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Noninvasive assessment of great cardiac vein flow by Doppler echocardiography: A validation study
Noninvasive Assessment of Great Cardiac Vein Flow by Doppler Echocardiography: A Validation Study Nozomi Watanabe, MD, Takashi Akasaka, MD, Yasuko Yamaura, MD, Norio Kamiyama, MD, Maki Akiyama, MD, Yuji Koyama, MD, Yoji Neishi, MD, and Kiyoshi Yoshida, MD, FACC, Kurashiki, Japan
The objectives of this study were (1) to compare great cardiac vein (GCV) flow velocity detected by pulsed Doppler echocardiography (PDE) with Doppler guide wire (DGW) in the experimental setting and (2) to clarify whether transthoracic Doppler echocardiography (TTDE) can detect GCV flow in humans. Using opened-chest dogs, we detected GCV flow by PDE under the guidance of color flow Doppler mapping. GCV flow velocity was recorded by PDE and DGW, simultaneously. In 23 volunteers,
G
reat cardiac vein (GCV) flow measurements have provided useful physiologic and clinical information.1-9 Several studies have reported that GCV flow after reperfusion can be used as an indicator of the success of mechanical reperfusion and can predict the degree of myocardial salvage.10,11 Although GCV flow has been assessed by thermodilution or Doppler guide wire (DGW) methods in the clinical laboratory, they are invasive, complicated, and available only in the catheterization laboratory. Thus, it has been difficult to evaluate GCV flow in routine clinical practice at bedside. Recent technological advancements have made it possible to take highly successful noninvasive measurements of coronary flow velocity in the left anterior descending coronary artery (LAD) by using transthoracic Doppler echocardiography (TTDE).12-14 With TTDE, although a color flow Doppler signal parallel to the LAD, which runs toward the base of the heart, is thought to be a signal from the GCV (Figure 1), it has not been validated yet. If GCV flow can be reliably measured by TTDE noninvasively, as well as LAD, it would provide From the Department of Cardiology, Kawasaki Medical School. Reprint requests: Nozomi Watanabe, MD, Department of Cardiology, Kawasaki Medical School, 577 Matsushima, Kurashiki, 701-0192, Japan (E-mail: [email protected]). Copyright 2002 by the American Society of Echocardiography. 0894-7317/2002/$35.00 + 0 27/1/119788 doi:10.1067/mje.2002.119788
GCV flow velocity was measured by TTDE. In the experimental setting, the prominent systolic flow wave of the GCV was obtained in PDE and DGW. There were good agreements between PDE and DGW for the measurements of GCV flow velocity (peak velocity: r = 0.98, y = 1.12χ-5.9; time velocity integral: r = 0.97, y = 1.10χ-0.71). In the human subjects, clear envelopes of GCV flow velocity were obtained in 21 (91%) of 23 subjects with the use of TTDE. (J Am Soc Echocardiogr 2002;15:253-8.)
useful clinical information. The aims of this study were (1) to evaluate whether pulsed Doppler echocardiography (PDE) can reliably measure GCV flow in the experimental setting and (2) to clarify whether TTDE can detect GCV flow in humans noninvasively.
METHODS Animal Experiments Animal preparations. The protocol was approved by the Committee on Animal Research at the Kawasaki Medical School.Three beagle dogs, weighing 12 to 14 kg, were premedicated with an intramuscular injection of ketamine (100 mg) and anesthetized with an intravenous injection of pentobarbital sodium (30 mg/kg body weight). Additional doses were given as needed throughout the experiment.After endotracheal intubation, the animals were ventilated by a respirator pump (3 to 5 L/min oxygen; VS600, Instrumental Development Corp, Pittsburgh, Pa).Arterial pH and blood gases were measured frequently and kept in the physiologic range by adjusting the inspired oxygen concentration and minute ventilation. An arterial pressure catheter was inserted into the left femoral artery to monitor the aortic pressure. All dogs were anticoagulated with intravenous heparin (1000 U/h). Electrocardiograms were recorded from standard leads. After median sternotomy and a left-side thoracotomy, the heart
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Figure 1 Left anterior descending artery (LAD) and great cardiac vein (GCV) flow by transthoracic echocardiography. Transthoracic Doppler echocardiography (top) and schematic representation (bottom) showing LAD and GCV flow by color flow Doppler echocardiography. LV, left ventricle.
