| | Assessment of Left Ventricular Function by Echocardiography: A Technique in EvolutionOne of the earliest applications of clinical echocardiography was the evaluation of left ventricular (LV) size and function. The accuracy of the determination of global and regional LV function with echocardiography has improved as the technology has matured. The following paper discusses the advances in LV function assessment starting with Inge Edler’s original A-mode and M-mode observation moving through two dimensional echocardiographic methods to new three dimensional echocardiographic assessment and even new Doppler and speckle myocardial methods. During the evolution of ultrasonic assessment of LV function, each new method has overcome limitations of previous ones, resulting in better appreciation of the LV geometry and volume and improved accuracy and reproducibility for quantitation. As discussed in this report, many of the echocardiographic methods used today to assess LV systolic function were envisioned by Harvey Feigenbaum more than 25 years ago. The future will undoubtedly see a new method of clinical cardiology care but with continued evolution, echocardiographic quantitation of LV function should remain a vital part of patient care. One of the earliest applications of clinical echocardiography was the evaluation of left ventricular (LV) size and function. The original monograph by Edler1 displayed A-mode signals from the posterior walls of bovine hearts in vitro and both A-mode and M-mode signals from human hearts. Edler1 also noted that the echo from the posterior wall of the heart moved anteriorly about 1 cm (Figure 1) and that with aortic valve incompetence the amplitude of motion of this echo increased. The moving signals from the LV posterior wall and those from the posterior mitral annulus were recognized early at Indiana University (Indianapolis, IN) as correlated with ventricular function. When the heart moved well, all parts had greater motion than when cardiac function was globally impaired. Harvey Feigenbaum attempted to measure LV function by using an index comprised of the anterior-posterior dimension of the heart, measured from the chest wall to the posterior LV signal multiplied by the M-mode excursion of the posterior-lateral mitral annulus measured from the cardiac apex. This did not work well in all cases but it was soon appreciated that in optimal cases one could see a signal putatively representing the interventricular septum. Measuring only the dimension of the LV improved results from this index. However, in 1966 the available equipment was not capable of consistently showing a signal from the interventricular septum (personal communication). Improved equipment from Smith-Kline Instruments (Palo Alto, CA) permitted more consistent imaging of signals from blood-endocardial interfaces.2 The origin of the signals was confirmed by a series of studies by Gramiak et al3 using intracardiac injections of microbubbles in green dye to create signals in the various cardiac chambers permitting them to be identified. This second generation of equipment allowed resolution of the anterior right ventricular wall thickness, right ventricular internal dimension, interventricular septum thickness, internal LV dimension, and posterior LV wall thickness.4 This advance provided the first system for observing changes in cardiac dimensions in real time with high temporal resolution (Figure 2). Those involved with the observations were immediately impressed that the dimensional change was a reflection of cardiac function. However, there were few involved with echocardiography at that time. Therefore, Feigenbaum et al5 arranged a collaborative study with Harold Dodge, in Birmingham, Ala. Dodge’s group was routinely performing high-quality quantitative radiograph contrast left ventriculography on patients. That study correlated LV volume by angiography with echocardiographic parameters for the first time. Attempts to use the change in the M-mode LV dimension from diastole to systole as an indication of stroke volume were successful in normally shaped hearts, but the method was not robust in conditions causing marked dilation of the heart or in those with either marked segmental wall-motion abnormalities or frank aneurysms. Because only the short-axis dimension of the LV was measured, the math for converting this measurement to LV volume in diastole or systole depended on a ratio6 of long-axis to short-axis of 2:1. Several groups came up with formulae for the calculation of LV volume that tried to compensate for the heart developing a long-axis to short-axis ratio closer to 1:1 with increasing dilation. In most cases a single dimension was used for these measurements but others attempted to directly measure a LV long axis. In all cases, the placement of the transducer relative to the optimal dimension of the heart was an additional variable all recognized as an inherent limitation of M-mode methods.7 Despite these limitations, M-mode echocardiography was used for estimation of LV volume, stroke volume, and wall thickness with good results in many clinical situations in the early 1970s.8 Measures of LV function based on the rate of contraction of the endocardium were also described9 but failed to add significantly to the basic parameters of volume and stroke volume. At the end of the M-mode era, the Indiana group developed the technique of M-mode scanning (Figure 3) that gave a sense of the shape and function of the LV but failed to record the apex and provided no additional quantitative information.10 The quest for more consistent measurement of cardiac size and function was a major impetus for development of two-dimensional (2D) echocardiography. Two-Dimensional Echocardiography  Bom et al11 in The Netherlands first developed a linear array of transducers that, when sequentially pulsed, displayed B-mode images of the returning signals from the heart. The aggregate