- Email: [email protected]
Estimation of right ventricular volume by modified echocardiographic subtraction method
Estimation of right ventricular volume by modified echocardiographic subtraction method To evaluate the accuracy and clinical utility of right ventricular volume estimated by a modified echocardiographic subtraction method versus Krebs’ original subtraction method, an experiment was performed on hearts excised from 25 animals (dogs, pigs, and cows) followed by a clinical study of 41 patients with heart disease. Right ventricular volume was measured by subtracting the left ventricular volume from that of the whole heart based on echocardiographic apical twoand four-chamber views by means of the area-length method. In the animal heart study, the coefficient of variation between the right ventricular volume estimated by the modified method and the true volume was + 13%. The regression equation was y = 0.94x + 4.15 (r = 0.987, p < 0.001) and showed good correlation, whereas the right ventricular volume obtained by the original method underestimated the true volume (coefficient of variation = + 25%, y = 0.59x + 1.11; r = 0.976, p < 0.001). In the clinical study, the coefficient of variation between right ventricular volume estimated by the modified echocardiographic method and RV volume estimated by radionuclide ventriculography was -+ 15%. The regression equation was y = 0.80x + 13.3 (I = 0.935, p < 0.001). This correlation was better than that obtained by the original method (coefficient of variation = + IS%), where the regression equation was y = 0.60x + 2.43 (r = 0.888, p < 0.001). Thus the accuracy of the modified subtraction method was validated, and this method showed a better correlation than the original method both experimentally and clinically. (AM HEART J 1992;123:1011.)
Masaaki Tomita, MD, Hiroshi Masuda, MD, Tomoichiro Sumi, MD, Hisashi Shiraki, MD, Kohshi Gotoh, MD, Yasuo Yagi, MD, Tatsuo Tsukamoto, MD, Yasushi Terashima, MD, Yoko Miwa, MD, and Senri Hirakawa, MD. Gifu, Japan
Accurate and convenient methods for measuring right ventricular volume have long been sought. Many investigators have attempted to estimate this parameter angiographically.l-10 Echocardiographic methods are complicated and seem impractical for clinical use.11-22In 1982 Krebs et a1.23attempted to approximate right ventricular volume geometrically by experimenting with a subtraction method in a plastic model. We have now modified the original subtraction method to yield a more accurate estimate of right ventricular volume. To test the accuracy and clinical utility of this estimate obtained by the original method versus a modified approach, the following studies were performed: (1) The accuracy of the original method and the modified method was compared in excised animal hearts, and (2) a clinical From the Second of Medicine. Received Reprint Medicine, Japan. 4/l/35351
Department
for publication requests: Masaaki Gifu University
of Internal Jan.
31, 1991;
Medicine, accepted
Gifu Sept.
University
School
20, 1991.
Tomita. MD, Second Department School of Medicine, Tsukasa-machi
of Internal 40, Gifu 500,
study was performed in patients with various heart diseasesin whom right ventricular volume was estimated by the original subtraction method and by the modified echocardiographic method. The greater accuracy of the modified method was demonstrated with the use of radionuclide angiocardiography asthe standard. METHODS
In an initial experiment we studied hearts excised from five mongrel dogs,11 pigs, and nine cows.A subsequent clinical study wasperformed in 41 patients (31 men and 10 women,aged 17 to 69 years) with the following diagnoses: dilated cardiomyopathy in nine, mitral valve prolapse in five, myocardial infarction in seven,valvular heart disease in four, coronary artery diseasein nine, congenital heart diseasein one, hypertrophic cardiomyopathy in two, and myocarditis in one; three normal subjectswere also studied. Echocardiographic recordswere obtained by meansof a Toshiba SSH40A device (3.5 MHZ transducer) (Toshiba Medical Co., Ltd., Tokyo, Japan). Experimental study. Animal hearts excised within the previous 24 hourswere placed in a water bath and fixed on a rubber stand. Apical two-chamber and four-chamber views were obtained by echocardiography. After echocar1011
April
1012
Tomita
et al.
American
(A+B) B -
F.gi .:.a”“L ,T;;:. .:.,. :.::.:: :.:.:.:.:: :,:, :.,.,, .: .:. ..A = .,.J.;.. :. ..:..;:.,:‘-‘, .:::,:.::. h’..;.:,::.:, .“$*y
Fig. 1. Subtraction methodsfor estimating right ventricular volume. A, Modified subtraction method. (A + B) representswhole heart surrounded by outer line; (A) represents left ventricle surrounded by outer line, which includesleft ventricular myocardium; 03) representsright ventricular volume. a, Anteroposterior minor axis of left ventricular outer surface; b, diameter of right ventricular side septal wall to outer surface of left ventricular lateral wall, c, diameter of right ventricular side septum to right ventricular free wall, h, height of left ventricle. B, Krebs’ original subtraction method. (A’ + B’) representsvolume surrounded by dotted line; (A’) representsleft ventricular volume surrounded by dotted line including septum; (B’) represents right ventricle surrounded by dotted line. Shaded area represents area underestimated by Krebs’ original method as compared with modified method. a’, Anteroposterior minor axis of inner surface of left ventricle; b ’ , diameter of right ventricular side septal wall to inner surface of left ventricular lateral wall; c’, diameter of right ventricular septal wall to right ventricular free wall; h’, height of left ventricle. In this schema,for simplicity, h’ is shown to be the samelength as h; h’ is shorter than h by thickness of apical myocardium.
diography was performed in these views, silicone rubber was injected into the right ventricle and castswere made. The actual right ventricular volume of the castswasmeasured by the water displacement method. Clinical study. Echocardiographic records were obtained from patients placed in a 45-degreeleft lateral decubitus position. Apical four- and two-chamber views were recorded while subjectsheld their breath at end expiration. Both the apical four- and two-chamber views wererecorded and pictured at end diastole,which falls on the peak of the R wave of the ECG, and at end systole, which falls on the aortic closure sound of the phonocardiogram. Videocassette recordings (CR-6600, Nippon Victor Inc., Gifu, Japan) were alsoobtained for useasa referencein tracing the echocardiograms.Calculation of the area was performed manually with a planimeter. Calculation of right ventricular volume. The modified subtraction method is shownin Fig. 1, A. According to the original method of Krebs et a1.,23right ventricular volume (B ‘) wascalculated by subtracting the left ventricular vol-
Heart
1992
Journal
ume including the interventricular septum (A’) from the whole heart volume including the right and left ventricles plus the interventricular septum (A’ + B’) (Fig. 1, B). Both (A’) and (A’ + B’) were consideredto be hemiellipsoid. In Krebs’ original method right ventricular volume (B’) was calculated as follows: Right ventricular volume (B’) = (A’ + B’) - (A’) (Fig. l,B) (equation 1). Thus (A’) and (A’ + B’) were calculated as shownin Fig. I, B by using two orthogonal planessuch asan apical four-chamber view and an apical two-chamber view. The anteroposterior minor axis of the left ventricular cavity (a’) wascalculated asfollows: (a’) = 4 (Sl’)/*h’ (equation Z), where Sl’ isthe area of the left ventricular cavity in the apical two-chamber view and (h’) is the greater height of the left ventricle measuredin two orthogonal planes. The diameter of the right ventricular side septal wall to the inner left ventricular lateral wall (b’) wascalculated as follows: (b’) = 4(S2’)lah’ (equation 3), where S2’ is the area of the left ventricle including the septumin the apical four-chamber view. The diameter of the right ventricular inner surface of the free wall to the inner left ventricular lateralwall(b’ + c’) wascalculatedasfollows:(b’ + c’) = 4 (S3’)/rh’ (equation 4), where S3’ is the area of the left ventricle including the septum and right ventricle in the apical four-chamber view. (A’) was calculated by the area-length method as follows: (A’) = (r/6) (h’) (a’) (b’). With the useof equations 2 and 3, (A’) was given as follows: (A’) = 8 (Sl’) (S2’)/ 3T(h’) (equation 5). (A’ + B’) wascalculated by the arealength method as follows: (A’ + B’) = (a/6) (h’) (a’) (b’ + c’). With the useof equations2 and 4, (A’ + B’) was given asfollows: (A’ + B’) = 8 (Sl’) (S3’)/3a(h’) (equation 6). Thus the right ventricular volume was calculated as follows: (B’) = (A’ + B’) - (A’) = 8(Sl’) (S3’)/ 3a(h’) - 8 (Sl’) (S2’)/37r(h’) (equation 7). In our modified method the right ventricular volume (B) wascalculated by subtracting the entire left ventricle (A) (including the left ventricular myocardium) from the entire heart (including the right ventricle and the entire left ventricle) (A + B) (Fig. 1, A). Both A and A + B were calculated as hemiellipsoidby the area-length method with the use of apical four- and two-chamber views. Thus in the modified method right ventricular volume was calculated as follows: Right ventricular volume (B) = (A + B) - (A) (Fig. 1, A) (equation 8). As in the original method, (a) is the anteroposterior minor axis of the left ventricular outer surface, which was calculated as follows: (a) = 4(Sl)lnh (equation 9), where Sl is the area of the left ventricle including the myocardium in the apical two-chamber view and (h) is the greater height of the left ventricle in two orthogonal planes. The diameter of the right ventricular side septal wall to the outer surfaceof the left ventricular lateral wall (b) was calculated as follows: (b) = 4(S2)/?rh (equation lo), where S2 is the areaof the left ventricle including the septum and the lateral wall in the apical four-chamber view. The diameter of the inner surface of the right ventricular free wall to the outer surface of the left ventricular lateral wall (b + c) wascalculated asfollows: (b + c) = 4(S3)/?rh(equa-
Volume123 Number 4, Part
RV volume by echo subtraction
1
1013
Fig. 2. Echocardiographic recordsof exciseddog heart. Left upper panel, Apical four-chamber view. Left lower panel, Tracing of epicardial and endocardial surfacesas shown by dotted lines. In the modified method, areasurroundedby outer dotted line wasplanimetered.In the original method, areaincluding right ventricle, left ventricular cavity, and septum wasplanimetered. Right upper panel, Apical two-chamber view of Ieft ventricle. Right lower panel, Tracing of epicardial and endocardial surfacesof left ventricle. In the modified method, area surrounded by outer dotted line wasplanimetered. In contrast, in the original method, area surrounded by inner dotted line, which is equal to left ventricular cavity, wasplanimetered. Right ventricular volume wascalculated by meansof above-measuredareasand equations 7 and 14. tion II), where S3 is the areaof the left ventricle including both the septum and the lateral wall and the right ventricle in the apical four-chamber view. Thus the left ventricle, including the myocardial muscle (A), was calculated by the area-length method as follows: (A) = (*/6)h a b. With the use of equations 9 and 10, (A) was given as follows: (A) = 8 (Sl) (S2)/3xh (equation 12). (A + B) was calculated by the area-length method as follows: (A + B) = (a/6)h a (b + c). With equations 9 and 11, (A + B) wasgiven asfollows: (A + B) = 8 (Sl) (S3)/3rh (equation 13). Thus in the modified method right ventricular volume (B) wascalculated asfollows: Right ventricular volume (B) = (A + B) - (A) = 8 (Sl) (S3)/3ah - 8 (Sl) (S2)/3Th (equation 14). Calculation
of right ventricular
volume in animal
hearts
(Fig. 2). As explained above, the apical four- and twochamber views obtained by echocardiography permitted calculation of (A + B) and (A) by the biplane area-length method by planimetering areas Sl, S2, and S3 and measuring the maximum height. Right ventricular volume was then obtained by equation 14, whereas in the original method it was obtained by equation 7. The actual right ventricular volume was measuredby the water displace-
ment method with the useof casts.Thus the actual right ventricular volume wascomparedwith two calculated volumes.Lengths measuredby the right ventricular cast and by echocardiography were compared in three directions suchasmaximum length (apical to tricuspid valve annular plane maximum length), maximum depth (right ventricular septal to free wall maximum diameter), and maximum width (anteroposterior maximum length at the tricuspid valve annular plane). Calculation
of right
ventricular
volume
in patients
(Figs. 3 and 4). The echocardiographicend-diastolic and end-systolic right ventricular volumes were obtained as explained previously by planimetering the area and obtaining the maximum height at both end diastole and end systole. End-diastolic and end-systolic volumeswere then calculated by meansof equation 7 in the original method and equation 14 in the modified method. Radionuclide ventriculography combined with thermodilution for measuring right ventricular volume. Data were obtained from the 45-degree left anterior oblique projection by a gamma camera (SiemensZLC, Siemens Gammasonics,Inc., Hoffman Estates,Ill.) and analyzed by computer (ScintiPack 2400 Shimadzu Corp., Tokyo, Ja-
1014
Tomita et al.
