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Systolic Dysfunction in Heart Failure with Normal Ejection Fraction: Speckle-Tracking Echocardiography
Systolic Dysfunction in Heart Failure with Normal Ejection Fraction: Speckle-Tracking Echocardiography Thor Edvardsen, Thomas Helle-Valle, and Otto A. Smiseth
Left ventricular (LV) ejection fraction (EF) and LV end-systolic volumes are important measures of LV global function. However, in many patients with symptoms of heart failure, these measures are within normal limits. This condition is classified as heart failure with normal ejection fraction (HFNEF). Reduced EF and increased end-systolic volume, however, require impaired function in a number of LV segments. Therefore, apparently normal systolic function in HFNEF may reflect limited sensitivity of global EF, and assessment of regional systolic function may provide important diagnostic information. The recently introduced method, speckle-tracking echocardiography (STE), represents a simplified, objective, and angle-independent modality for quantification of regional myocardial deformation. The software uses conventional gray-scale B-mode recordings and tracks myocardial speckles, which serve as natural acoustic markers. Radial and longitudinal myocardial deformation can be measured simultaneously from long-axis recordings, radial and circumferential deformation from short-axis recordings, and LV torsion from assessment of apical and basal short-axis rotation. Experimental and clinical studies have demonstrated that the STE method can assess myocardial function accurately in healthy subjects in the settings of acute and chronic ischemia, dyssynchrony, and cardiomyopathy. So far, no STE studies have been performed regarding HFNEF. The purpose of this article is therefore to illustrate the potential of this novel method. n 2006 Published by Elsevier Inc.
L
eft ventricular (LV) function has traditionally been evaluated noninvasively by global measures as left ventricular ejection fraction (LVEF) and LV end-systolic volume. These variables can relatively easily be obtained by
echocardiography, nuclear techniques and magnetic resonance imaging (MRI). The assessment of LVEF is important for diagnostics, prognosis and selection of treatment. Left ventricular endsystolic volume has been demonstrated to be even more useful for prognosis after myocardial infarction than LVEF.1 Many patients with symptoms of heart failure have, however, ejection fractions (EFs) and LV volumes which are regarded as normal.2 This condition has traditionally been classified as diastolic heart failure and, more recently, as heart failure with normal ejection fraction (HFNEF).3,4 Growing evidence suggest that the use of recent progress in echocardiographic techniques can reveal that these patients have abnormal systolic function.
Regional LV Function In principle, global LVEF reflects the sum of all regional shortening in the left ventricle. Impairment of regional function, however, does not cause reduction in global EF unless several segments are involved. Therefore, methods that measure LV regional function could be a more sensitive than global EF to identify systolic dysfunction. Regional myocardial function by echocardiography is usually evaluated by visual assessment of wall motion using 2-dimensional
From the Department of Cardiology, Rikshospitalet University Hospital, University of Oslo, Oslo, Norway. Address reprint requests to Otto A. Smiseth, MD, PhD, Department of Cardiology, Rikshospitalet University Hospital, N-0027 Oslo, Norway. E-mail: [email protected] 0033-0620/$ - see front matter n 2006 Published by Elsevier Inc. doi:10.1016/j.pcad.2006.08.008
Progress in Cardiovascular Diseases, Vol. 49, No. 3 (November/December), 2006: pp 207-214
207
208
EDVARDSEN ET AL
Fig 1. Speckle-tracking echocardiography: STE measures strain by tracking speckles in gray-scale echocardiographic images. A part of the myocardium (green box) from a left ventricular 4 chamber view is enlarged to visualize the speckles. The software allows tracking of speckles in multiple directions (arrows).
echocardiography. This approach, however, suffers from being subjective and provides only semiquantitative data. Furthermore, visual assessment has limited ability to detect more subtle changes in function and changes in timing of myocardial motion throughout systole and diastole.
