17 Echocardiographic Evaluation of Coronary Blood Flow
Approaches and Clinical Applications
Coronary flow velocity and coronary flow velocity reserve measurements provide useful clinical and physiologic information. Previously, coronary flow velocity has been assessed invasively by Doppler flow wire technique in the cardiac catheterization lab. Recent technologic advances in Doppler echocardiography provide noninvasive coronary flow detection by Doppler transthoracic echocardiography (TTE).1,2 The accuracy of these new noninvasive transthoracic coronary flow and coronary flow reserve (CFR) measurements has been validated compared to Doppler flow wire.3–7 Doppler TTE is widely available in the clinical setting, and this technique can be performed in an outpatient setting.8,9 The majority of the clinical data regarding this technique has been reported by European and Japanese groups, but Takeuchi and colleagues10 did a unique investigation testing the feasibility of transthoracic coronary flow detection in the relatively obese U.S. population and found a similar success rate for recording coronary flow and CFR. Intravenous contrast injection helps in detection of the coronary signal.11–14 This new, noninvasive imaging technique of the coronary arteries promises to expand the field of diagnostic echocardiography and bring new insight into the pathophysiology of ischemic heart disease.
Coronary Anatomy
It is important to understand the coronary arterial anatomy for assessment of coronary flow by Doppler TTE (Fig. 17-1). The left and right coronaries originate from the left and right coronary sinuses of the aortic root. The left main coronary artery bifurcates into the left anterior descending (LAD) artery, which runs over the anterior interventricular sulcus, and the left circumflex (LCx) artery in the left atrioventricular sulcus. The LAD artery often around beyond the apex. In this situation, the LAD artery extends up the posterior interventricular sulcus. The septal branches arise at an acute angle from the LAD artery, coursing close to the endocardium on the right side of the interventricular septum. The LCx artery is the other principal vessel originating from the left main coronary artery. It is covered by the left atrial (LA) appendage in its proximal portion, and then courses along the left atrioventricular sulcus. The right coronary artery (RCA) has its origin at the right coronary aortic sinus and follows the right atrioventricular sulcus. The posterior descending artery lies in the posterior interventricular sulcus.
Doppler Evaluation of Coronary Flow
Technical Aspects
There are some important technical issues for detecting coronary flow signals. First, a good high-resolution and high-sensitivity ultrasound system with a high-frequency transducer is required (7 to 12 MHz for mid to distal LAD artery; 2 to 5 MHz for proximal LAD artery, RCA, and LCx artery). Second, in color Doppler imaging, the Doppler velocity range should be set in the range of 10 to 30 cm/s to detect the coronary flow signal because the blood flow velocity is relatively slow. In cases in which it is difficult to detect a coronary flow signal, intravenous injection of contrast agent enhances the Doppler signal intensity.5,11 The contrast enhancer used in the most studies was Levovist (Schering AG, Berlin, Germany). Levovist, at a concentration of 300 mg/mL, was administered intravenously by using an infusion pump. The infusion rate is adjusted from 0.5 to 2 mL/min, according to the quality and intensity of the Doppler signal enhancement achieved. By positioning the Doppler sample volume in the coronary flow stream under the guidance of color Doppler flow imaging, the characteristic coronary flow spectrum, with biphasic predominantly diastolic flow velocities, can be recorded. In the pulsed Doppler technique, angle correction is required depending on the direction of coronary flow.
Detection
Left Main and Proximal Coronary Arteries
Patients should be examined in the left lateral decubitus position. To visualize the left main trunk and proximal left anterior descending artery, start with the image plane at the level of the aortic root, in a short-axis view (Fig. 17-2, A). This part of the exam can be performed using a relatively low-frequency transducer (2 to 4 MHz). The left main trunk is identified as a tubular structure that originates from the left coronary sinus. By adjusting the orientation of the ultrasound beam toward the distal side of the left main trunk, the proximal LAD artery, which runs from the bifurcation toward the anterior wall of the heart, can be visualized using color Doppler flow mapping. At the level of the left main bifurcation, the proximal circumflex artery is detected by rotating the transducer clockwise.
Figure 17-2 Schematic illustrations of coronary flow detection by transthoracic Doppler echocardiography.
The proximal RCA, which originates from right coronary sinus, can be identified at the aortic root, in short-axis or long-axis views (Fig. 17-3).
Left Anterior Descending Coronary Artery
In the short-axis images of the left ventricle (LV), the midportion of the LAD artery can be identified as a cross section of the tubular structure containing the color Doppler flow signal, located in the anterior interventricular sulcus (see Fig. 17-2, B and C). The color Doppler signal in the LAD artery, which typically appears as a red color, is mainly seen in diastole. After confirming its position, rotate the transducer counterclockwise to image the LV in a long-axis view aligned with the intraventricular sulcus under the guidance of color Doppler flow imaging. To visualize the distal portion of the LAD artery, image the LV in a long-axis view starting from the apex and searching for the coronary flow signal around the intraventricular sulcus. In this view, pericardial fluid may appear similar to a coronary flow signal near the epicardium. However, pericardial fluid is seen mainly in systole and can easily be discriminated by pulsed Doppler recording. The coronary flow pattern by pulsed Doppler is biphasic, but pericardial fluid generally has a systolic, bidirectional signal. Once the LAD artery is found as a cross section of the tubular structure containing the color Doppler flow signal, rotate the transducer clockwise (toward the two-chamber view position) to detect the flow signal in the long-axis view (Fig. 17-4). Coronary flow detection in the distal portion of the LAD artery is important, as CFR should be measured distal to any stenosis. Coronary blood flow velocity profiles are recorded by positioning a pulsed sample volume on the color flow signal. The incident angle between the Doppler beam and direction of blood flow should be used to correct the velocity scale.
Posterior Descending Coronary Artery
The posterior descending coronary artery usually is the distal extension of the RCA and runs along the posterior interventricular sulcus toward the apex. After obtaining an apical two-chamber image of the LV, angle the ultrasound beam superiorly to image the posterior interventricular sulcus (see Fig. 17-2, C). In this situation a lower frequency probe is recommended because this area is far from the transducer, compared to the anterior interventricular sulcus. Carefully examine this area using color Doppler flow imaging to locate the right posterior descending coronary artery (Fig. 17-5). Though the success rate in detecting coronary flow velocity profile in the right posterior descending coronary artery is lower compared with the LAD artery, a contrast-enhanced Doppler technique improves the success rate.15
Left Circumflex Coronary Artery
The LCx artery can be found in the modified four-chamber view (see Fig. 17-2, D). It is normally distinguished as a color flow signal running along the basal lateral wall16 (Fig. 17-6). However, visualization of circumflex arteries is relatively difficult because of their anatomic variations, and furthermore, these vessels are distant from the transducer.
Assessment of Coronary Flow Profile
Doppler spectral tracings of coronary flow velocity can be recorded by the pulsed-Doppler technique by positioning a sample volume (1.5 to 2.5 mm wide) on the color Doppler signal. Angle correction is needed in each examination. Coronary flow profile provides some useful clinical information, such as coronary flow direction, coronary flow velocity, and coronary flow pattern. Normal coronary flow is characterized by a biphasic flow profile, which consists of a small systolic and a large diastolic flow signal (Fig. 17-7). It should be noted that pulsed-Doppler recording provides coronary flow velocity and not the absolute volume of coronary blood flow. CFR by Doppler TTE is derived from changes in the velocity of coronary blood flow, which has been shown to correlate with absolute CFR.
Clinical Applications
Coronary Flow Velocity Reserve Measurement
CFR is expressed as a ratio of maximum flow to resting flow (Fig. 17-8). With a normal coronary artery, a vasodilatory stimulus results in an approximately fourfold increase in flow rate compared to baseline. With progressive coronary stenosis, baseline flow remains normal until the coronary artery is narrowed by 80% to 85% diameter stenosis. However, CFR begins to decrease at 40% to 50% diameter stenosis.17 CFR decreases to two times baseline at approximately 75% diameter stenosis, which indicates myocardial ischemia.
Figure 17-8 Coronary flow reserve (CFR) and percent diameter stenosis.
(From Gould KL, Lipscomb K: Effects of coronary stenoses on coronary flow reserve and resistance. Am J Cardiol 34:48-55, 1974.)
Coronary flow velocity reserve can be alternatively assessed as the ratio of hyperemic to basal coronary flow velocity after drug-induced coronary vasodilatation. Measurements of coronary flow velocity reserve by Doppler TTE have already been established as feasible and accurate.3,5,6
After recording baseline spectral Doppler signals in the distal portion of the LAD artery, administer the vasodilator, either adenosine 140 mcg/kg/min as an intravenous infusion for about 1 minute or dipyridamole 0.56 mg/kg intravenously for about 4 minutes, to achieve maximum flow. Then spectral Doppler signals are recorded during hyperemic conditions (Fig. 17-9) with measurement of the mean diastolic velocity and peak diastolic velocity of each flow spectrum. Coronary flow velocity reserve by the transthoracic-Doppler technique is measured from only diastolic mean velocities and not mean velocities throughout the entire cardiac cycle because, in some cases, cardiac motion makes it difficult to obtain a complete Doppler spectral envelope throughout the cardiac cycle. However, previous studies have reported that the ratio of hyperemic to basal mean diastolic velocity and peak diastolic velocity was useful in the evaluation of functional coronary stenosis. Coronary flow velocity reserve is defined as the ratio of hyperemic to basal peak diastolic coronary flow velocity or the ratio of hyperemic to basal mean diastolic coronary flow velocity. Adenosine starts to act generally in 30 seconds, and the coronary flow velocity comes to maximum in 1 minute. Dipyridamole starts to act in 4 to 6 minutes and has a prolonged duration of action (about 30 minutes after administration). The short-acting effect is an advantage of adenosine. Although both vasodilators can cause flushing, headache, hypotension, or bradycardia, the adverse effects of adenosine are alleviated immediately after the infusion is finished.
In the clinical setting, some factors that are related to coronary risk factors have been known to affect CFR. Passive smoking has been reported to reduce CFR in healthy nonsmokers, not in active smokers.18 Another study demonstrated that CFR was significantly higher in nonsmokers than in smokers, and interestingly, oral antioxidant vitamin C increased CFR in nonsmokers but not in smokers.19 Patients with hypertension showed lower CFR than did normotensive controls20; CFR is reduced in diabetic patients, especially in patients with retinopathy21,22; and CFR decreased after a single high-fat meal in young healthy men.23 Because of the noninvasive nature of transthoracic Doppler, it can be used for serial evaluation of drug effects on coronary microcirculation.24–27 CFR is also reduced in metabolic syndrome28 and nonalcoholic fatty liver disease.29 Another study showed that in premenopausal women, CFR varies during the menstrual cycle, and in postmenopausal women, CFR increases after acute estrogen replacement.30 Noninvasive CFR is expected to contribute to the evaluation of coronary microvascular function in various clinical situation other than ischemic heart disease, such as cardiomyopathy or heart failure.31 Several papers have reported its usefulness in the assessment of cardiac allograft vasculopathy in patients after heart transplantation.32,33
Noninvasive Diagnosis Of Coronary Stenosis
Coronary Flow Velocity Reserve Measurement Approach
Coronary flow velocity reserve defined as a mean diastolic velocity increase with hyperemia less than 2 had a sensitivity of 91% to 92% and a specificity of 75% to 86% for the presence of significant LAD artery stenosis.34,35 Compared with thallium-201 single photon emission computed tomography (SPECT), a mean CFR derived from transthoracic Doppler greater than or equal to 2 predicted reversible perfusion defects, with a sensitivity and specificity of 92% and 90%, respectively.36 CFR improves after coronary stenting,37 and a CFR less than 2 had high sensitivity (91%) and specificity (95%) in the diagnosis of in-stent restenosis after coronary intervention.38 Another paper similarly reported that CFR less than 2 predicted restenosis determined by thallium-201 SPECT, with a sensitivity of 94% and a specificity of 100%.39 Furthermore, Voci and colleagues40 reported that a CFR less than 1, which may reflect coronary steal phenomenon, could discriminate high-risk patients with severe stenosis from patients with nonsevere stenosis. A CFR of 2 or less can be applied to the prediction of the outcome in patients with intermediate coronary stenosis. In the population of medically treated patients with intermediate LAD stenosis (51% to 75% diameter), 30-month event-free survival was higher in patients with normal CFR and lower in patients with decreased CFR (86% vs. 30%).41
For coronary stenosis in the right coronary territory, coronary flow velocity reserve measured in the posterior descending coronary artery is useful. Detection of the posterior descending artery is more difficult than that of the LAD artery, but the use of an intravenous contrast injection improves Doppler signal recording.15 Using the cutoff value of 2 for coronary flow velocity reserve in the RCA, the sensitivity and specificity for detection of significant stenosis were 84% to 91% and 83% to 91%, respectively.6,15,35 Coronary flow velocity reserve less than 2 in the LCx artery has been reported to have a sensitivity of 92% and specificity of 96% for reversible perfusion defect detected by SPECT.16
A Japanese group has tested the feasibility and usefulness of CFR measurements in the three major coronary arteries as a screening examination. They found that the noninvasive technique is a promising tool for the detection of coronary stenosis in patients with chest pain42 and for the detection of restenosis after coronary intervention.43 Although each coronary risk factor influences the result of coronary flow velocity reserve, a cutoff value less than 2 was still adequate in terms of the diagnosis of significant coronary stenosis. A cutoff value less than 2 for CFR had a sensitivity of 90%, a specificity of 93%, a positive predictive value of 77%, and a negative predictive value of 97% for the presence of significant coronary stenosis in a population that included patients with various coronary risk factors.44
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