From the University of Colorado Health Sciences Center, The
Children's Hospital, Denver, Colo.
Correspondence to Curt G. DeGroff, MD, Cardiovascular Flow Dynamics Laboratory, University of Colorado Health Science Center, The Children's Hospital, 1056 E 19th Ave, B-100, Denver, CO 80218. E-mail degroff.curt{at}tchden.org
Methods and ResultsBy use of computational fluid dynamic (CFD)
software with turbulence modeling, three-dimensional axisymmetric
models of round stenotic orifices were created. Flow
simulations were run for various orifice area sizes (0.785, 1.13, 1.76,
and 3.14 cm2 ) and flow rates (0.37 to 25.0 L/min). Reynolds
numbers ranged from 100 to 8000. Once adequate convergence was obtained
with each simulation, the location of the vena contracta was
determined. For each run, maximum and average velocities across the
cross section of the vena contracta were tabulated and vena contracta
cross-sectional area (effective orifice area) determined. The
difference between the maximum velocity and the average velocity at the
vena contracta was smallest at high-flow states, with more of a
difference at low-flow states. At lower-flow states, the velocity
vector profile at the vena contracta was parabolic, whereas at
high-flow states, the profile became more flattened. Also, the
effective orifice area (vena contracta cross-sectional area) varied
with flow rate. At moderate-flow states, the effective orifice area
reached a minimum and expanded at low- and high-flow states, remaining
relatively constant at high-flow states.
ConclusionsWe have shown that significant differences exist
between the maximum velocity and the average velocity at the vena
contracta at low flow rates. A likely explanation for this is that
viscous effects cause lower velocities at the edges of the vena
contracta at low flow rates, resulting in a parabolic profile. At
higher-flow states, inertial forces overcome viscous drag, causing a
flatter profile. Effective orifice area itself varies with flow rate as
well, with the smallest areas seen at moderate-flow states. These
flow-dependent factors lead to flow ratedependent errors in the
Doppler continuity equation. Our results have strong relevance to
clinical measurements of stenotic valve areas by use of the
Doppler continuity equation under varying cardiac output
conditions.
Nonetheless, the assumption that the Doppler continuity equation is
flow independent has not been proved and may be erroneous. Although
some investigators have observed a marked flow dependence of valve
areas computed from the Doppler continuity equation in the clinical
setting,6 7 others have reported no
dependence,8 12 and still others have seen
results varying according to whether low or high flow rates are used in
in vitro flow models.5 Clinical studies examining
the effect of increasing flow volume through exercise or
dobutamine infusion on Doppler-calculated valve areas
have also been performed.7 9 10 11 12 Many of these
investigators have found variations in Doppler-calculated valve
area as a result of changing flow conditions and conclude that there
may be a flow dependence inherent in this method.
The purpose of this investigation was to use numerical modeling
experimentation to (1) determine whether the vena contracta
cross-sectional area, called the "effective" orifice area, changes
with flow rate; (2) determine whether orifice areas derived from the
Doppler continuity equation accurately measure effective orifice
areas; and (3) determine whether the results of the Doppler
continuity equation are flow dependent and if so provide explanations
for such dependencies by study of the basic fluid dynamics around a
stenotic orifice.
In this study, we use numerical experimentation to study the fluid
dynamics around stenotic orifices. Numerical methods allow for
a measurement window of the flow dynamics around such orifices, which
is more precise than other experimental techniques, such as in vitro
models.
Doppler Continuity Equation
Often in clinical practice, the velocity
(VDoppler) used in the Doppler continuity
equation is the temporal mean of the highest recorded CW velocities
through a pulsatile cycle (in conjunction with a reference mean flow
rate, Qreference). These temporal means are
generally obtained by measuring velocity-time
integrals.1 In this case, the Doppler
continuity equation is measuring a mean vena contracta
cross-sectional area and not the true orifice area, because (1) the
highest velocities along a properly aligned sample beam through a
stenotic orifice are thought to be at the vena contracta and
(2) the mean CW velocity is a temporal mean of the highest velocities
recorded along that sample beam.
Because of the constriction of flow at the vena contracta, this
effective orifice area is generally smaller than the true orifice area
(as in Fig 1
The assumption of a uniform velocity through the cross section of the
vena contracta (where the maximum velocity obtained by CW Doppler
is assumed to be representative of the velocities over
the entire cross section of the vena contracta) may not hold at certain
flow states. If this assumption of a flat velocity profile is
erroneous, inaccuracies will be introduced into the Doppler
continuity equation.
Grid Generation
Fig 2
Fluid Properties and Boundary Conditions
Flow Solution
A solution was considered proper once adequate convergence was
obtained. At each iteration, CFD-ACE calculates a "residual" for
each variable (variables defined in the governing equations of
fluid flow, see Appendix
Adequate convergence also depends on the total mass imbalance in the
system compared with the total mass flow rate through the boundaries of
the domain. Mass flow rate through a surface is the product of
fluid density, surface area, and the velocity normal to that
surface.15 The total mass imbalance of a system
is determined by subtracting the calculated mass flow rate through the
inflow boundaries from the calculated mass flow rate through the
outflow boundaries (in an ideal numerical solution, these should be
equal). A total mass imbalance of three to four orders of magnitude
less than the total mass flow rate through the boundaries is required
for a solution to be considered proper. The CFD analysis
package (CFD-ACE) used automatically calculates all of these
parameters for analysis.
Turbulence Modeling
Analysis of Flow Data Results
Once a proper solution was obtained with each simulation, the location
of the vena contracta was determined. The vena contracta was defined as
the location downstream of the orifice at which the outermost
streamline through the orifice had its narrowest constriction. The path
of a particle released from the outermost portion of the inlet side of
the orifice matched the outermost streamline and was used for
consistency of measurement. Thus, the narrowest portion of
the particle path was defined as the vena contracta (Fig 3
Contraction Coefficients
Statistical Analysis
In the results that follow, nondimensional Reynolds numbers (equation 2
Fig 5
Fig 6
Actual Contraction Coefficients: Laminar-Flow Model
Actual Contraction Coefficients: Turbulent-Flow Model
Doppler Contraction Coefficient: Laminar- and
Turbulent-Flow Models
These results signify that the Doppler continuity equation method
consistently underestimates the effective orifice area as well
as the true orifice area throughout the entire range of Reynolds
numbers tested (with differences in the level of underestimation in
specific Reynolds number ranges). At low Reynolds numbers (<500), the
underestimation of the effective orifice area by the Doppler method
tends to be greatest. At moderate Reynolds numbers (500 to 1000), the
effective orifice area approaches a minimum with less underestimation
of the effective orifice area by the Doppler method. However, at
these moderate Reynolds number ranges, the underestimation of the true
orifice area by the Doppler method tends to be greatest.
Reynolds Numbers, Flow States, and Flow Rates
Observations based on a dimensionless parameter such as the
Reynolds number allow the identification of certain trends across flow
experiments, experiments that include a wide spectrum of orifice sizes
and flow rates. However, the ranges of flow states or Reynolds numbers
discussed (ie, low, moderate, high) were based on analysis of
our results, and these ranges are not immediately applicable to cardiac
output flow rates used clinically. The
Table
Effective Orifice Area
Our results demonstrate that effective orifice areas (ie, vena
contracta cross-sectional areas) underestimate but approach true
orifice areas at low (<500) and high (>1000) Reynolds numbers,
corresponding to low- and high-flow states in these experiments. At
moderate Reynolds numbers (500 to 1000), the effective orifice area
narrows to 70% to 75% of true orifice area in our model. A probable
explanation is that at low Reynolds numbers, the velocity and thus the
momentum of the proximal streamlines converging into the orifice from
the sides is decreased. This reduction in momentum allows these flow
streamlines to change direction more rapidly when they encounter the