Tissue Doppler and Strain Rate Imaging Echocardiographic modalities for objective quantification of global and regional function have recently been developed. Assessment of tissue velocity, strain, and strain rate by tissue Doppler imaging (TDI) have proved to be more accurate methods than visual evaluation of global and regional function.5-7 Recently, peak early diastolic myocardial velocity has emerged as a useful marker of diastolic function.8,9 Furthermore, TDI-derived measures have been used in recent studies to show that systolic long-axis function is
Fig 2. Validation of strain by STE vs sonomicrometry: experimental data which confirms the ability of STE to accurately measure myocardial strain. Adapted with permission from J Am Coll Cardiol 2006;47:789-793.
reduced in many patients with presumable bisolatedQ diastolic heart failure.10-12 Since subendocardial myocardial fibers are mainly responsible for long-axis contraction, longitudinal function is considered an early systolic marker of disease and more susceptible to effects of fibrosis, hypertrophy, and ischemia.4 Myocardial strain by TDI is superior to myocardial velocities and wall motion score in assessment of regional ischemia, according to experimental and clinical studies.7,13-15 To our knowledge, however, there are no published reports that have compared these techniques in patients with HFNEF. The angle dependency is a serious limitation of all Doppler-based techniques including Dopplerderived myocardial velocities and strain.7 Therefore, it is essential that the ultrasound beam is aligned parallel to the LV wall in long-axis imaging and perpendicular to the wall for radial measurements in the short axis. This implies that strain measurements from myocardial segments
Fig 3. A, Transmitral flow velocities and myocardial function in a 62-year-old man with a normal heart: LVEF was 60%. Transmitral flow shows normal E/A ratio (upper left panel), and tissue Doppler shows normal systolic mitral annulus velocities of 5 to 6 cm/s (upper right panel). Speckle-tracking echocardiography shows uniform strains in the different LV segments, with systolic strain values from 17% to 27%, confirming normal systolic function. B, Diastolic dysfunction in 78-year-old man: the patient complains about dyspnea on exertion. Echocardiography showed LV hypertrophy, whereas coronary angiography demonstrated no significant stenoses. Ejection fraction was 55% by the biplane Simpson method. Transmitral flow shows inverted E/A ratio and prolonged E deceleration time (290 milliseconds) (upper left panel). Tissue Doppler shows reduced mitral annulus EV velocity, recorded at the septal and lateral part of the mitral annulus (upper right panel). Furthermore, peak systolic velocity at the lateral part of the mitral annulus is decreased (3.8 m/s). Regional longitudinal strains are displayed in the lower right panel and demonstrates marked nonuniformity of systolic strain. The colors of the traces correspond to locations with same color on the corresponding 2-dimensional image.
SYSTOLIC DYSFUNCTION IN HEART FAILURE WITH NORMAL EJECTION FRACTION
209
210 close to the LV apical curvature can not be reliably assessed by TDI.13 The angle dependency is thus a significant limitation when studying patients with coronary artery disease as pathology may be most pronounced in the apical segments.
Assessment of LV Function by speckle-tracking echocardiography Speckle-tracking echocardiography (STE) has been introduced as a method for angle-independent quantification of myocardial strain (Fig 1).16 Speckles are natural acoustic markers that occur as small and bright elements in conventional grayscale ultrasound images.17 The speckles are the result of constructive and destructive interference of ultrasound, back-scattered from structures smaller than a wavelength of ultrasound.16,18 These speckles are distributed equally around in the myocardium on the ultrasound image and can be identified and followed in consecutive frames during the heart cycles. A different software that has the ability to assess myocardial strain, strain rate, velocities and displacement from these speckles has recently been released.17,19-22 Measurements can be done simultaneously from multiple regions of interest (ROIs) within an image plane from conventional gray-scale B-mode recordings. The distance between selected speckles is measured within a predefined myocardial area as a function of time, and parameters of myocardial deformation can be calculated. This is in contrast to Doppler-based measurements where the sample volume is a fixed area in space, and all measurements are done with reference to an external point (the transducer). Strain measurements from the speckle-tracking technique are therefore direct measures of myocardial deformation while TDI calculates strain by integrating strain rate. Another important advantage by using the new technique is independence of insonation angle and cardiac translation.20,21,23 The different speckle-tracking algorithms have been validated in experimental and human studies and found to be within clinically acceptable ranges.19,20,21,24,25 These studies include left ventricles with normal systolic function, with acute or chronic ischemia, asynchrony, and different loading and inotropic conditions. It has been shown that 2 deformation components can be estimated simultaneously and accurately
EDVARDSEN ET AL
(eg, radial and longitudinal strain) and that analyses by STE is less time-consuming than Doppler-based analyses.19,21 Speckle-tracking echocardiography has also been used to predict response to cardiac resynchronization therapy and a recent clinical study demonstrated that assessment of radial strain by STE may quantify dyssynchrony and predict immediate and longterm response to cardiac resynchronization therapy.26 The authors concluded that strain by speckle tracking has potential for clinical
Fig 4. Circumferential strain by STE. A, Circumferential strain from the apical LV level in a healthy individual. Note the homogenous circumferential distribution of normal systolic strain. B, Circumferential strain at the LV apical level in a patient with a LADrelated myocardial infarction. Please note reduced systolic shortening (strain) in the anterior, septal, and inferior segments, with marked postsystolic contraction (white arrows). In addition, in the septal segments, there is early systolic stretching indicating dyskines (red arrow). Normal contraction is seen in the lateral segments.
