REVIEWS

The role of 3D wall motion tracking

in heart failure
Yiu-fai Cheung
Abstract | Heart failure is a major health problem in developed countries and a growing one in developing
countries. Cardiac remodeling in heart failure affects myocardial mechanics, which requires comprehensive
evaluation in three dimensions. The novel technique of 3D wall motion tracking applies speckle tracking
technology to full volume, 3D echocardiographic datasets. Quantification of conventional and novel left
ventricular (LV) parameters including volumes, ejection fraction, global and regional 3D strain, endocardial
area strain, twist, and dyssynchrony, and identification of the site of latest mechanical activation are
feasible on the basis of a single acquisition of a full-volume dataset. Clinical applications of 3D wall motion
tracking include the assessment of global and regional LV performance in ischemic and nonischemic heart
diseases, evaluation of mechanics in cardiomyopathies and congenital heart disease, potential selection of
patients for cardiac resynchronization therapy and prediction of their response, and detection of subclinical
cardiac dysfunction in diseases with likelihood of progression to heart failure. Technological advances with
improvement in spatial and temporal resolution of this novel imaging modality are expected. Although 3D wall
motion tracking is still in its infancy, this method has begun to provide new insights into LV mechanics and has
already found clinical applications. Future developments in 3D assessment of right ventricular and myocardial
layer-specific mechanics are awaited.
Cheung, Y.-F. Nat. Rev. Cardiol. 9, 644–657 (2012); published online 4 September 2012; doi:10.1038/nrcardio.2012.128

Introduction
Heart failure is a major health problem in developed
countries and a growing one in developing countries.1
The prevalence of heart failure is ~1.8% in the USA, 2
~1.9% in Europe,3,4 and ~1.0% in the UK.1 Although
data for developing countries are limited, the preva-
lence of heart failure in India has been estimated to be
0.1–0.4%,5 and 0.9% in China.6 In developed countries,
the most-important risk factors for heart failure are
coronary artery disease and hypertension.2 In develop-
ing countries, heart failure is mainly nonischemic in
etiology; causes include hypertension, rheumatic heart
disease, and cardiomyopathies related to infectious
agents such as HIV.7 Furthermore, almost 90% of chil-
dren with congeni­tal heart disease now have the prospect
of surviving to adulthood.8 Therefore, the prevalence of
heart failure in the growing population of adults with
congenita­l heart disease is expected to rise.9
Assessment of cardiac function is an integral part
of the management of heart failure. Given its non­
invasive nature and wide availability, echocardio­graphy
is the most-useful imaging modality for evaluating
heart failure and its response to treatment.10 Conven­
Division of Pediatric
tional echo­cardiographic assessment is based on 2D
Cardiology, Department
of Pediatrics and and M‑mode quantification of ventricular volumes and
Adolescent Medicine,
Queen Mary Hospital,
The University of
Competing interests
Hong Kong,
The author declares an association with the following
102 Pokfulam Road,
Hong Kong, China. company: Toshiba Medical Systems Corporation. See the
xfcheung@hku.hk article online for full details of the relationship.
ejection fraction, and Doppler assessment of hemo-
dynamics. The need for geometric assumptions in
the quantification of global ventricular ejection frac-
tion, the largely qualitative assessment of regional myo­
cardial wall motion and thickening, and the sensitivity of
conven­tional para­meters to loading conditions are, none-
theless, well-­recognized.11,12 These conventional indices
of cardiac function, in essence, reflect indirect changes
consequential to myocardial shortening and lengthening
throughout the cardiac cycle.
In the past decade, technological advances have enabled
the direct assessment of myocardial defor­mation for
evaluating global and regional myocardial function.13–15
Myocardial deformation analysis has evolved from the
1D tissue Doppler technique16,17 to 2D speckle track-
ing echocardiography.18–20 Cardiac motion is, however,
3D in nature. Therefore, comprehensive evaluation of
cardiac function in patients with heart failure would
ideally involve an echocardiographic method that allows
quantita­tive 3D assessment of global and regional myo-
cardial function. An important advance of the past
5 years is the development of 3D wall motion track-
ing,21,22 which involves the application of speckle tracking
technology to 3D echocardiographic datasets.
In this Review, the relevance of cardiac mechanics
in heart failure, the basics of myocardial deformation in
three dimensions, and the evolution of myocardial defor-
mation analysis are described. The principles of 3D wall
motion tracking, the assessment of global and regional

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© 2012 Macmillan Publishers Limited. All rights reserved

