Evaluation of Systolic Function of the Left Ventricle
Evaluation of Systolic Function of the Left Ventricle
General Principles
Virtually all forms of acquired heart diseases may be associated with abnormalities of systolic function at some point in their natural history. An assessment of left ventricular systolic function should be part of virtually all echocardiographic examinations. Assessment of systolic function provides valuable prognostic information, plays a crucial role in selection of medical therapy, and is instrumental in determining the timing of surgery for valvular heart disease. For patients with systolic dysfunction, or for patients with hypertension, congestive heart failure, or cardiomyopathy, diastolic function should be evaluated as well. The assessment of diastolic function is addressed in detail in Chapter 7.
Initial attempts to assess left ventricular systolic function involved only linear measurements, such as the left ventricular internal dimension in diastole and systole, from which parameters such as fractional shortening and velocity of circumferential shortening could be derived. With the advent of twodimensional echocardiography, area and volume calculations replaced linear measurements for assessment of left ventricular function. Doppler echocardiography provides information on systolic flow which can be related to ventricular function. Recently developed tissue Doppler tissue methodology and speckle tracking techniques allow a more detailed analysis of myocardial performance.
Linear Measurements
The first attempts to quantify left ventricular function involved linear measurements of the minor-axis dimension from a dedicated M-mode echocardiogram. Linear measurements have the disadvantage of determining ventricular function only along a single interrogation line. In the presence of normal ventricular geometry and symmetric function, linear measurements provide an adequate assessment of ventricular function. They are limited, however, in acquired heart disease, in which there is often substantial regional variation in function. M-mode measurements are also subject to error with respect to determining the true minor-axis dimensions. Two-dimensional imaging allows correction for off-axis interrogation and also for determination of the spatial heterogeneity of function. For this reason, measurements derived from two-dimensional echocardiography, whether linear, area, or volume based, have largely supplanted M-mode measurements for assessment of ventricular function. Although the temporal resolution of a dedicated M-mode beam is superior to that of two-dimensional echocardiography, the ability to visualize the entire left ventricle, and to ensure a true minor-axis dimension, mitigates this potential advantage for most purposes.
Table 6.1 Linear Measurements of Left Ventricular Size and Function
Parameter
Formula
Abbreviation
Units
LV internal dimension in diastole
LVIDd
mm (or cm)
LV internal dimension in systole
LVIDs
mm (or cm)
Fractional shortening
(LVIDd – LVIDs)/LVIDd
FS
% or 0.XX
Meridional wall stress in systole
PR/h
σm
mm Hg or dyne-cm2
Cubed LV volume in diastole
(LVIDd)3
cm3 or mL
Cubed LV + myocardial volume
(IVS + LVIDd + PW)3
cm3 or mL
Velocity of circumferential shortening
(LVIDd – LVIDs)/(LVIDd × ET)
VCf
Circumference/sec
ET, ejection time; h, wall thickness; LV, left ventricle; PR, pressure × radius; PW, posterior wall.
The precise location at which linear measurements are made has varied as the resolution of ultrasound instrumentation has improved. Initial ultrasound equipment had relatively poor gray-scale registration. As such, the precise boundary between the blood pool and tissue was often difficult to determine. One early approach to linear measurements involved a “leading-edge to leading-edge” technique. Using this technique, septal thickness was defined as the leading edge of the septum on its right ventricular side to the leading edge of bright endocardial echoes on the left ventricular side of the ventricular septum. Depending on gray scale, image intensity, and resolution, the leading edge itself could be as much as 1 or 2 mm in thickness. Refinements in image processing have allowed greater levels of gray-scale registration with a substantially refined visualization of the actual tissue-blood pool boundary. It is now common practice to measure chamber dimensions, as defined by the actual tissue-blood interface, rather than the distance between the leading-edge echoes. Table 6.1 outlines many of the linear measurements that can be made for assessment of left ventricular function. The location of these measurements is schematized in Figure 6.1 and further demonstrated in Figure 6.2.
