Intracardiac Flow Analysis of the Right

Ventricle in Pediatric Patients With Repaired

Tetralogy of Fallot Using a Novel Color
Doppler Velocity Reconstruction
Brett Meyers, PhD, Jonathan Nyce, MD, Jiacheng Zhang, BSc, Lowell H. Frank, MD, Elias Balaras, PhD,
Pavlos P. Vlachos, PhD, and Yue-Hin Loke, MD, West Lafayette, Indiana; and Washington, District of Columbia

Background: Repaired tetralogy of Fallot (RTOF) patients will develop right ventricular (RV) dysfunction from
chronic pulmonary regurgitation (PR). Cardiac magnetic resonance sequences such as four-dimensional
flow can demonstrate altered vorticity and flow energy loss (FEL); however, they are not as available as con-
ventional echocardiography (echo). The study determined whether a novel, vendor-independent Doppler ve-
locity reconstruction (DoVeR) could measure RV intracardiac flow in conventional echo of RTOF patients. The
primary hypothesis was that DoVeR could detect increased vorticity and diastolic FEL in RTOF patients.

Methods: Repaired tetralogy of Fallot patients with echo were retrospectively paired with age-/size-matched
controls. Doppler velocity reconstruction employed the stream function–vorticity equation to approximate intra-
cardiac flow fields from color Doppler. A velocity field of the right ventricle was reconstructed from the apical 4-
chamber view. Vortex strength (VS, area integral of vorticity) and FEL were derived from DoVeR. Cardiac mag-
netic resonance and exercise stress parameters (performed within 1 year of echo) were collected for analysis.

Results: Twenty RTOF patients and age-matched controls were included in the study. Mean regurgitant frac-
tion was 40.5% 6 7.6%, and indexed RV end-diastolic volume was 158 6 36 mL/m2. Repaired tetralogy of
Fallot patients had higher total, mean diastolic, and peak diastolic VS (P = .0013, P = .0012, P = .0032, respec-
tively) and higher total, mean diastolic, and peak diastolic body surface area–indexed FEL (P = .0016,
P = .0022, P < .001, respectively). Peak diastolic indexed FEL and peak diastolic VS had weak-to-moderate
negative correlation with RV ejection fraction (r =
0.52 [P = .019] and r =
0.49 [P = .030], respectively)
and left ventricular ejection fraction (r =
0.47 [P = .034] and r =
0.64 [P = .002], respectively). Mean diastolic
indexed FEL and VS had moderate-to-strong negative correlation with percent predicted maximal oxygen
consumption (r =
0.69 [P = .012] and r =
0.75 [P = .006], respectively).

Conclusions: DoVeR can detect alterations to intracardiac flow in RTOF patients from conventional color
Doppler imaging. Echo-based measures of diastolic VS and FEL correlated with ventricular function. DoVeR
has the potential to provide serial evaluation of abnormal flow dynamics in RTOF patients. (J Am Soc Echo-
cardiogr 2023;36:644-53.)

Keywords: Tetralogy of Fallot, Doppler velocity reconstruction, Vorticity, Energy loss, Congenital heart disease

Patients with tetralogy of Fallot (TOF) are at risk for exercise intolerance
and heart failure1,2 decades after surgical repair. Repaired TOF (RTOF)
patients experience chronic pulmonary regurgitation (PR), progressive
right ventricular (RV) dilation/dysfunction, eventual left ventricular
(LV) dysfunction, ventricular arrhythmias, and mortality.3-5 Therefore,
RTOF patients may require pulmonary valve replacement (PVR).
However, there is uncertainty and inconsistency regarding the ideal
timing for PVR,2,3 resulting in irreversible dysfunction if performed
too late2,6,7 or an increased number of lifetime procedures if performed
too early.8,9 Traditional RV volumetric ‘‘cutoffs’’ by cardiac magnetic

