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RVOT VTI ratio in pediatric pulmonary hypertension
International Journal of Cardiology 212 (2016) 274–276
Contents lists available at ScienceDirect
International Journal of Cardiology journal homepage: www.elsevier.com/locate/ijcard
Correspondence
Right ventricular outflow tract velocity time integral (RVOT VTI) and tricuspid regurgitation velocity/RVOT VTI ratio in pediatric pulmonary hypertension Martin Koestenberger a,⁎, Alexander Avian b, Gernot Grangl a, Ante Burmas a, Stefan Kurath-Koller a, Georg Hansmann c a b c
Division of Pediatric Cardiology, Department of Pediatrics, Medical University Graz, Austria Institute for Medical Informatics, Statistics and Documentation, Medical University Graz, Austria Department of Pediatric Cardiology and Critical Care, Hannover Medical School, Hannover, Germany
a r t i c l e
i n f o
Article history: Received 12 February 2016 Accepted 19 March 2016 Available online 24 March 2016 Keywords: Age Body surface area Pediatric Pulmonary hypertension Right ventricular outflow tract velocity time integral Tricuspid regurgitation velocity
Doppler echocardiography is a simple method of assessing hemodynamics in patients with pulmonary hypertension (PH). Determination of the right ventricular outflow tract velocity time integral (RVOT VTI) is a part of the non-invasive investigation of pulmonary flow in adults [1,2]. The normal range of RVOT VTI in adults is stable, and differences serve as indicators for changes in RV stroke volume. In children, noninvasive techniques to assess pulmonary blood flow are of interest because such investigations do not require invasive cardiac catheterization (CC) that is not without risk in PH children [3]. Recently, we provided normative age-related pediatric RVOT VTI values [4] in order to introduce RVOT VTI assessment to echocardiographic protocols for pediatric PH evaluation. The tricuspid regurgitation velocity (TRV)/RVOT VTI ratio, as a reliable measure of pulmonary blood flow in adults with PH [1,2,5], approximates the ratio of pulmonary artery pressure to pulmonary blood flow [6,7], with pediatric data to date missing. The aim of our study was to investigate RVOT VTI and TRV/RVOT VTI ratio in
⁎ Corresponding author at: Department of Pediatrics, Medical University Graz, Auenbruggerplatz 34/2, A-8036 Graz, Austria. E-mail addresses: [email protected], [email protected] (M. Koestenberger).
http://dx.doi.org/10.1016/j.ijcard.2016.03.111 0167-5273/© 2016 Elsevier Ireland Ltd. All rights reserved.
children with PH with respect to healthy controls and growth-related differences. The PH study group consisted of 59 children with PH (median age: 5.3; range 3 months to 18.3 years; 22 female): 36 children had PH associated with congenital heart disease (PH-CHD), 11 had PH associated with bronchopulmonary dysplasia (PH-BPD) (n = 11), and 12 had idiopathic PH (iPH). At time of enrollment, all patients were in a clinically stable condition without change of medications within the preceding 10 weeks. All PH patients had measurable mild to moderate TR so that TR jets could be reliably interrogated. RV systolic pressure was estimated by CW-Doppler of TRV (calculated from the modified Bernoulli equation) [7]. TRV N 2.8 m/s was considered a cut-off to define elevated pulmonary pressure in the absence of pulmonary stenosis [8]. Patients with PH-CHD and iPH underwent CC. The peak systolic RV pressure was divided by the peak systolic aortic pressure to express the RV pressure as a percentage of systemic pressure. CC data are given in Table 1. Echocardiograms were performed with a commercially available echocardiographic system (Sonos iE33, Philips, Andover, Mass, USA) using transducers of 5–1, 8–3, and 12–4 MHz depending on patient size. The RVOT VTI was obtained by placing a PW Doppler sample volume in the proximal RVOT in the parasternal short-axis view (Fig. 1a). After manually tracing the obtained Doppler spectrum, the RVOT VTI values are measured from 3 to 5 consecutive beats