Department of Pediatrics and Child Health, Kurume University School of Medicine, Kurume, 830 Japan. Received for publication October 26, 1992
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1 THE KURUME MEDICAL JOURNAL Vol.39, p , 1992 Jon-Invasive Evaluation of Pulmonary Arterial and Right Ventricular Pressures with Contrast Enhanced Doppler Signals of Tricuspid Regurgitation Flow Using Sonicated Albumin Solution MASAHIRO Department of Pediatrics and Child Health, Kurume University School of Medicine, Kurume, 830 Japan ISHII Received for publication October 26, 1992 Summary: To determine the feasibility of the non-invasive determination of systolic pressure of the pulmonary artery and the right ventricle in pediatric patients, the velocity of tricuspid regurgitation was measured in 30 patients using a contrast enhanced Doppler echocardiography. After sonicated albumin injection, trivial tricuspid regurgitation signals were enhanced in 27 patients (90%). Peak systolic velocity was not altered by before and after sonicated albumin injection in 2 patients. Right ventricular (RV) systolic pressure obtained by continuous wave Doppler during sonicated albumin enhancement corresponded very closely to that measured by catheter in 27 patients (r=0.96). In 27 patients, difference of estimation of RV systolic pressure by non-enhanced Doppler and enhanced Doppler with sonicated albumin was statistically significant (32.3 }27.6mmHg versus 2.9 }7.7mmHg p< 0.001). Systolic pressure of pulmonary artery was estimated by RV systolic pressure measurement (by enhanced Doppler method) minus peak pressure gradient across the pulmonary valve (non-enhanced Doppler method). Pulmonary arterial systolic pressure measured by enhanced Doppler method and that by catheter method were highly significant (sonicated albumin method, r=0.95). This technique may be a valuable non-invasive method for determining an accurate right ventricular and pulmonary arterial systolic pressures in this setting. Key words : pulmonary artery pressure \right ventricle pressure \contrast Doppler echocardiography albumin \tricuspid regurgitation Introduction Evaluation of pulmonary hypertension is essential for the diagnosis and management of congenital heart disease. However, cardiac catheterization is required for an accurate measurement of it. The pressure gradient across a tricuspid valve, the right ventricular (RV) systolic pressure minus right atrial pressure, can be calculated from the peak velocity of the tricuspid regurgitation by the modified Bernoulli equation (Hatle et al. 1981; Lima et al. 1983; Yock and Popp, 1984). However, in patients with trivial regurgitation, these regurgitation were made- This study in part was presented at the 65 th American Heart Association, New Orleans,
2 292 ISHII quate for estimation of peak pressure gradient (Tei et al. 1987). Although handagitated saline contrast techniques can enhance Doppler signals in such cases, those envelops easily contain a mechanical noise (Beard and Byrd, 1988; Himelman et al. 1988). Recently, sonicated albumin is reported as a useful echo-contrast, because its microbubbles are the smallest among the various agents (Beppu et al. 1991). The purpose of this study was to evaluate the possibility of the accurate measurements of systolic pressures of right ventricle and pulmonary artery using this contrast media in pediatric patients. Methods Patients Thirty patients with congenital heart disease which encluded 14 patients after surgery. There were 16 girls and 14 boys ranging from 2 months to 21 years (mean 7.9 years). Mean body weight was 27.3 kg ranged from 3.3 to 106 kg and on all were performed cardiac catheterization within 2 days from this study. Cardiac pressure was measured by 6F balloon catheter (ARROW INC.) and recorded instantaneously for measurement of systolic and diastolic pressure and maximally damped electrically for measurement of mean pressure. RV systolic pressure ranged from 24 to 130 mmhg (mean 58.0 mmhg). Table 1 indicates of patients profile and catheterization data. The written informed consent was obtained from the parents. Echocardiography Using a Aloka SSD-870, tricuspid regurgitant flow was analyzed by left parasternal or apical 4 chamber view. Continuous-wave Doppler signals (2.5 MHz) were recorded with assistance of the color flow mapping. The pressure gradient was estimated by modification of the Bernoulli formula. Systolic pressure of RV was computed as the sum of the transtricuspid gradient and 10 mmhg as a constant right atrial pressure (Currie et al. 1985). The flow velocity across the pulmonary valve was recorded in the parasternal short axis view, and pulmonary arterial systolic pressure was estimated as: (RV systolic pressure-peak pressure gradient across the pulmonary valve). Contrast Media Sonicated 5% human albumin was used as a contrast media. Sonication was performed at a 20 khz, 20 W for 30s (Beppu et al. 1991) (Heat Systems-Ultrasonics, INC. Model W-220 F). This solution was injected from a peripheral vein (0.1 ml/ kg) on dosal aspect of the hand via a 22 gauge needle. During this study there was no complication associated with this contrast media. Statistical Analysis The correlation between estimated RV and pulmonary arterial pressures by echo and catheter was evaluated by simple linear regression analysis. The difference of estimation by the non-enhanced Doppler and by sonicated albumin was compared by Student's paired t test. Statistical significance for p was Results considered<0.01. In 28 patients (93%), only trivial tricuspid regurgitation was recorded by the routine continuous Doppler method (Fig. 1). Contrary, these tricuspid regurgitation signals were clearly enhanced enough to estimate the peak systolic pressure gradient (Fig. 1) in 25 of 28 patients (89 %) Two patients had an adequate Doppler signal for estimating pressure gradient