was exposed and supported in a pericardial cradle. The LAD was isolated to measure LAD flow with a transit flow meter.A snare was placed around the proximal portion of the LAD to introduce occlusion.A DGW was inserted from the coronary sinus and the tip of the wire was positioned in the GCV along the mid LAD (Figure 2). Measurements of GCV flow by PDE and DGW. The PDE examinations were performed with a digital ultrasound system (HDI 5000,Advanced Technology Laboratories Inc, Bothell, Wash) with a frequency of 4.0 to 7.0 MHz (Doppler frequency, 4.0 MHz). In color flow Doppler mapping, velocity was set in the range of ±19.2 to ±24.0 cm/s. The color gain was adjusted to provide the optimal images. The ultrasound beam was transmitted from the surface of the heart through a hydrated polyacrylamide-agar sheet (SONAR-AID, Geistlich Inc, Wolhusen, Switzerland). Mid LAD artery and GCV flow signal were visualized by color flow Doppler echocardiography (Figure 3). Positioning a sample volume (1.5 mm wide) with guidance from the color signal in the GCV, Doppler spectral tracings of GCV flow velocity were recorded. GCV flow velocity was also recorded with the use of a DGW and a velocimeter (FloMap, JOMED, Inc, Rancho Cordova, Calif).A DGW was advanced into the GCV from the coronary sinus through a 5-F coronary angiography catheter (Selecon, Clinical Supply Inc, Gifu, Japan). The DGW used in this study was 0.014 inches (0.36 mm), 175 cm long, flexible and steerable, with a 15-MHz piezoelectric ultrasound transducer integrated on the tip (Flowire, JOMED, Inc).The ultrasound beam diverged at 28 degrees from the transducer.The sample volume was positioned at a distance of 4.2 mm from the transducer. The tip of the DGW was advanced to the
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GCV. An optimal Doppler signal was obtained by moving the guide wire slightly within the vessel lumen and adjusting the range gate control. We confirmed the position of the tip of the DGW under fluoroscopic monitoring and set the tip of the DGW at the same site of the sample volume in PDE.After recording baseline spectral Doppler signals in the GCV, by using both PDE and DGW simultaneously, the proximal LAD was occluded for 20 seconds to obtain spectral Doppler signals during hyperemia. We measured GCV flow velocity, first at rest and then during reactive hyperemic responses, from coronary reopening to the maximum hyperemia in each heartbeat.All studies were recorded on s-VHS videotape for off-line analysis. An arterial pressure flow waveform at the proximal LAD, by transit flow meter and electrocardiogram, was monitored continuously. Measurements were performed off-line by tracing the contour of the spectral Doppler signal, by using the computer analysis system incorporated in the ultrasound system. Peak velocities and time velocity integrals at baseline and during hyperemia were measured from the Doppler signal recordings. Clinical Study Great cardiac vein flow recording by TTDE. Twentythree healthy volunteers (18 men and 5 women; mean age 38.4 ± 10.2 years) were examined with TTDE. The TTDE examinations were performed with a digital ultrasound system (HDI 5000,Advanced Technology Laboratories Inc, Bothell, Wash) with a Doppler frequency of 4.0 MHz. In color flow Doppler mapping, velocity was set in the range of ±9.6 to ±28.8 cm/s.The color gain was adjusted to provide the optimal images.The acoustic window was around the midclavicular line in the fourth or fifth intercostal spaces, with the patient placed in the left lateral decubitus position.The ultrasound beam was transmitted toward the heart to visualize coronary flow in the GCV, with the use of color flow Doppler mapping. First, the left ventricle was imaged in the short-axis cross section to identify the LAD positioned in the anterior interventricular sulcus; then the transducer was rotated counterclockwise to visualize the mid portion of the LAD in the long-axis section. Next, the ultrasound beam was inclined laterally to search for GCV flow under the guidance of color flow Doppler mapping. GCV flow signal toward the base of the heart appeared in systole along the LAD flow.After positioning a sample volume (1.5-2.5 mm wide) on the color signal in the GCV, Doppler spectral tracings of flow velocity were recorded. Angle correction was needed in each examination (incident angle: 36 ± 13 degrees).All studies were recorded on s-VHS videotape for off-line analysis. GCV flow measurements. Measurements were performed off-line, tracing the contour of the spectral Doppler signal and using the computer analysis system incorporated into the ultrasound system. Peak velocities and
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Figure 2 Experimental setting. Great cardiac vein flow (GCV) velocity was recorded in anesthetized opened-chest dogs from surface of heart by pulsed Doppler echocardiography under the guidance of color flow Doppler mapping. Simultaneous recordings of GCV flow velocity by Doppler guide wire, which was inserted into GCV from coronary sinus, and pulsed Doppler echocardiography were performed. time velocity integrals were measured from the Doppler signal recordings. Analysis of GCV flow velocity data. Data are expressed as mean value ± SD. In the dog experiments, linear regression analysis was used to compare PDE with the DGW method for the assessment of peak velocity and time velocity integral. An analysis of the differences of the measurements was performed according to the technique of Bland and Altman.15 Interobserver and intraobserver variability were assessed for peak velocity and time velocity integral in 10 randomly selected recordings. Interobserver variability was calculated as the SD of the differences between the measurements of 2 independent observers, unaware of the other data, and expressed as a percentage of the average value. Intraobserver variability was calculated as the SD of the differences between the first and second determination (3-week interval) for a single observer and expressed as a percentage of the average value.
