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Color Doppler Evaluation of
Valvular Regurgitation in Normal Subjects
Kiyoshi Yoshida, MD, Junichi Yoshikawa, MD,
Masahiro Shakudo, MD, Takashi Akasaka, MD, Yasuko Jyo, MD, Seiichi Takao, MD,
Kenichi Shiratori, MD, Katsumi Koizumi, MD, Fukumaru Okumachi, MD,
Hiroshi Kato, MD, and Takashi Fukaya, MD
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To determine prospectively the prevalence of mitral, aortic, tricuspid, and pulmonary
regurgitation in normal persons, 211 consecutive, apparently healthy volunteers were examined
with a color Doppler flow imaging system. The subjects were divided into five age groups (group
1, 6-9 years old; group 2, 10-19 years old, group 3, 20-29 years old, group 4, 30-39 years old,
and group 5, 40-49 years old). The prevalence rate of mitral regurgitation in the normal
subjects was 38-45 % in each group. The mitral regurgitant jets came from the posteromedial
commissure in all but two subjects. No aortic regurgitant flow signals were detected in the
normal subjects. Tricuspid regurgitation was detected in 15-77% in each group, and
pulmonary regurgitation was detected in 28-88%. Regarding the tricuspid and pulmonic
valves, the prevalence rate of regurgitation is age dependent (p<0.01) and tends toward the
lower rate in groups over the age of 30 years. The tricuspid and pulmonary regurgitant jets
came from the center of the coaptation of each valve. The area of the regurgitant jet signals in
normal persons was significantly smaller (p<0.001) than that obtained from patients with
organic valve disease. Our study shows that in a large proportion of normal persons under the
age of 50 years color Doppler echocardiography permits recording of regurgitant signals behind
all valves except the aortic. In conclusion, one should be aware of the existence and
characteristics of regurgitation in normal persons when evaluating valvular regurgitation by
Doppler techniques. (Circulation 1988:78;840-847)
D oppler techniques now permit noninvasive
evaluation of intracardiac blood flow and
have a widely established record of accuracy in the detection of regurgitation of all four
cardiac valves. '-9 Ever since technical improvements have made the detection of even mild
regurgitation possible, regurgitant turbulent flow
signals have been detected in normal subjects.10-15
The recent development of color Doppler flow
imaging, which superimposes color-coded flow
See editorial comment, p 1075
patterns on real-time two-dimensional images, has
made it possible to map abnormal flow patterns
such as those seen in patients with valvular
regurgitation. 16-18 Being noninvasive, the color
From the Department of Cardiology, Kobe General Hospital,
Kobe, Japan.
Address for correspondence: Kiyoshi Yoshida, MD, Department of Cardiology, Kobe General Hospital, Minatojimanakamachi 4-6, Chuo-ku, Kobe 650, Japan.
Received November 2, 1987; revision accepted May 26, 1988.
Doppler technique is readily applicable to the evaluation of asymptomatic as well as symptomatic
patients. Little information is available concerning
the characteristics, prevalence, and mechanism of
regurgitation in normal subjects. In the present
study, the color Doppler technique was chosen to
determine the prevalence of valvular regurgitation
in a large, consecutive, and prospectively studied
series of normal subjects.
Subjects and Methods
Apparently healthy volunteers without cardiac
symptoms were studied. All were healthy persons
recruited at random from a mass survey at an
elementary school, a junior high school, a university, and from the general community. None had a
previous diagnosis of cardiovascular disease.
Patients were excluded if they had a pansystolic
murmur, late systolic murmur, long ejection systolic murmur, or diastolic murmur. The subjects
having abnormal electrocardiographic findings were
also excluded. Finally, of the 235 subjects recruited,
24 were excluded because of either abnormal elec-
Yoshida et al Color Doppler Evaluation of Valvular Regurgitation
841
TABLE 1. Prevalence of Valvular Regurgitation in Each Group
Age (yr)
Valvular regurgitation
Mitral regurgitation
Aortic regurgitation
Tricuspid regurgitation
Pulmonary regurgitation
6-9
(n = 40)
18 (45%)
0 (0%)
31 (78%)
35 (88%)
10-19
20-29
(n = 47)
21 (45%)
0 (0%)
31 (66%)
30 (64%)
(n = 44)
19 (43%)
0 (0%)
28 (64%)
30 (68%)
trocardiograms or examination, which left 211 subjects in our study population. There were 111 females
and 100 males, and their age ranged from 6 to 49
years (mean, 29 years). The subjects were divided
into five age groups (Table 1) by decades (group 1,
6-9 years; group 2, 10-19 years; group 3, 20-29
years; group 4, 30-39 years; group 5, 40-49 years).