and averaged. CW Doppler was used to determine the peak TRV (m/s) in the apical 4-chamber view. The highest velocity obtained from multiple views was used. The TRV/RVOT VTI ratio was then calculated. Data are presented as mean and standard deviation or median and range for continuous data and absolute and relative frequency for categorical data, respectively. If the assumption of normal distributed data was met, continuous variables were analyzed using t-test, ANOVA or Pearson's correlation coefficient. Otherwise non-parametric methods were used. Age adjusted RVOT VTI z-scores were calculated according to Koestenberger et al. [4]. A p-value less than 5% was considered significant. The authors of this manuscript have certified that they comply with the principles of ethical publishing in the International Journal of Cardiology. RVOT VTI values significantly correlated with age (r = 0.602), BW (r = 0.404), BL (r = 0.434), and BSA (r = 0.422). The median RVOT VTI values of our PH patients were 10.1 cm (range: 5.0 to 20.1 cm). 33
Correspondence Table 1 Demographic data of our children with PH. Abbreviations: BSA, body surface area; mPAP, mean pulmonary artery pressure; PVR, pulmonary vascular resistance; PH-CHD, PH secondary to congenital heart disease; PH-BPD, PH secondary to bronchopulmonary dysplasia; iPH, idiopathic PH; RVOT, right ventricular outflow tract; s, standard deviation, TRV/RVOT VTI ratio; tricuspid regurgitation velocity/RVOT velocity time integral ratio; WU, Wood units. Demographic data: PH patients All PH patients
Medication
Parameters
Fulfilled inclusion criteria [Female] Age median (range) Body weight (range) Body length (range) BSA range Bosentan Bosentan + Sildenafil Sildenafil Calcium antagonists Furosemide Warfarin TRV RVOT VTI TRV/RVOT VTI ratio % of systemic pressure mPAP PVR
PH-CHD TRV RVOT VTI TRV/RVOT VTI ratio % of systemic pressure mPAP PVR
iPH TRV RVOT VTI TRv/RVOT VTI ratio % of systemic pressure mPAP PVR
PH-BPD TRV RVOT VTI TRv/RVOT VTI ratio % of systemic pressure
(n) (n) (years) (kg) (cm) (m2) (n) (n) (n) (n) (n) (n) (m/s) (cm) (%) (mean ± range; mm Hg) (mean ± range; WU) (n) (m/s) (cm) (%) (mean ± range; mm Hg) (mean ± range; WU) (n) (m/s) (cm) (%) (mean ± range; mm Hg) (mean ± range; WU) (n) (m/s) (cm) (%)
n or median (range) 59 22 5.3 (0.3–18.3) 17.0 (3.6–83.0) 107 (48–190) 0.21–1.94 8 11 13 5 16 7 3.8 (2.8–5.4) 10.1 (5.0–20.1) 0.36 (0.16–0.98) 71 (39–143) 36.5 (28–57) 5.4 (3.5–18.4)
36 3.8 (2.9–5.0) 10.1 (5.0–20.1) 0.37 (0.17–0.98) 71 (39–143) 27 (18–55) 6.8 (0.8–25.0)
11 4.4 (3.3–5.4) 9.9 (7.0–20.0) 0.44 (0.16–0.61) 89.5 (45–119) 35 (26–57) 14.9 (5.9–29.9)
12 3.3 (2.8–4.7) 9.6 (7.0–14.2) 0.31 (0.21–0.55) 54 (39–73)
out of 59 PH patients (56%) were identified as having impaired RVOT VTI values compared to age-related normative values (z-score b − 2) (Fig. 1b). When using a cutoff point of z-score b − 2 for BSA, BW, or BL up to 58.8% of our PH patients were identified as having impaired RVOT VTI values. Female PH patients had higher RVOT VTI values (12.8 ± 4.0 cm vs. 10.0 ± 2.9 cm; p = 0.004). Using age normalized RVOT VTI z-score female and male patients had comparable values
Fig. 1. (a) Parasternal short axis-view. A PW Doppler sample volume is placed in the proximal RVOT just below the pulmonary valve to measure the RVOT VTI (yellow dots). The RVOT VTI of a 14 year old adolescent with PH is depicted. Note the enlarged RVOT size. (b) RVOT VTI values according to the patient's age in comparison to normal values are shown. Individual values are given with circles, mean normal values [3] are displayed with a black line and ±2 standard deviations from mean normal values are displayed with dashed lines. (c) Changes in systemic pressure according to TRV/RVOT VTI ratio are shown. Individual values are given with circles. Abbreviations: PW, pulsed wave; RVOT, right ventricular outflow tract; TRV/RVOT VTI ratio, tricuspid regurgitation velocity/RVOT velocity time integral ratio; System %, percentage of RV pressure divided by aortic pressure; z, z-score.
