Left and Right Ventricular Systolic Function
The degree of ventricular systolic dysfunction is a potent predictor of clinical outcome for a wide range of cardiovascular disease, including ischemic cardiac disease, cardiomyopathies, valvular heart disease, and congenital heart disease. Echocardiographic estimates of global and regional function, quantitative ventricular volumes and ejection fractions, and Doppler echocardiographic ejection phase indices all are valuable clinical tools. Even when evaluation of ventricular systolic function is not the primary focus of the echocardiographic examination, evaluation of ventricular systolic function is a key component of every clinical study. For research applications, echocardiographic measures of left ventricular (LV) systolic function provide important baseline data on disease severity and clinical endpoints for intervention trials in patients with ventricular dysfunction.
Systole is defined as the segment of the cardiac cycle from mitral valve closure to aortic valve closure (Fig. 6-1). The onset of systole is identified on the electrocardiogram (ECG) as ventricular depolarization (onset of the QRS complex), with the end of systole occurring after repolarization (end of T-wave). In terms of ventricular pressure curves over time, systole begins when LV pressure exceeds left atrial (LA) pressure, resulting in closure of the mitral valve. Mitral valve closure is followed by isovolumic contraction, during which the cardiac muscle depolarizes, calcium influx and myosin-actin shortening occur, and ventricular pressure rises rapidly at a constant ventricular volume (although shape changes may occur). When ventricular pressure exceeds aortic pressure, the aortic valve opens. During ejection (aortic valve opening to closing), LV volume falls rapidly as blood flows from the LV to the aorta. LV pressure exceeds aortic pressure for approximately the first half of systole, corresponding to a rapid acceleration of blood flow and a small pressure difference from the ventricle to the aorta. In the normal heart, pressure crossover occurs in midsystole, so during the second half of systole, aortic pressure exceeds LV pressure, resulting in continued forward blood flow but at progressively slower velocities (deceleration). Aortic valve closure occurs at the dicrotic notch of the aortic pressure tracing, immediately following end-ejection. In sum, systole includes isovolumic contraction and ventricular ejection (acceleration and deceleration phases). Ventricular volume ranges from a maximum at end-diastole (or onset of systole) to a minimum at end-systole.
Figure 6–1 The cardiac cycle.
LV, aortic (Ao), and LA pressures are shown with the corresponding Doppler LV outflow and inflow velocity curves. The isovolumic contraction time (IVCT) represents the time between mitral valve closure and aortic valve opening, while the isovolumic relaxation time (IVRT) represents the time between aortic valve closure and mitral valve opening.
During systole, ventricular myocardial fibers contract circumferentially and longitudinally, resulting in myocardial wall thickening and inward motion of the endocardium. The simultaneous decrease in ventricular size and increase in pressure results in ejection of a volume of blood (stroke volume) from the ventricle. Stroke volume reflects the pump performance of the heart. The decrease in chamber volume relative to end-diastolic volume, or ejection fraction, reflects overall ventricular function. Ventricular function and pump performance depend on:
Contractility is the intrinsic ability of the myocardium to contract, independent of loading conditions or geometry. Evaluation of contractility itself thus requires measurement of ventricular ejection performance under different loading conditions. Experimentally, contractility often is described by the slope of the end-systolic pressure-volume relationship (Emax). To derive this value, LV pressure is graphed on the vertical axis, with volume (not time) on the horizontal axis (Fig. 6-2). This pressure-volume “loop” then represents a single cardiac cycle, with different pressure-volume loops for the same ventricle representing different loading conditions (such as increasing or decreasing ventricular end-diastolic volume or changing afterload). Emax is the slope of the line that intersects the end-systolic pressure-volume point for each curve. A decrease in contractility results in a decrease in stroke volume and larger LV volumes (Fig. 6-3) Contractility itself can be affected by several physiologic parameters including heart rate, coupling interval, and metabolic factors, in addition to disease processes and pharmacologic agents.
Figure 6–2 Pressure-volume loop.
