The assessment of left ventricular (LV) systolic function is often the most important information obtained during clinical echocardiography. Although LV systolic function may be visually estimated in many patients with or without contrast opacification, technically difficult patients may require alternative methods for evaluating LV systolic function. In this review, the authors describe several surrogate echocardiographic methods that might be helpful for the evaluation of LV systolic function in patients with poor image quality, including endocardial border delineation by contrast agents, mitral annular plane systolic excursion, mitral annular velocity derived from tissue Doppler, systolic time intervals, mitral regurgitation–derived LV dP/dt, and estimation of cardiac output by Doppler echocardiography. After a short introduction to the various issues involved, the authors propose a method for suitable measurement. In addition, indications and clinical implications, as well as limitations, of the different methods are discussed.
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Contrast Echocardiography
Contrast echocardiography using ultrasound contrast agents plays an essential role in clinical diagnosis in patients with technically suboptimal echocardiographic images.
Contrast Agents
Contrast echocardiography involves the interaction of microscopic gas bubbles with ultrasonic waves to enhance the recognition of the blood pool and/or the blood-tissue interface. The first agents capable of left-heart contrast after intravenous injection (first-generation agents) were air bubbles stabilized by encapsulation (Albunex; Molecular Biosystems, Inc., San Diego, CA) or by adherence to microparticles (Levovist; Bayer Schering Pharma AG, Berlin, Germany). In second-generation agents, replacing air with a low-solubility fluorocarbon gas stabilized the bubbles (Optison, GE Healthcare, Waukesha, WI; Definity, Lantheus Medical Imaging, North Billerica, MA; SonoVue, Bracco Diagnostics Inc., Princeton, NJ), further increasing the duration of the contrast effect. The aforementioned agents are untargeted microbubbles, and targeted microbubbles are presently in preclinical development.
Implementation of Contrast Agents
Details of the implementation of contrast agent, including joint training of physicians, sonographers, and nurses, have been introduced in recent guidelines. Briefly, contrast enhancement is indicated in difficult-to-image patients at rest when echocardiographic image quality does not permit the adequate assessment of cardiac structure and function. Specifically, contrast enhancement for stress echocardiography is not recommended for all patients but should be considered on a case-by-case basis, depending on image quality. To ensure quality control and maximize benefit to patients, the American Society of Echocardiography recommends that contrast echocardiography be performed by appropriately trained cardiac sonographers and physicians with level 2 or level 3 training in laboratories that have been successful in establishing contrast agent use.
Optimization and Clinical Applications
The mechanical index reflects the output acoustic power. Standard clinical echocardiography imaging uses a mechanical index of about 1.0, but a lower setting (<0.6) is usually optimal for LV opacification during contrast echocardiography to avoid bubble destruction. Common causes of setting artifacts include inadequate focus position, inadequate ultrasound transmit frequency, and excessive receive gain. Tissue signals in the left ventricle may not be distinguishable from the contrast signals, because of inadequate contrast dose (the so-called anticontrast effect) and can be avoided by injecting a slightly larger contrast dose. Attenuation is particularly problematic in parasternal windows, in which dense opacification of the right ventricle may obviate visualization of the left ventricle, and can be prevented by using apical views, in which attenuation is lowest and usually subsides by waiting for contrast washout. Attenuation can also be caused by rapid infusion or high-concentration contrast agent. Instead of a bolus, continuous slow infusion and slow flush are recommended. Swirling artifacts may result from high mechanical index, high frame rate, insufficient contrast agent, or LV dysfunction with low flow at the apex. Moving the focus position toward the base may help avoid attenuation and swirling. Adjusting the transducer position along the rib space or holding respiration during image acquisition can help reduce chest wall artifacts and wall motion artifacts.
Contrast agent use is particularly valuable for the evaluation of LV structure and function in difficult-to-image patients with reduced image quality for rest or stress echocardiography. It can improve endocardial visualization and the assessment of LV structure and function and reduce variability and increase accuracy in LV volume and ejection fraction (EF) measurement. Contrast agent is recommended when two or more adjacent poorly visualized segments are seen on standard echocardiography. Contrast agent use also allows accurate assessment of LV volumes and EF in the intensive care unit when standard tissue harmonic imaging does not provide adequate cardiac structural definition. Stress echocardiography, in combination with contrast agent use, can obtain diagnostic assessment of segmental motion and thickening at rest and stress. Other suggested applications include confirming or excluding LV structural abnormalities (apical hypertrophic cardiomyopathy, LV noncompaction, LV aneurysm [ Figure 1 and Video 1 ; available at www.onlinejase.com ], pseudoaneurysm, and myocardial rupture) and intracardiac masses (tumors and/or thrombi).
Safety and Limitations
A large number of studies have proved that contrast echocardiography is safe in clinical practice. A large retrospective analysis of 18,000 patients showed that there was no significant difference in mortality between patients who received contrast and those who did not in the acute setting. However, serious allergic reactions have been observed at a very low incidence (1 in 12,000 to 1 in 15,000). As shown in the updated guidelines on the safety of echocardiographic contrast agents of the US Food and Drug Administration in June 2008, contraindications to perflutren-containing ultrasound contrast agents (Definity and Optison) include (1) right-to-left, bidirectional, or transient right-to-left cardiac shunts; (2) hypersensitivity to perflutren; and (3) hypersensitivity to blood, blood products, or albumin (Optison only). Additional contraindications include acute myocardial infarction, worsening or unstable heart failure, serious ventricular arrhythmias or high risk for arrhythmia, respiratory failure, severe emphysema, pulmonary emboli, or other conditions that cause pulmonary hypertension.
Contrast Echocardiography
Contrast echocardiography using ultrasound contrast agents plays an essential role in clinical diagnosis in patients with technically suboptimal echocardiographic images.
Contrast Agents
Contrast echocardiography involves the interaction of microscopic gas bubbles with ultrasonic waves to enhance the recognition of the blood pool and/or the blood-tissue interface. The first agents capable of left-heart contrast after intravenous injection (first-generation agents) were air bubbles stabilized by encapsulation (Albunex; Molecular Biosystems, Inc., San Diego, CA) or by adherence to microparticles (Levovist; Bayer Schering Pharma AG, Berlin, Germany). In second-generation agents, replacing air with a low-solubility fluorocarbon gas stabilized the bubbles (Optison, GE Healthcare, Waukesha, WI; Definity, Lantheus Medical Imaging, North Billerica, MA; SonoVue, Bracco Diagnostics Inc., Princeton, NJ), further increasing the duration of the contrast effect. The aforementioned agents are untargeted microbubbles, and targeted microbubbles are presently in preclinical development.
Implementation of Contrast Agents
Details of the implementation of contrast agent, including joint training of physicians, sonographers, and nurses, have been introduced in recent guidelines. Briefly, contrast enhancement is indicated in difficult-to-image patients at rest when echocardiographic image quality does not permit the adequate assessment of cardiac structure and function. Specifically, contrast enhancement for stress echocardiography is not recommended for all patients but should be considered on a case-by-case basis, depending on image quality. To ensure quality control and maximize benefit to patients, the American Society of Echocardiography recommends that contrast echocardiography be performed by appropriately trained cardiac sonographers and physicians with level 2 or level 3 training in laboratories that have been successful in establishing contrast agent use.
Optimization and Clinical Applications
The mechanical index reflects the output acoustic power. Standard clinical echocardiography imaging uses a mechanical index of about 1.0, but a lower setting (<0.6) is usually optimal for LV opacification during contrast echocardiography to avoid bubble destruction. Common causes of setting artifacts include inadequate focus position, inadequate ultrasound transmit frequency, and excessive receive gain. Tissue signals in the left ventricle may not be distinguishable from the contrast signals, because of inadequate contrast dose (the so-called anticontrast effect) and can be avoided by injecting a slightly larger contrast dose. Attenuation is particularly problematic in parasternal windows, in which dense opacification of the right ventricle may obviate visualization of the left ventricle, and can be prevented by using apical views, in which attenuation is lowest and usually subsides by waiting for contrast washout. Attenuation can also be caused by rapid infusion or high-concentration contrast agent. Instead of a bolus, continuous slow infusion and slow flush are recommended. Swirling artifacts may result from high mechanical index, high frame rate, insufficient contrast agent, or LV dysfunction with low flow at the apex. Moving the focus position toward the base may help avoid attenuation and swirling. Adjusting the transducer position along the rib space or holding respiration during image acquisition can help reduce chest wall artifacts and wall motion artifacts.
Contrast agent use is particularly valuable for the evaluation of LV structure and function in difficult-to-image patients with reduced image quality for rest or stress echocardiography. It can improve endocardial visualization and the assessment of LV structure and function and reduce variability and increase accuracy in LV volume and ejection fraction (EF) measurement. Contrast agent is recommended when two or more adjacent poorly visualized segments are seen on standard echocardiography. Contrast agent use also allows accurate assessment of LV volumes and EF in the intensive care unit when standard tissue harmonic imaging does not provide adequate cardiac structural definition. Stress echocardiography, in combination with contrast agent use, can obtain diagnostic assessment of segmental motion and thickening at rest and stress. Other suggested applications include confirming or excluding LV structural abnormalities (apical hypertrophic cardiomyopathy, LV noncompaction, LV aneurysm [ Figure 1 and Video 1 ; available at www.onlinejase.com ], pseudoaneurysm, and myocardial rupture) and intracardiac masses (tumors and/or thrombi).
Safety and Limitations
A large number of studies have proved that contrast echocardiography is safe in clinical practice. A large retrospective analysis of 18,000 patients showed that there was no significant difference in mortality between patients who received contrast and those who did not in the acute setting. However, serious allergic reactions have been observed at a very low incidence (1 in 12,000 to 1 in 15,000). As shown in the updated guidelines on the safety of echocardiographic contrast agents of the US Food and Drug Administration in June 2008, contraindications to perflutren-containing ultrasound contrast agents (Definity and Optison) include (1) right-to-left, bidirectional, or transient right-to-left cardiac shunts; (2) hypersensitivity to perflutren; and (3) hypersensitivity to blood, blood products, or albumin (Optison only). Additional contraindications include acute myocardial infarction, worsening or unstable heart failure, serious ventricular arrhythmias or high risk for arrhythmia, respiratory failure, severe emphysema, pulmonary emboli, or other conditions that cause pulmonary hypertension.
Mitral Annular Plane Systolic Excursion
LV longitudinal shortening is a sensitive parameter reflecting cardiac pump function and can be evaluated by measuring long-axis mitral annular plane systolic excursion (MAPSE). The measurement of M-mode-derived MAPSE does not require high imaging quality, because of the high echogenicity in the atrioventricular annulus.
Measurement
MAPSE can be measured from four sites of the atrioventricular plane corresponding to the septal, lateral, anterior, and posterior walls using the apical four-chamber and two-chamber views on M-mode echocardiography. In healthy hearts, the values of lateral MAPSE are usually somewhat higher than those of septal MAPSE. Mondillo et al. also demonstrated that MAPSE was lower at the septum and anterior wall in comparison with the lateral and inferior levels in healthy middle-aged individuals. The M-mode cursor should be aligned parallel to the LV walls. The systolic excursion of the mitral annulus should be measured from the lowest point at end-diastole to aortic valve closure (the end of the T wave on the electrocardiogram; Figure 2 ).
Clinical Implications
The average normal value of MAPSE derived from previous studies for the four annular regions (septal, anterior, lateral, and posterior) ranges from 12 to 15 mm. MAPSE < 8 mm was associated with a depressed LV EF (<50%), with specificity of 82% and sensitivity of 98%. Mean MAPSE ≥ 10 mm was linked with preserved EF (≥55%), with sensitivity of 90% to 92% and specificity of 87%. In addition, mean MAPSE < 7 mm could detect an EF < 30% with sensitivity of 92% and specificity of 67% in patients with dilated cardiomyopathy with severe congestive heart failure. A recent study by Matos et al. showed that MAPSE measurement by an untrained observer was a highly accurate predictor of EF determined by an expert echocardiographer.
Limitations
The association between MAPSE and EF is valid only in normal or dilated left ventricles, whereas the correlation is rather poor in patients with LV hypertrophy. Another limitation of this parameter is that small localized abnormalities (i.e., small areas of fibrosis) cannot be detected, because MAPSE can evaluate only the longitudinal function of the entire LV wall and is unable to evaluate segmental function.
Mitral Annular Velocity Derived from Tissue Doppler
Doppler tissue imaging (DTI) has become an established component of the diagnostic ultrasound examination. This technique detects low-velocity frequency shifts of ultrasound waves to calculate myocardial velocity. DTI offers the promise of an objective measure to quantify regional and global LV function through the assessment of myocardial velocity data. The velocity traces can be extracted from the basal segments of the left ventricle in most patients, even when the overall image quality is bad. The decrease in systolic velocity on pulsed DTI correlated significantly with both systolic shortening ( r = 0.90) and regional myocardial blood flow ( r = 0.96) in patients with reduced coronary blood flow.