main flow stream without causing a significant reduction in distal flow
area. Consequently, the vena contracta region for such low-flow states
would occupy almost the entire true orifice area. At moderate Reynolds
numbers, the effective orifice area narrows because of the increased
momentum of the proximal streamlines converging into the orifice from
the sides. At high Reynolds numbers, turbulence blunts this
constricting effect and the effective orifice area increases once
again, thereby approaching the true orifice area.
Vena Contracta Velocity Profile
A likely explanation for changes in the velocity profiles with
differing flow states comes from the flow dependence of viscous and
turbulent effects. At low-flow states, viscous effects from the sides
of the orifice retard outside velocities while centerline velocities
increase to maintain flow-rate equity, resulting in a velocity profile
that diverges from flat at the vena contracta. At moderate- and
high-flow states, viscous effects diminish, allowing turbulence effects
to play a more important role. Velocity profiles in turbulent flow are
known to be inherently blunt and flat,33 and our
results confirm this. To the best of our knowledge, no previous
investigations have studied the actual velocity profiles across the
vena contracta in stenotic lesions.
Doppler Continuity Equation
At low Reynolds numbers (<500), corresponding to low-flow states in
these experiments, the effective orifice area underestimates the true
orifice area and the vena contracta velocity shows a parabolic nonflat
profile. Both of these effects (especially the parabolic velocity
profile) cause the Doppler continuity equation to underestimate the
true orifice area.
At moderate Reynolds numbers (500 to 1000), corresponding to
moderate-flow states in these experiments, the effective orifice area
begins to succumb to constriction effects, and there is increasing
underestimation of true orifice area. The vena contracta velocity
profile is flatter. Thus, errors from velocity profile effects become
minimal and changes in the effective orifice area dominate, causing the
Doppler continuity equation to continue to underestimate the true
orifice area.
At high Reynolds numbers (>1000), corresponding to high-flow states in
these experiments, the effective orifice area increases because of
turbulence effects, and the vena contracta velocity profile continues
to be flat. Thus, errors from both of these effects are minimized, and
there is less underestimation of true orifice area by the Doppler
continuity equation.
Clinical Implications
Limitations
Numerical modeling was used because it provides a unique medium for
detailed examination of the fluid dynamics around the vena contracta
region. The limitations of all numerical models include the fact that a
selected number of numerical solutions should be validated with in
vitro models. Preliminary in vitro studies in our laboratory show
similar results for the deviation of the velocity profile away from
flat to more parabolic profiles across the vena contracta at low-flow
states as well as changes in effective orifice area from low- to
moderate-flow states.34 Work is in progress
comparing the velocity vector fields of the numerical and in vitro
models for further validation of our method.
Numerical modeling over such a wide range of Reynolds numbers
presents unique problems for any CFD algorithm. Our ranges of
Reynolds numbers include modeling laminar flow, transitional flow, and
turbulent flow. The decision to turn on turbulence modeling at Reynolds
numbers >1000 was done with some insight as to when turbulence occurs
in these types of problems.15 However, selecting
this turbulence threshold was still somewhat arbitrary.
A discontinuity between laminar and turbulent model contraction
coefficients (Fig 6
Our definition of the vena contracta relies on determining streamlines
and particle-tracking algorithms. How well these algorithms predict the
average path of a particle in turbulent flow is a question that we will
be addressing in future studies.
Our model considers steady flow. Pulsatile-flow numerical runs were
prohibitive in computing-power and time requirements to obtain solution
convergence practically. A relatively dense grid pattern in our model
was required for the detail that was necessary in examining the vena
contracta region. Dense grid patterns require relatively small time
increments in solving for pulsatile flow. Unfortunately, to obtain
proper numerical solutions, dense grid patterns and small time
increments require computational power beyond our present
capabilities. With this, we elected to run the required dense grid
patterns under steady-flow conditions.
We considered flow rates (6 to 400 mL/s, or 0.37 to 25 L/min) that
allow for comparison to mean and peak flow rates seen clinically.
Strictly speaking, simplifying the analysis of pulsatile flow
by comparing conditions at peak or mean flow states in a pulsatile
system with steady-flow conditions at equivalent flow states is not
entirely accurate. Thus, these steady-flow experiments do not allow for
the direct assessment of the ability of the Doppler continuity
equation method to measure the effective orifice area using peak or
mean flow rates and velocities under pulsatile conditions. However,
these steady-flow experiments have allowed us a unique window into the
complexities of the fluid dynamics near a stenotic orifice.
Further pulsatile-flow studies will be required. In preliminary
numerical and in vitro pulsatile-flow experiments in our laboratory,
similar trends in velocity profiles versus Reynolds number have been
noted.
Extending our results to the aortic valve does not account for the
effects of the aortic walls, which are much closer to the
stenotic orifice than in our model. In addition, we have not
examined errors introduced into the clinically applied Doppler
continuity equation as a result of calculations involved in the
determination of the reference flow rate (see equation 1
Conclusions
The clinical implications of our study are that (1) the underestimation
of true orifice area at low cardiac output states by the Doppler
continuity equation may lead to erroneous clinical assessments and
unnecessary therapeutic interventions, and (2) results of clinical
studies by other investigators that have shown an increase in the
Doppler continuity equationcalculated valve area with exercise or
dobutamine infusion can be explained by fundamentally sound
fluid dynamic principles that compound the generally accepted
explanation of increase in valve leaflet opening.
Turbulent flows are inherently unsteady and contain wide ranges of time
and length scales. Thus, in turbulent-flow situations, CFD-ACE uses
equations derived from averages of the governing equations over time to
yield Favre or density-averaged equations.19 20 21
Using Favre averaging introduces additional terms, known as Reynolds
stresses, in the governing equations listed above. CFD-ACE solves for
terms related to these Reynolds stresses as well as the variables
u, v, w, and p in turbulent-flow situations.
It is beyond the scope of this article to describe the various
turbulence models available or the details of the K Omega turbulence
model selected; the reader may refer to the references
noted.19 20 21 The K Omega turbulence model was
chosen because it is a "low Reynolds turbulent number" turbulence
model, since it permits integration of the momentum equations and the
turbulence equations all the way to the model walls, which was
necessary because of the grid resolution required near the wall of the
orifice.
The term "low Reynolds turbulent number" does not refer to the
standard Reynolds number (equation 1
The K Omega turbulence model requires that the first grid point from a
wall must be placed in the laminar sublayer. The laminar sublayer is
defined by a location in the grid at which the distance from the wall
specifies a value of a dimensionless number,
y+, between 0 and 5.
y+ is a dimensionless number at
the walls, defined as15 19 20 21
CFD-ACE automatically calculates
y+ (equation 11
Received June 24, 1997;
revision received November 10, 1997;
accepted December 1, 1997.
2.
Gorlin R, Gorlin SG. Hydraulic formula for calculation
of the area of the stenotic mitral valve, other cardiac valves,
and central circulatory shunts. Am Heart J. 1951;41:129.[Medline]
[Order article via Infotrieve]
3.
Kosturakis D, Allen HD, Goldberg SJ, Sahn DJ,
Valdes-Cruz LM. Non-invasive quantification of stenotic
semilunar valve areas by Doppler
echocardiography. J Am Coll
Cardiol. 1984;3:12561262.[Abstract]
4.
Skjaerpe T, Hegrenaes L, Hatle L. Noninvasive
estimation of valve area in patients with aortic stenosis by
Doppler ultrasound and two dimensional
echocardiography. Circulation. 1985;72:810818.
5.
Otto CM, Pearlman AS, Gardner CL, Enomoto DM, Togo T,
Tsuboi H, Ivey TD. Experimental validation of Doppler
echocardiographic measurement of volume flow through
the stenotic aortic valve. Circulation. 1988;78:435441.
6.
Dumensil JG, Yoganathan AP. Theoretical and practical