American
April 1992 Heart Journal
Fig. 3. Echocardiographic records of 50-year-old man with myocardial infarction taken at end diastole. Left upper panel, Apical four-chamber view. Left lower panel, Tracing of epicardial and endocardial surfaces. Right upper panel, Apical two-chamber view of left ventricle. Right lower panel, Tracing of epicardial and endocardial surfaces. Right ventricular volume was calculated as explained in Fig. 2. pan). Radionuclide ventriculography was performed by a technique in which red blood cells labeled with technetium 99m in vivo were used. Data were obtained from a 45-degree left anterior oblique projection at the equilibrium phase. The right ventricular ejection fraction (EF) was obtained by the count-based method; frame images were obtained during s-minute recordings at the equilibrium phase. The region of interest was placed over both the right and left ventricles on the phase images. Background region of interest was placed outside of the right ventricle at the end-systolic phase. The stroke volume (SV) was obtained from the cardiac output (CO) measured by the thermodilution method and the heart rate (HR) as follows: SV = CO/ HR. Right ventricular end-diastolic volume (EDV) and end systolic volume (ESV) were calculated as follows: EDV = (SV/EF) and ESV = EDV - SV. Statistics. Data obtained from each of the preceding methods were compared by linear regression analysis with standard statistical formulas. Student’s unpaired t test was used to analyze differences with p < 0.05 considered statistically significant. In this study variance is expressed as mean t SD. RESULTS Study of excised animal hearts. Right ventricular volume measured by the newly modified subtraction method showed good correlation with the actual vol-
ume measured in the casts (y = 0.94x + 4.15; r = 0.987, p < 0.001, coefficient of variation [CV] = +- 13 % ) (Fig. 5). On the other hand, right ventricular volume measured by Krebs’ original method underestimated the actual volume (Fig. 6) (y = 0.590x + 1.213; r = 0.976, p < 0.001, CV = ~~25%). Individual data are shown in Table I. We also compared the right ventricular dimension measured by echocardiography with that measured in the casts (Table II). As shown in Table II, agreement was good with respect to the length of the right ventricle (6.2 4 2.2 cm cast vs 5.5 +- 1.6 echocardiography, p = NS), its diameter (‘7.2 +- 2.7 cm cast vs 7.3 it_ 2.2 echocardiography, p = NS), and i t s maximum depth (2.5 s 1.0 cm cast vs 2.8 +- 0.9 echocardiography, p = NS). Clinical study. The modified subtraction method tended to slightly underestimate right ventricular volume, but there was good correlation with right ventricular volume as measured by the radionuclide method (y = 0.80x + 13.4; r = 0.94, p < 0.601, CV = +- 15 % ) (Fig. 7). On the other hand, Krebs’ original method underestimated right ventricular volume as measured by the radionuclide method (y = 0.60x + 2.43; r = 0.89, p < 0.001, CV = r17%) (Fig. 8). Data are shown in Table III.
Volume123 Number 4, Part 1
RV volume by echo subtraction
1015
Fig. 4. Recordingsobtained in preceding patient at end systole. Left upper panel, Apical four-chamber view. Left lower panel, Tracing of epicardial and endocardial surfaces. Right upper panel, Apical two-chamber view of left ventricle. Right lower panel, Tracing of epicardial and endocardialsurfaces.Right
ventricular volume was calculated as explained in Fig. 2.
DISCUSSION Accuracy of the modified
The original method underestimated right ventricular volume when the “gold standard” was the volume obtained by measuring casts or by radionuclide angiocardiography. One reason may be that in the original method, as shown in Fig. 1, B, right ventricular volume was calculated as (A’ + B’) (A’) = (B’) (equation l), where (A’ + B’) is the total volume of the left ventricle plus the interventricular septum plus the right ventricle. (A’) refers to the left ventricle plus the interventricular septum and (B’) is the right ventricle. As a result right ventricular volume measured by the original method underestimated the volume by the shaded portion of the volume of Fig. 1, B as compared with the modified method. The modified method estimated well the geometry of the crescentshaped right ventricle, which partially surrounds the left ventricle. The thickness of the right ventricular myocardium is about one half that of the left ventricular myocardium. Consequently, in the case of a thicker left ventricular myocardium, measurement of right ventricular volume by the original method apsubtraction
method.
peared to underestimate that volume to a greater extent than the modification. In 1986 Erbel et a1.24studied human hearts at autopsy and found that right ventricular volume measured by their method correlated well with the true volume. However, they maintained left and right ventricular pressures at approximately 30 mm Hg. As a consequence of using this unusually high pressure, they may have obtained good results in that the left ventricle dilated and the left ventricular wall became relatively thinner. In our study the animal hearts were evaluated within 24 hours of excision. Our excised heart preparations appeared to be comparable to those in the end-systolic state. For this reason the original method appeared to underestimate right ventricular volume as compared with the modified method. Our experimental design appeared to be more satisfactory than that used previously. Thus in the clinical setting our modified method appeared to approximate the geometry of the right ventricle more accurately than the original method. Comparison methods-review
of the subtraction of the literature)
method
versus
other
(Table IV). In 1963
1016
Tomita
American
et al.
0 0
April 1992 Heart Journal
EDV ESV
RN-Ventriculography
Fig. 5. Comparison of right ventricular volume measured in casts of animal hearts with volume estimates obtained by modified subtraction method. Regression equation is y = 0.94x + 4.15; r = 0.987, p < 0.001. Coefficient of variation = t 13 % (N = 25). Dotted line is line of identity. Solid line (regression) is virtually identical to line of identity.
Fig. 7. Comparison of right ventricular volume in patients estimated by radionuclide (RN) ventriculography with that measured by echocardiographic modified subtraction method. (Regressionequationisy = 0.80x + 13.3;r = 0.935, p < 0.001 [N = 821). Coefficient of variation = + 15%. Dotted line represents line of identity; solid line (regression) is shifted slightly downward as compared with line of identity. (ml) 200.
150.
100,
25
50 50 Cast
FFV Volumf! FFV Volumf!
125
150 (ml)
Fig. 6. Comparison of right ventricular volume measured in casts of animal hearts with volume estimates obtained by means of Krebs’ original subtraction method. Regression equation is y = 0.59x + 1.11, r = 0.976, p < 0.001. Coefficient of variation = ‘25% (N = 25). Dotted line is line of identity; solid line (regression) deviates downward as compared with that in Fig. 5 representing modified method.
Reedy and Chapman 25first described measurement of right ventricular volume by the subtraction method with the use of cineangiography. However, biventriculography was cumbersome and failed to achieve acceptance. With regard to other methods, 10 cineangiographic studies are listed in Table IV. In these studiesI-I0 right ventricular volume was estimated by means of biplane right ventriculography. Although several different methods were used to estimate right
50.
OL 0
50
100 RN
Fig. 6. Comparison
150
200
250 Cd)
ventriculography
of right ventricular
estimated by radionuclide (RN)
volume in patients
ventriculography with
volume measured by echocardiographic original subtraction method. Regression equation is y = 0.60x + 2.43; r = 0.89, p < 0.001. Coefficient of variation = + 16% (N = 82). Dotted line represents line of identity; solid line (regression) is shifted markedly downward as compared with Fig. 7.
ventricular volume, none was based on the theoretically correct assumption of a crescent-shaped right ventricle. The correlation was good in all 10 studies. Estimates of right ventricular volume by biplane cineangiography appeared to be accurate; however,
Volume Number
Table
123 4, Part
RV volume by echo subtraction
1
1017
I. Individual data on right ventricular volume in 25 animal hearts Cast RV volume (ml)
Animal h.earts
Modified WCC) RV volume cm!?)
Original (UCG) RV volume (ml)
Dog 1 2 3 4 5
16 15 9 12 11
16 16 11 14 13
10 6
15 18 17 15 18 35 52 33 28 43 46
18 20 18 23 20 41 50 38 34 41 46
11 11 12 13 9 26 35 20 19 32 24
114 121 79 92 102 80 97 129 132
102 113 76 100 89 97 96 116 141
61 62 50 63 65 41 64 68 94
4 8
Pig 1 2 3 4 5 6 7 8 9 10 11 cow 1 2 3 4 5 6 8 9 RV,
right ventricuiar;
Modified,
modified
subtraction
method;
Original,
original
these studies were unsatisfactory in that the geometric characteristics of the right ventricle (i.e., a crescent-shaped container partially surrounding the left ventricle) were not seriously considered. When considered geometrically estimates of right ventricular volume by biplane cineangiography with the use of the Simpson method or the area-length method appeared to overestimate the true volume. In four studies6-g right ventricular volume was overestimated by these two approaches. Most of the 11 studies that employed echocardiography used two orthogonal views. Some of those studies calculated the right ventricular volume separately, for example, right ventricular body volume and outflow volume. Results of five studie@lg were compared with those obtained by angiography. Virtually all of those methods underestimated the true right ventricular volume. One reason is that the echocardiographic estimation of volume tends to underestimate the true volume itself, because it is relatively difficult to record the maximum area as compared with the angiographic method. In theory angiographic and echocardiographic assumptions of right ventricular volume by means of the Simpson method
subtraction
method;
UCG, ecbocardiography.
or the area-length method also overestimate the actual right ventricular volume, because these methods do not reflect the crescent-shaped right ventricle. Contrast echocardiography had the same drawbacks as other echocardiographic methods, although it was superior in visualizing the ventricular chamber.21, 22 In 1986 Erbel et a1.24studied human hearts excised at autopsy. According to their study, the subtraction method yielded a better correlation with the true right ventricular volume compared with the pyramid and Simpson methods. The subtraction method underestimated the actual right ventricular volume by approximately 11% to 14 % . In the present study we estimated right ventricular volume by means of a modified subtraction method and found an excellent correlation with true right ventricular volume. This method approximated the geometry of the crescentshaped right ventricle, which partially surrounded the left ventricle (Fig. l), despite the limitation of the echocardiographic method, which presents difficulties in recording the maximum area. Bommer et aLz6 reported that in human hearts excised and studied at autopsy, measurements of right ventricular dimension in the apical four-chamber
1018
Tomita
et al.