3 TABLE 1. Diagnosis right ventricular and pulmonary artery systolic pressure RVSP : right ventricular systolic pressure; PASP : pulmonary artery systolic pressure VSD : ventricular septal defect; CoA : coarctation of the aorta; MR : mitral regurgitation; ASD : atrial septal defect; PDA : patent ductus arteriosus; AVR : aortic valve replacement; TAPVR : total anomalous pulmonary venous return; AS : aortic stenosis; PS : pulmonary stenosis; BVP : balloon valvulop1asty; PPH: primary pulmonary hypertention; TGA : transposition great arteries; MVP : mitral valve prolapse
4 ISHII 294 Fig. 1. An adequate tricuspid regurgitant jet could not be obtained by routine Doppler evaluation (left). After injection of sonicated albumin, enhanced signals were fine and smooth (right). without contrast medium injection. Signals were considered adequate when well demarcated smooth outlines of tricuspid regurgitation signals could be seen at the peak systole. Peak velocity was not altered by sonicated albumin injection in these patients. In 3 patients with large atrial septal defect, although weak tricuspid regurgitation signals were observed before enhancement, these signals could not be distinguished from noise on L-R shunt after injection of sonicated albumin. Correlation of noninvasive and invasive data RV systolic pressure measured without sonicated albumin solution was underestimated compared to catheterization data after injecting sonicated albumin (Fig. 2) despite of a weak correlation. In 6 patients, pulmonary arterial systolic pressure became<0mmhg. All of these pa- Fig. ventricular 2. Comparison systolic of calculated pressure by right Doppler method before and after contrast enhancement by sonicated albumin. Square indicates control value before enhancement; triangles, value after sonicated albumin; the value very near that measured catheter especially right ventricular tension group. by the hyper-
5 CONTRAST ENHANCED DOPPLER STUDY 295 Fig. 3. Plots of pulmonary arterial systolic pressure measured by catheter and that measured by sonicated albumin contrast enhanced Doppler in 27 patients. tients were associated with pulmonary stenosis. RV pressure estimated with sonicated albumin solution had very good correlation with catheterization data (Fig. 2). Similarly, pulmonary arterial systolic pressure measured by sonicated albumin injection and catheter measurement correlated very well (Fig. 3). The difference of estimation of RV systolic pressure by non-enhanced Doppler and enhanced Doppler with sonicated albumin was statistically significant (32.3 } 27.6 mmhg versus 2.9 }7.7 mmhg, p< 0.001). Discussion There are numerous reports about the usefulness of contrast echocardiography for detecting valve regurgitation, shunt and intracardiac flow dynamics (Hatle et al. 1981; Valdes-Cruz and Sahn, 1984). Previous reports suggested combined Doppler and contrast echocardiography to change the sensitivity of Doppler echocardiography for detecting trivial regurgitation (Hagler et al. 1987; Waggoner et al. 1990). In this study, RV systolic pressure estimated with sonicated albumin showed close correlation with RV systolic pressure determined with catheter, because the sonicated albumin provides a clear envelope of the Doppler signals of tricuspid regurgitation. The contrast medium had significantly smaller mean bubble size and standard deviation when sonicated than other method by Keller et al. (1988). In addition, sonicated albumin has already been used safely in myocardial contrast echocardiography (Kelley et al. 1988; Hirata, 1990; Matuda et al. 1992). Pulmonary arterial systolic pressure measured by the non-enhanced Doppler method was below 0 mmllg in 6 patients (pulmonary valve stenosis). Our data show the reason that right ventricular systolic pressure by non-enhanced Doppler was greatly under estimation and peak pressure gradient across the pulmonary valve was accurate in them. We did not visualize tricuspid regurgitation signals by the enhanced and nonenhanced Doppler methods in 3 patients, all of whom had large left to right atrial shunts. It was considered that contrast medium would fill the right atrium. However, noncontrasted, nonopacified left atrial blood passing through the defect may sometimes be visualized because it superimposed a negative or contrastfree area that outline the septal defect (Valdes-Cruz and Sahn, 1984; Morimoto et al. 1990). In conclusion, contrast enhanced Doppler evaluation of tricuspid regurgitation appears a very useful non-invasive method for determining pulmonary artery and right ventricular systolic pressure in infants, children and adolescents with heart disease. It is applicable to patient's care and making decision for heart surgery without cardiac catheterization.
