- Email: [email protected]
Noninvasive assessment of coronary flow velocity and coronary flow velocity reserve in the right coronary artery by transthoracic doppler echocardiography: Comparison with intracoronary doppler guidewire
Noninvasive Assessment of Coronary Flow Velocity and Coronary Flow Velocity Reserve in the Right Coronary Artery by Transthoracic Doppler Echocardiography: Comparison with Intracoronary Doppler Guidewire Yoshiki Ueno, MD, Yasuyuki Nakamura, MD, Hiroyuki Takashima, MD, Masahiko Kinoshita, MD, and Akira Soma, MD, Shiga, Japan
The aim of this study was to evaluate whether coronary flow velocity (CFV) and coronary flow velocity reserve (CFVR) in the posterior descending right coronary artery can be reliably measured by transthoracic Doppler echocardiography (TTDE). In 17 patients, CFV in the posterior descending right coronary artery was measured with TTDE at the time of Doppler guidewire examination. CFV was measured by both methods at baseline and under hyperemic conditions. TTDE data were obtained for 12
T
he measurement of coronary flow velocity (CFV) and coronary flow velocity reserve (CFVR) can provide useful clinical information.1-6 These parameters have mainly been measured by an invasive intracoronary Doppler guidewire (DGW), semi-invasive transesophageal Doppler echocardiography, and expensive positron emission tomography.7-12 Recent advances in transthoracic Doppler echocardiography (TTDE) have made it possible to measure CFV and CFVR in the left anterior descending coronary artery noninvasively.13-17 Recent studies have demonstrated that CFV and CFVR in the left anterior descending coronary artery measured noninvasively by TTDE accurately reflect measurements by the invasive DGW method, and can be used for the noninvasive assessment of coronary stenosis in the left anterior descending artery.13,14 A recent study found that CFV and CFVR in the posterior descending coronary artery (PD) can be measured by TTDE.18 If CFV and CFVR in PD could be reliably measured by TTDE, it should provide From the First Department of Internal Medicine, Shiga University of Medical Science, Otsu, Shiga; and Kohnan Hospital (A.S.), Kohnan, Shiga, Japan. Reprints requests: Yoshiki Ueno, MD, First Department of Internal Medicine, Shiga University of Medical Science, Tsukinowa, Otsu, Shiga, 520-2192, Japan (E-mail: [email protected]). Copyright 2002 by the American Society of Echocardiography. 0894-7317/2002/$35.00 ⫹ 0 27/1/122356 doi:10.1067/mje.2002.122356
1074
patients. CFV and CFVR by TTDE show a good correlation with those obtained by the Doppler guidewire method (average diastolic peak velocity: r ⴝ 0.98, y ⴝ 0.85x ⴙ 5.26; diastolic peak velocity: r ⴝ 0.97, y ⴝ 0.94x ⴙ 3.39; CFVR: r ⴝ 0.97, y ⴝ 0.87x ⴙ 0.56). CFV and CFVR in the posterior descending right coronary artery obtained noninvasively by TTDE accurately reflect these values obtained by the invasive Doppler guidewire method. (J Am Soc Echocardiogr 2002;15:1074-9.)
useful clinical information. However, the measurement of CFV and CFVR in the PD by TTDE has not yet been validated in a clinical study. We designed this study to evaluate whether CFV and CFVR in the PD can be reliably measured by TTDE.
METHODS Study Patients We examined 17 consecutive patients in whom CFV in the PD could be measured by the DGW method at the time of coronary angiography. Exclusion criteria were acute myocardial infarction, unstable angina, nonsinus rhythm, diabetes mellitus, and severe chronic obstructive pulmonary disease. All patients underwent TTDE at the time of DGW examination. Nine patients had coronary artery disease (2 with significant stenosis in the proximal right coronary artery, the remainder with angiographically normal right coronary artery), 6 patients had valvular heart disease (4 patients with aortic regurgitation, 2 patients with mitral regurgitation) and 2 patients had hypertrophic cardiomyopathy. The ethics committee of Shiga University of Medical Science approved the study protocol. All the patients gave their informed consent before cardiac catheterization. Coronary Angiography Diagnostic coronary angiography was performed according to a standard procedure, using a 5F guiding catheter
Journal of the American Society of Echocardiography Volume 15 Number 10
Ueno et al
1075
(Z2 Medtronic, Minneapolis, Minn) after an intravenous bolus injection of 5000 U of heparin. Images of coronary angiography were stored on compact disks for offline analysis (CMS, MEDIS, Leiden, The Netherlands).19 Significant coronary stenosis was defined as “70% or more by off-line analysis.” DGW Examination The DGW examinations were performed with a 0.014inch DGW (Flowire, Endosonics, Rancho Cordova, Calif). After diagnostic coronary angiography, the DGW was advanced to the PD through a 5F guiding catheter. We tried to set the tip of the DGW near the site of the sample volume in TTDE examination under fluoroscopic monitoring. If the Doppler spectral tracing of velocity was not clear, the DGW was moved slightly to obtain clear Doppler spectral signals. Doppler spectral signals were recorded on 0.5-inch super VHS video tape. In all cases, we recorded heart rate, 12-lead ECG, and blood pressure at the tip of the guiding catheter