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Effects of coil closure of patent ductus arteriosus on left anterior descending coronary artery blood flow using transthoracic Doppler echocardiography
Effects of Coil Closure of Patent Ductus Arteriosus on Left Anterior Descending Coronary Artery Blood Flow Using Transthoracic Doppler Echocardiography Kenji Harada, MD, Manotomo Toyono, MD, and Masamichi Tamura, MD, Akita, Japan
Transthoracic Doppler echocardiography provides noninvasive measurements of coronary blood flow in the left anterior descending coronary artery (LAD). This method has the potential to show the effects of acute changes in loading conditions on blood flow. Coil closure of patent ductus arteriosus (PDA) is a model of acute changes in blood pressure and left ventricular (LV) preload that influences coronary blood flow. We applied this technique to assess the coronary blood flow changes for patients with PDA before and immediately after PDA coil closure. We examined 9 patients (1.8 ⴞ 1.1 years) with simple PDA and 8 age-matched healthy children. LV dimensions and LV mass were measured. Maximum peak flow velocity and flow volume in the LAD were measured. Pulmonary to systemic flow ratios (Qp/Qs) were obtained by cardiac catheterization. After PDA coil closure, LV end-diastolic dimen-
Coronary flow velocity is known to increase for
patients with left ventricular (LV) hypertrophy secondary to volume overload.1-4 However, little information exists about the effects of acute change in preload on coronary flow. Coil closure of patent ductus arteriosus (PDA) is a model of acute changes in blood pressure and LV preload that influences coronary blood flow. Recently, several studies have reported that the flow velocity in the left anterior descending coronary artery (LAD) can be measured using 2-dimensional (2D) transthoracic echocardiography (TTE) and Doppler echocardiography in children.5-11 In addition, we have shown that noninvaive measurement of LAD coronary flow velocity with Doppler TTE accurately reflects invasive measurement of LAD flow velocity with Doppler guidewire method in pediatric patients with various heart diseases.12 Therefore, we applied this technique to From the Department of Pediatrics, Akita University School of Medicine. Reprint requests: Kenji Harada, MD, Department of Pediatrics, Akita University School of Medicine, Akita, Japan. (E-mail: [email protected]). 0894-7317/$30.00 Copyright 2004 by the American Society of Echocardiography. doi:10.1016/j.echo.2004.02.018
sion decreased, and systolic and diastolic blood pressures increased significantly. The maximum peak flow velocity, LAD flow volume, and the ratio of LAD flow volume to LV mass increased significantly. The changes in maximum peak flow velocity and the ratio of LAD flow volume to LV mass (F/M) correlated positively with the changes in diastolic pressure and Qp/Qs. In 5 patients who had Qp/Qs > 1.5, the mean F/M was significantly lower compared with control subjects, but they increased to normal values after coil closure of PDA. PDA coil closure increases diastolic pressure and decreases Qp/Qs, resulting in improvement of myocardial perfusion. These findings provide new insights into the relationship between cardiac function and coronary circulation in pediatric patients with heart diseases associated with PDA. (J Am Soc Echocardiogr 2004;17: 659-63.)
assess the coronary blood flow changes in patients with PDA before and immediately after PDA coil closure.
METHODS Study Subjects Between October 2000 and June 2002, 9 patients (1.8 ⫾ 1.1 years) with isolated PDA who underwent percutaneous coil closure of the PDA and 8 age-matched healthy children were prospectively enrolled in the study. Before the PDA coil closure, conventional right and left heart catheterizations were performed to determine pressures and oxygen saturation levels. Pulmonary to systemic flow ratio (Qp/Qs) by Fick’s method was 1.5 ⫾ 0.4 (range: 1.1-2.2). The patients with PDA were divided into 2 groups: Qp/Qs ⬍ 1.5 (n ⫽ 4); and Qp/Qs ⬎ 1.5 (n ⫽ 5). All parents received an explanation of the study and gave informed consent. In all cases, a 5F end-hole multipurpose catheter (Cordis, Miami, Fla) was advanced from the femoral vein to reach the descending aorta through the ductus arteriosus. A straight-tip 0.035-in guidewire (Terumo, Tokyo, Japan) was also used when it was difficult to cross the ductus with the catheter alone. In 4 patients whose minimum
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ductal diameter was ⬎2.5 mm, two catheters were simultaneously introduced through the left and right femoral veins. Detachable wire coils of 0.038-in wire diameter were used in this study. The herical diameter of the coils was 5 or 8 mm and at least 2 or 3 times greater than the minimum diameter of the ductus, as determined by angiography. Doppler color flow mapping showed complete closure in 7 of 9 (78%) patients immediately after the procedure. In 2 of 9 patients, a trivial shunt was observed after the procedure. During the coil closure of PDA, blood pressures in the ascending aorta were monitored. Echocardiography Two-dimensional echocardiography and M-mode recordings of the LV minor axis were obtained with a device (SSD ProSound 5500, Aloka Inc, Tokyo, Japan) with a 5.0or 7.5-MHz transducer before