6 296 ISHII Acknowledgments : The author wishes to thank Prof. H. Kato, Chairman of Pediatrics for his helpful comments and advice, and also thank Drs. O. Inoue, J. Takag i, T. Akagi, T. Miyake, Y. Maeno, T. Fukuda, Department of Pediatrics for their assistance on this study. References BEARD, J.T. and BYRD, B. F. (1988). Saline contrast enhancement of trivial Doppler tricuspid regurgitation signals for estimating pulmonary artery pressure. Am. J. Cardiol. 62, BEPPU, S., TANABE, K., SHIMIZU, T., ISHIKURA, F., NAKATANI, S. et al. (1991). Contrast enhancement of Doppler signals by sonicated albumin for estimating right ventricular systolic pressure. Am. J. Cardiol. 67, CURRIE, P. J., SEWARD, J. B., CHAN, K. L., FYFE, D. A., HAGLER, D. J. et al. (1985). Continuous wave Doppler determination of right ventricular pressure: A simultaneous Doppler-catheterization study in 127 patients. J. Am. Coil. Cardiol. 6, FEISTEN, S. B., LATE, F.J.T., ZWEHL, W., ONG, K., MAURER, G. et al. (1984). Two-dimensional contrast echocardiography. In vitro development and quantitative analysis of echo contrast agent. J. Am. Coll. Cardiol. 3, GOLDBERG, S. J., VALDES-CRUZ, L. M., FELDMAN, L., SAHN, D.J., ALLEN, H. et al. (1981). Range gated Doppler ultrasound detection contrast echographic microbubbles for cardiac and great vessel blood flow pattern. Am. J. Cardiol. 101, HAGLER, D. J., CURRIE, P. J., SEWARD, J. B., TAJIK, A. J., MAIR, D. D. et al. (1987). Echocardiographic contrast enhancement of poor or weak continuous-wave Doppler signals. Echocardiography 4, HATLE, L., ANGELSEN, B. A. J. and TROMSDAL, A. (1981). Non-invasive estimation of pulmonary artery systolic pressure with Doppler ultrasound. Br. Heart J. 45, HIMELMAN, R. B., STULBARG, M., KIRCHER, B., LEE, E., KEE, L. et al. (1988). Non-invasive evaluation of pulmonary artery pressure during exercise by saline-enhanced Doppler echocardiography in chronic pulmonary disease. Circulation 79, HIRATA, T. (1990). Intraoperative assessment of regional myocardial perfusion after myocardial revascularization using myocardial contrast echocardiography. Medical Journal of Osaka University 42, (in Japanese) KELLER, M.W., GLASHEEN, W., TEJA, K., GEAR, A. and KAUL, S. (1988). Myocardial contrast echocardiography without significant hemodynamic effects or reactive hyperemia ; A major advantage in the imaging of regional myocardial perfusion. J. Am. Coll. Cardiol. 12, LIMA, C.O., SAHN, D.J., VALDES-CRUZ, L.M., GOLDBERG, S.J., BARRON, J.V. et al. (1983). Non-invasive prediction of transvalvular pressure gradient in patient with pulmonary stenosis by quantitative two-dimensional echocardiographic Doppler studies. Circulation 67,
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