275
(− 2.3 ± − 1.4 vs. 1.8 ± 1.7, p = 0.21). The TRV/RVOT VTI ratio ranged between 0.16 and 0.98 (median = 0.36) in our PH patients. The TRV/RVOT VTI ratio was found to rise with increasing RV pressure (r = 0.849, p b 0.001) (Fig. 1c).
276
Correspondence
The RVOT VTI represents a simple method of gleaning insight into the pulmonary blood flow. With the pulmonary vascular resistance (PVR) increasing, changes of the pressure wave profile of RVOT appear along with a decrease in the RVOT VTI [6,9]. Following this relationship when the pulmonary pressure increases in PH patients the TRV will increase and the RVOT VTI will decrease. In adults a TRV/RVOT VTI ratio above 0.2 was shown to have a high sensitivity and specificity for a PVR N 6 WU [5]. Abbas et al. [2] showed that this method reliably identifies adults with elevated PVR with a TRV/RVOT VTI ratio of N0.28 to have a PVR of N 6 WU. The authors state that a correction for heart rate in RVOT VTI measurements was not necessary in adults, as all patients had a heart rate between 60 and 100 beats/min but suggested a heart rate correction for extreme heart rate variations [2]. It is important to use age-related RVOT VTI values in children as reference, due to the variability of echocardiographic data due to age and growth. To the best of our knowledge, we show for the first time that determination of RVOT VTI can identify those PH children with decreased pulmonary blood flow compared to age-related normative values [4]. The TRV/RVOT VTI ratio was found to increase with higher RV pressure in our PH cohort. For clinical practice, RVOT VTI values from now on can be judged as being normal or abnormally impaired in children with PH. As a non-invasive parameter to detect impaired pulmonary blood flow in children with PH, we suggest including RVOT VTI and the TRV/ RVOT VTI ratio in echocardiographic protocols when evaluating children with a suspected PH. Conflict of interest The authors report no relationships that could be construed as a conflict of interest.
References [1] A.E. Abbas, L.M. Franey, T. Marwick, et al., Noninvasive assessment of pulmonary vascular resistance by Doppler echocardiography, J. Am. Soc. Echocardiogr. 26 (2013) 1170–1177. [2] A.E. Abbas, F.D. Fortuin, N.B. Schiller, et al., A simple method for noninvasive estimation of pulmonary vascular resistance, J. Am. Coll. Cardiol. 41 (2003) 1021–1027. [3] M. Beghetti, I. Schulze-Neick, R.M. Berger, et al., Haemodynamic characterisation and heart catheterisation complications in children with pulmonary hypertension: insights from the Global TOPP Registry (tracking outcomes and practice in paediatric pulmonary hypertension), Int. J. Cardiol. 203 (2016) 325–330. [4] M. Koestenberger, B. Nagel, W. Ravekes, et al., Right ventricular outflow tract velocity time integral determination in 570 healthy children and in 52 pediatric atrial septal defect patients, Pediatr. Cardiol. 36 (2015) 1129–1134. [5] G.H. Ajami, S. Cheriki, H. Amoozgar, et al., Accuracy of Doppler-derived estimation of pulmonary vascular resistance in congenital heart disease: an index of operability, Pediatr. Cardiol. 32 (2011) 1168–1174. [6] H. Kouzu, S. Nakatani, S. Kyotani, et al., Noninvasive estimation of pulmonary vascular resistance by Doppler echocardiography in patients with pulmonary arterial hypertension, Am. J. Cardiol. 103 (2009) 872–876. [7] P.G. Yock, R.L. Popp, Noninvasive estimation of right ventricular systolic pressure by Doppler ultrasound in patients with tricuspid regurgitation, Circulation 70 (1984) 657–662. [8] B.M. McQuillan, M.H. Picard, M. Leavitt, A.E. Weyman, Clinical correlates and reference intervals for pulmonary artery systolic pressure among echocardiographically normal subjects, Circulation 104 (2001) 2797–2802. [9] Y. Nakahata, S. Hiraishi, N. Oowada, et al., Quantitative assessment of pulmonary vascular resistance and reactivity in children with pulmonary hypertension due to congenital heart disease using a noninvasive method: new Doppler-derived indexes, Pediatr. Cardiol. 30 (2009) 232–239.