differences between the Gorlin formula and the continuity equation for
calculating aortic and mitral valve areas. Am J
Cardiol. 1991;67:12681272.[Medline]
[Order article via Infotrieve]
7.
Burwash IG, Thomas DD, Sadahiro M, Pearlman AS,
Verrier ED, Thomas R, Kraft CD, Otto CM. Dependence of Gorlin
formula and continuity equation valve areas on transvalvular
volume flow rate in valvular aortic stenosis.
Circulation. 1994;89:827835.
8.
Segal J, Lerner DJ, Miller C, Mitchell RS, Alderman
EA, Popp RL. When should Doppler-determined valve area be better
than the Gorlin formula ? Variation in hydraulic constants in low flow
states. J Am Coll Cardiol. 1987;9:12941305.[Abstract]
9.
Pascoe RD, Roger VL, Pellikka PA, Seward JB, Tajik AJ.
Use of dobutamine stress
echocardiography in patients with aortic
stenosis, reduced left ventricular ejection
fraction, and low mean transvalvular gradient: preliminary
experience. J Am Soc Echocardiog.
1994;7(3-II):S8. Abstract.
10.
Vanoverschelde J-L, D'Hondt A-M, De Kock M.
Flow-dependence of aortic stenosis severity during
dobutamine infusion: comparison of the Gorlin and
continuity equations with measurements of aortic valve resistance.
Circulation. 1995;92(suppl I):I-464. Abstract.
11.
Otto CM, Pearlman AS, Kraft CD, Miyake-Hull CY, Burwash
IG, Gardner CJ. Physiologic changes with maximal exercise in
asymptomatic valvular aortic stenosis
assessed by Doppler echocardiography.
J Am Coll Cardiol. 1992;20:11601167.[Abstract]
12.
Casale PN, Palacios IF, Abrascal VM, Harrel L, Davidoff
R, Weyman AE, Fifer MA. Effects of dobutamine on Gorlin and
continuity equation valve areas and valve resistance in
valvular aortic stenosis. Am J Cardiol. 1992;70:11751179.[Medline]
[Order article via Infotrieve]
13.
Yoganathan AP, Woo YR, Sung HW, Williams FP, Franch RH,
Jones MJ. In-vitro hemodynamic
characteristics of tissue bioprostheses in the aortic position.
J Thorac Cardiovasc Surg. 1986;92:198209.[Abstract]
14.
Dumensil JG, Honos GN, Lemieux M, Beauchemin J.
Validation and applications of mitral prosthetic
valvular areas calculated by Doppler
echocardiography. Am J Cardiol. 1990;65:14431448.[Medline]
[Order article via Infotrieve]
15.
Fox RW, McDonald AT. Introduction to Fluid
Mechanics. 4th ed. New York, NY: John Wiley & Sons; 1992:98354.
16.
Shandas R, Kwon J, Kringlen M, Jones M, Valdes-Cruz LM.
Hysteresis behavior of stenotic aortic bioprosthesis as
a function of flow rate: in-vitro studies. J Am Coll
Cardiol. 1996;27(suppl A):233A. Abstract.
17.
Lemler MS, Shaffer EM, Valdes-Cruz LM, Wiggins JW, Cape
EG. Insights into catheter/Doppler discrepancies: a clinical study
of congenital aortic stenosis. Circulation.
1996;94(suppl I):I-415. Abstract.
18.
Cape EG, Jones M, Yamada I, VanAuker MD, Valdes-Cruz
LM. Turbulent/viscous interactions control Doppler/catheter
pressure discrepancies in aortic stenosis: the role of the
Reynolds number. Circulation. 1996;94:29752981.
19.
CFD Research Theory Manual. Version 1.0.
Huntsville, Ala: CFD Research; 1993:9.129.13.
20.
Wilcox DC. Turbulence Modeling for CFD. La
Canada, Calif: DCW Industries; 1993.
21.
Versteeg HK, Malalasekera W. An Introduction to
Computational Fluid Dynamics: The Finite Volume Method. New York,
NY: John Wiley & Sons; 1995.
22.
Patankar SV, Spalding DB. A calculation procedure for
heat, mass and momentum transfer in three-dimensional parabolic flows.
Int J Heat Mass Transfer. 1972;15:17871806.
23.
Van Doormal JP, Raithby GD. Enhancements of the SIMPLE
method for predicting incompressible fluid flows. Numerical Heat
Transfer. 1984;7:147163.
24.
Yang HQ, Habchi SD, Przekwas AJ. A general strong
conservation formulation of Navier-Stokes equations in non-orthogonal
curvilinear coordinates. AIAA J. 1994;32:936941.
25.
Makhijani VB, Yang HQ, Singhal AK, Hwang NC. An
experimental-numerical analysis of MHV cavitation: effects of
leaflet squeezing and rebound. J Heart Valve Dis.
1994;3(suppl 1):3548.
26.
Makhijani VB, Siegel JM, Hwang NC. Numerical
analysis of squeeze-flow in tilting disc mechanical heart
valves. J Heart Valve Dis. 1996;5:97103.[Medline]
[Order article via Infotrieve]
27.
Makhijani VB, Yang HQ, Dionne PJ, Thubrikar MJ.
Three-dimensional coupled fluid-structure simulation of pericardial
bioprosthetic aortic valve function. ASAIO J. 1997;43:M387M392.[Medline]
[Order article via Infotrieve]
28.
Sukumar R, Athavale MM, Makhijani VB, Przekwas AJ.
Application of computational fluid dynamics techniques to blood pumps.
Artif Organs. 1996;20:529533.[Medline]
[Order article via Infotrieve]
29.
Bergman HL, Siegel JM, Oshinski JN, Pettigrew RI, Ku
DN. Computational simulation of magnetic resonance angiograms in
stenotic vessels: effect of stenosis severity.
Adv Bioeng. 1996;33:295296.
30.
Voelker W, Reul H, Nienhaus G, Stelzer T, Schmitz B,
Steegers A, Karsch KR. Comparison of valvular resistance,
stroke work loss, and Gorlin valve area for quantification of aortic
stenosis: an in-vitro study in a pulsatile aortic flow model.
Circulation. 1995;91:11961204.
31.
Gorlin R. Calculations of cardiac valve
stenosis: restoring an old concept for advanced applications.
J Am Coll Cardiol. 1987;10:920922.[Medline]
[Order article via Infotrieve]
32.
Cannon SR, Richards KL, Crawford M. Hydraulic
estimation of stenotic orifice area: a correction of the Gorlin
formula. Circulation. 1985;71:11701178.
33.
Caro CG, Pedley TJ, Schroter RC, Seed WA. The
Mechanics of the Circulation. New York, NY: Oxford University
Press; 1978:5563.
34.
Shandas R, Kwon J, Valdes-Cruz LM. In-vitro studies of
velocity profiles within the proximal jet using digital particle image
velocimetry: implications for clinical Doppler method.
Circulation. 1996;94(suppl I):I-492. Abstract.
35.
Landahl MT, Mollo-Christensen E. Turbulence and
Random Processes in Fluid Mechanics. New York, NY: Cambridge
University Press; 1992.
© 1998 American Heart Association, Inc.
Clinical Investigation and Reports
Analysis of the Effect of Flow Rate on the Doppler Continuity Equation for Stenotic Orifice Area Calculations
A Numerical Study
![]()
Abstract
Top
Abstract
Introduction
Theoretical Considerations
Methods
Results
Discussion
Appendix 1
References
BackgroundFlow-rate dependencies of
the Doppler continuity equation are addressed in this
study.
Key Words: echocardiography stenosis blood flow
![]()
Introduction
Top
Abstract
Introduction
Theoretical Considerations
Methods
Results
Discussion
Appendix 1
References
The impetus for
assessing valve areas by Doppler techniques arose from the fact
that Doppler-estimated pressure gradients across stenotic
valves derived from the simplified Bernoulli equation are a
flow-dependent index of stenosis
severity.1 Valve area measurement methods using
Doppler techniques were developed as an attempt to provide a
flow-independent assessment of valve stenosis. Originally, a
modified form of the Gorlin and Gorlin equation2
was used in the Doppler quantification of valve
areas.3 Later, the continuity equation was
introduced4 as an alternative Doppler method
to estimate valve areas, and it has since become the most commonly used
technique.5 6 7 8 9 10 11 12 13 14
![]()
Theoretical Considerations
Top
Abstract
Introduction
Theoretical Considerations
Methods
Results
Discussion
Appendix 1
References
Vena Contracta
Fig 1
shows schematically the flow
dynamics around a stenotic orifice. Streamlines are lines drawn
within a flow field that are always parallel to the direction of flow.
The vena contracta represents a contraction in the edges of the
flow streamlines as they move through an
orifice.15 For orifices without a smoothly
tapering proximal geometry, inertia prevents proximal streamlines
entering from the side from changing direction instantly; in this
region, these streamlines are directed almost perpendicular to the
general flow direction. As the flow passes through the orifice, the
streamlines change direction to run parallel to the main flow direction
but not before "squeezing" the main flow and causing a constriction
in the cross-sectional area of flow immediately distal to the orifice.
The mechanism that causes this reduction in distal flow area has been
called the vena contracta effect.15 The resulting
constricted area (cross-sectional area of the vena contracta) is the
effective orifice area reflecting the actual area available for flow,
which is usually smaller than the true orifice
area.9 16 Flow separation just distal to the
orifice causes a recirculation zone to form. Through the middle of the
recirculation zone, the mainstream "fresh" flow continues to
accelerate from the orifice to its highest velocity, presumably where
the cross-sectional area of the mainstream flow is narrowest (ie, at
the vena contracta). Past the vena contracta, blood decelerates again
to fill the vessel. Velocity and pressure vary inversely along the
centerline of blood flow through the orifice. Proximal to the orifice,
pressures are high and velocities are low. Approaching the vena
contracta, pressures drop and velocities increase. Past the vena
contracta, in what is called the pressure recovery zone, pressures rise
toward their original magnitude and velocities
decrease.6 17 18