and immediately after PDA coil closure. The M-mode measurements were performed according to the recommendations of American Society of Echocardiography.13 LV mass was calculated according to the formula of Devereux et al14: LV mass ⫽ 1.04 ⫻ ([LVDd ⫹ VSd ⫹ PWd]3 ⫺ LVDd3) ⫻ 0.8 ⫹ 0.6, where LVDd is LV internal dimension, VSd is ventricular septal thickness, and PWd is posterior wall thickness (all these dimensions were measured at end-diastole). The studies were recorded on videotapes for later playback and analysis. To record LAD flow, 2D, color, and Doppler TTE were performed. The bifurcation of the left main coronary artery into the LAD and left circumflex coronary artery was imaged from the standard short-axis view of the great vessels. The LAD size was measured in a diastolic frame by zooming in as close as possible and then indexed for body surface area. The velocity scale was decreased to the minimum range (8 cm/s) and then gradually increased until color signals were optimized within the vessel lumen. The color gain was also adjusted to minimize color flow scatter, and the Doppler filter was set at 400 Hz. After demonstration of coronary color flow signals, the pulsed Doppler sample volume was placed within the LAD just distal to the bifurcation of the left main coronary artery, and the sample volume decreased from 0.5 to 1.0 mm. The spectral velocity scale was also reduced to include the upper range of diastolic velocity. Measurements of maximum peak flow velocity (MPV) and flow velocity time integral (FVI) were performed automatically using the internal analysis package of the ultrasound unit. Values were calculated considering the angle between the Doppler beam and coronary flow direction as determined by a 2D echocardiography. LAD flow volume (FV)/cardiac cycle was calculated as follows: LAD cross-sectional area ⫻ FVI. Coronary FV/min was calculated as the product of this equation multiplied by heart rate. Figure 1 shows an example of the change in LAD flow velocity patterns before and after PDA coil closure. All 2D and Doppler measurements of LAD flow were determined by one examiner (K. H.) and were averaged over 5 to 7 cardiac cycles.
Figure 1 Examples of left anterior descending coronary artery flow velocity recordings before (left) and after (right) patent ductus arteriosus coil closure obtained from transthoracic Doppler echocardiography. Statistics Data are expressed as the mean ⫾ SD. Group means of echocardiographic data were compared by unpaired Student t test. A paired 2-tailed t test was performed to compare the data before and after PDA coil closure. The relationships between LAD flow and other hemodynamic parameters were assessed by linear regression analysis. To evaluate the effects of observational variability on the measurement of LAD flow velocity and flow velocity integral, two independent observers (interobserver variability) analyzed 12 randomly selected Doppler velocity recordings. Intraobserver variability was assessed in 12 children who underwent flow measurements by Doppler echocardiography twice, 10 minutes apart. Analysis of the difference in the measurements was performed according to the technique of Bland and Altman.15
RESULTS Figure 1 shows examples of LAD flow velocity recordings before and after PDA coil closure obtained from Doppler TTE. Table shows the hemodynamic and echocardiographic data in control subjects, the patients with Qp/Qs ⬍ 1.5 (n ⫽ 4), and the patients with Qp/Qs ⬎ 1.5 (n ⫽ 5). The systolic and diastolic blood pressures, LV end-diastolic diameter, LV mass, and LAD MPV, LAD FVI, LAD flow, and LAD flow/LV mass did not differ between control subjects and the patients with Qp/Qs ⬍ 1.5. These parameters did not change after the PDA coil closure. In the patients with Qp/Qs ⬎ 1.5, LV end-diastolic diameter, LV mass, LAD MPV, LAD FVI, and LAD flow were significantly greater compared with those in control subjects (3.6 ⫾ 0.7 vs 2.8 ⫾ 0.2 cm, 57 ⫾ 14 vs 28 ⫾ 6 g, 47 ⫾ 6 vs 31 ⫾ 8 cm/s, 9.1 ⫾ 2.0 vs 6.4 ⫾ 1.6 cm, and 27 ⫾ 5 vs 19 ⫾ 8 mL, respectively;
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Table Echocardiographic data in control subjects and patients PDA with Qp/Qs < 1.5
Age (y) Heart rate (bpm) Qp/Qs Systolic blood pressure (mm Hg) Diastolic blood pressure (mm Hg) LV end-diastolic diameter (cm) LV mass (g) LAD diameter (cm) LAD MPV (cm/s) LAD FVI (cm) LAD flow (mL/min) LV flow/LV mass (mL/100 g)
Normal (n ⴝ 8)
Before PDA coil closure (n ⴝ 4)
1.8 ⫾ 0.9 103 ⫾ 12 1 87 ⫾ 9 51 ⫾ 7 2.8 ⫾ 0.2 28 ⫾ 6 0.19 ⫾ 0.03 31 ⫾ 8 6.4 ⫾ 1.6 19 ⫾ 8 66 ⫾ 15
1.3 ⫾ 0.5 113 ⫾ 9 1.20 ⫾ 0.06 78 ⫾ 12 49 ⫾ 13 2.6 ⫾ 0.5 27 ⫾ 3 0.18 ⫾ 0.03 34 ⫾ 5 6.4 ⫾ 2.5 23 ⫾ 3 72 ⫾ 12
After PDA coil closure (n ⴝ 4)
110 ⫾ 8 1 83 ⫾ 15 50 ⫾ 16 2.5 ⫾ 0.5 27 ⫾ 3 35 ⫾ 7 6.8 ⫾ 2.9 23 ⫾ 4 75 ⫾ 13
PDA with Qp/Qs > 1.5 Before PDA coil closure (n ⴝ 5)
1.8 ⫾ 1.3 110 ⫾ 14 1.80 ⫾ 0.29 88 ⫾ 11 47 ⫾ 8 3.6 ⫾ 0.7* 57 ⫾ 14* 0.20 ⫾ 0.03 47 ⫾ 6* 9.1 ⫾ 2.0* 27 ⫾ 5* 48 ⫾ 10*
After PDA coil closure (n ⴝ 5)
108 ⫾ 14 1 98 ⫾ 12† 59 ⫾ 7† 3.4 ⫾ 0.7† 57 ⫾ 14* 62 ⫾ 16*† 12.5 ⫾ 3.0*† 36 ⫾ 7*† 65 ⫾ 15†
FVI, Flow velocity time integral; LAD, left anterior descending coronary artery; LV, left ventricular; MPV, maximum peak flow velocity; PDA, patent ductus arteriosus; Qp/Qs, pulmonary to systemic flow ratio. *P ⬍ .05 vs normal; †P ⬍ .05 vs before PDA coil closure (Qp/Qs ⬎ 1.5).