Table
II. Size of right ventricle Maximum
Animal hearts Dog 1 2 3 4 5
Pig 1 2 3 4 5 6 7 8 9 10 11 cow 1 2 3 4 5 6 I 8 9 M&num Marimum
April 1992 Heart Journal
American
measured
by cast and by echocardiography
length {cm)
Maximum
in 25 animal
depth (cm)
hearts Muximum
CAST
UCG
CAST
UCG
3.8 3.9 3.5 3.2 3.8
4.3 4.4 3.3 3.8 4.0
1.9 1.7 1.2 1.9 0.9
1.6 1.9 1.8 1.9 1.4
4.8 4.2 4.7 4.8 4.8
4.3 3.9 4.3 4.6 4.3
4.2 4.6 4.1 4.8 4.7 6.4 6.3 4.1 5.3 7.4 7.7
4.8 4.8 4.6 4.2 4.1 4.9 5.0 4.6 4.9 4.9 5.6
1.7 1.7 1.8 1.2 1.7 1.7 3.1 2.4 2.1 2.1 2.4
1.9 1.9 2.7 2.7 1.8 2.4 3.3 2.7 2.7 3.5 2.6
4.7 5.0 3.9 4.4 4.1 6.2 6.5 7.9 6.6 6.8 6.5
5.8 6.1 6.4 6.1 6.0 6.8 7.3 7.4 7.0 7.2 7.4
8.1 7.9 7.7 7.8 9.8 9.9 7.1 9.9 9.1
7.9 6.2 6.5 7.3 7.8 6.1 6.7 8.9 8.2
3.4 4.4 3.5 3.9 3.0 3.3 4.2 3.0 3.6
3.3 5.1 3.8 3.9 3.5 3.8 3.3 3.4 4.0
9.7 10.5 10.0 10.8 10.6 8.7 10.7 10.9 11.2
10.8 10.0 10.3 9.5 9.8 9.8 9.4 10.0 9.2
length, Apical to tricuspid valve annular plane maximum length; Maximum depth, right ventricular luidth, anteroposterior maximum length at tricuspid valve annular plane; UCG, echocardiography.
view correlated well with the actual dimensions of the right ventricle. Kaul et a1.27estimated the right ventricular ejection fraction from the apical four-chamber view and showed a good correlation with the angiographic right ventricular ejection fraction. Results of these studies support the utility of the apical fourchamber view in estimating right ventricular volume. In the present study, with a modification of the subtraction method, apical four- and two-chamber views were used. Both views are easily obtained in adults, so this method appears to be suitable for clinical use. Radionuclide method. Berger et a1.,28who used the radionuclide first-pass method, reported that the right ventricular ejection fraction was reduced in patients with chronic obstructive lung disease. Tobinick et a1.2gassessedthe right ventricular ejection fraction by the first-pass method in patients with acute myocardial infarction. The first-pass method was thought to be useful in estimating the right ventricular ejection fraction. According to Maddahi et a1.,3oright ventricular ejection fraction measured by the gated multiple regions of interest method correlated with that measured by the first-pass method.
CAST
width {cmf I:CG
septum to free wall maximum
diameter;
Their method is virtually identical to that used in our study. Holman et al. 31 also compared the first-pass method with the equilibrium method and found a good correlation. Thus these studies support the accuracy of the radionuclide method used with the gated method for calculating the ejection fraction. Observer variability in measurements of right ventricular volume. We assessedthe variability between two
observers in a study of 18 patients (data not shown). The regression equation for the interobserver variability (two observers) is y = 0.85x + 1.89 (P = 0.94, p < 0.001, CV = f 14 % ). Concerning intraobserver variability, the regression equation between two measurements by one observer was y = 0.96x + 5.69 (r = 0.96, p < 0.001, CV = +ll%). Limitations. In our clinical study left ventricular volume calculated by the area-length method with the use of this method showed more underestimation of larger left ventricular volumes than smaller volumes when they were compared with those calculated by angiography as a standard in the 15 patients studied. The regression equation was y = 0.84x + 2.7 (r = 0.98, CV = & 10% ; data not shown). On average
Volume Number
Table
123 4, Part
RV volume by echo subtraction
1
III. Data on right ventricular
volume measured
in 41 patients ED V (ml)
Patient No.
Age
Sex
DX
RN
I
41 68 69 29 33 28 58 61 63 56 57 69 37 50 59 65 69 62 66 44 50 57 54 54 53 43 38 27 31 42 69 20 45 39 41 66 36 53 17 24 32
M F M M M M F F F M M M F M M M M M M M M M M M M M M F M M M M M F M F M M M F F
DCM DCM DCM DCM DCM DCM DCM DCM DCM AP AP AP AP AP AP AP AP AP OMI OMI OMI OMI OMI OMI OMI AR AR AR AR MR MVPIMR MVP/MR MVP MVP HCM HCM Myocarditis Normal Normal Normal Valsalva rupture
106 132 133 99 143 156 132 113 112 82 132 114 132 236 106 91 93 123 135 112 176 117 130 142 115 167 183 124 132 138 164 184 136 155 100 111 111 152 141 138 147
2 3 4 5 6 I 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41
1019
M(UCG) 110 112 120 97 123 163 101 136 125 79 103 97 120 179 107 81 119 104 120 109 153 114 107 138 110 170 159 98 131 144 140 200 126 110 98 118 103 141 136 95 129
ESV (ml) OKJCG) 90 77 82 83 88 123 60 98 88 55 64 73 76 112 84 39 72 63 90 73 101 74 71 90 72 133 117 72 90 92 95 138 105 78 68 64 68 99 95 68 128
RN
M(lJCG)
O(UCG)
41 87 51 38 56 73 65 68 79 33 48 53 46 134 36 41 39 61 72 38 84 39 56 61 47 80 93 59 63 106 103 77 72 84 32 51 31 75 71 63 63
53 64 51 40 50 83 69 88 64 38 38 44 50 94 48 43 49 53 79 42 82 56 56 61 55 80 73 47 68 100 79 99 79 58 42 51 37 70 70 61 63
42 42 29 32 29 47 40 56 43 24 23 25 24 49 35 17 33 28 53 26 42 30 32 34 35 54 54 31 39 55 44 63 55 36 13 22 46 37 42 35 37
DX, Diagnosis; RN, radionuclide method; UCG, echocardiography; M, modified subtraction method; 0, original subtraction method; EDV, right ventricular end-diastolic volume; ESV, right ventricular end-systolic volume; DCM, dilated cardiomyopathy; AP, angina pectoris; OMI, old myocardid infarction; fi, aortic regurgitation; MVP, mitral valve prolapse: MR, mitral regurgitation; HCM, hypertrophic cardiomyopathy.
this method underestimated left ventricular volume by 12.7 % . The results of our left ventricular study were similar to those of Wyatt et al.32 In their study of the formalin-fixed left ventricle with the use of the biplane area-length method, the regression equation with the actual left ventricle was y = 0.87x - 8.5. Generally, in echocardiographic studies of left ventricular volume, the end-diastolic left ventricular volume appears to be underestimated more often than the end-systolic volume because it appears to be technically more difficult to record the maximum
area of the larger end-diastolic heart than that of the smaller end-systolic heart. Our clinical study underestimated larger right ventricular volumes more than smaller volumes. One possible explanation for the underestimation appears to be related to possible underestimation of the total heart volume associated with underestimation of the left ventricular volume as described previously. A second possible explanation for underestimation of the larger volume may be related to underestimation of the right ventricular outflow tract volume. Our
1020
Tomita et al.
Table
IV. Review of the literature
American
SLd+Xt
Measures
Shimazaki et a1.l
H cast
Angio
Arcilla et al.” Horn et a1.3
H cast H cast
Angio Angio
Boak et a1.4
A cast H cast
Angio
Pietras et a1.5
H
Angio
Gentzler et al.‘j Ferlinz et al.’
H cast H cast
Angio Angio
Graham et a1.s Fisher et a1.g Thilenius and Arcilla’O Shimazaki et al.‘l
H cast A cast H
Angio Angio Angio
H cast
Echo Angio Echo
Reference
Levine et al.‘”
H cast
Watanabe et a1.l”
H
Starling et a1.14
H
Echo Angio Echo
Ninomiya et a1.15
H
Echo
Hiraishi et al.ls
Angio Echo
Method
Regression
equation
April 1992 He8r1 Journal
r
Biplane area-length Simpson Parallel-piped Biplane Simpson -(triangular)
a-l y = 0.79x + 0.24 Simpson y = 0.72x + 4.16 y = 0.74x + 4.1 y = 0.83x + 4.12
0.98 0.98 0.95 0.93
Biplane Simpson (hemielipsoid) Biplane Simpson (elliptical cylinder) Biplane Simpson Pyramid Biplane RAO, LAO Biplane Simpson Prism Biplane parallel-piped Apical 4-chamber RV area x-height of RV Apical 4-chamber view RV outflow tract view Apical 4-chamber view RV inflow view Pyramid
y = 0.95x + 3.5
0.996
y = 1.33x y = 1.27x -4.5
0.99 0.99
y = 1.54x y = 1.16x - 1.04
0.99 0.98
y = 0.29x
0.88 0.91 0.91 0.94 0.94 0.84
Simpson
+ 32.9
y = 0.52x + 32.9 y = 0.88x + 11.9 y = 1.0x + 4.6 EDV h = 0.56x + 10.1 ESV y = 0.55x + 8.0 Compared with radionuclide count Ejection fraction areas compared Angio, EF = 0.97 Echo EF + 0.020.98 0.92
Angio Echo
Regression analysis and EDV y = 0.96x - 1.14 apical 4-chamber RV area RV body and outflow volume
ESV x = 0.94x - 0.27 EDV y = 0.62x + 7.0
0.84 0.81
Saito et al.‘*
Angio Echo
measurepments separately Two subxiphoid views
ESV y = 0.82x + 1.4 y = 1.32x - 7.39 y = 0.91x - 7.35 7 = 0.42x + 1.36
0.85 0.85 0.85 0.82
Satomi et al.lg
Echo
Apical 4-chamber view and subxiphoid RAO equivalent view
Trowitzsch et a1.20 Wann et aLzl
Angio Echo Echo
Compared with ejection fraction of radionuclide method EDVy = 0.54x -6.8
0.97
Silverman and Hudson”
Lange et a1.22
Echo Angio
Two subxiphoid orthogonal views Ellipsoid, pyramid, Simpson (contrast) Contrast echocard iography
H, Human; A, animal; Angie, angiography; Echo, echocardiography; RN, radionuclide method; RAO, right anterior oblique; LAO, left anterior oblique; EDV, end-diastolic volume; ESV, end-systolic volume.
