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1398 CIRCULATION VOL 63, No 6, JUNE 1981 diographic assessment of cardiac anatomy and function in hypertensive subjects. Circulation 59: 623, 1979 24. Antman EM, Green LH, Grossman W: Physiologic determinants of the electrocardiographic diagnosis of left ventricular hypertrophy. Circulation 60: 386, 1979 25. Dunn RA, Pipberger HV, Holt JH Jr, Barnard ACL, Pipberger HA: Performance of conventional orthogonal and multipledipole electrocardiograms in estimating left ventricular muscle 21. Bennett DH, Evans DW: Correlation of left ventricular mass determined by echocardiography with vectorcardiographic and electrocardiographic voltage measurements. Br Heart J 36: 981, 1974 22. McFarland TM, Mohsin A, Goldstein S, Pickard SD, Stein PD: Echocardiographic diagnosis of left ventricular hypertrophy. Circulation 57: 1140, 1978 23. Savage DD, Drayer JIM, Henry WL, Mathews EC Jr, Ware JH, Gardin JM, Cohen ER, Epstein SE, Laragh JH: Echocar- mass. Circulation 60: 1350, 1979 Quantitation of Human Left Ventricular Mass and Volume by Two-dimensional Echocardiography: In Vitro Anatomic Validation JOSEPH W. HELAK, M.D., AND NATHANIEL REICHEK, M.D. Downloaded from http://circ.ahajournals.org/ by guest on June 17, 2017 SUMMARY The reliability of two-dimensional echocardiographic (2-DE) quantitation of left ventricular (LV) section area, volume and myocardial mass was assessed in Vitro in 13 postmortem human hearts (LV weight 115-454 g). The pathologic diagnoses included: two normal, five coronary artery disease with infarction and/or aneurysm, three valvular heart disease, two cardiomyopathy and one left ventricular hypertrophy. Hearts were divided into six to 24 short-axis slices (n = 123), imaged in a tank filled with mineral oil and the images planimetered. Calibrated photographs-and actual LV weight served as reference standards. Estimates of section LV cavity volume and myocardial volume were derived by multiplying the appropriate area by section thickness. Section LV mass was obtained by multiplying the myocardial volume by myocardial density. Total LV cavity volume and myocardial mass were derived using Simpson's rule and a short axis area-apical length method. In absolute terms, 2-DE underestimated LV cavity area but accurately estimated LV myocardial area. Excellent correlations were obtained between 2-DE and photographic standards for section cavity area (r = 0.95) and volume (r = 0.90). Simpson's rule (r = 0.97) and area-length (r =- 0.82, r = 0.90, excluding one heart with a bizarrely shaped LV cavity secondary to extensive mural thrombus) estimates of total LV cavity volume also correlated well with reference standards. Similarly, section LV myocardial area correlated well with photographic myocardial area (r = 0.89) and 2-DE and photographic estimates of section LV mass correlated well with actual LV weight (r = 0.92 and 0.96). Consequently, total LV mass obtained with Simpson's rule or the area-length method was highly reliable (r = 0.93 and 0.92, respectively). We conclude that 2DE can provide reliable estimates of LV volume and mass using the short-axis Simpson's rule or area-length methods and appropriate regression corrections. The area-length method is simple enough to permit clinical application. TWO-DIMENSIONAL ECHOCARDIOGRAPHY (2-DE) is a potentially valuable noninvasive tool for the quantitative assessment of left ventricular (LV) volume and myocardial mass in man. Validation studies of 2-DE in several laboratories have demonFrom the Noninvasive Laboratory, Hospital of the University of Pennsylvania, and Cardiovascular Section, Department of Medicine, the University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania. Presented in part at the 29th Annual Scientific Sessions of the American College of Cardiology, March 1980. Supported in part by a Southeastern Pennsylvania Heart Association Research Fellowship grant to Dr. Helak and a Commonwealth of Pennsylvania Health Services contract to Dr. Reichek. Dr. Helak's present address: Department of Cardiology, Upstate Medical Center, East Adams Street, Syracuse, New York 13210. Address for correspondence: Nathaniel Reichek. M.D., Noninvasive Laboratory, Hospital of the University of Pennsylvania. 