Reference values of tricuspid annular peak systolic velocity in healthy pediatric patients, calculation of z score, and comparison to tricuspid annular plane systolic excursion.

Abstract

The tricuspid annular peak systolic velocity (TAPSV) is an echocardiographic measurement assessing right ventricular systolic function in children and adults. We determined the growth-related changes of the TAPSV to establish the references values for the entire pediatric age group. A prospective study was conducted of a group of 860 healthy pediatric patients (age 1 day to 18 years; body surface area [BSA] 0.14 to 2.30 m(2)). We determined the effects of age, gender, and BSA on the TAPSV values. Stepwise linear multiple regression analysis was used to estimate the TAPSV from the age, BSA, and gender. A correlation of normal TAPSV with normal tricuspid annular plane systolic excursion values was performed. The TAPSV ranged from a mean of 7.2 cm/s (z score ± 2: 4.8 to 9.5 cm/s) in the newborn to 14.3 cm/s (z score ± 2: 10.6 to 18.6 cm/s) in the 18-year-old adolescent. The TAPSV values showed a positive correlation with age and BSA, with a nonlinear course. No significant difference was found in the TAPSV values according to gender. A significant correlation was found between the TAPSV and tricuspid annular plane systolic excursion values in our pediatric population. In conclusion, the z scores of the TAPSV values were calculated, and percentile charts were established to serve as reference data for patients with congenital heart disease.

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TricuspidAnnularPeakSystolicVelocity(S0)inChildren
and Young Adults with Pulmonary Artery Hypertension
Secondary to Congenital Heart Diseases, and in Those
with Repaired Tetralogy of Fallot: Echocardiography
and MRI Data
Martin Koestenberger, PhD, MD, Bert Nagel, MD, William Ravekes, MD, Alexander Avian, MSc,
Bernd Heinzl, MD, Andrea Fandl, MD, Thomas Rehak, MD, Erich Sorantin, MD, Gerhard Cvirn, PhD,
and Andreas Gamillscheg, MD, Graz, Austria; Baltimore, Maryland
Background: Tricuspid annular peak systolic velocity (S0), as an echocardiographic index to assess right ven-
tricular (RV) systolic function, has not been investigated thoroughly in children and young adults with repaired
tetralogyofFallot(TOF)andpulmonaryarteryhypertensionsecondarytocongenitalheartdisease(PAH-CHD).
Methods: S0values in patients with TOF (n = 183) and PAH-CHD (n = 55) were compared with those in normal
subjects. S0values were compared with RV ejection fraction and RV end-diastolic volume index (RVEDVi)
determined by magnetic resonance imaging.
Results: S0values became significantly reduced in PAH-CHD patients after 10.4 years of age and after
13.6 years of age in patients with TOF compared with the lower boundary of the 62-SD interval of normal
subjects. Significant positive correlations between S0and RV ejection fraction were seen in patients with
TOF (r =0.66,P <.001)and thosewith PAH-CHD(r =0.82,P <.001). Significant negative correlations between
S0and RVEDVi were also seen in patients with repaired TOF (r = ?0.29, P = .002) and in those with PAH-CHD
(r = –0.59, P < .001).
Conclusions: Although initially preserved, in this prospective study, impaired S0values with increasing age
were found in patients with repaired TOF and PAH-CHD. Persistent pressure overload in patients with
PAH-CHD as well as volume overload in those with repaired TOF might lead to systolic RV functional impair-
ment and increased RVEDVi. The validity of S0data was supported by magnetic resonance imaging data
(RVEDVi and RV ejection fraction). (J Am Soc Echocardiogr 2012;-:---.)
Keywords: Tricuspid annular peak systolic velocity, Right ventricular systolic function, Indexed end-diastolic
volume, Magnetic resonance imaging, Pediatric patients, Tetralogy of Fallot, Pulmonary artery hypertension
secondary to congenital heart disease
In patients with repaired tetralogy of Fallot (TOF), pulmonary
regurgitation is common after surgical relief of right outflow tract ob-
struction using a transannular patch and may lead to progressive right
ventricular (RV) dilatation and dysfunction with age.1Assessing RV
volume and systolic function in these patients is of interest.
