19 Echocardiography

Heart failure (HF) is a complex syndrome that can result from any structural or functional cardiac disorder that impairs the ability of the heart to function as a pump to support a physiological circulation. The most common cause of HF in the United Kingdom is coronary artery disease (CAD); other aetiologies include hypertension, atrial fibrillation, cardiomyopathies, valvular heart disease, pericardial disease, and intracardiac shunts.¹ Transthoracic echocardiography has a decisive role in the diagnosis, treatment, and follow-up of patients with HF.² Indeed, its importance was underscored in the UK 2003 NICE Guidelines for Heart Failure,³ and more recently in the American College of Cardiology/American Heart Association (ACC/AHA) guidelines for the diagnosis and management of HF, where echocardiography was endorsed as ‘the single most useful diagnostic test in the evaluation of patients with heart failure…’.⁴ Echocardiography utilizes ultrasound which has no known adverse biological effects, is noninvasive, and is a relatively low-cost imaging modality. The use of echocardiography in the diagnosis, therapeutic management, and serial follow-up of the increasing number of patients with HF has therefore potentially large health benefits with relatively low patient cost.

Abnormalities of left ventricular function may be apparent even before clinical signs of HF are evident. Comprehensive echocardiographic assessment of left ventricular function is therefore required. Table 19.1 outlines standard techniques for echo evaluation of left ventricular function. The minimal requirements are an assessment of (1) left ventricular size and shape, (2) global systolic function, (3) regional systolic function, (4) diastolic function, (5) intracardiac haemodynamics, and (6) left ventricular synchrony.

Measurements of left ventricular cavity size (end-diastolic dimension, EDD and end-systolic dimension, ESD) are made from M-mode or two-dimensional cross-sectional imaging of the left ventricle at the level of the mitral valve tips at end diastole (q wave of the preceding cardiac cycle) and at end systole (aortic valve closure) (Fig. 19.1). Segmental wall thickness at end diastole (and thickening fraction from measurements at end systole) may also be determined using either method. Normal ranges for left ventricular cavity size are presented in Table 19.2.⁴

Fractional shortening may be calculated using measures of left ventricular end-diastolic and end-systolic cavity size (as the percentage change in left ventricular cavity dimension in systole with respect to diastole):

Fractional shortening (%) = [(EDD – ESD)/EDD) × 100]

Although fractional shortening accurately quantifies basal left ventricular function, it is reliable only in a symmetrically contracting heart without regional variability and thus is frequently inappropriate for the remodelled ventricles of many HF patients. Assessment of left ventricular systolic function thus depends more on values of left ventricular ejection fraction (LVEF). Calculation of LVEF is based on guidelines from the American Society of Echocardiography using the principle of slicing the left ventricle from mitral valve annulus to apex into a series of 20 discs.⁵ The volume of each disc is calculated (using the diameter and thickness of the slice) and then all the discs are summated to provide left ventricular volumes at end diastole and end systole (Fig. 19.2). LVEF is calculated as:

[(EDV-ESV)/EDV) × 100]

Accuracy is improved by using diameters in two perpendicular planes (biplane—apical four- and two-chamber). Normal ranges for left ventricular fractional shortening and LVEF are presented in Table 19.2. The ASE guidelines define an abnormal LVEF as less than 55%, with the cut-offs for moderately and severely reduced LVEF as 36–44% and under 35% respectively.

The ‘summation of discs’ method assumes that the imaging planes are orthogonal and is absolutely dependent on detection of the endocardial border and therefore on image quality of the echocardiogram. Interobserver variability and beat-to-beat variability can be significant if image quality is suboptimal. Real-time three-dimensional echo imaging has the advantage of taking into account variation in ventricular shape in all directions rather than just the two biplane measurements (Fig. 19.3a), with good correlation with cardiac volumes obtained from cardiac magnetic resonance imaging (CMR). However, good-quality endocardial border definition is still required.⁶

Despite the historical use of LVEF as ‘a measure of left ventricular systolic function’, its use has distinct disadvantages. As an ejection-phase index, LVEF is highly load-dependent; thus, a change in LVEF over time may not necessarily be due to a change in the intrinsic contractility of the myocardium (a true measure of systolic function), but may merely reflect a change in the loading conditions. Nevertheless, LVEF and ‘systolic function’ continue to be used interchangeably in the literature. Moreover, since LVEF is affected by preload and afterload, it can give misleading information in several clinical situations; for example, the falsely high LVEF in severe mitral regurgitation when underlying left ventricular systolic function is abnormal, the low LVEF in severe aortic stenosis which can increase markedly after valve replacement, and the variable LVEF in atrial fibrillation. Furthermore, LVEF does not correlate with HF symptoms, exercise capacity, or myocardial oxygen consumption.⁷ Despite these major limitations, echo measurement of LVEF continues to be standard practice, providing as it does not only the standard entry criterion for many HF clinical trials,^8,–10 but guidance for therapeutic intervention such as defibrillator device therapy and timing of surgery for valve disease,^11,12 and affording prognostic information (predicting major adverse cardiac events, cardiovascular mortality, and sudden death) in the HF population.^13,14