There are several limitations of linear measurements of the left ventricle for determining ventricular performance. One of the most obvious is that many forms of acquired heart disease, especially coronary artery disease, result in regional variation in ventricular shape and function. By definition, a linear measurement provides information regarding dimension and contractility only along a single line. This may either underestimate the severity of dysfunction if only a normal region is interrogated or overestimate the abnormality if the M-mode beam exclusively transits the wall motion abnormality. A significant limitation of an M-mode measurement of the left ventricle is that it often does not reflect the true minor-axis dimension. This phenomenon is illustrated in Figure 6.2 and is very common in elderly patients in whom there is angulation of the ventricular septum. In this instance, an M-mode beam traverses the ventricle in a tangential manner and overestimates the true internal dimension. As a two-dimensionally guided M-mode cursor must still adhere to beam direction from the transducer, it is often not possible to align the beam truly perpendicular to the long axis of the ventricle so that it reflects the true minor-axis dimension. Newer generation platforms may allow an “anatomical M-mode” beam to be derived from a twodimensional data set and thereby remove this limitation. This may provide a slight advantage for timing events but confers no real advantage over direct two-dimensional measurements for chamber dimensions. When comparisons are made between M-mode and two-dimensional minor-axis dimensions, the M-mode dimension typically overestimates the true minor-axis of the left ventricle by 6 to 12 mm. This systematic discrepancy becomes greater with age and the attendant angulation of the heart. For any given patient, one can generally assume that the degree of off-axis interrogation will remain stable over time and this overestimation will remain constant. As such, in the absence of new regional abnormalities, differences in serial measurements retain their clinical validity, although the actual dimension may be incorrect.
FIGURE 6.1. Schematic of a parasternal long-axis view of the left ventricle depicting linear measurements. By convention, linear measurements of the left ventricle are made at the level of the mitral chordae. From the linear internal dimension of the left ventricle in diastole and systole, fractional shortening can be calculated as noted. When measuring ventricular septal thickness, caution is advised to avoid measuring the most proximal portion of septum, which is frequently an area of isolated hypertrophy and angulation that does not truly represent ventricular wall thickness. FS, fractional shortening; IVS, interventricular septum; LVIDd, left ventricular internal dimension in diastole; LVIDs, left ventricular internal dimension in systole; PW, posterior wall.
FIGURE 6.2. Parasternal long-axis echocardiogram and two-dimensional-derived M-mode echocardiogram in a patient with normal ventricular function. On the M-mode echocardiogram, note the internal dimension of the left ventricle of 5.5 cm and the derived values. On the two-dimensional echocardiogram, the longer white line represents the M-mode interrogation beam. Note that it traverses the left ventricle in a tangential manner and results in an internal dimension of 5.5 cm. The yellow line is the true short-axis dimension of the left ventricle which is substantially smaller at 4.5 cm. IVS, interventricular septum; PW, posterior wall.
There are several additional parameters of ventricular performance that can be derived from M-mode measurements. These include rates of systolic wall thickening of the posterior wall and calculation of velocity of circumferential shortening. For the latter calculation, the minor-axis is assumed to represent a circle of known diameter from which the circumference can be calculated and the rate of change of circumference determined. This measurement, typically standardized by normalizing to heart rate, is rarely used in contemporary practice.
An additional M-mode measurement that has been employed in the past is the descent of the base. During ventricular contraction, the base (annulus) of the heart moves toward the apex. In the presence of global left ventricular dysfunction, the magnitude of this motion is directly proportional to systolic function. M-mode interrogation is undertaken of the lateral mitral annulus, and annular excursion toward the transducer is then calculated (Fig. 6.3). There is a relatively linear correlation between the magnitude of systolic annular excursion and global systolic function. This technique is rarely used today, having given way to direct measures of ventricular volume and ejection fraction. Of note, this same principle is used in Doppler tissue imaging of the annulus for determination of systolic excursion as a marker of ventricular function.