Recently, quantification of RVsize and function by echocardiography
hasbeencomparedwithangiography2andmagneticresonanceimag-
ing (MRI).3RV volumes determined by three-dimensional echocardi-
ography were found to be comparable to MRI data.4New indices for
the assessment of RV function have been published, including tricus-
pid annular plane systolic excursion (TAPSE)5and tricuspid annular
peak systolic velocity (S0).6S0, measured using Doppler tissue imaging
(DTI), has been suggested as a good quantitative parameter of RV
systolic function.6,7Studies of pulsed-wave DTI measurements of S0
have been reported in children.8-10Reference values and calculated
Z-score values of S0in healthy pediatric patients have been
determined recently.11A few newer studies have shown that S0
may be a reproducible index of systolic RV function in patients
with congenital heart disease (CHD).12,13Still, little is known about
S0values in pediatric and young adult patients with repaired TOF
or with pulmonary artery hypertension (PAH) secondary to CHD
(PAH-CHD).
From the Division of Pediatric Cardiology, Department of Pediatrics (M.K., B.N.,
B.H., A.F., T.R., A.G.), the Institute for Medical Informatics, Statistics and
Documentation (A.A.), the Division of Pediatric Radiology, Department of
Radiology (E.S.), and the Institute of Physiological Chemistry, Centre of
Physiological Medicine (G.C.), Medical University Graz, Graz, Austria; the
Division of Pediatric Cardiology, Johns Hopkins University School of Medicine,
Baltimore, Maryland (W.R.).
Reprint requests: Martin Koestenberger, PhD, MD, Medical University Graz, De-
partment of Pediatrics, Auenbruggerplatz 34/2, A-8036 Graz, Austria (E-mail:
martin.koestenberger@medunigraz.at).
0894-7317/$36.00
Copyright 2012 by the American Society of Echocardiography.
http://dx.doi.org/10.1016/j.echo.2012.06.004
1

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The primary aim of this study
was to determine S0values in pe-
diatric patients and young adults
with RV volume overload (TOF)
and severe pressure overload
(PAH-CHD) and to compare
with normal values in a cross-
sectional study design. A second-
ary aim was to compare these S0
values with the RV ejection
fraction (RVEF) and RV end-
diastolic volume index (RVEDVi)
values measured by MRI. The fi-
nal aim was to compare RVEF
and RVEDVi values with age in
children and young adults with
PAH-CHD and TOF.
METHODS
Patient Population
All patient data were collected in
a prospective manner at our
institutions.
Group 1 consisted of 55 pa-
tientswithPAH-CHD
range, 0.6–34 years; mean age,
13.2 years; 34 male, 21 female;
body surface area [BSA] range,
(age
0.35–2.08 m2). Thirty-one patients with PAH-CHD were aged
# 18 years, and 24 were aged > 18 years. Patients with PAH were
all associated with CHD according to the 2009 updated clinical clas-
sification of pulmonary hypertension (group 1.4.4).14The cardiac di-
agnoses and the baseline characteristics of the patients are shown in
Table 1. Patients with more than moderate atrioventricular valve re-
gurgitation or conduit regurgitation were excluded from this study.
The respective CHDs were repaired in all patients at a mean age of
5.4 months (range, 0.5–15.8 months). None of our patients had
Eisenmenger syndrome, the most advanced form of PAH-CHD. At
the time of enrollment, all patients were in clinically stable condition,
with no new medications started within the previous 3 months.
Echocardiographic studies were performed in a cross-sectional man-
ner over a wide range of intervals between operation and the time
of echocardiography. All these patients had measurable mild to mod-
erate tricuspid regurgitation (TR) jets; patients with severe TR were
excluded from the study. RV systolic pressure was assessed by TR ve-
locity (calculated from the modified Bernoulli equation).15TR veloc-
ity > 2.8 m/sec (corresponding to a right atrioventricular pressure
gradient > 31 mm Hg) is considered a reasonable cutoff to define el-
evated pulmonary pressures in the absence of pulmonary stenosis.16
TR was measured in all of our patients at least as half of systemic sys-
tolic pressure, apart from three patients in whom mild TR made it im-
possible to obtain reliable data. Twenty-seven of our patients with
PAH-CHD (49% of all patients) underwent MRI. The time interval
between the MRI and echocardiography had a mean of 37 days
(range 0 to 117 days). All patients underwent right-heart catheteriza-
tion, which remains the gold standard for diagnosing PAH. Left-sided
filling pressure and cardiac output data were obtained to rule out en-
tities that can elevate pulmonary artery pressure other than pulmo-
nary vascular disorders, such as pulmonary venous hypertension.