The clinical importance of left ventricular mass relates to the identification of pathological left ventricular hypertrophy (LVH). In the echocardiographic substudy of the SOLVD trial, increased left ventricular mass was associated with high mortality and rate of cardiovascular hospital stays, independent of LVEF.¹⁴ LVH may be secondary to other pathology (aortic valve disease or hypertension) or it may be a primary myocardial problem (hypertrophic cardiomyopathy, infiltrative cardiomyopathy). Physiological hypertrophy (in athletes or during pregnancy) is usually reversible. In elderly people, there is sometimes septal angulation and thickening that creates the impression of septal hypertrophy but the left ventricular mass is usually unchanged.

Left ventricular mass may be calculated using M-mode techniques and the formula:

LV mass = 1.04 ([LVID + PWT + LVST]³ – LVID³) – 14 g

where LVID is the left ventricular internal dimension during diastole, PWT is the posterior wall thickness, and IVST is the interventricular septal thickness.¹⁵ Two-dimensional methods, including the truncated ellipsoid and the area–length formula, might be more appropriate for distorted ventricles with regional wall motion abnormalities. Both methods, however, rely heavily on geometric assumptions and are therefore subject to inaccuracies from foreshortening. These limitations may be partially overcome using three-dimensional echocardiographic techniques (Fig. 19.3b).

Normal ranges for left ventricular mass are presented in Table 19.2. LVH may be graded by reporting relative wall thickness (calculated as [2 × PWT]/LVEDD) and overall left ventricular mass, and reported as (1) normal; (2) concentric LVH (increased relative wall thickness with increased mass); (3) eccentric LVH (increased mass with normal relative wall thickness); (4) concentric remodelling (normal mass with increased relative wall thickness). Concentric changes suggest pressure overload (due to aortic stenosis or hypertension), while eccentric changes suggest volume overload (e.g. due to aortic regurgitation).

Doppler echocardiography can evaluate indices of the isovolumic contraction phases of the cardiac cycle, which may be more representative of the left ventricular contractile state. The change in left ventricular pressure over time (dP/dt) is closely related to the mitral regurgitation trace obtained using echocardiography using continuous-wave Doppler across the mitral valve (Fig. 19.4). Assuming any change in left atrial pressure during systole has negligible effect on this pressure difference, a plot of left ventricular dP/dt can be generated from the first derivative of the pressure difference plot.¹⁶ The faster the rise in ventricular pressure, the more coordinated the left ventricular systolic function.¹⁷

Alternatively, stroke distance can be calculated from the velocity time integral (VTI) of the left ventricular outflow tract using pulse-wave Doppler from an apical five-chamber view. The product of stroke distance (normally 18–22 cm) and left ventricular outflow tract area provides quantitative Doppler assessment of left ventricular stroke volume. Cardiac output may be subsequently calculated as the product of stroke volume and heart rate.

Regional wall motion abnormalities (RWMA) may occur in any dilated cardiomyopathy but are most commonly associated with CAD. Echocardiography is an extremely useful tool for identifying left ventricular RWMA. Basic assessment of regional wall motion or thickening is usually assessed subjectively, and attributed to specific coronary territories. The right coronary artery usually supplies the right ventricle and left ventricular inferioseptal segments, the left anterior descending artery supplies the left ventricular anterior, anterioseptal, and apical segments, and the circumflex artery supplies the left ventricular lateral wall. However, there may be considerable variation and/or overlap between individual patients.

A standard 16-segment model of the left ventricle (lateral, septal, inferior, anterior segments at the apex, midpapillary, and basal levels, and anteroseptal and posterior segments at the midpapillary and basal levels)¹⁸ or more recently, a 17-segment model that includes a true apical segment,¹⁹ is used to assess regional function. Each region is given a score where 1 is normal, 2 is hypokinetic (endocardial excursion 〈5 mm), 3 is akinetic (endocardial excursion 〈2 mm), and 4 is dyskinetic (endocardium moves outwards in systole). The overall wall motion score index, calculated by averaging the scores of all individual segments, is related to prognosis.²⁰ The technique is subjective, however, with variable reproducibility between centres, although its accuracy may be improved with the use of contrast agents that opacify the left ventricular cavity and enhance endocardial border delineation.

Quantitation of regional function has been performed with a number of echocardiographic and Doppler modalities with increasingly reliable reproducibility (Table 19.3). Some techniques, such as M-mode and tissue Doppler imaging (TDI) are in routine clinical practice, while others are being investigated as possible measures of regional function that can detect subclinical disease in a similar fashion.