image on a display screen produced a 2D echocardiogram. The Indiana group12 and others13 worked out systems for rocking a standard M-mode transducer over a 30-degree angular sector of a circular plane to create a narrow real-time 2D echocardiogram. The resulting sector scan was most useful for understanding heart valve disease and pericardial effusion, but the narrow field of view was not optimal for assessing global LV function. Initial studies using this device, however, provided the apical information missing in the M-mode scan and its portability facilitated many of the initial studies of the extent, functional significance, and complications of acute myocardial infarction.14, 15 Commercial development of this technology gave an angle of view of approximately 60 degrees. The bioengineering group at Duke University (Durham, NC),16 and later the Varian Corporation (Palo Alto, CA), developed electronic phased-array 2D echocardiographic imaging systems with a field of view of approximately 90 degrees that encompassed the majority of the heart in most patients when scanned from either the anterior chest wall or the cardiac apex.17 Once the entire LV could be recorded, more accurate quantitation of LV volume was possible using the dimensions and areas contained in these images in a variety of mathematic models. As illustrated in Figure 4, the simple M-mode anteroposterior LV dimension was a reasonably accurate estimate of LV function in patients with symmetric ventricles. However, this simple dimension could significantly overestimate or underestimate volume in more irregular ventricles (Figure 5). Addition of the LV long-axis measurement improved accuracy, while addition of area measurements into the formulas for a variety of geometric figures and the ventricular contours in Simpson’s rule calculations incrementally increased measurement accuracy. Numerous studies during the 1980s validated the accuracy of 2D volumes and ejection fraction measurements by comparison with a variety of reference standards.18 Despite the obvious improvement offered by 2D quantitation, there were several limitations: (1) the acquisition and assumed position of short-axis images along the ventricular long axis was based on internal ventricular landmarks and, thus, might not correspond precisely with the placement assumed by the geometric models; (2) the placement of the transducer in recording the ventricular long axis was assumed to be over the tip of the LV apex, which was often not the case, resulting in foreshortening of the ventricle; (3) apical views were assumed to be obtained by rotation around the ventricular long axis and separated by known degrees of rotation, which was generally not the case; and (4) in any acquisition format the majority of the ventricular surface was not recorded and, hence, spatial symmetry had to be assumed. For most applications, the errors introduced by these assumptions were small and the results acceptable. However, difficulties arose in studies requiring serial quantification of LV size and function where the degree of incremental changes was often within the error of the method. This led to a desire for more accurate spatial data and robust methods of quantitation. In a 1982 editorial on the future of echocardiography, Feigenbaum19 wrote that “the development of new clinical techniques, new instrumentation, stress echocardiography, new contrast agents, the ability to identify tissue types, Doppler echocardiography, three dimensional echocardiography, the ability to obtain ultrasonic information from catheters or during surgical exploration and especially new techniques for quantitating echocardiographic data, make the potential usefulness of echocardiography in assessing cardiac function and especially left ventricular function very exciting.” All of these predictions have subsequently come to pass. He went on to note that “the next logical step would be three-dimensional echocardiography.… It is also conceivable that by a fairly elaborate transducer design one could even send out a three-dimensional beam that could produce a real time three dimensional image of the heart. Irrespective of how a three-dimensional echocardiogram is obtained it should provide a more accurate spatial image of the heart and thus provide more accurate quantitative and qualitative information. Such a three dimensional display should improve our ability to quantitate aneurysms, infarcts or residual myocardium.”19 New Ultrasound Technologies to Assess LV Systolic Function Three-Dimensional Echocardiography The earliest approaches to three-dimensional (3D) echocardiography were based on the reconstruction of 2D images.20 With this approach, each of the component images can be obtained from varying transducer positions but the spatial location and time in the cardiac cycle at which each image is acquired must be known. Then the images obtained at the same point in the cardiac cycle can be positioned in their proper orientation relative to one another. The surface of this reconstructed object can then be rendered for display and the volume calculated. A variety of methods have been used to assure proper spatial location of the images. These include: (1) spatial locating devices attached to the transducer (mechanical arms, spark gaps, and electromagnetic position-sensing devices); (2) acquisition in a series of parallel planes of known separation; and (3) rotation of a stationary transducer in fixed increments through a 180-degree arc. Each of these approaches has unique requirements that pose challenges for image acquisition. The quality of the 3D images from the reconstruction methods are a function of the quality and number of images used in the reconstruction. The highest quality images are usually obtained using position-sensing devices because they allow each plane to be aligned independently to achieve optimal target definition. Quantitation of LV volume in 3D was shown to