European Heart Journal – Cardiovascular Imaging (2014) 15, 980–986 doi:10.1093/ehjci/jeu041
Reference values of the right ventricular outflow tract systolic excursion in 711 healthy children and calculation of z-score values Martin Koestenberger 1*, William Ravekes 2, Bert Nagel 1, Alexander Avian 3, Bernd Heinzl 1, Gerhard Cvirn 4, Peter Fritsch 1, Andrea Fandl 1, Thomas Rehak 1, and Andreas Gamillscheg 1 1 Division of Pediatric Cardiology, Department of Pediatrics, Medical University Graz, Graz, Austria; 2Division of Pediatric Cardiology, Johns Hopkins University School of Medicine, Baltimore, MD, USA; 3Institute for Medical Informatics, Statistics and Documentation, Medical University Graz, Graz, Austria; and 4Institute of Physiological Chemistry, Centre of Physiological Medicine, Medical University Graz, Graz, Austria
Received 1 October 2013; accepted after revision 17 February 2014; online publish-ahead-of-print 23 March 2014
Objective
----------------------------------------------------------------------------------------------------------------------------------------------------------Keywords
Right ventricular outflow tract systolic excursion † right ventricular systolic function † age † z-score † paediatric patients † reference values † body surface area
Introduction The right ventricular outflow tract systolic excursion (RVOT SE) as an echocardiographic tool to analyse right ventricular (RV) systolic function has recently been introduced in adults with and without acquired heart disease.1 Measurement of the RVOT SE has been shown to be an additional tool to assess RV systolic function in a simple and reproducible way using M-mode echocardiography.1 Various studies suggested the usefulness of determining the RVOT movement as an additional marker of RV function.2 – 6 As the
RVOT contributes to the contraction pattern of the RV, an impaired RVOT function in patients with congenital heart diseases (CHDs) may suggest an impaired overall RV systolic function. Other parameters of RV systolic function such as the tricuspid annular plane systolic excursion (TAPSE) and tricuspid annular peak systolic velocity (S’) have been shown to be good quantitative measures of longitudinal RV systolic function in adults and children with and without CHDs.7 – 13 Guidelines for chamber quantification have recommended the assessment of RV systolic function to be part of the standard echo exam.14 Determination of the RVOT SE might be
* Corresponding author. Tel: +43 316 385 84276; Fax: +43 316 385 13682, E-mail: [email protected] or [email protected] Published on behalf of the European Society of Cardiology. All rights reserved. & The Author 2014. For permissions please email: [email protected]
Downloaded from by guest on November 14, 2015
Quantitative determination of right ventricular (RV) function has gained more interest over the last years. The RV outflow tract systolic excursion (RVOT SE) has been recently proposed as an echocardiographic tool to assess RV systolic function in adults. We aimed to determine growth-related changes of RVOT SE in children and to establish references values. ..................................................................................................................................................................................... Study design A prospective study was conducted in a group of 711 healthy paediatric patients (age: 1 day to 18 years). We determined the effects of age and body surface area (BSA) on RVOT SE values. RVOT SE values were further correlated with the established RV systolic function parameters tricuspid annular plane systolic excursion (TAPSE) and tricuspid annular peak systolic velocity (S’). ..................................................................................................................................................................................... Results The RVOT SE ranged from a mean of 3.4 mm in neonates to 9.5 mm in 18-year-old adolescents. The RVOT SE values showed a positive correlation with age (r ¼ 0.90, P , 0.001) and BSA (r ¼ 0.91, P , 0.001). A significant positive correlation was seen between RVOT SE and TAPSE (r ¼ 0.93, P , 0.001) and also between RVOT SE and S’ (r ¼ 0.86, P , 0.001) in our patients. ..................................................................................................................................................................................... Conclusion RVOT SE provides a simple measure and, in combination with long-axis excursion parameters TAPSE and S’, a comprehensive assessment of RV systolic function. Z-scores of RVOT SE values were calculated, and percentile charts were established to serve as reference data.
981
References values of RVOT SE in 711 healthy children
useful in patients with pressure- or volume-loaded RVs owing to RVOT stenosis or pulmonary regurgitation (PR). As the RVOT SE is easy to perform, safe, and available on all cardiac ultrasound systems, it can be used as a non-invasive measurement to study RV systolic function in children in addition to the recommended RV systolic measurements for the performance of a paediatric echocardiogram.15 Reference values of RVOT SE measurements for the adult population are available.1 We hypothesized that the RVOT SE values of our tested healthy children will increase with increasing age and BSA. In a large paediatric cohort, we undertook a prospective study to determine the normal values for the RVOT SE correlated to age and BSA and calculate normal z-score values with the aim to serve as a reference for the assessment of RVOT systolic function. Our further aim was to determine the value of RVOT SE compared with established age-related echocardiographic parameters for defining longitudinal RV systolic function, such as the TAPSE and the S’.
Methods Ethics
Patient population Patients were selected from healthy individuals referred to our cardiology service from January 2012 to January 2013 for evaluation of a heart murmur or family history of CHD. For the purpose of the study, only echocardiograms with an official reading of a completely normal study except for patent foramen ovale with a diameter of ≤2 mm and trivial left-to-right shunt were accepted for analysis. All patients with CHD or acquired heart disease, family history of cardiomyopathy, chest and thoracic spine deformities, anorexia nervosa, or chromosomal syndromes were excluded from analysis. Patients were examined in a resting state without prior sedation. Infants were allowed to be bottle-fed during the examination.
Echocardiographic techniques Echocardiograms were performed using commercially available echocardiographic system (Sonos iE33, Philips, Andover, MA, USA) using transducers of 5 – 1, 8 – 3, and 12– 4 MHz depending on patient size. Images were recorded digitally and later analysed by one of the investigators (M.K.) using off-line software (Xcelera Echo; Philips Medical Systems, Eindhoven, The Netherlands). (i) RVOT SE was measured from magnified cine-loops of the RVOT area acquired from the parasternal short axis view using M-mode echocardiography. Imaging was performed at the level of the aortic valve at maximal RVOT diameter, with the ultrasound beam perpendicular to the RVOT walls, after optimization of focus, gain, and compression settings as previously described.1 Each data point was averaged from three to five measurements. A representative image of the RVOT SE in an 8-year-old child with normal RV and LV function is shown in Figure 1. (ii) Tricuspid annular peak systolic velocity (S’) was obtained by the following method: pulsed-wave tissue Doppler imaging was performed using transducer frequencies of 3 –8 MHz with spectral Doppler filters adjusted until a Nyquist limit of 15– 20 cm s21. The minimal optimal gain setting was used. Doppler measurements were
acquired with subjects in the left lateral decubitus position during shallow respiration. Guided by the four-chamber view, a 5 mm sample volume was placed at the lateral corner of tricuspid annulus at the attachment of the anterior leaflet of the tricuspid valve. Care was taken to obtain an alignment as parallel as possible to the direction of the tricuspid annular motion. Tricuspid annular peak annular velocities (S’) during systole were recorded and analysed off-line. The resulting velocities were recorded for three to five cardiac cycles and were averaged. (iii) TAPSE was measured by 2D echocardiography-guided M-mode recordings from the apical four-chamber view with the cursor placed at the free wall of the tricuspid annulus as previously described.16 Care was taken to align the sample volume as vertical as possible with respect to the cardiac apex. Angle correction and respiratory gating were not used.
Statistical analysis All data were measured from three well-trained observers (M.K, B.H, and B.N) from three to five consecutive beats and averaged as previously recommended.1,16 For data analysis, SPSS 19 was used. Data are presented as mean + 2 SD. In the first step, the correlation structure between age, BSA, and RVOT SE was analysed with Pearson’s correlation coefficient. For calculation of the BSA, we used the formula of Mosteller.17 Regression was used to estimate RVOT SE from age, BSA, and gender. Models using logarithmic (y ¼ a + b1ln[x]) and square root (y ¼ a + b0.5 1x ) relations were tested. White test and Breusch – Pagan test were used for heteroscedasticity. When significant heteroscedasticity was detected, weighted least square methods were used. Each value was weighted by the inverse residual of the linear regression. To test for normal distribution of Z-scores, Anderson– Darling test (A – D test) and Kolmogorov– Smirnov test (K – S test) were used. For data analysis, SPSS 20 and SAS 9.2 (REG procedure and MODEL procedure) were used. A P-value of ,0.05 was considered statistically significant. TAPSE
Downloaded from by guest on November 14, 2015
This study complies with all institutional guidelines related to patient confidentiality and research ethics including institutional review board approval. There are no financial or other potentially conflicting relationships to report.