From the School of Mechanical Engineering, Purdue University, West Lafayette,
Indiana (B.M., J.Z., P.P.V.); Department of Cardiology, Children’s National
Hospital, Washington, D.C. (J.N., L.H.F., Y.L.); and School of Engineering &
Applied Science, George Washington University, Washington, D.C. (E.B.).
Dr. Yue-Hin Loke receives partial salary support from NIH R01 HL143468-01 and
R21 HL156045.
Drs. Meyers and Nyce contributed equally to this work.
Conflicts of Interest: None.
644
Reprint requests: Yue-Hin Loke, MD, Division of Pediatric Cardiology, Children’s
National Hospital, 111 Michigan Avenue NW, Washington, DC, 20010 (E-mail:
yloke@childrensnational.org).
0894-7317/$36.00
Copyright 2023 by the American Society of Echocardiography.
https://doi.org/10.1016/j.echo.2023.02.008
Journal of the American Society of Echocardiography
Volume 36 Number 6
Abbreviations
resonance (CMR) have fluctu-
ated as studies suggest that ven-
2D = Two-dimensional tricular dysfunction can occur
4D = Four-dimensional even at modest volumes.2,4,7,10,11
Ultimately, the current PVR
BST = Blood speckle- guidelines do not account for
tracking the intracardiac flow effects of
CMR = Cardiac magnetic PR on power loss and cardiac effi-
resonance ciency.4
Intracardiac flow analysis (rep-
DoVeR = Doppler velocity
reconstruction
resenting blood flow as vectors
through the cardiac cycle) could
echo = Echocardiography potentially clarify the timing of
EKG = Electrocardiogram PVR by quantifying the altered
flow patterns in RTOF pa-
FEL = Flow energy loss tients12-18 such as abnormal
FELi = Flow energy loss index flow energy loss and vorticity.
Flow energy loss (FEL)
HR = Heart rate represents the viscous
ICC = Intraclass correlation dissipation across the flow field
coefficient from blood viscosity and
velocity gradient (shear), and
LV = Left ventricular
vorticity represents the
LVEF = Left ventricular magnitude of spinning motion
ejection fraction in blood.19 These flow patterns
MRI = Magnetic resonance are disrupted in RTOF patients
imaging and correlate with exercise intol-
erance16,20; thus FEL and
PR = Pulmonary regurgitation vorticity are promising hemody-
PVR = Pulmonary valve namic biomarkers that could be
replacement used to optimize PVR timing.
Flow energy loss and vorticity
RTOF = Repaired tetralogy of
Fallot
can be quantified by echocardi-
ography- (echo-) based vector
RV = Right ventricular,
flow mapping (VFM) or blood
ventricle
speckle-tracking (BST),21 as well
RVEDVi = Right ventricular as four-dimensional (4D) flow
end-diastolic volume index by CMR.22 Repaired TOF intra-
cardiac flow analysis has been
RVEF = Right ventricular
primarily driven by 4D flow;
ejection fraction
however, this technique is
TOF = Tetralogy of Fallot hampered by limitations in
VFM = Vector flow mapping spatial/temporal resolution22
and the need for sedation in
VS = Vortex strength
younger patients. For children,
echo-based intracardiac flow
analysis is ideally suitable with its rapid acquisition and higher tempo-
ral resolution23,24; however, current methods rely on vendor-specific
acquisitions, with limited accuracy and potential reconstruction errors
along the transverse plane. Vector flow mapping in particular does not
consider conservation of momentum, which is important for velocity
gradients (accelerations) and measuring quantities such as FEL.
To address these technical concerns and enhance the role of echo
in intracardiac flow analysis of RTOF, a novel color Doppler recon-
struction algorithm (Doppler velocity reconstruction [DoVeR]) has
been developed based on the stream function–vorticity (j - u) formu-
lation to resolve the underlying two-dimensional (2D) velocity field
for blood flow.25 This algorithm enforces both conservation of mass
and conservation of momentum (which is not preserved in VFM),
thereby being more mathematically complete and physically consis-
Meyers et al 645
tent than current VFM methods.23,25-30 This method has been
validated against VFM using synthetic LV data and small animal LV
scans25 as well as clinical 4D flow measurements (see
Supplemental Materials). This method is vendor independent and
can even be performed on retrospective conventional color
Doppler acquisition.
The purpose of this study was to determine whether retrospective
intracardiac flow analysis of conventional color Doppler acquisitions
could measure RV intracardiac flow biomarkers in RTOF patients.
Our primary hypothesis was that DoVeR can detect increased dia-
stolic FEL and vorticity in RTOF patients. Our secondary hypothesis
was that diastolic FEL and vorticity correlate with clinical dysfunction
in RTOF patients.
METHODS
This was a retrospective, single-center cohort study of TOF patients
who had both echo and CMR imaging at Children’s National
Hospital. This cohort of RTOF patients was subsequently age and
body surface area (BSA) matched (within 1 year and 0.4 m2, respec-
tively) to patients with normal cardiac anatomy. Collected informa-
tion included clinical information, routine echo images, and
measurements from CMR, exercise stress testing, and electrocardio-
gram. This study was reviewed and approved by the Children’s
National Hospital’s institutional review board. Since this was a retro-
spective analysis with minimal use for protected health information, a
waiver of informed consent was granted.
Inclusion and Exclusion Criteria
Included patients had an underlying anatomy of TOF with pulmo-
nary stenosis and subsequent transannular patch repair, at least 4 years
from their initial surgical procedure, with echo imaging within a year of
CMR. Patients with other variants of TOF were excluded, including
TOF with pulmonary atresia 6 major aortopulmonary collateral ar-
teries and TOF with absent pulmonary valve. Repaired TOF patients
with nontransannular patch repair (infundibular patch repair, valve-
sparing repair, right ventricle (RV)–to–pulmonary artery conduit) or
subsequent PVR were also excluded. Patients with residual pulmonary
outflow tract obstruction (defined by peak velocity >3.5 m/sec) were
excluded. Notably, patients were not excluded from the study if they
had reintervention shortly after initial repair or had nonsevere tricuspid
regurgitation. Control patients were identified from a retrospective re-
view of age-/size-matched patients who underwent echo as part of
their standard cardiac evaluation, demonstrated normal cardiac struc-
ture/function, and were within 1 year of RTOF studies (to ensure con-
sistency of echo lab standards and equipment at the time of studies).
Finally, patients were excluded if the retrospective echo acquisition pre-
cluded DoVeR analysis, either by having an improper color Nyquist
limit (allowing for too much aliasing or insufficient resolution of the
RV diastolic inflow jet) or by lacking visualization of the RV free wall.
Data Collection
Standard-of-care echo was performed using either a GE Vivid E-95
(General Electric) or Philips Epiq (Philips) following standard methodol-
ogy according to the American Society of Echocardiography.31 All
echos were collected as part of clinically indicated studies for routine
surveillance. Two-dimensional and color Doppler images of the apical
4-chamber view were reviewed to ensure good visualization of the right
646 Meyers et al Journal of the American Society of Echocardiography
June 2023

All CMR studies were performed with a Siemens 1.5 T scanner,

HIGHLIGHTS
 DoVeR can measure flow with conventional echo.
 RTOF patients have higher vorticity and energy loss when
compared with controls.
 Energy loss and vorticity correlated with function and exercise
capacity in RTOF.
atrium, tricuspid inflow, RV body, RV free wall and intraventricular
septum, optimized frame rates, and appropriate Nyquist limit with min-
imal aliasing. Images had an average frame rate of 19 Hz with a range of
13 to 25 Hz. Standard echo-derived measurements included LV frac-
tional shortening, LV ejection fraction (LVEF), mitral E and A waves,
and tissue Doppler indices of septal and lateral E’. Additional qualitative
measures of tricuspid regurgitation and PR were also recorded.
within 1 year of echo imaging. Cardiac magnetic resonance data
included cine imaging (long-axis and short-axis cine) and 2D phase
contrast across the pulmonary valve (VENC set between 2 and
2.5 m/sec). The cine acquisition sequence parameters included field
of view = 270-360  202 – 270 mm, matrix = 208-256  156-192,
echo time = 1.1 – 1.22 ms, flip angle = 50 , slice thickness = 6 –
8 mm, number of segments = 9–11 or 39–48, and number of accel-
eration factor = 2 or 4 depending on use of breath hold or motion-
corrected rebinning as per lab standards.32 Demographic and clinical
information were collected including age, BSA, gender, heart rate
(HR), exercise stress testing, and electrocardiogram results (also per-
formed within 1 year of echo) if available.
Intracardiac Flow Analysis With DoVeR
An in-house suite of semiautomated algorithms based on MATLAB
(Mathworks) was used to reconstruct the underlying blood flow

Table 1 Patient demographics and imaging characteristics in RTOF and control patients