LV volume is graphed on the horizontal axis, with pressure on the vertical axis. The temporal direction of pressure-volume changes is shown by the arrows. During diastole, volume increases with little rise in pressure. After mitral valve (MV) closure, isovolumic contraction (IVC) results in a rapid rise in pressure with no change in volume. At the onset of ejection, the aortic valve (AoV) opens with a rapid decrease in LV volume during systole. Aortic valve closure is followed by isovolumic relaxation (IVR).
Figure 6–3 Effect of changes in contractility on LV pressure-volume (P-V) loops.
A normal ventricle is shown in yellow and an acute decrease in contractile state in pink. The slope of the line intersecting the end-systolic pressure volume points at different loading conditions, shown as a green line for each P-V loop, is a measure of contractility known as elastance (Emax), which is insensitive to changes in loading conditions. With decreased contractility, the P-V loop is displaced to the right and the end-systolic P-V line shifts downward and to the right. The effect of an acute increase in contractile state is illustrated by the line on the left; the slope of the end-systolic P-V line is increased (the corresponding loop is not shown). (From Aurigemma GP, Gaasch WH, Villegas B, et al: Noninvasive assessment of left ventricular mass, chamber volume, and contractile function. Curr Probl Cardiol 20:418, 1995.)
The effect of preload on ventricular ejection performance is summarized by the Frank-Starling curve showing ventricular end-diastolic volume (or pressure) on the horizontal axis and stroke volume on the vertical axis (Fig. 6-4A). For a given degree of contractility, there is a curvilinear relationship between these variables such that increasing end-diastolic volume results in a greater stroke volume. An increase in contractility results in a greater increase in stroke volume for a given increase in preload; a decrease in contractility has the opposite effect.
Figure 6–4 Preload and afterload.
Top, The relationship between preload, often defined by end-diastolic volume (EDV) and stroke volume (SV) is shown for a normal (blue) LV. With increased contractility, there is a greater increase in SV for an increase in EDV (red); with decreased contractility, there is a smaller increase in SV for an increase in EDV (green dashed). Bottom: The inverse relationship between afterload, approximated by blood pressure (BP) or systemic vascular resistance, and LV myocardial shortening velocity is shown for a normal ventricle (blue). With increased contractility, shortening velocity (and stroke volume) can be maintained at higher afterloads (red); with decreased contractility, shortening velocity is lower for any given afterload (green dashed).
Afterload, defined by resistance or impedance, has an inverse relationship with myocardial fiber shortening such that increasing vascular resistance results in a decreased stroke volume (see Fig. 6-4). An increase in contractility allows maintenance of a normal stroke volume with a higher afterload. With a decrease in contractility, even slight increases in afterload further decrease myocardial fiber shortening and stroke volume.
Measurement of LV systolic function independent of loading conditions is difficult using echocardiographic or other clinical approaches. It rarely is possible to construct pressure-volume loops under different loading conditions because of the problem of measuring instantaneous LV volumes and the potential risk of altering loading conditions in ill patients. Thus clinical evaluation of ventricular function has focused on measurements of cardiac output, ejection fraction, and end-systolic dimension or volume, even though the load dependence of these measures is a clearly acknowledged limitation. Strain and strain rate measurements offer another approach to evaluation of ventricular function and may become more widely utilized in the future (see Chapter 4).
The normal shape of the LV is symmetric with two relatively equal short axes and with the long axis running from the base (mitral annulus) to the apex. In long-axis views, the apex is slightly rounded, so the apical half of the ventricle resembles a hemiellipse. The basal half of the ventricle is more cylindrical, so the ventricle appears circular in short-axis views. Various assumptions about LV shape have been used to derive formulas for calculating ventricular volumes from linear dimensions (M-mode) and cross-sectional areas (two-dimensional [2D] echo). Formulas using linear or cross-sectional measurements are simplifications to greater or lesser degrees, and there is variability among patients in the shape of the ventricle. Calculation of LV size from three-dimensional (3D) images avoids inaccuracy related to geometric assumptions.
While instantaneous ventricular volumes throughout the cardiac cycle are of interest, usually only end-diastolic volume (EDV) and end-systolic volume (ESV) are measured in the clinical setting. Ejection fraction (EF) is:
where stroke volume (SV) is calculated as:
with cardiac output obtained by multiplying stroke volume by heart rate.