Figure 1: The white broken lines indicate M-mode cursor placement at the parasternal short axis view at the level of the aortic valve. The RVOT SE measures the systolic excursion of the RVOT anterior wall. A representative M-mode image of the right ventricular outflow tract systolic excursion (RVOT SE) in an 8-year-old patient with normal right and left ventricular function is shown. The yellow horizontal lines mark the maximum anterior and posterior positions of the RVOT anterior wall during contraction. The vertical red lines mark the upper and lower measure points (mm) on the endocardial surface of the RVOT SE.
982
M. Koestenberger et al.
Table 1
Patients characteristics n
RVOT SE
TAPSE
S’
BSA
70 22
0.34 + 0.05 0.40 + 0.08
0.91 + 0.16 1.22 + 0.29
7.95 + 1.35 8.64 + 1.28
0.21 (0.14– 0.26) 0.27 (0.16– 0.49)
............................................................................................................................................................................... Month 1 2 3
16
0.39 + 0.06
1.29 + 0.16
8.73 + 0.95
0.29 (0.19– 0.38)
4 –6 7 –12
33 38
0.43 + 0.09 0.45 + 0.08
1.31 + 0.21 1.48 + 0.22
9.19 + 1.03 9.73 + 0.95
0.32 (0.26– 0.42) 0.38 (0.27– 0.50)
22 26
0.48 + 0.06 0.53 + 0.08
1.56 + 0.25 1.80 + 0.15
10.31 + 0.60 10.80 + 0.80
0.47 (0.39– 0.57) 0.60 (0.52– 0.70)
Year 2 3 4
36
0.56 + 0.07
1.80 + 0.18
11.02 + 0.88
0.66 (0.56– 1.17)
5 6
25 29
0.58 + 0.07 0.62 + 0.08
1.87 + 0.14 1.93 + 0.12
11.60 + 0.75 11.93 + 0.98
0.73 (0.60– 0.90) 0.81 (0.65– 1.09)
7
23
0.67 + 0.07
1.95 + 0.16
11.99 + 1.03
0.86 (0.77– 1.04)
8 9
25 16
0.67 + 0.08 0.71 + 0.08
2.01 + 0.16 2.00 + 0.17
12.28 + 1.20 12.08 + 0.92
0.92 (0.64– 1.26) 0.99 (0.81– 1.15)
10
31
0.74 + 0.09
2.11 + 0.15
12.49 + 1.05
1.11 (0.92– 1.44)
11 12
40 32
0.75 + 0.09 0.77 + 0.08
2.14 + 0.29 2.23 + 0.26
12.89 + 1.25 12.91 + 0.98
1.23 (1.01– 1.71) 1.36 (1.07– 1.70)
22
0.83 + 0.13
2.17 + 0.22
12.90 + 0.98
1.38 (1.18– 1.70)
37 36
0.86 + 0.11 0.87 + 0.11
2.33 + 0.30 2.24 + 0.23
13.57 + 1.51 13.58 + 1.35
1.55 (1.12– 2.10) 1.53 (0.87– 1.91)
16
39
0.91 + 0.11
2.35 + 0.24
13.93 + 1.11
1.62 (0.85– 2.14)
17 18
40 53
0.92 + 0.11 0.95 + 0.13
2.38 + 0.24 2.43 + 0.28
14.27 + 1.16 14.43 + 1.46
1.68 (1.25– 2.10) 1.74 (1.35– 2.26)
For each age group, the observed number of paediatric patients (n), the observed mean + SD for RVOT SE (cm), TAPSE (cm) and S’ (cm s21) and observed mean with range for BSA (m2) are given. RVOT SE, right ventricular outflow tract systolic excursion; TAPSE, tricuspid annular plane systolic excursion; S’, tricuspid annular peak systolic velocity, BSA, body surface area.
z-scores and S’ z-scores were calculated according to previous data.10,11 To analyse inter-observer reliability, two well-trained observers measured the RVOT SE from three to five consecutive beats and averaged. Therefore, 30 patients were randomly selected. For intra-observer reliability, one well-trained observer measured RVOT SE twice in the same patient. Time between these two measurements ranged between 1 and 5 days. No other analytical method beside intraclass correlation coefficient (ICC) was used. Inter- and intra-observer variability was found for RVOT SE with an intra-class correlation coefficient of 0.97 (CI 0.94– 0.99), P , 0.001, and 0.98 (CI 0.96– 0.99), P . 0.001. Our intra-observer and inter-observer variability was similar than that reported in the literature for the RVOT SE.1
Results The study group consisted of 711 paediatric patients (368 male; 343 female) with a normal echocardiogram. The study group encompassed neonates to adolescents (age: 1 day to 18 years; BSA: 0.14 to 2.26 m2), including 68 term neonates and 111 infants (Table 1). The RVOT SE ranged from a mean of 3.4 mm in neonates to 9.5 mm in 18-year-old adolescents. A significant positive correlation was seen between RVOT SE and TAPSE (r ¼ 0.93, P , 0.001) and also between RVOT SE and S’ (r ¼ 0.86, P , 0.001) in our paediatric
patients. The RVOT SE values increased from neonates to adolescents in a nonlinear way. Figure 2 shows the final model relating RVOT SE to age. Within this model, 85% of the Variance in RVOTSE could be explained by age. The regression equation relating age and RVOT SE is as follows: √ age
RVOT SEpred = e−1.011+0.230×
Age-related z-scores +2 SD and +3 SD for RVOT SE are shown in Table 2. An index was calculated for the RVOT SE for age divided by the BSA. The indexed value declines exponentially. It starts high in the neonates (1.66 cm s21 m22) and declines (0.55 cm s21 m22) to 18 years (Figure 3).The indexed values show that the increase in the absolute RVOT SE value overtime is not solely due to an increase in patient size and actually gets proportionally less in older patients. We did not find a significant difference of RVOT SE normal values between male and female patients. Correlation of RVOT SE z-scores to S’ z-scores values (r ¼ 0.23, P , 0.001) and correlation of RVOT SE z-scores to TAPSE z-scores values (r ¼ 0.19, P , 0.001) were significant but weak (Figure 4).
Downloaded from by guest on November 14, 2015
13 14 15
983
References values of RVOT SE in 711 healthy children
Table 2
Age-related z-scores for RVOT SE RVOT SEpred
22 SD
12 SD
23 SD
13 SD
1 2
0.37 0.38
0.27 0.28
0.50 0.51
0.18 0.19
0.56 0.58
3
0.39
0.29
0.52
0.19
0.59
4 –6 7 –12
0.41 0.43
0.3 0.32
0.54 0.58
0.20 0.22
0.61 0.65
2 3
0.47 0.51
0.35 0.39
0.63 0.68
0.24 0.26
0.70 0.76
4
0.55
0.42
0.72
0.29
0.81
5 6
0.58 0.61
0.44 0.47
0.77 0.80
0.31 0.33
0.86 0.9
7
0.64
0.49
0.84
0.35
0.94
8 9
0.67 0.70
0.52 0.54
0.88 0.92
0.36 0.38
0.98 1.02
10
0.73
0.56
0.95
0.4
1.06
11 12
0.76 0.79
0.58 0.61
0.98 1.02
0.42 0.44
1.10 1.13
13
0.81
0.63
1.05
0.46
1.17
14 15
0.84 0.87
0.65 0.67
1.09 1.12
0.47 0.49
1.21 1.24
16
0.90
0.7
1.15
0.51
1.28
17 18
0.92 0.95
0.72 0.74
1.18 1.22
0.53 0.55
1.32 1.35
................................................................................ Month
Year
Figure 2: Age vs. mean value of right ventricular outflow tract systolic excursion (RVOT SE) +2 or +3 SD for age vs. RVOT SE. The mean is given as the black solid line. The +2 and +3 SD lines are given as the black broken line and black dotted line, respectively.