RTOF (n = 20) Control (n = 20) P value

Age (at echo) 12.0 6 3.9 12.0 6 3.9 .99

Gender, female, % 45 40 .65
BSA, m2 1.32 6 0.34 1.25 6 0.32 .36
Echo:
LVEF, % 65.4 6 5.5 64.8 6 3.0 .66
Fractional shortening, % 37.0 6 3.8 36.7 6 4.1 .87
Mitral valve E, cm/sec 110.5 6 20.8 103.0 6 17.3 .26
Septal E’, cm/sec 11.8 6 2.9 13.2 6 1.8 .098
Lateral E’, cm/sec 17.3 6 2.8 19.2 6 3.2 .057
Septal E/E0 9.6 ± 2.8 7.9 ± 1.5 .027
Lateral E/E0 6.6 ± 1.7 5.5 ± 1.2 .034
Severe/free PR present 70% (n = 14)
Tricuspid annular plane systolic excursion, mm 19 ± 3.5
Fractional area change, % 36 ± 6
Pulmonary outflow tract, peak velocity, m/sec 2.1 ± 0.5
MRI:
LVEF, % 59.3 6 4.7
LV cardiac index, L/min/m2 3.5 6 0.8
RVEDVi, mL/m 2
158.1 6 35.5
RV end-systolic volume index, mL/m 2
78.3 6 16.4
RVEF, % 51.1 6 5.9
RV cardiac index, L/min/m 2
5.5 6 1.3
PR%, % 40.5 6 7.6
Indexed retrograde flow, mL/m2 28.8 6 13.4
EKG QRS duration, ms 136 6 23
Exercise stress testing, n: 10
VO2, mL/kg/min 36.2 6 9.8
VO2 percentile, % 84 6 25
Endurance percentile, % 53 6 34
Bold indicates statistically significant results (P < .05).
Journal of the American Society of Echocardiography Meyers et al 647
Volume 36 Number 6

Figure 1 Comparison of DoVeR-derived (A) VS and (B) FELi between normal controls and RTOF patients. Both parameters, when
measured over the entire cardiac cycle or as mean/peak diastole, are elevated in RTOF when compared with normal controls.

velocity vector field. The algorithms were initialized using 3 user-
selected feature points (RV apex, annulus free-wall edge, annulus
septal edge) in 3 frames of acquisition (first, middle, and last recording
frames). A machine vision algorithm identified the endocardium
edges of the RV for segmentation.33 The edges and color Doppler ve-
locity were then used to impose boundary and initial conditions for
the DoVeR algorithm, based on the relationship between volume
flow rate and fluid rotation.25 The algorithm took approximately 7 mi-
nutes to run a single case: 1 minute for the user to initialize or set up
the processing job (including the point selection) and 6 minutes of
fully automated use of computational resources for reconstructing
the velocity field. The reconstructed velocity vector fields were then
processed to quantify parameters of intracardiac flow–FEL and total
vortex strength (VS). Flow energy loss represents irreversible energy
loss due to flow redirection and viscous dissipation,34 computed as
an area average across the RV. Vortex strength quantifies the total
strength of all vortical flow, computed as an area average of absolute
vorticity across the RV. Further descriptions on these parameters are
provided in Supplemental Materials (Reconstruction Postprocessing).
DoVeR-derived values of FEL and VS were averaged over 2 cardiac
cycles. While the DoVeR formulation is theoretically applicable to any
chamber of the heart for both animal model and clinical cases, this al-
gorithm was retrospectively validated for the RV against 4D flow
magnetic resonance imaging (MRI) measurements (see
Supplemental Materials) in a cohort of 20 patients (combination of
RTOF, normal controls, and dilated RVs from atrial level shunts).
Both DoVeR-derived measurements and 4D flow MRI measure-
ments were obtained for FEL, VS, kinetic energy, and intraventricular
pressure difference. Each volume-averaged parameter across the
entire cardiac cycle was compared between modalities by correlation
and L2 norm difference. Results indicated DoVeR measurements
strongly correlated with 4D flow MRI (median r > 0.85) with minimal
differences (median L2 < 15%). More detailed descriptions on valida-
tion are provided in Supplemental Materials (Validation of
Reconstruction).
We performed intraobserver and interobserver variation between 2
observers, each running the setup procedure and processing 3 sepa-
rate times across 8 selected cases (4 controls and 4 RTOF). Intra-
and interobserver variation were computed by one-way analysis of
variance and intraclass correlation coefficient (ICC). Variation was
calculated for each of the primary outcome measurements obtained
from the DoVeR analysis.

Figure 2 Comparison of velocity flow field in the RV between normal (left) and RTOF (right) patients. In diastole of the normal RV, there
is a ring vortex forming near tricuspid inflow that dissipates near the RV apex. In RTOF patients, there are altered, broad-based
vortices that extend into the RV apex, leading to a dominant counterclockwise vortex.
648 Meyers et al Journal of the American Society of Echocardiography
June 2023

Table 2 Comparison of control and RTOF patient FEL and VS in systole and diastole

Control RTOF P value

Energy loss:
Mean diastolic FELi, mW/m/m2 2.58 ± 1.8 4.93 ± 3.0 .0022
Peak diastolic FELi, mW/m/m2 6.18 ± 3.5 12.23 ± 6.9 <.001
Mean systolic FELi, mW/m/m2 1.79 6 2.93 2.00 6 1.9 .14
Peak systolic FELi, mW/m/m 2
3.61 6 5.1 4.08 6 3.1 .14
Total FELi, mW/m/m2 2.29 ± 2.0 3.90 ± 2.5 .016
VS:
Mean diastolic VS, cm2/sec 142.57 ± 39.4 246.16 ± 95.2 .0012
2
Peak diastolic VS, cm /sec 267.84 ± 62.8 441.57 ± 180.0 .0032
Mean systolic VS, cm2/sec 103.80 6 58.3 136.25 6 55.8 .12
Peak systolic VS, cm2/sec 167.48 6 89.8 207.04 6 47.6 .19
Total VS, cm2/sec 127.49 ± 38.3 207.13 ± 78.8 .0013
Mean diastolic VSHR-BSA 0.0091 ± 0.003 0.017 ± 0.008 <.001
Mean systolic VSHR-BSA 0.0065 ± 0.004 0.009 ± 0.005 .036
Total VSHR-BSA 0.0081 ± 0.003 0.014 ± 0.006 <.001
Bold indicates statistically significant results (P < .05).