be accurate with a minimum of 8 intersecting, nonparallel 2D images.21 Although reconstruction methods are time-consuming, important studies have used these approaches to demonstrate the improved accuracy of assessment of LV size and function compared with 2D echocardiography.22, 23, 24 In addition, this approach improved our understanding of the shape and spatial relationships of many cardiac structures such as the mitral valve and its supporting structures.25 More recently, transducer technology has evolved at the same time that computing power has expanded and together they have facilitated the development of the matrix-array transducer. This transducer has elements arranged in a rectangular grid, and after transmission of a single pulse can acquire data from many lines of sight simultaneously to reconstruct a volume of ultrasound data in real time. The earliest of these transducers was a sparse array with 256 elements, which resulted in limitations in spatial and temporal resolution.26 Currently, these transducers have more than 3000 elements and enable a 30- × 50-degree volume to be acquired and displayed in real time. Although this is sufficient for visualization of valves, masses, the infant LV, and color Doppler jets, it is typically not a large enough volume to display the entire adult LV. To display and quantify the adult LV, a series of component volumes of the heart are obtained over consecutive cardiac cycles and then combined to obtain a larger volume. Currently,27 with this approach, 4 or more images are fused resulting in maximal frame rates of 25 Hz. In addition, the matrix-array transducer can record multiple individual planes simultaneously (Figure 6). When this full-volume 3D ultrasound data set is initially displayed, only the outer boundaries of the pyramid can be visualized (Figure 7). This provides minimal or no information. To see the cardiac structures within this pyramid, the volume must be dissected (cropped). Various dissection planes can be obtained to display cardiac structures from different perspectives (Figure 8). For example, a transverse cut of the ultrasound volume obtained from the apical transducer position will yield a short-axis view of the LV and this can be manipulated in space so that it can be viewed from the apex or the base of the heart. LV volume can be calculated from the 3D image in several ways. First, the volume elements or voxels enclosed by the endocardial borders of the 3D LV can be summed. This requires that the endocardial border be initially defined either manually from selected planes or automatically by a border-tracking algorithm. Alternatively, just as with 2D, a method of disks can be performed. With this method, a series of short-axis planes are derived from the data set to create partial volumes of the LV and these are then summed. For the volumetric method, the accuracy of the LV volume will be a function of the number of elements in the transducer, the voxel size, and the spatial resolution of the image. For the method of disks, the number of short-axis planes used will determine the accuracy. Compared with single plane and 2D approaches, 3D echocardiography has been shown to represent and quantify LV volumes and function more accurately.28 Although the early 3D reconstruction methods provide important data, real-time 3D acquisition has proven more rapid and, hence, practical for clinical application. Unfortunately, analysis time to this point remains relatively long. A large number of studies have compared real-time 3D echocardiography with magnetic resonance imaging and other reference standards and have shown excellent correlations, small mean differences, and acceptable interobserver variability.29, 30, 31 The improvement in LV volume calculation with 3D echocardiography over 2D echocardiography is easily explained by the fact that more of the LV endocardial surface is incorporated into the 3D echocardiographic quantification, the position of the transducer over the cardiac apex can be better appreciated, intersecting planes are precisely aligned, and no assumptions of shape are required (Figure 9). As with all ultrasonic techniques, the point spread function of the ultrasound beam and the variable inclusion of trabeculae typically results in volumes that are slightly smaller than those obtained by reference standards such as computed tomography and magnetic resonance imaging. Because the LV volumes calculated from 3D echocardiograms are more accurate, it is not surprising that LV stroke volume and ejection fraction derived from these volumes are also more accurate.32 This improved accuracy is most obvious in patients with ventricles that are distorted in shape and in those with regional wall-motion abnormalities caused by coronary artery disease. The addition of contrast for LV opacification leads to additional improvement in accuracy of 2D echocardiographic quantitation with a reduction in measurement variability as a result of more definitive identification of the chamber walls.33 Similar findings have been reported for contrast and 3D echocardiography.34 Because measurement variability is lower with the 3D technique than 2D technique, changes in LV size and function can be more precisely determined. Compared with 2D measurements, smaller serial changes will represent significant differences. This will have implications for clinical decisions that are based on changes in LV size or function such as decisions to operate for valvular regurgitation. Despite the many attractive features of 3D echocardiography, there remain a number of limitations of current real-time devices: (1) image quality is often poor because, despite parallel processing, the line density within the 3D volume is much lower than in a 2D image and more interpolation is necessary; (2) when the 3D volume is acquired from a fixed point many of the targets within the volume will not be optimally aligned to produce strong echoes