Within the various portions of the RV, the orientation of the myocardial fibres is different. Inlet and outlet long-axis of the RV are approximately at right angles to each other. Global assessment of the RV is difficult owing to the underlying anatomy.18 Non-invasive quantification of the RV function is, however, still challenging because of the complex geometry of the right ventricle. The RVOT is known to be distinct from the other parts of the RV in embryologic origin19 and in anatomy.20 The RVOT has superficial circumferential muscle fibres, which cause radial RVOT contraction during systole.21 Geva et al.2 have shown that the delay in the regional activation of the RVOT contributes to the peristalsis-like contraction pattern of the normal RV. The RVOT region has shown to be less susceptible to regional RV abnormalities than other areas such as the lateral free wall.14,21 The role of the RVOT contraction pattern has been suggested to be relevant in patients with CHD.22 The RVOT SE directly measures the contraction of the RVOT region.21 We assessed the RV systolic function using the parasternal short axis view for the determination of the RVOT SE, and using the apical four-chamber view for the determination of TAPSE and S’, in order to obtain analysis of the behaviour of both the longitudinal and RVOT systolic contraction. Our intention was to assess a method that can be easily applied and is reliable to provide an assessment of RVOT systolic function. In adults, the largest RVOT SE values were found when RV and LV systolic function are normal.1 The normal value of the RVOT SE in healthy adults is 9.6 + 1.5 mm, whereas in adult patients with reduced RV function the RVOT SE was dramatically decreased at only 1.7 + 1.1 mm. RVOT SE values of ,6 mm identified patients with a reduced RV systolic function with 100% sensitivity and 100% specifity.1 Asmer et al.1 also studied RVOT fractional shortening (FS), a related analysis of the RVOT. The RVOT FS differentiated well between patients with reduced and preserved RV function,
For each age group, the mean (RVOT SEpred) +2 SD and+3 SD according to the regression model are shown. These ranges represent the expectable normal intervals of deviation for a certainty level of 95 and 99%. In this regression model, RVOT SE is estimated by the given age and provides therefore normative data for the whole age range up to the age of 18 years. As a result, RVOT SEpred is continuously increasing. In contrast, observed values are slightly decreasing from the 2nd to the 3rd month, which is due individual outliners in the 2nd and 3rd months (Table 1). In each age group, the mean age was chosen for calculating the predicted mean (e.g. for the third year, the age of 2.5 years was chosen). RVOT SE, right ventricular outflow tract systolic excursion.
but the RVOT SE values have been described to show better differentiation between reduced and preserved RV function. They show that in patients with good LV function, the aorta is pushed anteriorly in systole, contributing to RVOT FS even in the presence of reduced RV function but not contributing to the RVOT SE.1 Lindqvist et al.4 reported that RVOT FS moderately correlated with TAPSE and inversely correlated with RV-right atrial pressure gradient. In patients with repaired tetralogy of Fallot (rTOF), RVOT aneurysm or dyskinesis is relatively common as a result of surgical reconstruction during initial repair. Repaired TOF patients were shown to have impaired systolic function of the RVOT.6 Determination of the RVOT SE might be useful in patients with pressure-loaded right ventricles owing to RVOT obstructions or in cases with pulmonary artery hypertension (PAH). On the other hand, RV volume overload owing to PR following pulmonary valve-sparing operations in patients with Tetralogy of Fallot,23 – 25 other CHD lesions with PR or shunt lesions on atrial level could influence RVOT systolic contraction. In rTOF patients, the systolic contraction of the RVOT and the systolic
Downloaded from by guest on November 14, 2015
Discussion
984
M. Koestenberger et al.
Figure 3: A calculated index of right ventricular outflow tract systolic excursion (RVOT SE) divided by the body surface area (BSA) vs. age. The mean is given as the black solid line. The +2 and +3 SD lines are given as the black broken line and black dotted line, respectively.
Downloaded from by guest on November 14, 2015
contraction of the RV-body are important parts of the global RV systolic function. Greutmann et al.6 found that in rTOF patients (inclusively patients after transannular patch repair) with preserved global systolic RV function, the severely decreased RVOT systolic function can be compensated for an increased radial and transverse shortening of the RV body whereas in rTOF patients with abnormal RV systolic function cannot compensate for the even more pronounced reduced RVOT systolic function by increased contractions of the RV body. Dysfunction of the RVOT may have an impact on the occurrence of ventricular arrhythmias and affects exercise capacity of these patients.26 Therefore, in our opinion, the RVOT SE is worth to measure in all (transannular and valve-sparing method) rTOF patients. We have to state that the RVOT SE in patients after transannular patch repair might behave different to those after a valvesparing procedure, but we support the notion that a reduced RVOT function may have a significant impact on long-time outcomes in all rTOF patients. While in the normal heart, the function of the inflow and outflow components of the RV is closely related,27 this relation has been shown to be weak and unpredictable in rTOF patients.28 The RVOT has also been shown to be the most commonly enlarged dimension in patients with arrhythmogenic RV dysplasia ARVD.29 Yoerger et al. state that a possible enlargement and dysfunction of the RVOT should be one of the main echocardiographic parameters to be investigated when the existence of an ARVD is suspected.29 This supports the notion of recent guideline that the RVOT size and function could be distorted in patients with chest and spine abnormalities.14 The RVOT SE may not reflect the systolic function of the entire RVOT but has the advantage of being a simple M-mode measurement. In clinical practice, this parameter may serve as an additional tool and together with the established longitudinal RV systolic function parameters TAPSE and S’ may provide more complete information of RV systolic function. For example in rTOF patients, both the contraction of the RVOT and that of the
Figure 4: (A) Correlation of the right ventricular outflow tract systolic excursion (RVOT SE) z-score and the S’ z-score in the paediatric age group. (B) Correlation of the right ventricular outflow tract systolic excursion (RVOT SE) z-score and the TAPSE z-score in the paediatric age group. The mean is given as the blue solid line.
RV-body are important determinants of the global RV systolic function. Although the accuracy of echo-determined systolic RV function parameters compared with MRI has been described to be suboptimal30 in patients with hypoplastic left heart syndrome (HLHS), it might be of interest to investigate the behaviour of the RVOT function and size after ventriculotomy in this patient group as it has been demonstrated for strain measurements.31 RVOT SE values of patients with PAH may be significantly different to normal controls, given the theory that the longer the RV suffers from severe pressure overload the more depressed systolic RV function becomes owing to the fact that the RV is not capable to sustain high long-term pressure overload.32 Patients with an atrial septal defect (ASD) usually have a preserved RV function despite mild RV volume overload. In ASD patients with mild left-to-right shunting, no significant differences of RV systolic function parameters such as the TAPSE compared with control subjects were found.12 We have previously shown significant
985
References values of RVOT SE in 711 healthy children
Limitation The relatively small sample size was a limitation of this study. One limitation of our study is that we did not assess the effect of preload variations related to respiration. In paediatric clinical practice, it would be cumbersome to apply respiratory gaiting to this method on a routine basis. RVOT SE has been proposed to be less sensitive to preload and afterload variations owing to the small diameter of the RVOT1 and therefore reduced wall stress according to Laplace’s law but to date conclusive data are missing. The low test– retest variability for a short time period is shown by the high intra-observer reliability (ICC). We have only a limited number of patients with more than one measurement over a longer time period. Therefore, changes in the patient over time could not be analysed. We have to state that it remains unclear how well RVOT SE will perform as an index of RV systolic function in children with CHDs, unless clinical studies will prove its usefulness.
Conclusion RVOT SE is a novel and promising echocardiographic parameter of systolic RV function. We have established normal reference values of RVOT SE in the paediatric age group. The RVOT SE values were lower in neonates and infants compared with older children and adolescents in our study, although RV systolic function was preserved. If
the markedly lower RVOT SE in infants is solely a marker of growth-related changes inside the paediatric population or if it is a sign of possible altered systolic function in infants owing to the immaturity of the ventricular muscle remains unclear. The indexed RVOT SE shows the opposite pattern and starts quite high in the neonates and declines in the adolescent age groups. In future, RVOT SE measurements may be included in the battery of echocardiographic markers in patients with CHD that affect the RV, as an impaired RVOT systolic function in patients with CHDs may suggest an impaired overall RV systolic function.
Funding No extramural funding was used to support this work. The authors are solely responsible for the design and conduct of this study, all study analyses, the drafting and editing of the paper, and its final contents.
Conflict of interest: None declared.