RESULTS Animal Experiments Prominent systolic flow wave was recorded, at rest and during hyperemia, with the use of PDE and DGW methods (Figures 4 and 5). It took 7 heartbeats in the first 2 dogs and 9 heartbeats in the third dog to reach the maximum hyperemia after the coronary reopening. There were excellent agreements between PDE and DGW methods for the measurements of peak velocity and time velocity integral
Figure 3 Left anterior descending artery (LAD) and great cardiac vein (GCV) flow by color flow Doppler echocardiography. Both LAD and GCV flow signals were visualized by cross-sectional echocardiography (left). LAD flow signal was obtained during diastole toward apex (middle). GCV flow signal was obtained during systole toward base of heart (right). D1, first diagonal branch.
(peak velocity: r = 0.98, y = 1.12χ-5.90; time velocity integral, r = 0.97, y = 1.10χ-0.71). For peak velocity measurements, the mean differences between PDE and DGW were 0.85 ± 5.12 cm/s. For time velocity integral measurements, the mean differences between PDE and DGW were 0.04 ± 0.91 cm (Figures 6 and 7). Clinical Study Clear envelopes of GCV flow were obtained in 21 (91%) of 23 subjects by TTDE.The spectral Doppler of GCV flow showed a characteristic prominent systolic flow wave, as observed in the animal experi-
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Figure 4 Simultaneous recording of great cardiac vein flow velocity by pulsed Doppler echocardiography (left) and Doppler guide wire (right) at rest.
ments (Figure 8). Mean peak velocity was 30.4 ± 8.1 cm/s, and time velocity integral was 17.6 ± 10.2 cm. It took within 5 minutes to obtain GCV signals in the volunteers. Observer Variability Interobserver and intraobserver variabilities for the peak velocity were 4.6% and 3.8%, and for the time velocity integral were 4.8% and 4.2%, respectively.
DISCUSSION Coronary flow measurement by TTDE has been reported to be a useful and feasible method to evaluate significant LAD stenosis by measuring coronary flow velocity reserve or stenotic coronary flow velocity ratio.13,14 The coronary artery flow shows a prominent diastolic pattern. On the other hand, the flow dynamics in the coronary venous system are characterized by the phasic flow predominant in systole. Thus, coronary circulation consists of 2 vascular systems with different dynamic characteristics. However, there have been few reports describing the coronary venous physiology, especially in the clinical setting.This is because the measurement of coronary venous flow has been difficult by using conventional invasive thermodilution or DGW methods. In this study, we evaluated the reliability of GCV flow velocity measurement obtained from PDE in the experimental setting. Our data also demonstrated that noninvasive measurement of GCV flow velocity by TTDE was feasible in the clinical laboratory. Animal Experiments In the experimental setting, prominent systolic flow wave was recorded by using PDE and DGW methods.This characteristic was the same as that reported previously by using laser Doppler and DGW. Peak
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Figure 5 Simultaneous recording of great cardiac vein flow velocity by pulsed Doppler echocardiography (left) and Doppler guide wire (right) during hyperemia.
velocity and time velocity integral measured from epicardial PDE and DGW showed an excellent agreement. As shown in Figures 4 and 5, noises, which were attributable to the cross talk of ultrasound from DGW and PDE, were consistent among the measurements. We believed this phenomenon provided the evidence that these measurements were performed at the exact same site. From these results, it is suggested that GCV flow recording by PDE is a reliable and available technique. Clinical Study In the clinical setting, Doppler signal along the LAD toward the base of the heart showed a characteristic prominent systolic flow wave, as observed in the animal experiments.This suggests that the Doppler signal is from the GCV and measurement of GCV flow velocity is feasible and reliable by TTDE, noninvasively. The current study demonstrated that GCV flow velocity could be assessed with a high success rate (91%) under the guidance of color flow Doppler mapping for the clinical application.With TTDE, GCV flow velocity recording was performed by setting the color flow Doppler mapping velocity lower (velocity range, ±9.6 to ±28.8 cm/s), compared with the usual setting in routine echocardiographic examination.This result establishes several potentially useful features of the noninvasive assessment of the GCV flow by TTDE. First,TTDE can be performed in an outpatient setting because TTDE is widely available in the clinical setting. DGW and thermodilution methods are invasive and can be performed only in the catheter laboratory. At the present time, only TTDE provides noninvasive assessment of GCV flow velocity in routine clinical practice, not only in the echocardiographic laboratory but also in the cardiac care unit or the emergency department. Finally, serial assessment can be performed by this technique because it is noninvasive and relatively inexpensive.
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Figure 6 Regression (top) and difference (bottom) plots comparing peak velocity by pulsed Doppler echocardiography (PDE) and Doppler guide wire (DGW) methods. There were excellent agreements between PDE and DGW methods for measurements of peak velocity. Mean differences between PDE and DGW were 0.85 ± 5.12 cm/s.
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Figure 7 Regression (top) and difference (bottom) plots comparing time velocity integral by pulsed Doppler echocardiography (PDE) and Doppler guide wire (DGW) methods. There were excellent agreements between PDE and DGW methods for measurements of time velocity integral. PDE and DGW were 0.04 ± 0.91 cm.