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Figure 1. Streamlines through an orifice. Streamlines are
lines drawn in a flow field such that they are always tangent
(parallel) to direction of flow. Vena contracta represents a
contraction in edges of flow streamlines as they move through an
orifice.
The Doppler continuity equation is derived from the concepts
of conservation of mass (continuity equation)15
and the control volume theory,15 whereby flow
rate through a reference point (Qreference) and
through an orifice along a flow stream must be
equal.1 We assume there is a means to accurately
measure flow rate through a reference location. The Doppler
continuity equation method assumes a uniform velocity profile along the
cross section of the orifice (VDoppler). The
Doppler continuity equation orifice area
(OADCE) is given as
Typically in clinical practice, when there is pulsatile flow, the
velocity (VDoppler) used in the Doppler
continuity equation is the peak continuous-wave (CW) spectral
Doppler velocity used in conjunction with a reference peak flow
rate (Qreference). Because CW Doppler
records all velocities along its sample beam, and the highest
velocities along a properly aligned sample beam through a
stenotic orifice are thought to be at the vena contracta, the
Doppler continuity equation is measuring the cross-sectional area
of the vena contracta, called the effective orifice area (at peak
flow), and not the true orifice area.6

(1)
) and reflects the actual area available for flow through
the orifice.9 18
![]()
Methods
Top
Abstract
Introduction
Theoretical Considerations
Methods
Results
Discussion
Appendix 1
References
Numerical Modeling
Numerical modeling flow experimentation consists of several
stages: (1) grid generation, (2) specification of fluid properties and
boundary conditions, (3) acquisition of flow solution, and (4)
analysis of flow-data results. A software package from CFD
Research was used in the numerical modeling experimentation. This
software package was chosen because of superior qualities offered in
(1) grid construction, (2) range of CFD solution schemes, (3) range of
turbulence model selections, (4) visualization and analysis
tools, and (5) technical support offered through CFD Research.
Grid generation is the division of a flow domain (eg, a
stenotic valve and the surrounding vessel structure) into a
number of small nonoverlapping subdomains called finite control
volumes. CFD-GEOM grid generation software was used to create all of
our three-dimensional axisymmetric grids.
shows the grid used in our
steady-flow experiments. The inlet chamber was 5 cm in length and 27.5
cm in diameter. The outlet chamber was 11.25 cm in length and 27.5 cm
in diameter. The width of the orifice was 0.1 cm. These dimensions were
chosen so that results could be directly compared with results obtained
from our in vitro model with these dimensions. Round stenotic
orifices with diameters of 1.0, 1.2, 1.5, and 2.0 cm (giving orifice
areas of 0.785, 1.13, 1.76, and 3.14 cm2 ,
respectively) were placed between the inlet and outlet chambers.