3400 Spruce Street, Philadelphia, Pennsylvania 19104. Received May 19, 1980; revision accepted September 24, 1980. Circulation 63, No. 6, 1981. strated the accuracy of in vitro canine LV volume and mass in symmetric and asymmetric ventricles,1-3 LV volume determination in a beating dog heart preparation,4' in vivo canine LV volume and mass,6-10 and in vitro human LV cast volume." Moderately good correlation of human in vivo 2-DE LV volume and ejection fraction with angiographic and/or radionuclide methods has also been reported.8 12-18 However, 2-DE assessments of LV volume and mass have not been validated directly with quantitative anatomy in man. The present study was designed to test the accuracy of 2-DE imaging of individual cardiac sections and of derived estimates of total LV volume and mass in the postmortem human heart. Methods Specimen Collection Thirteen postmortem human hearts, 300-1100 g, with a wide range of pathologic diagnoses (table 1) were obtained from the necropsy service. Nine were QUANTITATION OF LV MASS AND VOLUME/Helak and Reichek 1399 TABLE 1. Age, Sex, Pathologic Diagnosis and Heart Weight Downloaded from http://circ.ahajournals.org/ by guest on June 17, 2017 Pt 1 Sex M 2 F 3 F 4 F 5 6 F M 7 M 8 F 9 10 11 12 13 F M M M - Age Pathologic diagnosis (years) Rheumatic heart disease involving mitral valve; pros69 thetic aortic valve; biventricular hypertrophy; coronary artery disease with old anteroseptal myocardial infaretion. 74 Coronary artery disease with old anteroseptal and inferior wall infarctions, apical aneurysm. 56 Concentric left ventricular hypertrophy; coronary artery disease without infarction. 58 Coronary artery disease with old nontransmural arterolateral and inferior wall infarctions. 60 Normal 54 Severe three-vessel coronary artery disease with multiple old transmural and nontransmural infaretions and an apical aneurysm; right ventricular hypertrophy. 32 Mitral regurgitation due to myxomatous mitral valve s/p porcine valve replacement; infarcted posterolateral and posteroseptal regions of left ventricle due to coronary embolus; large left ventricular mural thrombus. 72 Coronary artery disease with old infarction posterior left ventricle and possible acute anteroseptal 63 43 37 66 infarction. Restrictive cardiomyopathy primary amyloidosis Congestive cardiomyopathy Aortic stenosis, biventricular hypertrophy Normal Concentric left ventricular hypertrophy formalin-fixed for 24 hours and hand-sectioned in the short-axis plane into six to 11 sections (0.5-3 cm thick) as part of the routine autopsy examination. Four were specially prepared after formalin fixation, being embedded in a gelatinous base and sectioned in the short-axis plane using a motorized slicer set at 0.5 cm thickness producing from 13-24 uniform sections per heart. The thickness of each short-axis section was directly measured at three to five sites with a millimeter rule and the mean thickness recorded. Because the sections could not be directly planimetered, the superior and inferior surfaces of each section were photographed with a calibration scale on a Xerox copier, model 4000 (fig. 1). Each section was then suspended on an 18gauge needle and a specially designed stand placed in a glass tank filled with mineral oil. Two-dimensional echocardiographic images were recorded of each section in a short-axis orientation using a Varian VR 3000 phased-array sector scanner with a 2.25-MHz transducer. The transducer was handheld, 8-10 cm from the section. Gain, reject, damping and compression controls were adjusted to produce as complete an image as possible with the least gain. In general, overall gain and compression were high, regional (slide-bar) amplification, contrast and damping low. Total heart weight (g) 1000 LV weight (g) 290 450 171 351 149 700 202 400 720 159 223 1010 454 300 116 850 1100 350 202 293 377 115 254 To obtain adequate images in some instances, two adjacent 0.5-cm sections were sutured together with 3-0 silk suture. To obtain slice thickness by 2-DE, sections were stacked up from base to apex and images recorded in a projection analogous to the in vivo apical view. Strong interfaces were generated between slices and 50% of each interface thickness was included in each slice thickness, which was traced onto clear plastic and measured on a digitizer. The thickness of the most superior section of each left ventricle could not be isolated in this view because of the attached great vessels and atria. Therefore, these 2-DE thicknesses were interpolated using a regression analysis and measured LV section thickness. The 2-DE images were recorded on a Sanyo ½/2-inch videotape recorder. With the corresponding anatomic specimen as a reference, LV epicardium and endocardium were highlighted on each of the photographic images (fig. 2A). Four or five representative, calibrated 2-DE images of each section were traced from videotape onto clear plastic