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Noninvasive Quantitation of Valvular Regurgitation
by Gated Equilibrium Radionuclide Angiography
SHERMAN G. SORENSEN, M.D., ROBERT A. O'ROURKE, M.D., AND TUHIN K. CHAUDHURI, M.D.
SUMMARY R-wave synchronous equilibrium radionuclide angiography (RNA) is a noninvasive method
that provides time-activity curve count information proportional to ventricular volumes and is used for relative
volume comparisons within the left or right ventricle to derive the ejection fraction. Comparison of the ventricular count output between both ventricles may permit quantitation of the relative amount of valvular
regurgitation, i.e., the regurgitant fraction. We performed resting gated RNA in 30 consecutive patients undergoing cardiac catheterization and quantitative contrast ventriculography for aortic or mitral valvular
regurgitation. RNA regurgitant fraction correlated well with cardiac catheterization regurgitant fraction (r
0.85). In 11 patients imaged before and 1-4 months after successful valve replacement, the regurgitant fraction
declined from 0.68 ± 0.11 to -0.09 ± 0.13 (p < 0.001). In 20 control patients without valvular regurgitation,
the calculated regurgitant fraction did not exceed 0.20. We conclude that valvular regurgitation may be accurately detected, quantitated and followed serially after therapeutic intervention using gated RNA.
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catheterization and quantitative single-plane right
anterior oblique contrast angiography were studied.
Two other patients with inadequate contrast ventriculograms because of arrhythmia or inadequate
opacification were excluded. Twenty-three of these 30
patients were catheterized for a primary clinical
diagnosis of valvular regurgitation. Three patients
were evaluated for valvular stenosis with associated
regurgitation and four patients were evaluated for a
primary clinical diagnosis of coronary artery disease
with associated mitral regurgitation. Of the 30
patients, 16 had aortic regurgitation and 14 had mitral
regurgitation. None of these patients had right-sided
regurgitation or cardiac shunt. Significant right-sided
regurgitation was excluded on the basis of physical examination and right-heart catheterization. None of
these patients had large "v" waves in the jugular
venous pulse, systolic or diastolic murmurs that increased with inspiration, systolic hepatic pulsations or
right ventricular enlargement and paradoxic septal
motion by M-mode echocardiography. Intracardiac
shunting was excluded by oximetry or dye-curve
analysis. Eleven of these patients were imaged 1-4
months after successful valve replacement.
MODERATE-TO-SEVERE volume overload of the
left ventricle due to mitral or aortic regurgitation may
be well tolerated symptomatically by many patients
for years. However, chronic valvular regurgitation
often results in ventricular dysfunction clinically
manifest as angina, arrhythmia or congestive heart
failure. Left ventricular dysfunction due to valvular
regurgitation may not improve despite successful
valve replacement in some patients.1-7 A method for
serially quantitating the severity of valvular regurgitation, ventricular volumes, and ejection fraction would
be highly desirable because selecting the appropriate
timing for valvular replacement in asymptomatic or
mildly symptomatic patients with aortic or mitral
regurgitation is a major problem. Gated equilibrium
radionuclide angiography, which provides timeactivity curve count information proportional to ventricular volumes, is a safe, noninvasive, easily
repeatable method of evaluating left and right ventricular function. In this report we describe the
application of gated equilibrium radionuclide
angiography for the serial noninvasive quantitation of
valvular regurgitant fraction, ventricular ejection fraction and relative ventricular end-diastolic enlargement
in patients with chronic mitral or aortic valvular
regurgitation.
Control Group (No Valvular Regurgitation)
To obtain control information in subjects without
valvular regurgitation, rest radionuclide angiography
was performed in 20 patients. Ten of these 20 patients
were normal by history, physical examination, ECG
and chest x-ray. Three of these normal patients had
undergone cardiac catheterization for atypical chest
pain. The remaining 10 patients had cardiac disease
but no evidence of valvular regurgitation or shunt:
Eight had coronary artery disease with significant wall
motion abnormality, one had aortic stenosis and one
had primary cardiomyopathy. Nine of these 10
patients were studied by cardiac catheterization. The
noncatheterized patient had coronary artery disease
but no murmur and a normal right ventricle and septal
motion by echocardiography. This study was approved by the Human Research Committee, and all
patients gave informed consent.