method did not take into account the outflow tract volume, although it appeared to be larger in diastole than in systole. This may explain the underestimation of the higher right ventricular volume by our method. Inasmuch as our excised heart preparation appeared to be comparable to the end-systolic state, in the animal heart study estimation of both right and
left ventricular volume was good. The regression equation for the left ventricular volume of the cast and that obtained by the area-length method by this method was y = 0.95x + 3.4 (r = 0.99). The coefficient of variation was it- 10.4 % , thus supporting the preceding explanation of the underestimation. Left ventricular volume was not underestimated as much at end systole, and right ventricular outflow tract
Volume Number
123 4, Part
RV volume by echo subtraction
1
volume was not as great at end systole. Thus estimation of right ventricular volume in the animal heart study appeared to be better than that in the clinical study. Despite these limitations our data suggest that the new modification is applicable clinically because of its simplicity and practicality. Clinical implications. In evaluating patients with myocardial infarction, a reduction in right ventricular function is a significant indicator of a poor prognosis. 33 Estimation of right ventricular function is also important in assessing patients with chronic obstructive lung disease. 28 Considering the clinical applicability of the method, easily obtainable apical views were used. Thus our method appears to be useful in clinical practice. Further studies may be required to assess the deformed right ventricle in volume- or pressure-overloaded patients. In addition, a comparison with such other methods as three-dimensional echocardiography and magnetic resonance imaging35 may also be indicated. REFERENCES
1. Shimazaki Y, Kawashima Y, Mori T, Beppu S, Yokota K. Angiographic volume estimation of right ventricle. Chest 1980; 77:390-5. 2. Arcilla R, Tsai P, Thilenius 0, Ranniger K. Angiographic method for volume estimation of right and left ventricles. Chest 1971;60:446-54. 3. Horn V, Mullins CB, Saffer SI, Jones DC, Freeborn WA, Knapp RS, Nixon JV. A comparison of mathematical models for estimating right ventricular volumes in animals and man. CIin Cardiol 1979;2:341-7. 4. Boak JG, Bove AA, Kreulen T, Spann JF. A geometric basis for calculation of right ventricular volume in man. Cathet Cardiovasc Diagn 1977;3:217-30. 5. Pietras RJ, Kondos GT, Kaplan D, Lam W. Comparative angiographic right and left ventricular volumes. AM HEARTJ
15.
16.
17. 18. 19.
20.
21.
22.
23.
24. 25. 26.
1985;109:321-6.
6. Gentzler RD, Briselli MF, Gault JH. Angiographic estimation of right ventricular volume in man. Circulation 1974;50:32430. 7. Ferlinz J, Gorlin R, Cohn PF, Herman MV. Right ventricular performance in patients with coronary artery disease. Circulation 1975;52:608-15. 8. Graham TP, Jarmakani JM, Atwood GF, Canent RV. Right ventricular volume determinations in children. Circulation 1973;47:144-53. 9. Fisher EA, Dubrow IW, Hastreiter AR. Right ventricular volume in congenital heart disease. Am J Cardiol 1975:36:67-75. 10. Thilenius GG, Arcilla RA. Angiographic right and’left ventricular volume determination in normal infants and children. Pediatr Res 1974;8:67-74. 11. Shimazaki Y, Kitamure S, Hata S, Nakano S, Ihara K, Yagihara T, Sato S, Kishimoto H, Ogawa M, Kawashima Y. Right ventricular volume estimation by two-dimensional echocardiogram. J Cardiogr 1981;11:187-98. 12. Levine RA, Gibson TC, Aretz T, Gillam LD, Guyer DE, King ME, Weyman AE. Echocardiographic measurement of right ventricular volume. Circulation 1984;69:497-505. 13. Watanabe T, Katsume H, Matsukubo H, Furukawa K, Ijichi H. Estimation of right ventricular volume with two-dimensional echocardiography. Am J Cardiol 1982;49:3 946-53. 14. Starling MR, Crawford MH, Sorensen SG, O’Rourke RA. A new two-dimensional echocardiographic technique for evalu-
27.
1021
ating right ventricular size and performance in patients with obstructive lung disease. Circulation 1982;66:612-20. Ninomiya K, Duncan WJ, Cook DH, Olley PM, Rowe RD. Right ventricular ejection fraction and volumes after Mustard repair: correlation of two-dimensional echocardiograms and cineangiograms. Am J Cardiol 1981;48:317-24. Hiraishi S, Disessa T, Jarmakani JM, Toshio N, Jones JBI, Friedman WF. Two-dimensional echocardiographic assessment of right ventricular volume in children with congenital heart disease. Am J Cardiol 1982;50:1368-75. Silverman NH, Hudson S. Evaluation of right ventricular volume and ejection fraction in children by two-dimensional echocardiography. Pediatr Cardiol 1983;4:197-204. Saito A, Ueda K, Nakano H. Right ventricular volume determination by two-dimensional echocardiography. J Cardiogr 1981;11:1159-68. Satomi G, Nakazawa M, Kanaya M, Narai S, Minami Y, Nakamura K, Takao A. A new method for the measurement of right ventricular volume in children by two-dimensional echocardiography. J Cardiogr 1982;12:481-8. Trowitzsch E, Colan SD, Sanders SP. Two-dimensional echocardiographic evaluation of right ventricular size and function in newborns with severe right ventricular outflow tract obstruction. J Am Co11 Cardiol 1985;6:388-93. Wann LS, Stickels KR, Bamrah VS, Gross CM. Digital processing of contrast echocardiograms: a new technique for measuring right ventricular ejection fraction. Am J Cardiol 1984;53:1164-8. Lange PE, Seiffert PA, Pries F, Wessel A, Onnasch DGW, Hahne H, Heintzen PH. Value of image enhancement and injection of contrast medium for right ventricular volume determination by two-dimensional echocardiography in congenital heart disease. Am J Cardiol 1985;55:152-7. Krebs W, Erbel R, Schweizer P, Schweizer P, Richter HA, Henn G, Massberg I, Meyer J, Effert S. Volumenbestimmung des richiten ventrikels mit hilfe der subtractions methode-eine vergleichende zweidimensional echokardiographische und rontgenologische studie an herzmodellen. Kardiologie 1982; 71:413-20. Erbel R, Richter HA, Krebs W, Schweizer P, Massberg I, Zotz R, Meyer J, Effert S. Right ventricular volume determination in isolated human hearts. J Clin Ultrasound 1986;14:89-97. Reedy T. Chapman CB. Measurement of right ventricular volume by cineangiofluorography. AM HEARTJ 1963;66:221-5. Bommer W, Weinert L, Neumann A, Neef J, Mason DT, Demaria A. Determination of right atria1 and riaht ventricular size by two-dimensional echocardiography. Circulation 1979;60:91-100. Kaul S, Tei C, Hopkins JM, Shah PM. Assessment of right ventricular function using two-dimensional echocardiography.
AM HEARTJ1984;107:526-31. 28. Berger HJ, Matthay RA, Loke J, Marshall RC, Gottschalk A, Zaret BL. Assessment of cardiac performance with quantitative radionuclide angiocardiography: right ventricular ejection fraction with reference to findings in chronic obstructive pulmonary disease. Am J Cardiol 1978;41:897-905. 29. Tobinick E, Schelbert HR, Henning H, Lewinter M, Taylor A, Ashburn WL, Karliner JS. Right ventricular ejection fraction in patients with acute anterior and inferior myocardial infarction assessed by radionuclide angiography. Circulation 1978; 57:1078-84. 30. Maddahi J, Berman DS, Matsuoka DT, Waxman AD, Stankus KE, Forrester JS, Swan HJC. A new technique for assessing right ventricular ejection fraction using rapid multiple-gated equilibrium cardiac blood pool scintigraphy. Circulation 1979;60:581-9. 31. Holman BL, Wynne J, Zieionka JS, Iodine JD. A simplified technique for measuring right ventricular ejection fraction using the equilibrium radionuclide angiocardioaram and the slant-hole collimator. Radiology 1981;i38:429-35. 32. Wyatt HL, Heng MK, Meerbaum S, Gueret P, Hestenes J, Dula E, Corday E. Cross-sectional echocardiography. Analy-
To&a
et al.
American
sis of mathematic models for quantifying volume of the formalin-fixed left ventricle. Circulation 1980;61:1119-25. 33. Polak JF, Holman BL, Wyn EJ, Colucci WS. Right ventricular ejection fraction: an indicator of increased moratlity in patients with congestive heart failure associated with coronary artery disease. 3 Am Co11 Cardiol 1983;2:217-23. 34. Linker DT, Moritz WE, Pearlman AS. A new three-dimen-
A dose-response
April 1992 Heart Journal
sional echocardiographic method of right ventricular volume measurement: in vitro validation. J Am Co11 Cardiol 1986; 8~101-6. 35. Sechtem U, Pflugfelder PW, Gould RG, Cassidy MM. Measurement of right and left ventricular volumes in healthy individuals with tine MR imaging. Radiology 1987;163:697-702.
trial of once-daily
diltiazem
This trial was performed to determine the safe and effective dosage range of once daily diltiarem (diltiazem CD) capsules for treatment of essential hypertension. Patients with essential hypertension having supine diastolic blood pressure values 195 mm Hg and 5110 mm Hg were randomly assigned to receive placebo or one of four doses of diltiazem CD: 90, 180, 360, or 540 mg. Blood pressure was measured at trough, 24 hours after the dose, and at the time of peak effect, 10 hours after the dose. Diltiazem CD lowered both supine diastolic and systolic blood pressure. A linear dose response was seen with changes in diastolic and systolic blood pressure and heart rate for trough and peak measurements. Trough/peak ratios for the 180, 360, and 540 mg doses were all greater than 0.50. Adverse effects were dose related; those most commonly reported were headache (8.6%), bradycardia (8.1%), and edema (7%), with bradycardia and edema possibly dose related. It is therefore concluded that diltiazem CD is a safe and effective antihypertensive agent. (AM HEART J 1992;123:1022.)
James V. Felicetta, MD, a Harry M. Serfer, DO, Neal R. Cutler, MD,b Thomas J. Comstock, PharmD,C Gary L. Huber, MD,d Matthew R. Weir, MD,e Kerry Hafner, PhD,f and Glen D. Park, PharmD.f Phoenix, Ark., Hollywood, Flu., Beverly Hills, Calif., Richmond, Vu., Tyler, Texas, Baltimore, Md., and Kansas City, MO. Diltiazem is a widely prescribed calcium channel blocker that is highly effective in the treatment of essential hypertensi0n.l A sustained-release capsule formulation (Cardizem SR) has been available for several years, but it has been approved only on a twice daily basis as therapy for essential hypertensiom2 Medication compliance is inversely related to the number of times each day a drug must be taken.3>4 As a consequence, once daily dosing has been recommended for antihypertensive treatment.5J 6It is therefore highly desirable to demonstrate that a sustainedrelease formulation of diltiazem, that is, diltiazem
From “the Carl T. Hayden Veterans Administration Medical Center, bthe California Clinical Trials Group, 9he Medical College of Virginia, dthe University of Texas Health Center, %he University of Maryland, and ‘Marion Merrell Dow, Inc. Received Reprint Center, 85012. 411135347
1022
for publication
June
10, 1991;
accepted
requests: James V. Felicetta, MD, Carl Medical Service (111),7th St. and Indian
Oct. 1, 1991. T. Hayden VA Medical School Rd., Phoenix, AZ
CD capsules, is safe and effective with once daily dosing in the management of essential hypertension. There has been increasing academic and regulatory interest in recent years in documenting antihypertensive effects at trough (end of the dosing interval) and at peak.7 This is particularly important for formulation of a relatively short-acting drug designed to extend the dosing interval to 24 hours. The duration of action of a drug can be increased by raising the dose to achieve an incremental effect at the end of the dosing interval, but this produces a substantially greater peak effect, which thus increases the risk of hypotension or other side effects. An effective sustained-release formulation should achieve effective blood pressure lowering at trough without producing increased side effects at peak. The primary objective of this study was to determine the safe and effective dosage range of diltiazem CD capsules prescribed on a once daily basis for treatment of essential hypertension. A secondary objective was to compare the peak and trough blood pressure-lowering responses to diltiazem CD capsules.