inserted into the right coronary artery. Measurements of CFV and CFVR by DGW Method First, we recorded baseline Doppler spectral signals in the PD and then hyperemic Doppler spectral signals during peak hyperemia induced by the intravenous infusion of 0.15 mg/kg/min adenosine triphosphate. A real-time analyzer (Flomap, Endosonics), was used to measure the average diastolic peak velocity and diastolic peak velocity. CFVR was calculated as the ratio of peak hyperemic to baseline average diastolic peak velocity. The final value for the flow velocity represents an average of 5 cardiac cycles. TTDE TTDE examinations were performed with an ultrasonographic system (Sequoia 512, Acuson, Mountain View, Calif) with a 3.5-MHz transducer. In Doppler color flow mapping by 2.5-MHz color Doppler, the velocity range was set at ⫾12.0 or ⫾24.0 cm/s. The color gain was adjusted to provide optimal imaging from an apical approach in the left lateral decubitus position. First, the ventricle was imaged in the 2-chamber view with the coronary sinus ostium. Next, the ultrasound beam was inclined laterally or rotated to visualize the coronary blood flow close to the epicardial layer of the proximal portion or midportion of the posterior interventricular sulcus under color flow mapping guidance. CFV was measured with a pulsed wave Doppler at minimum angle correction (from 0 to 15 degrees) (Figure 1). Care was taken to avoid including in the sample volume the right ventricular inflow, which is characterized by a biphasic anterograde diastolic flow. Stop frames and clips were digitally recorded on magneto-optical disks for offline analysis. Measurements of CFV and CFVR by TTDE Doppler spectral signal recordings were obtained by TTDE during the DGW examination. First, we recorded baseline Doppler spectral signals in the PD by TTDE
Figure 1 Transthoracic Doppler echocardiography (TTDE) (left) and schematic representation (right) of coronary blood flow (arrow) in posterior descending right coronary artery (PD). LA, left atrium; LV, left ventricle.
immediately after recording them by the DGW method. Next, we recorded hyperemic Doppler spectral signals during peak hyperemia induced by the intravenous infusion of 0.15 mg/kg/min adenosine triphosphate at the same point after recording them by DGW method. If visualization of the color Doppler was unsuccessful or if the Doppler spectral tracing of velocity was not clear, an echocardiographic contrast agent (Levovist, Schering, Berlin, Germany) was used (n ⫽ 13). Levovist was administered at a concentration of 300 mg/mL by intravenous infusion using an infusion pump. The rate of infusion was adjusted to improve the Doppler signals (from 0.5 to 2.0 mL/min). An observer who had no knowledge of other patient data obtained measurements from recordings of Doppler spectral signals. Because of the difficulty of obtaining complete Doppler spectral envelopes throughout the cardiac cycle as a result of cardiac motion, only diastolic velocity was measured. Average diastolic peak velocity and diastolic peak velocity were measured by manually tracing the Doppler spectral signals with an analysis system that was incorporated in the ultrasonographic system. CFVR was calculated as the ratio of peak hyperemic to baseline average diastolic peak velocity. The final value for the flow velocity represents an average of 5 cardiac cycles. Data Analysis Results are reported as mean ⫾ SD. A linear regression analysis was used to compare TTDE with the DGW method for assessing average diastolic peak velocity, diastolic peak velocity, and CFVR. Bland-Altman analysis20 was used to evaluate the differences between average diastolic peak velocity, diastolic peak velocity, and CFVR by TTDE and those by DGW. To test observer variability by TTDE, 2 independent observers measured Doppler indices from 10 randomly selected Doppler velocity recordings. Intraobserver variability was assessed in 6 patients who underwent the measurement of CFV by TTDE twice within 20 minutes.
Journal of the American Society of Echocardiography October 2002
1076 Ueno et al
Table Clinical characteristics and coronary flow velocity data Baseline
No
Age (y)
Clinical Sex diagnosis
1 2 3 4 5 6 7 8 9 10 11 12
77 67 70 59 68 78 72 71 71 77 50 72
M M M F F M F M F M F F
MR AR AP AP AP AR AR HCM AP AP HCM AP
RCA stenosis
⫺ ⫺ ⫹ ⫺ ⫺ ⫺ ⫺ ⫺ ⫺ ⫺ ⫺ ⫹
% DS (Site)
78%(P)
72%(P)
ADPV (cm/s)
Hyperemia
DPV (cm/s)
CFVR
ADPV (cm/s)
DPV (cm/s)
DGW
TTDE
DGW
TTDE
DGW
TTDE
DGW
TTDE
DGW
TTDE
17 13 23 28 18 17 23 25 23 21 18 17
25 14 26 28 18 16 22 25 24 21 20 20
28 20 40 42 24 27 32 39 32 32 25 25
34 19 38 39 27 22 30 35 36 30 29 33
25 39 41 63 57 34 66 40 66 50 46 27
35 38 44 56 57 32 60 42 63 45 43 32
44 53 60 89 77 52 88 61 88 66 57 40
55 50 63 78 81 41 88 64 91 61 59 50
1.47 3.00 1.78 2.25 3.17 2.00 2.87 1.60 2.87 2.38 2.56 1.59
1.40 2.71 1.69 2.00 3.17 1.97 2.67 1.68 2.62 2.14 2.15 1.60
ADPV, Average diastolic peak velocity; DPV, diastolic peak velocity; CFVR, coronary flow velocity reserve; RCA, right coronary artery; DS, diameter stenosis; DGW, Doppler guidewire; TTDE, transthoracic Doppler echocardiography; MR, mitral regurgitation; AR, aortic regurgitation; AP, angina pectoris; P, proximal; HCM, hypertrophic cardiomyopathy.