SYSTOLIC DYSFUNCTION IN HEART FAILURE WITH NORMAL EJECTION FRACTION
Fig 5. A, Schematic representation of LV shortening and torsion from end-diastole to end-systole. Courtesy of Stein Inge Rabben. B, End-diastolic and endsystolic apical 2D gray-scale echocardiographic images from an animal experiment: the ROIs (white squares) and best-fitted circle are indicated. The thin dashed arrows point at ROIs, and the thick solid arrows point at sonomicrometric crystals. The change in position of arrows from end diastole to end systole confirms counterclockwise rotation. Adapted with permission from Circ 2005;112:3149-3156.
application. In addition, the speckle-tracking method can be used for assessment of myocardial velocities and mitral annulus displacement.17 The results, so far, indicate strongly that strain measurements based on speckle tracking are able to reflect real myocardial deformation and also detect small alterations in systolic function. Fig 2 demonstrates the relationship between systolic strain by STE and sonomicrometry in an experimental study. In principle, STE provides a direct measure of myocardial deformation and appears to be a more robust method than Doppler-based strain imaging, which estimates strain as the time integral of spatial velocity gradients.11,27 The diagnostic value of STE in clinical practice, however, remains to be proven in appropriately designed trials. We are at an early stage of
211
development of the STE technology, and the purpose of this article is only to illustrate possible future applications of the technology. In Figs 3 and 4, we demonstrate how STE can identify regional myocardial dysfunction. In the setting of HFNEF, it may be of interest to quantify regional differences in systolic shortening and to identify postsystolic contractions. Another promising modality of strain measurements from speckle tracking is the ability to assess circumferential strain (Fig 4).24 This is possible because of independency of insonation angle. Assessment of circumferential strain by MRI tagging has, for long, been the preferred measure of regional deformation.28-30 Recently, it has also been demonstrated that circumferential strain by MRI tagging is able to detect subclinical changes in LV function in a large population group free of clinical signs of cardiovascular disease.31-33 Left ventricular torsion can be assessed accurately by STE (Figs 5 and 6).20,23,34 By measuring apical and basal rotation from LV short-axis recordings (Figs 5 and 6), torsion has been explored in both clinical and experimental studies (Fig 7). In a recently published clinical study on type I diabetic patients, increased LV peak systolic torsion and torsion rate was demonstrated in patients with normal EF when compared with healthy subjects.35 Reduced left ventricular twist/torsion has also been suggested
Fig 6. A representative example of regional LV rotation by STE at the apical LV level in a healthy individual. Please note the homogenous distribution of rotation between segments. The direction of rotation at the apex is counterclockwise when viewed from the LV apex.
212
EDVARDSEN ET AL
Fig 7. Left ventricular rotation and torsion—comparison between STE (solid lines) and sonomicrometry (dashed lines). Clockwise rotation is represented by positive numbers. Torsion was calculated as the difference between rotation at apex and base. Please note that LV rotation and torsion were increased by dobutamine infusion and reduced by ischemia. Adapted with permission from Circ 2005;112:3149-3156.
to have impact on LV suction.36 These findings can now be further explored by STE.
axis views. This makes STE suitable for the assessment of systolic LV function in patients with heart failure with a normal ejection fraction.
Limitations Regarding STE
References
The time resolution in studies using STE has been in the range of 60 to 100 frames per second to optimize the speckle quality. Higher frame rates may be required in order to obtain reliable results regarding peak systolic myocardial strain rate and velocity. At present, few studies exist, and the clinical value of this novel method needs to be better defined.