Measurement
The measurements of systolic mitral annular velocity (Sm) should be taken at the peak of myocardial systolic velocity, in accordance with recent guidelines. In the apical four-chamber view, the DTI cursor should be placed at the septal side of the mitral annulus in such a way that the mitral annulus at the septum moved along the sample volume line. In normal myocardium, a Doppler velocity range of −20 to 20 cm/sec is recommended to avoid aliasing. As shown in Figure 3 , three major velocities can be recorded: the positive systolic velocity when the mitral ring moves toward the apex (Sm) and two negative diastolic velocities when the mitral annulus moves away from the apex (one during the early phase of diastole [Em] and another in the late phase of diastole [Am]). By moving the sample volume to the lateral site of the mitral annulus, systolic and diastolic velocities of the LV lateral wall can be recorded. These velocities can be extracted by pulsed-wave tissue Doppler and in addition also by color tissue Doppler. It is important to note that color tissue Doppler data are mean data, and extracted velocities are approximately 20% lower than the pulsed-wave tissue Doppler velocities. Pulsed tissue Doppler–derived Sm measurement is more often used in daily practice. Pulsed tissue Doppler–derived Sm was significantly lower at the septum (8.3 ± 1.7 cm/sec) than at the inferior (9.5 ± 1.9 cm/sec) and lateral (9.9 ± 2.4 cm/sec) levels in healthy middle-aged individuals.
Clinical Implications
Tissue Doppler data can be rapidly acquired in almost all patients for the estimation of global LV function. Mitral annular velocity is also a quite sensitive indicator for inotropic stimulation–induced alterations in LV contractility. LV function assessment by mitral annular velocity on DTI is valuable especially when endocardial delineation is suboptimal. Ruan and Nagueh showed that Sm had the best correlation with LV EF ( r = 0.65, P < .03), and Sm < 7 cm/sec was the most accurate parameter in identifying patients with LV EFs < 45% (sensitivity, 93%; specificity, 87%). Sm was also a strong predictor of cardiac mortality or rehospitalization for worsening of chronic heart failure in patients with LV dysfunction. Nikitin et al. found that DTI-derived Sm < 2.8 cm/sec was associated with worse survival in patients with chronic heart failure and LV EFs < 45%.
Limitations
DTI only quantifies myocardial motion. It cannot differentiate whether velocities are caused by active or passive movement, so global cardiac motion and tethering effects of adjacent myocardium may result in “false” velocity increases of dysfunctional segments.
Systolic Time Intervals
Systolic time intervals can provide useful information concerning the performance of the left ventricle. Thus, isovolumetric contraction time, preejection period (PEP), LV ejection time (ET), and the PEP/LV ET index have been studied extensively as measures of cardiac systolic function. More recently, a combined myocardial performance index (termed the Tei index, the sum of isovolumetric contraction time and isovolumetric relaxation time divided by LV ET) was introduced and serves as a clinically useful parameter for analyzing global cardiac function. The longer the isovolumetric phases, the higher the Tei index and the worse the ventricular performance. The index is easily measured, noninvasive, and reproducible and is rather independent of heart rate and systolic or diastolic blood pressure. It can be used for LV and right ventricular function even when image quality is poor.
Measurement
The PEP consist of electromechanical delay and the isovolumetric contraction time, which is the time interval between the start of ventricular depolarization and the moment of aortic valve opening. The LV ET is defined as the time interval of LV ejection, which occurs between the opening of the aortic valve and its closure. A healthy heart exhibits a short PEP and a long ET, while myocardial dysfunction is typically evidenced by prolonged PEP and shortened LV ET. The Tei index can be measured by pulsed Doppler as well as by DTI. The Tei index can be easily derived using conventional pulsed Doppler echocardiography, as described by Tei et al. The mitral inflow velocity is recorded from apical four-chamber views, with the sample volume positioned at the tips of the mitral leaflets during diastole. The LV outflow tract (LVOT) velocity is recorded from apical long-axis views with the sample volume positioned just below the aortic valve. The index is defined by the equation ( a − b )/ b , where a represents the interval between the cessation and onset of mitral inflow, and b represents the ET of the LV outflow ( Figure 4 A). DTI has also been used to calculate the Tei index, which correlates well with pulsed Doppler measurements. All interval measurements by DTI can be performed within one cardiac cycle, as illustrated in Figure 4 B. The Tei index is calculated as ( a ′− b ′)/ b ′, where a ′ represents the interval from the end of Am wave to the onset of the Em wave, and b ′ represents the time from the onset to the end of the Sm wave. The mean normal values of the Tei index for the left ventricle by the pulsed Doppler and DTI methods are 0.39 ± 0.05 and 0.35 ± 0.09, respectively. In adults, LV indexes < 0.40 are considered normal.