CFV and CFVR Data Figure 2 shows CFV in the PD by the TTDE and DGW methods in the same patient. CFV (average diastolic peak velocity and diastolic peak velocity) by TTDE correlated with those obtained by the DGW method. The mean differences in average diastolic peak velocity and diastolic peak velocity between the TTDE and DGW methods were ⫺0.38 ⫾ 3.95 cm/s and ⫺0.50 ⫾ 5.68 cm/s, respectively (Figures 3 and 4). CFVR by TTDE correlated with that by the DGW method. The mean difference in CFVR between the TTDE and DGW methods was 0.14 ⫾ 0.15 (Figure 5). Observer Variability
Figure 2 Example of coronary flow velocity recordings at baseline (left) and during hyperemia (right) obtained by Doppler guidewire (DGW) (top) and transthoracic Doppler echocardiography (TTDE) (bottom) in same patient.
RESULTS Among the 17 study patients, adequate Doppler spectral signal recordings in the PD by TTDE were obtained for 12 (70%) (6 men and 6 women; mean age 69 ⫾ 8 years old), including 8 patients who were given an echocardiographic contrast agent to improve Doppler spectral signals. Two patients with adequate Doppler spectral signal recordings had a significant coronary stenosis in the proximal right coronary artery. The clinical and Doppler velocity data of the remaining 12 patients are shown in Table.
The mean percentages of interobserver variability for the measurement of average diastolic peak velocity and diastolic peak velocity were 3.3% and 3.6%, respectively. The mean percentages of intraobserver variability for the measurement of average diastolic peak velocity and diastolic peak velocity were 5.8% and 6.3%, respectively. Coefficients of interobserver and intraobserver variability were not significant.
DISCUSSION In this study, we demonstrated that CFV and CFVR in the PD can be reliably measured by TTDE and correlate with those obtained by the DGW method. Measurements of CFV and CFVR by Invasive Methods The measurement of CFV and CFVR can provide useful clinical information for the assessment of coronary artery stenosis and microvascular func-
Journal of the American Society of Echocardiography Volume 15 Number 10
Ueno et al
1077
Figure 3 Regression (left) and difference (right) plots comparing average diastolic peak velocity (ADPV) measured by transthoracic Doppler echocardiography (TTDE) and Doppler guidewire (DGW).
Figure 4 Regression (left) and difference (right) plots comparing diastolic peak velocity (DPV) measured by transthoracic Doppler echocardiography (TTDE) and Doppler guidewire (DGW).
Figure 5 Regression (left) and difference (right) plots comparing Coronary flow velocity reserve (CFVR) measured by transthoracic Doppler echocardiography (TTDE) and Doppler guidewire (DGW).
tion.1-6 These parameters have mainly been measured by invasive intracoronary DGW and semiinvasive transesophageal Doppler echocardiography.7-11 However, the DGW method is available only in the catheterization laboratory, whereas transesophageal Doppler echocardiography is semi-invasive and can measure only CFV in the proximal coronary artery. Thus, it has been difficult to assess CFV in routine clinical practice. Measurements of CFV and CFVR by Noninvasive Methods Positron emission tomography and TTDE are noninvasive.12-17 However, positron emission tomography is expensive and is available only at certain institutions. On the other hand, TTDE is relatively inexpensive and is frequently used in the clinical setting. Recent studies have found that the noninvasive
measurement of CFV and CFVR in the left anterior descending coronary artery by TTDE accurately reflected the values obtained by the invasive DGW method and could be used for the noninvasive assessment of coronary stenosis in the left anterior descending artery.13-17 However, these parameters have only been measured in the left anterior descending coronary artery. Measurements of CFV and CFVR in the Right Coronary Artery by TTDE A recent study found that CFV and CFVR in the posterior descending coronary artery can be measured by TTDE.18 If CFV and CFVR in the PD can be reliably measured by TTDE, it could provide useful clinical information. However, the measurement of CFV and CFVR in the PD by TTDE has not yet been validated in a clinical study. Therefore, in the cur-
1078 Ueno et al
rent study, we compared CFV and CFVR in the PD by TTDE with those obtained by the DGW method, which has already been validated.7,8 CFV (average diastolic peak velocity and diastolic peak velocity) and CFVR in the PD by TTDE strongly correlated with those by the DGW method. These results suggest that the measurement of CFV and CFVR in the PD by TTDE is reliable and can be used to assess coronary stenosis in the right coronary artery and in the left anterior descending coronary artery. Noninvasive measurement of CFV and CFVR in the PD may be helpful for analyzing coronary flow dynamics in cardiac disease.
Journal of the American Society of Echocardiography October 2002
in only 2. In previous studies that used TTDE, the ratio of peak hyperemic to baseline average diastolic peak velocity was useful for assessing coronary stenosis in the left anterior descending coronary artery.14,16,17 Conclusion CFV and CFVR in the PD measured noninvasively by TTDE accurately reflect these parameters measured by the invasive DGW method. We gratefully acknowledge the technical assistance of Haruko Kameda, the sonographer in this study.