PAH was defined as a mean pulmonary artery pressure $ 25 mm
Hg at rest, a pulmonary capillary wedge pressure < 15 mm Hg, and
pulmonary vascular resistance $ 3 mm (Wood units ? BSA
[m2]).17By directly measuring pressures and indirectly measuring
flow,wedeterminedmarkerssuchascardiacoutput(usingFick’sprin-
ciple), mixed venous oxygen saturation, and mean pulmonary artery
pressure. Right-heart catheterization data were as follows: mean pul-
monary artery pressure ranged from 30 to 65 mm Hg (mean, 39.2
mm Hg) at rest, pulmonary vascular resistance ranged from 3.8 to
20.2 Wood units ? BSA (m2) (mean, 5.6 Wood units ? BSA [m2]),
and mean mixed venous oxygen saturation was 65 6 9% in all
patients with PAH-CHD (Table 1). The time interval between right-
heart catheterization and echocardiography ranged from 0 to 52
days. All patients had RV systolic pressure $62% of systemic systolic
pressure. Twelve patients with initial diagnostic catheterization at the
time of this study underwent first-time vasodilator testing.
Group2consistedof183patientswithrepairedTOF(79male,104
female) who were undergoing routine clinical follow-up. The RV
outflow tract was repaired by means of a transannular patch made
of autologous untreated pericardium in all patients at a mean age of
8.7 months (range, 3.3–18.9 months). The patients were evaluated
from the newborn age to the age of 34 years (mean age, 15.2 years).
Echocardiographic studies were performed in a cross-sectional man-
ner over a wide range of intervals between operation and the time
of echocardiography. One hundred five patients with TOF were
aged # 18 years, while 78 patients were aged > 18 years. Patients
in group 2 had a mild mean residual RV outflow tract gradient of
16 6 8 mm Hg, as determined by routine echocardiography. The
baseline characteristics of the patients and their medications are
shown in Table 2. Patients with repaired TOF with higher degrees
ofRVoutflowtractobstructionorvalvularorpulmonaryarterybranch
stenosis were excluded from the study. In 33 patients (18% of all pa-
tients with TOF), RVoutflow tract aneurysms were present. Thirteen
patientswithrestrictivephysiologyoftherightventricle,definedasthe
presence of laminar antegrade diastolic main pulmonary artery flow
throughout the respiratory cycle by Doppler echocardiography,18
were excluded from the study. We used previous MRI data of 41 pe-
diatric patientswithTOF19,20(i.e., 37%of111studypatientshadMRI
scansavailableforthe currentstudy),whileallechocardiographicdata
were acquired solely for this study. Thirty-nine patients (21% of all
patients with TOF) underwent aortopulmonary shunt procedures
before surgical repair. In 111 patients (61% of all patients with TOF),
S0could be compared with RVEF and RVEDVi measured by MRI.
The time interval between MRI and echocardiography ranged from
0 to 43 days. Recordings and measurements of S0, RVEDVi, and
RVEF were performed without and with access to MRI data.
Group 3 consisted of 849 healthy patients (428 male, 421 female)
with normal results on echocardiography and measured S0values in-
side the previously published age-related normal Z-score range.11
Patients were selected from individuals referred to our cardiology ser-
viceforevaluationofheartmurmursorfamilyhistoryofheartdisease.
The study group encompassed neonates to adolescents (age range, 1
day to 18 years; BSA range, 0.18–2.30 m2) and was compared with
our patients with PAH-CHD and TOF. For the purposes of the study,
only echocardiograms with official readings of completely normal re-
sults or completely normal results except for patent foramen ovale
with diameter # 2 mm were accepted for analysis. All patients with
CHD, acquired heart disease, 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.
Abbreviations
BSA = Body surface area
CHD = Congenital heart
disease
CI = Confidence interval
DTI = Doppler tissue imaging
MRI = Magnetic resonance
imaging
PAH = Pulmonary artery
hypertension
PAH-CHD = Pulmonary
arteryhypertensionsecondary
to congenital heart disease
RV = Right ventricular
RVEDVi = Right ventricular
end-diastolic volume index
RVEF = Right ventricular
ejection fraction
TAPSE = Tricuspid annular
plane systolic excursion
TOF = Tetralogy of Fallot
TR = Tricuspid regurgitation
2 Koestenberger et al
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Echocardiographic Techniques
Echocardiography was performed using the Sonos iE33 echocardio-
graphic system (Philips Medical Systems, Andover, MA) with trans-
ducers of 5-1, 8-3, and 12-4 MHz depending on patient size.
