Equilibrium radionuclide gated angiography in patients with tricuspid regurgitation

Equilibrium radionuclide gated angiography in patients with tricuspid regurgitation

VALVUI AR HEART DISEASE Equilibrium Radionuclide Gated Angiography in Patients With Tricuspid Regurgitation BRUCE HANDLER, MD, DAN G . PAVEL, MD, RAY...

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VALVUI AR HEART DISEASE

Equilibrium Radionuclide Gated Angiography in Patients With Tricuspid Regurgitation BRUCE HANDLER, MD, DAN G . PAVEL, MD, RAYMOND PIETRAS, MD, STEVEN SWIRYN, MD, ERNEST BYROM, PhD, WILFRED LAM, MD, and KENNETH M . ROSEN, MD

Equilibrium gated radionuclide anglography was performed in 2 control groups (15 patients with no organic heart disease and 24 patients with organic heart disease but without right- or left-sided valvular regurgitation) and in 9 patients with clinical tricuspid regurgitation . The regurgitant index, or ratio of left to right ventricular stroke counts, was significantly lower in patients with tricuspid regurgitation than in either control group (range and mean f standard error of the mean 0 .4 to 1 .0, 0 .7 ± 0 .1 versus 1 .0 to 1 .5, 1 .3 ± 0 .1 and 1 .0 to 2.9, 1 .5 ± 0 .1, respectively, p <0.001) . Time-activity variation over the liver was used to compute a hepatic expansion fraction which was significantly higher in patients with tricuspid regurgitation than in either control group (1 .4 to 11 .4, 5 .8 f 1 .0 % versus 0 .6 to 3 .4, 1 .9 ± 0 .3 % and 1 .0 to 5 .1, 2.3 10 .2%, respectively, p <0 .001) . Fourier analysis of time-activity variation in each pixel was used to generate amplitude and phase images . Only

pixels with values for amplitude at least 7% of the maximum in the image were retained in the final display . All patients with tricuspid regurgitation had >100 pixels over the liver automatically retained by the computer . These pixels were of phase comparable to that of the right atrium and approximately 180 0 out of phase with the right ventricle . In contrast, no patient with no organic heart disease and only 1 of 24 patients with organic heart disease had any pixels retained by the computer . In conclusion, patients with tricuspid regurgitation were characterized on equilibrium gated angiography by an abnormally low regurgitant index (7 of 9 patients) reflecting Increased right ventricular stroke volume, increased hepatic expansion fraction (7 of 9 patients), and increased amplitude of count variation over the liver in phase with the right atrium (9 of 9 patients) .

Tricuspid regurgitation can present a difficult clinical diagnosis, particularly when other cardiac lesions are present. Although first-pass radionuclide angiography was used to support the diagnosis in 1 case of traumatic tricuspid regurgitation,' equilibrium radionuclide gated angiography has not previously been employed to establish a diagnosis of tricuspid regurgitation . In this study, computer-processed results of equilibrium radionuclide angiography including Fourier analysis of time-activity variation in patients with clinically

manifest tricuspid regurgitation were compared with results in 2 control groups, 1 consisting of patients with no organic heart disease and 1 consisting of patients with organic heart disease but no clinical evidence of right- or left-sided valvular regurgitation . Measurements of cardiac regurgitant index, hepatic expansion fraction, and amplitude and phase over the liver were abnormal in patients with tricuspid regurgitation . Methods Patient selection : Three groups of patients were studied : those with no organic heart disease, those with organic heart disease but without right- or left-sided valvular regurgitation, and those with tricuspid regurgitation . Criteria for inclusion of patients with no organic heart disease were normal results on cardiovascular examination, normal heart size on chest X-ray, and normal left ventricular ejection fraction and wall motion on equilibrium gated angiography . Absence of demonstrable organic heart disease was supported by M-mode echocardiography and cardiac catheterization with angiography in some patients .