with a fine-tip pen using real-time, slowmotion and stop-frame analysis and a 12-inch television screen. The LV cavity area excluded all endocardial echoes while the thickness of the finest outer line of epicardial echoes seen anywhere on the section 1400 CIRCULATION Vo1 63, No 6, JUNE 1981 Downloaded from http://circ.ahajournals.org/ by guest on June 17, 2017 FIGURE 1. Representative short-axis heart section (left) with corresponding calibrated photograph (center) and two-dimensional echocardiographic image (right). perimeter was excluded from total LV area throughout the image (fig. 2B). When, occasionally, image dropout occurred on the lateral margin of the section, the boundary was extrapolated. The 2-DE images were traced by blinded observers without knowledge of other data. Total LV area and LV cavity area were measured on each photographic and 2-DE image using a planimetry program validated by comparison to manual planimetry on irregular test images of known area and by comparison to calculated area of circular and rectangular test images of known radius or linear dimension. Program results were essentially identical with those of geometric calculation and manual planimetry. Images were digitized, calculations performed and statistical analysis was made on a Hewlett-Packard 9025A programmable calculator equipped with a high-resolution digitizing board (0.001 mm) and high-speed plotter. A F1GU R 2. (A ) Photographic image shown in figure 1 with endocardium and epicardium of the surface nearest to the camera outlined. (B) Two-dimensional echocardiographic image shown in figure 1, with total left ventricular (L V) area and L V cavity area outlined. L V cavity area excludes endocardial echoes, while the thickness of the finest outer line of epicardial echoes seen anywhere on the scection perimeter is excluded from total L V area throughout the image. The finest lin e of epicardial echoes is identified bh the arrow. QUANTITATION OF LV MASS AND VOLUME/Helak and Reichek Vmuscle Vcoity AmT = area-length volume was calculated as 5/6 (A pap) L, where A pap = area at high papillary muscle level and L = LV length (fig. 4). -m V A ACT 7rT3 = AT 2 LV Weight T FIGURE 3. Geometric derivation of section volumes from a single left ventricular slice. V = volume; Am = myocardial area; Ac = cavity area; T= slice thickness. Downloaded from http://circ.ahajournals.org/ by guest on June 17, 2017 For photographic images, the mean of the superior and inferior surface areas was used to represent the mean area of each section. For 2-DE images, the mean of at least four images was used to represent the section area. Both photographic and 2-DE LV myocardial areas were determined by subtraction of LV cavity area from total LV area. Videotapes of 69 2-DE sections were traced independently by two observers to determine interobserver variation. Geometric Models Photographic and 2-DE volumes were determined for each nonapical section by multiplying the appropriate area (A) (LV myocardium or LV cavity) by section thickness (T) (fig. 3). The directly measured section thickness was used to calculate the photographic volume. Apical section volume was determined using the formula for an ellipsoidal volume segment: rT3 AT 2 6 LV section mass was obtained by multiplying the LV myocardial volume by the accepted value for density of myocardium (1.055 g/ml). Total LV muscle volume and LV cavity volume for each heart were derived from the 2-DE and photographic images using Simpson's rule. We also tested an area-length method reported by Wyatt and coworkers to provide accurate LV volume and mass in the canine left ventricle.7 Simpson's rule merely added the volume of all sections together (fig. 4), while the Simpson's Rule (n-I) V = 11 AnT 7rTn3 n AT +- Area Length Method V= 5/6 APOPL 1401 L T Apap F:- FIGURE 4. Derivation of total left ventricular myocardial and cavity volumes using Simpson's rule and short-axis area-length method. V = volume, n = number of sections; A = area; T = thickness; AP.P = area at high papillary muscle level; L = length. After the photographic and 2-DE images were obtained, the sections were blotted dry, dissected with removal of the right ventricle, atria, great vessels and epicardial fat and the LV sections weighed on a triplebeam balance. All section weights were added to determine total LV weight per specimen. The specific gravity of portions of four left ventricles weighing 43-79 g was determined by volume displacement using a 250-ml beaker and 100-ml graduated cylinder. Statistics The 2-DE data, photographic data and LV weights were