FIGURE 6.3. Apical view recorded in two patients demonstrates the measurement of the descent of the base with M-mode echocardiography. The M-mode interrogation beam has been directed from the apex of the heart through the lateral annulus. A: Note the approximate 1.6 cm of annular motion toward the apex in systole. B: Recording in a patient with severe systolic dysfunction reveals substantially decreased annular motion of <1.0 cm in systole.
Indirect M-Mode Markers of Left Ventricular Function
Several indirect signs of left ventricular systolic dysfunction can be noted on M-mode echocardiography. These include an increased E-point to septal separation and gradual closure of the aortic valve during systole. The magnitude of opening of the mitral valve, as reflected by E-wave height, correlates with the volume of transmitral flow and, in the absence of significant mitral regurgitation, with left ventricular stroke volume. The internal dimension of the left ventricle correlates with diastolic volume. As such, the ratio of mitral excursion to left ventricular size parallels ejection fraction. Normally, the mitral valve E point (maximal early opening) is within 6 mm of the left side of the ventricular septum. In the presence of a decreased ejection fraction, this distance is increased (Fig. 6.4).
Inspection of the aortic valve opening pattern also provides indirect evidence regarding systolic function of the left ventricle. If left ventricular forward stroke volume is decreased, there may be a gradual reduction in forward flow in late systole. This results in a rounded appearance of aortic valve closure in late systole (Fig. 6.5). Reliance on these earlier observations and calculations have been supplanted by direct measures of ventricular size and performance available from modern ultrasound platforms.
FIGURE 6.4. M-mode echocardiograms recorded in two patients with significant systolic dysfunction. A: An E-point septal separation (EPSS) of 1.2 cm (normal, <6 mm). B: Recording in a patient with more significant left ventricular systolic dysfunction in which the EPSS is 3.0 cm. Also note the interrupted closure of the mitral valve with a B bump (top), indicating an increase in the left ventricular end-diastolic pressure.
FIGURE 6.5. M-mode echocardiogram recorded through the aortic valve in a patient with reduced cardiac function and decreased forward stroke volume. Note the rounded closure of the aortic valve, indicating decreasing forward flow at the end of systole. Normal and abnormal aortic valve opening patterns are noted in the schematic superimposed on the figure.
Table 6.2 Area-/Volume-Based Measurements for Ventricular Size and Functiona
aDetermined by the Simpson rule, area length method, etc.
Two-dimensional Measurements
Two-dimensional echocardiography provides inherently superior spatial resolution for determining left ventricular size and function. Its role in obtaining linear measurements has already been discussed. A number of different two-dimensional echocardiographic views have been used to provide information regarding ventricular systolic function, some of which rely exclusively on area measurements and others of which rely on calculation of ventricular volume. Table 6.2 outlines commonly used two-dimensional measurements and their derived calculations. Table 6.3 provides the American Society of Echocardiography-recommended normal ranges for commonly obtained measurements.
One of the simpler two-dimensional measures of left ventricular function is the determination of a fractional area change from a short-axis view of the midventricular level. This is calculated by comparing the diastolic area with the systolic area. The area change then represents the difference of these two values divided by the diastolic volume analogous to calculation of fractional shortening. For a symmetrically contracting ventricle, fractional area change directly reflects global ventricular function. Its obvious limitation is that it assesses ventricular function only at the level being interrogated. If regional dysfunction is present, which is not in the interrogation plane, it results in a misleading estimate of global ventricular function. This same view can be used to determine mean wall thickness for calculation of left ventricular mass.