Contents lists available at ScienceDirect
International Journal of Cardiology journal homepage: www.elsevier.com/locate/ijcard
Correspondence
Right ventricular outflow tract velocity time integral (RVOT VTI) and tricuspid regurgitation velocity/RVOT VTI ratio in pediatric pulmonary hypertension Martin Koestenberger a,⁎, Alexander Avian b, Gernot Grangl a, Ante Burmas a, Stefan Kurath-Koller a, Georg Hansmann c a b c
Division of Pediatric Cardiology, Department of Pediatrics, Medical University Graz, Austria Institute for Medical Informatics, Statistics and Documentation, Medical University Graz, Austria Department of Pediatric Cardiology and Critical Care, Hannover Medical School, Hannover, Germany
a r t i c l e
i n f o
Article history: Received 12 February 2016 Accepted 19 March 2016 Available online 24 March 2016 Keywords: Age Body surface area Pediatric Pulmonary hypertension Right ventricular outflow tract velocity time integral Tricuspid regurgitation velocity
Doppler echocardiography is a simple method of assessing hemodynamics in patients with pulmonary hypertension (PH). Determination of the right ventricular outflow tract velocity time integral (RVOT VTI) is a part of the non-invasive investigation of pulmonary flow in adults [1,2]. The normal range of RVOT VTI in adults is stable, and differences serve as indicators for changes in RV stroke volume. In children, noninvasive techniques to assess pulmonary blood flow are of interest because such investigations do not require invasive cardiac catheterization (CC) that is not without risk in PH children [3]. Recently, we provided normative age-related pediatric RVOT VTI values [4] in order to introduce RVOT VTI assessment to echocardiographic protocols for pediatric PH evaluation. The tricuspid regurgitation velocity (TRV)/RVOT VTI ratio, as a reliable measure of pulmonary blood flow in adults with PH [1,2,5], approximates the ratio of pulmonary artery pressure to pulmonary blood flow [6,7], with pediatric data to date missing. The aim of our study was to investigate RVOT VTI and TRV/RVOT VTI ratio in
⁎ Corresponding author at: Department of Pediatrics, Medical University Graz, Auenbruggerplatz 34/2, A-8036 Graz, Austria. E-mail addresses: [email protected], [email protected] (M. Koestenberger).
http://dx.doi.org/10.1016/j.ijcard.2016.03.111 0167-5273/© 2016 Elsevier Ireland Ltd. All rights reserved.
children with PH with respect to healthy controls and growth-related differences. The PH study group consisted of 59 children with PH (median age: 5.3; range 3 months to 18.3 years; 22 female): 36 children had PH associated with congenital heart disease (PH-CHD), 11 had PH associated with bronchopulmonary dysplasia (PH-BPD) (n = 11), and 12 had idiopathic PH (iPH). At time of enrollment, all patients were in a clinically stable condition without change of medications within the preceding 10 weeks. All PH patients had measurable mild to moderate TR so that TR jets could be reliably interrogated. RV systolic pressure was estimated by CW-Doppler of TRV (calculated from the modified Bernoulli equation) [7]. TRV N 2.8 m/s was considered a cut-off to define elevated pulmonary pressure in the absence of pulmonary stenosis [8]. Patients with PH-CHD and iPH underwent CC. The peak systolic RV pressure was divided by the peak systolic aortic pressure to express the RV pressure as a percentage of systemic pressure. CC data are given in Table 1. Echocardiograms were performed with a commercially available echocardiographic system (Sonos iE33, Philips, Andover, Mass, USA) using transducers of 5–1, 8–3, and 12–4 MHz depending on patient size. The RVOT VTI was obtained by placing a PW Doppler sample volume in the proximal RVOT in the parasternal short-axis view (Fig. 1a). After manually tracing the obtained Doppler spectrum, the RVOT VTI values are measured from 3 to 5 consecutive beats and averaged. CW Doppler was used to determine the peak TRV (m/s) in the apical 