Masaaki Tomita, MD, Hiroshi Masuda, MD, Tomoichiro Sumi, MD, Hisashi Shiraki, MD, Kohshi Gotoh, MD, Yasuo Yagi, MD, Tatsuo Tsukamoto, MD, Yasushi Terashima, MD, Yoko Miwa, MD, and Senri Hirakawa, MD. Gifu, Japan
Accurate and convenient methods for measuring right ventricular volume have long been sought. Many investigators have attempted to estimate this parameter angiographically.l-10 Echocardiographic methods are complicated and seem impractical for clinical use.11-22In 1982 Krebs et a1.23attempted to approximate right ventricular volume geometrically by experimenting with a subtraction method in a plastic model. We have now modified the original subtraction method to yield a more accurate estimate of right ventricular volume. To test the accuracy and clinical utility of this estimate obtained by the original method versus a modified approach, the following studies were performed: (1) The accuracy of the original method and the modified method was compared in excised animal hearts, and (2) a clinical From the Second of Medicine. Received Reprint Medicine, Japan. 4/l/35351
Department
for publication requests: Masaaki Gifu University
of Internal Jan.
31, 1991;
Medicine, accepted
Gifu Sept.
University
School
20, 1991.
Tomita. MD, Second Department School of Medicine, Tsukasa-machi
of Internal 40, Gifu 500,
study was performed in patients with various heart diseasesin whom right ventricular volume was estimated by the original subtraction method and by the modified echocardiographic method. The greater accuracy of the modified method was demonstrated with the use of radionuclide angiocardiography asthe standard. METHODS
In an initial experiment we studied hearts excised from five mongrel dogs,11 pigs, and nine cows.A subsequent clinical study wasperformed in 41 patients (31 men and 10 women,aged 17 to 69 years) with the following diagnoses: dilated cardiomyopathy in nine, mitral valve prolapse in five, myocardial infarction in seven,valvular heart disease in four, coronary artery diseasein nine, congenital heart diseasein one, hypertrophic cardiomyopathy in two, and myocarditis in one; three normal subjectswere also studied. Echocardiographic recordswere obtained by meansof a Toshiba SSH40A device (3.5 MHZ transducer) (Toshiba Medical Co., Ltd., Tokyo, Japan). Experimental study. Animal hearts excised within the previous 24 hourswere placed in a water bath and fixed on a rubber stand. Apical two-chamber and four-chamber views were obtained by echocardiography. After echocar1011
April
1012
Tomita
et al.
American
(A+B) B -
F.gi .:.a”“L ,T;;:. .:.,. :.::.:: :.:.:.:.:: :,:, :.,.,, .: .:. ..A = .,.J.;.. :. ..:..;:.,:‘-‘, .:::,:.::. h’..;.:,::.:, .“$*y
Fig. 1. Subtraction methodsfor estimating right ventricular volume. A, Modified subtraction method. (A + B) representswhole heart surrounded by outer line; (A) represents left ventricle surrounded by outer line, which includesleft ventricular myocardium; 03) representsright ventricular volume. a, Anteroposterior minor axis of left ventricular outer surface; b, diameter of right ventricular side septal wall to outer surface of left ventricular lateral wall, c, diameter of right ventricular side septum to right ventricular free wall, h, height of left ventricle. B, Krebs’ original subtraction method. (A’ + B’) representsvolume surrounded by dotted line; (A’) representsleft ventricular volume surrounded by dotted line including septum; (B’) represents right ventricle surrounded by dotted line. Shaded area represents area underestimated by Krebs’ original method as compared with modified method. a’, Anteroposterior minor axis of inner surface of left ventricle; b ’ , diameter of right ventricular side septal wall to inner surface of left ventricular lateral wall; c’, diameter of right ventricular septal wall to right ventricular free wall; h’, height of left ventricle. In this schema,for simplicity, h’ is shown to be the samelength as h; h’ is shorter than h by thickness of apical myocardium.
diography was performed in these views, silicone rubber was injected into the right ventricle and castswere made. The actual right ventricular volume of the castswasmeasured by the water displacement method. Clinical study. Echocardiographic records were obtained from patients placed in a 45-degreeleft lateral decubitus position. Apical four- and two-chamber views were recorded while subjectsheld their breath at end expiration. Both the apical four- and two-chamber views wererecorded and pictured at end diastole,which falls on the peak of the R wave of the ECG, and at end systole, which falls on the aortic closure sound of the phonocardiogram. Videocassette recordings (CR-6600, Nippon Victor Inc., Gifu, Japan) were alsoobtained for useasa referencein tracing the echocardiograms.Calculation of the area was performed manually with a planimeter. Calculation of right ventricular volume. The modified subtraction method is shownin Fig. 1, A. According to the original method of Krebs et a1.,23right ventricular volume (B ‘) wascalculated by subtracting the left ventricular vol-
Heart
1992
Journal
ume including the interventricular septum (A’) from the whole heart volume including the right and left ventricles plus the interventricular septum (A’ + B’) (Fig. 1, B). Both (A’) and (A’ + B’) were consideredto be hemiellipsoid. In Krebs’ original method right ventricular volume (B’) was calculated as follows: Right ventricular volume (B’) = (A’ + B’) - (A’) (Fig. l,B) (equation 1). Thus (A’) and (A’ + B’) were calculated as shownin Fig. I, B by using two orthogonal planessuch asan apical four-chamber view and an apical two-chamber view. The anteroposterior minor axis of the left ventricular cavity (a’) wascalculated asfollows: (a’) = 4 (Sl’)/*h’ (equation Z), where Sl’ isthe area of the left ventricular cavity in the apical two-chamber view and (h’) is the greater height of the left ventricle measuredin two orthogonal planes. The diameter of the right ventricular side septal wall to the inner left ventricular lateral wall (b’) wascalculated as follows: (b’) = 4(S2’)lah’ (equation 3), where S2’ is the area of the left ventricle including the septumin the apical four-chamber view. The diameter of the right ventricular inner surface of the free wall to the inner left ventricular lateralwall(b’ + c’) wascalculatedasfollows:(b’ + c’) = 4 (S3’)/rh’ (equation 4), where S3’ is the area of the left ventricle including the septum and right ventricle in the apical four-chamber view. (A’) was calculated by the area-length method as follows: (A’) = (r/6) (h’) (a’) (b’). With the useof equations 2 and 3, (A’) was given as follows: (A’) = 8 (Sl’) (S2’)/ 3T(h’) (equation 5). (A’ + B’) wascalculated by the arealength method as follows: (A’ + B’) = (a/6) (h’) (a’) (b’ + c’). With the useof equations2 and 4, (A’ + B’) was given asfollows: (A’ + B’) = 8 (Sl’) (S3’)/3a(h’) (equation 6). Thus the right ventricular volume was calculated as follows: (B’) = (A’ + B’) - (A’) = 8(Sl’) (S3’)/ 3a(h’) - 8 (Sl’) (S2’)/37r(h’) (equation 7). In our modified method the right ventricular volume (B) wascalculated by subtracting the entire left ventricle (A) (including the left ventricular myocardium) from the entire heart (including the right ventricle and the entire left ventricle) (A + B) (Fig. 1, A). Both A and A + B were calculated as hemiellipsoidby the area-length method with the use of apical four- and two-chamber views. Thus in the modified method right ventricular volume was calculated as follows: Right ventricular volume (B) = (A + B) - (A) (Fig. 1, A) (equation 8). As in the original method, (a) is the anteroposterior minor axis of the left ventricular outer surface, which was calculated as follows: (a) = 4(Sl)lnh (equation 9), where Sl is the area of the left ventricle including the myocardium in the apical two-chamber view and (h) is the greater height of the left ventricle in two orthogonal planes. The diameter of the right ventricular side septal wall to the outer surfaceof the left ventricular lateral wall (b) was calculated as follows: (b) = 4(S2)/?rh (equation lo), where S2 is the areaof the left ventricle including the septum and the lateral wall in the apical four-chamber view. The diameter of the inner surface of the right ventricular free wall to the outer surface of the left ventricular lateral wall (b + c) wascalculated asfollows: (b + c) = 4(S3)/?rh(equa-
Volume123 Number 4, Part
RV volume by echo subtraction
1
1013
Fig. 2. Echocardiographic recordsof exciseddog heart. Left upper panel, Apical four-chamber view. Left lower panel, Tracing of epicardial and endocardial surfacesas shown by dotted lines. In the modified method, areasurroundedby outer dotted line wasplanimetered.In the original method, areaincluding right ventricle, left ventricular cavity, and septum wasplanimetered. Right upper panel, Apical two-chamber view of Ieft ventricle. Right lower panel, Tracing of epicardial and endocardial surfacesof left ventricle. In the modified method, area surrounded by outer dotted line wasplanimetered. In contrast, in the original method, area surrounded by inner dotted line, which is equal to left ventricular cavity, wasplanimetered. Right ventricular volume wascalculated by meansof above-measuredareasand equations 7 and 14. tion II), where S3 is the areaof the left ventricle including both the septum and the lateral wall and the right ventricle in the apical four-chamber view. Thus the left ventricle, including the myocardial muscle (A), was calculated by the area-length method as follows: (A) = (*/6)h a b. With the use of equations 9 and 10, (A) was given as follows: (A) = 8 (Sl) (S2)/3xh (equation 12). (A + B) was calculated by the area-length method as follows: (A + B) = (a/6)h a (b + c). With equations 9 and 11, (A + B) wasgiven asfollows: (A + B) = 8 (Sl) (S3)/3rh (equation 13). Thus in the modified method right ventricular volume (B) wascalculated asfollows: Right ventricular volume (B) = (A + B) - (A) = 8 (Sl) (S3)/3ah - 8 (Sl) (S2)/3Th (equation 14). Calculation
of right ventricular
volume in animal
hearts
(Fig. 2). As explained above, the apical four- and twochamber views obtained by echocardiography permitted calculation of (A + B) and (A) by the biplane area-length method by planimetering areas Sl, S2, and S3 and measuring the maximum height. Right ventricular volume was then obtained by equation 14, whereas in the original method it was obtained by equation 7. The actual right ventricular volume was measuredby the water displace-
ment method with the useof casts.Thus the actual right ventricular volume wascomparedwith two calculated volumes.Lengths measuredby the right ventricular cast and by echocardiography were compared in three directions suchasmaximum length (apical to tricuspid valve annular plane maximum length), maximum depth (right ventricular septal to free wall maximum diameter), and maximum width (anteroposterior maximum length at the tricuspid valve annular plane). Calculation
of right
ventricular
volume
in patients
(Figs. 3 and 4). The echocardiographicend-diastolic and end-systolic right ventricular volumes were obtained as explained previously by planimetering the area and obtaining the maximum height at both end diastole and end systole. End-diastolic and end-systolic volumeswere then calculated by meansof equation 7 in the original method and equation 14 in the modified method. Radionuclide ventriculography combined with thermodilution for measuring right ventricular volume. Data were obtained from the 45-degree left anterior oblique projection by a gamma camera (SiemensZLC, Siemens Gammasonics,Inc., Hoffman Estates,Ill.) and analyzed by computer (ScintiPack 2400 Shimadzu Corp., Tokyo, Ja-
1014
Tomita et al.