Figure 2 Relationships between change in left anterior descending coronary artery (LAD) flow volume/ left ventricular (LV) mass and pulmonary to systemic flow ratio (Qp/Qs) and change in diastolic blood pressure (BP).
P ⬍ .05). However, LAD flow/LV mass was significantly lower in the patients with Qp/Qs ⬎ 1.5 than in control subjects (48 ⫾ 10 vs 66 ⫾ 15 mL/100 g; P ⬍ .05). After the PDA coil closure, systolic and diastolic blood pressures increased significantly (98 ⫾ 12 vs 88 ⫾ 11 mm Hg and 59 ⫾ 7 vs 47 ⫾ 8 mm Hg, respectively; P ⬍ .05). There was a significant decrease in LV end-diastolic diameter after the PDA coil closure (3.4 ⫾ 0.7 vs 3.6 ⫾ 0.7 cm; P ⬍ .05). Significant increases in the mean LAD MPV, LAD FVI, and LAD flow were observed after the PDA coil closure (62 ⫾ 16 vs 47 ⫾ 6 cm/s, 12.5 ⫾ 3.0 vs 9.1 ⫾ 2.0 cm, and 36 ⫾ 7 vs 27 ⫾ 5 mL, respectively; P ⬍ .05). LAD flow/LV mass increased to normal values after the PDA coil closure. As a whole, there were significant relationships between the change in LAD FV/LV mass and Qp/Qs (r ⫽ 0.91, P ⫽ .0002)
and the change in diastolic blood pressure (r ⫽ 0.72, P ⫽ .04), respectively, as shown in Figure 2. Interobserver Variability and Reproducibility There was a good agreement between the two independent observer measurements for LAD flow velocity, FVI, and the LAD diameter (r ⫽ 0.96, r ⫽ 0.92, and r ⫽ 0.95, respectively). The mean differences in the LAD flow velocity, FVI, and LAD diameter were 0.21 ⫾ 3.13 cm/s, ⫺0.45 ⫾ 0.87 cm, and 0.01 ⫾ 0.07 mm, respectively. Excellent correlation was also observed in the intraobserver measurements for LAD flow velocity, FVI, and LAD diameter (r ⫽ 0.96, r ⫽ 0.93, and r ⫽ 0.97, respectively). The mean differences in the LAD flow velocity, FVI, and LAD diameter were 0.09 ⫾ 3.55
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cm/s, 0.30 ⫾ 0.71 cm, and 0.01 ⫾ 0.06 mm, respectively.