Table 6.3 Reference Limits and Partition Values of Left Ventricular Sizea
Women
Men
Reference Range
Mildly Abnormal
Moderately Abnormal
Severely Abnormal
Reference Range
Mildly Abnormal
Moderately Abnormal
Severely Abnormal
LV dimension
LV diastolic diameter
3.9-5.3
5.4-5.7
5.8-6.1
≥6.2
4.2-5.9
6.0-6.3
6.0-6.8
≥6.9
LV diastolic diameter/BSA, cm/m2
2.4-3.2
3.3-3.4
3.5-3.7
≥3.8
2.2-3.1
3.2-3.4
3.5-3.6
≥3.7
LV diastolic diameter/height, cm/m
2.5-3.2
3.3-3.4
3.5-3.6
≥3.7
2.4-3.3
3.4-3.5
3.6-3.7
≥3.8
LV volume
LV diastolic volume, mL
56-104
105-117
118-130
≥131
67-155
156-178
179-201
≥201
LV diastolic volume/BSA, mL/m2
35-75
76-86
87-96
≥97
35-75
76-86
87-96
≥97
LV systolic volume, mL
19-49
50-59
60-69
≥70
22-58
59-70
71-82
≥83
LV systolic volume/BSA, mL/m2
12-30
31-36
37-42
≥43
12-30
31-36
37-42
≥43
aBold italic values; recommended and best validated.
BSA, body surface area.
Reprinted with permission of American Society of Echocardiography from Recommendations for Chamber Quantification: a report from the ASE Guidelines and Standards Committee and the Chamber Quantification Writing Group, developed in conjunction with the European Association of Echocardiography, a branch of the European Society of Cardiology. JASE 2005;18:1440-1463.
More commonly, apical images are used to determine ventricular volumes in diastole and systole, from which stroke volume and ejection fraction are calculated. There are several geometric assumptions and formulas that have been used in the past for calculating ventricular volume. The advantage of the geometric assumption techniques, such as an area-length or truncated ellipse formula, was that they require only limited visualization for calculation of ventricular volume. These formulas work only in a symmetrically contracting ventricle and have been supplanted by more direct calculation of ventricular volumes. A simplified method for calculation of ejection fraction involves determining the minor-axis dimension in diastole and systole at the base, mid, and distal left ventricle. These values are combined with a qualitative assessment of apical function (−5% to +15%) to derive the ejection fraction. This methodology has correlated well with standard methods for determination of the ejection fraction.
The advent of high-resolution, 90°, digital, two-dimensional scanners, as well as the computational capacity of quantitation packages incorporated in modern platforms and off-line analysis systems, has largely made these earlier methods for volume determination obsolete. Currently, the most common method for determining ventricular volumes is the Simpson rule, or the “rule of disks.” This technique requires recording an apical, four- and/or two-chamber view from which the endocardial border is outlined in end-diastole and end-systole. The ventricle is mathematically divided along its long axis into a series of disks of equal height. Individual disk volume is calculated as the product of height and disk area, where disc height is assumed to be the total length of the left ventricular long axis ÷ the number of segments or disks. The surface area of each disk is determined from the diameter of the ventricle at that point (area = πr2). The ventricular volume is calculated as the sum of the volume of the disks. This methodology is illustrated in Figure 6.6.
FIGURE 6.6. Schematic illustration of Simpson’s rule or the rule of disks for calculating left ventricular volume. In the upper panel, a schematized left ventricular volume has been subdivided into 10 sections, each of which is presumed to represent a disk of equal diameter at its top and bottom margins. The volume of each disk is calculated as area × height where height is defined as the left ventricular length from apex to base ÷ by the number of disks. The total volume of the ventricle is calculated as the sum of each disk volume. The lower panel is an apical four-chamber view recorded in a normal individual in which this algorithm has been used to calculate a left ventricular volume.