compared by standard least-squares linear regression analysis. The regression line for each relationship examined was compared with the line of identity for that variable using a standard statistical method for comparison of slopes.'9 The regression equations for Simpson's rule approximations and area-length approximations of the same variable were compared in a similar manner. Results Individual Cardiac Sections One hundred twenty-three cardiac sections were studied anatomically, photographically and with 2-DE to determine LV cavity area and volume and LV myocardial area and mass as described above. Section Area and Thickness The 2-DE LV cavity area showed a close linear correlation with photographic LV cavity area (r = 0.95) over the range 0-31.5 cm2 (fig. 5A). The least-squares linear regression equation relating 2-DE LV cavity area to photographically measured LV cavity area was A2-DE = 0.76 AphOto-0.1 (SEE = 1.8 cm2). Thus, in absolute terms, 2-DE markedly underestimated photographic cavity area. The 2-DE total LV area also correlated well with photographic total LV area (r = 0.94) over the range 6.4-85.8 cm2 (fig. 5B). The regression equation relating 2-DE total LV area to photographic total LV area was A2-DE = 0.96 Aphoto-0.21 (SEE = 6.8 cm2). The 2-DE LV myocardial area correlated slightly less well with photographic LV myocardial area (r = 0.89) (fig. SC). The regression equation relating 2-DE LV myocardial area to photographic LV myocardial area was myocardial A2-DE = 0.97 myocardial APhoto + 0.98 (SEE = 6.9 cm2 range 6.1-65.4 cm2). The 2-DE LV section thickness showed a close linear correlation with actual thickness (r = 0.88) over VOL 63, No 6, JUNE 1981 CIRCULATION 1402 SECTION LV CAVITY AREA n-123 r- .E95 S. E. E. -1. 13 so SECTION LV MYOCARDIAL AREA 90 aS e30 70 2n 80 E 0 I IL X 20 0 50 C-, C 40 1m W n=i23 30 10 r=. 20 5 10 ii a 0 .' -0. 120- y- a n1 (i a W) Ri Ni - Y-0.98-.- V_ PHOTO (cm 2) 0. 70X 0. ae- 20.97X c A & & 0.N m Downloaded from http://circ.ahajournals.org/ by guest on June 17, 2017 94 S.E.E.-6. 8 + 2.00 + . 1. 50 C 1. 00 40 00 C,- 30 I 20 LIJ U 50 2. so I 1 59 & S m0 n1 15 r-. 88 S. E. E. =. 14 r. 70 E 00 n-123 00 (0 m& SECTION THICKNESS 3. 1 00 0 & & PHTO +PHO TO (cm. ) SECTION TOTAL LV AREA 0 89 S. E.E. =6. 9 0. 50 10 a N Y- -0. a a 1t 't 211 0. 9m a O a 0 19 aO *- PHOTO (cmi) ACTUAL D B 9 89 0. 13- 0. BSX Sex 9 ATA a hi 19 V) (Cm. ) t FiDGURE 5. (A) Comparison of section left ventricular (LV) cavity area by two-dimensional echocardiography (2-DE) (vertical axis) and by calibratedphotograph (horizontal axis). Regression equation is at lower left. n = number ofslices. (B) Comparison of section total L V area by 2-DE and by calibrated photograph. (C) Comparison of section L V myocardial area by 2-DE and by calibrated photograph. (D) Comparison of 2-DE L V section thickness and actual L V section thickness. (0.3-1.6 cm, fig. 5D). The regression equation relating 2-DE section thickness to directly measured thickness was T2-DE = 0.85 T actual ± 0.13 a narrow range (SEE = 0. 14 cm). Section Volume and Mass absolute terms, 2-DE markedly weight. Similarly, photographic section close correlation (r = 0.96) with weight over the range 0.3-84 g overestimated LV LV mass showed a actual section LV (fig. 6B), but the regression equation relating photographic section LV directly measured LV section weight was Mphoto = 1.3 weight + 0.19 (SEE = 6.1 g). Thus, the photographic method also overestimated LV section weight. The relationships of 2-DE section LV mass and photographic section LV mass to actual section LV weight were not statistically different. mass to The 2-DE-section LV cavity volume correlated well with photographic section LV cavity volume (r 0.90) over the range 0-63.8 ml. The regression equation relating 2-DE section LV cavity volume to photographic section LV cavity volume was V2-DE = 0.65 Vphoto + 0.56 (SEE = 3.2 ml). While 2-DE LV section mass correlated well with actual section LV weight (r 0.92) over the range 0.3-84 g (fig. 6A), the regression equation relating 2-DE section LV mass to directly measured LV weight Total LV Mass and Volume = was M2.DE = 1.42 weight -1.8 (SEE = 9.9 g). Thus, in The 2-DE total LV mass and volume correlated extremely well with total LV weight and photographic reference standards. QUANTITATION OF LV MASS AND VOLUME/Helak and Reichek SECTION LV WEIGHT A rea-Length Method 1 BCo 140 1 30 100 1210 1 CZ0 0 C 70 n=123 r=0. 92 S. E. E. =9. 9 40 30 20C! 10 G8 68 8 1. 901. 