The basic function of the heart is as a pump, so measurements of cardiac output are useful in routine day-to-day patient management. Cardiac output is the volume of blood pumped by the heart per minute, with stroke volume being the amount pumped on a single beat. While cardiac output can be derived from ventricular volumes, as described above, a variety of other approaches to measurement are available, including right heart catheterization with indicator dilation methods (Fick, thermodilution); inert gas rebreathing approaches; angiographic, radionuclide, or cardiac magnetic resonance (CMR) ventricular volumes; and CMR or Doppler flow velocity methods.
Ventricular systolic function and cardiac output are dynamic, responding rapidly to the metabolic demands of the individual. Cardiac output increases from a mean of 6 L/min at rest to 18 L/min with exercise in young, healthy adults. Most of this increase in cardiac output is mediated by an increase in heart rate. With supine exercise, there is only a minimal increase in stroke volume (about 10%), whereas with upright exercise, the increase in stroke volume is approximately 20% to 35%. With exercise, end-diastolic volume is unchanged or slightly decreased, but ejection fraction increases and end-systolic volume decreases. With imaging techniques, endocardial motion and myocardial wall thickening are augmented with an appearance of “hypercontractility” during and immediately following exercise.
Both global and regional ventricular function can be evaluated with 2D echocardiography on a semiquantitative scale by an experienced observer. On transthoracic (TTE) imaging, overall LV systolic function is evaluated best from multiple tomographic planes, typically:
On transesophageal (TEE) imaging, equivalent views from a high TEE and transgastric position are used. Attention to image acquisition is needed in order to obtain adequate endocardial definition. Three-dimensional image acquisition allows simultaneous display of two or more tomographic planes and may become more widely utilized as 3D image quality and endocardial definition are improved.
The echocardiographer then integrates the degree of endocardial motion and wall thickening from these views to classify overall systolic function as normal, mildly reduced, moderately reduced, or severely reduced. Some experienced observers can estimate ejection fraction visually from 2D images with a reasonable correlation with ejection fractions measured quantitatively by echocardiography or other techniques. Typically, ejection fraction is estimated in intervals of 5% to 10% (i.e., 20%, 30%, 40%, and so on) or an estimated ejection fraction range is reported (e.g., 20% to 30%).
With normal systolic function, the anterior mitral leaflet opens to nearly fill the ventricular chamber resulting in little (0-5 mm) E-point septal separation. With systolic dysfunction, this distance is increased because of a combination of LV dilation and reduced motion of the mitral valve as a result of low transmitral volume flow. Similarly, LV systolic dysfunction results in reduced LA filling and emptying (low cardiac output), seen on M-mode as reduced anteroposterior motion of the aortic root.
On 2D echocardiography, the mitral annulus moves toward the ventricular apex in systole, with the magnitude of this motion proportional to the extent of shortening in ventricular length—a useful measure of overall LV systolic function. Normal subjects have motion of the mitral annulus toward the apex ≥8 mm, with a mean value of 12±2 mm in both four- and two-chamber views. The sensitivity of mitral annulus motion <8 mm is 98% with a specificity of 82% for identification of an ejection fraction <50%.
Qualitative evaluation of overall systolic function is a simple and highly predictive index that is of great clinical utility. On the other hand, several factors can limit the usefulness of this evaluation. First, the accuracy of the estimated ejection fraction is dependent on the experience of each observer. Second, inadequate endocardial definition can result in incorrect estimates of systolic function. Third, integration of data from multiple tomographic images can be difficult when the pattern of contraction is asynchronous (with conduction defects, pacers, postoperative septal motion) or when the pattern of contraction is asymmetric (with prior myocardial infarction or with ischemia), especially when dyskinesis is present. To some extent, these limitations are minimized by an experienced observer, optimal endocardial definition, and integration of data from multiple views. However, when possible, it is preferable to avoid the limitations of estimates of systolic function by performing quantitative measurements.