Study Limitations First, we obtained adequate Doppler spectral signal recordings in only 12 patients (70%), including 8 patients who were given an echocardiographic contrast agent to improve Doppler spectral signals, and this is much less than the success rate in the left anterior descending coronary artery (95%).17 Furthermore, whereas recent advances in TTDE have made it possible to measure CFVR noninvasively in the right coronary artery and left anterior descending coronary artery, it is difficult to measure CFV in the left circumflex coronary artery without a landmark such as the interventricular sulcus. Second, in this study, the posterior descending artery originated from the right coronary artery in all of the patients. If the posterior descending artery originated from the left circumflex coronary artery, CFVR in the posterior descending artery may not be suitable for assessing coronary stenosis in the right coronary artery. Third, we compared CFV and CFVR by TTDE with measurements obtained by the DGW method. Although the DGW method has been shown to be useful for the assessment of CFV and CFVR, it is limited in that CFV is dependent on the position of the tip of the DGW. In this study, we tried to set the tip of the DGW carefully at sites without tortuous segments under fluoroscopic monitoring. However, it may be difficult to set the tip of the DGW at the same point as the sample volume in TTDE examinations. Especially in patients with a small PD, the Doppler spectral tracing of velocity was not clear, and the DGW had to be moved to obtain clear Doppler spectral signals. This possible difference in the location of the sample point in each method may affect the measurement of CFV. Finally, we calculated CFVR from using only the average diastolic peak velocity, because it was difficult to obtain complete Doppler spectral envelopes throughout the cardiac cycle as a result of cardiac motion. Of the 12 patients with adequate Doppler spectral signal recordings of the diastolic phase, complete Doppler spectral signal envelopes throughout the entire cardiac cycle were obtained
REFERENCES 1. Gould KL, Lipscomb K, Hamilton GW. Physiologic basis for assessing critical coronary stenosis: instantaneous flow response and regional distribution during coronary hyperemia as measures of coronary flow reserve. Am J Cardiol 1974;33:8794. 2. Gould KL, Lipscomb K. Effects of coronary stenoses on coronary flow reserve and resistance. Am J Cardiol 1974;34: 48-55. 3. Marcus M, Wright C, Doty D, Eastham C, Laughlin D, Krumm P, et al. Measurements of coronary velocity and reactive hyperemia in the coronary circulation of humans. Circ Res 1981;49:877-91. 4. Hoffman JI. Maximal coronary flow and the concept coronary vascular reserve. Circulation 1984;70:153-9. 5. Marcus ML, Wilson RF, White CW. Methods of measurement of myocardial blood flow in patients: a critical review. Circulation 1987;76:245-53. 6. Klocke FJ. Measurements of coronary flow reserve: defining pathophysiology versus making decisions about patient care. Circulation 1987;76:1183-9. 7. Segal J, Kern MJ, Scott NA, King SB, Doucette JW, Heuser RR, et al. Alterations or phasic coronary artery flow velocity in humans during percutaneous coronary angioplasty. J Am Coll Cardiol 1992;20:276-86. 8. Doucette JW, Corl D, Payne HM, Flynn AE, Goto M, Nassi M, et al. Validation of a Doppler guide wire for intravascular measurement of coronary artery flow velocity. Circulation 1992;85:1899-911. 9. Yoshida K, Yoshikawa J, Hozumi T, Yamamura Y, Akasaka T, Shiratori K, et al. Value of transesophageal color Doppler echocardiography in the evaluation of coronary artery anatomy and blood flow. Jpn Circ J 1990;54:298-303. 10. Iliceto S, Marangelli V, Memmola C, Rizzon P. Transesophageal Doppler echocardiographic evaluation of coronary blood flow velocity in baseline conditions and during dipyridamole-induced coronary vasodilation. Circulation 1991;83: 61-9. 11. Redberg RF, Sobol Y, Chou TM, Malloy M, Kumar S, Botvinick E, et al. Adenosine-induced coronary vasodilation during transesophageal Doppler echocardiography: rapid and safe measurement of coronary flow reserve ratio can predict significant left anterior descending coronary stenosis. Circulation 1995;92:190-6. 12. Demer LL, Gould KL, Goldstein RA, Kirkeeide RL, Mullani NA, Smalling RW, et al. Assessment of coronary artery disease severity by positron emission tomography: comparison with
Journal of the American Society of Echocardiography Volume 15 Number 10
13.
14.
15.
16.
quantitative arteriography in 193 patients. Circulation 1989; 79:825-35. 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. 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. Caiati C, Montaldo C, Zedda N, Montisci R, Ruscazio M, Lai G, et al. Validation of a new noninvasive method (contrastenhanced transthoracic second harmonic echo Doppler) for the evaluation of coronary flow reserve: comparison with intracoronary Doppler flow wire. J Am Coll Cardiol 1999;34: 1993-2000. Caiati C, Zedda N, Montaldo C, Montisci R, Iliceto S. Con-
Ueno et al
17.
18.
19.
20.
1079
trast-enhanced transthoracic second harmonic echo Doppler with adenosine: a noninvasive, rapid and effective method for coronary flow reserve assessment. J Am Coll Cardiol 1999;34: 122-30. Pizzuto F, Voci P, Mariano E, Puddu PE, Sardella G, Nigri A. Assessment of flow velocity reserve by transthoracic Doppler echocardiography and venous adenosine infusion before and after left anterior descending coronary stenting. J Am Coll Cardiol 2001;38:155-62. Voci P, Pizzuto F. Imaging of the posterior descending coronary artery. The last frontier in echocardiography. Ital Heart J 2001;2:418-22. Hausleiter J, Nolte CW, Jost S, Wiese B, Sturm M, Lichtlen PR. Comparison of different quantitative coronary analysis systems: ARTREK, CAAS, and CMS. Catheter Cardiovasc Diagn 1996;37:14-22. Bland JM, Altman DG. Statistical methods for assessing agreement between two methods of clinical measurement. Lancet 1986;1:307-10.