myocardial deformation of the left ventricle by this novel
imaging modality, and its clinical applications are then
discussed. Finally, the current limitations and future
developments of 3D wall motion tracking are addressed.
Cardiac mechanics in heart failure
Congenital and acquired abnormalities of the heart affect
its function and can impair the processes of filling or
ejection, leading to heart failure. Advances in our under-
standing of the molecular and cellular processes and
pathophysiological mechanisms that contribute to the
development of clinical heart failure have been reviewed
elsewhere.23–25 The focus of this section will, therefore, be
on cardiac mechanics, which are altered by remodeling of
the cardiomyocyte and noncardiomyocyte components
of the heart.
Hypertrophy of cardiomyocytes is a prominent feature
in cardiac remodeling, occurring with either contractile
dysfunction and enlargement of cardiac chambers (sys-
tolic heart failure)23,25,26 or preserved contractile func-
tion with increased chamber thickness (heart failure
with preserved ejection fraction).27,28 Acute, substantial
loss of cardiomyocytes in myocardial infarction alters
ventricular load and renders the ventricle more spheri-
cal.23 Progressive loss of cardiomyocytes, albeit at a low
level, through apoptosis,29–31 necrosis,32–34 and possi-
bly autophagy,35,36 is also believed to contribute to the
remodeling process and contractile dysfunction in heart
failure. Changes in extracellular matrix related to fibro-
sis37,38 and activation of matrix metalloproteinases39,40
are implicated in the dilation of ventricular chambers.
Pathological remodeling with fibrosis and ventricu-
lar dilation is further promoted by disruption of coro-
nary angiogenesis, which contributes to the transition
from adaptive cardiac hypertrophy to heart failure.41 In
failing cardiomyocytes, impaired excitation–contraction
coupling occurs with reduced Ca2+ transient amplitude
and raised diastolic Ca2+ concentration, which contri­
bute to systolic and diastolic dysfunction, respectively.42
Furthermore, metabolic remodeling that occurs in failing
cardiomyocytes results in alteration of substrate utiliza-
tion, progressive loss of ATP and impairment of cardiac
contractile reserve.43
The mechanical consequences of these pathophysio­
logical, cellular processes include changes in 3D geo­
metry of the cardiac chambers, ventricular wall thickness,
dynamic contractile function of the cardiomyocytes, and
passive elastic properties of the myocardium, all of which
can affect myocardial deformation.44 Depending on the
nature and severity of the underlying processes, regional
or global myocardial deformation can be impaired, and
alteration of myocardial deformation in terms of the
magnitude, rate, and timing can also vary. Myocardial
deformation or strain analysis can reveal changes in
cardiac mechanics and facilitate the early detection,
serial assessment, and management of heart failure.
Indeed, the role of myocardial deformation analysis in
the diagnosis, understanding of pathophysiology, moni-
toring of therapeutic interventions, and prognostication
of heart failure is increasingly recognized.13–15,45
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REVIEWS
Key points
■■ Remodeling of the cardiomyocyte and noncardiomyocyte components of the
myocardium in heart failure influences cardiac mechanics
■■ Comprehensive evaluation of cardiac mechanics requires a 3D imaging approach
■■ Novel 3D wall motion tracking allows the assessment of left ventricular volumes,
global and regional myocardial deformation, twist mechanics, and mechanical
dyssynchrony with a single full volume image acquisition
■■ Wall motion tracking in three dimensions shows promise for the assessment
of myocardial function, the detection of subclinical cardiac dysfunction, and the
selection of patients for cardiac resynchronization therapy
■■ 3D wall motion tracking could also improve our understanding of the mechanics
involved in cardiomyopathies and congenital heart disease
■■ Optimization of spatial and temporal resolution of 3D myocardial deformation
analysis is expected with advances in 3D echocardiographic technology
3D myocardial deformation
The architectural design of the heart,46,47 a topic beyond
the scope of this Review, is key to our understanding
of the complex, yet coordinated, process of 3D cardiac
deformation. During cardiac systole, the ventricular
myo­cardium shortens in the longitudinal and circum-
ferential dimensions, thickens in the radial dimension,
and twists along the long axis of the left ventricle. Three
perpendi­cular axes, longitudinal, circumferential, and
radial, repre­sent the geometric coordinates of the left
ventricle. The magnitude of myocardial deformation
along these perpendicular dimensions is quantified by
strain, defined as the percentage change in the length of
myocardial segment relative to the unstressed, original
length at end-diastole. Negative strain represents short-
ening in the longitudinal and circumferential dimensions
and thinning in the radial dimension, whereas positive
strain describes longitudinal and circumferential myo-
cardial lengthening and radial myocardial thickening.
The speed of myocardial deformation is quantified by
the strain rate. In addition to the three ‘normal strain’
compo­nents along the three perpendicular axes, six ‘shear
strain’ compo­nents exist, which are related to forces that
act parallel to the surface of myocardial planes and slide
the myocardial layers over one another (Figure 1).45,48,49 The
normal strain components are frequently referred to as
‘principal strains’. In most studies of myocardial defor-
mation, the focus has been on the assessment of one
or more components of normal strain using 1D or 2D
e­chocardiographic imaging modalities.
Twist mechanics of the left ventricle (Figure 2) are
related to the helical arrangement of myocardial fibers,
which is important for equal redistribution of stress and
strain in the heart.50 The myocardial fibers change from
a right-handed helix in the subendocardium to a left-
handed helix in the subepicardium.51 During iso­volumic
contraction, an initial global anticlockwise rotation of
the heart occurs, as viewed from the cardiac apex. 52