Regional ventricular function also can be evaluated by imaging in multiple tomographic planes on TTE or TEE imaging. Regional function is evaluated qualitatively by dividing the ventricle into segments corresponding to the coronary artery anatomy and then grading wall motion on a 1 to 4+ scale as normal (score = 1), hypokinetic (score = 2), akinetic (score = 3), or dyskinetic (score = 4). In some cases, hyperkinesis—that is, a compensatory increase in wall motion in regions remote from an acute myocardial infarction or the normal increase seen with exercise—also is scored. Evaluation of segmental wall motion is discussed in detail in Chapter 8.
LV internal dimensions and wall thickness are routinely measured using 2D echocardiography. Measurements of LV size are most accurate when the ultrasound beam is perpendicular to the blood-endocardium interface because of the precision of axial, compared to lateral, resolution. In some specific situations, such as serial evaluation of the patient with chronic aortic or mitral regurgitation, 2D guided M-mode measurement are recommended, particularly when identification of the endocardium is suboptimal on the 2D images (Table 6-1).
On a standard examination, ventricular size is measured in the parasternal long-axis view, at the level of the mitral leaflet tips (mitral chordal level), perpendicular to the long axis of the ventricle (Fig. 6-5). Biplane imaging or scanning between the long- and short-axis views is also helpful to ensure that the measurements are centered in the short-axis plane. TEE measurements of LV internal dimensions are made in a transgastric two-chamber view at the junction between the basal third and apical portion of the ventricle. Wall thickness is measured in the transgastric short-axis view. On 2D images, LV internal dimensions are measured at end-diastole and end-systole from the tissue-blood interface (white-black transition). End-diastole is defined as the onset of the QRS, the first frame after mitral valve closure or maximum ventricular volume. End-systole is defined as the smallest ventricular volume or the frame just after aortic valve closure.
Figure 6–5 LV M-mode measurements.
LV end-diastolic (ED) and end-systolic (ES) dimensions (D) are measured from the parasternal window. 2D measurements are made for the white-black interface of the septum to the posterior wall, taking care to measure perpendicular to the long axis of the ventricle and centered in the short axis. Similarly, 2D-guided M-mode measurements are made after verifying that the M-line is centered in the LV in the short-axis view and perpendicular to the long axis of the LV in the long-axis view. The transducer should be in a high intercostal space to ensure that the M-line is not oblique. The high sampling rate of the M-mode recording allows more precise identification of the endocardium.
When 2D guided M-mode measurements are used, the transducer often needs to be moved cephalad to obtain a perpendicular angle between the M-line and the long axis of the ventricle. If only an oblique orientation is possible, correctly aligned measurements should be made from the 2D image instead. The major advantage of M-mode echocardiography is high time resolution, which facilitates recognition of endocardial motion and thus a more accurate measurement of ventricular internal dimensions. On M-mode, the LV posterior wall endocardium is the most continuous line with the steepest systolic motion (Fig. 6-6). The posterior wall epicardium is identified as the echo reflection immediately anterior to the pericardium. The septal endocardium also shows the steepest slope in systole with a continuous reflection through the cycle. On the right ventricular (RV) side of the septum, it is important to exclude any reflections that are caused by RV trabeculations. Conversely, a dark “mid-septal” stripe often is noted and should not be confused with the endocardial borders. LV wall thickness and dimensions are measured from the leading edge-to-leading edge of each interface of interest for optimal measurement accuracy. For example, ventricular internal dimensions are measured from the leading edge of the septal endocardium to the leading edge of the posterior wall endocardium. Normal values for these measurements are indicated in Table 2-8.
Figure 6–6 LV M-mode schematic diagram.
From a 2D-guided M-mode recording, diastolic measurements are made coincident with the Q-wave of the simultaneous electrocardiogram. Systolic measurements are made at the maximum posterior motion of the septum, when septal motion is normal. d, diastolic; LVID, LV internal dimensions; PWT, posterior wall thickness; s, systolic; ST, ventricular septal thickness in diastole. (From Aurigemma GP, Gaasch WH, Villegas B, et al: Noninvasive assessment of left ventricular mass, chamber volume, and contractile function. Curr Probl Cardiol 20:381, 1995.)