4ZX A 8 6 a 8 n o hI' N" 1 y- 88G E8 E a N aUo M 0 t a8 0 O " (gn.) ACTUAL SECTION LV WEIGHT 1 30 Downloaded from http://circ.ahajournals.org/ by guest on June 17, 2017 120 110 1 00 90 e0 g 70 m 00 50 cL n- 123 r=. 96 40 30 S. E. E. =6. 1 20 Area-length estimates of total LV mass and volume correlated well with reference standards in the 13 study hearts but not as well as Simpson's rule estimates. The 2-DE total LV cavity volume was related to photographically determined total LV cavity volume by the equation V2DE = 0.77 VPhOtO + 1.8 (r = 0.82, SEE = 38.4 ml). This relationship was markedly distorted by one heart (patient 7; table 1) that contained a large, markedly irregular thrombus that occupied more than 50% of the LV cavity and produced a bizarre cavity shape. With this heart excluded, the equation relating area-length 2-DE total LV cavity volume to photographically determined total LV cavity volume was V2DE = 1.07 Vphoto -11.76 (r = 0.90, SEE = 29.0, range 12.4-183.1 ml). (fig. 8A). The regression equation relating area-length 2-DE total LV mass to photographic total LV mass was MI-DE = 1.21 MPhOtO -4.61 (r = 0.93, SEE = 71.1 g, range = 146.5-612.6 g) (fig. 8B). This slope did not differ significantly from unity. In contrast, the equation relating area-length 2-DE total LV mass to actual total LV weight had a slope much greater than unity: MI-DE = 1.66 weight -23.83 (r = 0.92, SEE = 74.7 g) (fig. 8C). Photographically determined area-length total LV mass showed a similar relationship to actual total LV weight: MphotO = 1.67 weight -35.86 (r = 0.99, SEE = 29.4 g). Specific Gravity 10 H Y- 1403 N 0. 1 9- m UD 't U0 a88s N (I (gm.) ACTUAL The specific gravity of the LV myocardium from hearts in this study determined by volume displacement was 0.964 g/ml. 1. 30X B + FIGLR[ 6. (A) Comparison of two-dimensional echocardiographic section measurement of left ventricular (LV) mass (vertical axis) and actual section L V weight (horizontal axis). (B) Comparison ofphotographic section L V mass and actual section L V weight. Simpson's Rule Thirteen human left ventricles weighing 115-454 g had photographically determined LV cavity volumes of 12.4-217.9 ml. The regression equation relating total 2-DE LV cavity volume to photographically determined total LV cavity volume was V2-DE = 0.75 Vphoto -2 (r = 0.97, SEE = 13.9 ml) (fig. 7A). The re- gression equation relating 2-DE total LV mass to pho- tographically determined total LV mass was M2-DE = 1.05 Mphoto -6.1 (r = 0.94, SEE range 180-613 g) (fig. 7B). The regression equation relating 2-DE total LV mass to actual total LV weight was M2-DE = 1.43 weight -21.8 (r = 0.93, SEE = 59.5 g) (fig. 7C). As ex- pected, photographically determined total LV mass also correlated well with actual total LV weight (r = 0.98). The regression equation relating photographic total LV mass to actual total LV weight M2-DE = 1.36 weight -13.3 (SEE = 26.5 g). was Interobserver Variation Videotapes of 69 2-DE sections from seven hearts were reviewed and traced independently by two observers to determine interobserver variation in area measurement from the same recording. Excellent linear correlation was obtained for 2-DE section total LV area (slope = 0.99 r = 0.97, SEE = 4.9 cm2). Likewise, 2-DE section LV cavity area showed close linear correlation between observers (slope = 0.90 r = 0.91, SEE = 2.1 cm2). The 2-DE section thickness also correlated well between observers (r = 0.96, slope = 0.91, SEE = 0.1 cm). Interobserver variation in performing the recordings was not assessed. Discussion The accuracy of 2-DE assessment of LV volume and mass has been validated in canine models in ViVO7-10 and in vitro.1-6 Numerous studies8' 12-18 have also examined the validity of 2-DE quantitative assessment of LV volume, LV mass and ejection fraction in man by comparing 2-DE with angiographic and/or radionuclide methods. Overall, comparing 2DE to angiography, LV end-systolic volume has been more reliable (r = 0.86-0.96) than either ejection fraction (r = 0.73-0.94) or LV end-diastolic volume (r = CIRCULATION 1404 VOL 63, No 6, JUNE 1981 SIMPSON'S RULE SIMPSON'S RULE 225 TOTAL LV CAVITY VOLUME 200 - 650 41 500 175 150 700 n=13 r-. 97 14 sl0 E TOTAL LV MASS 1 450 + 400 + S. E. E. =13. 9 125 U) E C)'I 1 02 O 75 I LLI 350 + 300 250 n='3 r=. 94 S. E. E. =54. 7 50 25 50 X N Y- 2 u 1\ N 0 04 ^0 .4 2 2 N N 2 N 1. 05X PHOTO (m 1. ) Downloaded from http://circ.ahajournals.org/ by guest on June 17, 2017 700 TOTAL LV WEIGHT 1500 550 500 450 350 U 300 250 n=13 220 r=. 93 S.E. E. =59. 