DISCUSSION Previous Doppler TTE studies of the coronary arteries of children have mainly focused on flow velocity, FV, and flow velocity reserve. Doppler TTE can also provide information on the coronary flow changes during catheter intervention.16 This study demonstrated the application of Doppler TTE for the measurement of the coronary flow before and after PDA coil closure. In this study, the mean LAD FV and the ratio of LAD FV to LV mass ratio increased after the procedure in the patients with Qp/Qs ⬎ 1.5, suggesting the improvement of myocardial blood perfusion. Thus, this technique may provide additional information about coronary flow dynamics for patients with PDA. LAD Flow Changes Before and After the Procedure In this study, LAD flow and LAD flow/LV mass did not differ between control subjects and the patients with Qp/Qs ⬍ 1.5. However, LAD FV was significantly higher in the patients with Qp/Qs ⬎ 1.5 than in control subjects. An increased LV mass secondary to volume overload has been reported to increase resting LAD flow.1-4 An increased LAD FV is also observed for patients with ventricular septal defect who have an increased LV mass.10 Thus, it is likely that high resting coronary FV found in the patients with Qp/Qs ⬎ 1.5 reflects increased LV mass. Patients with increased LV mass usually have normal coronary blood flow per unit mass of LV at rest, and total flow may increase in proportion to the increase in LV mass.1,2 Augmented LAD FV in the patients with PDA may be a compensated mechanism for the increase in oxygen demand of hypertrophic myocardium of the LV. In the patients with PDA with a small left-toright shunt flow (Qp/Qs ⬍ 1.5), the mean LAD FV and LAD FV/LV mass ratio did not change after the PDA coil closure. However, in the patients with Qp/Qs ⬎ 1.5, the mean LAD FV increased dramatically after the procedure. In addition, LAD FV/LV mass ratio in these patients was significantly lower compared with control subjects, but they increased to normal values after coil closure of PDA. This suggests that the imbalance of the LAD flow supply/demand relation under increased LV mass improves after the procedure in these patients. PDA closure induces an increase in diastolic blood pressure and a reduction in Qp/Qs. In particular, in the patients with Qp/Qs ⬎ 1.5, PDA coil closure showed 26% increase in the diastolic blood pressure and 6% reduction in LV end-
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diastolic diameter without any changes in heart rate. Because coronary flow to the LV occurs mainly during diastole and depends on the systemic arterial-intramyocardial diastolic pressure differences, increases in diastolic pressure can increase coronary flow.17 In addition, the decrease in Qp/Qs after the PDA coil closure may cause LV end-diastolic pressure and may cause an increase in subendocardial intramyocardial pressure. In this study, there were significant relationships between the change in LAD FV/LV mass and Qp/Qs and the change in diastolic blood pressure. Thus, the combinations of the increase in diastolic blood pressure and the reduction in LV preload (decrease in Qp/Qs) appear to be major reason of increased LAD flow after the coil closure. Study Limitations In this study Doppler TTE was used to assess coronary flow. This method has been shown to reproducible and correlates well with intracoronary Doppler guidewire method. However, this study has important limitations. First, echocardiographic techniques are limited by spatial resolution. The diameter of the LAD in neonates is small, and accurate measurement of blood flow is particularly dependent on the accurate measurement of vessel diameter. The echocardiography unit used in this study is capable of measuring the LAD diameter to the nearest 0.1 mm. If this measurement was in error by 0.1 mm, the calculated FV of the LAD would differ by 21%. The availability of higher-frequency echocardiographic probes allowing better magnification would permit further improvements in accuracy by improving spatial resolution. Second, in this study, the ratio of the FV of the LAD to the LV mass was calculated as an index of LV myocardial blood supply. However, LV myocardium is also supplied by the FV of the left circumflex coronary artery. We were unable to assess the FV of the left main coronary artery. Our rate of detection of the left circumflex coronary artery flow velocity pattern was low.6 Third, the flow pattern of the coronary artery is basically a biphasic flow with a systolic and a diastolic components, of which the latter is predominant.18 However, the coronary flow could be detected only in the diastolic phase in our study. These seem to be limiting factors in the precise evaluation of the coronary blood flow dynamics. Finally, this study consisted of a small number of patients with PDA. In future studies, larger numbers of patients with PDA should be examined by this method. Conclusions Our study demonstrated the changes in LAD flow during the PDA coil closure in the patients with PDA
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using Doppler TTE. These findings provide new insights into the relationship between cardiac function and coronary circulation in pediatric patients with heart diseases associated with PDA.
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9.
10.