During ventricular ejection, the apex continues its anti-
clockwise rotation whereas the base rotates in a clock-
wise direction. In the isovolumic relaxation phase, the
apex recoils rapidly with clockwise rotation to generate a
steep decay of ventricular pressure and an active suction
force.53–55 Untwisting of the left ventricle is completed in
early diastole.
REVIEWS
a b y constitute stable patterns or ‘fingerprints’ that allow
x new location of speckle patterns in successive frames
Circumferential
z and provides spatial displacement for direct quantifi-
FXY
FYX
FZX
Radial
FZY
Longitudinal
FYZ
FXZ
Figure 1 | Myocardial deformation in three dimensions. a | Three perpendicular
axes—longitudinal, circumferential, and radial—represent the geometric
coordinates of the left ventricle. The three components of ‘normal strain’, often
referred to as ‘principal strains’, are related to forces that act along these
perpendicular dimensions. b | The six ‘shear strain’ components are related to
forces (F) that act parallel to the surfaces of the ‘cube’ of left ventricular
myocardium. The x, y, and z axes define the 3D Cartesian coordinate system and
represent, in terms of geometric coordinates of the left ventricle, circumferential,
longitudinal, and radial directions, respectively.
Several parameters have been used to quantify left
ventricular (LV) twist mechanics—rotation, twist (twist
angle), and torsion (twist gradient).15,56–58 Rotation refers
to the angular rotation of the myocardium in the short-
axis planes, as viewed from the cardiac apex, around
the LV longitudinal axis and is expressed in degrees
or radians. By convention, anticlockwise rotation is
assigned a positive value whereas clockwise rotation
is given a negative value. Twist is defined as the absolute
apex-to-base difference in rotation and is also expressed
in degrees or radians. Normalization of twist by LV
length gives torsion in degrees or radians per cm. This
normalization enables comparison of maximal twist
between left ventricles of different sizes.59
Evolution of deformation analysis
Tissue Doppler imaging is used to determine regional
myocardial tissue velocities in one dimension, on the basis
of which regional strain and strain rate are derived.16,17
Measurement of tissue velocities in multiple regions in
the LV short-axis planes enables assessment of LV tor-
sional deformation.56 However, this technique has major
limitations that include angle dependency, noisy signals
leading to poor quality Doppler-derived strain and strain
rate curves, assessment confined to myocardial segments
that move along the direction of the ultrasound beam,
and confounding of interpretation by tethering of non-
contractile scar tissue to adjacent contractile myocardium
and cardiac translational movements.14,15,58
2D speckle tracking echocardiography overcomes
some of the limitations of 1D tissue Doppler imaging,
and has emerged as a largely angle-independent modality
for analysis of myocardial deformation.18–20 Speckles that
appear in grayscale images are natural acoustic markers
generated from the reflection, interference, and scatter-
ing of ultrasound beams in myocardial tissue. Clusters
of speckles (kernels) within a defined region of interest
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tracking from frame to frame. The 2D speckle tracking
algorithm employs template matching to search for the
cation of myocardial strain and angular rotation in a
largely angle-independent manner. The strain rate and
rotational velocities can then be derived from the linear
and rotational displacement, respectively, of the speckle
patterns divided by the time interval between successive
frames. Using 2D speckle tracking, global and regional
LV longitudinal deformation can be determined from
the apical plane, circumferential and radial deforma-
tion from the short-axis planes, and twist mechanics
based on differences in rotation of the apical and basal
short-axis planes.
Notwithstanding the advantages of 2D speckle tracking
over tissue Doppler imaging, shortcomings inherent to
its 2D nature include the failure to track speckles moving
out of the 2D planes owing to cardiac motion (out-of-
plane motion), inability to monitor shear strain, use of
foreshortened views that can affect the accuracy of longi-
tudinal deformation assessment, and the need to perform
basal and apical acquisitions separately for assessment
of twist mechanics. To address these limitations and
provide a more-comprehensive evaluation of mechanics
from the 3D perspective, novel 3D wall motion tracking
technology has been developed and introduced over the
past 3 years into the clinical arena.21,22,60,61
3D wall motion tracking
3D wall motion tracking is the application of speckle
pattern matching technology to 3D echocardiographic
datasets. Early work on tissue-mimicking phantoms
and simulated data provided the theoretical basis for
this technique.62–65 In the past 2 decades, the develop-
ment of matrix array transducers, which contain arrays
of piezoelectric elements capable of scanning pyramidal
volumes, and new-generation ultrasound scanners with
real-time full volume capabilities have paved the way for
translation of 3D wall motion tracking technology into
clinical use. With the introduction of techniques such as
gated capture over several cardiac cycles66 and multiple
line acquisition for each transmitted pulse67 to optimize
frame rate, a 3D full volume frame rate of 20–30 volumes
per second can be achieved.
Whereas 2D speckle tracking involves template match-
ing over successive frames of 2D images,18–20,68 3D wall
motion tracking involves tracking of volumetric box
templates in the 3D dataset (Figure 3).22,69 Motion estima-
tion points, located in proximity to the endocardial and
epicardial boundary surfaces, are centered in the cubic
template volumes. The motion vector in three dimen-
sions for each of the motion estimation points between
successive volume frames is detected by the 3D template-
matching algorithm, which searches the most-similar
point in the next volume. Frame-by-frame integration of
the interpolated motion vectors enables points of interest
within the myocardium to be tracked, and thus deriva-
tion of various deformation parameters throughout the
 REVIEWS