Assessment of annular longitudinal function by either measurement of amplitude (M-mode) or velocity (tissue Doppler) is a clinically useful tool for assessing systolic left ventricular function. Normal left ventricular contraction depends on the coordinate function of longitudinally and circumferentially directed muscle fibres (twisting and untwisting with accompanying longitudinal shortening and lengthening), and loss of these interactions, evident early in left ventricular disease, are readily detected using echocardiography (Fig. 19.5). Abnormalities of the mitral annular motion have been described in a variety of conditions. Patients with acute myocardial infarction have reduced displacement more marked at the region of the annulus related to the site of infarct;²¹ systolic long axis abnormalities may occur in 38–52% of HF patients with normal LVEF;^22,23 and reductions in long axis amplitude and velocity can be detected before reduction in LVEF or symptoms develop in hypertension, diabetes, ‘diastolic HF’, and hypertrophic cardiomyopathy among others.^24,–26 Moreover, long axis amplitude is strongly related to LVEF,²⁷ and is a useful predictor of prognosis in a variety of clinical conditions.²⁸

From digitally recorded tissue Doppler loops of one or more heart beats containing velocity data from the entire myocardium, two new tissue Doppler entities can be derived: (1) strain rate (the rate of deformation between two points a predefined distance apart)²⁹ and (2) speckle (tissue) tracking (echo software detects frame-to-frame migration of two-dimensional speckle signals from the myocardium from high-resolution two-dimensional imaging and then calculates myocardial strain independent of the angle of incidence) (Fig. 19.6).³⁰ From a 16-segment left ventricular model, the average motion amplitude toward the apex in systole for each segment can be measured and a ‘global systolic contraction amplitude index’ calculated.³¹ Although reportedly useful in the early detection of subclinical heart disease, these newer techniques currently have the disadvantages of a large signal-to-noise ratio and wide inter- and intraobserver variability in measurements. Their specific advantages over M-mode or tissue velocity quantification of long axis function, that also detects subclinical disease therefore remain unclear. Their main use may be in the identification and measurement of left ventricular dyssynchrony.

A large proportion of patients who present with symptoms of HF have a LVEF within the normal range; these patients are frequently referred to as having ‘diastolic HF.’ The use of such a term is troublesome, not least because no simple definition of diastolic disease itself has emerged, but also because it presumes an understanding of the mechanisms leading to the disorder and therefore justification of the substitution of a mechanistic term for a descriptive phrase. ‘Increased resistance to filling’ has been suggested. However, whereas the resistance of a valve orifice or circulation can be readily identified in terms of pressure drop and flow, resistance to filling involves neither and so is poorly defined. This lack of gold standards by which discrete mechanisms can be assessed in individual patients is a major impediment to identifying and quantifying disturbances in disease. So is the reality that left ventricular filling is totally load-dependent. Nevertheless, a variety of echocardiographic techniques are frequently used to determine a series of abnormalities of diastolic function, the cornerstone of which is the measurement of transmitral flow (left ventricular filling) (Fig. 19.7). Pulmonary venous flow, left atrial size, and tissue doppler imaging (TDI) of the mitral annulus are also considered. These measurements have demonstrated considerable prognostic value in symptomatic and asymptomatic patients with either preserved or abnormal left ventricular systolic function.³²

Diastole has traditionally been defined as the period in the cardiac cycle from the end of aortic ejection to the onset of ventricular tension development of the succeeding beat. It has four distinct phases:

Diastolic function is traditionally characterized in the literature according to severity. So-called ‘mild diastolic dysfunction’, usually present early in disease development (ischaemia, aortic stenosis, hypertension, hypertrophy), is detected as prolongation of age-related isovolumic relaxation time (IVRT: time between aortic valve closure and mitral valve opening), decrease in early diastolic flow velocity (E-wave) and a greater reliance on atrial contraction (A-wave) to fill the left ventricle (E:A ratio 〈1). This pattern of left ventricular filling is usually attributed to ‘impaired relaxation’, although the exact meaning of the term is rarely specified in the literature (i.e. slow, delayed, or incomplete). In practice, it is nearly always associated with early diastolic incoordination (continued inward long axis shortening after the end of ejection, associated with outward motion elsewhere),³³ causing an abnormal shape change in early diastole which prevents the left ventricle from becoming spherical (Fig. 19.8). Such delayed contraction prolongs the fall in left ventricular pressure and profoundly affects early diastolic filling, reducing its peak velocity or suppressing it altogether. Clinically, this pattern is associated with the combination of ventricular disease and a low or normal filling pressure. It may thus be unmasked by a Valsalva manoeuvre. It is also common in patients initially presenting with restrictive filling who have responded favourably to treatment with diuretic and angiotensin converting enzyme (ACE) inhibitor (Fig. 19.9).³⁴ This sequence of events illustrates how a patient may improve clinically at the same time that diastolic measurements become more abnormal. Moreover, filling with a dominant A is common in inducible ischaemia, during either angioplasty³⁵ or dobutamine stress.³⁶ It is even associated with activation abnormalities.³⁷ Thus echocardiographic disturbances occurring during diastole, which result in abnormalities of ‘diastolic’ function, may in fact have their origins much earlier in the cardiac cycle, during systole or even earlier, during activation.

With disease progression, left ventricular fibrosis develops and chamber compliance reduces. Often referred to as ‘severe diastolic dysfunction’ in the literature, this form of left ventricular disease relates to the passive properties of the ventricle. It occurs when left atrial pressure is elevated such that early diastolic flow is extremely rapid, and left atrial and left ventricular pressures equalize quickly during early diastole. It is detected echocardiographically as a short (〈40 ms) isovolumic relaxation time, an increased E:A ratio (〉2) and a short E-wave deceleration time (〈150 ms), which is often accompanied by a third heart sound (Fig. 19.10).

Acceleration and deceleration rates of the E-wave are both increased, implying high pressure gradients, both forward and reversed. Reduced A-wave amplitude is not usually caused by failure of left atrial contraction, since mechanical function can be demonstrated by direct measurement of left atrial pressure, by its indirect effect on the apex cardiogram, or by detecting retrograde blood flow into the pulmonary veins. The combination of an increased atrial pressure wave with no flow across the mitral valve demonstrates increased end-diastolic ventricular stiffness. Such ‘restrictive filling’ is good evidence of a raised left atrial pressure, which overrides any relaxation abnormality. It gives no direct information about the underlying diastolic disease. This may be specific, as occurs in amyloid or eosinophilic heart disease, or the high filling pressure may represent a complication of cavity dilation, hypertrophy, or diabetes, or even the simple result of fluid overload distending an otherwise normal ventricle. Whatever the underlying aetiology, a restrictive filling pattern should be regarded as the result of a combination of diastolic disease and a high filling pressure, and identifies patients with a poor prognosis when detected at rest³⁸ or during stress.³⁹ Since a raised left atrial pressure is an important component of the clinical syndrome of HF, estimation of filling pressure should be an integral part of echocardiographic evaluation in these patients.

Just as with isovolumic relaxation time, a raised left atrial pressure and diastolic disease have opposite effects on the E:A ratio, and so the combination of the two leads to a ratio between 1.0 and 2.0, often referred to by the unsatisfactory term ‘pseudonormalization’.⁴⁰ The left ventricular filling pattern should not, however, be considered in isolation, so that recognizing pseudonormality is less of a problem than the literature might suggest. The majority of patients in whom the question arises are elderly people, in whom an E:A ratio greater than 1 would be unusual anyway. They also have clear evidence of structural left ventricular disease, either cavity dilatation or LVH. In a minority, pressure termination of forward atrial flow can be demonstrated, showing near restrictive filling. The ratio E:E′ (peak early diastolic velocity to peak ring velocity) may be useful in these circumstances. When this ratio is increased, then left atrial pressure is likely to be high. However, since a low value of E′ may be the result of reduced systolic amplitude, it may simply be a surrogate marker of left ventricular disease. A dominant E-wave in an elderly patient with ventricular disease should suggest a raised left ventricular filling pressure. Recognizing pseudonormality in young patients, in whom a dominant E-wave would in fact be normal, has received little attention in the literature.

Other measures of diastolic function include TDI, early left ventricular filling flow propagation slope (Vp), left atrial volumes, and pulmonary venous inflow. These measures are less dependent on loading conditions and heart rate and have been reported to be robust predictors of left ventricular filling pressures and cardiovascular mortality. For example, the ratio of peak early mitral inflow velocity to peak early diastolic myocardial velocity (E:E′ ratio) has been correlated with pulmonary capillary wedge pressure (an E:E′ ≤8 predicts a left ventricular end-diastolic pressure (LVEDP) of 〈15 mmHg while a ratio 〉15 predicts an LVEDP ≥15 mm Hg).⁴¹ The reliability of the E:E′ ratio when it is in the 8–15 range in predicting LVEDP is, however, less convincing.⁴² Moreover, with the extreme values (in which the relation is more certain), left atrial pressure is usually obvious from mitral filling pattern anyway. Alternative methods of estimating left atrial pressure include the ratio of peak early mitral inflow velocity to the slope of the propagation velocity (E:Vp ≥1.5 has been reported to predict a LVEDP 〉15 mmHg);⁴³ increased left atrial volume (〉32 mL/m² predicts morbidity);⁴⁴ and a difference of more than 30 ms between pulmonary vein atrial flow reversal and mitral A-wave durations (reported to be a sensitive predictor of LVEDP 〉18 mmHg).⁴⁵

Diastolic function is thus multifactorial; measurements made during diastole are not only highly load-dependent, but also depend on the patient’s age and therapeutic drug regime. Absolute demarcation between isolated ‘systolic’ HF and ‘diastolic’ HF may be misleading, since many measures of diastolic function depend on events occurring much earlier in the cardiac cycle. The sensitivity of echo Doppler techniques to estimate left atrial pressure, however, has proved to have real clinical significance in patients with the clinical syndrome of HF.

Intracardiac pressure measurements have traditionally required invasive methods. This limitation, which also precludes serial measurements except in the intensive care context, can be circumvented with the use of echocardiographic techniques, which convert regurgitant velocity measurements into pressure drops using the Bernoulli equation modified to give the formula 4V² (where V = velocity recorded across a regurgitant jet). Fig. 19.11 illustrates the use of echo Doppler in the estimation of right atrial pressure (from the properties of the inferior vena cava), right ventricular/pulmonary artery systolic pressure (from the tricuspid regurgitant trace), and pulmonary artery mean and diastolic pressures (from the pulmonary regurgitation trace).⁴⁶ As discussed earlier, a combination of long axis and echo Doppler can be used to estimate elevated left and right end-diastolic pressures.

Maximal energy transfer from the myocardium to the circulation is dependent on the coordinate, though nonuniform, action of both circumferentially and longitudinally directed myocardial fibres. Loss of this interaction leads to ventricular dyssynchrony, usefully defined as ‘incoordinate ventricular wall motion that reduces the extent of intrinsic energy transfer from myocardium to useful work on the circulation’. Its functional consequences are significant impairment of maximal cardiac function as a result of a reduction in the proportion of myocardial energy transmitted to the circulation (cycle efficiency).

Activation abnormalities are common in patients with HF and are a major contributor to left ventricular dyssynchrony. Patients with the combination of a long PR interval and left bundle branch block may have very early and prolonged left ventricular activation due to low action potentials that are not detected on a standard 12-lead ECG.⁴⁷ Such early left ventricular activation results in a ‘presystolic’ component of mitral regurgitation that lengthens the total duration of mitral regurgitation and significantly shortens available left ventricular filling time (Fig. 19.12, left).

Dyssynchrony is also major manifestation of CAD. Indeed, it has long been recognized that patients with chronic stable angina have asynchronous wall motion at rest, even in the absence of chest pain or ischaemic ECG changes. This is most obvious during the isovolumic periods, when the onset of long axis shortening may be so delayed during isovolumic contraction that it not only follows that of minor axis shortening, but results in long axis shortening during isovolumic relaxation.³⁵ Such continued inward movement is associated with ‘postejection’ mitral regurgitation and consequent shortening of left ventricular filling time at rest (Fig. 19.12, right).³³ This local mechanical dyssynchrony becomes even more exaggerated during pharmacological stress,³⁶ so that further shortening of left ventricular filling time at high heart rates (Fig. 19.13) may be enough to limit the normal increase in stroke volume during stress.

Measuring well-defined intervals in the cardiac cycle has long been established as a noninvasive means of assessing left ventricular function. The Tei index, described as ‘a Doppler index of combined systolic and diastolic performance’ is one such measure. It represents the sum of isovolumic contraction and relaxation times normalized to ejection time.⁴⁸ It thus depends on variables prev

iously shown to be closely related to abnormal activation. Moreover the inclusion of ejection time introduces noise and limits its applicability. A more sensitive measure is total isovolumic time (t-IVT), which can be readily measured using simple echo Doppler techniques and derived as [60 – (total ejection time+total filling time)]. (Fig. 19.14).⁴⁹ The duration of left ventricular filling time combined with the duration of left ventricular ejection time provides an indication of the effectiveness of global cardiac synchrony. Its reciprocal, the time in the cardiac cycle when the ventricle is neither ejecting nor filling (the isovolumic time or ‘wasted’ time) provides a useful method of expressing the effects of regional dyssynchrony on global cardiac function.⁵⁰ When t-IVT is expressed in terms of seconds per minute, it is independent of heart rate, which is an advantage when comparing changes in global dyssynchrony with time (i.e. between rest and stress, or between baseline assessment and follow-up).

Unlike many echo measures including ejection fraction, total isovolumic time is related to the amount of ventricular dyssynchrony, peak stress cardiac output, and exercise capacity. Patients with the longest total isovolumic times are those with the most ventricular dyssynchrony,⁵⁰ the lowest cardiac output at peak stress (Fig. 19.15a)⁵² and the lowest peak oxygen consumption during cardiopulmonary exercise testing (Fig. 19.15b).⁵³ Patients with the longest total isovolumic time (i.e. most global dyssynchrony) are potentially those most likely to benefit from cardiac resynchronization therapy (CRT).⁵⁴

Thus, simple echo Doppler measures of global cardiac dyssynchrony may have benefit in the expanding field of predicting responders to CRT, quantifying the degree of response, and optimizing pacemaker settings.

Echocardiography not only provides clinical measures and prognostic assessments in patients with HF but can also supply information to guide application of HF therapies.

Echocardiographic LVEF is an entry criterion in many clinical trials designed to assess the therapeutic effect of various medical therapies in HF, including ACE inhibitors, β-blockers, and aldosterone antagonists.^8,–10 A reduction in LVEF may highlight the detrimental effects on left ventricular function of cardiotoxic medications, including anthracycline chemotherapeutic agents.⁵⁵ A more detailed echocardiographic examination, assessing specifically left ventricular filling pattern and segmental incoordination, may demonstrate the beneficial effect of ACE inhibitors in off-loading the left ventricle, particularly in patients with raised left atrial pressure (restrictive filling pattern), reducing LVEDP, and unmasking segmental incoordination.³⁴

Strategies for implantable cardioverter-defibrillators (ICDs) rely on LVEF for selecting patients for the devices.¹¹ Repeat LVEF assessment at 30–40 days after myocardial infarction and after initiation of optimal HF medical therapy is necessary to determine candidacy for ICD.

CRT reduces mortality, improves functional status, and increases LVEF in patients with severe left ventricle disease.^56,–58 Current recommendations advocate that patients with LVEF 35% or less, moderate-to-severe HF symptoms, a widened QRS interval, and sinus rhythm should undergo CRT. Debate continues as to whether existing echo methods of assessing left ventricular dyssynchrony provide additional predictive value in determining those patients most likely to benefit from resynchronization.⁵⁹ The difficulty may lie in the type of echo measurement that is being used. In order for CRT to be successful, the baseline abnormality (regional dyssynchrony) not only needs to be present, but such regional dyssynchrony should also be haemodynamically limiting (i.e. result in global dyssynchrony). Indeed, patients with the most global dyssynchrony (long total isovolumic time 〉15 s/min and/or long interventricular delay 〉40 ms, as measured by the electromechanical delay between the right and left pre-ejection periods), have been shown to demonstrate significant clinical response to CRT.^54,58 Most studies, however, have concentrated on regional assessment of intraventricular dyssynchrony.

Intraventricular dyssynchrony may be measured using a variety of echo techniques (M-mode, tissue Doppler, tissue tracking, and three-dimensional imaging). Although the assessment of regional dyssynchrony has gained great impetus in the literature in recent years, the relation between specific areas of regional dyssynchrony and their effect on global dyssynchrony, particularly during exercise, remains undefined. Moreover, since the publication of the PROSPECT trial, the reproducibility of various echo techniques for quantifying intraventricular dyssynchrony across different echo institutions has been seriously questioned.⁶⁰ Despite difficulties with reproducibility, multiple methods for assessing intraventricular dyssynchrony are quoted in the literature, including:

Assuming it is useful to use an echo-derived mechanical index to decide whether a patient should have CRT, and despite reported difficulties with the reproducibility of assessment of regional left ventricular dyssynchrony using techniques such as described above, determining the precise site of mechanical delay, especially if epicardial lead placement is being considered, should be useful in a patient being considered for CRT. It would also be helpful in confirming that mechanical dyssynchrony is indeed the cause of a reduction in global left ventricular synchrony. Thus, when considering which echo index of dyssynchrony to use, a combination of both segmental and global measures is likely to produce the most useful information on both the degree and severity of mechanical dyssynchrony and its consequences on global left ventricular function. However, echo indices of dyssynchrony will only become credible and applicable after they have been shown to be predictive in large prospective randomized trials.

Continued presystolic mitral regurgitation in patients after implantation of a DDD or CRT pacing device(see Chapters 48 and 49) is associated with little or no clinical improvement. Echo Doppler techniques may be used to optimize the delay between pacing the right atrium and right ventricle (AV delay) in order to shorten or remove presystolic mitral regurgitation and thereby increase left ventricular filling time (Fig. 19.17).

The aim is to choose the shortest AV delay that still allows complete left ventricular filling by either the iterative method (whereby a long AV delay (e.g. 150 ms) is programmed on the pacemaker, the AV delay is then shortened in 20 ms stages until the A wave starts to be truncated, then the AV delay is gradually extended by 10-ms steps until the A wave is just complete) or the Ritter method (whereby a short AV delay (e.g. 50 ms) is programmed and the time from start QRS to end of A wave is measured (QAshort), then a long AV delay (e.g. 150 ms) is programmed and the time from start QRS to end of A wave (QAlong) is measured; the optimal delay is then calculated as ‘AVlong delay +QAlong – QAshort’). In theory, optimization of delay between pacing left and right ventricles (VV delay) with atriobiventricular pacemakers is possible, but no morbidity or mortality benefit has been documented for any of this. Moreover, optimization of pacemaker settings at rest takes no account of haemodynamic changes that occur during exercise or stress, which remains a major limitation of this technique.