REFERENCES 1. Pichard AD, Smith H, Holt J, Meller J, Gorlin R. Coronary vascular reserve in left ventricular hypertrophy secondary to chronic aortic regurgitation. Am J Cardiol 1983;51:315-20. 2. Nitenberg A, Foult J, Antony I, Blanchet F, Rahali M. Coronary flow and resistance reserve in patients with chronic regurgitation, angina pectoris and normal coronary arteries. J Am Coll Cardiol 1988;11:478-86. 3. McGinn AL, White CW, Wilson RF. Interstudy variability of coronary flow reserve: influence of heart rate, arterial pressure, and ventricular preload. Circulation 1990;81:1319-30. 4. Akasaka T, Yoshida K, Hozumi T, Takagi T, Kaji S, Kawamoto T, et al. Restricted coronary flow reserve in patients with mitral regurgitation improves after mitral reconstructive surgery. J Am Coll Cardiol 1998;32:1923-30. 5. Noto N, Karasawa K, Ayusawa M, Misawa M, Sumitomo N, Okada T, et al. Measurement of coronary flow reserve in children by transthoracic Doppler echocardiography. Am J Cardiol 1997;80:1638-9. 6. Harada K, Orino T, Hironaka C, Takahashi Y, Takada G. Coronary blood flow velocity in normal infants and young adults assessed by transthoracic echocardiography. Am J Cardiol 1999;83:1583-5. 7. Jureidini SB, Marino CJ, Waterman B, Syamasunder Rao P, Balfour IC, Chen SC, et al. Transthoracic Doppler echocardiography of normally originating coronary arteries in children. J Am Soc Echocardiogr 1998;11:409-20. 8. Jureidini SB, Marino CJ, Singh GK, Fiore A, Balfour IC. Main coronary artery and coronary ostial stenosis in children: detec-
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tion by transthoracic color flow and pulsed Doppler echocardiography. J Am Soc Echocardiogr 2000;13:255-63. Jureidini SB, Singh GK, Marino CJ, Fiore AC. Aberrant origin of the left coronary artery from the right aortic sinus: surgical intervention based on echocardiographic diagnosis. J Am Soc Echocardiogr 2000;13:1117-20. Harada K, Tamura M, Takahashi Y, Takada G. Coronary blood flow assessed by transthoracic echocardiography. Pediatr Cardiol 2001;22:189-93. Yasuoka K, Harada K, Tamura M, Toyono M. Left anterior descending coronary artery flow and its relation to age in children. J Am Soc Echocardiogr 2002;15:69-75. Harada K, Yasuoka K, Tamura M, Toyono M. Coronary flow reserve assessment by Doppler echocardiography in children with and without congenital heart disease: comparison with invasive technique. J Am Soc Echocardiogr 2002;15:1121-6. American Society of Echocardiography Committee of Standards. Recommendation for quantification of the left ventricle by two-dimensional echocardiography. J Am Soc Echocardiogr 1989;2:358-67. Devereux RB, Alonso DR, Lutas EM, Gottlieb GJ, Campo E, Sachs I, et al. Echocardiographic determination of left ventricular hypertrophy: comparison to necropsy findings. Am J Cardiol 1986;57:450-8. Bland JM, Altman DG. Statistical methods for assessing agreement between two methods of clinical measurements. Lancet 1986;1:307-10. Harada K, Toyono M, Tamura M. Effects of balloon valvuloplasty on left anterior descending coronary artery blood flow in a neonate with critical aortic stenosis with transthoracic Doppler echocardiography. J Am Soc Echocardiogr 2003;16: 88-90. Hoffman JIE, Buckberg GD. Regional myocardial ischemia: cause, prediction, and prevention. Vasc Surg 1974;8:115-31. Benchimol A, Stegall HF, Gartlan JL. New method to measure phasic coronary blood flow velocity in man. Am Heart J 1971;81:93-101.
Transthoracic Doppler echocardiography provides noninvasive measurements of coronary blood flow in the left anterior descending coronary artery (LAD). This method has the potential to show the effects of acute changes in loading conditions on blood flow. Coil closure of patent ductus arteriosus (PDA) is a model of acute changes in blood pressure and left ventricular (LV) preload that influences coronary blood flow. We applied this technique to assess the coronary blood flow changes for patients with PDA before and immediately after PDA coil closure. We examined 9 patients (1.8 ⴞ 1.1 years) with simple PDA and 8 age-matched healthy children. LV dimensions and LV mass were measured. Maximum peak flow velocity and flow volume in the LAD were measured. Pulmonary to systemic flow ratios (Qp/Qs) were obtained by cardiac catheterization. After PDA coil closure, LV end-diastolic dimen-
Coronary flow velocity is known to increase for
patients with left ventricular (LV) hypertrophy secondary to volume overload.1-4 However, little information exists about the effects of acute change in preload on coronary flow. Coil closure of patent ductus arteriosus (PDA) is a model of acute changes in blood pressure and LV preload that influences coronary blood flow. Recently, several studies have reported that the flow velocity in the left anterior descending coronary artery (LAD) can be measured using 2-dimensional (2D) transthoracic echocardiography (TTE) and Doppler echocardiography in children.5-11 In addition, we have shown that noninvaive measurement of LAD coronary flow velocity with Doppler TTE accurately reflects invasive measurement of LAD flow velocity with Doppler guidewire method in pediatric patients with various heart diseases.12 Therefore, we applied this technique to From the Department of Pediatrics, Akita University School of Medicine. Reprint requests: Kenji Harada, MD, Department of Pediatrics, Akita University School of Medicine, Akita, Japan. (E-mail: [email protected]). 0894-7317/$30.00 Copyright 2004 by the American Society of Echocardiography. doi:10.1016/j.echo.2004.02.018
sion decreased, and systolic and diastolic blood pressures increased significantly. The maximum peak flow velocity, LAD flow volume, and the ratio of LAD flow volume to LV mass increased significantly. The changes in maximum peak flow velocity and the ratio of LAD flow volume to LV mass (F/M) correlated positively with the changes in diastolic pressure and Qp/Qs. In 5 patients who had Qp/Qs > 1.5, the mean F/M was significantly lower compared with control subjects, but they increased to normal values after coil closure of PDA. PDA coil closure increases diastolic pressure and decreases Qp/Qs, resulting in improvement of myocardial perfusion. These findings provide new insights into the relationship between cardiac function and coronary circulation in pediatric patients with heart diseases associated with PDA. (J Am Soc Echocardiogr 2004;17: 659-63.)
assess the coronary blood flow changes in patients with PDA before and immediately after PDA coil closure.