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Color Doppler Echocardiography
Color Doppler examinations were performed with
available system (SSH-65A, Toshiba,
Tokyo, Japan) and a 2.5- or 3.5-MHz transducer.
Pulse repetition frequencies of 4, 6, or 8 kHz were
available. A frequency of 4 kHz was routinely used,
which allowed measurement of velocities up to 75
cm/sec. The scanning rate used in this study was 12
frames/sec. Flow directed toward the transducer was
a commercially
30-39
(n =41)
17 (41%)
0 (0%)
14 (34%)
14 (34%)
40-49
(n = 39)
15 (38%)
0 (0%)
6 (15%)
11(28%)
conventionally coded in red, whereas flow directed
away was coded in blue. Variations in velocity are
presented by brightness and intensity of color.
Because the color Doppler system is based on a
pulse mode, the magnitude of flow velocity is limited
in all points of the ultrasound sector. If turbulence
occurs, green is added to the red or blue underlying
color, thus changing the basic color tonality, which
results in a mosaic pattern. Doppler color gain was
optimized as described previously. 17 Briefly, the gain
was first turned down completely and then increased
very gradually until the static background noise barely
appeared. All images were permanently recorded on a
3/4 in. (U-Matic) Sony videotape. Pictures were
obtained with a Polaroid camera placed in front of a
color television monitor. Color flow mapping was
also performed in an M-mode format (superim-
FIGURE 1. Color Doppler echocardiograms from an 18-year-old normal woman. Left panel: Parasternal long-axis view
shows bluish green signals (arrow) in the left atrium during systole, which is indicative of mitral regurgitation. Right
panel: Short-axis view at the level of the mitral valve shows the regurgitant jet originates from the posteromedial
commissure. AO, aorta; LA, left atrium; LV, left ventricle; LVOT, left ventricular outflow tract.
842
Circulation Vol 78, No 4, October 1988
TOWARDi
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FIGURE 2. Pulsed Doppler echocardiogram from the same subject as in Figure 1. Disturbed flow signals are observed
behind the mitral valve in systole, which is indicative of mitral regurgitation. MV, mitral valve.
posed on conventional M-mode echocardiographic
images) by selective placement of a line cursor on
two-dimensional echocardiographic images.
Doppler windows were parasternal long-axis,
parasternal short-axis, and apical long-axis views
for the aortic valve and parasternal long-axis,
parasternal short-axis, and apical four-chamber
views for the mitral valve. For the tricuspid valve,
the traces were recorded in the right ventricular
inflow view and parasternal and apical fourchamber views. For the pulmonic valve, we recorded
the traces in the long-axis view of the right ventricular outflow tract and high left parasternal shortaxis view. The flow signal was judged as a regurgitation when it was observed as a reversed flow
away from the valve by color Doppler echocardiography and when its duration was more than 100
msec by M-mode color flow mapping. Mitral regurgitation was considered to be present if blue, green,
or mosaic signals were seen originating from the
mitral valve and spreading into the left atrium
during systole. Aortic regurgitation was considered
to be present if red, yellow, or mosaic signals were
seen originating from the aortic valve and spreading
into the left ventricle during diastole. Tricuspid
regurgitation was judged to be present if blue,
green, or mosaic signals were seen originating from
the tricuspid valve and spreading into the right
atrium during systole. Pulmonary regurgitation was
judged to be present if red, yellow, or mosaic
signals were seen originating from the pulmonic
valve and spreading into the right ventricular outflow tract during diastole.
