Applied Radiology

Dr. Chandwaney is a Cardiology Fellow at Northwestern University Medical School, Section of Cardiology, Chicago, IL. He received his MD from the University of Illinois at Chicago in 1996 and completed his internal medicine residency at Baylor College of Medicine, Houston, TX, in 1999.

Since the introduction of coronary angioplasty by Andreas Gruentzig in 1977, ¹ percutaneous coronary intervention has evolved rapidly as an integral component in the management of patients with coronary artery disease (CAD). More than 700,000 percutaneous coronary interventions are performed annually in the United States, and it has been estimated that more than 1,000,000 procedures are performed worldwide each year. ²

Generally, in terms of coronary angiography, critical coronary stenoses are defined as those that appear to have >50% luminal diameter narrowing in the left main coronary artery or >70% luminal diameter narrowing elsewhere. ^3,4 Interventional cardiologists commonly encounter situations in which they are faced with intermediate coronary lesions of indeterminate significance. These intermediate lesions present a special challenge to cardiologists as it is difficult to determine whether the potential benefits of a mechanical intervention outweigh the potential risks. Several adjunctive technologies have been developed that enable interventional cardiologists to better assess intermediate coronary lesions.

Quantitative coronary angiography

In many catheterization laboratories, clinical decision-making regarding coronary stenoses is based on qualitative readings of angiographic lesions rather than quantitative assessment. Qualitative visual assessment of angiographic lesions is limited by bias, intraobserver variability, and interobserver variability. ^5-8 Quantitative methods use automated or manual edge-detection systems to quantify coronary stenoses more accurately. When compared with quantitative coronary angiography, visual estimation of lesion stenosis correlates poorly. ⁹ Clearly, the difficult assessment of intermediate coronary lesions is improved by the more accurate and reproducible determination of luminal narrowing obtained with quantitative coronary angiography.

Despite the more accurate assessment of luminal narrowing provided by quantitative coronary angiography, the technique has limitations. Several studies have challenged the accuracy of coronary angiography to assess the true extent of atherosclerosis. ^10,11 Necropsy studies demonstrate that angiography significantly underestimates the extent of atherosclerosis. ^12,13 Quantitative coronary angiography compares the luminal diameter within a lesion with the caliber of an adjacent normal-appearing reference segment. Autopsy studies reveal that coronary atherosclerosis is often diffuse, involving long segments of the diseased vessel. Therefore, in many patients, no truly normal segment exists, which precludes accurate assessment of disease severity. ¹⁴ Diffuse, concentric, and symmetric coronary disease can affect the entire length of the vessel, resulting in an angiographic appearance of a small artery with minimal luminal irregularities. ¹⁵

Precise assessment of the severity of coronary atherosclerosis by angiography is further limited by the phenomenon of remodeling, ¹⁶ which is the process in which the external vessel wall enlarges in areas of atherosclerosis. During the early development of atherosclerosis, outward displacement of the external vessel wall prevents plaque from encroaching into the lumen, thereby limiting the detection of a lesion by angiography.

Evidently, the limitations of quantitative coronary angiography often hamper the interventional cardiologist's ability to assess intermediate coronary lesions adequately. Adjunctive techniques that provide more detailed anatomical information are often required to perform a complete evaluation.

Intravascular ultrasound

Intravascular ultrasound uses miniaturized transducers that are advanced through guide catheters into coronary arteries of interest. The technique permits detailed, high-quality, cross-sectional imaging of the coronary arteries in vivo. Intravascular ultrasound allows detection of coronary artery anatomy and coronary plaque characteristics in a manner otherwise not possible by conventional contrast angiography. ¹⁴

Several characteristics of intravascular ultrasound imaging allow more precise quantification of atherosclerotic coronary disease that may be useful in assessing intermediate coronary lesions. ¹⁴ The tomographic orientation of ultrasound enables visualization of the full 360° circumference of the vessel wall, rather than a two-dimensional projection of the lumen. Measurement of lumen area is performed by direct planimetry on cross-sectional images. Since the velocity of sound within soft tissues is essentially constant, ultrasound measurements are accurate and require no special calibration methods. Ultrasound images rely only on an electronic distance scale that is generated internally and overlaid on the image. The tomographic perspective of intravascular ultrasound facilitates visualization of the true extent of ath-erosclerotic disease. This tomographic perspective enables examination of lesions such as diffusely diseased segments, bifurcation lesions, ostial stenoses, and highly eccentric plaques ¹⁵ that are typically difficult to assess by angiographic techniques.

Several studies demonstrate the utility of intravascular ultrasound in assessing angiographically intermediate lesions. In two large prospective series, intracoronary ultrasound imaging performed immediately prior to coronary intervention changed the management strategy in more than 20% of the examinations by providing a better understanding of the severity of disease. ^17,18 Another study demonstrated low event rates during the long-term follow-up of patients in whom percutaneous coronary intervention was deferred based on intravascular ultrasound findings. ¹⁹ The authors reported especially low event rates in patients with a minimum lumen area >= 4.0 mm ² . In another study by the same authors, 1-year follow-up after intravascular ultrasound assessment of moderate left main CAD in patients with ambiguous angiograms was reported. ²⁰ Intravascular ultrasound-derived minimum lumen diameter was the most important quantitative predictor of cardiac events.

