Echocardiographic Assessment of Myocardial Strain

Journal of the American College of Cardiology Vol. 58, No. 14, 2011 © 2011 by the American College of Cardiology Foundation ISSN 0735-1097/$36.00 Published by Elsevier Inc. doi:10.1016/j.jacc.2011.06.038

STATE-OF-THE-ART PAPER

John Gorcsan III, MD, Hidekazu Tanaka, MD Pittsburgh, Pennsylvania

Echocardiographic strain imaging, also known as deformation imaging, has been developed as a means to objectively quantify regional myocardial function. First introduced as post-processing of tissue Doppler imaging velocity converted to strain and strain rate, strain imaging has more recently also been derived from digital speckle tracking analysis. Strain imaging has been used to gain greater understanding into the pathophysiology of cardiac ischemia and infarction, primary diseases of the myocardium, and the effects of valvular disease on myocardial function, and to advance our understanding of diastolic function. Strain imaging has also been used to quantify abnormalities in the timing of mechanical activation for heart failure patients undergoing cardiac resynchronization pacing therapy. Further advances, such as 3-dimensional speckle tracking strain imaging, have emerged to provide even greater insight. Strain imaging has become established as a robust research tool and has great potential to play many roles in routine clinical practice to advance the care of the cardiovascular patient. This perspective reviews the physiology of myocardial strain, the technical features of strain imaging using tissue Doppler imaging and speckle tracking, their strengths and weaknesses, and the state-of-the-art present and potential future clinical applications. (J Am Coll Cardiol 2011;58:1401–13) © 2011 by the American College of Cardiology Foundation

Noninvasive assessment of regional myocardial function is Physiology of Left Ventricular Strain important to the field of cardiovascular medicine to diag- nose disease, assess therapeutic interventions, and predict D’Hooge et al. (2), Dandel and Hetzer (6), and Mor-Avi et al. (7) clinical outcomes. Although magnetic resonance imaging published scholarly reviews of the technical features of strain and computed tomography imaging are useful diagnostic imaging in detail previously. Briefly, myocardial regional mechan- alternatives, echocardiography remains advantageous for ics assessed by echocardiographic approaches have been described widespread clinical use because of its portability, low risk, by 4 principal types of strain or deformation: longitudinal, radial, and comparatively high temporal resolution. Echocardio- circumferential, and rotational (Fig. 1). Although myocardial fiber graphic strain imaging, also known as deformation imaging, orientation results in these strain vectors occurring 3 dimensionally is a technological advancement that has been developed as a in an integrated manner, most investigative works have been done means to objectively quantify regional myocardial function using individual strain assessments. The term strain applied to (1–3). First introduced as a post-processing feature of tissue echocardiography in a simplistic sense is to describe lengthening, shortening, or thickening, also known as regional deformation. Doppler imaging (TDI) with velocity data converted to ␧ ϭ⌬ strain and strain rate, strain imaging information has more Strain may be L/L0 understood as an example of an recently also been derived from speckle tracking computer infinitesimally thin bar where the only possible deformation is processing (4,5). Currently, most echocardiography labora- lengthening or shortening. Accordingly linear strain or the tories continue to use the subjective visual assessment of wall amount of deformation can be defined by the change in length divided by the original length expressed by the formula: ␧ ϭ motion for resting and stress imaging for everyday clinical ⌬ ␧ ϭ ⌬ ϭ ϭ use, and strain imaging has been more often regarded as a L/L0, where strain, L change in length, and L0 research tool. Adoption of strain imaging in clinical practice original length. In reality, the myocardial wall as a 3-dimensional appears to have been gaining momentum more recently. (3D) object has strain that may occur along 3 planes (x-, y-, and This paper reviews the physiology of myocardial strain, the z-axes), known as normal strains, and 6 shear strains (2,3,6). technical features of strain imaging using both TDI and Despite the complexities of myocardial wall dynamics, some speckle tracking, their strengths and weaknesses, and the meaningful information has been derived using the simplified potential present and future clinical applications. linear strain or deformation model by echocardiography.