4-chamber view. The highest velocity obtained from multiple views was used. The TRV/RVOT VTI ratio was then calculated. Data are presented as mean and standard deviation or median and range for continuous data and absolute and relative frequency for categorical data, respectively. If the assumption of normal distributed data was met, continuous variables were analyzed using t-test, ANOVA or Pearson's correlation coefficient. Otherwise non-parametric methods were used. Age adjusted RVOT VTI z-scores were calculated according to Koestenberger et al. [4]. A p-value less than 5% was considered significant. The authors of this manuscript have certified that they comply with the principles of ethical publishing in the International Journal of Cardiology. RVOT VTI values significantly correlated with age (r = 0.602), BW (r = 0.404), BL (r = 0.434), and BSA (r = 0.422). The median RVOT VTI values of our PH patients were 10.1 cm (range: 5.0 to 20.1 cm). 33
Correspondence Table 1 Demographic data of our children with PH. Abbreviations: BSA, body surface area; mPAP, mean pulmonary artery pressure; PVR, pulmonary vascular resistance; PH-CHD, PH secondary to congenital heart disease; PH-BPD, PH secondary to bronchopulmonary dysplasia; iPH, idiopathic PH; RVOT, right ventricular outflow tract; s, standard deviation, TRV/RVOT VTI ratio; tricuspid regurgitation velocity/RVOT velocity time integral ratio; WU, Wood units. Demographic data: PH patients All PH patients
Medication
Parameters
Fulfilled inclusion criteria [Female] Age median (range) Body weight (range) Body length (range) BSA range Bosentan Bosentan + Sildenafil Sildenafil Calcium antagonists Furosemide Warfarin TRV RVOT VTI TRV/RVOT VTI ratio % of systemic pressure mPAP PVR
PH-CHD TRV RVOT VTI TRV/RVOT VTI ratio % of systemic pressure mPAP PVR
iPH TRV RVOT VTI TRv/RVOT VTI ratio % of systemic pressure mPAP PVR
PH-BPD TRV RVOT VTI TRv/RVOT VTI ratio % of systemic pressure
(n) (n) (years) (kg) (cm) (m2) (n) (n) (n) (n) (n) (n) (m/s) (cm) (%) (mean ± range; mm Hg) (mean ± range; WU) (n) (m/s) (cm) (%) (mean ± range; mm Hg) (mean ± range; WU) (n) (m/s) (cm) (%) (mean ± range; mm Hg) (mean ± range; WU) (n) (m/s) (cm) (%)
n or median (range) 59 22 5.3 (0.3–18.3) 17.0 (3.6–83.0) 107 (48–190) 0.21–1.94 8 11 13 5 16 7 3.8 (2.8–5.4) 10.1 (5.0–20.1) 0.36 (0.16–0.98) 71 (39–143) 36.5 (28–57) 5.4 (3.5–18.4)
36 3.8 (2.9–5.0) 10.1 (5.0–20.1) 0.37 (0.17–0.98) 71 (39–143) 27 (18–55) 6.8 (0.8–25.0)
11 4.4 (3.3–5.4) 9.9 (7.0–20.0) 0.44 (0.16–0.61) 89.5 (45–119) 35 (26–57) 14.9 (5.9–29.9)
12 3.3 (2.8–4.7) 9.6 (7.0–14.2) 0.31 (0.21–0.55) 54 (39–73)
out of 59 PH patients (56%) were identified as having impaired RVOT VTI values compared to age-related normative values (z-score b − 2) (Fig. 1b). When using a cutoff point of z-score b − 2 for BSA, BW, or BL up to 58.8% of our PH patients were identified as having impaired RVOT VTI values. Female PH patients had higher RVOT VTI values (12.8 ± 4.0 cm vs. 10.0 ± 2.9 cm; p = 0.004). Using age normalized RVOT VTI z-score female and male patients had comparable values
Fig. 1. (a) Parasternal short axis-view. A PW Doppler sample volume is placed in the proximal RVOT just below the pulmonary valve to measure the RVOT VTI (yellow dots). The RVOT VTI of a 14 year old adolescent with PH is depicted. Note the enlarged RVOT size. (b) RVOT VTI values according to the patient's age in comparison to normal values are shown. Individual values are given with circles, mean normal values [3] are displayed with a black line and ±2 standard deviations from mean normal values are displayed with dashed lines. (c) Changes in systemic pressure according to TRV/RVOT VTI ratio are shown. Individual values are given with circles. Abbreviations: PW, pulsed wave; RVOT, right ventricular outflow tract; TRV/RVOT VTI ratio, tricuspid regurgitation velocity/RVOT velocity time integral ratio; System %, percentage of RV pressure divided by aortic pressure; z, z-score.