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Figure 2. Grid of numerical model used in flow experiments.
Inlet chamber is 5 cm long and 27.5 cm in diameter. Outlet chamber is
11.25 cm long and 27.5 cm in diameter. Round stenotic orifices
with diameters ranging between 1.0 and 2.5 cm were placed between inlet
and outlet chambers. Width of orifice was 0.1 cm.
All models had fixed boundaries (ie, noncompliant vessel walls).
Blood was assumed to be a viscous, incompressible Newtonian fluid of
density
=1060 kg/m3 and kinematic viscosity
=4x10-6 m2/s. Flow
rates (6 to 400 mL/s, or 0.37 to 25 L/min) were prescribed by setting
uniform flow velocities at the inlet boundary. Because of computing
hardware constraints (ie, size of grids required), not all flow rates
were run through all orifices. Reynolds numbers ranged from 100 to
8000.
Grids were fed into a finite-volume computational fluid dynamics
(CFD) analysis package (CFD-ACE) by use of laminar and
turbulence modeling. The finite-volume numerical algorithm consists of
three steps19 20 21 : integration of the governing
equations of fluid flow (Appendix
) over all the control volumes in the
flow domain, conversion of these integral equations into a system of
algebraic equations (called discretization), and solution of the
algebraic equations by an iterative method called
SIMPLEC.22 23 24 We used a second-orderaccurate
central differencing discretization scheme19 20 21
available in CFD-ACE. The performance of CFD-ACE in
cardiovascular applications has previously been well
documented.25 26 27 28 29
) for all control volumes. A residual is the
difference in value of a variable in a control volume from one
iterative step to the next. Adequate convergence occurs when there is a
reduction of four to five orders of magnitude in the maximum residual
over all control volumes for all variables.
Turbulence modeling19 20 21 was done with
the K Omega turbulence model19 20 (Appendix
).
Turbulence modeling was used for the simulations in which the Reynolds
number at the orifice was >1000. Reynolds number
(NRe) is given as
where