The aim of this study was to evaluate whether coronary flow velocity (CFV) and coronary flow velocity reserve (CFVR) in the posterior descending right coronary artery can be reliably measured by transthoracic Doppler echocardiography (TTDE). In 17 patients, CFV in the posterior descending right coronary artery was measured with TTDE at the time of Doppler guidewire examination. CFV was measured by both methods at baseline and under hyperemic conditions. TTDE data were obtained for 12
T
he measurement of coronary flow velocity (CFV) and coronary flow velocity reserve (CFVR) can provide useful clinical information.1-6 These parameters have mainly been measured by an invasive intracoronary Doppler guidewire (DGW), semi-invasive transesophageal Doppler echocardiography, and expensive positron emission tomography.7-12 Recent advances in transthoracic Doppler echocardiography (TTDE) have made it possible to measure CFV and CFVR in the left anterior descending coronary artery noninvasively.13-17 Recent studies have demonstrated that CFV and CFVR in the left anterior descending coronary artery measured noninvasively by TTDE accurately reflect measurements by the invasive DGW method, and can be used for the noninvasive assessment of coronary stenosis in the left anterior descending artery.13,14 A recent study found that CFV and CFVR in the posterior descending coronary artery (PD) can be measured by TTDE.18 If CFV and CFVR in PD could be reliably measured by TTDE, it should provide From the First Department of Internal Medicine, Shiga University of Medical Science, Otsu, Shiga; and Kohnan Hospital (A.S.), Kohnan, Shiga, Japan. Reprints requests: Yoshiki Ueno, MD, First Department of Internal Medicine, Shiga University of Medical Science, Tsukinowa, Otsu, Shiga, 520-2192, Japan (E-mail: [email protected]). Copyright 2002 by the American Society of Echocardiography. 0894-7317/2002/$35.00 ⫹ 0 27/1/122356 doi:10.1067/mje.2002.122356
1074
patients. CFV and CFVR by TTDE show a good correlation with those obtained by the Doppler guidewire method (average diastolic peak velocity: r ⴝ 0.98, y ⴝ 0.85x ⴙ 5.26; diastolic peak velocity: r ⴝ 0.97, y ⴝ 0.94x ⴙ 3.39; CFVR: r ⴝ 0.97, y ⴝ 0.87x ⴙ 0.56). CFV and CFVR in the posterior descending right coronary artery obtained noninvasively by TTDE accurately reflect these values obtained by the invasive Doppler guidewire method. (J Am Soc Echocardiogr 2002;15:1074-9.)
useful clinical information. However, the measurement of CFV and CFVR in the PD by TTDE has not yet been validated in a clinical study. We designed this study to evaluate whether CFV and CFVR in the PD can be reliably measured by TTDE.
METHODS Study Patients We examined 17 consecutive patients in whom CFV in the PD could be measured by the DGW method at the time of coronary angiography. Exclusion criteria were acute myocardial infarction, unstable angina, nonsinus rhythm, diabetes mellitus, and severe chronic obstructive pulmonary disease. All patients underwent TTDE at the time of DGW examination. Nine patients had coronary artery disease (2 with significant stenosis in the proximal right coronary artery, the remainder with angiographically normal right coronary artery), 6 patients had valvular heart disease (4 patients with aortic regurgitation, 2 patients with mitral regurgitation) and 2 patients had hypertrophic cardiomyopathy. The ethics committee of Shiga University of Medical Science approved the study protocol. All the patients gave their informed consent before cardiac catheterization. Coronary Angiography Diagnostic coronary angiography was performed according to a standard procedure, using a 5F guiding catheter
Journal of the American Society of Echocardiography Volume 15 Number 10
Ueno et al
1075
(Z2 Medtronic, Minneapolis, Minn) after an intravenous bolus injection of 5000 U of heparin. Images of coronary angiography were stored on compact disks for offline analysis (CMS, MEDIS, Leiden, The Netherlands).19 Significant coronary stenosis was defined as “70% or more by off-line analysis.” DGW Examination The DGW examinations were performed with a 0.014inch DGW (Flowire, Endosonics, Rancho Cordova, Calif). After diagnostic coronary angiography, the DGW was advanced to the PD through a 5F guiding catheter. We tried to set the tip of the DGW near the site of the sample volume in TTDE examination under fluoroscopic monitoring. If the Doppler spectral tracing of velocity was not clear, the DGW was moved slightly to obtain clear Doppler spectral signals. Doppler spectral signals were recorded on 0.5-inch super VHS video tape. In all cases, we recorded heart rate, 12-lead ECG, and blood pressure at the tip of the guiding catheter inserted into the right coronary artery. Measurements of CFV and CFVR by DGW Method First, we recorded baseline Doppler spectral signals in the PD and then hyperemic Doppler spectral signals during peak hyperemia induced by the intravenous infusion of 0.15 mg/kg/min adenosine triphosphate. A real-time analyzer (Flomap, Endosonics), was used to measure the average diastolic peak velocity and diastolic peak velocity. CFVR was calculated as the ratio of peak hyperemic to baseline average diastolic peak velocity. The final value for the flow velocity represents an average of 5 cardiac cycles. TTDE TTDE examinations were performed with an ultrasonographic system (Sequoia 512, Acuson, Mountain View, Calif) with a 3.5-MHz transducer. In Doppler color flow mapping by 2.5-MHz color Doppler, the velocity range was set at ⫾12.0 or ⫾24.0 cm/s. The color gain was adjusted to provide optimal imaging from an apical approach in the left lateral decubitus position. First, the ventricle was imaged in the 2-chamber view with the coronary sinus ostium. Next, the ultrasound beam was inclined laterally or rotated to visualize the coronary blood flow close to the epicardial layer of the proximal portion or midportion of the posterior interventricular sulcus under color flow mapping guidance. CFV was measured with a pulsed wave Doppler at minimum angle correction (from 0 to 15 degrees) (Figure 1). Care was taken to avoid including in the sample volume the right ventricular inflow, which is characterized by a biphasic anterograde diastolic flow. Stop frames and clips were digitally recorded on magneto-optical disks for offline analysis. Measurements of CFV and CFVR by TTDE Doppler spectral signal recordings were obtained by TTDE during the DGW examination. First, we recorded baseline Doppler spectral signals in the PD by TTDE
Figure 1 Transthoracic Doppler echocardiography (TTDE) (left) and schematic representation (right) of coronary blood flow (arrow) in posterior descending right coronary artery (PD). LA, left atrium; LV, left ventricle.