If a ventricle is symmetrically contracting, either the four- or two-chamber view will reflect the true ventricular volume. For accurate volume determination, the transducer must be at the true apex and the ultrasonic beam must be through the center of the left ventricle. These conditions are frequently not met, resulting in underestimation of true ventricular volumes. There are several clues that help determine whether the transducer is at the true apex. Normally, the true apex is the thinnest area of the left ventricle. If the visualized apex has the same or greater thickness as the surrounding walls, and appreciable motion in systole, it is likely to be a tangential cut through the left ventricle rather than a true on-axis view. In addition, a properly recorded apical view is defined as the one with the greatest long-axis (apex to base) dimension. In any view, foreshortening of the ventricular apex will result in underestimation of ventricular volume. In clinical practice, the apical two-chamber view is often imaged tangentially, and the volume derived from this view may underestimate the true left ventricular volume. Because of cardiac translational motion, tangential imaging (i.e., not through the midline of the ventricle) is more common in systole. This results in an artifactually small systolic left ventricular cavity and may result in overestimation of ejection fraction. It is common to encounter minor degrees of off-axis imaging in the apical view in which tangentially located myocardium appears to fill in the apex because of beam width imaging. Evaluating the location of the true apical myocardium in real time, before tracing the boundary, and purposefully placing the boundary within the vague tangential echoes can reduce the magnitude of this problem. For determination of left ventricular volume, the endocardial border is traced with papillary muscles and trabeculae excluded from the cavity (Fig. 6.7). The widely reported underestimation of left ventricular volume by echocardiography, compared to a standard such as cardiac magnetic resonance imaging, is, in part, due to failure to, or the difficulty of, excluding trabeculae from the cavity tracing. If there is asymmetry of ventricular geometry or a systolic wall motion abnormality, a single-plane view will have reduced accuracy for the reasons previously alluded to. In this instance, averaging of volumes from multiple views or use of three-dimensional echocardiography will increase accuracy (Fig. 6.8).
FIGURE 6.7. Apical four-chamber view recorded in a patient with normal ventricular size and function. The upper panel is the apical four-chamber view from which volume can be calculated. Notice the vague echoes at the apical septal and apical lateral wall due to a combination of beam width imaging and trabeculae (arrows) as well as the papillary muscle protruding into the left ventricular cavity (arrow). The lower panel outlines three separate contours which could be drawn from this view. The white line represents the true inner endocardial border of the left ventricle, excluding trabeculation, beam width imaging and the papillary muscle from the cavity, and results in a left ventricle cavity volume of 97 mL. The yellow line excludes the papillary muscle tip but includes the apical trabeculations and tangential beam-related echoes and results in a left ventricular volume of 70 mL. The red line further excludes the papillary muscle tip from the left ventricular volume and would result in a left ventricular volume of 60 mL.
FIGURE 6.8. Apical views recorded in a patient with an extensive inferior-posterior myocardial infarction and basilar inferior aneurysm (arrows). The apical four-chamber view and apical long-axis view are presented in the top panels. The bottom panels are the apical two-chamber view in diastole on the left and systole on the right. The end-diastolic volume and ejection fraction for each view are as noted. Note that if only the four-chamber view is used for analysis, there is a substantial overestimation of ejection fraction as the regional wall motion abnormality is seen only in the two-chamber and apical long-axis views. EF, Ejection fraction; LVVd, left ventricular volume in diastole.
Once the diastolic and systolic volumes have been determined, stroke volume can be calculated as the difference between these two volumes. Assuming the absence of mitral or aortic insufficiency, forward cardiac output then equals the product of heart rate times stroke volume. Because the difference between the diastolic and systolic left ventricular volume represents the total volume pumped by the ventricle, it represents the sum of forward-going stroke volume plus the volume of mitral and aortic regurgitation, if present. Ejection fraction can be calculated from these volumes as: stroke volume ÷ enddiastolic volume.
Instrumentation is commercially available that can automatically identify and track the endocardial border of the left ventricle. The automatically tracked borders are then subject to calculation of volume using the methodology described above, thereby providing an instantaneous ventricular volume display. Stroke volume and ejection fraction can be calculated from the maximal and minimal volumes. While “automatically” detecting the tissue-blood interface, substantial manual manipulation of the contour is commonly needed to insure an accurate left ventricular cavity boundary, as the border detection algorithms often include trabeculation on the base of a papillary muscle in the cavity (Fig. 6.9). This is particularly true in less than optimal studies.