From the Section of Cardiology, Department of Medicine, and the Section of Nuclear Medicine, Department of Radiology, The Abraham Lincoln School of Medicine, University of Illinois, Chicago, Illinois . This study was supported in part by Training Grant 07387 from the National Institutes of Health, Bethesda, Maryland, and by a grant from the Eleanor B . Pillsbury Resident Trust Fund, Chicago, Illinois . Manuscript received October 12, 1981 ; revised manuscript received July 6, 1982, accepted July 9, 1982 .

Address for reprints : Steven Swiryn, MD, Cardiology Section, University of Illinois, PO Box 6998, Chicago, Illinois 60680 .

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Criteria for inclusion of patients with organic heart, disease were the presence of diagnosed heart disease without clinical evidence of right- or left-sided valvular regurgitation on history, physical examination, and noninvasive studies . All patients in the group had cardiac catheterization to confirm the diagnosis and all had equilibrium gated angiographic study . Criteria for inclusion of patients with tricuspid regurgitation were the presence of at least 2 of the following 3 findings on physical examination : abnormal CV wave in the internal jugular venous pulse, a systolic murmur at the left lower sternal border that increased in intensity on inspiration, and a palpable expansile liver . An equilibrium radionuclide angiographic study was performed in each patient . Other independent data for the presence of tricuspid regurgitation were elevated right atrial pressures and large right atrial CV waves at cardiac catheterization, saline microbubbles visualized for at least 4 heats at the right atrial inferior vena caval junction on 2-dimensional echocardiography,z •s visible systolic bulging (of an enlarged right atrium and a palpable thrill over the right atrial wall) during cardiac surgery, regurgitation of contrast material into the right atrium during right ventricular angiography, surgical tricuspid valvectomy, and autopsy evidence of a grossly dilated right atrium, ventricle, and tricuspid valve anulus . Equilibrium gated radionuclide angiography : Each study was performed with the patient in the supine position using in vivo red blood cell labeling with technetium-99m .4

A large field of view camera (Siemens) was positioned to obtain the best septal left anterior oblique view of the heart with a 10 to 15° caudal tilt . Data were acquired (Informatek Simis 3 computer) using 64 frames per cardiac cycle with 250,000 to 300,000 counts per frame and stored on tape for processing . Computer processing for calculation of left ventricular ejection fraction and assessment of left ventricular regional wall motion employed methods previously described . 5-8 The left ventricular regurgitant index was calculated as the ratio of left ventricular stroke counts to right ventricular stroke counts . 9 The stroke counts were obtained from left and right ventricular time-activity curves of the respective regions of interest by subtraction of the respective ventricular endsystolic from the end-diastolic counts for each patient studied . '1'his allowed for right ventricular end-systole to occur during a different frame from left ventricular end -systole . Hepatic expansion fraction : In each patient the entire field-of-view image at end-diastole was used to manually outline for computer processing a region of high activity below and to the right of the heart thought to correspond to the liver . The upper border of this region of interest was determined by following a trough of activity between the heart and the liver . This border was drawn tightly to avoid including the heart itself. Hepatic counts for each time frame were determined by the computer . A time-activity curve for the liver was then generated. A hepatic expansion fraction was calculated using the following formula : hepatic expansion fraction = (maximal counts - minimal counts)/minimal counts . Maximal and minimal counts were chosen by numerical value regardless of the frame in which they occurred during the cardiac cycle (see section on Fourier analysis) . Interobserver variability in the measurement of hepatic expansion fraction was evaluated in 4 study patients . Independently calculated values by 2 of us differed by 0.1, 0.1, .2, 0 and 0 .3 percentage points, respectively . Fourier analysis : Amplitude and phase analysis was performed using the first Fourier harmonic of time-activity variation in each pixel to generate amplitude and phase images . Each displayed pixel was color coded according to its value for amplitude and phase, respectively .1a12

TABLE I Results of Equilibrium Gated Angiography

OHD, LVEF(%) RI

HEF(%) Hepatic amplitude present/ total patients

p

No OHD

No TI

TI

68±2 1 .3±0 .1 1 .9±0 .3 0/15

48±6 1 .510 .1 2 .3±0 .2 1/24

53±5 0.7±0 .1 5.811 .0 9/9

Value NS ~ <0 .001 <0 .001

Values are the mean ± standard error of the mean . HEF = hepatic expansion fraction ; LVEF = left ventricular ejection fraction ; OHD = organic heart disease ; RI = regurgitant index ; TI = tricuspid insuffi • clency .