1. White HD, Norris RM, Brown MA, et al: Left ventricular end-systolic volume as the major determinant of survival after recovery from myocardial infarction. Circulation 76:44 - 518 1987 2. How to diagnose diastolic heart failure. European Study Group on Diastolic Heart Failure. Eur Heart J 19:990 - 10038 1998 3. Hogg K, Swedberg K, McMurray J: Heart failure with preserved left ventricular systolic function; epidemiology, clinical characteristics, and prognosis. J Am Coll Cardiol 43:317 - 3278 2004 4. Sanderson JE: Heart failure with a normal ejection fraction. Heart, 2005, doi:10.1136/hrt.2005.074187. [Epub ahead of print] 5. Edvardsen T, Gerber BL, Garot J, et al: Quantitative assessment of intrinsic regional myocardial deformation by Doppler strain rate echocardiography in humans: Validation against three-dimensional tagged magnetic resonance imaging. Circulation 106:50 - 568 2002
Summary Speckle-tracking echocardiography allows direct assessment of myocardial deformation independent of insonation angle. Left ventricular function can be interpreted from longitudinal and short-
SYSTOLIC DYSFUNCTION IN HEART FAILURE WITH NORMAL EJECTION FRACTION 6. Heimdal A, Stoylen A, Torp H, et al: Real-time strain rate imaging of the left ventricle by ultrasound. J Am Soc Echocardiogr 11:1013 - 10198 1998 7. Urheim S, Edvardsen T, Torp H, et al: Myocardial strain by Doppler echocardiography. Validation of a new method to quantify regional myocardial function. Circulation 102:1158 - 11648 2000 8. Garcia MJ, Thomas JD, Klein AL: New Doppler echocardiographic applications for the study of diastolic function. J Am Coll Cardiol 32:865 - 8758 1998 9. Sohn DW, Chai IH, Lee DJ, et al: Assessment of mitral annulus velocity by Doppler tissue imaging in the evaluation of left ventricular diastolic function. J Am Coll Cardiol 30:474 - 4808 1997 10. Nikitin NP, Witte KK, Clark AL, et al: Color tissue Doppler–derived long-axis left ventricular function in heart failure with preserved global systolic function. Am J Cardiol 90:1174 - 11778 2002 11. Yip G, Wang M, Zhang Y, et al: Left ventricular long axis function in diastolic heart failure is reduced in both diastole and systole: Time for a redefinition? Heart 87:121 - 1258 2002 12. Yu CM, Lin H, Yang H, et al: Progression of systolic abnormalities in patients with bisolatedQ diastolic heart failure and diastolic dysfunction. Circulation 105:1195 - 12018 2002 13. Edvardsen T, Skulstad H, Aakhus S, et al: Regional myocardial systolic function during acute myocardial ischemia assessed by strain Doppler echocardiography. J Am Coll Cardiol 37:726 - 7308 2001 14. Stoylen A, Heimdal A, Bjornstad K, et al: Strain rate imaging by ultrasonography in the diagnosis of coronary artery disease. J Am Soc Echocardiogr 13:1053 - 10648 2000 15. Voigt JU, Exner B, Schmiedehausen K, et al: Strainrate imaging during dobutamine stress echocardiography provides objective evidence of inducible ischemia. Circulation 107:2120 - 21268 2003 16. Bohs LN, Trahey GE: A novel method for angle independent ultrasonic imaging of blood flow and tissue motion. IEEE Trans Biomed Eng 38:280 - 2868 1991 17. Leitman M, Lysyansky P, Sidenko S, et al: Twodimensional strain—a novel software for real-time quantitative echocardiographic assessment of myocardial function. J Am Soc Echocardiogr 17: 1021 - 10298 2004 18. Smith SW, Trahey GE, Hubbard SM, et al: Properties of acoustical speckle in the presence of phase aberration. Part II: Correlation lengths. Ultrason Imaging 10:29 - 518 1988 19. Amundsen BH, Helle-Valle T, Edvardsen T, et al: Noninvasive myocardial strain measurement by speckle tracking echocardiography: Validation against sonomicrometry and tagged magnetic resonance imaging. J Am Coll Cardiol 47:789 - 7938 2006 20. Helle-Valle T, Crosby J, Edvardsen T, et al: New noninvasive method for assessment of left ventricular rotation: Speckle tracking echocardiography. Circulation 112:3149 - 31568 2005