Intravenous contrast for left ventricular opacification is also a valuable technique for enhancing endocardial border definition. It has been recommended that if two or more ventricular segments are poorly visualized, there is incremental yield of intravenous contrast for left ventricular opacification both for regional wall motion assessment and for reproducibility of volume determination. Intravenous contrast can be employed either with two-dimensional or with three-dimensional imaging and, as discussed in Chapter 4, requires attention to detail with respect to mechanical index and other technical factors of imaging.
Assessment of Left Ventricular Function with Three-dimensional Echocardiography
As discussed in Chapter 3 on specialized techniques and methods, a three-dimensional echocardiographic data set can be acquired through a number of methods from which left ventricular borders can be extracted. This ability to generate a threedimensional volume independent of imaging plane provides more accurate information regarding left ventricular volume when compared to a standard such as cardiac magnetic resonance imaging. The advantage of three-dimensional volumetric calculations appears greatest in irregularly shaped ventricles which do not conform to a predictable geometric shape. A previous limitation of three-dimensional echocardiography was the time required to reconstruct the ventricular chamber and calculate volume. Three-dimensional data sets have been merged with a variety of edge detection algorithms allowing semiautomatic extraction of a three-dimensional volume after user identification of a limited number of points. This advancement has dramatically reduced the time required for derivation of accurate three-dimensional volumes (Figs. 6.10 and 6.11). As with automated algorithms for determination of left ventricular volume from two-dimensional echocardiography, manual adjustment of the automatically defined ventricular border is commonly necessary. Once generated, the three-dimensional volume can be further subdivided into a 16- or 17-segment model as done with two-dimensional echocardiography. A variety of sophisticated measures of global and regional ventricular function can be extracted from the same three-dimensional volume (Fig. 6.11). The data that can be extracted is platform specific but includes regional volume change in 16- or 17-segments as well as parameters of volume change over time which have shown promise for evaluation of mechanical dyssynchrony. Numerous studies have demonstrated the superiority of threedimensional echocardiography over two-dimensional echocardiography for determination of left ventricular volumes when compared to a standard such as cardiac magnetic resonance imaging (Table 6.4). While the accuracy and inter- and intraobserver reproducibility of left ventricular volumes derived from three-dimensional data sets exceed that of two-dimensional imaging, the magnitude of improvement in accuracy is not always at a level likely to result in a change in clinical decision making. Most studies have suggested that left ventricular volumes determined with real-time three-dimensional echocardiography underestimate both end-diastolic and end-systolic volume. As with two-dimensional imaging, this is apparently due to inclusion of left ventricular trabeculae and papillary muscles within the cavity and is a more prominent problem with less experienced operators.
FIGURE 6.9. Apical four-chamber view recorded in a young patient with normal ventricular function and fairly prominent trabeculae along the lateral ventricular wall. The upper panel is an apical four-chamber view in which the papillary muscle and trabeculae can be seen on the lateral wall (arrows). The lower left panel is the initial, unaltered, automatically determined endocardial border from a commercially available platform. Note that the algorithm for identifying the endocardial border has included papillary muscles and the trabeculae within the ventricular cavity which results in a calculated left ventricular volume of 99 mL. The lower right panel was recorded after manual adjustment of the previously automatically determined border. Only the lateral border has required adjustment. After adjustment, notice the calculated left ventricular volume is 158 mL.
FIGURE 6.10. Reconstructed three-dimensional echocardiogram from a real-time three-dimensional volumetric scanner recorded in a patient with a dilated cardiomyopathy and reduced left ventricular function. The upper two panels depict apical four-chamber and short-axis views extracted from the same three-dimensional data set as well as the corresponding three-dimensional shell subdivided into 17 segments. The lower right table provides automatically extracted measurements including calculation of an ejection fraction of approximately 35%. Parameters of dispersion of contractility based on subvolume analysis, as would be relevant for determination of dyssynchrony, are also provided. The lower left panel is a graph of instantaneous volume change in each of the predefined segments.