References 1. Asmer I, Adawi S, Ganaeem M, Shehadeh G, Shiran A. Right ventricular outflow tract systolic excursion. A novel echocardiographic parameter of right ventricular function. Eur Heart J Cardiovasc Imaging 2012;13:871 –7. 2. Geva T, Powell AJ, Crawford EC, Chung T, Colan SD. Evaluation of regional differences in right ventricular systolic function by acoustic quantification echocardiography and cine magnetic resonance imaging. Circulation 1998;98:339 –45. 3. Kukulski T, Hubbert L, Arnold M, Wranne B, Hatle L, Sutherland G. Normal regional right ventricular function and its change with age: a Doppler myocardial imaging study. J Am Soc Echocardiogr 2000;13:194–204. 4. Lindqvist P, Henein M, Kazzam E. Right ventricular outflow-tract fractional shortening: an applicable measure of right ventricular systolic function. Eur J Echocardiography 2003;4:29 –35. 5. Kutty S, Zhou J, Gauvreau K, Trincado C, Powell AJ, Geva T. Regional dysfunction of the right ventricular outflow tract reduces the accuracy of Doppler tissue imaging assessment of global right ventricular systolic function in patients with repaired tetralogy of Fallot. J Am Soc Echocardiogr 2011;24:637 –43. 6. Greutmann M, Tobler D, Biaggi P, Mah ML, Crean A, Wald RM et al. Echocardiography for assessment of regional and global right ventricular systolic function in adults with repaired tetralogy of Fallot. Int J Cardiol 2012;157:53 –8. 7. Meluzin J, Spinarova L, Bakala J, Toman J, Krejcı´ J, Hude P et al. Pulsed Doppler tissue imaging of the velocity of tricuspid annular systolic motion; a new, rapid, and noninvasive method of evaluating right ventricular systolic function. Eur Heart J 2001; 22:340–8. 8. Saxena N, Rajagopalan N, Edelman K, Lo´pez-Candales A. Tricuspid annular systolic velocity: a useful measurement in determining right ventricular systolic function regardless of pulmonary artery pressures. Echocardiography 2006;23:750 –5. 9. Koestenberger M, Nagel B, Ravekes W, Everett AD, Stueger H, Heinzl B et al. Systolic right ventricular (RV) function in pediatric and adolescent patients with TOF: echocardiography versus MRI. J Am Soc Echocardiogr 2011;24:45–52. 10. Koestenberger M, Nagel B, Ravekes W, Avian A, Heinzl B, Cvirn G et al. Reference values of the tricuspid annular peak systolic velocity in healthy pediatric patients, calculation of z-score values, and comparison to the tricuspid annular plane systolic excursion. Am J Cardiol 2012;109:116–21. 11. Koestenberger M, Ravekes W, Everett A, Stueger H, Heinzl B, Gamillscheg A et al. Right ventricular function in infants, children and adolescents: reference values of the tricuspid annular plane systolic excursion (TAPSE) in 640 healthy patients and calculation of z-score values. J Am Soc Echocardiogr 2009;22:715–19. 12. Koestenberger M, Nagel B, Ravekes W, Everett AD, Stueger H, Heinzl B et al. Tricuspid annular plane systolic excursion (TAPSE) and right ventricular ejection fraction in pediatric and adolescent patients with tetralogy of Fallot, patients with atrial septal defect, and age-matched normal subjects. Clin Res Cardiol 2011;100:67– 75. 13. Koestenberger M, Nagel B, Ravekes W, Avian A, Heinzl B, Fandl A et al. Tricuspid annular peak systolic velocity (S’) in children and young adults with pulmonary artery hypertension secondary to congenital heart diseases, and in those with repaired tetralogy of fallot: echocardiography and MRI data. J Am Soc Echocardiogr 2012;25:1041 – 9. 14. Rudski LG, Lai WW, Afilalo J, Hua L, Handschumacher MD, Chandrasekaran K, Solomon SD et al. Guidelines for the echocardiographic assessment of the right heart in adults: a report from the American Society of Echocardiography endorsed by the European Association of Echocardiography, a registered branch of the
Downloaded from by guest on November 14, 2015
growth-related changes for the longitudinal RV systolic function parameters S’ and TAPSE,10,11,33 and therefore, we expected significant growth-related changes for RVOT SE. Before determining possible reductions of RVOT SE in patients with HLHS, PAH, or ASD, sufficient quantitative reference data of echocardiographic normal patients from infants to large adolescents are required. We found that RVOT SE values increase with age and BSA. Recently, Willis et al.34 demonstrated in 205 healthy adults that the BSA plays an important part in the determination of normal RV reference values. RVOT SE is affected by increasing age and increasing BSA with a steeper course of the curve in neonates and infants when compared with older children and adolescents. As expected, our normal values for RVOT SE in the older adolescents are very similar to adult RVOT SE normal reference data.1 The difference between the high correlation of RVOT SE and TAPSE or S’ and the weak correlation between RVOT SE z-scores and TAPSE or S’ z-scores reflects the age dependency of all of these parameters. Owing to the strong age dependency of all of these parameters, the high correlations of the actual measurements do reflect the age dependency of these measurements more than the direct association of these measurements. This suggests the growth-related changes in normal values to be similar for parameters of longitudinal RV systolic function and for the RVOT SE but demonstrates that the RVOT SE does not provide the same information about RV behaviour as the longitudinal RV systolic function parameters. In our opinion, an explanation might be the different age-related increase of TAPSE, S’, and RVOT SE values during childhood. Measuring RVOT SE consequently gives us additional information of what is a ‘normal’ systolic function for the healthy paediatric RVOT and together with TAPSE and S’ provides an assessment of RV systolic function in the paediatric age group.
986
15.
16.
17. 18. 19.
20. 21.
22. 23.
24.
European Society of Cardiology, and the Canadian Society of Echocardiography. J Am Soc Echocardiogr 2010;23:685 –713. Lopez L, Colan SD, Frommelt PC, Ensing GJ, Kendall K, Younoszai AK et al. Recommendations for quantification methods during the performance of a pediatric echocardiogram: a report from the Pediatric Measurements Writing Group of the American Society of Echocardiography Pediatric and Congenital Heart Disease Council. J Am Soc Echocardiogr 2010;23:465 –95. Lee CY, Chang SM, Hsiao SH, Tseng JC, Lin SK, Liu CP. Right heart function and scleroderma: insights from tricuspid annular pane systolic excursion. Echocardiography 2007;24:118–25. Mosteller RD. Simplified calculation of body-surface area. N Engl J Med 1987;317: 1098. Redington AN. Right ventricular function. Cardiol Clin 2002;20:341 –9. Sugishita Y, Watanabe M, Fisher SA. The development of the embryonic outflow tract provides novel insights into cardiac differentiation and remodelling. Trends Cardiovasc Med 2004;14:235 –41. Dell’Italia LJ. The right ventricle: anatomy, physiology, and clinical importance. Curr Probl Cardiol 1991;16:653–720. Haddad F, Hunt SA, Rosenthal DN, Murphy DJ. Right ventricular function in cardiovascular disease, part I: anatomy, physiology, aging, and functional assessment of the right ventricle. Circulation 2008;117:1436 –48. Bashore TM. Adult congenital heart disease: right ventricular outflow tract lesions. Circulation 2007;115:1933 –47. Bove T, Bouchez S, De Hert S, Wouters P, De Somer F, Devos D et al. Acute and chronic effects of dysfunction of right ventricular outflow tract components on right ventricular performance in a porcine model: implications for primary repair of tetralogy of fallot. J Am Coll Cardiol 2012;60:64–71. Bove´ T, Franc¸ois K, Van De Kerckhove K, Panzer J, De Groote K, De Wolf D et al. Assessment of a right-ventricular infundibulum-sparing approach in transatrial – transpulmonary repair of tetralogy of fallot. Eur J Cardiothorac Surg 2012;41:126 – 33.