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21. Langeland S, D’hooge J, Wouters PF, et al: Experimental validation of a new ultrasound method for the simultaneous assessment of radial and longitudinal myocardial deformation independent of insonation angle. Circulation 112:2157 - 21628 2005 22. Vannan MA, Pedrizzetti G, Li P, et al: Effect of cardiac resynchronization therapy on longitudinal and circumferential left ventricular mechanics by velocity vector imaging: Description and initial clinical application of a novel method using high–frame rate B-mode echocardiographic images. Echocardiography 22:826 - 8308 2005 23. Notomi Y, Lysyansky P, Setser RM, et al: Measurement of ventricular torsion by two-dimensional ultrasound speckle tracking imaging. J Am Coll Cardiol 45:2034 - 20418 2005 24. Cho GY, et alChan J, Leano R, et al: Comparison of two-dimensional speckle and tissue velocity based strain and validation with harmonic phase magnetic resonance imaging. Am J Cardiol 97:1661 - 16668 2006 25. Langeland S, D’hooge J, Claessens T, et al: RFbased two-dimensional cardiac strain estimation: A validation study in a tissue-mimicking phantom. IEEE Trans Ultrason Ferroelectr Freq Control 51: 1537 - 15468 2004 26. Suffoletto MS, Dohi K, Cannesson M, et al: Novel speckle-tracking radial strain from routine black-andwhite echocardiographic images to quantify dyssynchrony and predict response to cardiac resynchronization therapy. Circulation 113:960 - 9688 2006 27. Petrie MC, Caruana L, Berry C, et al: bDiastolic heart failureQ or heart failure caused by subtle left ventricular systolic dysfunction? 28. MacGowan GA, Shapiro EP, Azhari H, et al: Noninvasive measurement of shortening in the fiber and cross-fiber directions in the normal human left ventricle and in idiopathic dilated cardiomyopathy. Circulation 96:535 - 5418 1997 29. Moore CC, O’Dell WG, McVeigh ER, et al: Calculation of three-dimensional left ventricular strains from biplanar tagged MR images. J Magn Reson Imaging 2:165 - 1758 1992 30. Prinzen FW, Hunter WC, Wyman BT, et al: Mapping of regional myocardial strain and work during ventricular pacing: Experimental study using magnetic resonance imaging tagging. J Am Coll Cardiol 33: 1735 - 17428 1999 31. Edvardsen T, Rosen BD, Pan L, et al: Regional diastolic dysfunction in individuals with left ventricular hypertrophy measured by tagged magnetic resonance imaging—the Multi-Ethnic Study of Atherosclerosis (MESA). Am Heart J 151:109 - 1148 2006 32. Edvardsen T, Detrano R, Rosen BD, et al: Coronary artery atherosclerosis is related to reduced regional left ventricular function in individuals without history of clinical cardiovascular disease: The Multiethnic Study of Atherosclerosis. Arterioscler Thromb Vasc Biol 26:206 - 2118 2006 33. Rosen BD, Edvardsen T, Lai S, et al: Left ventricular concentric remodeling is associated with decreased
214 global and regional systolic function: The Multi-Ethnic Study of Atherosclerosis. Circulation 112:984 - 9918 2005 34. Becker M, Bilke E, Kuhl H, et al: Analysis of myocardial deformation based on pixel tracking in 2D echocardiographic images allows quantitative assessment of regional left ventricular function. Heart 2005. doi:10.1136/hrt.2005.074187. [Epub ahead of print]
EDVARDSEN ET AL 35. Chung J, Abraszewski P, Yu X, et al: Paradoxical increase in ventricular torsion and systolic torsion rate in type I diabetic patients under tight glycemic control. J Am Coll Cardiol 47:384 - 3908 2006 36. Ashikaga H, Criscione JC, Omens JH, et al: Transmural left ventricular mechanics underlying torsional recoil during relaxation. Am J Physiol Heart Circ Physiol 286:H640 - H6478 2004
Left ventricular (LV) ejection fraction (EF) and LV end-systolic volumes are important measures of LV global function. However, in many patients with symptoms of heart failure, these measures are within normal limits. This condition is classified as heart failure with normal ejection fraction (HFNEF). Reduced EF and increased end-systolic volume, however, require impaired function in a number of LV segments. Therefore, apparently normal systolic function in HFNEF may reflect limited sensitivity of global EF, and assessment of regional systolic function may provide important diagnostic information. The recently introduced method, speckle-tracking echocardiography (STE), represents a simplified, objective, and angle-independent modality for quantification of regional myocardial deformation. The software uses conventional gray-scale B-mode recordings and tracks myocardial speckles, which serve as natural acoustic markers. Radial and longitudinal myocardial deformation can be measured simultaneously from long-axis recordings, radial and circumferential deformation from short-axis recordings, and LV torsion from assessment of apical and basal short-axis rotation. Experimental and clinical studies have demonstrated that the STE method can assess myocardial function accurately in healthy subjects in the settings of acute and chronic ischemia, dyssynchrony, and cardiomyopathy. So far, no STE studies have been performed regarding HFNEF. The purpose of this article is therefore to illustrate the potential of this novel method. n 2006 Published by Elsevier Inc.