Fractional shortening is a rough measurement of LV systolic function, with the normal range being about 25% to 45% (95% confidence limits). Instead of endocardial fractional shortening, as shown in equation 6-3, mid-wall fractional shortening is a better reflector of contractility, because it reflects both the inward motion of the endocardium and the degree of wall thickening. However, mid-wall shortening calculations are rarely used in clinical practice because 2D measures of ventricular systolic function are more robust.
Two-dimensional echocardiographic calculation of ventricular volumes is based on endocardial border tracing at end-diastole and end-systole in one or more tomographic planes on TTE or TEE images (Table 6-2). Prerequisites for quantitative evaluation by 2D echocardiography are:
Data sources: Schiller et al: Circulation 60:547-555, 1979; Folland et al: Circulation 60:760-766, 1979; Parisi et al: Clin Cardiol 2:257-263, 1979; Silverman et al: Circulation 62:548-557, 1980; Starling et al: Circulation 63:1075-1084, 1981; Quinones et al: Circulation 64:744-753, 1981; Tortoledo et al: Circulation 67:579-584, 1983; Erbel et al: Circulation 67:205-215, 1983; Zoghbi et al: JACC 15:610-617, 1990; Smith et al: JACC 19:1213-1222, 1992.
In some patients, image quality is inadequate for endocardial definition. Even when image quality is adequate, endocardial borders must be traced manually by an experienced physician or sonographer for accurate quantitation of LV systolic function by echocardiography. Because 2D echocardiography is a tomographic technique, LV volume calculations are based on geometric assumptions about the shape of the LV. By convention, the papillary muscles are included in the ventricular chamber, with endocardial borders extrapolated along the base of the papillary muscle, following the expected curvature of the ventricular wall. Obviously, accuracy in individual patients will be highest with methods that have the fewest geometric assumptions and that use data from multiple tomographic images.
Several approaches for the calculation of LV volumes from tomographic data, based on different geometric assumptions, have been proposed, ranging from a simple ellipsoid shape to complex hemicylindrical hemiellipsoid shapes (Fig. 6-7). The most robust and practical method for clinical use is Simpson’s rule or method of disks which calculates ventricular volume as the sum of a series of parallel “slices” from apex to base.
Figure 6–7 2D LV volume calculations.
Examples of three formulas for LV volume calculations showing the 2D echocardiographic views and measurements on the left and the geometric model on the right. For the biplane apical method, endocardial borders are traced in apical four-chamber and two-chamber views, which are used to define a series of orthogonal diameters (a and b). A “Simpson’s rule” assumption based on stacked disks is used to calculate volume. The single-plane ellipsoid method uses the 2D area (A) and length (L) in a single (usually apical four-chamber) view. The hemisphere-cylinder method uses a short-axis endocardial area at the midventricular level (Am) and a long-axis length (L). For each method, both end-diastolic and end-systolic measurements are needed for calculation of end-diastolic and end-systolic volumes, respectively, and for ejection fraction determination.
This approach is accurate even when ventricular geometry is distorted; it is also the approach recommended in consensus guidelines. The apical biplane approach requires tracing of endocardial borders at end-diastole and end-systole in both four-chamber and two-chamber views, from either TTE or TEE images (Fig. 6-8). These borders are then used to calculate cross-sectional areas of a series of elliptical disks. End-diastolic volume is calculated from end-diastolic images and end-systolic volume is calculated from end-systolic images. Stroke volume, then, is the difference between end-diastolic volume (EDV) and end-systolic volume (ESV) (Eq. 6-2), while ejection fraction (EF) is calculated with Eq. 6-1.
Figure 6–8 Apical biplane LV volumes.
Examples of apical four-chamber (top) and two-chamber (bottom) views at end-diastole (left) and end-systole (right), showing the traced endocardial borders for calculation of biplane LV systolic (76mL) and diastolic (205 mL) volumes and ejection fraction (63%).