entire cardiac cycle. The computation becomes more a b

complex and, theoretically, more time consuming as 3D
template matching increases the template size and the
search volume. With a matching algorithm specifically
designed for 3D speckle tracking, a processing time of
≤0.5 s per volume is possible.22 An estimated processing
time within 10–15 s for analysis of one cardiac cycle in a
patient with a heart rate of 60 bpm, therefore, becomes
practical for clinical use.
Notwithstanding the lower frame rate and more-
complex processing of 3D wall motion tracking than
the 2D technique, this novel imaging modality confers
several potential advantages over 2D speckle tracking.
First, the capability to track speckles irrespective of
their directions in three dimensions. Second, avoidance c d
of errors caused by heart-rate variability with separate
acquisitions. Third, efficient single acquisition with
simultaneous assessment of global and regional myo-
cardial mechanics and, fourth, assessment of truly 3D
global and regional strain (Figure 4).
Analysis of LV 3D wall motion requires the acquisition
of a full-volume dataset from the cardiac apex. Capturing
four subvolumes over four consecutive cardiac cycles is
preferred to a single-cycle acquisition. Care should be
taken to include the entire LV cavity during acquisi-
tion using a wide sector. The full volume mode, with
inclusion of four cardiac subvolumes of 90° × 22.5°,
enables the acquisition of a large sector of 90° × 90° to
cater for dilated left ventricles in the setting of heart Figure 2 | Twist mechanics of the left ventricle. a | Isovolumic contraction. An initial,
failure. On the basis of the 3D dataset, five 2D cross- global anticlockwise rotation of the heart occurs. b | Ventricular ejection. The apex
sectional planes can be generated for tracing the endo- continues its anticlockwise rotation, whereas the base rotates in a clockwise
direction. c | Angular rotation of basal and apical myocardial planes as viewed from
cardium and epicardium—an apical four-chamber
the cardiac apex is assessed for calculation of left ventricular twist (twist angle).
plane, an orthogonal two-chamber plane, and three d | Ventricular twist and torsion (twist gradient). Twist is defined as the absolute
short-axis planes (near the apex, mid-level, and the base apex-to-base difference in rotation. Normalization of twist by the ventricular length
of the left ventricle). Although the LV endo­c ardium gives torsion. The dotted line represents the left ventricular central axis, the solid
and epicardium can be traced automatically by the 3D lines show the relative angular rotation of the cardiac base and apex.
wall motion tracking software, verification and manual
adjustment should be performed where necessary on
the basis of the 2D cross-sectional planes. The soft- reported superior accuracy and reproducibility for the
ware further automatically divides the left ventricle 3D technique. 61 Compared with the 2D method, 3D
into 16 segments, as defined by the American Society of speckle tracking had a better correlation with CMR
Echocardiography,70 or 17 segments as proposed by the parameters (intraclass correlation coefficient (r) = 0.87–
AHA,71 for the assessment of magnitude and timing of 0.92 versus 0.72–0.88), smaller biases (1–16 ml versus
regional myocardial deformation. 10–30 ml), narrower limits of agreement (SD = 28–37 ml
versus 36–51 ml), and lower interobserver (11–14% versus
Assessment of LV mechanics 16–17%) and intraobserver (12–13% versus 12–16%)
Ventricular and atrial volumes variability.61 In another study, 3D speckle tracking echo-
Whereas direct quantification of ventricular volume cardiography was found to have excellent accuracy for
by 3D echocardiography relies on a semi-automated quantifying LV ejection fraction (r = 0.91) compared with
algorithm that detects cavity–endocardial wall inter- CMR, although the LV volumes were under­estimated
face, 72 3D wall motion tracking involves tracking of with larger biases (13–34 ml).74 The reported r values of
speckle templates at the endocardial border throughout 0.85–0.99, for measurement of LV volumes and ejection
the cardiac cycle. 61,73 The LV end-diastolic and end- fraction based on consecutive recordings performed
systolic volumes are derived from counting the voxels within 1 h, suggest good test–retest reliabi­lity for 3D
(‘bricks’ of pixels in the 3D volume dataset) within the speckle tracking.73 Kleijn et al. confirmed the reproduci­
endocardial surface, and the ejection fraction is calcu- bility of this 3D technique in LV volume quantifi­cation,
lated accordingly. Nesser et al. compared 3D speckle and demonstrated comparability of the results with
tracking echocardiography with the 2D method, using those obtained using the 3D direct volumetric method.75
cardiac magnetic resonance (CMR) as a reference, These findings indicate the interchangeability of the two
for the quantifi­cation of LV volumes in humans, and methods in clinical practice.

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REVIEWS
a Starting frame Next frame
b Starting volume Next volume
Figure 3 | Comparison between 2D speckle tracking and 3D wall motion
tracking. a | 2D speckle tracking with template matching of speckle patterns
over successive frames of 2D gray-scale images. Clusters of speckles
represent natural acoustic markers generated from the reflection, interference,
and scattering of ultrasound beams in myocardial tissue. They form stable
patterns within a defined region of interest (white square) for tracking. The 2D
speckle tracking algorithm searches for the new location of the region of
interest (blue square) from one frame to the next frame (red arrow) of 2D images.
b | 3D wall motion tracking involves tracking of volumetric box templates (white
cube) in the full-volume echocardiographic dataset over successive volumes.
Motion estimation points are centered in the cubic template volumes. The 3D
template matching algorithm detects the motion vector (red arrow) of these
points and tracks the volume of interest (blue cube) from the starting volume
frame to the next.
Strong evidence exists for an association between left
atrial enlargement and adverse cardiovascular outcomes
in patients with heart failure.76,77 Although a software
package dedicated to 3D wall motion tracking of the
left atrium is currently not available, Kleijn et al. traced
the left atrial endocardial border with exclusion of the
appendage and pulmonary veins and obtained minimum
and maximal left atrial volumes comparable to those
obtained by direct 3D volumetric quantification.75
Global and regional deformation
3D speckle tracking-derived strain has been validated
against sonomicrometry in anesthetized sheep.69 Good
correlations with sonomicrometric data have been found
for segmental longitudinal (r = 0.89), circumferential
(r = 0.90), and radial (r = 0.84) strain components at
baseline, during pharmacological stress, and with induc-
tion of myocardial ischemia by coronary artery occlu-
sion. The technique could, therefore, be useful clinically
for the detection of altered regional myocardial func-
tion during stress testing. Notably, however, validation
of this technique for derivation of 3D strain in humans
is not feasible, as noninvasive gold-standard methods
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© 2012 Macmillan Publishers Limited. All rights reserved
are unavailable. Nonetheless, a good correlation with 2D
tagged CMR for global circumferential strain, albeit with
a mean difference of 10% between CMR-derived and 3D
speckle tracking-derived values, has been reported in
healthy humans.74
As global longitudinal, circumferential, and radial
systolic strain and regional strain of the 16 LV segments
can be analyzed with one acquisition using 3D wall
motion tracking, the time required for data acquisition
and strain analysis can be shortened to one-third of that
required for 2D speckle tracking echocardiography.78,79
Low intraobserver and interobserver variability, with
r values of 0.79–0.87 for longitudinal strain, 0.81–0.82
for circumferential strain, and 0.77–0.91 for radial strain
measurements, has been reported for this method.78,79
Normal (reference) strain values based on 3D speckle
tracking are limited. In a group of 46 healthy volunteers
aged 29 ± 7 years, Saito et al. reported an average global
longitudinal systolic strain of –17.0% ± 5.5%, circum-
ferential strain of –31.6% ± 8.0%, and radial strain of
34.4% ± 11.4%.79 Comparisons of global79 and regional60,78
strain data between 3D and 2D speckle tracking have,
nonetheless, yielded discordant results. The discrepancy
has been attributed to the use of different algorithms in
strain calculation, and because the novel 3D technique
takes into account the complex 3D cardiac motion and
the twisting and longitudinal shortenin­g of the left
v­entricle during systole.60,79
Endocardial area strain
An innovative feature of 3D wall motion tracking is
the ability to monitor regional changes in endocardial
surface area (area tracking) throughout the cardiac cycle.
During ventricular contraction, the endocardial surface
area decreases as a result of myocardial shortening in
the longitudinal and circumferential dimensions and
myocardial thickening in the radial dimension. Area
strain refers to the percentage change in the endo­cardial
surface area during the cardiac cycle relative to the end-
diastolic endocardial area (Figure 5). This measure
can be regarded as a composite parameter that inte-
grates the regional consequences of deformation in the
longitudinal, circumferential, and radial dimensions.80,81
Endocardial surface area tracking has been validated
against measurements obtained from sonomicrometry
crystals implanted on the LV endocardium in anesthe-
tized sheep.80 In this animal study, area strain correlated
strongly with the sonomicrometry-derived area change
ratio (r = 0.87) and with longitudinal (r = 0.73) and
circum­ferential (r = 0.79) strain derived from the same
3D speckle tracking dataset. The area strain, however,
showed greater changes compared with individual strain
components during pharmacological stress and acute
myocardial ischemia induced by coronary occlusion.
As the endocardium is more sensitive to ischemia than
the epicardium,82 incorporation of area strain measure-
ments during stress echocardiography could increase the
sensitivity of detecting myocardial ischemia. Kleijn et al.
reported a global LV area strain of –43.1% ± 2.1% among
56 healthy adults. 83 They further showed excellent
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a C3 A B b