Thus, GCV flow measurement, with the use of TTDE, will provide important physiologic information in coronary circulation and applicability of GCV flow measurement, and it needs to be further evaluated with patients who have various hemodynamic conditions. Study Limitations The current study has some important limitations. First, GCV flow velocity obtained from PDE was compared with that from the DGW method. Although the DGW technique has been established for the assessment of coronary flow velocity in the clinical setting, there is a limitation in GCV flow measurement by this technique. The value of the peak velocity is dependent on positioning of the wire in tortuous segments and regions with varying luminal dimensions or configurations. However, in this study, we carefully positioned the tip of the DGW to obtain a good signal from the GCV, which did not include the tortuous segment. Second, although it may be difficult to set the tip of the DGW at the exact same site
Figure 8 Great cardiac vein (GCV) flow velocity by Doppler transthoracic echocardiography. GCV flow toward base of heart was obtained in systole.
as the sample volume set in PDE, we confirmed the location of the tip of the DGW under the guidance of fluoroscopy and noises that were attributable to the cross talk of ultrasound from DGW and PDE was
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thought to be the evidence that these measurements were performed at the exact same site. Finally, in the clinical study, angle correction was needed in each examination because of incident Doppler angle, although we tried to align ultrasound beam direction to GCV flow as parallel as possible. Conclusion TTDE is feasible for detecting GCV flow noninvasively in vivo. We gratefully acknowledge Paul Kalman, BScRT, in the preparation of the manuscript.
REFERENCES 1. Kajiya F, Tsujioka K, Goto M, Wada Y, Tadaoka S, Nakai M, et al. Evaluation of phasic blood flow velocity in the great cardiac vein by a laser Doppler method. Heart Vessels 1985;1:16-23. 2. Kajiya F, Tsujioka K, Ogasawara Y, Mito K, Hiramatsu O, Goto M, et al. Mechanical control of coronary artery inflow and vein outflow. Jpn Circ J 1989;53:431-9. 3. Kajiya F, Tsujioka K, Goto M, Wada Y, Chen X, Nakai M, et al. Functional characteristics of intramyocardial capacitance vessels during diastole in the dog. Circ Res 1986;58:476-85. 4. Cohen MV, Matsuki T, Downey JM. Pressure-flow characteristics and nutritional capacity of coronary veins in dogs. Am J Physiol 1988;255:H834-46. 5. Rosen JD, Oskarsson H, Stenberg RG, Braun P, Talman CL, Winniford MD. Simultaneous measurement of coronary flow reserve by left anterior descending coronary artery Doppler and great cardiac vein thermodilution methods. J Am Coll Cardiol 1992;20:402-7. 6. Manginas A, Pavlides G, Voudris V, Vassilikos V, Cokkinos DV. Coronary vein flow velocity changes during transluminal balloon angioplasty: a study using the Doppler guide wire. Cathet Cardiovasc Diagn 1997;40:85-91.
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7. Kern MJ, Deligonul U, Vandormael M, Labovits A, Gudipati CV, Gabliani G, et al. Impaired coronary vasodilator reserve in the immediate postcoronary angioplasty period: analysis of coronary artery flow velocity indexes and regional cardiac venous efflux. J Am Coll Cardiol 1989;13:860-72. 8. Rothman MT, Baim DS, Simson JB, Harrison DC. Coronary hemodynamics during percutaneous transluminal coronary angioplasty. Am J Cardiol 1982;49:1615-22. 9. Yamagishi M, Hotta D, Tamai J, Nakatani A, Miyatake K. Validity of catheter-tip Doppler technique in assessment of coronary flow velocity and application of spectrum analysis method. Am J Cardiol 1991;67:758-62. 10. Nicklas JM, Dilts EA, O’Neil WW, Bourdillon PDV, Walton JA, Pitt B. Quantitative measurement of coronary flow during medical revascularization (thrombolysis or angioplasty) in patients with acute infarction. J Am Coll Cardiol 1987;10: 284-9. 11. Komamura K, Kitakaze M, Nishida K, Naka M, Tamai J, Uematsu M, et al. Progressive decreases in coronary vein flow during reperfusion in acute myocardial infarction: clinical documentation of the no reflow phenomenon after successful thrombolysis. J Am Coll Cardiol 1994;24:370-7. 12. Hozumi T, Yoshida K, Akasaka T, Asami Y, Ogata Y, Takagi T, et al. Noninvasive assessment of coronary flow velocity and coronary flow velocity reserve in the left anterior descending coronary artery by Doppler echocardiography: comparison with invasive technique. J Am Coll Cardiol 1998;32:1251-9. 13. Hozumi T, Yoshida K, Ogata Y, Akasaka T, Asami Y, Takagi T, et al. Noninvasive assessment of significant left anterior descending coronary artery stenosis by coronary flow velocity reserve with transthoracic color Doppler echocardiography. Circulation 1998;97:1557-62. 14. Hozumi T, Yoshida K, Akasaka T, Asami Y, Kanzaki Y, Ueda Y, et al. Value of acceleration flow and the restenotic to stenotic coronary flow velocity ratio by transthoracic color Doppler echocardiography in noninvasive diagnosis of restenosis after percutaneous transluminal coronary angioplasty. J Am Coll Cardiol 2000;35:164-8. 15. Bland JM, Altman DG. Statistical methods for assessing agreement between two methods of clinical measurement. Lancet 1986;1:307-10.