(2)
is density, V is velocity, d is diameter, and µ is
absolute viscosity.
Flow results were analyzed with flow visualization
software (CFD-VIEW).
), and its radius (r) was recorded.
The effective orifice area (OAeffective) was
calculated as
From the solutions of our numerical runs, the maximum velocity
in the vena contracta was noted with the visualization software
available (CFD-VIEW). Custom software was written in the graphics
software language IDL (Research Systems, Inc) to determine the
three-dimensional spatial average velocity in the vena contracta of the
axisymmetric results for all runs.

(3)

View larger version (82K):
[in a new window]
Figure 3. Demonstration of technique used in determination
and measurement of vena contracta. Vena contracta is defined as
location downstream of orifice at which path of a particle released
from outermost portion of inlet side of orifice (ie, outermost
streamline) was closest to axisymmetric axis.
The actual and Doppler-predicted contraction coefficients as
a function of Reynolds number for all orifices were calculated. The
actual contraction coefficient (CCactual) is
defined by use of the recorded effective orifice area
(OAeffective; equation 3
) and the true orifice
area (OAtrue) as
The Doppler contraction coefficient
(CCDoppler) is defined by use of the
calculated Doppler continuity equation orifice area
(OADCE; equation 1

(4)
) and the true orifice area
(OAtrue) as

(5)
The actual and Doppler-predicted contraction coefficients
were compared by standard paired Student's t test. Values
of P<.05 for paired t tests were considered
significant.
![]()
Results
Top
Abstract
Introduction
Theoretical Considerations
Methods
Results
Discussion
Appendix 1
References
As an example of our results, velocity profiles from two separate
flow rates through the 20-mm orifice are shown in Fig 4a
and 4b
(6 mL/s, or 0.37 L/min, and 60
mL/s, or 3.7 L/min, respectively). The velocity vectors shown are from
a cross-sectional sampling through the vena contracta. Note that the
velocity vector profile for the low flow rate (Fig 4a
) is parabolic and
the velocity profile at the moderate flow rate (Fig 4b
) is flattened
compared with Fig 4a
. Note that with the higher flow rate, where there
is a flat velocity profile at the vena contracta, the peak velocity and
the average velocity will be similar in value, whereas with the low
flow rate, where there is a parabolic velocity profile, the peak
velocity and the average velocity will differ significantly.

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[in a new window]
Figure 4. Velocity vector profile at vena contracta for
2.0-cm orifice at (a) low flow rate (6 mL/s, or 0.37 L/min) and (b)
moderate flow rate (60 mL/s, or 3.7 L/min). Lengths of individual
vectors represent magnitude of each velocity vector. To
adequately display velocity profile differences, scales for vector
length are not equivalent for (a) and (b). Note that shape of profile
is parabolic for low-flow-rate case (a) and flattened and less
parabolic in moderate-flow-rate case (b).
) are used to allow the identification of trends across all flow
experiments, because the experiments performed involve a wide spectrum
of orifice sizes and flow rates.
illustrates the concept of
differences between average and peak velocities for all Reynolds
numbers and orifices considered. Fig 5
shows the percent differences
between maximum and spatial mean velocities across the vena contracta
as a function of Reynolds number. The percent difference between the
maximum and spatial mean velocities across the vena contracta was
greatest at low Reynolds numbers (<500).

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[in a new window]
Figure 5. Percent difference between maximum and average
velocities at vena contracta vs Reynolds number for 1.0-, 1.2-, 1.5-,
and 2.0-cm-diameter orifice numerical model simulations. At low
Reynolds numbers (<500), velocity profile is parabolic and difference
between maximum and average velocities is greatest. At higher Reynolds
numbers (>500), velocity profile flattens and difference between
maximum and average velocity lessens (see also Fig 4
).
shows the actual and
Doppler-predicted contraction coefficients as a function of
Reynolds number for all orifices considered. Solutions using the
laminar-flow model (with Reynolds numbers <1000) and the
turbulent-flow model (with Reynolds numbers >1000) are shown. (Please
refer to the "Limitations" section for a discussion of why the
laminar and turbulent solutions are discontinuous.) P values
for paired t tests are shown in parentheses in Fig 6
, comparing results between CCactual and
CCDoppler. P value results for the
laminar and turbulent models are shown separately; all values were
P<.05.