L0

C5

C7 80%
EDV 116.93 ml 0 ms
ESV 46.52 ml 293 ms
EF 60.22%
1.05* MV 163.58 g est. LV MASS

L – L0
3D strain = × 100%
L0
–80%

c
Longitudinal strain Circumferential strain Radial strain
Time: 148 msec Time: 791 msec Time: 49 msec
10 5
90 Max1
5 3.38 0 2.77 80 82.34 Max2
0 [ms] –5 [ms] Min1
70
Min2
–5 –10 60 Auto
–10 –15 50
Percentage

40
–15 –20
30
–20 –25
20
–25 –30
10
–30 –35 [ms]
0
–35 –35.55 –40 –40.36 –10
–8.79
–40 –45 –20

Figure 4 | Measurements of left ventricular strain using 3D wall motion tracking. a | Analysis of 3D strain. On the basis of
the full-volume 3D dataset acquired from the cardiac apex, five 2D cross-sectional planes are generated for tracing the
endocardial and epicardial surfaces: (A) apical four-chamber, (B) apical two-chamber, (C3) apical short axis, (C5) mid short-
axis, and (C7) basal short-axis. b | True 3D strain is calculated from tracking of speckle templates in three dimensions.
Lo represents the unstressed, original length at end-diastole, L is the length of myocardial segment during the cardiac cycle
along the 3D vector. c | Simultaneous analysis of global (white curve) and regional (colored curves) longitudinal,
circumferential, and radial systolic strain of the 16 left ventricular segments in a healthy young adult. The respective
systolic strain values are measured from the y‑axis. The time to trough regional longitudinal and circumferential strain and
peak regional radial strain can be measured from the x‑axis for calculation of indices of left ventricular dyssynchrony.

intraobserver and interobserver reproducibility for
both global and regional area strain measurements in
patients with various heart diseases. Low variability for
intraobserver and interobserver measurements of global
area strain (~6% and ~10%, respectively) has also been
reported in other studies.81,84
LV twist mechanics
Assessment by tissue Doppler imaging 56 and 2D speckle
tracking echocardiography 57,58 of LV twist mechanics
is feasible. Nonetheless, the need to acquire apical and
basal short-axis cine loops from different cardiac cycles,
the varying localization of the apical and basal planes
among individuals, and out-of-plane speckle motion
constitute the main sources of errors in twist measure-
ment by these methods. 3D wall motion tracking, by con-
trast, enables simultaneous determination of rotation of
all the 16 LV segments. The average magnitude of rota-
tion of the six basal (septal, inferior, posterior, lateral,
anterior, and anteroseptal) and four apical (septal, infe-
rior, lateral, and anterior) segments can be calculated.
LV twist is derived from systolic rotation of the apical
relative to the basal segments (Figure 6). Division of LV
twist by the distance between apical and basal segments
yields torsion to adjust for differences in LV dimensions
among individuals.59