There is still no consensus regarding the intravascular ultrasound measurement at which left main stenosis is considered critical. However, an absolute area <7.0 mm ² or >50% area stenosis are criteria often used as thresholds for left main stenosis requiring revascularization. ¹⁴ An ongoing multicenter registry of intermediate left main coronary lesions will assist in defining these patients. An example of the application of intravascular ultrasound to assess an intermediate coronary stenosis is demonstrated in figure 1. ¹⁴

Although intravascular ultrasound provides an accurate anatomic assessment of intermediate coronary lesions, it does not provide data concerning the physiologic significance of a coronary lesion. Adjunctive techniques exist that allow one to measure the physiologic significance of a coronary lesion rapidly.

Coronary flow velocity reserve

Measurements of coronary flow velocity reserve are obtained utilizing a Doppler-sensor-tipped intracoronary wire to determine the ratio of hyperemic to basal mean flow velocity just distal to the coronary stenosis in question. ²¹ This ratio is obtained from flow measurements before and immediately after the administration of a vasodilator, such as adenosine. The coronary flow velocity reserve in angiographically normal vessels from adult patients with CAD risk factors is approximately 2.7. ²² A coronary flow velocity reserve <2.0 is reproducibly and positively correlated to abnormal stress perfusion testing ^23,24 and is therefore used as a threshold to determine if an intermediate coronary lesion is physiologically significant.

The major limitation in assessing an intermediate stenosis using coronary flow velocity reserve is microcirculatory impairment. ²¹ In the absence of coronary stenosis, the coronary flow velocity reserve may be <2.0 (abnormal) when the microcirculation is compromised by left ventricular hypertrophy, chronic or acute ischemia, or diabetes mellitus. An abnormal coronary flow velocity reserve does not differentiate whether an abnormality exists in the epicardial coronary artery or in the microcirculation. To overcome this limitation of coronary flow velocity reserve, the concept of relative coronary flow velocity reserve has been introduced.

Relative coronary flow velocity reserve requires that an additional measurement of coronary flow velocity reserve be performed in an adjacent normal vessel as a reference value. The relative coronary flow velocity reserve is calculated by dividing the target vessel coronary flow velocity reserve by the reference vessel coronary flow velocity reserve. Assuming that hemodynamic and microcirculatory abnormalities affect different regions of the myocardium similarly, the relative coronary flow velocity reserve provides a better discrimination of flow impairment due to a stenosis. ²⁵ A normal measurement of the relative coronary flow velocity is >0.8 and has been shown to be similar to negative stress testing in prognostic value. ²⁶ An example of the applications of coronary flow velocity and relative coronary flow velocity to assess an intermediate coronary stenosis is demonstrated in figure 2. ²¹

The major limitation in assessing coronary lesions with coronary flow reserve velocity is the question of microcirculatory impairment. ²¹ This limitation can usually be overcome by the use of relative coronary flow velocity reserve. However, in patients who have three-vessel coronary disease, a suitable normal reference vessel may not exist. Additionally, physicians may no longer assume the microcirculation is uniform in patients with a history of myocardial infarction. Hence, the application of relative coronary flow velocity reserve may be invalid in some patients.

Fractional flow reserve

Fractional flow reserve is defined as the maximal blood flow to the myocardium in the presence of a stenosis in the supplying coronary artery divided by the theoretical normal maximal flow in the same distribution. ²⁷ This index represents the fraction of the normal maximal myocardial flow that can be achieved despite coronary stenosis. Fractional flow reserve can be derived from the ratio of the mean distal coronary artery pressure to the aortic pressure during maximal vasodilation. ²⁷ Measurements are obtained readily by advancing a fiberoptic pressure-monitoring guidewire through a standard coronary guide catheter distal to the coronary lesion of interest. After the administration of adenosine to achieve maximal hyperemia, the fractional flow reserve is calculated as the ratio of the mean distal intracoronary pressure measured by the wire to the mean arterial pressure measured by the coronary catheter. ²⁸

The normal fractional flow reserve for all vessels under all hemodynamic conditions is 1.0, regardless of the status of the microcirculation. An intermediate coronary lesion with a fractional flow reserve <0.75 is considered abnormal. ² Several studies have correlated abnormal fractional flow reserve values with the presence of myocardial ischemia on exercise treadmill testing, nuclear stress imaging, and/or stress echocardiography. ^27,29,30 Other studies have demonstrated that deferring intervention of an intermediate stenosis on the basis of fractional flow reserve values >0.75 is safe and is associated with a low clinical event rate. ^{27, 31} An example of the application of fractional flow reserve in a patient with a moderately severe coronary lesion is presented in figure 3. ²⁷

The calculation of fractional flow reserve from measurements of pressure is limited by the presence of small-vessel disease, diffuse CAD, and left ventricular hypertrophy. These conditions restrict the increase in blood flow after pharmacologic vasodilatation and the corresponding decrease in distal coronary pressure. Under these conditions, the severity of the stenosis may be underestimated because of the limited increase in flow and the associated limitation in the pressure gradient. ²⁷ Furthermore, several potential pitfalls that may influence the accuracy of fractional flow reserve measurements have been described. ²⁸ These include pressure damping by guide catheters, side-hole catheters leading to inaccurate proximal coronary pressure measurements, signal drift during procedures, paradoxical gradients because the aortic root is lower than the apex of the heart in the recumbent position, and inadequate hyperemia. Most of these potential pitfalls can be remedied if the interventional cardiologist is aware of them.

Conclusion

Coronary lesions of intermediate stenosis present a challenging dilemma for the interventional cardiologist. Modern adjunctive technologies such as quantitative coronary angiography, intravascular ultrasound, coronary flow velocity reserve, and fractional flow reserve, are able to more precisely examine the potential significance of an intermediate coronary lesion. A thorough understanding of each technique's advantages and limitations is required so that physicians can determine which technique, or combination of techniques, is best suited for the individual patient.