When only a four-chamber view is available, a single plane ejection fraction can be calculated, which summates a series of disks with a circular cross-sectional area. Another alternative is the area-length method, which assumes that the base of the ventricle is approximated by a cylinder and the apex by an ellipsoid, sometimes called the “bullet” formula; this formula uses a long-axis length L and the cross-sectional area Am of an orthogonal short-axis view at the mid-papillary level:
In the presence of a distorted ventricular shape or regional wall motion abnormalities, these alternate methods will be less accurate, because, if the region of abnormal wall motion is included in the dimension or area measurements, volumes will be overestimated and vice versa.
Three-dimensional echocardiography provides more accurate measurements of LV volumes and ejection fraction that are independent of geometric assumptions (Table 6-3). Current instrumentation allows semiautomated border detection from the 3D volumetric data set with calculation of end-diastolic and end-systolic volumes and ejection fraction (Table 6-4). From an apical window, the key steps in 3D data acquisition for evaluation of the LV are as follows:
angio, angiography; CMR, cardiac magnetic resonance imaging; CT, computed tomography; DOP, Doppler; EDV, end-diastolic volume; ESV, end-systolic volume; RN, radionuclide angiography; SEE, standard error of the estimate.
Data sources: Gopal et al: JACC 22:258-70, 1993; Sapin et al: JACC 24:1054, 1994; Gopal et al: J Am Soc Echo 10:853, 1997; Kuehl et al: J Am Soc Echo 11: 1113-24, 1998; Mele et al: 11:1001, 1998; Qin et al: J Am Coll Cardiol 36:900-907, 2000; Lee et al: J Am Soc Echocardiogr 14:1001-1009, 2001; Kawai et al: J Am Soc Echo 16:11011-5. 2003; Jenkins et al: J Am Coll Cardiol. 18:878-886, 2004; Jenkins et al: J Am Soc Echocardiogr 19:1119-1128, 2006; Soliman et al: Am J Cardiol 15:778-783, 2008; Muraru et al: Eur J Echocardiogr 11:359-368, 2010.
ED, end-diastole; ES, end-systole.
Data are displayed as a cine loop 3D rendered LV volume, a graph of LV volume over the cardiac cycle, and images showing regional wall motion or regional ejection fraction, depending on the specific ultrasound system (Fig. 6-9). In clinical practice, limitations of 3D evaluation of the LV include lower temporal and spatial resolution compared to 2D imaging and difficulty including the entire LV chamber within the 3D volume data set. However, 3D volumes and ejection fraction are more accurate than 2D measurements, so quantitative evaluation of LV systolic function 3D echocardiography is recommended, whenever possible.
Figure 6–9 3D LV volumes.
LV volumes are derived from a 3D volume acquisition with three orthogonal planes corresponding to four-chamber, two–chamber, and short-axis views shown along with the 3D volume rendered from semiautomated border tracing. The LV volume curve is shown at the bottom starting with the largest volume at end-diastole and the smallest (end-systolic) volume at the nadir of the curve. This 3D volume is from the same patient shown in Figure 6-8.
LV mass is the total weight of the myocardium, derived by multiplying the volume of myocardium by the specific density of cardiac muscle. LV mass can be estimated from M-mode dimensions of septal thickness (ST), posterior wall thickness (PWT), and LV internal dimensions (LVID) at end-diastole as:
On 2D or 3D echocardiography, LV mass theoretically can be determined by tracing epicardial borders to calculate the total ventricular volume (walls plus chamber), subtracting the volumes determined from endocardial border tracing, and then multiplying by the specific density of myocardium:
However, epicardial definition rarely is adequate for this approach. Instead, mean wall thickness is calculated from epicardial (A1) and endocardial (A2) cross-sectional areas in a short-axis view at the papillary muscle level. LV mass measurements often are indexed for body size (either as body surface area or height) using gender-specific normal values (see Table 2-8).
Relative wall thickness is a simpler measure of ventricular geometry in patients with hypertrophy that reflects the relative thickness of the walls compared to chamber size. Relative wall thickness (RWT) is calculated from posterior wall thickness (PWT) and LV internal dimension (LVID), both at end-diastole, as: