial viability, this non-invasive technique should be a useful tool for clinical practice,” stated Muro.

The value of MCE in assessing collateral vessel function compared to coronary angiography (CA) was studied by Lim and colleagues. Visualization of epicardial coronary collateral vessels by CA does not provide functional information about these vessels, because the presence of collaterals does not necessarily mean that myocardial perfusion is occurring, explained Young-Jae Lim, MD, Department of Cardiology, Kawachi General Hospital. CA visualizes vessels > 100 microns and demonstrates epicardial arterial conduits. MCE uses microbubbles that can traverse smaller collateral networks, can visualize myocardial tissue perfusion, and delineates the occluded bed area and pre-perfusion residual flow.

MCE is an alternative method to CA for the assessment of dynamic collateral circulation at rest and during stress. Intravenous MCE would be a unique noninvasive method of assessing coronary collateral function, if studies show that intravenous and intracoronary MCE are equally valuable methods of assessing collateral function. However, several problems remain to be overcome before intravenous MCE can be applied in the clinical setting, including the need for real-time imaging instead of intermittent imaging, the limited angular view possible at present, and the need for improved clarity of myocardial staining.

For many years, it has been generally assumed that resistance due to coronary stenosis prevents an increase in hyperemic myocardial blood flow, which leads to a reduction in coronary blood flow reserve. Kaul and colleagues performed studies using contrast echocardiography, which demonstrated that, in fact, an increase in capillary resistance is the major reason for decreased coronary flow reserve in the presence of a stenosis. “The resistance offered by the stenosis itself plays only a small role in reducing coronary flow reserve,” stated Sanjiv Kaul, MD, University of Virginia, USA.

Contrast echocardiography allows visualization of the capillary circulation. The capillaries are the “bottleneck” for hyperemic flow during maximal hyperemia in normal people. Any condition, including hyperlipidemia and hyperglycemia, that changes capillary resistance and blood viscosity will change hyperemic flow.

The greater the number of capillaries present, the less resistance and the higher the hyperemic coronary blood flow. If the capillary number is reduced, as in diabetes, hypertension, or myocardial infarction, coronary blood flow is reduced even in the absence of a stenosis. In the presence of a stenosis, there is de-recruitment of capillaries distal to the stenosis during hyperemia, resulting in increased capillary resistance.

Even in the presence of stenosis, capillaries remain the major determinant of reduction in hyperemic flow because of de-recruitment of capillaries distal to the stenosis. This in turn causes perfusion defects. This may be the reason that hyperlipidemia plus stenosis may be much worse than hyperlipidemia in the absence of stenosis or vice-versa. It appears that more than one factor can cause an increase in capillary resistance, a decrease in capillary blood volume and a change in blood viscosity.