immediately after recording them by the DGW method. Next, we recorded hyperemic Doppler spectral signals during peak hyperemia induced by the intravenous infusion of 0.15 mg/kg/min adenosine triphosphate at the same point after recording them by DGW method. If visualization of the color Doppler was unsuccessful or if the Doppler spectral tracing of velocity was not clear, an echocardiographic contrast agent (Levovist, Schering, Berlin, Germany) was used (n ⫽ 13). Levovist was administered at a concentration of 300 mg/mL by intravenous infusion using an infusion pump. The rate of infusion was adjusted to improve the Doppler signals (from 0.5 to 2.0 mL/min). An observer who had no knowledge of other patient data obtained measurements from recordings of Doppler spectral signals. Because of the difficulty of obtaining complete Doppler spectral envelopes throughout the cardiac cycle as a result of cardiac motion, only diastolic velocity was measured. Average diastolic peak velocity and diastolic peak velocity were measured by manually tracing the Doppler spectral signals with an analysis system that was incorporated in the ultrasonographic system. CFVR was calculated as the ratio of peak hyperemic to baseline average diastolic peak velocity. The final value for the flow velocity represents an average of 5 cardiac cycles. Data Analysis Results are reported as mean ⫾ SD. A linear regression analysis was used to compare TTDE with the DGW method for assessing average diastolic peak velocity, diastolic peak velocity, and CFVR. Bland-Altman analysis20 was used to evaluate the differences between average diastolic peak velocity, diastolic peak velocity, and CFVR by TTDE and those by DGW. To test observer variability by TTDE, 2 independent observers measured Doppler indices from 10 randomly selected Doppler velocity recordings. Intraobserver variability was assessed in 6 patients who underwent the measurement of CFV by TTDE twice within 20 minutes.
Journal of the American Society of Echocardiography October 2002
1076 Ueno et al
Table Clinical characteristics and coronary flow velocity data Baseline
No
Age (y)
Clinical Sex diagnosis
1 2 3 4 5 6 7 8 9 10 11 12
77 67 70 59 68 78 72 71 71 77 50 72
M M M F F M F M F M F F
MR AR AP AP AP AR AR HCM AP AP HCM AP
RCA stenosis
⫺ ⫺ ⫹ ⫺ ⫺ ⫺ ⫺ ⫺ ⫺ ⫺ ⫺ ⫹
% DS (Site)
78%(P)
72%(P)
ADPV (cm/s)
Hyperemia
DPV (cm/s)
CFVR
ADPV (cm/s)
DPV (cm/s)
DGW
TTDE
DGW
TTDE
DGW
TTDE
DGW
TTDE
DGW
TTDE
17 13 23 28 18 17 23 25 23 21 18 17
25 14 26 28 18 16 22 25 24 21 20 20
28 20 40 42 24 27 32 39 32 32 25 25
34 19 38 39 27 22 30 35 36 30 29 33
25 39 41 63 57 34 66 40 66 50 46 27
35 38 44 56 57 32 60 42 63 45 43 32
44 53 60 89 77 52 88 61 88 66 57 40
55 50 63 78 81 41 88 64 91 61 59 50
1.47 3.00 1.78 2.25 3.17 2.00 2.87 1.60 2.87 2.38 2.56 1.59
1.40 2.71 1.69 2.00 3.17 1.97 2.67 1.68 2.62 2.14 2.15 1.60
ADPV, Average diastolic peak velocity; DPV, diastolic peak velocity; CFVR, coronary flow velocity reserve; RCA, right coronary artery; DS, diameter stenosis; DGW, Doppler guidewire; TTDE, transthoracic Doppler echocardiography; MR, mitral regurgitation; AR, aortic regurgitation; AP, angina pectoris; P, proximal; HCM, hypertrophic cardiomyopathy.