L
eft ventricular (LV) function has traditionally been evaluated noninvasively by global measures as left ventricular ejection fraction (LVEF) and LV end-systolic volume. These variables can relatively easily be obtained by
echocardiography, nuclear techniques and magnetic resonance imaging (MRI). The assessment of LVEF is important for diagnostics, prognosis and selection of treatment. Left ventricular endsystolic volume has been demonstrated to be even more useful for prognosis after myocardial infarction than LVEF.1 Many patients with symptoms of heart failure have, however, ejection fractions (EFs) and LV volumes which are regarded as normal.2 This condition has traditionally been classified as diastolic heart failure and, more recently, as heart failure with normal ejection fraction (HFNEF).3,4 Growing evidence suggest that the use of recent progress in echocardiographic techniques can reveal that these patients have abnormal systolic function.
Regional LV Function In principle, global LVEF reflects the sum of all regional shortening in the left ventricle. Impairment of regional function, however, does not cause reduction in global EF unless several segments are involved. Therefore, methods that measure LV regional function could be a more sensitive than global EF to identify systolic dysfunction. Regional myocardial function by echocardiography is usually evaluated by visual assessment of wall motion using 2-dimensional
From the Department of Cardiology, Rikshospitalet University Hospital, University of Oslo, Oslo, Norway. Address reprint requests to Otto A. Smiseth, MD, PhD, Department of Cardiology, Rikshospitalet University Hospital, N-0027 Oslo, Norway. E-mail: [email protected] 0033-0620/$ - see front matter n 2006 Published by Elsevier Inc. doi:10.1016/j.pcad.2006.08.008
Progress in Cardiovascular Diseases, Vol. 49, No. 3 (November/December), 2006: pp 207-214
207
208
EDVARDSEN ET AL
Fig 1. Speckle-tracking echocardiography: STE measures strain by tracking speckles in gray-scale echocardiographic images. A part of the myocardium (green box) from a left ventricular 4 chamber view is enlarged to visualize the speckles. The software allows tracking of speckles in multiple directions (arrows).
echocardiography. This approach, however, suffers from being subjective and provides only semiquantitative data. Furthermore, visual assessment has limited ability to detect more subtle changes in function and changes in timing of myocardial motion throughout systole and diastole.
Tissue Doppler and Strain Rate Imaging Echocardiographic modalities for objective quantification of global and regional function have recently been developed. Assessment of tissue velocity, strain, and strain rate by tissue Doppler imaging (TDI) have proved to be more accurate methods than visual evaluation of global and regional function.5-7 Recently, peak early diastolic myocardial velocity has emerged as a useful marker of diastolic function.8,9 Furthermore, TDI-derived measures have been used in recent studies to show that systolic long-axis function is
Fig 2. Validation of strain by STE vs sonomicrometry: experimental data which confirms the ability of STE to accurately measure myocardial strain. Adapted with permission from J Am Coll Cardiol 2006;47:789-793.