Organs that have large changes in blood volume during the cardiac cycle, such as the heart, have high amplitude and well defined areas of coherent phase . However, organs not exhib . iting ordered variation of blood volume during the cardiac cycle, even though they may contain a large volume of blood, such as the spleen, have low amplitude values and random phase . The former accentuates the statistical uncertainty in the calculation of phase values in such organs . Therefore, to eliminate areas of low amplitude and uncertain phase, 2 steps were taken . An amplitude threshold of 7% (of the maximal amplitude value of the entire image) was used to eliminate all pixels of low amplitude. The specific value of 7% was chosen empirically to best separate the control and study groups. Isolated clusters of 4 or fewer pixels, which also may represent statistical uncertainty, were automatically eliminated from the final amplitude image . The final phase image was derived from the final amplitude image . Thus, pixels eliminated from the amplitude image were also eliminated from the final phase image. The phase image depicts pixels according to their respective phase relative to a 0° phase referencelo ,11 (with the entire cardiac cycle representing 360°) and represents the relative timing of count variation . Structures that fill and empty synchronously, such as the right and left ventricles, have similar phase . Structures that fill and empty in opposition, such as the left atrium and left ventricle, have a-phase difference in the vicinity of 180° . Statistical analysis: The left ventricular ejection fraction, regurgitant index, hepatic expansion fraction, and amplitude and phase images for the 3 groups of patients were compared . Statistical analysis was carried out using Scheffe's method for analysis of variance . Results

Clinical characteristics : Fifteen patients with no organic heart disease comprised the first control group . They were aged 15 to 58 years (mean ± standard deviation 31 ± 12) . Six patients were women and 9 were men . The clinical diagnosis was supraventricular tachycardia in 6 patients, noncardiac chest pain in 3, primary conduction disease in 2, and pancreatitis, pneumonia, gastroenteritis, and vasovagal syncope in 1 patient each . By study design, each patient had essentially normal findings on cardiovascular examination and normal cardiac size on chest X-ray . Additional independent data for the absence of heart disease included no significant abnormalities on M-mode echocardiography (11 of 11 patients) and normal cardiac catheterization with angiography (8 of 8 patients) .



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I I .01 9.0 1 .9

a 8 .0 1 .7

0 H U Q

1 .5 x z

1 .3

z

1 .1

§ mean ! SEM

z 7.0 6 .0

O z

5 .0

rc 0,9

a w 4 .0

0

U

w

a a

0 .7 § mean ± SEM

L

3.0

W

20

0.5

1 .0

0.3_r

no OHD

OHD, no TI

TI no OHO

OHD, no TI

TI

FIGURE 1 .

Regurgitant index is plotted on the ordinate . Each point represents 1 patient. Left column, values for patients with no organic heart disease (no OHD) ; middle column, values for patients with organic heart disease but without valvular insufficiency (OHD, no TI) ; right column, values for patients with tricuspid insufficiency (TI). Mean value for control patients is significantly higher than that of patients with tricuspid insufficiency (p <0 .001) . SEM = standard error of the mean .

FIGURE 2 .