Outcome Measures Statistical Analysis

The primary outcome for our study was a comparison of BSA-
indexed diastolic FEL (FELi) and VS (the area integral of vorticity) be-
tween RTOF patients and control patients. Mean (systole or diastole),
peak (systole or diastole), and total (systole and diastole combined)
parameters were considered. Indexed parameters were considered
as VFM studies of normal controls have shown that flow parameters
are dependent on BSA and HR.35,36 Secondary outcome measures
included comparison of VS indexed against both HR and BSA
(VSHR-BSA). Additional secondary analysis assessed the correlation be-
tween measures of diastolic FEL and VS with CMR indices including
BSA-indexed RVend-diastolic volume (RVEDVi), RVejection fraction
(RVEF), and LVEF. Lastly, clinical testing including maximal oxygen
consumption (VO2-max) and percentage of predicted VO2 (VO2 %)
during exercise stress testing and electrocardiogram (EKG) QRS dura-
tion was collated.
All statistical analysis was performed using GraphPad Prism
version 9.4.1 (GraphPad Software). Baseline demographic, echo,
and clinical measures are presented as mean and SD or as num-
ber and percentage, depending on the data type. Paired analysis
was performed, comparing between DoVeR-derived measures
FEL and VS in RTOF versus control patients using Wilcoxon
signed-rank tests. Our primary hypothesis was that RTOF patients
would have increased diastolic FELi and diastolic VS compared
with normal controls. Additional comparison of DoVeR-derived
measures against CMR measures of RVEDVi, RVEF, and LVEF
were performed using Pearson correlation. Correlation coefficients
were interpreted as follows: <0.3 was considered negligible, 0.3 to
0.5 weak, > 0.5 to 0.7 moderate, 0.7 to 0.9 strong, and >0.9 very
strong.37 P values < .05 were considered statistically significant for
all analyses.

Figure 3 Correlation of RV/LV systolic function against peak diastolic flow. Peak diastolic VS and peak diastolic FELi were moderately
correlated with lower ventricular systolic function.
Journal of the American Society of Echocardiography Meyers et al 649
Volume 36 Number 6

RESULTS
Demographics
Twenty-seven RTOF and 27 age-/BSA-matched controls were identi-
fied for this study; however, 7 pairs from each group were excluded
due to inadequate color Doppler acquisition, leaving 20 RTOF and
20 matched controls included in this analysis (Table 1). There was
no significant difference in age (12.0 6 3.9 years in RTOF vs
12.0 6 3.9 years in normal, P = .99) or BSA (1.34 6 0.34 m2 and
1.25 6 0.32 m2, P = .36). All RTOF patients had transannular patch
repair at a mean age of 7.4 months. When compared with normal
controls, there was no significant difference in LV systolic function
and only slight alteration to LV diastolic function. Severe/free PR
was noted by echo in 70% of RTOF patients. All RTOF patients
had CMR studies collected within 1 year of echo (mean absolute dif-
ference of 1.8 6 9.8 months). The mean severe PR% by CMR was
42% 6 10% and mean RVEDVi was 149 6 35 mL/m2.
Flow Energy Loss and VS
For normal patients, there was moderate correlation between mean
diastolic FEL and BSA (r =
0.56, P = .009), age (r =
0.57,
P = .008), and HR (r =
0.52, P = .02) within normal patients, which
was not present in RTOF patients. Repaired TOF patients had higher
total, mean, and peak VS compared with control patients (P = .0013,
P = .0012, P = .0032, respectively; Figure 1A). Similarly, RTOF pa-
tients had higher total, mean, and peak diastolic FELi compared
with control patients (P = .0016, P = .0022, P < .001, respectively;
Figure 1B). There was no difference between systolic FELi or VS be-
tween normal and RTOF patients. Meanwhile, VSHR-BSA, mean sys-
tolic VSHR-BSA, and mean diastolic VSHR-BSA were found to be
significantly higher than in control patients (P < .001, P = .036,
P < .001, respectively). These results are summarized in Table 2.
Qualitative Comparison
Qualitative evaluation of the vector flow fields in control patients in
diastole demonstrates the formation of a ring vortex from the
tricuspid inflow toward the RV free wall. In controls, the ring vortex
consists of a small counterclockwise vortex forming from the septal
leaflet and a larger clockwise vortex forming from the anterior leaflet.
In RTOF patients, there is increased velocity and dispersion of septal
RV vortex toward the RV apex leading to a dominant counterclock-
wise vortex and smaller clockwise vortex (Figure 2, Videos 1 and 2;
available at www.onlinejase.com).
MRI Comparison
Diastolic FELi and VS did not correlate with RVEDVi or PR% but
correlated with ventricular function. Right ventricular ejection frac-
tion was moderately negatively correlated with peak diastolic FELi
(r =
0.518, P = .019) as well as peak diastolic VS (r =
0.486
P = .03, Figure 3A). Similar findings were observed for LV systolic
function. Peak diastolic FELi weakly negatively correlated with
LVEF (r =
0.475, P = .035). Peak diastolic VS was also moderately
negatively correlated with LVEF (r =
0.644, P = .002 respectively;
Figure 3B). These results are summarized in Table 3.
Clinical Outcomes
QRS duration did not correlate with either VS or FELi. In a subset
analysis of patients who underwent exercise stress testing (n = 12),
there was a moderate-to-strong negative correlation between VO2
% and mean diastolic, peak diastolic, and total FELi (r =
0.694,
P = .012; r =
0.581, P = .048; and r =
0.717, P = .009, respec-
tively). A similar strong negative correlation was observed with dia-
stolic VS and total VS (r =
0.749, P = .006; and r =
0.736,
P = .006; respectively). These results are summarized in Table 4.
Interobserver Variation Testing
Intraobserver relative variation did not exceed 3% for any one param-
eter (the largest mean relative variation was on peak diastolic FELi at
2.41%). Furthermore, interobserver relative variation did not exceed
5% for any one parameter (the largest mean relative variation was on
peak systolic FELi at 4.16%). Intraobserver and interobserver ICC

Table 3 Correlation between FEL and VS with CMR measures in systole and diastole

RVEDVi P value PR% P value RVEF P LVEF P value

Energy loss
Mean diastolic FELi, mW/m/m2 0.175 .461 0.030 .90
0.315 .18
0.279 .233
Peak diastolic FELi, mW/m/m2 0.264 .081 0.187 .43
0.518 .019
0.475 .035
Mean systolic FELi, mW/m/m 2
0.400 .261 0.174 .46
0.170 .48 0.068 .774
Peak systolic FELi, mW/m/m2 0.240 .308 0.255 .28
0.010 .98 0.188 .427
Total FELi, mW/m/m2 0.266 .256 0.100 .68
0.352 .13
0.245 .298
VS:
Mean diastolic VS, cm2/sec 0.074 .755
0.158 .51
0.359 .12
0.473 .035
Peak diastolic VS, cm2/sec 0.308 .186
0.031 .90
0.486 .03
0.644 .002
Mean systolic VS, cm2/sec 0.191 .419
0.021 .93
0.280 .232
0.122 .609
Peak systolic VS, cm2/sec 0.321 .167 0.212 .37 0.011 .96 0.061 .798
Total VS, cm2/sec 0.074 .497
0.122 .61
0.425 .06
0.478 .033
Peak diastolic VSHR-BSA 0.411 .072
0.078 .74
0.474 .035
0.539 .014
Peak systolic VSHR-BSA 0.364 .115 0.041 .82
0.021 .93 0.108 .651
Total VSHR-BSA 0.258 .273
0.034 .89
0.381 .09
0.237 .137
Bold indicates statistically significant results (P < .05).
650 Meyers et al Journal of the American Society of Echocardiography
June 2023