5 150 100 50 a 0 S S N 0 N IX M S t 5 t U U U) S a C & G 0 t a 77 Y- -2413 ACTUAL C M l 0 0 h t 400 o) wi MC) FIGURE 7. (A) Comparison of Simpson's rule total left ventricular (L V) cavity volume by two-dimensional echocardiography (2-DE) (vertical axis) and by calibrated photograph (horizontal axis). (B) Comparison of Simpson's rule total L V mass by 2-DE and by calibrated photograph. (C) Comparison of Simpson's rule 2-DE total L V mass and actual total L V weight. B50 m N PHOTO (gm. ) a SIMPSON'S RULE g N Y_ - . 13- -2. 05- 0. 75X A a W c' 5 In (gm.) 1. 43x 0.46-0.94). When 2-DE was compared only to biplane angiography,12' 115 18 the apparent reliability of ejection fraction increased (r = 0.84-0.94) but the reliability of LV volume estimates was not significantly altered. In a comparison of 2-DE and radionuclide studies to biplane angiography, one study'5 showed no major difference in reliability between 2DE and radionuclide estimates of end-diastolic volume index, end-systolic volume index or ejection fraction. However, others have observed a poorer correlation between radionuclide ejection fraction and angiographic ejection fraction than between 2-DE and angiographic ejection fraction (2-DE vs angio, r = 0.94; radionuclide vs angio, r = 0.80).18 Comparisons of 2-DE and radionuclide ejection fractions have shown correlation coefficients of 0.75 and 0.92. 14,17 Excellent results have been obtained in canine studies of in vitro and in vivo 2-DE LV mass , compared to actual LV weight (r = 0.86 -0.97).2 8-10 However, comparison of human 2-DE in vivo LV mass estimates to those of biplane angiography has given less satisfactory results (r = 0.80).8 Most investigators have concluded that 2-DE ejec- tion fraction has a close enough correlation with angiography to allow meaningful clinical application. However, volume measurements by 2-DE in four studies'2-14, 18 have underestimated angiographic LV volume with a large standard error, which limits clinical applicability. In contrast, one study indicates that 2-DE can accurately predict angiographic LV volume.'5 The 2-DE estimation of LV mass has appeared to have limited clinical applicability.8 This inconsistency in conclusions is not surprising, given the many variables that must influence the results reported. A fundamental problem is the inherent limitation of 2-DE image resolution, which is accentuated by the need to trace images using stopframe analysis, and results in limited accuracy of boundary identification of endocardium and epicardium. A second problem relates to the many different geometric formulas for estimating LV volume used in different studies (table 2). Moreover, even when similar geometric methods are used, the 2-DE data are often derived from different 2-DE projections. Finally, use of angiographic and radionuclide methods to validate quantitative 2-DE can be misleading because these methods also indirectly estimate quantitative anatomy. This was demonstrated by Bommer et al.11 in a recent study comparing angiographic and 2-DE estimates of LV volume to direct measurements of LV casts and working LV models in vitro. When compared to this independent reference system, angiography appeared no more accurate than 2-DE. A previous report from our laboratory20 comparing Mmode echocardiographic LV mass estimates to anatomic weight also showed the importance of using an anatomic reference rather than angiography for QUANTITATION OF LV MASS AND VOLUME/Helak and Reichek AREA LENGTH TOTAL LV MASS AREA LENGTH E00 250 TOTAL LV CAVITY VOLUME 1405 700 200 600 500 150 -4 400 E n=12 r-, 90 S.E.E. =29.6 100 C3 sI w0 ° U u n=13 r-. 93 S. E. E. =71. 1 300 200 1 00 Y- - 1 . 76- ^4 T4 N N y- PHOTO (m l. ) 1. 21X l. 07X A -4. 51-.- 0N 0 0 0 0 In D h 09 & m U U 0 (D PHOTO (,gm. ) B FIGURE 8. (A) Comparison of area-length total left ventricular (L V) cavity volume by two-dimensional echocardiography (2-DE) (vertical axis) and by calibrated photograph (horizontal axis). One heart with a large irregular thrombus occupying greater than 50% of the LV cavity was excluded from this analysis (see Results). (B) Comparison of area-length total L V mass by 2-DE and by calibrated photograph. (C) Comparison of area-length 2-DE total L V mass and actual total L V weight. AREA LENGTH Downloaded from http://circ.ahajournals.org/ by guest on June 17, 2017 900 TOTAL LV WEIGHT 700 600 500 al 400 0 I LIL 300 n=13 92 S. E. E. 200 r=. =74. 