The objectives of this study were (1) to compare great cardiac vein (GCV) flow velocity detected by pulsed Doppler echocardiography (PDE) with Doppler guide wire (DGW) in the experimental setting and (2) to clarify whether transthoracic Doppler echocardiography (TTDE) can detect GCV flow in humans. Using opened-chest dogs, we detected GCV flow by PDE under the guidance of color flow Doppler mapping. GCV flow velocity was recorded by PDE and DGW, simultaneously. In 23 volunteers,
G
reat cardiac vein (GCV) flow measurements have provided useful physiologic and clinical information.1-9 Several studies have reported that GCV flow after reperfusion can be used as an indicator of the success of mechanical reperfusion and can predict the degree of myocardial salvage.10,11 Although GCV flow has been assessed by thermodilution or Doppler guide wire (DGW) methods in the clinical laboratory, they are invasive, complicated, and available only in the catheterization laboratory. Thus, it has been difficult to evaluate GCV flow in routine clinical practice at bedside. Recent technological advancements have made it possible to take highly successful noninvasive measurements of coronary flow velocity in the left anterior descending coronary artery (LAD) by using transthoracic Doppler echocardiography (TTDE).12-14 With TTDE, although a color flow Doppler signal parallel to the LAD, which runs toward the base of the heart, is thought to be a signal from the GCV (Figure 1), it has not been validated yet. If GCV flow can be reliably measured by TTDE noninvasively, as well as LAD, it would provide From the Department of Cardiology, Kawasaki Medical School. Reprint requests: Nozomi Watanabe, MD, Department of Cardiology, Kawasaki Medical School, 577 Matsushima, Kurashiki, 701-0192, Japan (E-mail: [email protected]). Copyright 2002 by the American Society of Echocardiography. 0894-7317/2002/$35.00 + 0 27/1/119788 doi:10.1067/mje.2002.119788
GCV flow velocity was measured by TTDE. In the experimental setting, the prominent systolic flow wave of the GCV was obtained in PDE and DGW. There were good agreements between PDE and DGW for the measurements of GCV flow velocity (peak velocity: r = 0.98, y = 1.12χ-5.9; time velocity integral: r = 0.97, y = 1.10χ-0.71). In the human subjects, clear envelopes of GCV flow velocity were obtained in 21 (91%) of 23 subjects with the use of TTDE. (J Am Soc Echocardiogr 2002;15:253-8.)
useful clinical information. The aims of this study were (1) to evaluate whether pulsed Doppler echocardiography (PDE) can reliably measure GCV flow in the experimental setting and (2) to clarify whether TTDE can detect GCV flow in humans noninvasively.
METHODS Animal Experiments Animal preparations. The protocol was approved by the Committee on Animal Research at the Kawasaki Medical School.Three beagle dogs, weighing 12 to 14 kg, were premedicated with an intramuscular injection of ketamine (100 mg) and anesthetized with an intravenous injection of pentobarbital sodium (30 mg/kg body weight). Additional doses were given as needed throughout the experiment.After endotracheal intubation, the animals were ventilated by a respirator pump (3 to 5 L/min oxygen; VS600, Instrumental Development Corp, Pittsburgh, Pa).Arterial pH and blood gases were measured frequently and kept in the physiologic range by adjusting the inspired oxygen concentration and minute ventilation. An arterial pressure catheter was inserted into the left femoral artery to monitor the aortic pressure. All dogs were anticoagulated with intravenous heparin (1000 U/h). Electrocardiograms were recorded from standard leads. After median sternotomy and a left-side thoracotomy, the heart
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Figure 1 Left anterior descending artery (LAD) and great cardiac vein (GCV) flow by transthoracic echocardiography. Transthoracic Doppler echocardiography (top) and schematic representation (bottom) showing LAD and GCV flow by color flow Doppler echocardiography. LV, left ventricle.
was exposed and supported in a pericardial cradle. The LAD was isolated to measure LAD flow with a transit flow meter.A snare was placed around the proximal portion of the LAD to introduce occlusion.A DGW was inserted from the coronary sinus and the tip of the wire was positioned in the GCV along the mid LAD (Figure 2). Measurements of GCV flow by PDE and DGW. The PDE examinations were performed with a digital ultrasound system (HDI 5000,Advanced Technology Laboratories Inc, Bothell, Wash) with a frequency of 4.0 to 7.0 MHz (Doppler frequency, 4.0 MHz). In color flow Doppler mapping, velocity was set in the range of ±19.2 to ±24.0 cm/s. The color gain was adjusted to provide the optimal images. The ultrasound beam was transmitted from the surface of the heart through a hydrated polyacrylamide-agar sheet (SONAR-AID, Geistlich Inc, Wolhusen, Switzerland). Mid LAD artery and GCV flow signal were visualized by color flow Doppler echocardiography (Figure 3). Positioning a sample volume (1.5 mm wide) with guidance from the color signal in the GCV, Doppler spectral tracings of GCV flow velocity were recorded. GCV flow velocity was also recorded with the use of a DGW and a velocimeter (FloMap, JOMED, Inc, Rancho Cordova, Calif).A DGW was advanced into the GCV from the coronary sinus through a 5-F coronary angiography catheter (Selecon, Clinical Supply Inc, Gifu, Japan). The DGW used in this study was 0.014 inches (0.36 mm), 175 cm long, flexible and steerable, with a 15-MHz piezoelectric ultrasound transducer integrated on the tip (Flowire, JOMED, Inc).The ultrasound beam diverged at 28 degrees from the transducer.The sample volume was positioned at a distance of 4.2 mm from the transducer. The tip of the DGW was advanced to the
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GCV. An optimal Doppler signal was obtained by moving the guide wire slightly within the vessel lumen and adjusting the range gate control. We confirmed the position of the tip of the DGW under fluoroscopic monitoring and set the tip of the DGW at the same site of the sample volume in PDE.After recording baseline spectral Doppler signals in the GCV, by using both PDE and DGW simultaneously, the proximal LAD was occluded for 20 seconds to obtain spectral Doppler signals during hyperemia. We measured GCV flow velocity, first at rest and then during reactive hyperemic responses, from coronary reopening to the maximum hyperemia in each heartbeat.All studies were recorded on s-VHS videotape for off-line analysis. An arterial pressure flow waveform at the proximal LAD, by transit flow meter and electrocardiogram, was monitored continuously. Measurements were performed off-line by tracing the contour of the spectral Doppler signal, by using the computer analysis system incorporated in the ultrasound system. Peak velocities and time velocity integrals at baseline and during hyperemia were measured from the Doppler signal recordings. Clinical Study Great cardiac vein flow recording by TTDE. Twentythree healthy volunteers (18 men and 5 women; mean age 38.4 ± 10.2 years) were examined with TTDE. The TTDE examinations were performed with a digital ultrasound system (HDI 5000,Advanced Technology Laboratories Inc, Bothell, Wash) with a Doppler frequency of 4.0 MHz. In color flow Doppler mapping, velocity was set in the range of ±9.6 to ±28.8 cm/s.The color gain was adjusted to provide the optimal images.The acoustic window was around the midclavicular line in the fourth or fifth intercostal spaces, with the patient placed in the left lateral decubitus position.The ultrasound beam was transmitted toward the heart to visualize coronary flow in the GCV, with the use of color flow Doppler mapping. First, the left ventricle was imaged in the short-axis cross section to identify the LAD positioned in the anterior interventricular sulcus; then the transducer was rotated counterclockwise to visualize the mid portion of the LAD in the long-axis section. Next, the ultrasound beam was inclined laterally to search for GCV flow under the guidance of color flow Doppler mapping. GCV flow signal toward the base of the heart appeared in systole along the LAD flow.After positioning a sample volume (1.5-2.5 mm wide) on the color signal in the GCV, Doppler spectral tracings of flow velocity were recorded. Angle correction was needed in each examination (incident angle: 36 ± 13 degrees).All studies were recorded on s-VHS videotape for off-line analysis. GCV flow measurements. Measurements were performed off-line, tracing the contour of the spectral Doppler signal and using the computer analysis system incorporated into the ultrasound system. Peak velocities and
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Figure 2 Experimental setting. Great cardiac vein flow (GCV) velocity was recorded in anesthetized opened-chest dogs from surface of heart by pulsed Doppler echocardiography under the guidance of color flow Doppler mapping. Simultaneous recordings of GCV flow velocity by Doppler guide wire, which was inserted into GCV from coronary sinus, and pulsed Doppler echocardiography were performed. time velocity integrals were measured from the Doppler signal recordings. Analysis of GCV flow velocity data. Data are expressed as mean value ± SD. In the dog experiments, linear regression analysis was used to compare PDE with the DGW method for the assessment of peak velocity and time velocity integral. An analysis of the differences of the measurements was performed according to the technique of Bland and Altman.15 Interobserver and intraobserver variability were assessed for peak velocity and time velocity integral in 10 randomly selected recordings. Interobserver variability was calculated as the SD of the differences between the measurements of 2 independent observers, unaware of the other data, and expressed as a percentage of the average value. Intraobserver variability was calculated as the SD of the differences between the first and second determination (3-week interval) for a single observer and expressed as a percentage of the average value.
RESULTS Animal Experiments Prominent systolic flow wave was recorded, at rest and during hyperemia, with the use of PDE and DGW methods (Figures 4 and 5). It took 7 heartbeats in the first 2 dogs and 9 heartbeats in the third dog to reach the maximum hyperemia after the coronary reopening. There were excellent agreements between PDE and DGW methods for the measurements of peak velocity and time velocity integral
Figure 3 Left anterior descending artery (LAD) and great cardiac vein (GCV) flow by color flow Doppler echocardiography. Both LAD and GCV flow signals were visualized by cross-sectional echocardiography (left). LAD flow signal was obtained during diastole toward apex (middle). GCV flow signal was obtained during systole toward base of heart (right). D1, first diagonal branch.