American
April 1992 Heart Journal
Fig. 3. Echocardiographic records of 50-year-old man with myocardial infarction taken at end diastole. Left upper panel, Apical four-chamber view. Left lower panel, Tracing of epicardial and endocardial surfaces. Right upper panel, Apical two-chamber view of left ventricle. Right lower panel, Tracing of epicardial and endocardial surfaces. Right ventricular volume was calculated as explained in Fig. 2. pan). Radionuclide ventriculography was performed by a technique in which red blood cells labeled with technetium 99m in vivo were used. Data were obtained from a 45-degree left anterior oblique projection at the equilibrium phase. The right ventricular ejection fraction (EF) was obtained by the count-based method; frame images were obtained during s-minute recordings at the equilibrium phase. The region of interest was placed over both the right and left ventricles on the phase images. Background region of interest was placed outside of the right ventricle at the end-systolic phase. The stroke volume (SV) was obtained from the cardiac output (CO) measured by the thermodilution method and the heart rate (HR) as follows: SV = CO/ HR. Right ventricular end-diastolic volume (EDV) and end systolic volume (ESV) were calculated as follows: EDV = (SV/EF) and ESV = EDV - SV. Statistics. Data obtained from each of the preceding methods were compared by linear regression analysis with standard statistical formulas. Student’s unpaired t test was used to analyze differences with p < 0.05 considered statistically significant. In this study variance is expressed as mean t SD. RESULTS Study of excised animal hearts. Right ventricular volume measured by the newly modified subtraction method showed good correlation with the actual vol-
ume measured in the casts (y = 0.94x + 4.15; r = 0.987, p < 0.001, coefficient of variation [CV] = +- 13 % ) (Fig. 5). On the other hand, right ventricular volume measured by Krebs’ original method underestimated the actual volume (Fig. 6) (y = 0.590x + 1.213; r = 0.976, p < 0.001, CV = ~~25%). Individual data are shown in Table I. We also compared the right ventricular dimension measured by echocardiography with that measured in the casts (Table II). As shown in Table II, agreement was good with respect to the length of the right ventricle (6.2 4 2.2 cm cast vs 5.5 +- 1.6 echocardiography, p = NS), its diameter (‘7.2 +- 2.7 cm cast vs 7.3 it_ 2.2 echocardiography, p = NS), and i t s maximum depth (2.5 s 1.0 cm cast vs 2.8 +- 0.9 echocardiography, p = NS). Clinical study. The modified subtraction method tended to slightly underestimate right ventricular volume, but there was good correlation with right ventricular volume as measured by the radionuclide method (y = 0.80x + 13.4; r = 0.94, p < 0.601, CV = +- 15 % ) (Fig. 7). On the other hand, Krebs’ original method underestimated right ventricular volume as measured by the radionuclide method (y = 0.60x + 2.43; r = 0.89, p < 0.001, CV = r17%) (Fig. 8). Data are shown in Table III.
Volume123 Number 4, Part 1
RV volume by echo subtraction
1015
Fig. 4. Recordingsobtained in preceding patient at end systole. Left upper panel, Apical four-chamber view. Left lower panel, Tracing of epicardial and endocardial surfaces. Right upper panel, Apical two-chamber view of left ventricle. Right lower panel, Tracing of epicardial and endocardialsurfaces.Right
ventricular volume was calculated as explained in Fig. 2.
DISCUSSION Accuracy of the modified
The original method underestimated right ventricular volume when the “gold standard” was the volume obtained by measuring casts or by radionuclide angiocardiography. One reason may be that in the original method, as shown in Fig. 1, B, right ventricular volume was calculated as (A’ + B’) (A’) = (B’) (equation l), where (A’ + B’) is the total volume of the left ventricle plus the interventricular septum plus the right ventricle. (A’) refers to the left ventricle plus the interventricular septum and (B’) is the right ventricle. As a result right ventricular volume measured by the original method underestimated the volume by the shaded portion of the volume of Fig. 1, B as compared with the modified method. The modified method estimated well the geometry of the crescentshaped right ventricle, which partially surrounds the left ventricle. The thickness of the right ventricular myocardium is about one half that of the left ventricular myocardium. Consequently, in the case of a thicker left ventricular myocardium, measurement of right ventricular volume by the original method apsubtraction
method.
peared to underestimate that volume to a greater extent than the modification. In 1986 Erbel et a1.24studied human hearts at autopsy and found that right ventricular volume measured by their method correlated well with the true volume. However, they maintained left and right ventricular pressures at approximately 30 mm Hg. As a consequence of using this unusually high pressure, they may have obtained good results in that the left ventricle dilated and the left ventricular wall became relatively thinner. In our study the animal hearts were evaluated within 24 hours of excision. Our excised heart preparations appeared to be comparable to those in the end-systolic state. For this reason the original method appeared to underestimate right ventricular volume as compared with the modified method. Our experimental design appeared to be more satisfactory than that used previously. Thus in the clinical setting our modified method appeared to approximate the geometry of the right ventricle more accurately than the original method. Comparison methods-review
of the subtraction of the literature)
method
versus
other
(Table IV). In 1963
1016
Tomita
American
et al.
0 0
April 1992 Heart Journal
EDV ESV
RN-Ventriculography
Fig. 5. Comparison of right ventricular volume measured in casts of animal hearts with volume estimates obtained by modified subtraction method. Regression equation is y = 0.94x + 4.15; r = 0.987, p < 0.001. Coefficient of variation = t 13 % (N = 25). Dotted line is line of identity. Solid line (regression) is virtually identical to line of identity.
Fig. 7. Comparison of right ventricular volume in patients estimated by radionuclide (RN) ventriculography with that measured by echocardiographic modified subtraction method. (Regressionequationisy = 0.80x + 13.3;r = 0.935, p < 0.001 [N = 821). Coefficient of variation = + 15%. Dotted line represents line of identity; solid line (regression) is shifted slightly downward as compared with line of identity. (ml) 200.
150.
100,
25
50 50 Cast
FFV Volumf! FFV Volumf!
125
150 (ml)
Fig. 6. Comparison of right ventricular volume measured in casts of animal hearts with volume estimates obtained by means of Krebs’ original subtraction method. Regression equation is y = 0.59x + 1.11, r = 0.976, p < 0.001. Coefficient of variation = ‘25% (N = 25). Dotted line is line of identity; solid line (regression) deviates downward as compared with that in Fig. 5 representing modified method.
Reedy and Chapman 25first described measurement of right ventricular volume by the subtraction method with the use of cineangiography. However, biventriculography was cumbersome and failed to achieve acceptance. With regard to other methods, 10 cineangiographic studies are listed in Table IV. In these studiesI-I0 right ventricular volume was estimated by means of biplane right ventriculography. Although several different methods were used to estimate right
50.
OL 0
50
100 RN
Fig. 6. Comparison
150
200
250 Cd)
ventriculography
of right ventricular
estimated by radionuclide (RN)
volume in patients
ventriculography with
volume measured by echocardiographic original subtraction method. Regression equation is y = 0.60x + 2.43; r = 0.89, p < 0.001. Coefficient of variation = + 16% (N = 82). Dotted line represents line of identity; solid line (regression) is shifted markedly downward as compared with Fig. 7.
ventricular volume, none was based on the theoretically correct assumption of a crescent-shaped right ventricle. The correlation was good in all 10 studies. Estimates of right ventricular volume by biplane cineangiography appeared to be accurate; however,
Volume Number
Table
123 4, Part
RV volume by echo subtraction
1
1017
I. Individual data on right ventricular volume in 25 animal hearts Cast RV volume (ml)
Animal h.earts
Modified WCC) RV volume cm!?)
Original (UCG) RV volume (ml)
Dog 1 2 3 4 5
16 15 9 12 11
16 16 11 14 13
10 6
15 18 17 15 18 35 52 33 28 43 46
18 20 18 23 20 41 50 38 34 41 46
11 11 12 13 9 26 35 20 19 32 24
114 121 79 92 102 80 97 129 132
102 113 76 100 89 97 96 116 141
61 62 50 63 65 41 64 68 94
4 8
Pig 1 2 3 4 5 6 7 8 9 10 11 cow 1 2 3 4 5 6 8 9 RV,
right ventricuiar;
Modified,
modified
subtraction
method;
Original,
original
these studies were unsatisfactory in that the geometric characteristics of the right ventricle (i.e., a crescent-shaped container partially surrounding the left ventricle) were not seriously considered. When considered geometrically estimates of right ventricular volume by biplane cineangiography with the use of the Simpson method or the area-length method appeared to overestimate the true volume. In four studies6-g right ventricular volume was overestimated by these two approaches. Most of the 11 studies that employed echocardiography used two orthogonal views. Some of those studies calculated the right ventricular volume separately, for example, right ventricular body volume and outflow volume. Results of five studie@lg were compared with those obtained by angiography. Virtually all of those methods underestimated the true right ventricular volume. One reason is that the echocardiographic estimation of volume tends to underestimate the true volume itself, because it is relatively difficult to record the maximum area as compared with the angiographic method. In theory angiographic and echocardiographic assumptions of right ventricular volume by means of the Simpson method
subtraction
method;
UCG, ecbocardiography.
or the area-length method also overestimate the actual right ventricular volume, because these methods do not reflect the crescent-shaped right ventricle. Contrast echocardiography had the same drawbacks as other echocardiographic methods, although it was superior in visualizing the ventricular chamber.21, 22 In 1986 Erbel et a1.24studied human hearts excised at autopsy. According to their study, the subtraction method yielded a better correlation with the true right ventricular volume compared with the pyramid and Simpson methods. The subtraction method underestimated the actual right ventricular volume by approximately 11% to 14 % . In the present study we estimated right ventricular volume by means of a modified subtraction method and found an excellent correlation with true right ventricular volume. This method approximated the geometry of the crescentshaped right ventricle, which partially surrounded the left ventricle (Fig. l), despite the limitation of the echocardiographic method, which presents difficulties in recording the maximum area. Bommer et aLz6 reported that in human hearts excised and studied at autopsy, measurements of right ventricular dimension in the apical four-chamber
1018
Tomita
et al.