Twenty-four patients, aged 50 ± 14 years (range 14 to 69), with organic heart disease but without right- or left-sided valvular regurgitation comprised the second control group . There were 8 women and 16 men . The clinical diagnosis was atherosclerotic heart disease in 10 patients, cardiomyopathy in 8, mitral stenosis in 1, and miscellaneous cardiovascular diagnoses in the remaining 5 . In each patient, the cardiovascular examination was appropriate for the clinical diagnosis and did not specifically suggest any right- or left-sided valvular regurgitation. The clinical diagnosis in each patient was confirmed by cardiac catheterization and angiography . Nine patients, aged 41 ± 8 years (range 20 to 45), with tricuspid regurgitation comprised the study group . Five patients were women and 4 men. The clinical diagnosis was rheumatic heart disease in 5 patients, tricuspid valvectomy for bacterial endocarditis in 2, congenital heart disease in 1, and mixed-connective tissue disease with secondary pulmonary hypertension in 1 . On physical examination, 7 patients had abnormal jugular venous CV waves, a positive Carvallo's sign, and an expansile liver . The remaining 2 patients had abnormal jugular venous CV waves and an expansile liver without documented Carvallo's sign to establish the presence of tricuspid regurgitation on clinical grounds . Independent data for the presence of tricuspid regurgitation were cardiac catheterization with elevated mean right atrial pressure and an increased right atria] CV wave (6 of 6 patients), positive contrast echocardiography (4 of 4 patients), positive findings at cardiac surgery (2 of 2

patients), positive contrast right ventricular angiography (1 of 1 patient), surgical tricuspid valvectomy in 2 patients, and postmortem evidence of a grossly dilated right atrium, ventricle, and tricuspid valve anulus in 1 patient . Equilibrium radionuclide angiography (Table I) : For patients with no organic heart disease, left ventricular ejection fraction ranged from 60 to 75% (mean f standard error of the mean 68 ± 2%) . For patients with organic heart disease without valvular regurgitation, left ventricular ejection fraction ranged from 19 to 82% (mean 48 ± 6%) . For patients with tricuspid regurgitation, the left ventricular ejection fraction ranged from 22 to 74% (mean 53 -L 7%) . Differences between each control group and the study group were not statistically significant . For patients with no organic heart disease, the regurgitant index ranged from 1 .0 to 1 .5 (mean 1 .3 f 0 .1) . Normal in our laboratory is 0 .9 to 1 .7 . 9 For patients with organic heart disease but without valvular insufficiency, the regurgitant index ranged from 1 .0 to 2 .9 (mean 1 .5 f 0 .1.) . There was no significant difference in regurgitant index between these 2 control groups . In contrast, in patients with tricuspid regurgitation, the regurgitant index ranged from 0 .4 to 1 .0 (mean 0 .7 ± 0 .1), which was significantly lower than that in each control group (p <0 .001) (Fig . 1) . Two patients with tricuspid regurgitation had a regurgitant index within the normal range . One of these patients had concomitant severe periprosthetic aortic regurgitation demonstrated by aortic root angiography . The other patient

Hepatic expansion fraction in percentage is plotted on the ordinate . Each point represents 1 patient . Left column, values for patients with no organic heart disease (no OHD) ; middle column, values for patients with organic heart disease but without valvular insufficiency (OHD, no TI); right column, values for patients with tricuspid insufficiency (TI). Mean value for control patients is significantly lower than that of patients with tricuspid insufficiency (p <0.001).



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FIGURE 3 . Hepatic expansion fraction . Left, end-diastolic image and outlined hepatic region of interest in a control patient (above) and a patient with tricuspid insufficiency (below) . Right, corresponding time-activity curves for the hepatic regions of interest . Counts are represented on the ordinate and frame number on the abscissa . Note the ordered variation of hepatic activity during the cardiac cycle in the patient with tricuspid insufficiency .