7 100 V- -23. E331 s ACTUAL s F @ (gm.) esesx C validation whenever possible. ]In that study, several echo LV mass methods valiidated previously by angiography correlated relativetly poorly with actual LV weight, while the optimal method obtained by direct comparison to LV weight was far more reliable. To better define the limitatiorns of the 2-DE method itself in man, we chose to asset ss the quantitative accuracy of 2-DE imaging of the,area of individual cardiac short-axis sections obtainled from postmortem human hearts. Short-axis sections were selected because they generally provide optimal endocardial imaging, and thus, should have the greatest potential for accurate quantitation. The 2-DE data were compared to two direct anatomic rteference standards: an in vitro photographic method 1for sectional LV area and volume and the actual LV soection weight. Derived estimates of total LV cavity volume and mass obtained using Simpson's rule and an area-length method shown7 to be potentiallly clinically applicable were also compared with the photographic and LV weight standards. Direct compairison of photographic and 2-DE image areas permittec assessment of the impact of image properties per se on quantitation. Conversely, use of the Simpson s rule and area-length approximation for both 2-DE and photographic methods made it possible to assess the impact of the geometric method independent of a particular image type. A wide range of pathologic findings, including myocardial infarction, LV aneurysm and severe LV dilation, present in this series. Our results show that, in this in vitro system, excellent correlations are obtained between 2-DE and photographic standards for section LV cavity area and volume. Thus, Simpson's rule estimates of total LV cavity volume are also reliable. Area-length estimates of total LV cavity volume also correlate well with our reference standard when cavity shape is not bizarrely distorted. In one heart, a huge irregular thrombus did markedly affect the area-length volume estimate, but a second heart (no. 10) with an ordinary apical thrombus was accurately assessed. Moreover, myocardial infarction (five hearts), LV dilatation (five hearts) or LV aneurysm (two hearts) did not invalidate the arealength volume estimate. Therefore, this simple arealength method may give reliable results in the common types of LV shape distortion that are clinically was encountered. Volume and mass estimates based on long-axis, four-chamber and two-chamber views, which include more of the LV perimeter, would probably deal more effectively with abnormalities of LV shape than a short-axis area-length method. However, endocardial identification may not be as reliable as in short axis. Unfortunately, in the present study, the sectioning method, which permitted direct comparison of echo image with original target, also precluded evaluation of other 2-DE views. The reliability of 2-DE volume estimates obtained using VOL 63, No 6, JUNE 1981 CI RCU LATION 1406 TABLE 2. Summary of Geometric Formulas, Two-dimensional Echocardiographic Projections and Reference Methods Used in Different Studies to Approximate Left Ventricular Volume Authors Bommer et al.11 Starling et al.18 2-1) E projections Biplane, apical Biplanie, apical Reference method GeometXic formiilas Simpson's ruile Simpson's ruile Biplane anigiography Biplane angiography and radionuclide niethod Carr et al.12 Long axis Short axis Axial (RAO equi-ivalent) lleimiaxial (4-chamber) V Li L2 L3 6 1-, from image with longest apparent long axis L2 from same view as L,3 from orthogonal view Biplane angiography anid silngle-planie angiography Schiller et al.13 Short axis, mnitral leaflet tips (equiivalentt to LAO) Two-chamber apical view (RAO Simpsoii's rulle Biplane angiography Folland et al.14 Short axis, mitral leaflet tips Short axis, base of pIapillartmuscle M\odified Simpsoni's ruile lPlipsoid using biplanie data Ellipsoid uising sinigle-plane data Hemisphere-cylinder model M\lodified ellipsoid model V _ 4 /3 w L/2 Dr f2 1D 2 Biplane angiography, radionuclide ventriculograms equiivalent) Apical view (4-chamber) Downloaded from http://circ.ahajournals.org/ by guest on June 17, 2017 Chaudry et a116 Quinones et al.17 Short axis, mitral valve tip apical view (RAO equiivalent) Measure short axis at base, mid-LV anld dist al LV in 4-chamber view and 4-chsamb)er apicalapical apical R{AO equivalent view Measuire short axis at base and mid-LV in long axis Estimate fractional shortening of LV long axis from apical contraction Abbreviations: IIAO = right aniterior obliquie; LAO Dd2 - ---2 + 1)d2 = J)D2 left anterior oblique; LV either method we tested appears to be comparable statistically to that reported for angiographic methods in vitro.21' 22 However, in absolute terms, 2-DE underestimates LV cavity volume as compared to Simpson's rule photographic estimates. This suggests that underestimation is related