Images were recorded digitally and later analyzed by one of the
investigators (M.K.) using offline software (Xcelera Echo; Philips
Medical Systems, Eindhoven, The Netherlands).
Pulsed-wave DTI was performed using transducer frequencies of
2.5 to 3.5 MHz with spectral Doppler filters adjusted until a Nyquist
limit of 15 to 20 cm/sec was reached. The minimal optimal gain set-
ting was used. Doppler measurements were acquired with subjects
in the 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, exactly at the attachment
of the anterior leaflet of the tricuspid valve. Care was taken to ob-
tain an ultrasound beam parallel to the direction of tricuspid annular
motion. Peak annular velocities during systole were recorded and
analyzed offline. The resulting velocities were recorded for three
to five cardiac cycles and were averaged. To assess day-to-day
variability of S0, pulsed-wave DTI was repeated 24 hours later under
the same conditions in 22 subjects. The investigation of S0was
performed in a quiet state. RV conditions were assessed. Patients
were classified as having RV pressure overload on the basis of
elevated TR velocities, RV outflow tract gradients, and/or systolic
septal flattening.
MRI
RV volumes were quantified by means of breath-hold cine steady-
state free precession sequences in 111 patients with repaired TOF
and 27 patients with PAH-CHD using a 1.5-T machine (Symphony;
Table 1 Demographic data of patients with PAH-CHD
VariableValue
All (outpatients)
Patients fulfilling inclusion criteria
Female
Age (y), mean (range)
BSA (m2), range
New York Heart Association
functional class
I
II
III
Time of surgical repair (mo),
mean (range)
Diagnosis
Atrioventricular septal defect
VSD
Pulmonary atresia with VSD
Total anomalous pulmonary
venous return
Treatment
Bosentan
Bosentan plus sildenafil
Sildenafil
Calcium antagonists
Furosemide
Warfarin
Echocardiography
S0data available
Mild TR
Moderate TR
MRI
Patients with PAH
RVEDVi (mL/m2), mean 6 (range)
RVEDVi > 150 mL/m2(% of measured)
RVEF (%)
>50
40–50
30–40
<30
Electrocardiography
Patients with PAH
QRS duration (msec), mean 6 (range)
QRS duration $ 180 msec
(% of measured)
Right-heart catheterization
Mean pulmonary artery pressure
(mm Hg), mean (range)
Pulmonary vascular resistance
(Wood units), mean (range)
Mixed venous saturation (%),
mean 6 SD
94
55
21
13.2 (0.6–34)
0.35–2.08
11
26
12
5.4 (0.5–15.8)
23
16
11
5
11
15
17
6
21
12
55
16
39
27
147.3 6 40.2 (87–238)
13 (48%)
3
9
11
4
49
126 6 33 (80–220)
4 (8.2%)
39.2 (30–65)
5.6 (3.8–20.2)
65 6 9
VSD, Ventricular septal defect.
Table 2 Demographic data of patients with TOF
VariableValue
All (outpatients)
Patients fulfilling inclusion criteria
Female
Age (y), mean (range)
BSA (m2), range
New York Heart Association functional
class
I
II
Time of surgical repair (mo), mean
(range)
Aortopulmonary shunts (% of
measured)
Echocardiography
S0data available
Residual pulmonary stenosis (mm Hg),
mean 6 SD
MRI
Patients with TOF
RVEDVi (ml/m2), mean 6 SD (range)
RVEDVi > 150 mL/m2(% of measured)
Regurgitation fraction (%), mean 6 SD
(range)
Electrocardiography
QRS duration (msec), mean 6 SD
(range)
QRS duration $ 180 msec (% of
measured)
296
183
104
15.2 (0–34)
0.18–2.30
131
52
8.7 (3.3–18.9)
39 (21%)
183
16 6 8
111
140.6 6 37.9 (69–228)
43 (38.1%)
38.8 6 15.5 (18–71)
153 6 26 (70–210)
11 (7%)
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Siemens Medical Systems, Forchheim, Germany). Patients with
implantable cardioverter-defibrillators were excluded from this study
because MRI is contradicted in patients with such implants. The right
ventricle was encompassed by means of continuous short-axis views
from base to apex. RV volumes were calculated after delineation of
the endocardial surfaces of the end-diastolic and end-systolic images.