To compute the maximum area of the regurgitant
jet signals with orthogonal planes, videotapes were
carefully analyzed frame by frame. By means of a
software program already incorporated in the equipment, the outline of the regurgitant jet area was
traced with a joystick, and the area was measured
by computerized planimetry. The maximum area of
the regurgitant jet signals was obtained by measuring the largest jet area of those obtained from
orthogonal planes. The regurgitant jet area obtained
from normal persons was compared with the regurgitant area obtained from 40 patients with mitral
valve disease and compared with that in 40 patients
with tricuspid regurgitation in association with leftsided valvular disease confirmed by angiography.
The patient population consisted of 23 patients with
mitral regurgitation due to ruptured chordae tendineae associated with tricuspid regurgitation and of
17 patients who had rheumatic mitral stenosis and
regurgitation combined with tricuspid regurgitation.
Conventional pulsed Doppler echocardiography
was also performed by selective placement of a
sample volume on the color Doppler echocardiographic regurgitation signals in all subjects. Maximal examination time was limited to
15 minutes for each valve.
Statistical Analysis
Statistical analysis was performed with nonparametric techniques with respect to the prevalence of
valvular regurgitation in each age group. A KruskallWallis test was applied to assess the correlation
between the prevalence of valvular regurgitation
and age groups. A probability value less than 0.01
was considered significant. Observer variability in
the subjective assessment of the presence or absence
of regurgitation and in the quantitative estimation of
Yoshida et al Color Doppler Evaluation of Valvular Regurgitation
843
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FIGURE 3. Color Doppler echocardiogramsfrom a 15-year-old normal girl. Left panel: View of right ventricular inflow
tract shows bluish green signals in the right atrium during systole, which is indicative of tricuspid regurgitation. Right
panel: These regurgitant signals are detected in almost the entirety of systole with an M-mode format color Doppler
echocardiogram by selective placement of a line on the regurgitant signals. RV, right ventricle; RA, right atrium; TV,
tricuspid valve.
regurgitant jet area in our laboratory has been
determined in 40 randomly selected patients. From
the accumulated data, there was no interobserver or
intraobserver variability in the subjective assessment of the presence or absence of regurgitation.
The average intraobserver variability for the quantitative estimation of regurgitant jet area was 2.9%
of the mean value, and the average interobserver
variability was 4.4% of the mean.
Results
Mitral Valve
Regurgitant flow signals were detected in 38-45%
in each age group (Table 1). The regurgitant flow
signals (Figures 1 and 2) came from the posteromedial
commissure in the mitral valve in all but two subjects.
Regurgitant flow signals were localized in the vicinity
of the mitral valve, and the regurgitant area ranged
from 0.03 to 0.88 cm2 (mean, 0.26+0.24 cm2).
Aortic Valve
No regurgitant flow signal was detected as originating from the aortic valve in any subject.
Tricuspid Valve
Regurgitant flow signals (Figure 3 and Figure 4)
were detected in 15-78% in each group. The prevalence of tricuspid regurgitation decreased in proportion to aging. The tricuspid regurgitant jets originated at the center of coaptation of the tricuspid
valve, and the regurgitant area ranged from 0.04 to
1.52 cm2 (mean, 0.42 + 0.40 cm2).
Pulmonic Valve
Regurgitant flow signals (Figure 5) were detected
in 28-88% in each group. The prevalence of pulmonary regurgitation decreased in proportion to aging.
The regurgitant jets came from the center of the
coaptation of the pulmonic valve, and the regurgitant area ranged from 0.03 to 1.04 cm2 (mean,
0.28 ±0.26 cm2).
The mitral regurgitant jet area obtained from 40
patients with mitral valve disease ranged from 0.60
to 17.8 cm2 (mean, 5.63+4.15 cm2). The tricuspid
regurgitant jet area obtained from 40 patients with
tricuspid regurgitation in association with left-sided
valvular disease ranged from 0. 30 to 16.6 cm2 (mean,
5.93 + 4.24 cm2).
With conventional pulsed Doppler echocardiography, regurgitation signals were detected in all
subjects in whom regurgitation signals were detected
by color Doppler echocardiography.