M. Koestenberger et al.
25. Morales DL, Zafar F, Heinle JS, Ocampo EC, Kim JJ, Relyea K et al. Right ventricular infundibulum sparing (RVIS) tetralogy of fallot repair: a review of over 300 patients. Ann Surg 2009;250:611 –7. 26. Wald RM, Haber I, Wald R, Valente AM, Powell AJ, Geva T. Effects of regional dysfunction and late gadolinium enhancement on global right ventricular function and exercise capacity in patients with repaired tetralogy of fallot. Circulation 2009; 119:1370 –7. 27. Lytrivi ID, Ko HH, Srivastava S, Norton K, Goldman J, Parness IA et al. Regional differences in right ventricular systolic function as determined by cine magnetic resonance imaging after infundibulotomy. Am J Cardiol 2004;94:970–3. 28. Bodhey NK, Beerbaum P, Sarikouch S, Kropf S, Lange P, Berger F et al. Functional analysis of the components of the right ventricle in the setting of tetralogy of Fallot. Circ Cardiovasc Imaging 2008;1:141–7. 29. Yoerger DM, Marcus F, Sherill D, Calkins H, Towbin JA, Zareba W et al. Echocardiographic findings in patients meeting task force criteria for arrhythmogenic right ventricular dysplasia. J Am Coll Cardiol 2005;45:860 –5. 30. Bellsham-Revell HR, Simpson JM, Miller OI, Bell AJ. Subjective evaluation of right ventricular systolic function in hypoplastic left heart syndrome: how accurate is it? J Am Soc Echocardiogr 2013;26:52 –6. 31. Menon SC, Erickson LK, McFadden M, Miller DV. Effect of ventriculotomy on rightventricular remodeling in hypoplastic left heart syndrome: a histopathological and echocardiography correlation study. Pediatr Cardiol 2013;34:354 –63. 32. Bogaard HJ, Abe K, Vonk Noordegraaf A, Voelkel NF. The right ventricle under pressure: cellular and molecular mechanisms of right-heart failure in pulmonary hypertension. Chest 2009;135:794–804. 33. Koestenberger M, Nagel B, Ravekes W, Urlesberger B, Raith W, Avian A et al. Systolic right ventricular function in preterm and term neonates: reference values of the tricuspid annular plane systolic excursion (TAPSE) in 258 patients and calculation of z-score values. Neonatology 2011;100:85 –92. 34. Willis J, Augustine D, Shah R, Stevens C, Easaw J. Right ventricular normal measurements: time to index? J Am Soc Echocardiogr 2012;25:1259 –67. Downloaded from by guest on November 14, 2015
Reference values of the right ventricular outflow tract systolic excursion in 711 healthy children and calculation of z-score values Martin Koestenberger 1*, William Ravekes 2, Bert Nagel 1, Alexander Avian 3, Bernd Heinzl 1, Gerhard Cvirn 4, Peter Fritsch 1, Andrea Fandl 1, Thomas Rehak 1, and Andreas Gamillscheg 1 1 Division of Pediatric Cardiology, Department of Pediatrics, Medical University Graz, Graz, Austria; 2Division of Pediatric Cardiology, Johns Hopkins University School of Medicine, Baltimore, MD, USA; 3Institute for Medical Informatics, Statistics and Documentation, Medical University Graz, Graz, Austria; and 4Institute of Physiological Chemistry, Centre of Physiological Medicine, Medical University Graz, Graz, Austria
Received 1 October 2013; accepted after revision 17 February 2014; online publish-ahead-of-print 23 March 2014
Objective
----------------------------------------------------------------------------------------------------------------------------------------------------------Keywords
Right ventricular outflow tract systolic excursion † right ventricular systolic function † age † z-score † paediatric patients † reference values † body surface area
Introduction The right ventricular outflow tract systolic excursion (RVOT SE) as an echocardiographic tool to analyse right ventricular (RV) systolic function has recently been introduced in adults with and without acquired heart disease.1 Measurement of the RVOT SE has been shown to be an additional tool to assess RV systolic function in a simple and reproducible way using M-mode echocardiography.1 Various studies suggested the usefulness of determining the RVOT movement as an additional marker of RV function.2 – 6 As the
RVOT contributes to the contraction pattern of the RV, an impaired RVOT function in patients with congenital heart diseases (CHDs) may suggest an impaired overall RV systolic function. Other parameters of RV systolic function such as the tricuspid annular plane systolic excursion (TAPSE) and tricuspid annular peak systolic velocity (S’) have been shown to be good quantitative measures of longitudinal RV systolic function in adults and children with and without CHDs.7 – 13 Guidelines for chamber quantification have recommended the assessment of RV systolic function to be part of the standard echo exam.14 Determination of the RVOT SE might be
* Corresponding author. Tel: +43 316 385 84276; Fax: +43 316 385 13682, E-mail: [email protected] or [email protected] Published on behalf of the European Society of Cardiology. All rights reserved. & The Author 2014. For permissions please email: [email protected]
Downloaded from by guest on November 14, 2015
Quantitative determination of right ventricular (RV) function has gained more interest over the last years. The RV outflow tract systolic excursion (RVOT SE) has been recently proposed as an echocardiographic tool to assess RV systolic function in adults. We aimed to determine growth-related changes of RVOT SE in children and to establish references values. ..................................................................................................................................................................................... Study design A prospective study was conducted in a group of 711 healthy paediatric patients (age: 1 day to 18 years). We determined the effects of age and body surface area (BSA) on RVOT SE values. RVOT SE values were further correlated with the established RV systolic function parameters tricuspid annular plane systolic excursion (TAPSE) and tricuspid annular peak systolic velocity (S’). ..................................................................................................................................................................................... Results The RVOT SE ranged from a mean of 3.4 mm in neonates to 9.5 mm in 18-year-old adolescents. The RVOT SE values showed a positive correlation with age (r ¼ 0.90, P , 0.001) and BSA (r ¼ 0.91, P , 0.001). A significant positive correlation was seen between RVOT SE and TAPSE (r ¼ 0.93, P , 0.001) and also between RVOT SE and S’ (r ¼ 0.86, P , 0.001) in our patients. ..................................................................................................................................................................................... Conclusion RVOT SE provides a simple measure and, in combination with long-axis excursion parameters TAPSE and S’, a comprehensive assessment of RV systolic function. Z-scores of RVOT SE values were calculated, and percentile charts were established to serve as reference data.
981
References values of RVOT SE in 711 healthy children
useful in patients with pressure- or volume-loaded RVs owing to RVOT stenosis or pulmonary regurgitation (PR). As the RVOT SE is easy to perform, safe, and available on all cardiac ultrasound systems, it can be used as a non-invasive measurement to study RV systolic function in children in addition to the recommended RV systolic measurements for the performance of a paediatric echocardiogram.15 Reference values of RVOT SE measurements for the adult population are available.1 We hypothesized that the RVOT SE values of our tested healthy children will increase with increasing age and BSA. In a large paediatric cohort, we undertook a prospective study to determine the normal values for the RVOT SE correlated to age and BSA and calculate normal z-score values with the aim to serve as a reference for the assessment of RVOT systolic function. Our further aim was to determine the value of RVOT SE compared with established age-related echocardiographic parameters for defining longitudinal RV systolic function, such as the TAPSE and the S’.
Methods Ethics
Patient population Patients were selected from healthy individuals referred to our cardiology service from January 2012 to January 2013 for evaluation of a heart murmur or family history of CHD. For the purpose of the study, only echocardiograms with an official reading of a completely normal study except for patent foramen ovale with a diameter of ≤2 mm and trivial left-to-right shunt were accepted for analysis. All patients with CHD or acquired heart disease, family history of cardiomyopathy, chest and thoracic spine deformities, anorexia nervosa, or chromosomal syndromes were excluded from analysis. Patients were examined in a resting state without prior sedation. Infants were allowed to be bottle-fed during the examination.
Echocardiographic techniques Echocardiograms were performed using commercially available echocardiographic system (Sonos iE33, Philips, Andover, MA, USA) using transducers of 5 – 1, 8 – 3, and 12– 4 MHz depending on patient size. Images were recorded digitally and later analysed by one of the investigators (M.K.) using off-line software (Xcelera Echo; Philips Medical Systems, Eindhoven, The Netherlands). (i) RVOT SE was measured from magnified cine-loops of the RVOT area acquired from the parasternal short axis view using M-mode echocardiography. Imaging was performed at the level of the aortic valve at maximal RVOT diameter, with the ultrasound beam perpendicular to the RVOT walls, after optimization of focus, gain, and compression settings as previously described.1 Each data point was averaged from three to five measurements. A representative image of the RVOT SE in an 8-year-old child with normal RV and LV function is shown in Figure 1. (ii) Tricuspid annular peak systolic velocity (S’) was obtained by the following method: pulsed-wave tissue Doppler imaging was performed using transducer frequencies of 3 –8 MHz with spectral Doppler filters adjusted until a Nyquist limit of 15– 20 cm s21. The minimal optimal gain setting was used. Doppler measurements were
acquired with subjects in the left lateral decubitus position during shallow respiration. Guided by the four-chamber view, a 5 mm sample volume was placed at the lateral corner of tricuspid annulus at the attachment of the anterior leaflet of the tricuspid valve. Care was taken to obtain an alignment as parallel as possible to the direction of the tricuspid annular motion. Tricuspid annular peak annular velocities (S’) during systole were recorded and analysed off-line. The resulting velocities were recorded for three to five cardiac cycles and were averaged. (iii) TAPSE was measured by 2D echocardiography-guided M-mode recordings from the apical four-chamber view with the cursor placed at the free wall of the tricuspid annulus as previously described.16 Care was taken to align the sample volume as vertical as possible with respect to the cardiac apex. Angle correction and respiratory gating were not used.
Statistical analysis All data were measured from three well-trained observers (M.K, B.H, and B.N) from three to five consecutive beats and averaged as previously recommended.1,16 For data analysis, SPSS 19 was used. Data are presented as mean + 2 SD. In the first step, the correlation structure between age, BSA, and RVOT SE was analysed with Pearson’s correlation coefficient. For calculation of the BSA, we used the formula of Mosteller.17 Regression was used to estimate RVOT SE from age, BSA, and gender. Models using logarithmic (y ¼ a + b1ln[x]) and square root (y ¼ a + b0.5 1x ) relations were tested. White test and Breusch – Pagan test were used for heteroscedasticity. When significant heteroscedasticity was detected, weighted least square methods were used. Each value was weighted by the inverse residual of the linear regression. To test for normal distribution of Z-scores, Anderson– Darling test (A – D test) and Kolmogorov– Smirnov test (K – S test) were used. For data analysis, SPSS 20 and SAS 9.2 (REG procedure and MODEL procedure) were used. A P-value of ,0.05 was considered statistically significant. TAPSE
Downloaded from by guest on November 14, 2015
This study complies with all institutional guidelines related to patient confidentiality and research ethics including institutional review board approval. There are no financial or other potentially conflicting relationships to report.
Figure 1: The white broken lines indicate M-mode cursor placement at the parasternal short axis view at the level of the aortic valve. The RVOT SE measures the systolic excursion of the RVOT anterior wall. A representative M-mode image of the right ventricular outflow tract systolic excursion (RVOT SE) in an 8-year-old patient with normal right and left ventricular function is shown. The yellow horizontal lines mark the maximum anterior and posterior positions of the RVOT anterior wall during contraction. The vertical red lines mark the upper and lower measure points (mm) on the endocardial surface of the RVOT SE.