Stunned or hibernating myocardium denotes viable but dysfunctional tissue. Increasing myocardial oxygen demand by stressing the heart with pharmacological agents (dobutamine or dipyridamole) can identify segments that are viable and potentially functional by inducing them to contract. Traditionally this requires qualitative assessment of wall motion score (whereby an akinetic segment becomes hypokinetic, or a hypokinetic segment thickens normally during low dose stress and then deteriorates again at high dose (biphasic response;⁶⁶ similar abnormalities may be quantitatively demonstrated using M-mode techniques, Fig. 19.18).⁶⁷

‘Functional’ mitral regurgitation is multifactorial in patients with HF, and may be due to dilatation of the mitral annulus, malcoaptation of the mitral valve leaflets, and/or tethering of the mitral valve leaflets from remodelling-induced displacement of one or both papillary muscles. Physiological stress echo may be useful in planning mitral valve repair, particularly when combined with three-dimensional assessment during stress, since surgery has demonstrated efficacy even in advanced HF.⁶⁸

Ventricular assist devices (a left ventricular assist device, LVAD or biventricular assist device, bi-VAD) are commonly used as bridges to heart transplantation or ventricular recovery. The pump sucks from the ventricle and ejects directly into the aorta, thus reducing wall stress and allowing the myocardium to recover. Echo can detect significant valvular disease, intracardiac shunts, significant right ventricular disease, or pulmonary hypertension preoperatively, and thrombus formation within the VAD or other causes of inflow cannula obstruction postoperatively.

Many attempts have been made to assess the echocardiographic predictors of acute rejection, as the noninvasive diagnosis of episodes of rejection might obviate the need for repeated myocardial biopsy. Echocardiographic changes associated with rejection after cardiac transplantation include an increase in posterior wall thickness, an increase in left ventricular mass, and a decrease in diastolic compliance, with associated development of a restrictive mitral inflow pattern. Unfortunately, most of these changes indicate advanced rejection and therefore are of limited use as screening tools.

Echocardiographic findings in dilated cardiomyopathy include left ventricular dilatation, increased left ventricular end-diastolic volume, LVEF less than 40%, functional mitral regurgitation to varying degrees (Fig. 19.19), reduced left ventricular long axis amplitude, global and regional dyssynchrony, and pulmonary hypertension. There is no definite echocardiographic picture that differentiates different stages, but as the left ventricle becomes more dilated, wall stress increases (Laplace’s law), resulting in both increased sphericity and myocardial oxygen consumption. RWMA are not specific to ischaemic cardiomyopathy and may be present in idiopathic cardiomypathy; dobutamine stress echo may be useful in differentiating between the two.⁶⁷

The presence of right ventricular enlargement and dysfunction is variable but a poor prognostic sign if present. Tricuspid regurgitation is common and varies in severity.

The left ventricular filling pattern is highly variable in dilated cardiomyopathy, whether idiopathic or ischaemic. The early diastolic E wave is often dominant, and is associated with a short isovolumic relaxation time and a third heart sound which strongly suggests elevated LVEDP. Alternatively, ventricular filling may occur entirely during atrial systole, and be associated with a long isovolumic relaxation time and a fourth heart sound, which strongly suggests low or normal LVEDP. Finally, with sinus tachycardia, filling time at rest may be so short that only a single filling peak is recorded, consisting of superimposed E and A waves, and accompanied by a summation gallop. As discussed above, left ventricular filling time may be shortened even further during stress, and may become the rate-limiting step during exercise.

The echo pattern in hypertrophic cardiomyopathy is highly variable; there may be disproportionate septal hypertrophy in relation to the left ventricle posterior wall (ratio 〉 1.3:1.0), concentric LVH, in which the septal and posterior walls are equal in thickness, or hypertrophy confirmed to the apical segments. Significant left ventricular outflow tract obstruction is usual if asymmetric septal hypertrophy and systolic anterior motion of the mitral valve (SAM) are present (Fig. 19.20), but midcavity obstruction is also common, particularly when there is concentric LVH and the patient is hypovolaemic or on inotropes. Colour Doppler is useful for identifying the level of obstruction.