Multiplication of the delineated cavity area by the slice thickness
yielded the slice volume, and summation of all slice volumes yielded
ventricularvolumeatend-diastoleandend-systole.ValuesofRVEDVi
> 150 mL/m2were defined on the basis of MRI data reported for
adults and adapted for the pediatric age group, corresponding to
150% of the upper limit of normal for RVEDVi in children, which is
100 mL/m2.21Pulmonary regurgitation was quantified by velocity-
encoded imaging. The regurgitation fraction was determined by
calculating the percentage of reverse volume from forward volume.
All volume and flow measurements were indexed for BSA and ex-
pressed as milliliters per beat per square meter. Measurements were
made by E.S. blinded to the echocardiographic data.
Statistical Analysis
All S0data were measured by three well-trained observers (M.K, B.H.,
and B.N.) from three to five consecutive beats and averaged. For data
analysis, SPSS version 19 (SPSS, Inc., Chicago, IL) and SAS version
9.2 (SAS Institute Inc., Cary, NC) were used. Data are presented
as mean 6 2 SDs. In a first-step analysis in the healthy controls,
the correlation between age and S0was analyzed using Pearson’s
correlation coefficient. A regression was used to estimate in healthy
patients S0from age. In a second step in patients with PAH-CHD and
TOF, the deviation from normal S0values was calculated. A regres-
sion was used to estimate in patients with PAH-CHD and repaired
TOF the deviation of normal S0from age. The cutoff value for this
age, at which the S0value in patients with PAH-CHD and repaired
TOF is lower than the reference value, was taken from this linear
regression analysis. This was done by using the lower bound of the
62-SD interval of the mean value of normal S0. The correlation
structure between age and MRI-determined RVEF and RVEDVi in
the TOF and PAH-CHD groups was analyzed using Pearson’s corre-
lation coefficient.
Interobserver variability was also assessed. Data were measured by
two observers (M.K. and B.N.) who were blinded to each other’s
results. Intraobserver variability was considered in 24 participants
by repeating the measurements on two occasions. Interobserver
and intraobserver variability was found for S0, with intraclass correla-
tion coefficients of 0.97 (confidence interval [CI], 0.94–0.99; P <
.001) and 0.98 (CI, 0.96–0.99; P < .0001). Intraobserver and interob-
server variability in our study was similar to that reported in the
literature for S0.6,22
Ethics
This study was in compliance with all institutional guidelines related
to patient confidentiality and research ethics, including institutional
review board approval (EK-Nr. 23-059 ex 11/12).
RESULTS
Data from Healthy Subjects
S0and age were correlated in our control group: Pearson’s correlation
coefficient was 0.64 for age and S0(P < .001) and 0.67 for BSA and S0
(P<.001).Therewasnostatisticallysignificantdifference ofnormalS0
values between female and male patients (P = .95). Normal S0values
increase with age, as shownpreviously.11Regression analysis revealed
that 56.9% of the variance in S0could be explained using a regression
model by age alone. These results show that adding BSA resulted in
only a minor increase of explained variance (57.1%). The regression
equation relating age and predicted S0in healthy patients was pre-
dicted S0= 7.599 + 3.157 ? age1/2? 0.414 ? age. For calculating
CIs, the residual SD of 1.7 was used.
S0Values in Patients with PAH-CHD and Repaired TOF
A representative image of S0in an 18-year-old patient with PAH-
CHD and a 16-year-old adolescent is shown in Figure 1. For patients
up to 18 years of age, S0was analyzed by calculating the deviation to
normal to the age S0values as estimated above (S0D). For patients
aged > 18 years, the deviation to the maximum predicted S0value
of patients aged 18 years (13.5 cm/sec) was used. S0Dvalues in
patients with PAH-CHD and in those with repaired TOF showed
significantly different courses compared with normal controls. In
patients with PAH-CHD, a negative correlation (r = ?0.76, P <
.001) was found between increasing age and S0Dvalues (Figure 2).