982
M. Koestenberger et al.
Table 1
Patients characteristics n
RVOT SE
TAPSE
S’
BSA
70 22
0.34 + 0.05 0.40 + 0.08
0.91 + 0.16 1.22 + 0.29
7.95 + 1.35 8.64 + 1.28
0.21 (0.14– 0.26) 0.27 (0.16– 0.49)
............................................................................................................................................................................... Month 1 2 3
16
0.39 + 0.06
1.29 + 0.16
8.73 + 0.95
0.29 (0.19– 0.38)
4 –6 7 –12
33 38
0.43 + 0.09 0.45 + 0.08
1.31 + 0.21 1.48 + 0.22
9.19 + 1.03 9.73 + 0.95
0.32 (0.26– 0.42) 0.38 (0.27– 0.50)
22 26
0.48 + 0.06 0.53 + 0.08
1.56 + 0.25 1.80 + 0.15
10.31 + 0.60 10.80 + 0.80
0.47 (0.39– 0.57) 0.60 (0.52– 0.70)
Year 2 3 4
36
0.56 + 0.07
1.80 + 0.18
11.02 + 0.88
0.66 (0.56– 1.17)
5 6
25 29
0.58 + 0.07 0.62 + 0.08
1.87 + 0.14 1.93 + 0.12
11.60 + 0.75 11.93 + 0.98
0.73 (0.60– 0.90) 0.81 (0.65– 1.09)
7
23
0.67 + 0.07
1.95 + 0.16
11.99 + 1.03
0.86 (0.77– 1.04)
8 9
25 16
0.67 + 0.08 0.71 + 0.08
2.01 + 0.16 2.00 + 0.17
12.28 + 1.20 12.08 + 0.92
0.92 (0.64– 1.26) 0.99 (0.81– 1.15)
10
31
0.74 + 0.09
2.11 + 0.15
12.49 + 1.05
1.11 (0.92– 1.44)
11 12
40 32
0.75 + 0.09 0.77 + 0.08
2.14 + 0.29 2.23 + 0.26
12.89 + 1.25 12.91 + 0.98
1.23 (1.01– 1.71) 1.36 (1.07– 1.70)
22
0.83 + 0.13
2.17 + 0.22
12.90 + 0.98
1.38 (1.18– 1.70)
37 36
0.86 + 0.11 0.87 + 0.11
2.33 + 0.30 2.24 + 0.23
13.57 + 1.51 13.58 + 1.35
1.55 (1.12– 2.10) 1.53 (0.87– 1.91)
16
39
0.91 + 0.11
2.35 + 0.24
13.93 + 1.11
1.62 (0.85– 2.14)
17 18
40 53
0.92 + 0.11 0.95 + 0.13
2.38 + 0.24 2.43 + 0.28
14.27 + 1.16 14.43 + 1.46
1.68 (1.25– 2.10) 1.74 (1.35– 2.26)
For each age group, the observed number of paediatric patients (n), the observed mean + SD for RVOT SE (cm), TAPSE (cm) and S’ (cm s21) and observed mean with range for BSA (m2) are given. RVOT SE, right ventricular outflow tract systolic excursion; TAPSE, tricuspid annular plane systolic excursion; S’, tricuspid annular peak systolic velocity, BSA, body surface area.
z-scores and S’ z-scores were calculated according to previous data.10,11 To analyse inter-observer reliability, two well-trained observers measured the RVOT SE from three to five consecutive beats and averaged. Therefore, 30 patients were randomly selected. For intra-observer reliability, one well-trained observer measured RVOT SE twice in the same patient. Time between these two measurements ranged between 1 and 5 days. No other analytical method beside intraclass correlation coefficient (ICC) was used. Inter- and intra-observer variability was found for RVOT SE with an intra-class correlation coefficient of 0.97 (CI 0.94– 0.99), P , 0.001, and 0.98 (CI 0.96– 0.99), P . 0.001. Our intra-observer and inter-observer variability was similar than that reported in the literature for the RVOT SE.1
Results The study group consisted of 711 paediatric patients (368 male; 343 female) with a normal echocardiogram. The study group encompassed neonates to adolescents (age: 1 day to 18 years; BSA: 0.14 to 2.26 m2), including 68 term neonates and 111 infants (Table 1). The RVOT SE ranged from a mean of 3.4 mm in neonates to 9.5 mm in 18-year-old adolescents. A significant positive correlation was seen between RVOT SE and TAPSE (r ¼ 0.93, P , 0.001) and also between RVOT SE and S’ (r ¼ 0.86, P , 0.001) in our paediatric
patients. The RVOT SE values increased from neonates to adolescents in a nonlinear way. Figure 2 shows the final model relating RVOT SE to age. Within this model, 85% of the Variance in RVOTSE could be explained by age. The regression equation relating age and RVOT SE is as follows: √ age
RVOT SEpred = e−1.011+0.230×
Age-related z-scores +2 SD and +3 SD for RVOT SE are shown in Table 2. An index was calculated for the RVOT SE for age divided by the BSA. The indexed value declines exponentially. It starts high in the neonates (1.66 cm s21 m22) and declines (0.55 cm s21 m22) to 18 years (Figure 3).The indexed values show that the increase in the absolute RVOT SE value overtime is not solely due to an increase in patient size and actually gets proportionally less in older patients. We did not find a significant difference of RVOT SE normal values between male and female patients. Correlation of RVOT SE z-scores to S’ z-scores values (r ¼ 0.23, P , 0.001) and correlation of RVOT SE z-scores to TAPSE z-scores values (r ¼ 0.19, P , 0.001) were significant but weak (Figure 4).
Downloaded from by guest on November 14, 2015
13 14 15
983
References values of RVOT SE in 711 healthy children
Table 2
Age-related z-scores for RVOT SE RVOT SEpred
22 SD
12 SD
23 SD
13 SD
1 2
0.37 0.38
0.27 0.28
0.50 0.51
0.18 0.19
0.56 0.58
3
0.39
0.29
0.52
0.19
0.59
4 –6 7 –12
0.41 0.43
0.3 0.32
0.54 0.58
0.20 0.22
0.61 0.65
2 3
0.47 0.51
0.35 0.39
0.63 0.68
0.24 0.26
0.70 0.76
4
0.55
0.42
0.72
0.29
0.81
5 6
0.58 0.61
0.44 0.47
0.77 0.80
0.31 0.33
0.86 0.9
7
0.64
0.49
0.84
0.35
0.94
8 9
0.67 0.70
0.52 0.54
0.88 0.92
0.36 0.38
0.98 1.02
10
0.73
0.56
0.95
0.4
1.06
11 12
0.76 0.79
0.58 0.61
0.98 1.02
0.42 0.44
1.10 1.13
13
0.81
0.63
1.05
0.46
1.17
14 15
0.84 0.87
0.65 0.67
1.09 1.12
0.47 0.49
1.21 1.24
16
0.90
0.7
1.15
0.51
1.28
17 18
0.92 0.95
0.72 0.74
1.18 1.22
0.53 0.55
1.32 1.35
................................................................................ Month
Year
Figure 2: Age vs. mean value of right ventricular outflow tract systolic excursion (RVOT SE) +2 or +3 SD for age vs. RVOT SE. The mean is given as the black solid line. The +2 and +3 SD lines are given as the black broken line and black dotted line, respectively.