Strain by TDI From the University of Pittsburgh, Pittsburgh, Pennsylvania. Dr. Gorcsan has received research grant support from GE and Toshiba. Dr. Tanaka has reported that The ﬁrst description of echocardiographic strain was derived he has no relationships relevant to the contents of this paper to disclose. Manuscript received August 8, 2010; revised manuscript received May 31, 2011, from TDI velocity data using the Doppler equation to accepted June 10, 2011. convert ultrasound frequency shifts to velocity information 1402 Gorcsan III and Tanaka JACC Vol. 58, No. 14, 2011 Myocardial Strain September 27, 2011:1401–13

Abbreviations along the scan lines. Because the lines. The important technical features of TDI acquisition and and Acronyms fundamental data produced by analysis appear in the Online Appendix. TDI were velocity information, cardiac magnetic Strain by Speckle Tracking ؍ CMR resonance strain rate (strain per unit of time) was derived from the ve- cardiac A more recent echocardiographic approach to strain analysis ؍ CRT locity data using the equation: resynchronization therapy is speckle tracking. Speckle tracking is a post-processing ␧ ϭ V Ϫ V /L, where ␧ ϭ strain dobutamine stress 1 2 computer algorithm that uses the routine grayscale digital ؍ DSE echocardiography rate, V ϭ velocity at point 1, 1 images. Although several manufacturers have devised V ϭ velocity at point 2, and L ϭ ؍ EF ejection fraction 2 speckle tracking echocardiographic approaches, the funda- length, usually set at 10 mm. -left bundle branch mental approach is similar (4,12,13). Briefly, routine gray ؍ LBBB block Strain rate and strain data using scale digital images of the myocardium contain unique TDI required the direction of the ؍ LV left ventricular speckle patterns. A user-defined region of interest is placed myocardial wall motion to be tissue Doppler on the myocardial wall. Within this region of interest, the ؍ TDI along the ultrasound scan line imaging image-processing algorithm automatically subdivides re- (1,3). Longitudinal shortening dimensional gions into blocks of pixels tracking stable patterns of-2 ؍ 2D using the apical windows was dimensional speckles. Subsequent frames are then automatically analyzed-3 ؍ 3D often used because of the favor- by searching for the new location of the speckle patterns able Doppler angle of incidence within each of the blocks using correlation criteria and the (3)(Fig. 2). The alternative was from the parasternal views sum of absolute differences (Fig. 4). The location shift of where the relative transmural change in velocity could be these acoustic markers from frame to frame representing calculated as the velocity gradient, similar to strain rate (e.g., tissue movement provides the spatial and temporal data in the posterior wall) (8–10). TDI strain rate data could be used to calculate velocity vectors. Temporal alterations in integrated over time to determine strain (Fig. 3). Because all these stable speckle patterns are identified as moving farther TDI information is affected by the Doppler angle of apart or closer together and create a series of regional strain incidence, Doppler angle correction analysis programs were vectors. Because strain information is not dependent on the developed to determine wall motion for regions where the Doppler angle of incidence like TDI strain, several more motion was not aligned with the Doppler scan line (11). strain analyses are possible, including longitudinal, circum- However, it remained impossible to assess wall motion by ferential, radial, and rotational. Additional technical fea- TDI when the angle of motion was close to 90o. Accord- tures of speckle tracking acquisition and analysis appear in ingly, the majority of the published literature on echocar- the Online Appendix. diographic strain imaging using TDI assessed longitudinal strain from the apical windows with left ventricular (LV) Strain Imaging for shortening and lengthening aligned with the Doppler scan Myocardial Ischemia and Viability Significant insights pertaining to the pathophysiology of ischemic heart disease have resulted from echocardiographic strain imaging over the past decade (14–18). Previously, the clinical assessment of wall motion abnormalities at rest or with stress by exercise or dobutamine has consisted of visual assessment of endocardial excur- sion and wall thickening. The addition of strain imaging has refined the ability of echocardiography to detect and objectively qualify specific patterns of ischemia and infarction. Because ischemic wall motion abnormalities are often associated with passive motion, such as passive expansion and recoil and tethering from adjacent segments, strain imaging has the advantage of differentiating active contraction from passive motion, which often is difficult visually (19). Strain imaging has been validated in animal models of acute ischemia and infarction (20,21) (Fig. 5). Edvardsen et al. (16) used TDI longitudinal strain Figure 1 Myocardial Fiber Orientation and Principal Vectors of Left Ventricular Strain in humans to demonstrate patterns of LV wall lengthening with acute ischemia while patients underwent occlu- Echocardiographic application of strain imaging has assessed longitudinal strain from apical windows and radial, circumferential, and rotational strain sion of the left anterior descending coronary artery (16). from parasternal windows. With permission from H. Tanaka. Specifically, strain quantified expansion in the apical septal segments (7.5 Ϯ 6.5% vs. Ϫ17.7 Ϯ 7.2%, JACC Vol. 58, No. 14, 2011 Gorcsan III and Tanaka 1403 September 27, 2011:1401–13 Myocardial Strain