reduced in many patients with presumable bisolatedQ diastolic heart failure.10-12 Since subendocardial myocardial fibers are mainly responsible for long-axis contraction, longitudinal function is considered an early systolic marker of disease and more susceptible to effects of fibrosis, hypertrophy, and ischemia.4 Myocardial strain by TDI is superior to myocardial velocities and wall motion score in assessment of regional ischemia, according to experimental and clinical studies.7,13-15 To our knowledge, however, there are no published reports that have compared these techniques in patients with HFNEF. The angle dependency is a serious limitation of all Doppler-based techniques including Dopplerderived myocardial velocities and strain.7 Therefore, it is essential that the ultrasound beam is aligned parallel to the LV wall in long-axis imaging and perpendicular to the wall for radial measurements in the short axis. This implies that strain measurements from myocardial segments
Fig 3. A, Transmitral flow velocities and myocardial function in a 62-year-old man with a normal heart: LVEF was 60%. Transmitral flow shows normal E/A ratio (upper left panel), and tissue Doppler shows normal systolic mitral annulus velocities of 5 to 6 cm/s (upper right panel). Speckle-tracking echocardiography shows uniform strains in the different LV segments, with systolic strain values from 17% to 27%, confirming normal systolic function. B, Diastolic dysfunction in 78-year-old man: the patient complains about dyspnea on exertion. Echocardiography showed LV hypertrophy, whereas coronary angiography demonstrated no significant stenoses. Ejection fraction was 55% by the biplane Simpson method. Transmitral flow shows inverted E/A ratio and prolonged E deceleration time (290 milliseconds) (upper left panel). Tissue Doppler shows reduced mitral annulus EV velocity, recorded at the septal and lateral part of the mitral annulus (upper right panel). Furthermore, peak systolic velocity at the lateral part of the mitral annulus is decreased (3.8 m/s). Regional longitudinal strains are displayed in the lower right panel and demonstrates marked nonuniformity of systolic strain. The colors of the traces correspond to locations with same color on the corresponding 2-dimensional image.
SYSTOLIC DYSFUNCTION IN HEART FAILURE WITH NORMAL EJECTION FRACTION
209
210 close to the LV apical curvature can not be reliably assessed by TDI.13 The angle dependency is thus a significant limitation when studying patients with coronary artery disease as pathology may be most pronounced in the apical segments.
Assessment of LV Function by speckle-tracking echocardiography Speckle-tracking echocardiography (STE) has been introduced as a method for angle-independent quantification of myocardial strain (Fig 1).16 Speckles are natural acoustic markers that occur as small and bright elements in conventional grayscale ultrasound images.17 The speckles are the result of constructive and destructive interference of ultrasound, back-scattered from structures smaller than a wavelength of ultrasound.16,18 These speckles are distributed equally around in the myocardium on the ultrasound image and can be identified and followed in consecutive frames during the heart cycles. A different software that has the ability to assess myocardial strain, strain rate, velocities and displacement from these speckles has recently been released.17,19-22 Measurements can be done simultaneously from multiple regions of interest (ROIs) within an image plane from conventional gray-scale B-mode recordings. The distance between selected speckles is measured within a predefined myocardial area as a function of time, and parameters of myocardial deformation can be calculated. This is in contrast to Doppler-based measurements where the sample volume is a fixed area in space, and all measurements are done with reference to an external point (the transducer). Strain measurements from the speckle-tracking technique are therefore direct measures of myocardial deformation while TDI calculates strain by integrating strain rate. Another important advantage by using the new technique is independence of insonation angle and cardiac translation.20,21,23 The different speckle-tracking algorithms have been validated in experimental and human studies and found to be within clinically acceptable ranges.19,20,21,24,25 These studies include left ventricles with normal systolic function, with acute or chronic ischemia, asynchrony, and different loading and inotropic conditions. It has been shown that 2 deformation components can be estimated simultaneously and accurately
EDVARDSEN ET AL
(eg, radial and longitudinal strain) and that analyses by STE is less time-consuming than Doppler-based analyses.19,21 Speckle-tracking echocardiography has also been used to predict response to cardiac resynchronization therapy and a recent clinical study demonstrated that assessment of radial strain by STE may quantify dyssynchrony and predict immediate and longterm response to cardiac resynchronization therapy.26 The authors concluded that strain by speckle tracking has potential for clinical
Fig 4. Circumferential strain by STE. A, Circumferential strain from the apical LV level in a healthy individual. Note the homogenous circumferential distribution of normal systolic strain. B, Circumferential strain at the LV apical level in a patient with a LADrelated myocardial infarction. Please note reduced systolic shortening (strain) in the anterior, septal, and inferior segments, with marked postsystolic contraction (white arrows). In addition, in the septal segments, there is early systolic stretching indicating dyskines (red arrow). Normal contraction is seen in the lateral segments.