METHODS Study Subjects Between October 2000 and June 2002, 9 patients (1.8 ⫾ 1.1 years) with isolated PDA who underwent percutaneous coil closure of the PDA and 8 age-matched healthy children were prospectively enrolled in the study. Before the PDA coil closure, conventional right and left heart catheterizations were performed to determine pressures and oxygen saturation levels. Pulmonary to systemic flow ratio (Qp/Qs) by Fick’s method was 1.5 ⫾ 0.4 (range: 1.1-2.2). The patients with PDA were divided into 2 groups: Qp/Qs ⬍ 1.5 (n ⫽ 4); and Qp/Qs ⬎ 1.5 (n ⫽ 5). All parents received an explanation of the study and gave informed consent. In all cases, a 5F end-hole multipurpose catheter (Cordis, Miami, Fla) was advanced from the femoral vein to reach the descending aorta through the ductus arteriosus. A straight-tip 0.035-in guidewire (Terumo, Tokyo, Japan) was also used when it was difficult to cross the ductus with the catheter alone. In 4 patients whose minimum
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ductal diameter was ⬎2.5 mm, two catheters were simultaneously introduced through the left and right femoral veins. Detachable wire coils of 0.038-in wire diameter were used in this study. The herical diameter of the coils was 5 or 8 mm and at least 2 or 3 times greater than the minimum diameter of the ductus, as determined by angiography. Doppler color flow mapping showed complete closure in 7 of 9 (78%) patients immediately after the procedure. In 2 of 9 patients, a trivial shunt was observed after the procedure. During the coil closure of PDA, blood pressures in the ascending aorta were monitored. Echocardiography Two-dimensional echocardiography and M-mode recordings of the LV minor axis were obtained with a device (SSD ProSound 5500, Aloka Inc, Tokyo, Japan) with a 5.0or 7.5-MHz transducer before and immediately after PDA coil closure. The M-mode measurements were performed according to the recommendations of American Society of Echocardiography.13 LV mass was calculated according to the formula of Devereux et al14: LV mass ⫽ 1.04 ⫻ ([LVDd ⫹ VSd ⫹ PWd]3 ⫺ LVDd3) ⫻ 0.8 ⫹ 0.6, where LVDd is LV internal dimension, VSd is ventricular septal thickness, and PWd is posterior wall thickness (all these dimensions were measured at end-diastole). The studies were recorded on videotapes for later playback and analysis. To record LAD flow, 2D, color, and Doppler TTE were performed. The bifurcation of the left main coronary artery into the LAD and left circumflex coronary artery was imaged from the standard short-axis view of the great vessels. The LAD size was measured in a diastolic frame by zooming in as close as possible and then indexed for body surface area. The velocity scale was decreased to the minimum range (8 cm/s) and then gradually increased until color signals were optimized within the vessel lumen. The color gain was also adjusted to minimize color flow scatter, and the Doppler filter was set at 400 Hz. After demonstration of coronary color flow signals, the pulsed Doppler sample volume was placed within the LAD just distal to the bifurcation of the left main coronary artery, and the sample volume decreased from 0.5 to 1.0 mm. The spectral velocity scale was also reduced to include the upper range of diastolic velocity. Measurements of maximum peak flow velocity (MPV) and flow velocity time integral (FVI) were performed automatically using the internal analysis package of the ultrasound unit. Values were calculated considering the angle between the Doppler beam and coronary flow direction as determined by a 2D echocardiography. LAD flow volume (FV)/cardiac cycle was calculated as follows: LAD cross-sectional area ⫻ FVI. Coronary FV/min was calculated as the product of this equation multiplied by heart rate. Figure 1 shows an example of the change in LAD flow velocity patterns before and after PDA coil closure. All 2D and Doppler measurements of LAD flow were determined by one examiner (K. H.) and were averaged over 5 to 7 cardiac cycles.