Figure 2 Strain Imaging in a Normal Subject

Examples of tissue Doppler imaging velocity, strain rate, and strain curves for a cardiac cycle from a subject with normal cardiac function. L ϭ length; V ϭ velocity. p Ͻ 0.001) and reduced compression in the mid-septal Although radionuclide single-photon emission computed segments. Skulstad et al. (19) used radial and longitudinal tomography imaging or gadolinium-enhanced cardiac mag- strain imaging to define the pattern of post-systolic netic resonance (CMR) imaging appear to be preferred shortening with acute coronary occlusion in an animal currently to quantify myocardial scar, strain imaging con- model with sonomicronometry validation. Kukulski et al. tinues to emerge as a new potential approach (25,26). Roes (22) extended the concept of post-systolic shortening et al. (27,28) used speckle tracking longitudinal strain to using TDI strain in humans undergoing coronary angio- assess viable myocardium compared with contrast-enhanced plasty with peak strain occurring after aortic valve closure CMR imaging in 90 patients with chronic ischemic LV and restoration of strain after reperfusion (Fig. 6). dysfunction. A favorable correlation was found between Weidemann et al. (18) proposed a post-systolic strain resting longitudinal LV strain and the extent of scarring by index as being predictive of the extent of transmurality of CMR imaging. The mean longitudinal strain in segments myocardial infarction. Lim et al. (23) subsequently without scarring was Ϫ10.4 Ϯ 5.2% compared with 0.6 Ϯ showed that time-to-peak TDI strain was significantly 4.9% in segments with transmural scarring (p Ͻ 0.001). A correlated with the percentage of infarct transmurality strain cutoff value of Ϫ4.5% had a sensitivity of 81.2% and with a modest correlation coefficient of r ϭ 0.69. a specificity of 81.6% for predicting viable myocardium from An important contribution of strain imaging has been segments with transmural scarring by contrast-enhanced as an adjunct to low-dose dobutamine stress echocardi- CMR imaging. Bansal et al. (29) compared speckle tracking ography (DSE) to assess myocardial viability. Hanekom longitudinal strain with TDI of strain during low-dose DSE et al. (24) examined 55 patients with ischemic heart disease to determine viability in 55 patients with subsequent revas- by DSE with both visual wall motion assessment and cularization. They reported TDI of strain to be more longitudinal strain and strain rate imaging followed by accurate to determine viability than speckle tracking longi- revascularization by coronary bypass or percutaneous tudinal strain. The precise reason for this difference is interventions. Patients were re-examined 9 months later unknown; however, the lower temporal resolution of speckle to determine LV functional recovery after revasculariza- tracking strain compared with TDI of strain is a potential tion as evidence of viability. Visual wall motion assess- factor. Future refinements of speckle tracking for patients ment alone had a sensitivity of 71% and a specificity of with ischemic heart disease are likely forthcoming. 77% for detecting viable segments by DSE. Sensitivity was modestly but significantly improved by longitudinal Applications of Strain Imaging for strain and strain rate imaging, with the most favorable Cardiac Resynchronization Therapy results achieved by a combination of visual assessment and strain imaging with a sensitivity 84% and a specificity Strain imaging by both TDI and speckle tracking ap- of 80%. proaches have been reported to assess abnormal regional 1404 Gorcsan III and Tanaka JACC Vol. 58, No. 14, 2011 Myocardial Strain September 27, 2011:1401–13