Table 4 Correlation between FEL and VS with clinical measures

QRS (n = 20) P VO2 % (n = 12) P VO2 max (n = 12) P

Energy loss:
Mean diastolic FELi, mW/m/m2 0.213 .366
0.694 .012
0.685 .014
Peak diastolic FELi, mW/m/m2 0.295 .207
0.581 .048
0.451 .141
Mean systolic FELi, mW/m/m2 0.169 .476
0.244 .43
0.271 .40
2
Peak systolic FELi, mW/m/m 0.090 .706 0.445 .12 0.125 .71
Total FELi, mW/m/m2 0.263 .263
0.717 .009
0.654 .021
VS:
Mean diastolic VS, cm2/sec 0.261 .267
0.749 .006
0.559 .033
Peak diastolic VS, cm /sec2
0.313 .179
0.497 .060
0.249 .25
Mean systolic VS, cm2/sec 0.138 .267
0.472 .012
0.297 .073
Peak systolic VS, cm2/sec
0.196 .407 0.118 .499 0.212 .62
Total VS, cm2/sec 0.308 .187
0.736 .006
0.615 .045
Total VSHR-BSA 0.223 .344
0.55 .067
0.063 .085
Bold indicates statistically significant results (P < .05).

ranged from strong to very strong (0.880-0.993). These results are
summarized in Table 5.
DISCUSSION
This study was a retrospective, case-control comparison of RTOF pa-
tients versus normal controls using novel intracardiac flow analysis by
echo. This study demonstrated that DoVeR can analyze intracardiac
flow fields throughout the cardiac cycle from both RTOF and normal
patients using conventional echo acquisitions. In our primary analysis,
we found that diastolic FELi and VS were higher in RTOF patients. In
our secondary analysis, we found that these flow biomarkers corre-
lated with dysfunction in RTOF patients. These findings demonstrate
the potential for DoVeR as an advanced imaging technique to assess
the altered hemodynamics in RTOF patients using standard bedside
echo.
Repaired TOF patients require sensitive and timely assessment of
the underlying physiology to improve timing of PVR, and part of
the challenge are the uncertainties underlying CMR in guiding ther-
apy. Multiple CMR studies have sought to identify clear thresholds
for intervention,2 although it is now recognized that neither RV size
nor PR% are the driving determinants for RV deterioration or patient
outcomes.5,38-40 While advanced 4D flow may provide
measurements of the direct impact of PR on ventricular function
and remodeling, CMR has a longer scan time, often requiring
sedation or anesthesia in young children.41 Lastly, socioeconomic fac-
tors impact resource utilization for congenital heart disease patients,42
with significant disparities affecting access to tertiary care centers,43
thus limiting the availability to follow RTOF patients serially with
CMR. Meanwhile, echo is still the frontline resource for cardiologists,
available at most outpatient facilities, and frequently used for serial
assessment. However, conventional echo analysis of the RV remains