Statistical Analysis
No differences were found between men and
women in each group. In the tricuspid and pulmonic valves, the prevalence rate of regurgitation
depends on the age (p<0.01) with a tendency
toward lower rates in the groups over the age of 30
years. The regurgitant jet area (Figure 6) in normal
persons was significantly smaller (p<0.001) than
the regurgitant area obtained from patients with
organic valvular disease.
Discussion
Doppler echocardiography has proven to be a
highly accurate and objective noninvasive technique
844
Circulation Vol 78, No 4, October 1988
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FIGURE 4. Pulsed Doppler echocardiogram from the same subject as in Figure 3. Disturbedflow signals are observed
behind the tricuspid valve during systole, which is indicative of tricuspid regurgitation. TV, tricuspid valve.
for detecting valvular regurgitation. In patients with
a variety of cardiovascular diseases necessitating left
ventriculography, the sensitivity of pulsed Doppler
echocardiography in detecting mitral regurgitation
has ranged from 87% to 94%, and the specificity has
ranged from 77% to 96%.1-5 With aortic regurgitation, pulsed Doppler echocardiography has been
reported to have a sensitivity of 94% and a specificity
of 82% compared with results of aortography.2
In the present study with color Doppler, mitral
regurgitation, tricuspid regurgitation, and pulmonary regurgitation were detected in 45-88% of the
apparently healthy persons less than 20 years of
age. An extremely high prevalence of mitral, tricuspid, and pulmonary regurgitation may indicate that
all normal persons may have silent physiological
regurgitation. However, the regurgitant flow signals
were localized in the vicinity of valve closure, and
the regurgitant jet area in normals was significantly
smaller than the regurgitant jet area obtained from
patients with organic mitral valve disease. Although
some investigators78 have not detected tricuspid or
pulmonary regurgitation, others10,1 1,14,15 have
detected signals suggestive of tricuspid or pulmonary regurgitation in many apparently healthy subjects. Although little information is available concerning the prevalence, characteristics, and
mechanisms of these flows in normal subjects, such
data appear essential for a Doppler echocardiographic definition of pathological regurgitation. Using
continuous wave Doppler echocardiography in 20
normal subjects, Yock et al10 reported that the
prevalence rates were 95% in the tricuspid valve,
35% in the pulmonic valve, 10% in the mitral valve,
and 0% in the aortic valve. In a recent study with
pulsed Doppler echocardiography, Kostucki et al14
showed prevalence rates of 92% pulmonic, 44%
tricuspid, 40% mitral, and 33% aortic regurgitation.
In their study, however, the Doppler aortic regurgitant flow signal was always in early diastole. It
had no clearly distinguishable audio signal, had
very low velocities, and could only be recorded
adjacent to the valve. The flow pattern that they
have reported was clearly different from that of
well-established aortic regurgitant signals, and artifacts cannot be ruled out even when small sample
volume and high-pass filters are used.
The recently developed technique of color Doppler flow imaging, which superimposes color-coded
flow patterns on real-time two-dimensional images,
has made it possible to map abnormal flow patterns
such as those seen in patients with valvular
regurgitation. 16-18 The ability to scan the cardiac
chamber quickly and thoroughly for abnormal flow
signals makes color Doppler examination more comprehensive and less tedious than conventional pulsed
Doppler echocardiography.
The reason why the regurgitant signals were
detected easily in younger normal persons may be
the superior ultrasonic penetration obtainable in
such subjects. The prevalence of tricuspid regurgitation and pulmonary regurgitation decreased in
proportion to aging. This may be because ultrasonic
penetration becomes poorer in proportion to aging.
As a matter of fact, in certain adult individuals,
such as those with obesity or emphysema, the
ultrasound may be too attenuated to permit adequate detection of Doppler signals from distally
located areas. Furthermore, in middle-aged subjects, just as it is sometimes difficult to visualize the
Yoshida et al Color Doppler Evaluation of Valvular Regurgitation
845
FIGURE 5. Color Doppler echocardiogram from a
7-year-old normal girl. Right ventricular outflow
view shows orange signals in the right ventricular
outflow tract during diastole, which is indicative of
pulmonary regurgitation. Regurgitant jet originates from the center of the coaptation of the
pulmonic valve. RVOT, right ventricular outflow
tract; PA, pulmonary artery.