CFV and CFVR Data Figure 2 shows CFV in the PD by the TTDE and DGW methods in the same patient. CFV (average diastolic peak velocity and diastolic peak velocity) by TTDE correlated with those obtained by the DGW method. The mean differences in average diastolic peak velocity and diastolic peak velocity between the TTDE and DGW methods were ⫺0.38 ⫾ 3.95 cm/s and ⫺0.50 ⫾ 5.68 cm/s, respectively (Figures 3 and 4). CFVR by TTDE correlated with that by the DGW method. The mean difference in CFVR between the TTDE and DGW methods was 0.14 ⫾ 0.15 (Figure 5). Observer Variability
Figure 2 Example of coronary flow velocity recordings at baseline (left) and during hyperemia (right) obtained by Doppler guidewire (DGW) (top) and transthoracic Doppler echocardiography (TTDE) (bottom) in same patient.
RESULTS Among the 17 study patients, adequate Doppler spectral signal recordings in the PD by TTDE were obtained for 12 (70%) (6 men and 6 women; mean age 69 ⫾ 8 years old), including 8 patients who were given an echocardiographic contrast agent to improve Doppler spectral signals. Two patients with adequate Doppler spectral signal recordings had a significant coronary stenosis in the proximal right coronary artery. The clinical and Doppler velocity data of the remaining 12 patients are shown in Table.
The mean percentages of interobserver variability for the measurement of average diastolic peak velocity and diastolic peak velocity were 3.3% and 3.6%, respectively. The mean percentages of intraobserver variability for the measurement of average diastolic peak velocity and diastolic peak velocity were 5.8% and 6.3%, respectively. Coefficients of interobserver and intraobserver variability were not significant.
DISCUSSION In this study, we demonstrated that CFV and CFVR in the PD can be reliably measured by TTDE and correlate with those obtained by the DGW method. Measurements of CFV and CFVR by Invasive Methods The measurement of CFV and CFVR can provide useful clinical information for the assessment of coronary artery stenosis and microvascular func-
Journal of the American Society of Echocardiography Volume 15 Number 10
Ueno et al
1077
Figure 3 Regression (left) and difference (right) plots comparing average diastolic peak velocity (ADPV) measured by transthoracic Doppler echocardiography (TTDE) and Doppler guidewire (DGW).
Figure 4 Regression (left) and difference (right) plots comparing diastolic peak velocity (DPV) measured by transthoracic Doppler echocardiography (TTDE) and Doppler guidewire (DGW).
Figure 5 Regression (left) and difference (right) plots comparing Coronary flow velocity reserve (CFVR) measured by transthoracic Doppler echocardiography (TTDE) and Doppler guidewire (DGW).
tion.1-6 These parameters have mainly been measured by invasive intracoronary DGW and semiinvasive transesophageal Doppler echocardiography.7-11 However, the DGW method is available only in the catheterization laboratory, whereas transesophageal Doppler echocardiography is semi-invasive and can measure only CFV in the proximal coronary artery. Thus, it has been difficult to assess CFV in routine clinical practice. Measurements of CFV and CFVR by Noninvasive Methods Positron emission tomography and TTDE are noninvasive.12-17 However, positron emission tomography is expensive and is available only at certain institutions. On the other hand, TTDE is relatively inexpensive and is frequently used in the clinical setting. Recent studies have found that the noninvasive
measurement of CFV and CFVR in the left anterior descending coronary artery by TTDE accurately reflected the values obtained by the invasive DGW method and could be used for the noninvasive assessment of coronary stenosis in the left anterior descending artery.13-17 However, these parameters have only been measured in the left anterior descending coronary artery. Measurements of CFV and CFVR in the Right Coronary Artery by TTDE A recent study found that CFV and CFVR in the posterior descending coronary artery can be measured by TTDE.18 If CFV and CFVR in the PD can be reliably measured by TTDE, it could provide useful clinical information. However, the measurement of CFV and CFVR in the PD by TTDE has not yet been validated in a clinical study. Therefore, in the cur-
1078 Ueno et al
rent study, we compared CFV and CFVR in the PD by TTDE with those obtained by the DGW method, which has already been validated.7,8 CFV (average diastolic peak velocity and diastolic peak velocity) and CFVR in the PD by TTDE strongly correlated with those by the DGW method. These results suggest that the measurement of CFV and CFVR in the PD by TTDE is reliable and can be used to assess coronary stenosis in the right coronary artery and in the left anterior descending coronary artery. Noninvasive measurement of CFV and CFVR in the PD may be helpful for analyzing coronary flow dynamics in cardiac disease.
Journal of the American Society of Echocardiography October 2002
in only 2. In previous studies that used TTDE, the ratio of peak hyperemic to baseline average diastolic peak velocity was useful for assessing coronary stenosis in the left anterior descending coronary artery.14,16,17 Conclusion CFV and CFVR in the PD measured noninvasively by TTDE accurately reflect these parameters measured by the invasive DGW method. We gratefully acknowledge the technical assistance of Haruko Kameda, the sonographer in this study.