Table 5 Intra- and interobserver variation on DoVeR calculated measurements

Intraobserver Interobserver Intraobserver Intraobserver

variation (%) variation (%) ICC (observer 1) ICC (observer 2) Interobserver ICC

Energy loss:
Mean diastolic FELi, mW/m/m2 0.509 3.341 0.993 0.990 0.989
Peak diastolic FELi, mW/m/m2 2.411 3.283 0.880 0.902 0.934
Mean systolic FELi, mW/m/m2 1.589 2.371 0.977 0.995 0.984
Peak systolic FELi, mW/m/m2 1.187 4.156 0.967 0.993 0.946
2
Total FELi, mW/m/m 0.773 1.390 0.988 0.996 0.994
VS:
Mean diastolic VS, cm2/sec 0.256 0.629 0.990 0.988 0.981
Peak diastolic VS, cm2/sec 0.358 0.804 0.984 0.962 0.974
Mean systolic VS, cm2/sec 0.785 1.845 0.971 0.970 0.958
Peak systolic VS, cm2/sec 0.264 1.140 0.980 0.980 0.969
Total VS, cm2/sec 0.245 0.457 0.989 0.992 0.989
Tests were performed on 8 selected cases (4 controls, 4 rTOF) between 2 observers, running the setup procedure and processing 3 separate times
across 8 selected cases.
Journal of the American Society of Echocardiography
Volume 36 Number 6
inferior to CMR, and there is minimal validation data to facilitate its
role in intracardiac flow analysis of RTOF. With DoVeR, there is
now a frontline means of detecting and trending intracardiac flow ab-
normalities in RTOF patients.
Recent echo studies have focused on intracardiac flow analysis by
VFM or BST, measuring blood flow and vortical efficiency that may
be sensitive to biomechanics of the heart. An initial study by
Hayashi et al.35 evaluated LV vortex formation patterns and energy
loss in normal children, finding that energy loss is dependent on age
and HR. Honda et al.44 demonstrated in ventricular septal defect pa-
tients that FEL in the LV correlated with catheterization measures of
RV afterload and serum B-type natriuretic peptide. While intracardiac
flow analysis of the RV poses challenges owing to its asymmetric
three-dimensional shape, Chen et al.17 demonstrated this feasibility
in healthy patients, also showing that diastolic energy loss in the RV
correlated with increasing HR and decreasing age. These associations
were also found in the normal controls of our study but not in the
RTOF cohort, which indicates that the alterations to flow observed
in this study are independent of baseline characteristics.
Our findings in the RTOF cohort are consistent with other intracar-
diac flow analyses by VFM and BST, highlighting the abnormal flow
generated from PR. Using BST, Mawad et al.45 found increased dia-
stolic energy loss and vorticity in 21 RTOF patients compared with
controls, similar to volume-loaded RVs from atrial shunts.
Additionally, they identified altered vortex formation that extends to-
ward the RVapex along the septal wall. In a VFM study, Shibata et al.18
demonstrated elevated diastolic energy loss in the RV outflow tract
(RVOT). Both studies required modifications to include visualization
of the RVOT, either from a parasternal short-axis view46 or from an
apical view.45 Vector flow mapping and BST also have technical lim-
itations, such as reconstruction errors along the transverse compo-
nent26 and limited accuracy when depth penetration is >8 cm.47
Furthermore, vendor-specific equipment was required for BST/
VFM, whereas we were able to use vendor-independent DoVeR to
demonstrate similar results from the standard apical view using con-
ventional color Doppler acquisitions. Despite the absence of RVOT
imaging, alterations to diastolic flow were still present throughout
the RV body and apex.
Four-dimensional flow and in vitro computational modeling
studies have elaborated on the altered flow environment contributing
to increased FEL and vorticity in RTOF patients.12,16,20,48 In normal
diastole, the tricuspid inflow typically develops a natural ring vortex
that propagates toward the RVOT with minimal contribution to the
RV apex.16,49,50 In contrast, RV vortices in RTOF patients tend to
be disorganized in the setting of retrograde flow from PR, disrupting
the tricuspid inflow propagation and redirecting flow toward the
apex, consistent with Mawad et al. and our current study.12
Evaluation of the flow dynamics in aortic regurgitation demonstrates
similar patterns of increased FEL/vorticity when the regurgitant jet
collides with mitral inflow vortex formation, generating shearing
and turbulence.51,52 The altered flow environment creates an intra-
cardiac hemodynamic force that is associated with shape maladapta-
tion and cardiac dysfunction.53-55 In addition to the jet collision
against the tricuspid inflow, electromechanical dyssynchrony can
contribute to weakened tricuspid inflow velocity and likely energy
loss.56 Loke et al.16 and Zhao et al.20 determined that this intracardiac
flow environment correlates with exercise intolerance, whereas con-
ventional RV function parameters such as RVEF did not. These find-
ings suggest that beyond correlation with RV dysfunction, intracardiac
flow analysis may also predict exercise intolerance. With DoVeR,
Meyers et al 651
there is now a potential method for echo to provide complementary
data to further inform timing of PVR.
Based on the correlation analysis, DoVeR-derived flow biomarkers
in the RV body appear more related to ventricular function than RV
size for RTOF patients. The positive association between vorticity and
RVEDVi appears more evident in the RVOT than in the body, as
demonstrated by 4D flow studies including Hirtler et al.12 and Loke
et al.16 Furthermore, there was no association with FELi and RV size
in this study. Shibata et al.18 also found only modest associations be-
tween VFM-derived FEL and RVEDVi, although their sample size
was smaller (n = 9). There was also no significant correlation to PR
%, more likely a result of our study design that predominantly
selected RTOF with severe regurgitation (i.e., none with none/
mild). Nonetheless, peak diastolic FELi and VS correlated with both
RVEF by CMR and exercise capacity VO2 %, reflecting an association
between the phenomenon of jet collision with right heart function.
The correlation of diastolic FEL and reduced LVEF (a late finding in
RTOF patients) is also consistent with potential interventricular inter-
actions in RTOF, where severe RV dysfunction impacts LV wall mo-
tion and function.2 The links between intracardiac flow,
hemodynamic force, and ventricular shape54,57 may also contribute
to this correlation. Overall, these findings support a hypothesis that
flow alterations are associated with ventricular dysfunction in RTOF
and that DoVeR can be used to detect these alterations. Thus, the po-
tential application of flow biomarkers could be considered and fol-
lowed serially by echo to monitor disease progression in RTOF
patients.
Limitations
This was a single-center retrospective study with limited sample size,
due to the availability of retrospective echo imaging with color
Doppler imaging of the RV that was appropriate for DoVeR analysis.
As DoVeR analysis requires the entirety of the RV free wall, this may
be challenging for patients with significant RV dilation. Additional lim-
itations included inadequate frame rate and Nyquist limit for appro-
priate color flow estimation, which resulted in an approximately 
25% failure rate for DoVeR. Furthermore, the lower acquisition frame
rates in the retrospective data would have been less sensitive to rapid
changes in blood flow characteristics. We also suspect that flashing ar-
tifacts would preclude accurate DoVeR, although we did not
encounter this issue in the retrospective acquisitions. Conventional