This is an inherited condition characterized by marked trabeculation, usually within the left ventricular apex. LVEF may be reduced, and areas of noncompaction may become substrates for left-sided thrombi and arrhythmias. To identify noncompaction, left-sided contrast agents are usually required. In apical views the trabeculation is usually seen as a partially contrast-filled layer. A ratio of 〉2:1 noncompacted (trabeculations) myocardium to compacted (normal) myocardium at end systole suggests left ventricular noncompaction.

Restrictive cardiomyopathy is a group of disorders characterized by limitation of left ventricular filling caused by increased left ventricular stiffness (decreased left ventricular compliance) during mid and late diastole. Amyloid infiltration is present in about half of these cases, and the aetiology is often undefined in the remainder. Left ventricular cavity size is usually normal, although LVEF may be significantly reduced. Biatrial enlargement is usually present and peak inflow velocity during early diastole is often normal, but its duration is short, so acceleration and deceleration times are reduced, reflecting the combined effects of increased myocardial stiffness and a high left atrial pressure.⁴³ Restrictive filling does not represent a specific diagnosis, as patients with dilated cardiomyopathy or severe LVH may show restrictive physiology. Regardless of the underlying aetiology, these features regress when the left atrial pressure falls.

Right ventricular function has significant clinical relevance since it is highly related to prognosis⁶⁹ and has an important role in determining exercise capacity.⁷⁰ Assessing the size of the right ventricle may be difficult, because of its complex shape, but measuring end-diastolic length, the diameter at midcavity, and the diameter of the tricuspid annulus usually suffice (the latter should be 〈40 mm). Right ventricular function is assessed qualitatively and quantitatively, the latter by measuring tricuspid annular motion using M-mode (normal right ventricular amplitude is 15–20 mm in the absence of severe tricuspid regurgitation or pulmonary hypertension).

Identifying right ventricular pressure or volume overload can aid clinical assessment of right heart function. Although often considered together, they usually represent two different initial pathologies; right ventricular volume overload suggests right-sided valvular regurgitation or a right-to-left shunt. Pressure overload suggests pulmonary hypertension or pulmonary stenosis. Pressure overload can develop from volume overload, and occasionally vice versa, in which case features of both will be present. Assessing right ventricular size, free wall thickness, and septal motion are key since volume overload usually leads to increased cavity size and pressure overload usually leads to increased wall thickness (though the two findings may coexist), and volume overload is related to a flattened septum in diastole, whereas pressure overload is associated with a flattened septum in both systole and diastole.

Severe tricuspid regurgitation may be present in late left ventricular disease or if the primary pathology involves the right ventricle. In this case, the right atrium and right ventricle are usually both dilated, the right atrial pressure is increased, and the peak right AV pressure drop declines. The decline in pressure drop should not be taken as a sign of reduction in pulmonary artery pressure, particularly in patients who show clinical deterioration, but as a sign of increasing right atrial pressure. Restrictive right ventricular filling physiology is associated with poor prognosis in a fashion similar to left ventricular haemodynamics.

A rare, but clinically important, cause of HF is pericardial disease, and chronic constrictive pericarditis is an example of pure diastolic HF with a low cardiac output state. It is characterized by a thickened, adherent pericardium (Fig. 19.21) that restricts ventricular filling and limits chamber expansion and maximal diastolic volumes. Elevated filling pressures are required to maintain adequate cardiac output. End-diastolic pressures in all heart chambers are usually elevated and equalized. Compensatory mechanisms are activated but may ultimately fail, leading to elevated venous pressure, salt and water retention, and reduced cardiac output.

The clinical similarity between constrictive pericarditis and restrictive cardiomyopathy may make the differential diagnosis difficult in some cases, since both have stiff and incompliant left ventricle in late diastole and the left ventricle is unable to fill without a significant rise in LVEDP. However, constrictive pericarditis is an extracardiac constraint while restrictive cardiomyopathy is an intrinsic disease of the myocardium. Thus motion of the ventricular long axes and associated influence on vena caval flow help differentiate between the two conditions.

Echocardiography is the single most useful noninvasive imaging tool in the HF population. It readily identifies patterns of disease, rapidly differentiating myocardial from structural or pericardial heart disease, and the dilated left ventricle from the hypertrophied left ventricle in a widely available clinical setting. More subtle echo techniques quantify the degree of left ventricular impairment, determine the presence of RWMA, differentiate restrictive left ventricular physiology from reduced early diastolic filling rates, quantify the degree of functional mitral regurgitation and pulmonary hypertension, identify occult right ventricular disease, and define the effects of abnormal activation on ventricular function. Echocardiography not only provides insights into the pathophysiological mechanisms underlying the various aetiologies of HF, but also identifies patients at high risk for cardiovascular morbidity and mortality and provides important data for therapeutic decision-making, including defining candidacy for medications, implantable cardiac devices, surgical procedures, and resynchronization. Thus, echocardiography continues to play a central role in the diagnosis and management of patients with HF.