Methods
Patient Selection
Regurgitant Group
Thirty consecutive patients with mitral or aortic
regurgitation who underwent diagnostic cardiac
From the Cardiology Section and Nuclear Medicine Service,
Audie Murphy Veterans Administration Hospital, and the
Departments of Medicine and Radiology, University of Texas
Health Science Center at San Antonio, San Antonio, Texas.
Supported in part by the American Heart Association, Texas
Affiliate, grant 79-9.
Address for correspondence: Sherman G. Sorensen, M.D., Cardiology Division, Department of Medicine, University of Texas
Health Science Center, 7703 Floyd Curl Drive, San Antonio, Texas
78284.
Received August 31, 1979; revision accepted April 4, 1980.
Circulation 62, No. 5, 1980.
1089
1090
QUANTITATION OF VALVULAR REGURGITATION/Sorensen
et al.
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Cardiac Catheterization
Radionuclide Angiography
In the fasting state, all patients underwent rightand left-heart catheterization and coronary arteriography by the brachial or percutaneous transfemoral approach. Pressures were measured through
fluid-filled catheters with Statham transducers and
recorded on an Electronics for Medicine VRl6 recorder. Forward cardiac output was measured by
Fick and dye-dilution techniques immediately after
pressure recordings and immediately before left
ventricular contrast angiography. When indicated,
aortography was performed after ventriculography.
Left ventricular contrast angiography was performed in the 300 right anterior oblique position by
the injection of 45-60 ml of Renografin at 15-20
ml/sec through a retrograde #8F angiographic
catheter during 35-mm cine filming at 60 frames/sec.
Coronary arteriography followed ventriculography or
aortography in all cases. Ventricular angiograms were
analyzed as described by Kennedy et al.8 by selecting a
well-opacified, normally conducted cycle not preceded
by a premature ventricular complex. The longest
length and area for end-diastole and end-systole were
determined and ventricular volumes were calculated
using a high-resolution projector and a computerinterfaced digitizing table. Correction for magnification was made by grid filming at the level of the midleft ventricle as determined from 300 right anterior
oblique patient position and 600 left anterior oblique
fluoroscopy. Left ventricular ejection fraction, enddiastolic volume, end-systolic volume, stroke volume
and angiographic cardiac output were then obtained
or derived. Regurgitation was quantitated as the left
ventricular regurgitant fraction, which expresses the
relationship between regurgitant flow and total ventricular flow.9 The regurgitant fraction was calculated
as
Within 1-10 days of cardiac catheterization,
without change in clinical status or therapy, resting
anterior and straight left anterior oblique view, Rwave synchronous equilibrium radionuclide angiography was performed after the i.v. injection of technetium-99m-labeled human serum albumin. Eleven
patients were also imaged 1-4 months after successful
valve replacement. Supine blood pressure and heart
rate were obtained immediately before imaging.
Imaging was performed with a gamma scintillation
camera using a low-energy, all-purpose, parallel-hole
collimator. Using a dedicated computer system (Medical Data Systems), images were acquired under electrocardiographic control such that consecutive corresponding 40-msec segments of each cardiac cycle were
summed and stored in the computer core memory until each synchronized 40-msec image contained at least
300,000 counts. Images were processed by nine-point
spatial smoothing and background subtraction was
determined from a light-pen-defined 90° region-of- interest arc (3 o'clock to 6 o'clock) two to three pixels
removed from the left anterior oblique left ventricular
end-diastolic edge. Left ventricular time-activity
curves were then generated by the Medical Data
Systems MUGE program that, in an edge-detection
program with operator intervention, defined new left
ventricular regions of interest for each frame of the
composite cardiac cycle. Figure 1 shows selected enddiastolic, midsystolic and end-systolic images.
Computer-defined regions of interest edges demonstrate the varying size of regions of interest throughout the composite cardiac cycle. Computer-assigned
increases in background subtraction from an endsystolic region of interest were accepted for left
ventricular curves. Because this edge-detection
algorithm functioned infrequently when applied to the
right ventricle, the multiple region method of right
ventricular analysis of Maddahi et al.'0 was used. By
this method, a right ventricular end-diastolic region of
interest was defined by magnetic light pen on
angiographic output - forward output
angiographic output
FIGURE 1. Gated equilibrium radionuclide
Counts are obtained for endangiography.
each ventricle
diastole and
I
by
end-systolefor
varying region-of-interest methods that
minimize overlap of ventricular and atrial
activity.