had concomitant severe mitral regurgitation demonstrated on left ventriculography . Hepatic expansion fraction (Table I) : For patients with no organic heart disease, the hepatic expansion fraction ranged from 0 .6 to 3 .4% (mean 1 .9 10 .3%), reflecting the absence of substantial count variation over the liver during the cardiac cycle . For patients with organic heart disease without valvular regurgitation, the hepatic expansion fraction ranged from 1 .0 to 5.1% (mean 2 .3 ± 0.2%) . There was no significant difference in the hepatic expansion fraction between these 2 control groups . Four of 24 patients (17%) with organic heart disease without valvular regurgitation had values for hepatic expansion fraction that were above the range of those in patients with no organic heart disease . However, in none of these patients did the peak of hepatic activity occur simultaneously with or within I frame of the nadir of right ventricular activity (see later), For patients with tricuspid regurgitation, the hepatic expansion fraction ranged from 1 .4 to 11 .4% (mean 5.8 ± 1 .0%), which was significantly higher than that in each control group (p <0.001) (Fig . 2) . Two patients with tricuspid regurgitation had values for hepatic expansion fraction that were within the range of those in patients with no organic heart disease . Except in 1 of these patients, peak hepatic activity occurred simultaneously with or within 1 frame of the nadir of right ventricular activity in patients with tricuspid regurgitation . The outlined hepatic regions of interest and time-activity curves from representative patients with no organic heart disease versus those in the study group are illustrated in Figure 3 . Amplitude and phase images (Fig. 4) : All patients with no organic heart disease and 23 of 24 patients with organic heart disease without valvular insufficiency had

FIGURE 4 . Final amplitude and phase images . Left, amplitude images in a control patient (above) and a patient with tricuspid insufficiency (below). Right, corresponding phase images . Note that in the control patient all pixels over the liver have been eliminated automatically (<7% maximal amplitude) . In the patient with tricuspid insufficiency, pixels representing the liver have been retained (>7% maximal amplitude) . The liver is of similar phase to the right atrium and of opposite phase to the right ventricle .

amplitude values for all pixels over the liver of <7% of the maximal amplitude in the image . Therefore, these pixels were automatically eliminated from the amplitude and phase images . In contrast, all patients with tricuspid regurgitation had at least 100 pixels over the liver with an amplitude >7% of the maximal amplitude in the image . Therefore, these pixels were automatically retained in the amplitude and phase images . Thus, substantial amplitude of hepatic blood volume variation with the cardiac cycle was present in all 9 patients with tricuspid regurgitation . On the phase images there is uniform phase for the atria and uniform (but 180° opposite) phase for the ventricles in all 3 groups of patients, reflecting that the atria fill when the ventricles empty (Fig. 4) . Pixels over the liver in all patients with tricuspid regurgitation were in phase with the right atrium . Summary of data: In summary, 3 variables were examined in each patient: regurgitant index, hepatic expansion fraction, and amplitude over the liver . All patients with no organic heart disease had a normal regurgitant index, low hepatic expansion fraction, and absence of significant amplitude over the liver. Of patients with organic heart without valvular regurgitation, all had a normal (17 patients) or increased (7 patients) regurgitant index. Twenty of 24 patients (83%) had low hepatic expansion fractions . Twenty-three of 24 (96%) had absence of significant amplitude over the liver . In contrast, 7 of 9 patients (78%) with tricuspid regurgitation had a below-normal regurgitant index . Seven of 9 patients (78%) with tricuspid regurgitation had an above-normal hepatic expansion fraction . All 9