275
(− 2.3 ± − 1.4 vs. 1.8 ± 1.7, p = 0.21). The TRV/RVOT VTI ratio ranged between 0.16 and 0.98 (median = 0.36) in our PH patients. The TRV/RVOT VTI ratio was found to rise with increasing RV pressure (r = 0.849, p b 0.001) (Fig. 1c).
276
Correspondence
The RVOT VTI represents a simple method of gleaning insight into the pulmonary blood flow. With the pulmonary vascular resistance (PVR) increasing, changes of the pressure wave profile of RVOT appear along with a decrease in the RVOT VTI [6,9]. Following this relationship when the pulmonary pressure increases in PH patients the TRV will increase and the RVOT VTI will decrease. In adults a TRV/RVOT VTI ratio above 0.2 was shown to have a high sensitivity and specificity for a PVR N 6 WU [5]. Abbas et al. [2] showed that this method reliably identifies adults with elevated PVR with a TRV/RVOT VTI ratio of N0.28 to have a PVR of N 6 WU. The authors state that a correction for heart rate in RVOT VTI measurements was not necessary in adults, as all patients had a heart rate between 60 and 100 beats/min but suggested a heart rate correction for extreme heart rate variations [2]. It is important to use age-related RVOT VTI values in children as reference, due to the variability of echocardiographic data due to age and growth. To the best of our knowledge, we show for the first time that determination of RVOT VTI can identify those PH children with decreased pulmonary blood flow compared to age-related normative values [4]. The TRV/RVOT VTI ratio was found to increase with higher RV pressure in our PH cohort. For clinical practice, RVOT VTI values from now on can be judged as being normal or abnormally impaired in children with PH. As a non-invasive parameter to detect impaired pulmonary blood flow in children with PH, we suggest including RVOT VTI and the TRV/ RVOT VTI ratio in echocardiographic protocols when evaluating children with a suspected PH. Conflict of interest The authors report no relationships that could be construed as a conflict of interest.
References [1] A.E. Abbas, L.M. Franey, T. Marwick, et al., Noninvasive assessment of pulmonary vascular resistance by Doppler echocardiography, J. Am. Soc. Echocardiogr. 26 (2013) 1170–1177. [2] A.E. Abbas, F.D. Fortuin, N.B. Schiller, et al., A simple method for noninvasive estimation of pulmonary vascular resistance, J. Am. Coll. Cardiol. 41 (2003) 1021–1027. [3] M. Beghetti, I. Schulze-Neick, R.M. Berger, et al., Haemodynamic characterisation and heart catheterisation complications in children with pulmonary hypertension: insights from the Global TOPP Registry (tracking outcomes and practice in paediatric pulmonary hypertension), Int. J. Cardiol. 203 (2016) 325–330. [4] M. Koestenberger, B. Nagel, W. Ravekes, et al., Right ventricular outflow tract velocity time integral determination in 570 healthy children and in 52 pediatric atrial septal defect patients, Pediatr. Cardiol. 36 (2015) 1129–1134. [5] G.H. Ajami, S. Cheriki, H. Amoozgar, et al., Accuracy of Doppler-derived estimation of pulmonary vascular resistance in congenital heart disease: an index of operability, Pediatr. Cardiol. 32 (2011) 1168–1174. [6] H. Kouzu, S. Nakatani, S. Kyotani, et al., Noninvasive estimation of pulmonary vascular resistance by Doppler echocardiography in patients with pulmonary arterial hypertension, Am. J. Cardiol. 103 (2009) 872–876. [7] P.G. Yock, R.L. Popp, Noninvasive estimation of right ventricular systolic pressure by Doppler ultrasound in patients with tricuspid regurgitation, Circulation 70 (1984) 657–662. [8] B.M. McQuillan, M.H. Picard, M. Leavitt, A.E. Weyman, Clinical correlates and reference intervals for pulmonary artery systolic pressure among echocardiographically normal subjects, Circulation 104 (2001) 2797–2802. [9] Y. Nakahata, S. Hiraishi, N. Oowada, et al., Quantitative assessment of pulmonary vascular resistance and reactivity in children with pulmonary hypertension due to congenital heart disease using a noninvasive method: new Doppler-derived indexes, Pediatr. Cardiol. 30 (2009) 232–239.