Within the various portions of the RV, the orientation of the myocardial fibres is different. Inlet and outlet long-axis of the RV are approximately at right angles to each other. Global assessment of the RV is difficult owing to the underlying anatomy.18 Non-invasive quantification of the RV function is, however, still challenging because of the complex geometry of the right ventricle. The RVOT is known to be distinct from the other parts of the RV in embryologic origin19 and in anatomy.20 The RVOT has superficial circumferential muscle fibres, which cause radial RVOT contraction during systole.21 Geva et al.2 have shown that the delay in the regional activation of the RVOT contributes to the peristalsis-like contraction pattern of the normal RV. The RVOT region has shown to be less susceptible to regional RV abnormalities than other areas such as the lateral free wall.14,21 The role of the RVOT contraction pattern has been suggested to be relevant in patients with CHD.22 The RVOT SE directly measures the contraction of the RVOT region.21 We assessed the RV systolic function using the parasternal short axis view for the determination of the RVOT SE, and using the apical four-chamber view for the determination of TAPSE and S’, in order to obtain analysis of the behaviour of both the longitudinal and RVOT systolic contraction. Our intention was to assess a method that can be easily applied and is reliable to provide an assessment of RVOT systolic function. In adults, the largest RVOT SE values were found when RV and LV systolic function are normal.1 The normal value of the RVOT SE in healthy adults is 9.6 + 1.5 mm, whereas in adult patients with reduced RV function the RVOT SE was dramatically decreased at only 1.7 + 1.1 mm. RVOT SE values of ,6 mm identified patients with a reduced RV systolic function with 100% sensitivity and 100% specifity.1 Asmer et al.1 also studied RVOT fractional shortening (FS), a related analysis of the RVOT. The RVOT FS differentiated well between patients with reduced and preserved RV function,
For each age group, the mean (RVOT SEpred) +2 SD and+3 SD according to the regression model are shown. These ranges represent the expectable normal intervals of deviation for a certainty level of 95 and 99%. In this regression model, RVOT SE is estimated by the given age and provides therefore normative data for the whole age range up to the age of 18 years. As a result, RVOT SEpred is continuously increasing. In contrast, observed values are slightly decreasing from the 2nd to the 3rd month, which is due individual outliners in the 2nd and 3rd months (Table 1). In each age group, the mean age was chosen for calculating the predicted mean (e.g. for the third year, the age of 2.5 years was chosen). RVOT SE, right ventricular outflow tract systolic excursion.
but the RVOT SE values have been described to show better differentiation between reduced and preserved RV function. They show that in patients with good LV function, the aorta is pushed anteriorly in systole, contributing to RVOT FS even in the presence of reduced RV function but not contributing to the RVOT SE.1 Lindqvist et al.4 reported that RVOT FS moderately correlated with TAPSE and inversely correlated with RV-right atrial pressure gradient. In patients with repaired tetralogy of Fallot (rTOF), RVOT aneurysm or dyskinesis is relatively common as a result of surgical reconstruction during initial repair. Repaired TOF patients were shown to have impaired systolic function of the RVOT.6 Determination of the RVOT SE might be useful in patients with pressure-loaded right ventricles owing to RVOT obstructions or in cases with pulmonary artery hypertension (PAH). On the other hand, RV volume overload owing to PR following pulmonary valve-sparing operations in patients with Tetralogy of Fallot,23 – 25 other CHD lesions with PR or shunt lesions on atrial level could influence RVOT systolic contraction. In rTOF patients, the systolic contraction of the RVOT and the systolic
Downloaded from by guest on November 14, 2015
Discussion
984
M. Koestenberger et al.
Figure 3: A calculated index of right ventricular outflow tract systolic excursion (RVOT SE) divided by the body surface area (BSA) vs. age. The mean is given as the black solid line. The +2 and +3 SD lines are given as the black broken line and black dotted line, respectively.
Downloaded from by guest on November 14, 2015
contraction of the RV-body are important parts of the global RV systolic function. Greutmann et al.6 found that in rTOF patients (inclusively patients after transannular patch repair) with preserved global systolic RV function, the severely decreased RVOT systolic function can be compensated for an increased radial and transverse shortening of the RV body whereas in rTOF patients with abnormal RV systolic function cannot compensate for the even more pronounced reduced RVOT systolic function by increased contractions of the RV body. Dysfunction of the RVOT may have an impact on the occurrence of ventricular arrhythmias and affects exercise capacity of these patients.26 Therefore, in our opinion, the RVOT SE is worth to measure in all (transannular and valve-sparing method) rTOF patients. We have to state that the RVOT SE in patients after transannular patch repair might behave different to those after a valvesparing procedure, but we support the notion that a reduced RVOT function may have a significant impact on long-time outcomes in all rTOF patients. While in the normal heart, the function of the inflow and outflow components of the RV is closely related,27 this relation has been shown to be weak and unpredictable in rTOF patients.28 The RVOT has also been shown to be the most commonly enlarged dimension in patients with arrhythmogenic RV dysplasia ARVD.29 Yoerger et al. state that a possible enlargement and dysfunction of the RVOT should be one of the main echocardiographic parameters to be investigated when the existence of an ARVD is suspected.29 This supports the notion of recent guideline that the RVOT size and function could be distorted in patients with chest and spine abnormalities.14 The RVOT SE may not reflect the systolic function of the entire RVOT but has the advantage of being a simple M-mode measurement. In clinical practice, this parameter may serve as an additional tool and together with the established longitudinal RV systolic function parameters TAPSE and S’ may provide more complete information of RV systolic function. For example in rTOF patients, both the contraction of the RVOT and that of the
Figure 4: (A) Correlation of the right ventricular outflow tract systolic excursion (RVOT SE) z-score and the S’ z-score in the paediatric age group. (B) Correlation of the right ventricular outflow tract systolic excursion (RVOT SE) z-score and the TAPSE z-score in the paediatric age group. The mean is given as the blue solid line.
RV-body are important determinants of the global RV systolic function. Although the accuracy of echo-determined systolic RV function parameters compared with MRI has been described to be suboptimal30 in patients with hypoplastic left heart syndrome (HLHS), it might be of interest to investigate the behaviour of the RVOT function and size after ventriculotomy in this patient group as it has been demonstrated for strain measurements.31 RVOT SE values of patients with PAH may be significantly different to normal controls, given the theory that the longer the RV suffers from severe pressure overload the more depressed systolic RV function becomes owing to the fact that the RV is not capable to sustain high long-term pressure overload.32 Patients with an atrial septal defect (ASD) usually have a preserved RV function despite mild RV volume overload. In ASD patients with mild left-to-right shunting, no significant differences of RV systolic function parameters such as the TAPSE compared with control subjects were found.12 We have previously shown significant
985
References values of RVOT SE in 711 healthy children
Limitation The relatively small sample size was a limitation of this study. One limitation of our study is that we did not assess the effect of preload variations related to respiration. In paediatric clinical practice, it would be cumbersome to apply respiratory gaiting to this method on a routine basis. RVOT SE has been proposed to be less sensitive to preload and afterload variations owing to the small diameter of the RVOT1 and therefore reduced wall stress according to Laplace’s law but to date conclusive data are missing. The low test– retest variability for a short time period is shown by the high intra-observer reliability (ICC). We have only a limited number of patients with more than one measurement over a longer time period. Therefore, changes in the patient over time could not be analysed. We have to state that it remains unclear how well RVOT SE will perform as an index of RV systolic function in children with CHDs, unless clinical studies will prove its usefulness.
Conclusion RVOT SE is a novel and promising echocardiographic parameter of systolic RV function. We have established normal reference values of RVOT SE in the paediatric age group. The RVOT SE values were lower in neonates and infants compared with older children and adolescents in our study, although RV systolic function was preserved. If
the markedly lower RVOT SE in infants is solely a marker of growth-related changes inside the paediatric population or if it is a sign of possible altered systolic function in infants owing to the immaturity of the ventricular muscle remains unclear. The indexed RVOT SE shows the opposite pattern and starts quite high in the neonates and declines in the adolescent age groups. In future, RVOT SE measurements may be included in the battery of echocardiographic markers in patients with CHD that affect the RV, as an impaired RVOT systolic function in patients with CHDs may suggest an impaired overall RV systolic function.
Funding No extramural funding was used to support this work. The authors are solely responsible for the design and conduct of this study, all study analyses, the drafting and editing of the paper, and its final contents.
Conflict of interest: None declared.