Figure 1 Examples of left anterior descending coronary artery flow velocity recordings before (left) and after (right) patent ductus arteriosus coil closure obtained from transthoracic Doppler echocardiography. Statistics Data are expressed as the mean ⫾ SD. Group means of echocardiographic data were compared by unpaired Student t test. A paired 2-tailed t test was performed to compare the data before and after PDA coil closure. The relationships between LAD flow and other hemodynamic parameters were assessed by linear regression analysis. To evaluate the effects of observational variability on the measurement of LAD flow velocity and flow velocity integral, two independent observers (interobserver variability) analyzed 12 randomly selected Doppler velocity recordings. Intraobserver variability was assessed in 12 children who underwent flow measurements by Doppler echocardiography twice, 10 minutes apart. Analysis of the difference in the measurements was performed according to the technique of Bland and Altman.15
RESULTS Figure 1 shows examples of LAD flow velocity recordings before and after PDA coil closure obtained from Doppler TTE. Table shows the hemodynamic and echocardiographic data in control subjects, the patients with Qp/Qs ⬍ 1.5 (n ⫽ 4), and the patients with Qp/Qs ⬎ 1.5 (n ⫽ 5). The systolic and diastolic blood pressures, LV end-diastolic diameter, LV mass, and LAD MPV, LAD FVI, LAD flow, and LAD flow/LV mass did not differ between control subjects and the patients with Qp/Qs ⬍ 1.5. These parameters did not change after the PDA coil closure. In the patients with Qp/Qs ⬎ 1.5, LV end-diastolic diameter, LV mass, LAD MPV, LAD FVI, and LAD flow were significantly greater compared with those in control subjects (3.6 ⫾ 0.7 vs 2.8 ⫾ 0.2 cm, 57 ⫾ 14 vs 28 ⫾ 6 g, 47 ⫾ 6 vs 31 ⫾ 8 cm/s, 9.1 ⫾ 2.0 vs 6.4 ⫾ 1.6 cm, and 27 ⫾ 5 vs 19 ⫾ 8 mL, respectively;
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Table Echocardiographic data in control subjects and patients PDA with Qp/Qs < 1.5
Age (y) Heart rate (bpm) Qp/Qs Systolic blood pressure (mm Hg) Diastolic blood pressure (mm Hg) LV end-diastolic diameter (cm) LV mass (g) LAD diameter (cm) LAD MPV (cm/s) LAD FVI (cm) LAD flow (mL/min) LV flow/LV mass (mL/100 g)
Normal (n ⴝ 8)
Before PDA coil closure (n ⴝ 4)
1.8 ⫾ 0.9 103 ⫾ 12 1 87 ⫾ 9 51 ⫾ 7 2.8 ⫾ 0.2 28 ⫾ 6 0.19 ⫾ 0.03 31 ⫾ 8 6.4 ⫾ 1.6 19 ⫾ 8 66 ⫾ 15
1.3 ⫾ 0.5 113 ⫾ 9 1.20 ⫾ 0.06 78 ⫾ 12 49 ⫾ 13 2.6 ⫾ 0.5 27 ⫾ 3 0.18 ⫾ 0.03 34 ⫾ 5 6.4 ⫾ 2.5 23 ⫾ 3 72 ⫾ 12
After PDA coil closure (n ⴝ 4)
110 ⫾ 8 1 83 ⫾ 15 50 ⫾ 16 2.5 ⫾ 0.5 27 ⫾ 3 35 ⫾ 7 6.8 ⫾ 2.9 23 ⫾ 4 75 ⫾ 13
PDA with Qp/Qs > 1.5 Before PDA coil closure (n ⴝ 5)
1.8 ⫾ 1.3 110 ⫾ 14 1.80 ⫾ 0.29 88 ⫾ 11 47 ⫾ 8 3.6 ⫾ 0.7* 57 ⫾ 14* 0.20 ⫾ 0.03 47 ⫾ 6* 9.1 ⫾ 2.0* 27 ⫾ 5* 48 ⫾ 10*
After PDA coil closure (n ⴝ 5)
108 ⫾ 14 1 98 ⫾ 12† 59 ⫾ 7† 3.4 ⫾ 0.7† 57 ⫾ 14* 62 ⫾ 16*† 12.5 ⫾ 3.0*† 36 ⫾ 7*† 65 ⫾ 15†
FVI, Flow velocity time integral; LAD, left anterior descending coronary artery; LV, left ventricular; MPV, maximum peak flow velocity; PDA, patent ductus arteriosus; Qp/Qs, pulmonary to systemic flow ratio. *P ⬍ .05 vs normal; †P ⬍ .05 vs before PDA coil closure (Qp/Qs ⬎ 1.5).
Figure 2 Relationships between change in left anterior descending coronary artery (LAD) flow volume/ left ventricular (LV) mass and pulmonary to systemic flow ratio (Qp/Qs) and change in diastolic blood pressure (BP).
P ⬍ .05). However, LAD flow/LV mass was significantly lower in the patients with Qp/Qs ⬎ 1.5 than in control subjects (48 ⫾ 10 vs 66 ⫾ 15 mL/100 g; P ⬍ .05). After the PDA coil closure, systolic and diastolic blood pressures increased significantly (98 ⫾ 12 vs 88 ⫾ 11 mm Hg and 59 ⫾ 7 vs 47 ⫾ 8 mm Hg, respectively; P ⬍ .05). There was a significant decrease in LV end-diastolic diameter after the PDA coil closure (3.4 ⫾ 0.7 vs 3.6 ⫾ 0.7 cm; P ⬍ .05). Significant increases in the mean LAD MPV, LAD FVI, and LAD flow were observed after the PDA coil closure (62 ⫾ 16 vs 47 ⫾ 6 cm/s, 12.5 ⫾ 3.0 vs 9.1 ⫾ 2.0 cm, and 36 ⫾ 7 vs 27 ⫾ 5 mL, respectively; P ⬍ .05). LAD flow/LV mass increased to normal values after the PDA coil closure. As a whole, there were significant relationships between the change in LAD FV/LV mass and Qp/Qs (r ⫽ 0.91, P ⫽ .0002)
and the change in diastolic blood pressure (r ⫽ 0.72, P ⫽ .04), respectively, as shown in Figure 2. Interobserver Variability and Reproducibility There was a good agreement between the two independent observer measurements for LAD flow velocity, FVI, and the LAD diameter (r ⫽ 0.96, r ⫽ 0.92, and r ⫽ 0.95, respectively). The mean differences in the LAD flow velocity, FVI, and LAD diameter were 0.21 ⫾ 3.13 cm/s, ⫺0.45 ⫾ 0.87 cm, and 0.01 ⫾ 0.07 mm, respectively. Excellent correlation was also observed in the intraobserver measurements for LAD flow velocity, FVI, and LAD diameter (r ⫽ 0.96, r ⫽ 0.93, and r ⫽ 0.97, respectively). The mean differences in the LAD flow velocity, FVI, and LAD diameter were 0.09 ⫾ 3.55
662 Harada, Toyono, Tamura
cm/s, 0.30 ⫾ 0.71 cm, and 0.01 ⫾ 0.06 mm, respectively.