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End–diastole End–systole
Aed – Aes
Aed Area strain = × 100% Aes
Aed
Figure 5 | Area tracking of endocardial surface and calculation of peak area strain.
The changes in endocardial surface area of the 16 regional segments are tracked
throughout the cardiac cycle. During ventricular contraction, the endocardial
surface area decreases as a result of myocardial shortening in the longitudinal
and circumferential dimensions and myocardial thickening in the radial dimension.
Area strain, the percentage change in endocardial surface relative to the end-
diastolic surface area, is regarded as a composite parameter that integrates the
regional consequences of deformation in the longitudinal, circumferential, and
radial dimensions. Peak area strain is calculated as percentage change in the
end-systolic endocardial surface area relative to the end-diastolic endocardial area.
Abbreviations: Aed, endocardial surface area at end-diastole; Aes, endocardial
surface area at end-systole.
In vitro validation studies using pig hearts mounted
on rotary motors have suggested accurate tracking of
LV rotation by 3D wall motion tracking.85,86 Although
it overestimates rotation magnitude, the 3D technique
showed smaller biases compared with 2D speckle track-
ing echocardiography.86 Limited data from 39 healthy
young adults showed a smaller degree of peak LV twist
derived from the 3D method than from 2D tracking
(10.2 ± 7.6° versus 13.4 ± 8.2°).87 Intrinsic methodological
differences between the two techniques probably account
for the observed differences.
LV dyssynchrony
The role of echocardiographic evaluation of dyssynchro-
nous myocardial contraction in the selection of patients
for, and predicting response to, cardiac resynchro­nization
therapy (CRT) has been extensively explored. LV mecha­
nical dyssynchrony has been assessed using tissue Doppler
imaging,88 2D speckle tracking echo­cardiography,89 and
3D volumetric technique.90 Although the gold-standard
method of assessment has yet to be defined, 3D wall
motion tracking could offer potential advantages over
other modalities. First, by enabling simultaneous evalu-
ation of 3D motion in all the 16 LV segments. Second,
through concomitant assessment of regional wall motion
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© 2012 Macmillan Publishers Limited. All rights reserved
40% abnormalities and global ventri­cular ejection fraction.
Third, by utilizing different strain (longi­tudinal, circum­
ferential, and radial, 3D, and area strain) and twist
parameters to assess ventricular dyssynchrony.
Several 3D wall motion tracking-based parameters
have been used to quantify LV mechanical dyssynchrony
in the 16 LV segments. These measures include, standard
deviation of time to peak regional systolic strain,84,91–93
standard deviation of time to minimum endocardial
surface area,81,84,94 maximal opposing wall delay in time
to peak radial strain,91,92 and area tracking-based strain
dyssynchrony index.95–97 The last of these indices involves
calculation of the mean absolute differences between
peak area strain and end-systolic area strain, and has
–40%
been regarded as an index of circumferential and longi­
tudinal mechanical dyssynchrony and residual endo-
myocardial function.95 Additionally, a rotation disper­sion
index to quantify rotational heterogeneity on the basis
of the standard deviation of time to peak r­otation has
been described.98
Activation imaging
Imaging of cardiac activation could facilitate the defini­
tion of ventricular dyssynchrony, identification of the site
of latest mechanical activation,91 assessment of myo­cardial
scarring, and understanding of mechanisms and manage-
ment of cardiac arrhythmias.99,100 Given the close tempo-
ral relationship between electrical activation and regional
wall motion,101 an activation imaging techno­logy based
on 3D wall motion tracking has been newly developed.102
This new technology defines the onset of myo­cardial
segmen­tal deformation and displays the time delay in
various color codes. Further validation of this technolog­y
and assessment of its reproducibility are required.
Clinical applications in heart failure
Assessing global LV performance
Global LV myocardial performance can be assessed by
systolic strain parameters (longitudinal, circumferential,
radial, 3D, and area strain). Global area strain has been
shown to be a sensitive parameter for detection of even
subtle LV systolic dysfunction. Wen et al. investigated
a cohort of healthy individuals and patients with either
stage A, B, C, or D heart failure (ACC/AHA classifi­
cation). They showed a progressive decrease in all the
3D speckle tracking global strain parameters and in 2D
echocardiography-derived LV ejection fraction from
healthy adults to patients with progressive stages of heart
failure, with stage D being associated with the lowest
values.103 However, only global area strain was found
to differentiate patients with stage A heart failure from
healthy individuals. A cut-off area strain value of –29%
resulted in a high level of agreement with measure-
ments of ejection fraction for detection of reduced LV
function (ejection fraction cut-off 50%).103 Global area
strain has also been demonstrated to correlate better
with 3D echocardiography-derived LV ejection fraction
and indexed LV output than with global longitudinal,
circumferential, and radial strain. 104 The strength of
global area strain as an index of global LV performance

15º
a b
Degrees
–15º
Figure 6 | Assessment of left ventricular twist by 3D wall motion tracking. a | Color-coded 3D left ventricular display of the
base-to-apex increase in the magnitude of twist. b | Time–twist curve showing left ventricular twist (arrow) derived from
average rotation of the four apical segments relative to the cardiac base.
in patients with heart failure could be related to its
com­posite reflection of longitudinal, circumferential,
and radial myocardial deformation80,81 and the greater
suscepti­bility of the endocardium than the epicardium
to ischemic injury.82
Load dependency of 3D wall motion tracking para­
meters has been explored in patients with chronic renal
failure undergoing hemodialysis.105 Whereas LV end-
diastolic volume and ejection fraction were signifi­
cantly reduced after dialysis, global LV radial strain,
longitudinal strain, rotation, and twist remained similar
to baseline values. Nonetheless, earlier studies demon-
strated the load dependency of strain106 and twist 107 as
assessed by either tissue Doppler imaging or 2D speckle
tracking echocardiography.
In the assessment of global LV performance, 3D track-
ing strain parameters might be less dependent on loading
conditions than on LV ejection fraction, although further
studies are needed to confirm this preliminary obser­
vation.105 Of all the strain parameters, global area strain
seems to be the most promising for the early detection
of subtle LV dysfunction.
Quantifying regional function
Assessment of regional myocardial function is important
in the assessment of ischemic and nonischemic heart dis-
eases. Maffessanti et al. reported the first utilization of
3D speckle tracking echocardiography for the assessment
of regional wall motion in a cohort comprising healthy
individuals and patients with ischemic heart disease,
dilated cardiomyopathy, or valvular heart disease.60 In LV
segments with abnormal wall motion, as defined by inde-
pendent review of CMR images, segmental, longitudinal,
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© 2012 Macmillan Publishers Limited. All rights reserved
REVIEWS
14.0
Twist Max1
13.0 Time: 293 ms Max2
12.58 Min1
12.0 Min2
Auto
11.0
10.0
9.0
8.0
7.0
6.0
5.0
4.0
3.0
2.0
1.0
0.0 [ms]
0.00
–1.0
and radial strain and displacement and circumferential
strain were significantly reduced.60 Kleijn et al. compared
segmental area strain measurements with visual assess-
ment of segmental wall motion abnormalities by experi-
enced echocardiographers in patients with ischemic or
nonischemic cardiac conditions.83 Segmental area strain
was significantly lower in akinetic and hypokinetic seg-
ments compared with normokinetic segments. Global
area strain correlated with the average wall motion score
of all segments analyzed. Agreement between the two
assessment methods was found in 94% of normokinetic,
55% of hypokinetic, and 91% of akinetic segments, using
cut-off segmental area strain values of –32% and –24%
for hypokinetic and akinetic segments, respectively.83
The lower agreement for hypokinetic segments was
attributed by Kleijn et al. to greater subjectivity involved
in visual classification of hypokinesia.83 In patients with
a history of myocardial infarction, all the 3D speckle
tracking strain parameters (longitudinal, circum­ferential,
radial, 3D, and area strain) have been found to differ
between transmural and nontransmural necrotic seg-
ments as identified by delayed contrast-enhanced CMR
imaging.108 Global longitudinal, circumferential, and
area strain measurements correlated best with global
scar extent. Furthermore, 3D speckle tracking-derived
longitudinal and area strain values, but not 2D speckle
tracking parameters, were found to be impaired early,
even in segments with limited (<25%) necrosis.108 Taken
together, these studies suggest that 3D segmental myo-
cardial deformation analysis is feasible and potentially
useful in the clinical setting for quantitative assessment
of regional wall motion abnormalities and extent of
m­yocardial scarring.
REVIEWS