and, thus, may be either missing or poorly recorded (a problem that is often not recognized until the data are examined); (3) when the entire LV is reconstructed from multiple subvolumes, arrhythmias and respiration can cause movement of the heart between cycles and result in artifacts in the images (stitch artifacts); and (4) although acquisition time for one volume is much less than for multiple planes, the analysis time to this point has limited general application and the technique has been primarily used in research studies. It can be anticipated that over time, 3D image quality will improve, as has been the case with 2D images, and this together with more accurate edge detection algorithms will extend the initial positive results to the routine clinical evaluation of LV function. Coronary Artery Disease In the 1970s, the Indiana group first described the M-mode echocardiographic features of the abnormal wall motion seen in myocardial dyssynergy,35, 36, 37 acute myocardial ischemia and infarction,38 scar formation,39 and ventricular aneurysms.14 Because the M-mode technique only provided information about local motion, it was not until the development of 2D echocardiography that it became possible to measure the spatial extent and associated structure abnormalities found in these conditions.14, 15 Unfortunately, quantitation of abnormal motion (endocardial excursion) proved extremely difficult because of difficulties in defining a center of reference, wide variation in absolute values, and the effects of translation and rotation on derived measurements.40, 41, 42, 43, 44 Thickening was initially proposed as an ideal, translation-independent measure of local function. Again, however, application was limited by difficulties in defining both the endocardium and epicardium, and the large variation in percent change produced by small changes in absolute thickening. As a result, until recently, wall motion has generally been assessed by visual inspection, but there has been an ongoing search for more accurate methods of quantitation. Tissue Doppler, Strain Rate, and Strain Two recent additions to the echocardiography toolbox, tissue Doppler and speckle tracking, are potentially important methods for measuring local myocardial function. Although tissue Doppler and speckle techniques have been used predominantly to assess timing of events such as for the assessment of mechanical dyssynchrony in patients with heart failure, myocardial peak velocity, strain rate, and strain have identified regional myocardial dysfunction both at rest and during stress echocardiography.45, 46, 47 Radial strain rate has been shown to correlate with regional myocardial blood flow and to discriminate ischemic myocardial segments in experimental models.48 Thus, these quantitative methods are promising adjuncts to assist in regional wall-motion analysis. Currently, they can confirm the qualitative assessments of regional wall motion, especially when the wall motion is confusing. In addition, these techniques may improve the novice’s interpretation of regional LV function. There are many challenges to the incorporation of myocardial Doppler and speckle techniques in the assessment of regional ventricular function, but the combination of 3D speckle tracking with 3D imaging could provide an extremely powerful tool for the evaluation of local and global LV function. Future As computing power increases it is easier to reduce the size of many of the components of the echocardiography machine and, thus, our devices can be miniaturized. The future will undoubtedly see a new model of clinical cardiology care that incorporates the equivalent of an ultrasound stethoscope.49 In addition, as investigators continue to make advances in understanding the molecular and genetic controls over cardiac physiology and disease, they will look to noninvasive imaging with echocardiography to assist in these correlations. Thus, ultrasonic quantitation of LV function will be crucial in assessing the results of pharmacologic, molecular, and genetic manipulations of the failing heart to determine whether observations at the bench can be translated to effective therapies in patients50, 51 (Figure 10). Fifty years ago few could have imagined how vital echocardiography would become for the assessment of ventricular function and its daily role in patient care. Without the vision and persistence of Harvey Feigenbaum, we would not have advanced as far as we have traveled on this journey. References 1. 1Edler I. The diagnostic use of ultrasound in heart disease. Acta Med Scand Suppl. 1955;308:32. 2. 2Feigenbaum H, Popp RL, Chip JN, Haine CL. Left ventricular wall thickness measured by ultrasound. Arch Intern Med. 1968;121:391–395. MEDLINE 3. 3Gramiak R, Shah PM, Kramer DH. Ultrasound cardiography: contrast studies in anatomy and function. Radiology. 1969;92:939–948. MEDLINE 4. 4Popp RL, Wolfe SB, Hirata T, Feigenbaum H. Estimation of right and left ventricular size by ultrasound: a study of the echoes from the interventricular septum. Am J Cardiol. 1969;24:523–530. MEDLINE |
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50. 50Hataishi R, Rodrigues AC, Neilan TG, Morgan JG, Buys E, Shiva S, et al. Inhaled nitric oxide decreases infarction size and improves left ventricular function in a murine model of myocardial ischemia-reperfusion injury. Am J Physiol Heart Circ Physiol. 2006;291:H379–H384. MEDLINE |
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a Massachusetts General Hospital, and Harvard Medical School, Boston, Massachusetts b Stanford University School of Medicine, Stanford, California.  Reprint requests: Michael H. Picard, MD, Massachusetts General Hospital, 55 Fruit St, Yawkey 5300, Boston, MA 02114.
PII: S0894-7317(07)00811-5 doi:10.1016/j.echo.2007.11.007 © 2008 American Society of Echocardiography. Published by Elsevier Inc. All rights reserved. | |
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