In patients with repaired TOF, a negative correlation (r = ?0.69,
P < .001) was found between age and S0Dvalues (Figure 2). By re-
gression analysis, 71.2% of the variance in S0D in patients with
PAH-CHD and 62.7% of the variance in S0Din patients with TOF
could be explained. Considering values outside of the 62-SD
interval of S0in healthy subjects, the age at which patients with
PAH-CHD and repaired TOF leave this interval was calculated.
Therefore, the regression equation of S0D for patients with
PAH-CHD and repaired TOF was used. S0values in patients with
PAH-CHD were significantly reduced after 10.4 years of age, and
S0values in patients with repaired TOF were significantly reduced
after 13.6 years of age compared with the lower bound of the
?2-SD interval of normal controls (Figure 2).
MRI Data of Patients with PAH-CHD and Repaired TOF
For patients with PAH-CHD, the data were as follows: RV volume
overload was seen by a mean RVEDVi of 147.3 6 40.9 mL/m2
(range, 87–238 mL/m2) in all of our 27 patients with PAH-CHD
(mean age, 14.8 years) measured by MRI (Table 1). The correlation
coefficient between RVEDVi and S0was r = ?0.59 (CI, ?0.79 to
?0.27; P < .001) and between RVEDVi and S0Dwas r = ?0.64
(CI,?0.82to?0.35;P< .001)(Figure3). RVEFswere>50%inthree
patients, between 40% and 50% in nine patients, between 30% and
40% in 11 patients, and #30% in four patients with PAH-CHD. A
positive correlation between RVEF and S0(r = 0.82; CI, 0.64 to
0.91; P < .001) and a positive correlation between RVEF and S0D
(r = 0.88; CI, 0.75 to 0.95; P < .001) was seen in all patients with
PAH-CHD (Figure 4). A positive correlation was observed between
age and RVEDVi (r = 0.71; CI, 0.46 to 0.86; P < .001) in all patients
with PAH-CHD (Figure 5), and a negative correlation (r = ?0.71; CI,
?0.85 to ?0.45; P < .001) was seen between age and RVEF
(Figure 6).
For patients with repaired TOF, the data were as follows: With in-
creasing postoperative period, significant RV volume overload was
seen (mean RVEDVi, 140.6 6 37.9 mL/m2; range, 69–228 mL/m2),
as measured in all of our 111 patientswithTOF (mean age,16.1 years)
whounderwent MRI (Table 2). The correlation between RVEDVi and
S0Dwas r = ?0.35 (CI, ?0.50 to ?0.18; P < .001) and between
RVEDVi and S0was r = ?0.29 (CI, ?0.45 to ?0.11; P = .002) in
4 Koestenberger et al
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repaired patients with TOF (Figure 3). Positive correlations were seen
between RVEF and S0(r = 0.66; CI, 0.54 to 0.75; P < .001) and
between RVEF and S0D(r = 0.70; CI, 0.58 to 0.78; P < .001) in all
patients with TOF (n = 111) investigated by MRI (Figure 4). A positive
correlation was observed between age and RVEDVi (r = 0.29; CI,
0.11 to 0.45; P < .002; Figure 5), and a negative correlation (r =
–0.47; CI, ?0.60 to ?0.31; P < .001) was seen between age and
RVEF (Figure 6).
DISCUSSION
The systolic velocity of the tricuspid annulus of the RV free wall has
been shown to be a reliable indicator of global RVsystolic function.5,6
The tricuspid annulus has been shown to have the greatest motion
along its lateral aspect in healthy adults.23Harada et al.13showed
that for patients with TOF after surgical repair, the mean velocity
during systolic ejection was lower compared with control subjects.
In a group of 22 patients who underwent surgical repair of TOF,
decreased RV myocardial velocity compared with control subjects
was demonstrated.24Meluzin et al.6demonstrated that S0< 11.5
cm/sec can predict RV impairment in adults. A similar cutoff value
(S0< 10.8 cm/sec) was found in adults to be a predictor of poor prog-
nosis in patients with dilated cardiomyopathy.25,26
published guidelines for the assessment of right-heart function in
the adult population confirmed that S0, measured by DTI, is a simple
and reproducible measure to assess basal free wall function, and they
recommend that S0< 10 cm/sec should raise suspicion for abnormal
RV function.27
Normal S0values have recently been published for healthy chil-
dren,11and S0has been reported to be abnormal in patients with
CHD.28Wefound that S0valuescorrelate with TAPSE measurements
Recently
Figure 1 Apical four-chamber view. The white broken line indicates M-mode cursor placement at the tricuspid lateral annulus. Rep-
resentative image of DTI-measured S0in an 18-year-old patient with PAH-CHD (A) and in a 16-year-old healthy adolescent (B).