Observations to Study Predictors of Events in the Coronary Tree) study suggested that the TDI opposing wall delay performed relatively better than other dyssynchrony indexes for predicting LV reverse remodeling; however, echocardiographic dyssynchrony was not considered reliable enough to replace current selection criteria for CRT (36). Accordingly, interest in the quantification of LV dyssynchrony by strain imaging has continued. Yu et al. (35) observed that the 12-segment SD of time-to-peak TDI velocities was supe- rior to TDI strain for predicting LV reverse remodeling after CRT in 256 patients. On the other hand, Miyazaki et al. (37) showed contrary findings that TDI of longitudinal strain might be a preferred dyssynchrony technique to longitudinal velocities. In their study of 120 heterogeneous subjects including normal subjects and patients with left bundle branch block (LBBB) and reduced ejection fraction (EF). They observed considerable overlap of TDI velocities between groups and difficulties with analysis of multiple velocity spikes even in normal subjects. In contrast, they believed that longitudinal strain more reliably distinguished patients with LBBB or decreased EF from those with normal EF and normal QRS duration. However, TDI of longitudinal strain is severely affected by the Doppler angle of incidence, which is a limitation for enlarged spherical left ventricles, commonly encountered in the CRT patients. We showed more recently in a prospective study of 229 CRT patients that a TDI velocity opposing wall delay of Ն80 ms and Yu Index Ն32 ms were significantly associated with long-term survival over a 4-year period (38).

Speciﬁc Speckle Tracking Figure 3 Longitudinal Strain by Speckle Tracking Imaging in a Normal Subject and a Heart Failure Patient Applications of Strain for Dyssynchrony

(A) An example of speckle tracking imaging of longitudinal strain using the Four different speckle tracking dyssynchrony approaches apical 4-chamber view in a normal subject demonstrating peak longitudinal strain of Ϫ16.5% and Ϫ21.5%, respectively. (B) An example of speckle track- have been suggested, including radial strain (myocardial ing imaging of longitudinal strain using the apical 4-chamber view in a heart thickening) and circumferential strain (myocardial short- failure patient with depressed ejection fraction demonstrating smaller peak lon- ening) assessed from short-axis views (Figs. 7 and 8) and gitudinal strain of Ϫ8.0% and Ϫ12.5%, respectively. AVC ϭ aortic valve closure. longitudinal strains (myocardial shortening) and trans- mechanical activation patterns, known as dyssynchrony, with particular interest for patients undergoing cardiac resynchronization therapy (CRT). Interest has focused on dyssynchrony as a means to predict response to CRT because approximately one-third of patients do not appear to beneﬁt using standard clinical selection criteria (30,31). LV longitudinal shortening velocities by TDI from the apical views have been introduced as a means to quantify LV dyssynchrony (32–34). The 2 most popular applications of TDI velocities have included the differences in timing of peak velocity between LV walls (opposing wall delay) and Figure 4 Speckle Tracking Strain by Echocardiography the SD in time to peak velocities from 12 sites (Yu Index) (32–35). The advantage of TDI velocities is that the Diagram of speckle tracking strain from 2-dimensional short-axis echocardio- signal-to-noise ratio is high, but a major limitation is the graphic images. Information about myocardial strain is generated by changes in speckles from frame to frame. Strain is calculated as the change in length (⌬L) inability of velocity to differentiate active from passive divided by the original length (L0) and expressed as a percentage. motion. The multicenter PROSPECT (Providing Regional JACC Vol. 58, No. 14, 2011 Gorcsan III and Tanaka 1405 September 27, 2011:1401–13 Myocardial Strain