QUANTITATION OF VALVULAR REGURGITATION/Sorensen et al.
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smoothed, background-subtracted images, and a timeactivity curve was generated. From this curve, the endsystolic frame was identified as the frame containing
the fewest right ventricular counts. End-systolic
counts were obtained from this frame by light pen
region-of-interest definition of the right ventricle, excluding the right atrium. From these right and left
ventricular time-activity curve data, end-diastolic
counts, end-systolic counts, stroke counts or ventricular count output (end-diastolic counts minus endsystolic counts), and ejection fraction were obtained or
derived for each ventricle.
Because time-activity curve information is proportional to volume and provides a good estimate of ejection fraction using relative volume comparisons of a
single ventricle, we reasoned that regurgitant fraction
could be calculated by relative volume comparisons
between the right and left ventricles. The method of
calculating the radionuclide regurgitant fraction
(analagous to catheterization methods) and a
representative left ventricular time-activity curve
derived from the MUGE program are shown in figure
2. Left ventricular count output was obtained by subtracting minimum curve counts (end-systolic counts)
from maximum curve counts (end-diastolic counts). A
right ventricular time-activity curve for the same
patients is also shown in figure 2. In contrast to the left
ventricular time-activity curve, which was generated
by a variable region-of-interest method, the timeactivity curve for the right ventricle shown here was
generated from a right ventricular, end-diastolic, fixed
region of interest and displayed using a computerfixed region program (Medical Data Systems,
MGCV). The arrow at the nadir of the curve indicates
that the end-systolic frame was identified from the
fixed region right ventricular curve. However, actual
end-systolic counts were obtained from a separate
right ventricular end-systolic region of interest,
defined using a light pen. Right ventricular count output was then obtained by subtracting right ventricular
end-systolic counts (from the end-systolic region of interest) from right ventricular end-diastolic counts
(maximum counts from the fixed region curve). Accordingly, for the curves in figure 2, the left ventricular
count output was 25,000 counts (34,000 minus 9000),
the right ventricular count output was 8000 counts
(16,000 minus 8000), and regurgitant fraction was
0.68 ( [25,000-8000]/25,000).
To determine the reproducibility of the method,
gated equilibrium studies from the 10 normal control
Regurgitant Fraction (RF) Calculation
Forward Output
Cath RF = Anglo Output
Angio - Output
Output -RV Count Output
RF= LLV Count
RNA
RNARF=
LV Count Output
Right Ventricle (RV)
1091
Left Ventricle(LV)
FIGURE 2. Regurgitant fraction (RF) calculation. Cath = cardiac catheterization RNA = gated
radionuclide angiography. Right and left ventricular time-activity curves from which count outputs (enddiastolic counts minus end-systolic counts) are derived are shown. Left ventricular output exceeded right
ventricular output resulting in a regurgitant fraction of 0.68.
1092
CIRCULATION
patients and the first 10 consecutive patients with
valvular regurgitation were analyzed by having an experienced technician repeat each analysis on different
days without knowledge of patient identity or
previously determined results.
Statistical Analysis
A paired t test was used for statistical comparison
of variables before and after a single intervention,
where each patient served as his own control. An unpaired t test was used to compare different groups of
patients or variables. For tests of relationships, leastsquares linear regression analysis and Pearson's
coefficient of correlation were used. All values in the
text are given as mean ± SD.
Results
Reproducibility
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Correlation coefficients for right and left ventricular
ejection fraction analyses performes on separate days
by an experienced technician were 0.90 and 0.94,
respectively. Right ventricular count output (r =
0.90), left ventricular count output (r - 0.92) and
regurgitant fraction (r = 0.89) were also highly
reproducible.