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in healthy pediatric subjects.11Similar to our data, a significant corre-
lation between S0and TAPSE has been shown in adults with PAH.7
Because this group compared its data with adult values, this conse-
quently cannot be extrapolated to children. The correlation of S0
and TAPSE in our children was shown to be significant but weak
(r = 0.260).11An explanation might be the different age-related in-
crease of TAPSE and S0values during childhood. In our opinion, con-
sequently, one measurement cannot replace the other for the
appropriate determination of systolic RV function in a pediatric pop-
ulation. So far, S0has not been prospectively investigated for RVfunc-
tion assessment in a sizable pediatric population with repaired TOF
and/or PAH-CHD.
AbdelRahmanetal.29showedpersistentpostoperativeRVsystolic
and diastolic dysfunction in postoperative patients with TOF. In our
patients with repaired TOF, who underwent surgical repair in early
life,S0wasfoundtobesignificantlyreducedcomparedwithpublished
normal values11when measured in a cross-sectional manner in
patients aged $ 13.6 years. This indicates that RV systolic function
is significantly reduced after this time interval, most likely because
of long-standing pulmonary regurgitation and RV volume overload.
This is supported by a significant positive correlation between S0
and RVEF and by a significant negative correlation of S0and
RVEDVi in our study.
Bogaard et al.30showed that in patients with PAH-CHD, an impor-
tant adaptation of the right ventricle to high pressure is to increase
wall thickness by accumulating muscle mass (hypertrophy) and to
assume a more rounded shape. Among adults with PAH, only about
11% have PAH-CHD,31which is in contrast to children, in whom
about half of those with PAH have underlying CHD.32Although
many cases of PAH-CHD begin in childhood, the demographics
have changed with an increased prevalence of CHD in recent
Figure 2 Deviation of S0values (S0D) in patients with PAH-CHD
andthosewithrepairedTOFfrommeanreferencevaluesplotted
against increasing age. The S0Dvalue data points for patients
with PAH-CHD and repaired TOF are represented by blue dia-
monds and red triangles, respectively. The interpolated mean
values of the control group are represented by the black line.
The ?2-SD line of the control group measurements is repre-
sented by the black smooth-dashed line. The absolute deviation
of the measured mean S0values of our patients compared with
age-related S0reference values (interpolated black thin line) is
demonstrated. The red line is an interpolation for a linear trend
for patients with repaired TOF and the blue broken line for those
with PAH-CHD.
Figure3 RelationshipbetweenS0valuesandRVEDViinpatients
with PAH-CHD and repaired TOF. S0Dvalue data are repre-
sented by blue diamonds for patients with PAH-CHD and red
triangles for patients with repaired TOF. Deviation of S0Dvalues
in patients with PAH-CHD and repaired TOF from mean age-
related reference values is shown. The horizontal broken line
at zero indicates normal S0values. The blue broken and solid
red lines are interpolations for linear trends in patients with
PAH-CHD and repaired TOF, respectively.
Figure 4 Relationship between S0values and RVEF in patients
with PAH-CHD and repaired TOF. S0Dvalues are represented
by blue diamonds for patients with PAH-CHD and red triangles
for those with repaired TOF. Deviation of S0Dvalues in patients
with PAH-CHD and TOF from mean age-related reference
values is shown. The horizontal broken line at zero indicates
normal S0values. The blue broken and the solid red lines are
interpolations for linear trends in patients with PAH-CHD and
those with repaired TOF, respectively.
6 Koestenberger et al
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years, possibly because of more pediatric patients’ surviving into
adulthood.33With progress in cardiac surgery, there is an increase
in thenumberof patientswithcomplex physiologywhomaydevelop
pulmonary vascular lesions after surgical repairs in early childhood, as
in our patients.34In a recent study Fang et al.35demonstrated that RV
long-axis function is sensitive in revealing RV myocardial damage in
patients with chronic pressure overload. PAH-CHD has been shown
to be essentially the same in adults and in the pediatric age group, al-
though there may be differences reflecting the natural history of
PAH.36PAH-CHD has been described to be an ongoing, progressive
disease, as some patients may present with less (albeit increasingly)
severe PAH-CHD at an advanced age.36
Little is known of systolic RV function in PAH-CHD in the pediat-
ric age group. Because of the preserved RV systolic function in our in-
fants and young children with PAH-CHD, we assume that they were
inthestageof‘‘adaptivehypertrophy,’’asdescribedbyBogaardetal.30
S0values in patients with PAH-CHD become significantly reduced
compared to controls after the age of 10.4 years (i.e., the longer the
right ventricle experiences severe pressure overload, the more de-
pressed systolic RV function becomes). This might be explained by
the fact that the right ventricle cannot sustain high long-term pressure
overload over a long period of time.30
Advances in the field of cardiac MRI established this technique as
the ‘‘goldstandard’’ for the assessment ofRVvolumeand RVfunction
in children and in adults.21In our subjects with PAH-CHD, a signifi-
cant positive correlation was found between S0and RVEF, and
a significant negative correlation was found between S0and
RVEDVi, supporting the value of the measured S0data. Our mea-
sured S0values confirm the decreased RVEF and increased RVEDVi
measurements using the MRI in adolescents and young adults with
PAH-CHD. Therefore, we assume that long-standing severe RV pres-
sure overload also leads to ‘‘maladaptive cardiac growth and contrac-
tile function,’’ as generally has been described for PAH,30also in our
patients with PAH-CHD. Theincreased RVEDVi can be explained by
the fact that with increasing afterload, the ventricular septum be-
comes flat and eventually inverts into the left ventricular cavity with
time. Geometry and rate of contraction of the right ventricle change
and therefore might explain the reduced RVEF and S0in patients with
PAH-CHD.
Limitations
A limitation of our study is that invasive data were available only in
patients with PAH-CHD but not in those with repaired TOF, particu-
larly on absolute pulmonary artery pressure, which might have ex-
plained other contributing factors. We did not assess the effects of
preload variations related to respiration. In pediatric clinical practice,
itwouldbecumbersometoapplyrespiratorygatingtothismethodon
aroutine basis.Although S0is agood parameter to assess RVfunction,
it does not take into account segmental RV function. The population
described in the present study was relatively small, because patients
were enrolled at only two centers. It cannot be excluded that recent
advances in surgery may have affected our results. S0is not a good
parameter to assess preload and afterload variations for the right
ventricle but simply reflects impaired RV function of our patients
with repaired TOF and of our patients with PAH-CHD. We cannot
exclude the possibility that the patient population enrolled in this
study was biased toward more significant residual lesions after trans-
annular patch repair for our patients with TOF. We excluded patients
with TOF with additional lesions, and by doing so, our study popula-
tion may not be representative of a larger population of patients with
repaired TOF. A sedation protocol for right-heart catheterization and
echocardiography does exist at our institution, but the adapting of
drug doses and the use of additional drugs if necessary were left to
the discretion of the treating cardiologist.
CONCLUSIONS
Our results show that in infants and young children with repaired
TOF and PAH-CHD, S0values were similar to those in our healthy
Figure 5 Relationship between age and RVEDVi in patients with
PAH-CHD and repaired TOF. S0Dvalues are represented by blue
diamonds for patients with PAH-CHD and red triangles for those
with repaired TOF. The blue broken and solid red lines are inter-
polations for linear trends in patients with PAH-CHD and those
with repaired TOF, respectively.
Figure 6 Relationship between age and RVEF in patients with
PAH-CHD and repaired TOF. S0Dvalues are represented by
blue diamonds for patients with PAH-CHD and red triangles
for those with repaired TOF. The blue broken and the solid red
lines are interpolations for linear trends in patients with
PAH-CHD and those with repaired TOF patients.
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patients. We demonstrate that persistent volume overload in patients
withrepairedTOFledtoan increasein RVEDVi andadecreasein RV
systolic function, measured by RVEF and S0on MRI. Interestingly, our
patients with PAH-CHD showed similar changes. Persistent ongoing
pressure overload seems to reduce RVEF and S0and increase
RVEDVi with time in this patient group. This occurred at a younger
age than in the repaired TOF group, suggesting that the regurgitant
volume can better tolerate chronic volume overload compared
with chronic pressure overload.
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