January 15, 1983 THE AMERICAN JOURNAL OF CARDIOLOGY Volume 51

patients (100%) with tricuspid regurgitation had substantial amplitude over the liver . Looked at another wa y, in 5 of 9 patients with tricuspid regurgitation, all 3 measures gave abnormal values ; 4 of 9 patients had abnormal values in only 2 measures . Discussion Currently, the diagnosis of tricuspid regurgitation is established on the basis of physical findings . However, these findings may be obscured by multivalvular disease or after valve replacement for left-sided lesions . Right ventricular angiography and direct surgical evaluation are invasive and have been criticized as unreliable . 13 Contrast M-mode and 2-dimensional echocardiography ,2,3 sometimes with pulsed Doppler echocardiography, 14 has recently been useful in establishing the presence of tricuspid regurgitation . Intracardiac phonocardiography has also been useful when combined with right ventricular angiography .l 5 Equilibrium radionuclide gated angiography provides a noninvasive method for evaluating aortic or mitral insufficiency, or both 9,16-19 However, there are no reports of a series of patients with right-sided valvular regurgitation . Patients with left-sided regurgitation have an increased left ventricular stroke volume and therefore an elevated regurgitant index . Patients with right-sided regurgitation would logically be expected to have an increased right ventricular stroke volume and consequently a decreased regurgitant index . In the present study, 7 of 9 patients with tricuspid regurgitation had a low regurgitant index compared with that of patients without evidence of tricuspid regurgitation (Fig . 1) . However, a low regurgitant index might be expected in many situations characterized by right ventricular volume overload . The physical findings of pulmonary regurgitation producing right ventricular volume overload are distinctive and usually not confused with those of tricuspid regurgitation . Intracardiac left to right shunting in atrial septal defect results in an increased Qp/Qs ratio because of right-sided volume overload . 20 However, concomitant left-sided regurgitation with increased left-sided stroke volume, depending on the degree, tends to normalize the ratio of left to right ventricular stroke counts . This was the case in 2 patients in the present series with tricuspid regurgitation whose values for regurgitant index were within the normal range . To our knowledge, no reports have appeared analyzing the results of time-activity variation over noncardiac structures during equilibrium gated angiography . Eight of 9 patients with tricuspid regurgitation demonstrated ordered time-activity variation over the liver during the cardiac cycle (Fig . 2 and 3) . Comparing the time-activity curves over the liver and the right ventricle, the peak of hepatic activity occurred within 1 frame or simultaneously with the nadir of right ventricular activity for 8 of 9 patients with tricuspid regurgitation . It seems doubtful that transmitted right ventricular, diaphragmatic, or abdominal aortic pulsations could result in an increased hepatic expansion fraction to the degree seen in patients with tricuspid regurgitation. A left ventricular to right atrial shunt as

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might occur in some patients with atrioventricular canal defects or ruptured sinus of Valsalva into the right atrium or right ventricle might mimic similar hemodynamic results and consequently an expansile liver . However, the clinical history and physical findings should allow differentiation of these patients . At present, manual determination of a hepatic region of interest is somewhat subjective, depending as it does on outlining an area of high activity where the liver is located. The critical boundary of this region is found between the liver and the heart, especially in patients with right heart enlargement . Therefore, we made this border tight on the liver side . The finding that the apex of the hepatic time-activity curve corresponded to the nadir of the right ventricular time-activity curve (opposition of phase) is reassuring, because inclusion of a large area of right ventricle in the hepatic region of interest should obliterate this . Inclusion of the inferior vena cava within the hepatic region of interest seems probable, and this structure may also contribute to some of our findings. Our group and others previously reported results of Fourier analysis in left ventricular regional wall motion abnormalities and in abnormall electrical activation including left bundle branch block and ventricular tachycardia . 10,12,21 In the present study, Fourier analysis was applied to each pixel from a large field-of-view image . The resulting amplitude image in all control patients had no pixels with substantial (>7% of maximum) amplitude over the liver . All patients with tricuspid regurgitation had ?100 pixels with substantial amplitude over the liver . The maximal amplitude in the image should usually occur over the left ventricle . When a patient with tricuspid regurgitation has a low left ventricular ejection fraction, pixels over the liver may be included as having ?7% of a low maximal amplitude and might not have substantial amplitude in an absolute sense . That the mean value of left ventricular ejection fraction in patients with organic heart disease without valvular regurgitation was lower than that in patients with tricuspid regurgitation argues against errors in resulting amplitude images . Pixels corresponding to the right atrial and hepatic regions of interest were of similar phase to each other and of opposite phase to pixels corresponding to the right ventricular region of interest . Thus, pixels over the hepatic region of interest with substantial amplitude correspond to the physical finding of an expansile liver. Clinical significance : We did not explore this technique in patients with severe right heart failure and hepatic congestion but without tricuspid regurgitation, although they would he an important control group . It would be very difficult to know conclusively that such patients did not have small degrees of tricuspid regurgitation . Because no strong standard is available for determining tricuspid regurgitation, no statement can be made about sensitivity or specificity of this method in such patients . In summary, equilibrium gated angiography and Fourier analysis were used to distinguish patients with from those without clinical tricuspid regurgitation .