FIGURE 6.11. This illustration depicts multiple parameters of left ventricular function which can be extracted from a single threedimensional volume (small inset). The lower graph is an individual volume curve for 17 subvolumes in a patient with a dilated cardiomyopathy and an ejection fraction of approximately 32%. From this volume, end-diastolic and end-systolic volumes (EDV, ESV) as well as stroke volumes (SV) and ejection fraction are all calculated. In addition, polar maps are derived from endocardial excursion in each of 17 segments and expressed as an average, standard deviation, maximum and minimum excursion. The timing to maximum excursion is also depicted as a histogram. Various parameters are available for determination of global and regional left ventricular function as well as for timing of contraction which may have relevance for decision making regarding resynchronization therapy, all of which are extracted from a single three-dimensional volume.
Table 6.4 Accuracy of Three-dimensional Echocardiography for Determination of Left Ventricular Volumea
Correlation
Mean Differences
Interobserver Variability
Author (Year)
n
EDV (mL)
ESV (mL)
EF (%)
EDV (mL)
ESV (mL)
EF (%)
EDV
ESV
Kuhl (2004)
24
.98
.99
.98
−13.6 ± 18.9
−12.8 ± 20.5
0.9 ± 4.4
0.9 ± 6.9 mL
0.7 ± 9.6 mL
Jenkins et al. (2004)
50
−4.0 ± 29
−3.0 ± 18
−3 ± 10 mL
−2 ± 6 mL
Sugeng et al. (2006)
31
.94
.93
.93
−5.0
−6.0
11%
14%
Mor-Avi et al. (2008)
92
.91
.93
.81
−67 + 47
−41 + 46
−3%
8%
5%
A
.93
.92
−37 ± 27
−18 ± 30
D
.89
.90
89 ± 33
−63 ± 39
Soliman et al. (2008)
24
.98
.98
.97
−7.1
−4.2
0.2%
5%
6%
aOutline of results from five studies comparing the accuracy of real-time three-dimensional echocardiography for determination of left ventricular volume in comparison to cardiac magnetic resonance imaging. Semiautomated edge detection was used for three-dimensional volume determination. Mean differences were calculated as bias from Bland-Altman analysis. For the Mor-Avil study, data are presented for all 92 patients and for the most experienced and least experienced laboratories (A and D), separately. Note the near three-fold difference in variability when comparing experienced and inexperienced laboratories.
FIGURE 6.12. Schematic representation of the cubed formula for determining left ventricular mass. All measurements can be taken from either a two-dimensional or an M-mode echocardiogram of the minor axis of the left ventricle. The formula for calculation of left ventricular mass is as noted. Based on comparison with anatomic specimens, several regression equations have been developed that are variations on the basic cubed formula. IVS, interventricular septum; LVIDd, left ventricular internal dimension in diastole; PW, posterior wall.
Determination of Left Ventricular Mass
Echocardiography was one of the first imaging modalities used clinically for determination of left ventricular mass. It has seen widespread acceptance in epidemiologic studies of hypertension in which the presence of hypertrophy has been associated with worsened outcomes and its regression has been a goal of therapy. Left ventricular mass can be determined using a number of echocardiographic algorithms.
The earliest methodology for determining left ventricular mass was based on M-mode measurement of septal and posterior wall thickness and the left ventricular internal dimension. M-mode calculations assume a predefined ventricular geometry, and their accuracy will diminish in instances in which the left ventricular shape is abnormal. One of the methods for determining left ventricular mass is the cubed (Teichholz) formula, which assumes that the left ventricle is a sphere. The diameter of this sphere is the interior dimension of the left ventricle and the sphere wall thickness is that of ventricular myocardium. The formula calculates the outer dimensions of the sphere and then the inner dimension, the difference being the presumed left ventricular myocardial volume. The cubed formula is expressed as left ventricular mass = (interventricular septum + left ventricular interior dimension + posterior wall)3 − left ventricular interior dimension3 (Figs. 6.12 and 6.13). This then gives the volume of the stylized sphere of the myocardium, which, when multiplied by the specific gravity of muscle (1.05 g/cm3), provides an estimate of left ventricular mass. Several investigators subsequently modified this approach using regression analysis. This cubed volume approach has the obvious limitation of determining ventricle size and wall thickness only along a single line. As it is common for the M-mode dimension to exceed the true minor axis dimension, the calculated mass will be artificially high (Fig. 6.13). Although the regression equations allow calculation of mass that correlates with autopsy specimens, there can be substantial error in the actual mass determination. The cubed methodology has been widely used, especially in serial evaluations, because for any given patient, the magnitude and direction of the error is expected to remain constant.