Control Subjects
The reliability of any method of quantitating the
regurgitant fraction is dependent on accurate definition of forward and regurgitant flow. The count outputs of the left and right ventricles were compared for
28-1
24W
Patients with Aortic or Mitral Regurgitation
x Abnormal Without
Table 1 shows the cardiac catheterization hemodynamic data and radionuclide data for the 30
patients with regurgitation studies. At catheterization,
the mean systolic blood pressure was 140 mm Hg and
averaged 10 mm Hg greater than mean blood pressure
before radionuclide angiography (p < 0.05). The mean
heart rate at catheterization was 77 beats/min and exceeded the mean rate of 72 beats/min during imaging
(p < 0.05). The regurgitant fraction at catheterization
was 0.48 ± 0.19, which was less than the mean radionuclide regurgitant fraction of 0.54 ± 0.19 (p < 0.05).
The left ventricular ejection fractions were similar by
both methods (0.55 vs 0.54). The mean radionuclide
right ventricular ejection fraction was 0.39.
Regurgitation
,, 20-
C X 16x
12-
C
8
i:F
8-
n =20
r = .97
y =.92 x + 854
4r,l i
U
6
normal controls and controls with cardiac disease but
without regurgitation or shunt (fig. 3). Agreement
between outputs of both ventricles was excellent (r =
0.97) and the regression equation approached the line
of identity. This agreement is apparent for both normal subjects and patients with left ventricular dysfunction, despite marked differences between normal and
abnormal nonregurgitant controls. Table 1 shows
radionuclide ejection fraction data for patients with
valvular regurgitation and controls. For the 10 normal
subjects, the mean left ventricular ejection fraction
was 0.62 ± 0.07 (range 0.53-0.70), whereas for the 10
cardiac patients without valvular regurgitation, the
mean left ventricular ejection fraction was 0.38 ± 0.14
(range 0.23-0.63) (p < 0.01). The mean normal and
abnormal control right ventricular ejection fractions
were 0.51 ± 0.07 (range 0.42-0.60) and 0.43 i 0.10
(range 0.22-0.62) (p < 0.05), respectively. The
calculated mean regurgitant fraction for the 20 control
subjects was 0.0 1 ± 0. 1 1 (range -0.19-0.19).
Of the 20 control patients, 12 had undergone cardiac catheterization. Calculation of a regurgitant fraction in these patients without regurgitation or shunt
was possible in 10 of these 12 patients. One patient
was excluded because only right-heart catheterization
was performed (and therefore no angiographic cardiac
output was performed) and one was excluded due to
ventricular tachycardia during contrast ventriculography. Six of the 10 patients had forward cardiac output determined by both dye-dilution and Fick
techniques, two had Fick outputs only, and two had
dye-dilution outputs only. The calculated regurgitant
fraction by the angiographic/dye-dilution method was
0.07 ± 0.17 and by the angiographic/Fick output
method 0.07 ± 0.18.
* Normal
3O
=
VOL 62, No 5, NOVEMBER 1980
l
4
8
12
16
20
Counts x 103
Left Ventricle
24
28
FIGURE 3. Radionuclide ventricular count outputs for
both ventricles for 20 control patients without regurgitation
or shunt show close agreement, and the regression line approaches unity.
End-diastolic Volume Ratio
In figure 4, regression lines for the 10 normal
subjects and 30 regurgitant patients compare countdefined left and right ventricular end-diastolic
volumes. The 10 cardiac control patients are not included because they had left ventricular enlargement
due to coronary disease. For normal subjects, the
mean right ventricular end-diastolic counts exceeded
QUANTITATION OF VALVULAR REGURGITATION/Sorensen et al.
1093
TABLE 1. Radionuclide Ejection Fraction Data
BP
(mm Hg)
Valvular regurgitation (n = 30)
140
CATH
130
RNA
-
25
30*
HR
(beats/min)
77
72
-
LVEF
RF
0.48
0.54
15
15*
-
0.19
0.19*
0.56
0.55
RVEF
0.15
0.15
0.39
-
0.15
No valvular regurgitation (n = 20)
0.01 - 0.11
0.62 0.07
0.51 - 0.07
Normal (n = 10)
0.38 0.14* 0.43 - 0.10*
Abnormal (n = 10)
Values are mean - SD.
*p < 0.05.
Abbreviations: BP = systolic blood pressure; HR = heart rate; RF = regurgitant fraction; LVEF
left ventricular ejection fraction; RVEF = right ventricular ejection fraction; CATH = catheterization;
RNA = radionuclide angiography.
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left ventricular end-diastolic counts (23,450 ± 8750 vs
18,730 ± 7850, p = NS). Regurgitant patients,
however, had significantly greater left than right ventricular end-diastolic volumes.