SYSTOLIC DYSFUNCTION IN HEART FAILURE WITH NORMAL EJECTION FRACTION
Fig 5. A, Schematic representation of LV shortening and torsion from end-diastole to end-systole. Courtesy of Stein Inge Rabben. B, End-diastolic and endsystolic apical 2D gray-scale echocardiographic images from an animal experiment: the ROIs (white squares) and best-fitted circle are indicated. The thin dashed arrows point at ROIs, and the thick solid arrows point at sonomicrometric crystals. The change in position of arrows from end diastole to end systole confirms counterclockwise rotation. Adapted with permission from Circ 2005;112:3149-3156.
application. In addition, the speckle-tracking method can be used for assessment of myocardial velocities and mitral annulus displacement.17 The results, so far, indicate strongly that strain measurements based on speckle tracking are able to reflect real myocardial deformation and also detect small alterations in systolic function. Fig 2 demonstrates the relationship between systolic strain by STE and sonomicrometry in an experimental study. In principle, STE provides a direct measure of myocardial deformation and appears to be a more robust method than Doppler-based strain imaging, which estimates strain as the time integral of spatial velocity gradients.11,27 The diagnostic value of STE in clinical practice, however, remains to be proven in appropriately designed trials. We are at an early stage of
211
development of the STE technology, and the purpose of this article is only to illustrate possible future applications of the technology. In Figs 3 and 4, we demonstrate how STE can identify regional myocardial dysfunction. In the setting of HFNEF, it may be of interest to quantify regional differences in systolic shortening and to identify postsystolic contractions. Another promising modality of strain measurements from speckle tracking is the ability to assess circumferential strain (Fig 4).24 This is possible because of independency of insonation angle. Assessment of circumferential strain by MRI tagging has, for long, been the preferred measure of regional deformation.28-30 Recently, it has also been demonstrated that circumferential strain by MRI tagging is able to detect subclinical changes in LV function in a large population group free of clinical signs of cardiovascular disease.31-33 Left ventricular torsion can be assessed accurately by STE (Figs 5 and 6).20,23,34 By measuring apical and basal rotation from LV short-axis recordings (Figs 5 and 6), torsion has been explored in both clinical and experimental studies (Fig 7). In a recently published clinical study on type I diabetic patients, increased LV peak systolic torsion and torsion rate was demonstrated in patients with normal EF when compared with healthy subjects.35 Reduced left ventricular twist/torsion has also been suggested
Fig 6. A representative example of regional LV rotation by STE at the apical LV level in a healthy individual. Please note the homogenous distribution of rotation between segments. The direction of rotation at the apex is counterclockwise when viewed from the LV apex.
212
EDVARDSEN ET AL
Fig 7. Left ventricular rotation and torsion—comparison between STE (solid lines) and sonomicrometry (dashed lines). Clockwise rotation is represented by positive numbers. Torsion was calculated as the difference between rotation at apex and base. Please note that LV rotation and torsion were increased by dobutamine infusion and reduced by ischemia. Adapted with permission from Circ 2005;112:3149-3156.
to have impact on LV suction.36 These findings can now be further explored by STE.
axis views. This makes STE suitable for the assessment of systolic LV function in patients with heart failure with a normal ejection fraction.
Limitations Regarding STE
References
The time resolution in studies using STE has been in the range of 60 to 100 frames per second to optimize the speckle quality. Higher frame rates may be required in order to obtain reliable results regarding peak systolic myocardial strain rate and velocity. At present, few studies exist, and the clinical value of this novel method needs to be better defined.
1. White HD, Norris RM, Brown MA, et al: Left ventricular end-systolic volume as the major determinant of survival after recovery from myocardial infarction. Circulation 76:44 - 518 1987 2. How to diagnose diastolic heart failure. European Study Group on Diastolic Heart Failure. Eur Heart J 19:990 - 10038 1998 3. Hogg K, Swedberg K, McMurray J: Heart failure with preserved left ventricular systolic function; epidemiology, clinical characteristics, and prognosis. J Am Coll Cardiol 43:317 - 3278 2004 4. Sanderson JE: Heart failure with a normal ejection fraction. Heart, 2005, doi:10.1136/hrt.2005.074187. [Epub ahead of print] 5. Edvardsen T, Gerber BL, Garot J, et al: Quantitative assessment of intrinsic regional myocardial deformation by Doppler strain rate echocardiography in humans: Validation against three-dimensional tagged magnetic resonance imaging. Circulation 106:50 - 568 2002
Summary Speckle-tracking echocardiography allows direct assessment of myocardial deformation independent of insonation angle. Left ventricular function can be interpreted from longitudinal and short-
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