A more accurate determination of left ventricular mass can be obtained with two-dimensional echocardiography. When using two-dimensional echocardiography, geometric assumptions of the ventricular shape are typically still employed but the assumption is that of a bullet-shaped ventricle rather than a sphere. In addition, mean left ventricular wall thickness is determined rather than wall thickness at only one point on the septum and posterior wall. Mean wall thickness can be calculated by determining the epicardial and endocardial areas of the short-axis of the left ventricle at the midcavity level. The difference between these two areas then represents myocardial area. Left ventricular mass can then be calculated either by an area length method or by assuming a truncated ellipse geometry. Figure 6.14 depicts this approach and provides formulas used for calculation of left ventricular mass with this technique. More recently, three-dimensional echocardiography has been used to extract epicardial and endocardial borders from multiple orthogonal planes, from which left ventricular mass can be determined in a similar manner. Limited studies have suggested excellent correlation of three-dimensional mass with anatomic and magnetic resonance imaging as standards.
FIGURE 6.13. Two-dimensionally guided M-mode echocardiogram recorded in a patient with mild hypertension. Note in the small inset, the tangential M-mode interrogation beam which is a result of beam orientation and slight angulation of the heart. The M-mode is as displayed from which a left ventricular internal dimension of 5.77 cm is measured. The true minor axis dimension of the left ventricle is 4.7 cm. The bottom panel represents the calculated M-mode report from the measured values. The numbers in parentheses are the corresponding values from a true minor axis dimension (4.7 cm) used rather than the off-axis 5.77 cm. Note the substantial overstatement of left ventricular mass using the dedicated M-mode measurement versus a true minor axis dimension from the two-dimensional echocardiogram.
FIGURE 6.14. Demonstration of the methodology for determining left ventricular mass from two-dimensional echocardiography. Mean wall thickness is calculated by tracing the epicardial and endocardial boundaries (A1, A2) and average mass (Am) calculated as the difference between the two. Left ventricular mass can then be calculated using an area length (AL) or a truncated ellipse (TE) formula. (Reproduced with permission from the American Society of Echocardiography from Recommendations for Chamber Quantification: a report from the ASE Guidelines and Standards Committee and the Chamber Quantification Writing Group, developed in conjunction with the European Association of Echocardiography, a branch of the European Society of Cardiology. JASE 2005;18:1440-1463.)
Physiologic Versus Pathologic Hypertrophy
Left ventricular hypertrophy can be characterized as concentric, eccentric, or physiologic (Fig. 6.15). It should be emphasized that calculation of left ventricular mass is a determination of the mass of the left ventricular muscle and may not relate to overall cardiac enlargement. Increases in left ventricular mass can occur with chamber enlargement and relatively normal wall thickness (eccentric hypertrophy), as is seen in regurgitant valvular lesions, or secondary to a predominant increase in wall thickness with normal chamber sizes, as is seen in the pressure overload of systemic hypertension. When evaluating patients for left ventricular hypertrophy, it is important to characterize the hypertrophy as being due to either chamber enlargement or increased wall thickness. One additional index of hypertrophy is relative wall thickness which is defined as (posterior wall thickness + interventricular septal thickness)/left ventricular internal dimension. Relative wall thickness of ≥0.42 has been used as a threshold of pathologic left ventricular hypertrophy.
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