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[in a new window]
Figure 6. Actual contraction coefficients (equation 4
,
CCactual) and Doppler contraction coefficients
(equation 5
, CCDoppler) vs Reynolds number for (A)
1.0-, (B) 1.2-, (C) 1.5-, and (D) 2.0-cm-diameter orifices for laminar
and turbulent numerical model simulations. For all orifices shown, the
following general results apply. CCactual in laminar-flow
models ranges between 0.7 and 0.9 at low Reynolds numbers (<500). At
moderate Reynolds numbers (500 to 1000), CCactual
decreases. In turbulent-flow models (Reynolds number >1000),
CCactual remains fairly constant (
0.9).
CCDoppler in laminar-flow model at low Reynolds numbers
(<500) significantly underestimates CCactual. At moderate
Reynolds numbers (500 to 1000), CCDoppler reaches its
minimum; here it begins to track, while still underestimating
CCactual. In turbulent-flow models (Reynolds number
>1000), CCDoppler tracks but remains less than
CCactual. See text for significance of these findings.
P values for paired t tests are shown in
parentheses, comparing results between CCactual and
CCDoppler. Results for laminar and turbulent models are
shown separately.
When the laminar-flow-model runs at low Reynolds numbers (<500)
are used for all orifices considered (Fig 6
), the actual contraction
coefficients are in the range of 0.7 to 0.9, signifying that the
effective orifice area underestimates but closely approximates the
anatomic area of the orifice in low Reynolds number ranges. With
moderate Reynolds numbers (500 to 1000), the actual contraction
coefficients decrease, signifying that in this Reynolds number range,
the effective orifice area decreases with increasing underestimation of
true orifice area.
When the turbulent-flow model at high Reynolds numbers (>1000) is
used for all orifices considered, the curve for the actual contraction
coefficients as a function of Reynolds number (Fig 6
) is nearly flat,
remaining close to the value of 0.9, signifying that the effective
orifice area remains close to and slightly less than the true orifice
area at high Reynolds numbers.
As shown in Fig 6
, at low Reynolds numbers (<500), the
Doppler contraction coefficient significantly underestimates the
actual contraction coefficient for all orifices considered. At moderate
Reynolds numbers (500 to 1000), the Doppler contraction coefficient
reaches its minimum; here it begins to track, while still
underestimating the actual contraction coefficient for all orifices
considered in the laminar-flow models. Throughout these low and
moderate Reynolds number ranges (<1000), in the laminar-flow models,
the Doppler contraction coefficient remains between 0.65 and 0.7
for all orifices considered. At high Reynolds numbers (>1000) in the
turbulent-flow models, the Doppler contraction coefficient
underestimates but tracks the actual contraction coefficient with
values
0.85 for all orifices considered.
![]()
Discussion
Top
Abstract
Introduction
Theoretical Considerations
Methods
Results
Discussion
Appendix 1
References
The Doppler continuity equation has become a popular
noninvasive means of assessing stenosis severity. This
present investigation was designed to study, in isolation, the
various factors that may influence differences between the true orifice
area, the effective orifice area, and the orifice area calculated by
the Doppler continuity equation in stenotic orifices.
Results from our numerical modeling indicate that (1) the effective
orifice area underestimates true orifice area; (2) the effective
orifice area is flow dependent (ie, it changes with differing flow
states) regardless of whether the true orifice is flow dependent,
although the effective orifice area remains fairly constant at high
Reynolds numbers; (3) the Doppler continuity equation
underestimates the effective orifice area and the true orifice area
throughout all conditions considered; and (4) the Doppler
continuity equation is flow dependent, with the greatest
underestimation of effective orifice area at low Reynolds numbers
(<500) and the greatest underestimation of true orifice area at
moderate Reynolds numbers (500 to 1000).
In the discussion that follows, we use modifiers to the terms
"Reynolds number" and "flow state" interchangeably (eg, high
flow state and high Reynolds number). If we examine the equation for
the Reynolds number (equation 2
), as the Reynolds number changes,
orifice velocity changes proportionately if all other Reynolds number
parameters are held constant, including orifice size.
Qualitatively, at least, flow state changes occur proportionately to
changes in velocity.
gives flow rates for low, moderate,
and high Reynolds number ranges for each orifice considered.
View this table:
[in a new window]
Table 1. Flow Rate Ranges for All Orifices Considered According to
Low, Moderate, and High Reynolds Number Ranges Referred to in Text
Several investigators have explored the relationship between
effective orifice area and flow rate.5 6 7 8 9 10 11 12 13 30 31 32
However, all of these previous studies have relied on the Doppler
continuity equation or the Gorlin and Gorlin formula to calculate
effective orifice area, both of which may have other inherent
dependencies on flow rate. Numerical modeling provides a "gold
standard" method of predicting effective orifice area.
Our results show that the velocity profile at the vena contracta
is not flat, especially for low Reynolds numbers (corresponding to
low-flow states in these experiments), at which it assumes a more
parabolic profile (Fig 4a
). At moderate Reynolds numbers (500 to 1000),
corresponding to moderate-flow states in these experiments, the
velocity profile flattens out (Fig 4b
). Fig 5
shows graphically the
percent difference between maximum and mean velocities at the vena
contracta relative to Reynolds numbers.
Our results elucidate two fundamental reasons why the Doppler
continuity equation underestimates true orifice area and is flow
dependent. First, because of the vena contracta effect, the Doppler
continuity equation theoretically measures the effective orifice area
(see "Theoretical Considerations"). As we have demonstrated, the
effective orifice area itself underestimates true orifice area and is
flow dependent. Second, the Doppler continuity equation does not
accurately track the effective orifice area. The inaccuracies in
tracking the effective orifice area can be explained by the fact that
the maximum velocity obtained clinically with CW Doppler and used
in the Doppler continuity equation is thought to be
representative of the spatial average of velocities
over the entire cross section of the vena contracta. This holds true
only in the presence of a flat velocity profile throughout the vena
contracta. Any variation from a flat velocity profile will lead to
overestimation of the spatial average of velocities and consequently to
an underestimation of orifice area in the Doppler continuity
equation, because velocity is in the denominator (see equation 1
).
The flow rate dependence of the Doppler continuity equation
has been explored by investigators in the clinical setting by exercise
or dobutamine stress echocardiography
in aortic stenosis.7 9 10 11 12 Most of these
studies demonstrate changing Doppler valve areas with varying
cardiac outputs. Investigators who have shown an increase in
Doppler valve areas with increasing flow theorize that the valve
leaflets open farther when exposed to the greater pressure
gradient.7 9 10 11 Although this may undoubtedly be
part of the explanation, our studies on rigid orifices offer an
additional reason for the Doppler underestimation of effective
orifice area at low cardiac outputs, which is inherent in the
assumptions of the equation itself. These assumptions must be kept in
mind when we apply Doppler methods in clinical practice. If
treatment decisions are to be based on the measurements derived from
the Doppler continuity equation, understanding these flow-rate
dependencies becomes quite important.
With our numerical experimentation tools, we performed detailed
investigations of the flow dynamics through stenotic orifices,
which provided a unique means of assessing the accuracy of the
Doppler continuity method. Although the fixed rigid orifices in our
model are admittedly a simplification of a complex three-dimensional
structure of a stenotic valve, they allow isolation of the
effects of flow on vena contracta or effective orifice area without the
added complexity of possible anatomic expansion of a
physiological orifice as flow rate
increases.7 8 9 11
) occurs at this turbulence threshold. We believe
this represents a weakness of the CFD algorithm we used in
predicting results in the transitional flow range. To the best of our
knowledge, this weakness is shared by all CFD algorithms developed to
date. A weakness of a CFD algorithm in predicting results in this
transitional flow range does not negate its results in the laminar and
turbulence ranges. Such a sharp discontinuity in the contraction
coefficient curves probably does not occur in reality. It is more
likely that there is a much smoother transition from one curve to the
other in the transitional-flow Reynolds number region (
1000).
Overall, however, the finite-volume CFD analysis package
(CFD-ACE) we used provides a robust solution algorithm, as suggested by
the agreement with our in vitro validation studies to
date.34 A complete description of the transition
from laminar- to turbulent-flow processes is beyond the scope of this
investigation; for further discussion, the reader is referred to
Landahl et al.35
), in which
this reference flow rate (Qreference) is
typically determined by use of spectral Doppler measurements.
Our results demonstrate the flow dependency of the Doppler
continuity equation. This flow dependency is due to flow-dependent
changes of the effective orifice area (cross-sectional area of the vena
contracta) as well as to changes in the vena contracta velocity
profile. At low-flow states, the velocity profile is skewed, causing
underestimation of true orifice areas. At moderate-flow states, the
velocity profile becomes more flattened, lessening its effects on
orifice area errors; however, the vena contracta (effective orifice
area) becomes more constricted, causing continued underestimation of
true orifice areas. At high-flow states, the velocity profile remains
flattened, and there is less constriction at the vena contracta (ie,
greater effective orifice area), causing less underestimation of true
orifice areas.
![]()
Appendix 1
Top
Abstract
Introduction
Theoretical Considerations
Methods
Results
Discussion
Appendix 1
References
The set of governing equations for fluid flow consists of
the equations for conservation of mass (continuity equation) and
conservation of momentum (Navier-Stokes
equations).15 19 20 21 We consider blood to be an
incompressible Newtonian fluid for which the equations for conservation
of mass (equation 6
) and conservation of momentum (equations 7 through 9![]()
![]()
) become (in Cartesian coordinates)