Table
II. Size of right ventricle Maximum
Animal hearts Dog 1 2 3 4 5
Pig 1 2 3 4 5 6 7 8 9 10 11 cow 1 2 3 4 5 6 I 8 9 M&num Marimum
April 1992 Heart Journal
American
measured
by cast and by echocardiography
length {cm)
Maximum
in 25 animal
depth (cm)
hearts Muximum
CAST
UCG
CAST
UCG
3.8 3.9 3.5 3.2 3.8
4.3 4.4 3.3 3.8 4.0
1.9 1.7 1.2 1.9 0.9
1.6 1.9 1.8 1.9 1.4
4.8 4.2 4.7 4.8 4.8
4.3 3.9 4.3 4.6 4.3
4.2 4.6 4.1 4.8 4.7 6.4 6.3 4.1 5.3 7.4 7.7
4.8 4.8 4.6 4.2 4.1 4.9 5.0 4.6 4.9 4.9 5.6
1.7 1.7 1.8 1.2 1.7 1.7 3.1 2.4 2.1 2.1 2.4
1.9 1.9 2.7 2.7 1.8 2.4 3.3 2.7 2.7 3.5 2.6
4.7 5.0 3.9 4.4 4.1 6.2 6.5 7.9 6.6 6.8 6.5
5.8 6.1 6.4 6.1 6.0 6.8 7.3 7.4 7.0 7.2 7.4
8.1 7.9 7.7 7.8 9.8 9.9 7.1 9.9 9.1
7.9 6.2 6.5 7.3 7.8 6.1 6.7 8.9 8.2
3.4 4.4 3.5 3.9 3.0 3.3 4.2 3.0 3.6
3.3 5.1 3.8 3.9 3.5 3.8 3.3 3.4 4.0
9.7 10.5 10.0 10.8 10.6 8.7 10.7 10.9 11.2
10.8 10.0 10.3 9.5 9.8 9.8 9.4 10.0 9.2
length, Apical to tricuspid valve annular plane maximum length; Maximum depth, right ventricular luidth, anteroposterior maximum length at tricuspid valve annular plane; UCG, echocardiography.
view correlated well with the actual dimensions of the right ventricle. Kaul et a1.27estimated the right ventricular ejection fraction from the apical four-chamber view and showed a good correlation with the angiographic right ventricular ejection fraction. Results of these studies support the utility of the apical fourchamber view in estimating right ventricular volume. In the present study, with a modification of the subtraction method, apical four- and two-chamber views were used. Both views are easily obtained in adults, so this method appears to be suitable for clinical use. Radionuclide method. Berger et a1.,28who used the radionuclide first-pass method, reported that the right ventricular ejection fraction was reduced in patients with chronic obstructive lung disease. Tobinick et a1.2gassessedthe right ventricular ejection fraction by the first-pass method in patients with acute myocardial infarction. The first-pass method was thought to be useful in estimating the right ventricular ejection fraction. According to Maddahi et a1.,3oright ventricular ejection fraction measured by the gated multiple regions of interest method correlated with that measured by the first-pass method.
CAST
width {cmf I:CG
septum to free wall maximum
diameter;
Their method is virtually identical to that used in our study. Holman et al. 31 also compared the first-pass method with the equilibrium method and found a good correlation. Thus these studies support the accuracy of the radionuclide method used with the gated method for calculating the ejection fraction. Observer variability in measurements of right ventricular volume. We assessedthe variability between two
observers in a study of 18 patients (data not shown). The regression equation for the interobserver variability (two observers) is y = 0.85x + 1.89 (P = 0.94, p < 0.001, CV = f 14 % ). Concerning intraobserver variability, the regression equation between two measurements by one observer was y = 0.96x + 5.69 (r = 0.96, p < 0.001, CV = +ll%). Limitations. In our clinical study left ventricular volume calculated by the area-length method with the use of this method showed more underestimation of larger left ventricular volumes than smaller volumes when they were compared with those calculated by angiography as a standard in the 15 patients studied. The regression equation was y = 0.84x + 2.7 (r = 0.98, CV = & 10% ; data not shown). On average
Volume Number
Table
123 4, Part
RV volume by echo subtraction
1
III. Data on right ventricular
volume measured
in 41 patients ED V (ml)
Patient No.
Age
Sex
DX
RN
I
41 68 69 29 33 28 58 61 63 56 57 69 37 50 59 65 69 62 66 44 50 57 54 54 53 43 38 27 31 42 69 20 45 39 41 66 36 53 17 24 32
M F M M M M F F F M M M F M M M M M M M M M M M M M M F M M M M M F M F M M M F F
DCM DCM DCM DCM DCM DCM DCM DCM DCM AP AP AP AP AP AP AP AP AP OMI OMI OMI OMI OMI OMI OMI AR AR AR AR MR MVPIMR MVP/MR MVP MVP HCM HCM Myocarditis Normal Normal Normal Valsalva rupture
106 132 133 99 143 156 132 113 112 82 132 114 132 236 106 91 93 123 135 112 176 117 130 142 115 167 183 124 132 138 164 184 136 155 100 111 111 152 141 138 147
2 3 4 5 6 I 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41
1019
M(UCG) 110 112 120 97 123 163 101 136 125 79 103 97 120 179 107 81 119 104 120 109 153 114 107 138 110 170 159 98 131 144 140 200 126 110 98 118 103 141 136 95 129
ESV (ml) OKJCG) 90 77 82 83 88 123 60 98 88 55 64 73 76 112 84 39 72 63 90 73 101 74 71 90 72 133 117 72 90 92 95 138 105 78 68 64 68 99 95 68 128
RN
M(lJCG)
O(UCG)
41 87 51 38 56 73 65 68 79 33 48 53 46 134 36 41 39 61 72 38 84 39 56 61 47 80 93 59 63 106 103 77 72 84 32 51 31 75 71 63 63
53 64 51 40 50 83 69 88 64 38 38 44 50 94 48 43 49 53 79 42 82 56 56 61 55 80 73 47 68 100 79 99 79 58 42 51 37 70 70 61 63
42 42 29 32 29 47 40 56 43 24 23 25 24 49 35 17 33 28 53 26 42 30 32 34 35 54 54 31 39 55 44 63 55 36 13 22 46 37 42 35 37
DX, Diagnosis; RN, radionuclide method; UCG, echocardiography; M, modified subtraction method; 0, original subtraction method; EDV, right ventricular end-diastolic volume; ESV, right ventricular end-systolic volume; DCM, dilated cardiomyopathy; AP, angina pectoris; OMI, old myocardid infarction; fi, aortic regurgitation; MVP, mitral valve prolapse: MR, mitral regurgitation; HCM, hypertrophic cardiomyopathy.
this method underestimated left ventricular volume by 12.7 % . The results of our left ventricular study were similar to those of Wyatt et al.32 In their study of the formalin-fixed left ventricle with the use of the biplane area-length method, the regression equation with the actual left ventricle was y = 0.87x - 8.5. Generally, in echocardiographic studies of left ventricular volume, the end-diastolic left ventricular volume appears to be underestimated more often than the end-systolic volume because it appears to be technically more difficult to record the maximum
area of the larger end-diastolic heart than that of the smaller end-systolic heart. Our clinical study underestimated larger right ventricular volumes more than smaller volumes. One possible explanation for the underestimation appears to be related to possible underestimation of the total heart volume associated with underestimation of the left ventricular volume as described previously. A second possible explanation for underestimation of the larger volume may be related to underestimation of the right ventricular outflow tract volume. Our
1020
Tomita et al.
Table
IV. Review of the literature
American
SLd+Xt
Measures
Shimazaki et a1.l
H cast
Angio
Arcilla et al.” Horn et a1.3
H cast H cast
Angio Angio
Boak et a1.4
A cast H cast
Angio
Pietras et a1.5
H
Angio
Gentzler et al.‘j Ferlinz et al.’
H cast H cast
Angio Angio
Graham et a1.s Fisher et a1.g Thilenius and Arcilla’O Shimazaki et al.‘l
H cast A cast H
Angio Angio Angio
H cast
Echo Angio Echo
Reference
Levine et al.‘”
H cast
Watanabe et a1.l”
H
Starling et a1.14
H
Echo Angio Echo
Ninomiya et a1.15
H
Echo
Hiraishi et al.ls
Angio Echo
Method
Regression
equation
April 1992 He8r1 Journal
r
Biplane area-length Simpson Parallel-piped Biplane Simpson -(triangular)
a-l y = 0.79x + 0.24 Simpson y = 0.72x + 4.16 y = 0.74x + 4.1 y = 0.83x + 4.12
0.98 0.98 0.95 0.93
Biplane Simpson (hemielipsoid) Biplane Simpson (elliptical cylinder) Biplane Simpson Pyramid Biplane RAO, LAO Biplane Simpson Prism Biplane parallel-piped Apical 4-chamber RV area x-height of RV Apical 4-chamber view RV outflow tract view Apical 4-chamber view RV inflow view Pyramid
y = 0.95x + 3.5
0.996
y = 1.33x y = 1.27x -4.5
0.99 0.99
y = 1.54x y = 1.16x - 1.04
0.99 0.98
y = 0.29x
0.88 0.91 0.91 0.94 0.94 0.84
Simpson
+ 32.9
y = 0.52x + 32.9 y = 0.88x + 11.9 y = 1.0x + 4.6 EDV h = 0.56x + 10.1 ESV y = 0.55x + 8.0 Compared with radionuclide count Ejection fraction areas compared Angio, EF = 0.97 Echo EF + 0.020.98 0.92
Angio Echo
Regression analysis and EDV y = 0.96x - 1.14 apical 4-chamber RV area RV body and outflow volume
ESV x = 0.94x - 0.27 EDV y = 0.62x + 7.0
0.84 0.81
Saito et al.‘*
Angio Echo
measurepments separately Two subxiphoid views
ESV y = 0.82x + 1.4 y = 1.32x - 7.39 y = 0.91x - 7.35 7 = 0.42x + 1.36
0.85 0.85 0.85 0.82
Satomi et al.lg
Echo
Apical 4-chamber view and subxiphoid RAO equivalent view
Trowitzsch et a1.20 Wann et aLzl
Angio Echo Echo
Compared with ejection fraction of radionuclide method EDVy = 0.54x -6.8
0.97
Silverman and Hudson”
Lange et a1.22
Echo Angio
Two subxiphoid orthogonal views Ellipsoid, pyramid, Simpson (contrast) Contrast echocard iography
H, Human; A, animal; Angie, angiography; Echo, echocardiography; RN, radionuclide method; RAO, right anterior oblique; LAO, left anterior oblique; EDV, end-diastolic volume; ESV, end-systolic volume.
method did not take into account the outflow tract volume, although it appeared to be larger in diastole than in systole. This may explain the underestimation of the higher right ventricular volume by our method. Inasmuch as our excised heart preparation appeared to be comparable to the end-systolic state, in the animal heart study estimation of both right and
left ventricular volume was good. The regression equation for the left ventricular volume of the cast and that obtained by the area-length method by this method was y = 0.95x + 3.4 (r = 0.99). The coefficient of variation was it- 10.4 % , thus supporting the preceding explanation of the underestimation. Left ventricular volume was not underestimated as much at end systole, and right ventricular outflow tract
Volume Number
123 4, Part
RV volume by echo subtraction
1
volume was not as great at end systole. Thus estimation of right ventricular volume in the animal heart study appeared to be better than that in the clinical study. Despite these limitations our data suggest that the new modification is applicable clinically because of its simplicity and practicality. Clinical implications. In evaluating patients with myocardial infarction, a reduction in right ventricular function is a significant indicator of a poor prognosis. 33 Estimation of right ventricular function is also important in assessing patients with chronic obstructive lung disease. 28 Considering the clinical applicability of the method, easily obtainable apical views were used. Thus our method appears to be useful in clinical practice. Further studies may be required to assess the deformed right ventricle in volume- or pressure-overloaded patients. In addition, a comparison with such other methods as three-dimensional echocardiography and magnetic resonance imaging35 may also be indicated. REFERENCES
1. Shimazaki Y, Kawashima Y, Mori T, Beppu S, Yokota K. Angiographic volume estimation of right ventricle. Chest 1980; 77:390-5. 2. Arcilla R, Tsai P, Thilenius 0, Ranniger K. Angiographic method for volume estimation of right and left ventricles. Chest 1971;60:446-54. 3. Horn V, Mullins CB, Saffer SI, Jones DC, Freeborn WA, Knapp RS, Nixon JV. A comparison of mathematical models for estimating right ventricular volumes in animals and man. CIin Cardiol 1979;2:341-7. 4. Boak JG, Bove AA, Kreulen T, Spann JF. A geometric basis for calculation of right ventricular volume in man. Cathet Cardiovasc Diagn 1977;3:217-30. 5. Pietras RJ, Kondos GT, Kaplan D, Lam W. Comparative angiographic right and left ventricular volumes. AM HEARTJ
15.
16.
17. 18. 19.
20.
21.
22.
23.
24. 25. 26.
1985;109:321-6.
6. Gentzler RD, Briselli MF, Gault JH. Angiographic estimation of right ventricular volume in man. Circulation 1974;50:32430. 7. Ferlinz J, Gorlin R, Cohn PF, Herman MV. Right ventricular performance in patients with coronary artery disease. Circulation 1975;52:608-15. 8. Graham TP, Jarmakani JM, Atwood GF, Canent RV. Right ventricular volume determinations in children. Circulation 1973;47:144-53. 9. Fisher EA, Dubrow IW, Hastreiter AR. Right ventricular volume in congenital heart disease. Am J Cardiol 1975:36:67-75. 10. Thilenius GG, Arcilla RA. Angiographic right and’left ventricular volume determination in normal infants and children. Pediatr Res 1974;8:67-74. 11. Shimazaki Y, Kitamure S, Hata S, Nakano S, Ihara K, Yagihara T, Sato S, Kishimoto H, Ogawa M, Kawashima Y. Right ventricular volume estimation by two-dimensional echocardiogram. J Cardiogr 1981;11:187-98. 12. Levine RA, Gibson TC, Aretz T, Gillam LD, Guyer DE, King ME, Weyman AE. Echocardiographic measurement of right ventricular volume. Circulation 1984;69:497-505. 13. Watanabe T, Katsume H, Matsukubo H, Furukawa K, Ijichi H. Estimation of right ventricular volume with two-dimensional echocardiography. Am J Cardiol 1982;49:3 946-53. 14. Starling MR, Crawford MH, Sorensen SG, O’Rourke RA. A new two-dimensional echocardiographic technique for evalu-
27.
1021
ating right ventricular size and performance in patients with obstructive lung disease. Circulation 1982;66:612-20. Ninomiya K, Duncan WJ, Cook DH, Olley PM, Rowe RD. Right ventricular ejection fraction and volumes after Mustard repair: correlation of two-dimensional echocardiograms and cineangiograms. Am J Cardiol 1981;48:317-24. Hiraishi S, Disessa T, Jarmakani JM, Toshio N, Jones JBI, Friedman WF. Two-dimensional echocardiographic assessment of right ventricular volume in children with congenital heart disease. Am J Cardiol 1982;50:1368-75. Silverman NH, Hudson S. Evaluation of right ventricular volume and ejection fraction in children by two-dimensional echocardiography. Pediatr Cardiol 1983;4:197-204. Saito A, Ueda K, Nakano H. Right ventricular volume determination by two-dimensional echocardiography. J Cardiogr 1981;11:1159-68. Satomi G, Nakazawa M, Kanaya M, Narai S, Minami Y, Nakamura K, Takao A. A new method for the measurement of right ventricular volume in children by two-dimensional echocardiography. J Cardiogr 1982;12:481-8. Trowitzsch E, Colan SD, Sanders SP. Two-dimensional echocardiographic evaluation of right ventricular size and function in newborns with severe right ventricular outflow tract obstruction. J Am Co11 Cardiol 1985;6:388-93. Wann LS, Stickels KR, Bamrah VS, Gross CM. Digital processing of contrast echocardiograms: a new technique for measuring right ventricular ejection fraction. Am J Cardiol 1984;53:1164-8. Lange PE, Seiffert PA, Pries F, Wessel A, Onnasch DGW, Hahne H, Heintzen PH. Value of image enhancement and injection of contrast medium for right ventricular volume determination by two-dimensional echocardiography in congenital heart disease. Am J Cardiol 1985;55:152-7. Krebs W, Erbel R, Schweizer P, Schweizer P, Richter HA, Henn G, Massberg I, Meyer J, Effert S. Volumenbestimmung des richiten ventrikels mit hilfe der subtractions methode-eine vergleichende zweidimensional echokardiographische und rontgenologische studie an herzmodellen. Kardiologie 1982; 71:413-20. Erbel R, Richter HA, Krebs W, Schweizer P, Massberg I, Zotz R, Meyer J, Effert S. Right ventricular volume determination in isolated human hearts. J Clin Ultrasound 1986;14:89-97. Reedy T. Chapman CB. Measurement of right ventricular volume by cineangiofluorography. AM HEARTJ 1963;66:221-5. Bommer W, Weinert L, Neumann A, Neef J, Mason DT, Demaria A. Determination of right atria1 and riaht ventricular size by two-dimensional echocardiography. Circulation 1979;60:91-100. Kaul S, Tei C, Hopkins JM, Shah PM. Assessment of right ventricular function using two-dimensional echocardiography.
AM HEARTJ1984;107:526-31. 28. Berger HJ, Matthay RA, Loke J, Marshall RC, Gottschalk A, Zaret BL. Assessment of cardiac performance with quantitative radionuclide angiocardiography: right ventricular ejection fraction with reference to findings in chronic obstructive pulmonary disease. Am J Cardiol 1978;41:897-905. 29. Tobinick E, Schelbert HR, Henning H, Lewinter M, Taylor A, Ashburn WL, Karliner JS. Right ventricular ejection fraction in patients with acute anterior and inferior myocardial infarction assessed by radionuclide angiography. Circulation 1978; 57:1078-84. 30. Maddahi J, Berman DS, Matsuoka DT, Waxman AD, Stankus KE, Forrester JS, Swan HJC. A new technique for assessing right ventricular ejection fraction using rapid multiple-gated equilibrium cardiac blood pool scintigraphy. Circulation 1979;60:581-9. 31. Holman BL, Wynne J, Zieionka JS, Iodine JD. A simplified technique for measuring right ventricular ejection fraction using the equilibrium radionuclide angiocardioaram and the slant-hole collimator. Radiology 1981;i38:429-35. 32. Wyatt HL, Heng MK, Meerbaum S, Gueret P, Hestenes J, Dula E, Corday E. Cross-sectional echocardiography. Analy-
To&a
et al.
American
sis of mathematic models for quantifying volume of the formalin-fixed left ventricle. Circulation 1980;61:1119-25. 33. Polak JF, Holman BL, Wyn EJ, Colucci WS. Right ventricular ejection fraction: an indicator of increased moratlity in patients with congestive heart failure associated with coronary artery disease. 3 Am Co11 Cardiol 1983;2:217-23. 34. Linker DT, Moritz WE, Pearlman AS. A new three-dimen-
A dose-response
April 1992 Heart Journal
sional echocardiographic method of right ventricular volume measurement: in vitro validation. J Am Co11 Cardiol 1986; 8~101-6. 35. Sechtem U, Pflugfelder PW, Gould RG, Cassidy MM. Measurement of right and left ventricular volumes in healthy individuals with tine MR imaging. Radiology 1987;163:697-702.
trial of once-daily
diltiazem
This trial was performed to determine the safe and effective dosage range of once daily diltiarem (diltiazem CD) capsules for treatment of essential hypertension. Patients with essential hypertension having supine diastolic blood pressure values 195 mm Hg and 5110 mm Hg were randomly assigned to receive placebo or one of four doses of diltiazem CD: 90, 180, 360, or 540 mg. Blood pressure was measured at trough, 24 hours after the dose, and at the time of peak effect, 10 hours after the dose. Diltiazem CD lowered both supine diastolic and systolic blood pressure. A linear dose response was seen with changes in diastolic and systolic blood pressure and heart rate for trough and peak measurements. Trough/peak ratios for the 180, 360, and 540 mg doses were all greater than 0.50. Adverse effects were dose related; those most commonly reported were headache (8.6%), bradycardia (8.1%), and edema (7%), with bradycardia and edema possibly dose related. It is therefore concluded that diltiazem CD is a safe and effective antihypertensive agent. (AM HEART J 1992;123:1022.)
James V. Felicetta, MD, a Harry M. Serfer, DO, Neal R. Cutler, MD,b Thomas J. Comstock, PharmD,C Gary L. Huber, MD,d Matthew R. Weir, MD,e Kerry Hafner, PhD,f and Glen D. Park, PharmD.f Phoenix, Ark., Hollywood, Flu., Beverly Hills, Calif., Richmond, Vu., Tyler, Texas, Baltimore, Md., and Kansas City, MO. Diltiazem is a widely prescribed calcium channel blocker that is highly effective in the treatment of essential hypertensi0n.l A sustained-release capsule formulation (Cardizem SR) has been available for several years, but it has been approved only on a twice daily basis as therapy for essential hypertensiom2 Medication compliance is inversely related to the number of times each day a drug must be taken.3>4 As a consequence, once daily dosing has been recommended for antihypertensive treatment.5J 6It is therefore highly desirable to demonstrate that a sustainedrelease formulation of diltiazem, that is, diltiazem
From “the Carl T. Hayden Veterans Administration Medical Center, bthe California Clinical Trials Group, 9he Medical College of Virginia, dthe University of Texas Health Center, %he University of Maryland, and ‘Marion Merrell Dow, Inc. Received Reprint Center, 85012. 411135347
1022
for publication
June
10, 1991;
accepted
requests: James V. Felicetta, MD, Carl Medical Service (111),7th St. and Indian
Oct. 1, 1991. T. Hayden VA Medical School Rd., Phoenix, AZ
CD capsules, is safe and effective with once daily dosing in the management of essential hypertension. There has been increasing academic and regulatory interest in recent years in documenting antihypertensive effects at trough (end of the dosing interval) and at peak.7 This is particularly important for formulation of a relatively short-acting drug designed to extend the dosing interval to 24 hours. The duration of action of a drug can be increased by raising the dose to achieve an incremental effect at the end of the dosing interval, but this produces a substantially greater peak effect, which thus increases the risk of hypotension or other side effects. An effective sustained-release formulation should achieve effective blood pressure lowering at trough without producing increased side effects at peak. The primary objective of this study was to determine the safe and effective dosage range of diltiazem CD capsules prescribed on a once daily basis for treatment of essential hypertension. A secondary objective was to compare the peak and trough blood pressure-lowering responses to diltiazem CD capsules.