(peak velocity: r = 0.98, y = 1.12χ-5.90; time velocity integral, r = 0.97, y = 1.10χ-0.71). For peak velocity measurements, the mean differences between PDE and DGW were 0.85 ± 5.12 cm/s. For time velocity integral measurements, the mean differences between PDE and DGW were 0.04 ± 0.91 cm (Figures 6 and 7). Clinical Study Clear envelopes of GCV flow were obtained in 21 (91%) of 23 subjects by TTDE.The spectral Doppler of GCV flow showed a characteristic prominent systolic flow wave, as observed in the animal experi-
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Figure 4 Simultaneous recording of great cardiac vein flow velocity by pulsed Doppler echocardiography (left) and Doppler guide wire (right) at rest.
ments (Figure 8). Mean peak velocity was 30.4 ± 8.1 cm/s, and time velocity integral was 17.6 ± 10.2 cm. It took within 5 minutes to obtain GCV signals in the volunteers. Observer Variability Interobserver and intraobserver variabilities for the peak velocity were 4.6% and 3.8%, and for the time velocity integral were 4.8% and 4.2%, respectively.
DISCUSSION Coronary flow measurement by TTDE has been reported to be a useful and feasible method to evaluate significant LAD stenosis by measuring coronary flow velocity reserve or stenotic coronary flow velocity ratio.13,14 The coronary artery flow shows a prominent diastolic pattern. On the other hand, the flow dynamics in the coronary venous system are characterized by the phasic flow predominant in systole. Thus, coronary circulation consists of 2 vascular systems with different dynamic characteristics. However, there have been few reports describing the coronary venous physiology, especially in the clinical setting.This is because the measurement of coronary venous flow has been difficult by using conventional invasive thermodilution or DGW methods. In this study, we evaluated the reliability of GCV flow velocity measurement obtained from PDE in the experimental setting. Our data also demonstrated that noninvasive measurement of GCV flow velocity by TTDE was feasible in the clinical laboratory. Animal Experiments In the experimental setting, prominent systolic flow wave was recorded by using PDE and DGW methods.This characteristic was the same as that reported previously by using laser Doppler and DGW. Peak
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Figure 5 Simultaneous recording of great cardiac vein flow velocity by pulsed Doppler echocardiography (left) and Doppler guide wire (right) during hyperemia.
velocity and time velocity integral measured from epicardial PDE and DGW showed an excellent agreement. As shown in Figures 4 and 5, noises, which were attributable to the cross talk of ultrasound from DGW and PDE, were consistent among the measurements. We believed this phenomenon provided the evidence that these measurements were performed at the exact same site. From these results, it is suggested that GCV flow recording by PDE is a reliable and available technique. Clinical Study In the clinical setting, Doppler signal along the LAD toward the base of the heart showed a characteristic prominent systolic flow wave, as observed in the animal experiments.This suggests that the Doppler signal is from the GCV and measurement of GCV flow velocity is feasible and reliable by TTDE, noninvasively. The current study demonstrated that GCV flow velocity could be assessed with a high success rate (91%) under the guidance of color flow Doppler mapping for the clinical application.With TTDE, GCV flow velocity recording was performed by setting the color flow Doppler mapping velocity lower (velocity range, ±9.6 to ±28.8 cm/s), compared with the usual setting in routine echocardiographic examination.This result establishes several potentially useful features of the noninvasive assessment of the GCV flow by TTDE. First,TTDE can be performed in an outpatient setting because TTDE is widely available in the clinical setting. DGW and thermodilution methods are invasive and can be performed only in the catheter laboratory. At the present time, only TTDE provides noninvasive assessment of GCV flow velocity in routine clinical practice, not only in the echocardiographic laboratory but also in the cardiac care unit or the emergency department. Finally, serial assessment can be performed by this technique because it is noninvasive and relatively inexpensive.
Journal of the American Society of Echocardiography Volume 15 Number 3
Figure 6 Regression (top) and difference (bottom) plots comparing peak velocity by pulsed Doppler echocardiography (PDE) and Doppler guide wire (DGW) methods. There were excellent agreements between PDE and DGW methods for measurements of peak velocity. Mean differences between PDE and DGW were 0.85 ± 5.12 cm/s.
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Figure 7 Regression (top) and difference (bottom) plots comparing time velocity integral by pulsed Doppler echocardiography (PDE) and Doppler guide wire (DGW) methods. There were excellent agreements between PDE and DGW methods for measurements of time velocity integral. PDE and DGW were 0.04 ± 0.91 cm.