DISCUSSION Previous Doppler TTE studies of the coronary arteries of children have mainly focused on flow velocity, FV, and flow velocity reserve. Doppler TTE can also provide information on the coronary flow changes during catheter intervention.16 This study demonstrated the application of Doppler TTE for the measurement of the coronary flow before and after PDA coil closure. In this study, the mean LAD FV and the ratio of LAD FV to LV mass ratio increased after the procedure in the patients with Qp/Qs ⬎ 1.5, suggesting the improvement of myocardial blood perfusion. Thus, this technique may provide additional information about coronary flow dynamics for patients with PDA. LAD Flow Changes Before and After the Procedure In this study, LAD flow and LAD flow/LV mass did not differ between control subjects and the patients with Qp/Qs ⬍ 1.5. However, LAD FV was significantly higher in the patients with Qp/Qs ⬎ 1.5 than in control subjects. An increased LV mass secondary to volume overload has been reported to increase resting LAD flow.1-4 An increased LAD FV is also observed for patients with ventricular septal defect who have an increased LV mass.10 Thus, it is likely that high resting coronary FV found in the patients with Qp/Qs ⬎ 1.5 reflects increased LV mass. Patients with increased LV mass usually have normal coronary blood flow per unit mass of LV at rest, and total flow may increase in proportion to the increase in LV mass.1,2 Augmented LAD FV in the patients with PDA may be a compensated mechanism for the increase in oxygen demand of hypertrophic myocardium of the LV. In the patients with PDA with a small left-toright shunt flow (Qp/Qs ⬍ 1.5), the mean LAD FV and LAD FV/LV mass ratio did not change after the PDA coil closure. However, in the patients with Qp/Qs ⬎ 1.5, the mean LAD FV increased dramatically after the procedure. In addition, LAD FV/LV mass ratio in these patients was significantly lower compared with control subjects, but they increased to normal values after coil closure of PDA. This suggests that the imbalance of the LAD flow supply/demand relation under increased LV mass improves after the procedure in these patients. PDA closure induces an increase in diastolic blood pressure and a reduction in Qp/Qs. In particular, in the patients with Qp/Qs ⬎ 1.5, PDA coil closure showed 26% increase in the diastolic blood pressure and 6% reduction in LV end-
Journal of the American Society of Echocardiography June 2004
diastolic diameter without any changes in heart rate. Because coronary flow to the LV occurs mainly during diastole and depends on the systemic arterial-intramyocardial diastolic pressure differences, increases in diastolic pressure can increase coronary flow.17 In addition, the decrease in Qp/Qs after the PDA coil closure may cause LV end-diastolic pressure and may cause an increase in subendocardial intramyocardial pressure. In this study, there were significant relationships between the change in LAD FV/LV mass and Qp/Qs and the change in diastolic blood pressure. Thus, the combinations of the increase in diastolic blood pressure and the reduction in LV preload (decrease in Qp/Qs) appear to be major reason of increased LAD flow after the coil closure. Study Limitations In this study Doppler TTE was used to assess coronary flow. This method has been shown to reproducible and correlates well with intracoronary Doppler guidewire method. However, this study has important limitations. First, echocardiographic techniques are limited by spatial resolution. The diameter of the LAD in neonates is small, and accurate measurement of blood flow is particularly dependent on the accurate measurement of vessel diameter. The echocardiography unit used in this study is capable of measuring the LAD diameter to the nearest 0.1 mm. If this measurement was in error by 0.1 mm, the calculated FV of the LAD would differ by 21%. The availability of higher-frequency echocardiographic probes allowing better magnification would permit further improvements in accuracy by improving spatial resolution. Second, in this study, the ratio of the FV of the LAD to the LV mass was calculated as an index of LV myocardial blood supply. However, LV myocardium is also supplied by the FV of the left circumflex coronary artery. We were unable to assess the FV of the left main coronary artery. Our rate of detection of the left circumflex coronary artery flow velocity pattern was low.6 Third, the flow pattern of the coronary artery is basically a biphasic flow with a systolic and a diastolic components, of which the latter is predominant.18 However, the coronary flow could be detected only in the diastolic phase in our study. These seem to be limiting factors in the precise evaluation of the coronary blood flow dynamics. Finally, this study consisted of a small number of patients with PDA. In future studies, larger numbers of patients with PDA should be examined by this method. Conclusions Our study demonstrated the changes in LAD flow during the PDA coil closure in the patients with PDA
Journal of the American Society of Echocardiography Volume 17 Number 6
using Doppler TTE. These findings provide new insights into the relationship between cardiac function and coronary circulation in pediatric patients with heart diseases associated with PDA.
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