a Patient A Patient B ▶ Figure 7 | Identification of the site of latest mechanical

Apex Apex 40% activation and monitoring of response to CRT by 3D wall
motion tracking. a | Examples of color-coded 3D left
ventricular displays and bull’s-eye plots from two patients
undergoing CRT. The site of latest mechanical activation
(arrow) was the mid-posterior segment in patient A and
mid-lateral segment in patient B. b | Examples of color-
Inf Lat Inf Lat coded 3D left ventricular displays and time-strain curves in
a patient before and the day after CRT, demonstrating
acute improvement in left ventricular synchrony. Reprinted
from Am. J. Cardiol. 105 (2), Tanaka, H. et al. Usefulness of
three-dimensional speckle tracking strain to quantify
dyssynchrony and the site of latest mechanical activation.
Base Base 235–242 © 2010, with permission from Elsevier.
Abbreviations: Ant, anterior; Ant-sept, anterior-septum; CRT,
Ant-sept Ant-sept cardiac resynchronization therapy; ECG, electrocardiogram;
Inf, inferior; Lat, lateral; Post, posterior; Sept, septal.
Sept Ant Sept Ant
methods were used, tempered initial enthusiasm. At
6 months after implantation of CRT devices, predic-
tion of the clinical composite score response by the 12
parameters varied widely (sensitivity 6–74%, specifi­
Inf Lat Inf Lat city 35–91%), and for the prediction of LV end-systolic
volume response (≥15% reduction; sensitivity 9–77%,
specificity 31–93%). On the other hand, a meta-analysis
Post Post –40%
published in February 2012 suggested that assessment
b Pre CRT Day after CRT of LV dyssynchrony by 3D echocardiography could
Apex Apex 40%
add value to current selection criteria for prediction of
response to CRT.113 The prospective Speckle Tracking
and Resynchronization (STAR) study 114 provides
further evidence of the utility of myocardial deformation
assessment in multiple dimensions for the prediction of
Sept Post Sept Post response and long-term outcomes after CRT.
In patients with heart failure, LV ejection fraction
≤35%, and a QRS duration ≥120 ms who were referred
for CRT, Tanaka et al. successfully quantified the magni­
tude of LV dyssynchrony using two 3D speckle track-
ing parameters—maximal opposing wall delay in time
Base Base
to peak radial strain, and standard deviation of time to
–40% peak radial strain in 16 segments.91 Additionally, on the
38.64
39.0
35.0
basis of time to peak segmental radial strain, they identi-
35.1 34.30
31.2 31.5 fied the most-common sites of latest mechanical activa-
27.2 28.0
24.5 tion as the mid posterior, basal posterior, mid lateral, and
23.4
19.5 21.0 basal lateral segments, and documented improvements
Radial strain

17.5
15.6 14.0 in 3D mechanical dyssynchrony in patients who under-
11.7 10.5
7.8 7.0 went CRT (Figure 7). Identification of the site of latest
3.9 3.5
0.0 0.0
mechanical activation would probably be facilitated by
–3.9 –3.5 novel color-coded activation imaging technology,102 and
–7.8 –7.0
–11.7 –10.5 could help to guide the positioning of the LV pacing lead.
–15.6 –14.0 –13.83 Tatsumi et al. demonstrated LV dyssynchrony (increased
–19.5 –18.47 area strain dyssynchrony index) in patients with heart
ECG ECG failure and short QRS duration compared with healthy
control individuals.95
Cardiac resynchronization The results of a small cohort study (n = 14) by the same
Cardiac resynchronization is an established treatment investigators suggested that the area strain dyssynchrony
for patients with advanced heart failure.109–111 Interest index might be a better predictor of response to CRT than
has developed in the use of echocardiography to select conventional dyssynchrony parameters, such as inter-
patients with heart failure for, and predict their response ventricular mechanical delay, tissue Doppler analysis
to, CRT. Nonetheless, the results of the multicenter of longitudinal dyssynchrony, and 2D speckle analysis of
Predictors of Response to CRT (PROSPECT) trial,112 radial dyssynchrony.96 This preliminary finding, however,
in which 12 parameters of LV dyssynchrony based on requires confirmation in controlled studies with a larger
conventional echocardiographic and tissue Doppler patient population. Tatsumi et al. used the longitudinal,