Thus, GCV flow measurement, with the use of TTDE, will provide important physiologic information in coronary circulation and applicability of GCV flow measurement, and it needs to be further evaluated with patients who have various hemodynamic conditions. Study Limitations The current study has some important limitations. First, GCV flow velocity obtained from PDE was compared with that from the DGW method. Although the DGW technique has been established for the assessment of coronary flow velocity in the clinical setting, there is a limitation in GCV flow measurement by this technique. The value of the peak velocity is dependent on positioning of the wire in tortuous segments and regions with varying luminal dimensions or configurations. However, in this study, we carefully positioned the tip of the DGW to obtain a good signal from the GCV, which did not include the tortuous segment. Second, although it may be difficult to set the tip of the DGW at the exact same site
Figure 8 Great cardiac vein (GCV) flow velocity by Doppler transthoracic echocardiography. GCV flow toward base of heart was obtained in systole.
as the sample volume set in PDE, we confirmed the location of the tip of the DGW under the guidance of fluoroscopy and noises that were attributable to the cross talk of ultrasound from DGW and PDE was
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thought to be the evidence that these measurements were performed at the exact same site. Finally, in the clinical study, angle correction was needed in each examination because of incident Doppler angle, although we tried to align ultrasound beam direction to GCV flow as parallel as possible. Conclusion TTDE is feasible for detecting GCV flow noninvasively in vivo. We gratefully acknowledge Paul Kalman, BScRT, in the preparation of the manuscript.
REFERENCES 1. Kajiya F, Tsujioka K, Goto M, Wada Y, Tadaoka S, Nakai M, et al. Evaluation of phasic blood flow velocity in the great cardiac vein by a laser Doppler method. Heart Vessels 1985;1:16-23. 2. Kajiya F, Tsujioka K, Ogasawara Y, Mito K, Hiramatsu O, Goto M, et al. Mechanical control of coronary artery inflow and vein outflow. Jpn Circ J 1989;53:431-9. 3. Kajiya F, Tsujioka K, Goto M, Wada Y, Chen X, Nakai M, et al. Functional characteristics of intramyocardial capacitance vessels during diastole in the dog. Circ Res 1986;58:476-85. 4. Cohen MV, Matsuki T, Downey JM. Pressure-flow characteristics and nutritional capacity of coronary veins in dogs. Am J Physiol 1988;255:H834-46. 5. Rosen JD, Oskarsson H, Stenberg RG, Braun P, Talman CL, Winniford MD. Simultaneous measurement of coronary flow reserve by left anterior descending coronary artery Doppler and great cardiac vein thermodilution methods. J Am Coll Cardiol 1992;20:402-7. 6. Manginas A, Pavlides G, Voudris V, Vassilikos V, Cokkinos DV. Coronary vein flow velocity changes during transluminal balloon angioplasty: a study using the Doppler guide wire. Cathet Cardiovasc Diagn 1997;40:85-91.
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7. Kern MJ, Deligonul U, Vandormael M, Labovits A, Gudipati CV, Gabliani G, et al. Impaired coronary vasodilator reserve in the immediate postcoronary angioplasty period: analysis of coronary artery flow velocity indexes and regional cardiac venous efflux. J Am Coll Cardiol 1989;13:860-72. 8. Rothman MT, Baim DS, Simson JB, Harrison DC. Coronary hemodynamics during percutaneous transluminal coronary angioplasty. Am J Cardiol 1982;49:1615-22. 9. Yamagishi M, Hotta D, Tamai J, Nakatani A, Miyatake K. Validity of catheter-tip Doppler technique in assessment of coronary flow velocity and application of spectrum analysis method. Am J Cardiol 1991;67:758-62. 10. Nicklas JM, Dilts EA, O’Neil WW, Bourdillon PDV, Walton JA, Pitt B. Quantitative measurement of coronary flow during medical revascularization (thrombolysis or angioplasty) in patients with acute infarction. J Am Coll Cardiol 1987;10: 284-9. 11. Komamura K, Kitakaze M, Nishida K, Naka M, Tamai J, Uematsu M, et al. Progressive decreases in coronary vein flow during reperfusion in acute myocardial infarction: clinical documentation of the no reflow phenomenon after successful thrombolysis. J Am Coll Cardiol 1994;24:370-7. 12. Hozumi T, Yoshida K, Akasaka T, Asami Y, Ogata Y, Takagi T, et al. Noninvasive assessment of coronary flow velocity and coronary flow velocity reserve in the left anterior descending coronary artery by Doppler echocardiography: comparison with invasive technique. J Am Coll Cardiol 1998;32:1251-9. 13. Hozumi T, Yoshida K, Ogata Y, Akasaka T, Asami Y, Takagi T, et al. Noninvasive assessment of significant left anterior descending coronary artery stenosis by coronary flow velocity reserve with transthoracic color Doppler echocardiography. Circulation 1998;97:1557-62. 14. Hozumi T, Yoshida K, Akasaka T, Asami Y, Kanzaki Y, Ueda Y, et al. Value of acceleration flow and the restenotic to stenotic coronary flow velocity ratio by transthoracic color Doppler echocardiography in noninvasive diagnosis of restenosis after percutaneous transluminal coronary angioplasty. J Am Coll Cardiol 2000;35:164-8. 15. Bland JM, Altman DG. Statistical methods for assessing agreement between two methods of clinical measurement. Lancet 1986;1:307-10.