measurements did not routinely collect RV tissue Doppler imaging,
which may aid in further characterizing RV function. Nevertheless,
these limitations can be corrected with a prospective, intracardiac
flow-specific color Doppler imaging protocol, which we intend to
use as part of prospective studies. We also intentionally limited
RTOF analysis to transannular patch repair, most of which had severe
PR; thus, the study results may not necessarily be generalizable to the
entire spectrum of TOF and may have limited the correlations be-
tween DoVeR and CMR end points such as PR%, but this may not
be the case in future prospective studies. Similar to VFM/BST,
DoVeR is limited by the 2D imaging plane; therefore measurement
of energy loss and vorticity do not account for through-plane turbu-
lence from the RVOT, which likely contributes to a significant portion
of total RV energy loss and vorticity. While this may have diminished
some of the correlations in this study, the use of standard echo views
may be helpful for performing these measurements at routine clinic
visits. Finally, the echos/CMRs/exercise stress tests were not per-
formed on the same day, although the 1-year time interval between
652 Meyers et al
each test is still within recommended surveillance guidelines of RTOF
patients and would be unlikely to significantly alter results based on
previous longitudinal exercise studies.58,59
Future studies will focus on the longitudinal evaluation of RTOF
patients to characterize the natural history of intracardiac flow dy-
namics (by both DoVeR and 4D flow) following initial surgical repair
and subsequent RV deterioration. Within this current cohort, prelim-
inary retrospective longitudinal analysis of the younger RTOF patients
(n = 6) demonstrated variable/nonlinear trends toward intracardiac
flow during preadolescence (Supplemental Figure 2). The clinical sig-
nificance of these findings requires further investigation. We also
anticipate focusing on evaluation of intracardiac flow change
following PVR. At the same time, further prospective work (with opti-
mizing imaging protocols) will aim to better characterize these intra-
cardiac flow measurements with functional measures such as
exercise capacity. Together, these studies will help determine factors
predictive of eventual RV deterioration to better inform timing of
PVR.
CONCLUSION
By analyzing standard echo, DoVeR can derive measurements of dia-
stolic FEL and VS that are higher in RTOF patients. Furthermore,
DoVeR-derived flow biomarkers correlated with reduced ventricular
function. These findings demonstrate the feasibility and utility of
DoVeR-derived flow biomarkers as an advanced imaging technique
to assess changes in RV dynamics with standard bedside echo in
RTOF patients.
ACKNOWLEDGMENTS
We thank the scientific oversight committee reviewers, including Drs.
Chris Spurney, Shri Deshpande, and Robin Puente.
SUPPLEMENTARY DATA
Supplementary data to this article can be found online at https://doi.
org/10.1016/j.echo.2023.02.008.
REFERENCES
1. Kempny A, Dimopoulos K, Uebing A, et al. Reference values for exercise
limitations among adults with congenital heart disease. Relation to activ-
ities of daily life–single centre experience and review of published data.
Eur Heart J 2012;33:1386-96.
2. Geva T. Indications for pulmonary valve replacement in repaired tetralogy
of fallot: the quest continues. Circulation 2013;128:1855-7.
3. Bhatt AB, Foster E, Kuehl K, et al. Congenital heart disease in the older
adult: a scientific statement from the American Heart Association. Circu-
lation 2015;131:1884-931.
4. Fogel MA, Sundareswaran KS, de Zelicourt D, et al. Power loss and right
ventricular efficiency in patients after tetralogy of Fallot repair with pulmo-
nary insufficiency: clinical implications. J Thorac Cardiovasc Surg 2012;
143:1279-85.
5. Valente AM, Gauvreau K, Assenza GE, et al. Contemporary predictors of
death and sustained ventricular tachycardia in patients with repaired tetral-
ogy of Fallot enrolled in the INDICATOR cohort. Heart 2014;100:247-53.
Journal of the American Society of Echocardiography
June 2023
6. Therrien J, Siu SC, McLaughlin PR, et al. Pulmonary valve replacement in
adults late after repair of tetralogy of Fallot: are we operating too late? J Am
Coll Cardiol 2000;36:1670-5.
7. Therrien J, Provost Y, Merchant N, et al. Optimal timing for pulmonary
valve replacement in adults after tetralogy of Fallot repair. Am J Cardiol
2005;95:779-82.
8. Bhagra CJ, Hickey EJ, Van De Bruaene A, et al. Pulmonary valve proced-
ures late after repair of tetralogy of fallot: current perspectives and contem-
porary approaches to management. Can J Cardiol 2017;33:1138-49.
9. Huygens SA, Rutten-van M€ olken MPMH, Noruzi A, et al. What is the po-
tential of tissue-engineered pulmonary valves in children? Ann Thorac
Surg 2019;107:1845-53.
10. O’Byrne ML, Glatz AC, Mercer-Rosa L, et al. Trends in pulmonary valve
replacement in children and adults with tetralogy of fallot. Am J Cardiol
2015;115:118-24.
11. Tweddell JS, Simpson P, Li S-H, et al. Timing and technique of pulmonary
valve replacement in the patient with tetralogy of Fallot. Semin Thorac
Cardiovasc Surg Pediatr Card Surg Annu 2012;15:27-33.
12. Hirtler D, Garcia J, Barker AJ, et al. Assessment of intracardiac flow and
vorticity in the right heart of patients after repair of tetralogy of Fallot by
flow-sensitive 4D MRI. Eur Radiol 2016;26:3598-607.
13. Francois CJ, Srinivasan S, Schiebler ML, et al. 4D cardiovascular magnetic
resonance velocity mapping of alterations of right heart flow patterns and
main pulmonary artery hemodynamics in tetralogy of Fallot. J Cardiovasc
Magn Reson 2012;14:16.
14. Fredriksson A, Trzebiatowska-Krzynska A, Dyverfeldt P, et al. Turbulent ki-
netic energy in the right ventricle: potential MR marker for risk stratifica-
tion of adults with repaired Tetralogy of Fallot. J Magn Reson Imaging
2018;47:1043-53.
15. Robinson JD, Rose MJ, Joh M, et al. 4-D flow magnetic-resonance-imaging-
derived energetic biomarkers are abnormal in children with repaired te-
tralogy of Fallot and associated with disease severity. Pediatr Radiol
2019;49:308-17.
16. Loke Y-H, Capuano F, Cleveland V, et al. Moving beyond size: vorticity
and energy loss are correlated with right ventricular dysfunction and exer-
cise intolerance in repaired Tetralogy of Fallot. J Cardiovasc Magn Reson
2021;23:98.
17. Chen Z, Li Y, Li C, et al. Right ventricular dissipative energy loss detected
by vector flow mapping in children: characteristics of normal values. J Ul-
trasound Med 2019;38:131-40.
18. Shibata M, Itatani K, Hayashi T, et al. Flow energy loss as a predictive
parameter for right ventricular deterioration caused by pulmonary regur-
gitation after tetralogy of fallot repair. Pediatr Cardiol 2018;39:731-42.
19. Nakaji K, Itatani K, Tamaki N, et al. Assessment of biventricular hemody-
namics and energy dynamics using lumen-tracking 4D flow MRI without
contrast medium. J Cardiol 2021;78:79-87.
20. Zhao X, Hu L, Leng S, et al. Ventricular flow analysis and its association
with exertional capacity in repaired tetralogy of Fallot: 4D flow cardiovas-
cular magnetic resonance study. J Cardiovasc Magn Reson 2022;24:4.
21. Mele D, Smarrazzo V, Pedrizzetti G, et al. Intracardiac flow analysis: tech-
niques and potential clinical applications. J Am Soc Echocardiogr 2019;32:
319-32.
22. Itatani K, Miyazaki S, Furusawa T, et al. New imaging tools in cardiovascu-
lar medicine: computational fluid dynamics and 4D flow MRI. Gen
Thorac Cardiovasc Surg 2017;65:611-21.