(6)

(7)

(8)
Here, u, v, and w are the velocity components in the
x, y, and z directions, p is pressure,
t is time, and

(9)
is kinematic viscosity (absolute viscosity/density).
The CFD analysis package (CFD-ACE) solves for the variables
u, v, w, and p in laminar-flow situations.
). The standard Reynolds number
represents a ratio between inertia (momentum) forces and
viscous (friction) forces. A low Reynolds turbulent number refers to a
qualifier on the Reynolds turbulent number
(NRet)19 :
where

(10)
is turbulent kinetic energy,
is rate of
dissipation of kinetic energy,
is density, and µ is absolute
viscosity. The NRet represents the ratio
between eddy viscosity and molecular viscosity. Molecular viscosity
relates shear stress to the strain rate. Eddy viscosity relates
Reynolds (turbulent) stresses to the mean strain rate.
where y equals the distance to closest grid point from the wall
and u

(11)
is the friction velocity
[u
=
(
w/
)1/2, where
w is wall shear stress].
) at the walls.
To ensure that the first grid point from any wall was in the viscous
sublayer (for those runs requiring turbulence modeling), the grid was
checked (and modified if necessary) for each run so that the value of
y+ at the walls was between 0
and 5.15 19
![]()
Acknowledgments
This study was supported in part by a Pilot Grant from The
Children's Hospital Research Institute, Denver, Colo.
![]()
Footnotes
Presented in part at the 69th Annual Scientific Sessions of the American Heart Association, New Orleans, La, November 1114, 1996, and published in abstract form (Circulation. 1997;96(suppl I):I-471).
![]()
References
Top
Abstract
Introduction
Theoretical Considerations
Methods
Results
Discussion
Appendix 1
References
1.
Snider AR, Serwer GA.
Echocardiography in Pediatric Heart
Disease. Baltimore, Md: Mosby Year Book; 1990:108.
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