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tricuspid valve and pulmonic valve clearly by twodimensional echocardiography, it is also difficult to
detect regurgitant signals by Doppler techniques.
However, as the quantification of the quality of the
two-dimensional echocardiographic images may be
difficult, fuirther investigation is necessary in reference to the question of why the prevalence of
regurgitation appears to decrease with age. We19
have already reported that valvular regurgitation as
detected by pulsed Doppler echocardiography
increases progressively in proportion to aging in
apparently healthy subjects who are 60 years or
older and is almost uniformly observed in subjects
who are 80 years or older. The high prevalence rate
of Doppler-detected regurgitation in the older age
groups may represent a true increase in the prevalence of regurgitation.20-22 Grossly, the valves
become thicker and more opaque with advancing
age. The grade of these changes is, in part, genetically determined and, in part, age related.23 Longstanding mechanical stress also may play a role in
producing regurgitation.20 In our previous study of
aged individuals, aortic regurgitation was most frequent, mitral regurgitation was the next most frequent, and right-sided valvular regurgitation was
less frequent. The left-sided valves, aortic and
mitral, are exposed, of course, to high pressures
and may therefore undergo degenerative changes
earlier than right-sided valves. No aortic regurgitant
signals were detected in young normal subjects in
the present study. The reason for the absence of
signals of aortic regurgitation in normal persons
remains unclear. We believe that this represents a
true difference between the prevalence of aortic and
both mitral and right-sided regurgitations.
In the last few years, color Doppler flow mapping
has been the object of great interest. This new
technique, unlike other invasive and noninvasive
procedures, provides a dynamic method for study-
ing the spatial distribution of intracavitary flow
patterns while observing cardiac structure dynamics in real time. In the present study, the prevalence
rate of regurgitation with conventional pulsed
Doppler echocardiography was the same as that of
color Doppler echocardiography because conventional pulsed wave examinations were performed
with the guidance of color Doppler echocardiography. The prevalence rate may become lower if
conventional pulsed wave examinations were performed without the aid of color Doppler echocardiography. It is possible to identify unexpected and
extremely eccentric or trivial regurgitant flow signals by color Doppler, whereas it is time consuming
and often difficult by conventional pulsed Doppler
echocardiography. With conventional pulsed Doppler echocardiography, the possibility of falsenegative results is very real. Because many regurgitant jets in normal persons are very localized,
failure to position the sample volume in the jet may
result in failure to detect regurgitation.
Limitations
Because of the nature of the subject population,
which was made up of apparently healthy volunteers, cardiac catheterization was not performed.
Therefore, we were unable to confirm the presence
or absence of valvular regurgitation by angiography. Although color Doppler flow imaging has many
advantages, it is possible that false-positive or false-
negative diagnoses may have been made. Using
conventional, pulsed Doppler echocardiography,
previous investigators5224 of the mitral and tricuspid
valves have reported negative deflections in early
systole in patients without apparent regurgitation.
However, as stated by previous investigators,5 these
signals are limited in time and have a typically
high-pitched audio signal that can be separated from
regurgitant signals. In the present study, signals
846
Circulation Vol 78, No 4, October 1988
3. Abbasi AS, Decristofaro D, Anabtawi J, Irwin L: Mitral valve
prolapse: Comparative value of M-mode, two-dimensional and
Doppler echocardiography. J Am Coil Cardiol 1983;2:1219
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Iia
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i~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~
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MR
TR
LEW, Thomsen JH: Pulsed Doppler echocardiography in
VALVULAR
DISEASE
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FIGURE 6. Plot of regurgitant jet area in normal sub10.