Regurgitant Fraction
Regurgitant fractions by cardiac catheterization
and by radionuclide regurgitant fraction were compared (fig. 5). Good correlation exists at all levels of
volume overload (r = 0.85). Because regurgitant fraction by radionuclide angiography was somewhat
greater than regurgitant fraction by cardiac
catheterization (0.48 ± 0.19 vs 0.54 ± O.l9, p < 0.05),
separate comparisons were made for aortic and mitral
regurgitation. In the 14 patients with mitral regurgita-
tion, regurgitant fractions by catheterization (0.50 ±
0.21) and radionuclide angiography (0.54 ± 0.20) did
not differ significantly. However, the regurgitant fractions by catheterization (0.46 ± 0.19) and
radionuclide (0.54 ± 0.19) methods for patients with
aortic regurgitation were significantly different (p =
0.01). Correlation coefficients for catheterization and
radionuclide methods did not differ when aortic and
mitral patients were analyzed separately. Ten of the
30 patients had a regurgitant fraction less than 0.50,
and the radionuclide value slightly exceeded the
catheterization value (0.31 ± 0.09 vs 0.26 ± 0.09,p =
NS). The radionuclide regurgitant fraction also exceeded the catheterization regurgitant fraction (0.66 ±
0.10 vs 0.59 ± 0.13,p < 0.05) in the 20 patients with a
regurgitant fraction greater than 0.50. The correlation
coefficient for each subgroup did not differ from the
correlation for the entire group. The radionuclide
method, therefore, appears to overestimate regurgi80- * Mitral
* Aortic
50-
a
CL)
a
X,,, re
=
x
?-
40_E
m
LU1 as40-o
DC
/
a
0
0
10-
0
-o
'D
o
Em
C
.3 W
0
--0 20n. f
im0
.60-
E
>4-c)3U)
c X 30-c
a
.20-
1
6o
20 30 40 50
Counts x 103
Left Ventricle
FIGURE 4. End-diastolic counts. This graph compares the
right and left ventricular end-diastolic count relationships
for normal (n = 10) subjects and patients with left-sided
valvular regurgitation (n = 30).
a
a
n=30
r = 0.85
y=.85x+14
0
p<.001
O-
40
60
20
8
Cardiac Catheterization
FIGURE 5. Valvular regurgitant fraction. Cardiac
catheterization regurgitant fraction is compared with
radionuclide regurgitant fraction.
CIRCULATION
1094
tant fraction to a mild degree. However, because of
differences in blood pressure and heart rate between
these nonsimultaneous studies, such a conclusion may
only be inferred.
VOL 62, No 5, NOVEMBER 1980
operation, left ventricular end-diastolic volume
enlargement assessed by left/right end-diastolic count
ratios decreased. The ratio fell from 1.63 ± 0.28
preoperatively to 1.08 ± 0.19 postoperatively (p =
0.001).
Preoperative vs Postoperative Regurgitant Fraction
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Figure 6 shows the results of successful valvular
replacement in 11 patients with moderate-to-severe
valvular regurgitation studied by gated radionuclide
angiography before and 1-4 months after surgery.
Preoperatively, the regurgitant fraction was 0.68 ±
0. 11. After surgery, the regurgitant fraction of -0.09
0.13 (p = 0.001) was well within the nonregurgitant
range established by the control population. No
patient had postoperative regurgitation. Postoperatively, left ventricular ejection fraction declined (0.57
0.09 to 0.37 + 0.19; p < 0.01), whereas right ventricular ejection fraction was unchanged (0.36 ± 0.14
to 0.39 ± 0.15, p = NS). In four patients imaged
within 3 weeks of surgery and more than 4 months
after surgery, left ventricular ejection fraction
decreased precipitously early after operation (mean
0.53 0.04 to 0.18 ± 0.06; p < 0.01); individually,
ejection fraction declines were 0.57 to 0.28, 0.47 to
0.17, 0.55 to 0.15 and 0.54 to 0.14. The mean ejection
fraction improved by 4-6 months (0.37 ± 0.13, p <
0.05); individual values were 0.60, 0.29, 0.20 and 0.31,
respectively. In all 11 patients studied before and after
+
.90X
80~
C-
701
e
6050~1)
cr
40-
Ci)
30-
02
O
01r
~~~~~~.5
~
~~
~
~
~
~
~
~
0-~~~~~~~~~~
o10
p<0OOI
-20
Before
Surgery
n-ll
After
Surgery
n=ll
No
Regurgitation
n=20
FIGURE 6. Results of successful valve surgery in 11
patients imaged before and after surgery. The mean
preoperative regurgitant fraction declined to within the
range defined by 20 patients without valvular regurgitation.