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Characteristic findings of patients with tricuspid regurgitation included an abnormally low regurgitant index in 7 of 9 patients, an increased hepatic expansion fraction in 7 of 9 patients, and increased amplitude over the liver with pixels in phase with the right atrium in all 9 patients . These results imply that gated angiography can he used to confirm the presence of tricuspid regurgitation or to detect unsuspected tricuspid regurgitation . It is not known whether this method will allow quantification of the severity of this lesion .

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KM. Assessment of left ventricular function by radionuclide anglograph y during induced supraventricular tachycardia . Am J Cardiol 198147 . 555-561 . 9 . Lam W, Pavel DG, Byrom E, Sheik A, Best D, Rosen K . Radionuclid e regurgitant index-value and limitations . Am J Cardiol 1981 ;47:292-298 10 . Adam WE, Tarkowska A, Biller F, Stauch M, Geffers H . Equilibrium ra . dionuclide ventriculography . Cardiovasc Radial 1979 ;2 :161-173 . 11 . Byrom E, Pavel DG, Swiryn 5, Meyer-Pavel C . Phase images of gated studies : a standard evaluation procedure . In : Esser P, ed . Functional Mapping of Organ Systems and Other Computer Topics . New York : Society of Nuclear Medicine, 1981 :129-138 . 12. Swiryn S, Pavel DG, Byrom E, Witham D, Meyer-Pawl C, Wyndham CRC, Handler B, Rosen K. Sequential regional phase mapping of radlonuclida gated biventriculograms in patients with left bundle branch block . Am Heart J 1981 ;102 :1000-1010, 13 . Llngamneni R, Cha SD, Maranhao V, Goach AS, Goldberg H . Tricuspid regurgitation: clinical and angiographic assessment . Cathet Cardiovaso Diagn 1979 :5:7-17 . 14. Waggoner AD, Qulnones MA, Young JB, Brenda TA, Shah AA, Verani MS, Miller RR . Pulsed Doppler echocardiographic detection of right-sided valve regurgitation. Experimental results and clinical significance . Am J Cardiol 1981 ;47:279-886 . 15 . Cha SD, Gooch AS, Maranhao V, Koehler E . Intracardiac phonocardiography in tricuspid regurgitation : relation to clinical and angiographl c findings . Am J Cardiol 1981 ;48 :576-583 . 16. Rlgo P, Alderson PO, Robertson RM, Becker LC, Wayner Hill . Measurement of aortic and mltral regurgitation by gated cardiac blood pool scans . Circulation 1979 ;60 :306-31 . 17. Sorensen SG, O'Rourke RA, Chadhuri TK. Non-invasive quantiatlon of valvular regurgitation by gated equilibrium radionuclide angiography . Circulation 1980 ;62:1089--1098 . 19. Bough EW, Gansman E, North 0, Shulsman RS . Gated radionuclide angiographic evaluation of valve regurgitation . Am J Cardiol 1980 ;46 :42342a19 . Boucher CA, Orada RD, Pohost GM . Current status of radionuclide imaging in valvular heart disease. Am J Cardiol 1981 ;46 :1153-1163 . 20 . Bough EW, Gandsman EJ, Benham ID, Boden WE, North DL, Shulman RS Detection and quantification of atrial shunts in adults by gated radionuclide anglography (abstr) . Am J Cardiol 1980 ;45 :409. 21 . Swiryn S, Pavel DO, Byrom E, Bauemfelnd RA, Strasberg B, Polilee E, Lam W, Wyndham CRC, Rosen KM . Sequential regional phase mapping of radionuclide gated biventriculograms in patients with sustained ventricular tachycardia : close correlation with electrophysiologic characteristics . Am Heart J 1982;103 :319-332.