Yock PG, Naasz C, Schnittger I, Popp RL: Doppler tricusand
in
with
valvular
disease.
jects
patients
Regurgitant
pid regurgitation in normals: Is it real? (abstract). Circulajet area in normal subjects is significantly smaller
tion 1984;70(suppl II):II-40
(p<O.OOl) than that in patients with organic valvular
11. Takao S, Miyatake K, Izumi S, Kinoshita N, Sakakibara H,
disease. MR, mitral regurgitation; TR, tricuspid regurgiNimura Y: Physiological pulmonary regurgitation detected
by Doppler technique and its differential diagnosis (abstract).
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J Am Coll Cardiol 1985;5:499
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Detection of coronary flow by pulsed Doppler and color
with a duration of less than 100 msec by M-mode
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color Doppler echocardiography were excluded to
insufficiency (abstract). J Am Coil Cardiol 1986;7:14A
avoid such confusion.
13. Yock PG, Schnittger I, Popp RL: Is continuous wave
Doppler too sensitive in diagnosing pathologic valvular
Clinical Implications
regurgitation? (abstract). Circulation 1984;70(suppl I):I-381
14. Kostucki W, Vandenbossche JL, Friart A, Englert M:
The principal clinical implication of realizing the
Pulsed Doppler regurgitant flow patterns of normal valves.
possibility of silent Doppler regurgitation is to avoid
Am J Cardiol 1986;58:309
iatrogenic heart disease. Our study reveals a high
15. Come PC, Riley MF, Carl LV, Nakao S: Pulsed Doppler
echocardiographic evaluation of valvular regurgitation in
prevalence of hemodynamically insignificant degrees
patients with mitral valve prolapse: Comparison with normal
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monic valves in normal persons. When valvular
16. Omoto R, Yokote Y, Takamoto S, Kyo S, Ueda K, Asano
regurgitation is recognized by color Doppler echoH, Namekawa K, Kasai C, Kondo Y, Koyano A: The
cardiography, other clinical and laboratory evidence
development of real-time two-dimensional Doppler echocardiography and its clinical significance in acquired heart
of heart disease should be carefully evaluated to avoid
diseases with special reference to the evaluation of valvular
the
characteristics
of
overdiagnosis. Furthermore,
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Doppler-detected valvular regurgitation in normal sub17. Miyatake K, Izumi S, Okamoto M, Kinoshita N, Asonuma
jects should be taken into consideration. Whatever
H, Nakagawa H, Yamamoto K, Takamiya M, Sakakibara H,
Nimura Y: Semiquantitative grading of severity of mitral
the mechanisms of these regurgitant signals, one
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valvular regurgitation by Doppler techniques.
18. Helmcke F, Nanda NC, Hsiung MC, Soto B, Adey CK,
Goyal RG, Gatewood RP: Color Doppler assessment of
Acknowledgment
mitral regurgitation with orthogonal planes. Circulation 1987;
75:175
We gratefully acknowledge the assistance of Dr.
19. Akasaka T, Yoshikawa J, Yoshida K, Okumachi F, Koizumi
Ernest Craige in preparation of the manuscript.
K, Shiratori K, Takao S, Shakudo M, Kato H: Age-related
valvular
regurgitation: A study by pulsed Doppler echocarReferences
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Boston, Little, Brown & Co, 1981, p 1
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ingstone, Inc, 1983, p 87
17.0
16.0
15.0
14.0
13.0
E
12.0
9.0
7.0
D
0
6.0
5.0
4.0
3.0
2.0
1.0
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TR
Yoshida et al Color Doppler Evaluation of Valvular Regurgitation
22. Booth DC, Demaria AM: Valvular heart disease in the
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847
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KEY WORDS * Doppler techniques
valvular heart disease
*
normal persons
.
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Color Doppler evaluation of valvular regurgitation in normal subjects.
K Yoshida, J Yoshikawa, M Shakudo, T Akasaka, Y Jyo, S Takao, K Shiratori, K Koizumi, F
Okumachi and H Kato
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Circulation. 1988;78:840-847
doi: 10.1161/01.CIR.78.4.840
Circulation is published by the American Heart Association, 7272 Greenville Avenue, Dallas, TX 75231
Copyright © 1988 American Heart Association, Inc. All rights reserved.
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