Cine Differentiation of Mitral and Aortic Regurgitation
Characteristic appearances of normal, severe aortic
regurgitation and severe mitral regurgitation images
in the 450 left anterior oblique view are shown in
figure 7. In aortic regurgitation, the left ventricle is
displaced laterally and downward and is well
separated from the right ventricle. In mitral regurgitation, however, the right and left ventricles are not
separated and together form a heart-shaped configuration. Cine display of anterior and left anterior oblique
gated radionuclide images were viewed in random sequence and without knowledge of diagnosis for all
regurgitant and control patients. In all 21 patients
with a regurgitant fraction greater than 0.40, mitral
and aortic insufficiency were identified and correctly
differentiated. Cine display in five of nine patients with
a regurgitant fraction less than 0.40 were incorrectly
interpreted. Three patients with mild regurgitation
were considered normal and two with coronary artery
disease and pronounced wall motion abnormality were
considered to have coronary disease alone. None of
the nonregurgitant control normal or control abnormal patients were considered to have regurgitation.
Discussion
Surgical therapy for aortic or mitral regurgitation is
beneficial in many symptomatic patients for relief of
symptoms and prolongation of life.1 11-13 However,
some symptomatic patients do not improve or die
from congestive heart failure despite successful
valve replacement. Such observations confirmed by
echocardiographic, angiographic, actuarial and
pathologic studies have prompted suggestion of extending valvular surgery to asymptomatic patients
with moderate or severe valvular regurgitation.'
Further, recent studies using exercise radionuclide
angiography in patients with aortic and mitral
regurgitation have shown abnormal exercise ejection
fraction reserve in as many as 40% of asymptomatic
patients with significant valvular regurgitation.14 15
However, enthusiasm for early surgical intervention
has been tempered by the potential complications of
valve replacement.3 4'1 Unfortunately, retrospective
information regarding the natural history of aortic
and mitral valve disease has lacked hemodynamic
verification and is of limited application in this era of
potent medical therapy, improved surgical techniques
and prostheses, and changing patterns of valvular
heart disease."'-"8 In patients with valvular regurgitation, invasive studies relying upon pressure data alone
have shown conflicting results and generally have not
been helpful in predicting subsequent course.2' 19. 20
A number of angiographic2l-24 and echocardiographic2' 25-27 studies have evaluated pre- and
postoperative ejection fraction, ventricular volume
QUANTITATION OF VALVULAR REGURGITATION/Sorensen et al.
Normal
Aortic
Regurgitation
1095
Mitral
Regurgitation
End
Diastole
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Systole
1
1
FIGLRI 7. Cine differentiation oJ mitral and aortic regurgitation by radionuclide angiography in the left
anterior oblique view.
and left ventricular mass in patients undergoing
valvular replacement for valvular regurgitation. These
investigations have uniformly shown that patients with
preoperative myocardial dysfunction tend to show no
improvement in ventricular function and have poorer
long-term results.
Gated equilibrium radionuclide angiography is a
useful addition to these other modalities because it is a
safe, noninvasive and reproducible method of
evaluating both ventricular volume change and ventricular function. Others have reported on the application of radioisotope methods to valvular insufficiency,28"30 but have relied on qualitative assessment of the
severity of regurgitation. Using a nonimaging detector, Hildner et al.28 quantitated the severity of aortic
regurgitation from time-activity curve count information after intraventricular isotope injection and found
good agreement with qualitative supravalvular
angiography. Rigo et al.29 obtained changes in the
ratios of left and right ventricular stroke counts from
unprocessed blood pool images and reported good
correlation with qualitative angiographic assessment
of regurgitation in 20 patients. Janowitz et al.30 used
first-pass radionuclide angiography in 10 patients to
quantitate regurgitant fraction from the total count
output of each ventricle and reported good correlation
with catheterization.