Study Limitations First, we obtained adequate Doppler spectral signal recordings in only 12 patients (70%), including 8 patients who were given an echocardiographic contrast agent to improve Doppler spectral signals, and this is much less than the success rate in the left anterior descending coronary artery (95%).17 Furthermore, whereas recent advances in TTDE have made it possible to measure CFVR noninvasively in the right coronary artery and left anterior descending coronary artery, it is difficult to measure CFV in the left circumflex coronary artery without a landmark such as the interventricular sulcus. Second, in this study, the posterior descending artery originated from the right coronary artery in all of the patients. If the posterior descending artery originated from the left circumflex coronary artery, CFVR in the posterior descending artery may not be suitable for assessing coronary stenosis in the right coronary artery. Third, we compared CFV and CFVR by TTDE with measurements obtained by the DGW method. Although the DGW method has been shown to be useful for the assessment of CFV and CFVR, it is limited in that CFV is dependent on the position of the tip of the DGW. In this study, we tried to set the tip of the DGW carefully at sites without tortuous segments under fluoroscopic monitoring. However, it may be difficult to set the tip of the DGW at the same point as the sample volume in TTDE examinations. Especially in patients with a small PD, the Doppler spectral tracing of velocity was not clear, and the DGW had to be moved to obtain clear Doppler spectral signals. This possible difference in the location of the sample point in each method may affect the measurement of CFV. Finally, we calculated CFVR from using only the average diastolic peak velocity, because it was difficult to obtain complete Doppler spectral envelopes throughout the cardiac cycle as a result of cardiac motion. Of the 12 patients with adequate Doppler spectral signal recordings of the diastolic phase, complete Doppler spectral signal envelopes throughout the entire cardiac cycle were obtained
REFERENCES 1. Gould KL, Lipscomb K, Hamilton GW. Physiologic basis for assessing critical coronary stenosis: instantaneous flow response and regional distribution during coronary hyperemia as measures of coronary flow reserve. Am J Cardiol 1974;33:8794. 2. Gould KL, Lipscomb K. Effects of coronary stenoses on coronary flow reserve and resistance. Am J Cardiol 1974;34: 48-55. 3. Marcus M, Wright C, Doty D, Eastham C, Laughlin D, Krumm P, et al. Measurements of coronary velocity and reactive hyperemia in the coronary circulation of humans. Circ Res 1981;49:877-91. 4. Hoffman JI. Maximal coronary flow and the concept coronary vascular reserve. Circulation 1984;70:153-9. 5. Marcus ML, Wilson RF, White CW. Methods of measurement of myocardial blood flow in patients: a critical review. Circulation 1987;76:245-53. 6. Klocke FJ. Measurements of coronary flow reserve: defining pathophysiology versus making decisions about patient care. Circulation 1987;76:1183-9. 7. Segal J, Kern MJ, Scott NA, King SB, Doucette JW, Heuser RR, et al. Alterations or phasic coronary artery flow velocity in humans during percutaneous coronary angioplasty. J Am Coll Cardiol 1992;20:276-86. 8. Doucette JW, Corl D, Payne HM, Flynn AE, Goto M, Nassi M, et al. Validation of a Doppler guide wire for intravascular measurement of coronary artery flow velocity. Circulation 1992;85:1899-911. 9. Yoshida K, Yoshikawa J, Hozumi T, Yamamura Y, Akasaka T, Shiratori K, et al. Value of transesophageal color Doppler echocardiography in the evaluation of coronary artery anatomy and blood flow. Jpn Circ J 1990;54:298-303. 10. Iliceto S, Marangelli V, Memmola C, Rizzon P. Transesophageal Doppler echocardiographic evaluation of coronary blood flow velocity in baseline conditions and during dipyridamole-induced coronary vasodilation. Circulation 1991;83: 61-9. 11. Redberg RF, Sobol Y, Chou TM, Malloy M, Kumar S, Botvinick E, et al. Adenosine-induced coronary vasodilation during transesophageal Doppler echocardiography: rapid and safe measurement of coronary flow reserve ratio can predict significant left anterior descending coronary stenosis. Circulation 1995;92:190-6. 12. Demer LL, Gould KL, Goldstein RA, Kirkeeide RL, Mullani NA, Smalling RW, et al. Assessment of coronary artery disease severity by positron emission tomography: comparison with
Journal of the American Society of Echocardiography Volume 15 Number 10
13.
14.
15.
16.
quantitative arteriography in 193 patients. Circulation 1989; 79:825-35. 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. 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. Caiati C, Montaldo C, Zedda N, Montisci R, Ruscazio M, Lai G, et al. Validation of a new noninvasive method (contrastenhanced transthoracic second harmonic echo Doppler) for the evaluation of coronary flow reserve: comparison with intracoronary Doppler flow wire. J Am Coll Cardiol 1999;34: 1993-2000. Caiati C, Zedda N, Montaldo C, Montisci R, Iliceto S. Con-
Ueno et al
17.
18.
19.
20.
1079
trast-enhanced transthoracic second harmonic echo Doppler with adenosine: a noninvasive, rapid and effective method for coronary flow reserve assessment. J Am Coll Cardiol 1999;34: 122-30. Pizzuto F, Voci P, Mariano E, Puddu PE, Sardella G, Nigri A. Assessment of flow velocity reserve by transthoracic Doppler echocardiography and venous adenosine infusion before and after left anterior descending coronary stenting. J Am Coll Cardiol 2001;38:155-62. Voci P, Pizzuto F. Imaging of the posterior descending coronary artery. The last frontier in echocardiography. Ital Heart J 2001;2:418-22. Hausleiter J, Nolte CW, Jost S, Wiese B, Sturm M, Lichtlen PR. Comparison of different quantitative coronary analysis systems: ARTREK, CAAS, and CMS. Catheter Cardiovasc Diagn 1996;37:14-22. Bland JM, Altman DG. Statistical methods for assessing agreement between two methods of clinical measurement. Lancet 1986;1:307-10.