Figure 5 TDI of Radial Strain of a Myocardial Infarction

This is a pig model of myocardial infarction with angle-corrected tissue Doppler imaging (TDI) of radial strain demonstrating preserved radial thickening in the noninfarct region and dyskinesis in the infarct region. LV ϭ left ventricle; RV ϭ right ventricle. verse (myocardial thickening) assessed from apical views septal radial thickening, followed by delayed posterior (Figs. 9 and 10). Radial and transverse strains have and lateral wall thickening. Suffoletto et al. (13) first positive curves, reflecting myocardial thickening. Con- reported the utility of speckle tracking radial strain in versely, longitudinal and circumferential strains have quantifying dyssynchrony, defined as the time difference negative curves, reflecting myocardial shortening. Dys- in peak anteroseptum to posterior wall strain Ն130 ms, to synchrony is typically characterized in LBBB by early be associated with EF response to CRT. A combined

Figure 6 Post-Systolic Thickening During Acute Ischemia

Examples of radial and longitudinal strain during coronary occlusion and reperfusion in a patient with coronary disease demonstrating the pattern of post-systolic thickening occurring after aortic valve closure (AVC). Modiﬁed, with permission, from Kukulski et al. (22). 1406 Gorcsan III and Tanaka JACC Vol. 58, No. 14, 2011 Myocardial Strain September 27, 2011:1401–13

Figure 7 Radial Strain by 2D Speckle Tracking in a Normal Subject and a Heart Failure Patient With LBBB

(A) An example of speckle tracking radial strain using the midventricular short-axis view in a normal subject demonstrating synchronous peak radial strain curves (arrow). (B) An example of speckle tracking radial strain using the midventricular short-axis view in a heart failure patient with left bundle branch block (LBBB) referred for resynchronization therapy demonstrating dyssynchrony; early anteroseptal peak strain followed by late posterior wall peak strain (arrow). AVC ϭ aortic valve closure; 2D ϭ 2-dimensional. approach of using both TDI longitudinal velocity oppos- the ischemic (r ϭ 0.68) and nonischemic (r ϭ 0.68) ing wall delay and speckle tracking radial strain was patients (p Ͻ 0.0001 for both). The STAR (Speckle shown to be of additive value for predicting response to Tracking and Resynchronization) study was the ﬁrst CRT (39). Lim et al. (40) reported the strain delay index prospective multicenter study to associate speckle track- determined by longitudinal speckle tracking strain from ing strain dyssynchrony with EF response and long-term standard apical views was a marker of both LV dyssyn- survival after CRT (41). Speckle tracking radial strain chrony and myocardial contractility. They demonstrated from short-axis views and transverse strain from apical that the strain delay index Ն25% strongly predicted views were associated with response to CRT in 132 response to CRT with a 95% sensitivity and an 83% patients, whereas longitudinal and circumferential strain speciﬁcity and correlated with reverse remodeling in both appeared less sensitive in detecting important dyssyn- JACC Vol. 58, No. 14, 2011 Gorcsan III and Tanaka 1407 September 27, 2011:1401–13 Myocardial Strain

Figure 8 Circumferential Strain by 2D Speckle Tracking in a Normal Subject and a Heart Failure Patient With LBBB

(A) An example of 2D speckle tracking circumferential (Circum.) strain using the midventricular short-axis view in a normal subject demonstrating synchronous peak circumferential strain curves (arrow). (B) An example of 2D speckle tracking circumferential strain using the midventricular short-axis view in a heart failure patient with LBBB referred for resynchronization therapy demonstrating early anteroseptal peak strain followed by late posterior wall peak strain, resulting in dyssynchrony (arrow). Abbreviations as in Figure 7. chrony. A lack of dyssynchrony before CRT by radial or appears promising as an adjunct for patient selection for transverse strain (or both) was signiﬁcantly associated CRT with borderline QRS duration (42,43). with death, heart transplantation, or LV assist device implantation. Dyssynchrony by speckle tracking radial 3D Speckle Tracking Strain strain was shown to be strongly associated with long-term survival after CRT in another study of 229 patients. A A newer speckle tracking approach to quantify LV dyssyn- lack of radial dyssynchrony was particularly associated chrony is 3D speckle tracking echocardiography (44,45). 3D with an unfavorable outcome in those with a shorter QRS speckle tracking provides a more comprehensive evaluation duration of 120 to 150 ms. Most recently, Delgado et al. of LV mechanics from pyramidal 3D datasets than was (26) showed an association of a lack of dyssynchrony by previously possible. 3D cine loops of regional strain are color speckle tracking radial strain with death or heart failure coded and divided into 16 segments for time-strain curves, hospitalization in a series of 397 CRT patients with polar maps, and 3D displays (Fig. 11). Maximum opposing ischemic heart disease. Similar results for dyssynchrony wall delay and SD by 3D speckle tracking strain signiﬁcantly analysis using speckle tracking radial strain may be correlated with similar 2-dimensional (2D) strain measures, achieved using different software approaches, and it with 3D having the advantage of more precise mechanical 1408 Gorcsan III and Tanaka JACC Vol. 58, No. 14, 2011 Myocardial Strain September 27, 2011:1401–13

Figure 9 Longitudinal Strain by 2D Speckle Tracking in a Normal Subject and a Heart Failure Patient With LBBB

(A) An example of speckle tracking longitudinal (Long.) strain using the apical 4-chamber view in a normal subject demonstrating synchronous peak longitudinal strain curves (arrow). (B) An example of speckle tracking longitudinal strain using the apical 4-chamber view in a heart failure patient with LBBB referred for resynchronization therapy demonstrating early septal peak strain followed by late lateral wall peak strain, resulting in dyssynchrony (arrow). Abbreviations as in Figure 7. activation mapping to assist with LV lead positioning (45) The combination of these rotational strain vectors was (Fig. 12). 3D speckle tracking strain was also useful for described as torsion. They validated rotational and tor- showing differences in the sites of earliest activation in right sion measures against tagged cine magnetic resonance ventricle–paced patients compared with those with LBBB, imaging using TDI during systole and early diastole but similar sites of latest activation and similar response to (apical and basal rotation, r ϭ 0.87 and 0.90, respectively; CRT (44). Future advancements with expansion of appli- for torsion, 0.84; p Ͻ 0.0001). In a second related study, cations for 3D speckle tracking are anticipated. they performed similar comparisons using speckle tracking measures of rotation and torsion in 13 patients also Assessment of Rotational Strain demonstrating a strong correlation with tagged magnetic ϭ ϩ ϭ Ͻ Notomi et al. (12,46) used TDI and speckle tracking resonance imaging (y 0.95x 0.19, r 0.93, p strain methods to assess LV rotational mechanics and 0.0001). This group went on to describe a temporal link calculate torsion. They elegantly reported the normal between LV untwisting, relaxation, and suction in an pattern of slight clockwise basal rotation and greater animal model, showing that the peak untwisting rate was counterclockwise apical rotation as viewed in the stan- an independent predictor of tau and intraventricular dard short-axis echocardiographic view orientation (Fig. 13). pressure gradient (p Ͻ 0.0001 for both) (47–49). Tan et JACC Vol. 58, No. 14, 2011 Gorcsan III and Tanaka 1409 September 27, 2011:1401–13 Myocardial Strain

Figure 10 Transverse Strain by 2D Speckle Tracking in a Normal Subject and a Heart Failure Patient With LBBB

(A) An example of speckle tracking transverse (Trans.) strain using the apical 4-chamber view in a normal subject demonstrating synchronous peak transverse strain curves (arrow). (B) An example of speckle tracking transverse strain using the apical 4-chamber view in a heart failure patient with LBBB referred for resynchronization therapy demonstrating early septal peak strain followed by late lateral wall peak strain, resulting in dyssynchrony (arrow). Abbreviations as in Figure 7. al. (50) reported on the role of LV untwisting in patients hypertension or those with athlete’s heart. Kato et al. (56) with heart failure and normal EF, observing reduced and more recently found that TDI of longitudinal strain of delayed diastolic untwisting resulting in reduced LV Ͻ10.6% (average of the anterior, inferior, septal, and suction at rest and on exercise. Bertini et al. (51) lateral) was associated with a sensitivity of 85% and a demonstrated reduced subendocardial LV twist in pa- specificity of 100% for the detection of hypertrophic tients with ST-segment elevation myocardial infarction, cardiomyopathy. Furthermore, Yang et al. (57) reported and Andrade et al. (52) recently applied 3D speckle unique findings that longitudinal strain by TDI was tracking to assess LV twist. significantly lower in the mid-septum than that of the apical and basal segments in patients with hypertrophic Applications of Strain Imaging cardiomyopathy (p Ͻ 0.01), and 55% of patients had a for Cardiomyopathies positive peak strain value (paradoxical systolic expan- TDI and speckle tracking strain have been used to sion). Yajima et al. (59) recently reported regional peak characterize patients with primary myocardial diseases longitudinal speckle tracking strain can distinguish fi- including hypertrophic cardiomyopathy, cardiac amyloid- brotic from nonfibrotic lesions in LV myocardium in osis, drug-induced cardiomyopathy, and arrhythmogenic patients with hypertrophic cardiomyopathy and normal right ventricular dysplasia (9,53–58). Palka et al. (9) LV myocardium in healthy controls. demonstrated that early diastolic strain rates were signif- Koyama et al. (53) first demonstrated the incremental icantly lower in patients with hypertrophic cardiomyop- value of longitudinal strain and strain rate for the athy compared with patients with hypertrophy related to diagnosis of cardiac amyloidosis. They proposed that 1410 Gorcsan III and Tanaka JACC Vol. 58, No. 14, 2011 Myocardial Strain September 27, 2011:1401–13

Detection of chemotherapeutic cardiac toxicity is of great clinical importance. Ho et al. (54) reported the long-term effects of standard chemotherapy including trastuzumab on myocardial function in asymptomatic breast cancer survivors using 2D speckle tracking strain. They found that the chemotherapy group had reduced global longitudinal speckle tracking strain in comparison with normal controls (Ϫ18.1 Ϯ 2.2% vs. Ϫ19.6 Ϯ 1.8%, p ϭ 0.0001), even though the EF was similar (62 Ϯ 4% vs. 60 Ϯ 3%). In contrast, global radial speckle tracking strain did not differ signiﬁcantly between the 2 groups. Prakasa et al. (58) evaluated the utility of TDI of longitudinal strain in patients with arrhythmogenic right ventricular dysplasia to determine whether these modalities could provide complemen- tary and incremental diagnostic information. They found that a value of Ϫ18% of right ventricular free wall longitudinal strain provided the greatest discriminatory power for differentiating patients with arrhythmogenic right ventricular dysplasia from normal controls. Importantly, 4 patients had a diagnosis of arrhythmogenic right ventricular dysplasia by TDI of strain with morphologically normal right ventricles by 2D echocardiography.

Applications of Strain Imaging for Effects of Valvular Heart Disease

The chronic effects of abnormal loading from valvular disease on myocardial function may be difficult to detect by conventional means, and strain imaging may play a role Figure 11 3D Speckle Tracking Radial Strain in a Normal Subject and a Heart Failure Patient With LBBB (61–67). Delgado et al. (62) demonstrated that patients with severe aortic stenosis and preserved EF exhibited (A) The color-coded 3-dimensional (3D) left ventricular (LV) display (top left) and bull’s eye plot image (bottom left) and corresponding time-to-strain curves decreased radial, circumferential, and longitudinal speckle from 16 LV sites (right) in a normal subject demonstrating synchronous time- tracking strain. In addition, significant improvement in to-peak strain curves represented by homogeneous coloring at end-systole these parameters was observed at long-term follow-up after (arrow). A maximum opposing wall delay was 20 ms and 16-segment SD was 6 ms. (B) The color-coded display (top left) and bull’s eye plot image (bottom aortic valve replacement, whereas EF remained unchanged. left) and corresponding time-to-strain curves from 16 LV sites (right) in a heart de Isla et al. (63) reported that preoperative speckle tracking failure patient with left bundle branch block (LBBB) demonstrating dyssynchro- longitudinal strain at the level of the interventricular septum nous time to peak strain curves represented by heterogeneous coloring at end- systole, with early peak strain in septal segments and delayed peak strain in from the apical 4-chamber view strongly predicted a post- posterior lateral segments (arrow). A maximum opposing wall delay was 378 operative EF decrease of Ͼ10% in patients with chronic ms and 16-segment SD was 165 ms. ant ϭ anterior; ant-sept ϭ anterior-sep- severe mitral regurgitation. Tayyareci et al. (64) demon- tum; inf ϭ inferior; lat ϭ lateral; post ϭ posterior; sept ϭ septal. strated that longitudinal and circumferential strains assessed by velocity vector imaging were significantly decreased in longitudinal strain imaging could identify a group of asymptomatic patients with severe aortic regurgitation and patients with probable subclinical cardiac amyloidosis normal EF compared with normal volunteers. Furthermore, earlier in the course of the disease process at a time when Onishi et al. (61) recently reported that preoperative systolic routine 2D echocardiography and Doppler assessment of radial strain rate derived from TDI was the best predictor of diastolic function was normal. In 119 patients with post-operative LV systolic dysfunction of an EF Ͻ50% in cardiac amyloidosis, they reported a basal longitudinal patients with severe aortic regurgitation and a normal EF. strain value of less than Ϫ12.0% was predicted of cardiac These findings highlight that TDI of or 2D speckle tracking death over a year (60). They concluded that strain and strain enables an early detection of subtle changes in LV strain rate displayed greater sensitivity than velocity or systolic function in patients with valvular heart disease. displacement for detecting subtle abnormalities in the longitudinal contraction early in the patient’s course with Conclusions amyloidosis. Bellavia et al. (55) also reported similar findings from 103 patients with biopsy-proven cardiac Echocardiographic strain imaging, also known as defor- amyloidosis. mation imaging, has provided a means to objectively JACC Vol. 58, No. 14, 2011 Gorcsan III and Tanaka 1411 September 27, 2011:1401–13 Myocardial Strain

Figure 12 Color-Coded 3D Speckle Tracking Radial Strain Maps From 3 Different Heart Patients With LBBB

Patient A has the site of latest mechanical activation in the midposterior segment (red arrow). In contrast, Patient B has the site of latest mechanical activation in the midlateral segment (red arrow). Patient C has a broad site of latest mechanical activation (red arrow). Abbreviations as in Figure 11. quantify myocardial mechanical function. Originally in- myocardium, assessment of dyssynchrony for CRT, the troduced as a product of TDI, speckle tracking is a more effects of valvular disease on myocardial function, and the recent extension of strain imaging. Strain imaging has mechanics of diastolic function. Strain by 3D speckle provided greater understanding of the pathophysiology of tracking has emerged as a further advance to provide even cardiac ischemia and infarction, primary diseases of the greater insight. Strain imaging has become established as

Figure 13 Rotational Strain Imaging From a Normal Subject

Short-axis views at the basal and apical levels with speckle tracking demonstrating clockwise basal rotation (red line) and counterclockwise apical rotation (blue line) in a subject with normal cardiac function. The combination of basal and apical rotation in opposite directions results in left ventricular (LV) torsion. ECG ϭ electrocardiogram. 1412 Gorcsan III and Tanaka JACC Vol. 58, No. 14, 2011 Myocardial Strain September 27, 2011:1401–13 a robust research tool and has great potential to play 17. Urheim S, Edvardsen T, Steine K, et al. Postsystolic shortening of many roles to advance the care of the cardiovascular ischemic myocardium: a mechanism of abnormal intraventricular filling. Am J Physiol Heart Circ Physiol 2003;284:H2343–50. patient. 18. Weidemann F, Dommke C, Bijnens B, et al. 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