In this study we used the traditional catheterization
and angiographic concept of "regurgitant fraction" to
quantitate mitral and aortic regurgitation by means of
a noninvasive count-based method. Intuitively, symptoms and prognosis in valvular insufficiency should
relate to the severity or volume of regurgitation.31
Hemodynamic studies of quantitatively varied aortic
valvular regurgitation in acute open-chest dogs have
shown a reduced forward cardiac output, increased
end-diastolic pressure and peripheral resistance, and
left ventricular myocardial depression with increasing
regurgitant flow.32 Similar experimental studies for
mitral regurgitation have shown increased left atrial
pressure and reduced forward output with increasing
regurgitant flow.33 In man, the accurate assessment of
the severity of regurgitation requires cardiac catheterization and contrast angiography and is dependent on
the application of quantitative ventriculography for
determining regurgitant volume.9 34'35 Qualitative
methods such as cineaortography have been shown to
be less sensitive in assessing regurgitant flow,36 and
limitations of noninvasive methods have not permitted
quantitation of regurgitation. A number of reports
have described the accuracy of quantitating the
regurgitant fraction in valvular heart disease.37-41
The application of equilibrium radionuclide
angiography in this context rests upon several
previously confirmed features of gated blood pool imaging. First, quantitation of left ventricular ejection
fraction using counts defined by radionuclide
angiography as relative volume equivalents has correlated well with ejection fraction determined by contrast ventriculography at cardiac catheterization.42 46
Second, information derived from the time-activity
curve accurately reflects the timing and magnitude of
volume change during ventricular systole. Green et
al.47 performed simultaneous gated radionuclide
angiography and electromagnetic flow measurements
in baboons and found equivalent curve profiles from
both methods (r - 0.95). Sorensen et al.48 performed
simultaneous gated radionuclide angiography and
1096
CIRCULATION
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Fick cardiac output determination in normal men and
showed close agreement in relative cardiac output
change throughout exercise. Third, right ventricular
count measurements may be accurately defined with
conventional blood pool techniques.'0 Right and left
ventricular count information may then be compared
to obtain volume relationships between the two ventricles. Thus, in the absence of shunt or regurgitation,
count outputs (end-diastolic minus end-systolic
counts) of both ventricles should be equal. Conversely,
in the presence of aortic, mitral or combined aortic
and mitral regurgitation, the count output of the left
ventricle should be greater than that of the right ventricle and proportional to the left ventricular angiographic stroke volume or cardiac output. The count
output of the right ventricle would remain proportional to pulmonary or forward cardiac output. Basic
to this radionuclide method of quantitating regurgitant fraction is the assumption that ventricular volume
overload is unilateral. Accordingly, if right- and leftsided regurgitation are present, the severity of either
lesion cannot be quantitated. The presence of significant right-sided volume overload in our subjects was
excluded on the basis of physical examination,
echocardiography, analysis of right-heart pressures
obtained at catheterization and dye-dilution curves.
In the present study, we performed gated blood pool
imaging and cardiac catheterization with quantitative
ventriculography in 30 patients with valvular insufficiency of varying severity (regurgitant fraction
ranging 0. 17-0.83) and found a close correlation
between regurgitant fractions determined by
catheterization and by radionuclide angiography (r =
0.85) (fig. 5). Agreement was good for all degrees of
regurgitation. The method we used compares ventricular time-activity curve count output information
using a varying region-of-interest method for each
ventricle,'0 42 which decreases the error due to
atrioventricular overlap by more accurately defining
ventricular end-systole and thereby more accurately
quantitating count output (or stroke counts) and ejection fraction. Caudal angulation of the gamma
camera in the 450 left anterior oblique position may
also improve separation of atria and ventricles.
However, we used an unmodified straight 450 left
anterior oblique projection based on experience showing good correlation of radionuclide and contrast ejection fraction42 and serial increases in left ventricular
count output compared with Fick output during exercise48 using an unmodified left anterior oblique projection. The problem of atrioventricular overlap is illustrated in our series by comparing calculated
radionuclide regurgitant fraction for aortic regurgitation and mitral regurgitation with left atrial enlargement. Using our method, the mean radionuclide
regurgitant fraction for the 30 patients (0.54 ± 0.19)
exceeded catheterization regurgitant fraction (0.48 ±
0.19; p = 0.05). However, when analyzed separately,
radionuclide regurgitant fraction significantly exceeded catheterization regurgitant fraction for aortic
regurgitation (p < 0.01) but not mitral regurgitation.