to the properties of the echo image. The relatively thick endocardial echo display probably encroaches on the cavity area. This problem is compounded in heavily trabeculated areas or those containing papillary muscle, where fine extensions of LV cavity may actually be obliterated by thick endocardial echoes. Echo line thickness is gain-dependent, but images used in this study were all done at the lowest gain that provided a complete image. Also, problems of this type may be heavily dependent on the 2-DE instrument used. Validation of quantitation obtained with one type of 2-DE system may not therefore be applicable to others. Using Simpson's rule, 2-DE reliably predicts actual LV weight (r = 0.93). Results are similar using the area-length method (r - 0.92). The reliability of the 2DE estimates of LV mass in this in vitro system is similar to that noted in a canine in vitro study.2 However, 2-DE LV mass appears to be less accurate than biplane angiographic LV mass has been reported to be when compared to LV weight in vitro.21 In absolute terms, 2-DE systematically overestimates LV weight (slope = 1.43 for Simpson's rule, 1.66 for area- I)d2 , AL Single-plane angiography Single-plane angiographv, Gated blond pool imaging left ventricuilar. length). Similar overestimation occurs when photographic images are used to estimate LV mass with either Simpson's rule or area-length geometry, so the major problem is not due to 2-DE imaging. One component of the overestimate is the unexpectedly low specific gravity of our formalin-fixed, oil-immersed sections. However, the reduction in specific gravity accounted for only 22% of the mean overestimate of LV weight. We conclude that most of the LV mass overestimate results from the geometric methods used. The Simpson's rule approximation, the best available geometric method, ignores the irregularity of the trabeculated endocardial surface, which can be marked in hearts which are fixed at small cavity volume, and can vary throughout the thickness of even a thin section of LV. Inclusion of small recesses of the LV cavity in LV mass probably results. Because postmortem LV volume is often smaller than in vivo enddiastolic volume, this problem may be less important in vivo. In any event, use of a regression relationship compensates for the problem. Because of the many differences between in vitro and in vivo 2-DE, estimates of in vivo human LV mass must also be compared to anatomic LV weight, as has been done with M-mode echocardiography20 and biplane angiography.23 The 2-DE LV volume methods evaluated in this study must also be compared with in vivo angiographic volumes. Moreover, further evalua- QUANTITATION OF LV MASS AND VOLUME/Helak and Reichek tion in vitro and in vivo of other geometric approaches is clearly necessary. However, this quantitative in vitro study provides a useful basis for such efforts, demonstrates the limitations of quantitative 2-DE imaging with present instrumentation, and shows the potential clinical applicability of a simple short-axis area-length method to the human left ventricle for quantitation of both mass and volume. Acknowledgment The authors acknowledge the technical assistance of Theodore Plappert and Ali Muhammad, the assistance of Drs. Eugene Pearlman and Karl Weber in providing pathologic material, the secretarial assistance of Patricia Wyatt and the support and encouragement of Dr. John Kastor, Chief of the Cardiovascular Section. References Downloaded from http://circ.ahajournals.org/ by guest on June 17, 2017 1. 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J W Helak and N Reichek Downloaded from http://circ.ahajournals.org/ by guest on June 17, 2017 Circulation. 1981;63:1398-1407 doi: 10.1161/01.CIR.63.6.1398 Circulation is published by the American Heart Association, 7272 Greenville Avenue, Dallas, TX 75231 Copyright © 1981 American Heart Association, Inc. All rights reserved. Print ISSN: 0009-7322. Online ISSN: 1524-4539 The online version of this article, along with updated information and services, is located on the World Wide Web at: http://circ.ahajournals.org/content/63/6/1398.citation Permissions: Requests for permissions to reproduce figures, tables, or portions of articles originally published in Circulation can be obtained via RightsLink, a service of the Copyright Clearance Center, not the Editorial Office. Once the online version of the published article for which permission is being requested is located, click Request Permissions in the middle column of the Web page under Services. 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