References 1. Asmer I, Adawi S, Ganaeem M, Shehadeh G, Shiran A. Right ventricular outflow tract systolic excursion. A novel echocardiographic parameter of right ventricular function. Eur Heart J Cardiovasc Imaging 2012;13:871 –7. 2. Geva T, Powell AJ, Crawford EC, Chung T, Colan SD. Evaluation of regional differences in right ventricular systolic function by acoustic quantification echocardiography and cine magnetic resonance imaging. Circulation 1998;98:339 –45. 3. Kukulski T, Hubbert L, Arnold M, Wranne B, Hatle L, Sutherland G. Normal regional right ventricular function and its change with age: a Doppler myocardial imaging study. J Am Soc Echocardiogr 2000;13:194–204. 4. Lindqvist P, Henein M, Kazzam E. Right ventricular outflow-tract fractional shortening: an applicable measure of right ventricular systolic function. Eur J Echocardiography 2003;4:29 –35. 5. Kutty S, Zhou J, Gauvreau K, Trincado C, Powell AJ, Geva T. Regional dysfunction of the right ventricular outflow tract reduces the accuracy of Doppler tissue imaging assessment of global right ventricular systolic function in patients with repaired tetralogy of Fallot. J Am Soc Echocardiogr 2011;24:637 –43. 6. Greutmann M, Tobler D, Biaggi P, Mah ML, Crean A, Wald RM et al. Echocardiography for assessment of regional and global right ventricular systolic function in adults with repaired tetralogy of Fallot. Int J Cardiol 2012;157:53 –8. 7. Meluzin J, Spinarova L, Bakala J, Toman J, Krejcı´ J, Hude P et al. Pulsed Doppler tissue imaging of the velocity of tricuspid annular systolic motion; a new, rapid, and noninvasive method of evaluating right ventricular systolic function. Eur Heart J 2001; 22:340–8. 8. Saxena N, Rajagopalan N, Edelman K, Lo´pez-Candales A. Tricuspid annular systolic velocity: a useful measurement in determining right ventricular systolic function regardless of pulmonary artery pressures. Echocardiography 2006;23:750 –5. 9. Koestenberger M, Nagel B, Ravekes W, Everett AD, Stueger H, Heinzl B et al. Systolic right ventricular (RV) function in pediatric and adolescent patients with TOF: echocardiography versus MRI. J Am Soc Echocardiogr 2011;24:45–52. 10. Koestenberger M, Nagel B, Ravekes W, Avian A, Heinzl B, Cvirn G et al. Reference values of the tricuspid annular peak systolic velocity in healthy pediatric patients, calculation of z-score values, and comparison to the tricuspid annular plane systolic excursion. Am J Cardiol 2012;109:116–21. 11. Koestenberger M, Ravekes W, Everett A, Stueger H, Heinzl B, Gamillscheg A et al. Right ventricular function in infants, children and adolescents: reference values of the tricuspid annular plane systolic excursion (TAPSE) in 640 healthy patients and calculation of z-score values. J Am Soc Echocardiogr 2009;22:715–19. 12. Koestenberger M, Nagel B, Ravekes W, Everett AD, Stueger H, Heinzl B et al. Tricuspid annular plane systolic excursion (TAPSE) and right ventricular ejection fraction in pediatric and adolescent patients with tetralogy of Fallot, patients with atrial septal defect, and age-matched normal subjects. Clin Res Cardiol 2011;100:67– 75. 13. Koestenberger M, Nagel B, Ravekes W, Avian A, Heinzl B, Fandl A et al. Tricuspid annular peak systolic velocity (S’) in children and young adults with pulmonary artery hypertension secondary to congenital heart diseases, and in those with repaired tetralogy of fallot: echocardiography and MRI data. J Am Soc Echocardiogr 2012;25:1041 – 9. 14. Rudski LG, Lai WW, Afilalo J, Hua L, Handschumacher MD, Chandrasekaran K, Solomon SD et al. Guidelines for the echocardiographic assessment of the right heart in adults: a report from the American Society of Echocardiography endorsed by the European Association of Echocardiography, a registered branch of the
Downloaded from by guest on November 14, 2015
growth-related changes for the longitudinal RV systolic function parameters S’ and TAPSE,10,11,33 and therefore, we expected significant growth-related changes for RVOT SE. Before determining possible reductions of RVOT SE in patients with HLHS, PAH, or ASD, sufficient quantitative reference data of echocardiographic normal patients from infants to large adolescents are required. We found that RVOT SE values increase with age and BSA. Recently, Willis et al.34 demonstrated in 205 healthy adults that the BSA plays an important part in the determination of normal RV reference values. RVOT SE is affected by increasing age and increasing BSA with a steeper course of the curve in neonates and infants when compared with older children and adolescents. As expected, our normal values for RVOT SE in the older adolescents are very similar to adult RVOT SE normal reference data.1 The difference between the high correlation of RVOT SE and TAPSE or S’ and the weak correlation between RVOT SE z-scores and TAPSE or S’ z-scores reflects the age dependency of all of these parameters. Owing to the strong age dependency of all of these parameters, the high correlations of the actual measurements do reflect the age dependency of these measurements more than the direct association of these measurements. This suggests the growth-related changes in normal values to be similar for parameters of longitudinal RV systolic function and for the RVOT SE but demonstrates that the RVOT SE does not provide the same information about RV behaviour as the longitudinal RV systolic function parameters. In our opinion, an explanation might be the different age-related increase of TAPSE, S’, and RVOT SE values during childhood. Measuring RVOT SE consequently gives us additional information of what is a ‘normal’ systolic function for the healthy paediatric RVOT and together with TAPSE and S’ provides an assessment of RV systolic function in the paediatric age group.
986
15.
16.
17. 18. 19.
20. 21.
22. 23.
24.
European Society of Cardiology, and the Canadian Society of Echocardiography. J Am Soc Echocardiogr 2010;23:685 –713. Lopez L, Colan SD, Frommelt PC, Ensing GJ, Kendall K, Younoszai AK et al. Recommendations for quantification methods during the performance of a pediatric echocardiogram: a report from the Pediatric Measurements Writing Group of the American Society of Echocardiography Pediatric and Congenital Heart Disease Council. J Am Soc Echocardiogr 2010;23:465 –95. Lee CY, Chang SM, Hsiao SH, Tseng JC, Lin SK, Liu CP. Right heart function and scleroderma: insights from tricuspid annular pane systolic excursion. Echocardiography 2007;24:118–25. Mosteller RD. Simplified calculation of body-surface area. N Engl J Med 1987;317: 1098. Redington AN. Right ventricular function. Cardiol Clin 2002;20:341 –9. Sugishita Y, Watanabe M, Fisher SA. The development of the embryonic outflow tract provides novel insights into cardiac differentiation and remodelling. Trends Cardiovasc Med 2004;14:235 –41. Dell’Italia LJ. The right ventricle: anatomy, physiology, and clinical importance. Curr Probl Cardiol 1991;16:653–720. Haddad F, Hunt SA, Rosenthal DN, Murphy DJ. Right ventricular function in cardiovascular disease, part I: anatomy, physiology, aging, and functional assessment of the right ventricle. Circulation 2008;117:1436 –48. Bashore TM. Adult congenital heart disease: right ventricular outflow tract lesions. Circulation 2007;115:1933 –47. Bove T, Bouchez S, De Hert S, Wouters P, De Somer F, Devos D et al. Acute and chronic effects of dysfunction of right ventricular outflow tract components on right ventricular performance in a porcine model: implications for primary repair of tetralogy of fallot. J Am Coll Cardiol 2012;60:64–71. Bove´ T, Franc¸ois K, Van De Kerckhove K, Panzer J, De Groote K, De Wolf D et al. Assessment of a right-ventricular infundibulum-sparing approach in transatrial – transpulmonary repair of tetralogy of fallot. Eur J Cardiothorac Surg 2012;41:126 – 33.
M. Koestenberger et al.
25. Morales DL, Zafar F, Heinle JS, Ocampo EC, Kim JJ, Relyea K et al. Right ventricular infundibulum sparing (RVIS) tetralogy of fallot repair: a review of over 300 patients. Ann Surg 2009;250:611 –7. 26. Wald RM, Haber I, Wald R, Valente AM, Powell AJ, Geva T. Effects of regional dysfunction and late gadolinium enhancement on global right ventricular function and exercise capacity in patients with repaired tetralogy of fallot. Circulation 2009; 119:1370 –7. 27. Lytrivi ID, Ko HH, Srivastava S, Norton K, Goldman J, Parness IA et al. Regional differences in right ventricular systolic function as determined by cine magnetic resonance imaging after infundibulotomy. Am J Cardiol 2004;94:970–3. 28. Bodhey NK, Beerbaum P, Sarikouch S, Kropf S, Lange P, Berger F et al. Functional analysis of the components of the right ventricle in the setting of tetralogy of Fallot. Circ Cardiovasc Imaging 2008;1:141–7. 29. Yoerger DM, Marcus F, Sherill D, Calkins H, Towbin JA, Zareba W et al. Echocardiographic findings in patients meeting task force criteria for arrhythmogenic right ventricular dysplasia. J Am Coll Cardiol 2005;45:860 –5. 30. Bellsham-Revell HR, Simpson JM, Miller OI, Bell AJ. Subjective evaluation of right ventricular systolic function in hypoplastic left heart syndrome: how accurate is it? J Am Soc Echocardiogr 2013;26:52 –6. 31. Menon SC, Erickson LK, McFadden M, Miller DV. Effect of ventriculotomy on rightventricular remodeling in hypoplastic left heart syndrome: a histopathological and echocardiography correlation study. Pediatr Cardiol 2013;34:354 –63. 32. Bogaard HJ, Abe K, Vonk Noordegraaf A, Voelkel NF. The right ventricle under pressure: cellular and molecular mechanisms of right-heart failure in pulmonary hypertension. Chest 2009;135:794–804. 33. Koestenberger M, Nagel B, Ravekes W, Urlesberger B, Raith W, Avian A et al. Systolic right ventricular function in preterm and term neonates: reference values of the tricuspid annular plane systolic excursion (TAPSE) in 258 patients and calculation of z-score values. Neonatology 2011;100:85 –92. 34. Willis J, Augustine D, Shah R, Stevens C, Easaw J. Right ventricular normal measurements: time to index? J Am Soc Echocardiogr 2012;25:1259 –67. Downloaded from by guest on November 14, 2015