Although these data suggest that left atrial enlarge-
VOL 62, No 5, NOVEMBER 1980
ment results in greater overlap with the left ventricle
and lower left ventricular count output, overlap of the
left atrium and right ventricle may occur in cases of
severe left atrial enlargement. We evaluated one
patient with severe mitral regurgitation and a large
left atrium (8.0 cm by echocardiography) in whom
right ventricular ejection fraction and right ventricular
count output could not be obtained due to an increase
(rather than decrease) in end-systolic counts resulting
from overlapping regurgitant atrial counts.
Mild overestimation of regurgitation is also
suggested by higher systolic blood pressures (and
thereby higher afterload) at catheterization compared
with imaging (140 ± 6 vs 130 ± 7 mm Hg, p < 0.05).
However, the heart rate during invasive study was
greater than during radionuclide angiography.
Brawley and Morrow49 studied six patients with aortic
regurgitation by direct pressure and flow measurements during pacing-varied heart rate and concluded
that there was no predictable direction of change in regurgitant flow. Judge et al.50 evaluated eight patients
with aortic regurgitation during catheterization comparing quantitative angiography and forward outputs
in sinus rhythm and with atrial pacing. Patients with
lower regurgitant fractions tended to decrease regurgitant flow at higher heart rates. The mean regurgitant
fraction fell from 0.58 ± 0.06 to 0.47 ± 0.12 (p <
0.05) with increased heart rate. Systolic pressure and
systemic resistance were unchanged. Thus, in our
study, the effect of greater afterload may have been
negated by greater heart rates. However, the
radionuclide method appears to provide a reasonable
and accurate estimate of the regurgitant fraction. This
impression is further strengthened in our pre- and
postoperative studies in 11 patients with successful
correction of regurgitation, which clearly show a
decline in the mean regurgitant fraction (0.68 to -0.09
(fig. 6). All postoperative regurgitant fraction values
were within the range defined by our control normal
and abnormal population. Further, left ventricular
ejection fractions in these operated subjects declined
from 0.57 ± 0.09 to 0.37 ± 0.19 (p < 0.05). The mean
right ventricular ejection fraction, however, was unchanged (0.36 ± 0.14 preoperatively vs 0.39 ± 0.15
postoperatively, p = NS).
Although we did not attempt to convert end-diastolic counts to actual volumes, comparisons of left
and right ventricular end-diastolic counts gave a
reasonable estimation of left ventricular enlargement.
Using cardiac catheterization, other investigators37 38 40 have emphasized determination of enddiastolic volumes in these disorders due to the discordance of left ventricular enlargement and regurgitant
fraction in patients with myocardial dysfunction. In
our operated patients, the ratio of left ventricular to
right ventricular end-diastolic counts decreased from
1.63 ± 0.28 to 1.08 ± 0.18 (p 0.001) postoperatively.
Our control population defines the range of error of
this method and validates the concept of comparing
ventricular count outputs (fig. 3), which compares well
with the error of stroke volume comparisons or
=
QUANTITATION OF VALVULAR REGURGITATION/Sorensen et al.
regurgitant fraction calculation in nonregurgitant subjects by cardiac catheterization and quantitative ventriculographyY29 3 36, 51, 52 For example, in seven
patients with isolated mitral regurgitation reported by
Kennedy et al.,22 the "regurgitant fraction" after
successful surgery was 0.17 ± 0.14 (SD).
We conclude that gated equilibrium radionuclide
angiography is a useful method of evaluating valvular
regurgitation and permits noninvasive, accurate quantitation of ejection fraction, relative ventricular
enlargement and regurgitant fraction. Such information is highly reproducible and should provide a means
of serially monitoring these patients.
Acknowledgment
We are grateful to Mariette Jones and J. Jimenez for their
technical assistance and to Anna Fackenthall for preparation of the
manuscript.
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S G Sorensen, R A O'Rourke and T K Chaudhuri
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Circulation. 1980;62:1089-1098
doi: 10.1161/01.CIR.62.5.1089
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