23. Garcia D, del Alamo JC, Tanne D, et al. Two-dimensional intraventricular
flow mapping by digital processing conventional color-Doppler echocardi-
ography images. IEEE Trans Med Imaging 2010;29:1701-13.
24. Sengupta PP, Pedrizzetti G, Kilner PJ, et al. Emerging trends in CV flow
visualization. JACC Cardiovasc Imaging 2012;5:305-16.
25. Meyers BA, Goergen CJ, Segers P, et al. Colour-Doppler echocardiogra-
phy flow field velocity reconstruction using a streamfunction-vorticity
formulation. J R Soc Interface 2020;17:20200741.
26. Assi KC, Gay E, Chnafa C, et al. Intraventricular vector flow mapping—a
Doppler-based regularized problem with automatic model selection.
Phys Med Biol 2017;62:7131-47.
Journal of the American Society of Echocardiography
Volume 36 Number 6
27. Jang J, Ahn CY, Jeon K, et al. A reconstruction method of intra-ventricular
blood flow using color flow ultrasound: a simulation study. Proc SPIE
2015;9417:941728.
28. Pedrizzetti G, Tonti G. Method of transforming a Doppler velocity dataset
into a velocity vector field. U.S. Patent No. 8,858,437. Available at: https://
image-ppubs.uspto.gov/dirsearch-public/print/downloadPdf/885
8437. Accessed March 22, 2023.
29. Uejima T, Koike A, Sawada H, et al. A new echocardiographic method for
identifying vortex flow in the left ventricle: numerical validation. Ultra-
sound Med Biol 2010;36:772-88.
30. Itatani K, Okada T, Uejima T, et al. Intraventricular flow velocity vector
visualization based on the continuity equation and measurements of
vorticity and wall shear stress. Jpn J Appl Phys 2013;52. 07HF16-7.
31. Lai WW, Geva T, Shirali GS, et al. Guidelines and standards for perfor-
mance of a pediatric echocardiogram: a report from the task force of
the pediatric council of the American society of echocardiography. J Am
Soc Echocardiogr 2006;19:1413-30.
32. Merlocco A, Olivieri L, Kellman P, et al. Improved workflow for quantifi-
cation of right ventricular volumes using free-breathing motion corrected
cine imaging. Pediatr Cardiol 2019;40:79-88.
33. Brindise M, Meyers B, Kutty S, et al. Automated peak prominence-based
iterative Dijkstras algorithm for segmentation of B-mode echocardio-
grams. IEEE Trans Biomed Eng 2022;69:1595-607.
34. Elbaz MSM, van der Geest RJ, Calkoen EE, et al. Assessment of viscous
energy loss and the association with three-dimensional vortex ring forma-
tion in left ventricular inflow: in vivo evaluation using four-dimensional
flow MRI. Magn Reson Med 2017;77:794-805.
35. Hayashi T, Itatani K, Inuzuka R, et al. Dissipative energy loss within the left
ventricle detected by vector flow mapping in children: normal values and
effects of age and heart rate. J Cardiol 2015;66:403-10.
36. Zhong Y, Liu Y, Wu T, et al. Assessment of left ventricular dissipative en-
ergy loss by vector flow mapping in patients with end-stage renal disease. J
Ultrasound Med 2016;35:965-73.
37. Mukaka MM. Statistics corner: a guide to appropriate use of correlation
coefficient in medical research. Malawi Med J 2012;24:69-71.
38. Geva T, Sandweiss BM, Gauvreau K, et al. Factors associated with
impaired clinical status in long-term survivors of tetralogy of Fallot repair
evaluated by magnetic resonance imaging. J Am Coll Cardiol 2004;43:
1068-74.
39. Wald RM, Valente AM, Gauvreau K, et al. Cardiac magnetic resonance
markers of progressive RV dilation and dysfunction after tetralogy of Fallot
repair. Heart 2015;101:1724.
40. Ferraz Cavalcanti PE, Sa MPBO, Santos CA, et al. Pulmonary valve
replacement after operative repair of tetralogy of fallot. J Am Coll Cardiol
2013;62:2227-43.
41. Christopher AB, Quinn RE, Zoulfagharian S, et al. Motion-corrected car-
diac MRI is associated with decreased anesthesia exposure in children. Pe-
diatr Radiol 2020;50:1709-16.
42. Agarwal S, Sud K, Khera S, et al. Trends in the burden of adult congenital
heart disease in US emergency departments: burden of ACHD in US EDs.
Clin Cardiol 2016;39:391-8.
43. Salciccioli KB, Oluyomi A, Lupo PJ, et al. A model for geographic and so-
ciodemographic access to care disparities for adults with congenital heart
disease. Congenit Heart Dis 2019;14:752-9.
Meyers et al 653
44. Honda T, Itatani K, Takanashi M, et al. Exploring energy loss by vector flow
mapping in children with ventricular septal defect: pathophysiologic sig-
nificance. Int J Cardiol 2017;244:143-50.
45. Mawad W, Løvstakken L, Fadnes S, et al. Right ventricular flow dynamics
in dilated right ventricles: energy loss estimation based on blood speckle
tracking echocardiography—a pilot study in children. Ultrasound Med
Biol 2021;47:1514-27.
46. Honda T, Itatani K, Miyaji K, et al. Assessment of the vortex flow in
the post-stenotic dilatation above the pulmonary valve stenosis in an in-
fant using echocardiography vector flow mapping. Eur Radiol 2014;35:
306.
47. Nyrnes SA, Fadnes S, Wigen MS, et al. Blood speckle-tracking based on
high–frame rate ultrasound imaging in pediatric cardiology. J Am Soc
Echocardiogr 2020;33:493-503.e5.
48. Loke Y-H, Capuano F, Balaras E, et al. Computational modeling of right
ventricular motion and intracardiac flow in repaired tetralogy of fallot.
Cardiovasc Eng Technol 2022;13:41-54.
49. Fredriksson AG, Zajac J, Eriksson J, et al. 4-D blood flow in the human right
ventricle. Am J Physiol Heart Circ Physiol 2011;301:H2344-50.
50. Pasipoularides A, Shu M, Shah A, et al. Diastolic right ventricular filling
vortex in normal and volume overload states. Am J Physiol Heart Circ
Physiol 2003;284:H1064-72.
51. Okafor I, Raghav V, Condado JF, et al. Aortic regurgitation generates a ki-
nematic obstruction which hinders left ventricular filling. Ann Biomed Eng
2017;45:1305-14.
52. Stugaard M, Koriyama H, Katsuki K, et al. Energy loss in the left ventricle
obtained by vector flow mapping as a new quantitative measure of
severity of aortic regurgitation: a combined experimental and clinical
study. Eur Heart J Cardiovasc Imaging 2015;16:723-30.
53. Sj€
oberg P, T€oger J, Hedstr€om E, et al. Altered biventricular hemodynamic
forces in patients with repaired tetralogy of Fallot and right ventricular vol-
ume overload because of pulmonary regurgitation. Am J Physiol Heart
Circ Physiol 2018;315:H1691-702.
54. Kollar S, Balaras E, Olivieri LJ, et al. Statistical shape modeling reveals the
link between right ventricular shape, hemodynamic force, and myocardial
function in repaired Tetralogy of Fallot patients. Am J Physiol Heart Circ
Physiol 2022;323:H449-60.
55. Loke Y-H, Capuano F, Kollar S, et al. Abnormal diastolic hemodynamic
forces: a link between right ventricular wall motion, intracardiac flow,
and pulmonary regurgitation in repaired tetralogy of fallot. Front Cardio-
vasc Med 2022;9:929470.
56. Lumens J, Fan CS, Walmsley J, et al. Relative impact of right ventricular
electromechanical dyssynchrony versus pulmonary regurgitation on right
ventricular dysfunction and exercise intolerance in patients after repair of
tetralogy of fallot. J Am Heart Assoc 2019;8:e010903.
57. Sch€afer M, Browne LP, Jaggers J, et al. Abnormal left ventricular flow orga-
nization following repair of tetralogy of Fallot. J Thorac Cardiovasc Surg
2020;160:1008-15.
58. Bhat M, Mercer-Rosa L, Fogel MA, et al. Longitudinal changes in adoles-
cents with TOF: implications for care. Eur Heart J Cardiovasc Imaging
2017;18:356-63.
59. Kipps AK, Graham DA, Harrild DM, et al. Longitudinal exercise capacity
of patients with repaired tetralogy of fallot. Am J Cardiol 2011;108:
99-105.