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© 2012 Macmillan Publishers Limited. All rights reserved

circumferential, and radial strain dys­synchrony index
(mean absolute differences between peak strain and
end-systolic strain in 16 segments) to predict long-term
outcomes after CRT over a 4‑year period.97 They found
that combining the three types of strain dys­synchrony
index enabled more-accurate prediction of the combined
end point of death or hospitalization owing to worsening
heart failure than the use of each indivi­dual index alone.
One advantage of 3D speckle tracking over the 3D volu-
metric method90 for the identi­fication of dys­synchrony is
direct assessment and quanti­fication of active myo­cardial
deformation in individual LV segments. Intuitively,
segments with substantially reduced deformation
would contribute little to global LV function despite
synchronizing the timing of contraction. Therefore,
3D speckle tracking-derived time-strain curves of the
16 LV segments, which provide infor­mation on both
the timing and the magnitude of peak strain, could
improve prediction of response to CRT.
3D wall motion tracking has also contributed to our
understanding of LV mechanics in patients undergoing
right ventricular pacing. Thebault et al. documented an
acute increase in all strain parameters and improvement
of dyssynchrony (standard deviation of time to peak
strain) with switching of right ventricular to biventricu-
lar pacing mode in patients undergoing optimization of
an implanted cardiac resynchronization device.84 They
expressed the results in terms of a global LV performance
index that provided composite information on both the
severity of LV dyssynchrony and magnitude of global
systolic strain. Tanaka et al. found that the pattern of dys-
synchronous mechanical activation was similar between
patients undergoing right ventricular pacing and those
with left bundle branch block.92 Sites of latest mechanical
activation were most commonly the posterior or lateral
segments in both groups. In addition, the investigators
found that LV ejection response and survival free from
transplantation or mechanical support after CRT was
similar between the two groups. Taken together, these
findings support the use of CRT in patients with heart
failure undergoing right ventricular pacing.
In another study in which 3D speckle tracking echo-
cardiography was used, Tanaka et al. showed that patients
with reduced LV ejection fraction who were undergoing
right ventri­cular pacing had greater dyssynchrony and
lower strain in all three dimensions than patients with
preserved ejection fraction who were undergoing right
ventricular pacing or healthy individuals.93 On the whole,
studies to date suggest a promising role for 3D speckle
tracking in the quantification of LV dyssynchrony; selec-
tion of patients for, and prediction of their response to,
CRT; and guidance of positioning of LV pacing leads.
Cardiac mechanics in the cardiomyopathies
In patients with nonischemic dilated cardiomyopathy,
both 2D speckle tracking 115 and 3D wall motion track-
ing have revealed a significant reduction in longitu-
dinal, circum­ferential, and radial strain.116 In healthy
indivi­duals, longitudinal and circumferential strain
increases from the base to cardiac apex, whereas radial
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REVIEWS
strain is greatest in the mid region and smallest at the
apical region. However, these regional differences were
not found by Duan et al. in patients with nonischemic
dilated cardiomyopathy.116 In another study, a novel
association between LV dyssynchrony and rotational
hetero­geneity in patients with idiopathic dilated cardio-
myopathy was demonstrated. 98 LV dyssynchrony and
rotational dispersion indices were found to be greater,
whereas twist and torsion were smaller, in patients with
wide QRS complexes than in those with narrow QRS
complexes. Furthermore, LV torsion was inversely
related to LV dyssynchrony and rotational dispersion
indices. Improvement of LV dyssynchrony after CRT in
patients with wide QRS complexes was associated with
reduction in rotation dispersion index and increase in
LV twist.98
3D speckle tracking echocardiography has also pro-
vided insights into LV twist and untwist mechanics in
the setting of hypertrophic cardiomyopathy.117 Patients
with this condition were found to have increased LV
twist owing to greater apical rotation, which was more
marked in those with obstructed LV outflow, compared
with healthy control individuals. Despite enhanced LV
contraction, the onset of untwist was delayed, comple-
tion of untwist during early diastole was limited, and the
untwisting velocity was lower in patients with hyper­
trophic cardiomyopathy than in the control group.117
These findings enhance our understanding of impaired
relaxation in hypertrophic cardiomyopathy.
Baccouche et al. used 3D speckle tracking echo­
cardiography to differentiate between amyloidosis and
hypertrophic cardiomyopathy, both of which cause LV
hypertrophy.118 Whereas the base-to-apex decrease in
radial strain was preserved in patients with hyper­trophic
cardiomyopathy, the pattern was reversed in those with
amyloidosis. The pattern of changes in base-to-apex
strain was found to have a diagnostic sensitivity of 83%
using CMR as the reference standard.118 The utility of
3D speckle tracking in diagnostic imaging and follow-
up of basal hypercontractility and apical dyskinesia in
Takotsubo cardiomyopathy has been described in a
79-year-old woman admitted with acute coronary syn-
drome.119 The 3D technique might enable early recog­
nition of the characteristic wall motion abnormalities
and serial monitoring of their recovery.
Congenital heart disease
To date, only one study of 3D wall motion tracking for
the assessment of ventricular function in patients with
congenital heart disease has been published. Li et al.
examined global LV performance in 30 patients who had
undergone repair of tetralogy of Fallot by simultaneously
measuring global LV area strain and standard deviation of
time to peak area strain in 16 segments as a percentage
of RR interval.81 The global performance plot of the two
parameters identified 87% of patients as having impaired
LV performance. This composite assessment can be per-
formed conveniently with a single acquisition, which is
not possible with 2D imaging modalities, and could be
useful for serial tracking of LV performance.
REVIEWS
Other potential applications
Myocardial deformation analysis has been used to define
subclinical cardiac dysfunction and to improve our under-
standing of its progression to overt heart failure.13,45,120 In
patients with untreated hypertension and normal LV
ejection fraction, 3D speckle tracking echo­cardiography
has been shown to identify early LV functional changes
characterized by reduced global longitudinal, radial, and
area strain.121 Global area strain, in particular, was inde-
pendently associated with mean blood pressure and LV
mass index. Differential myocardial deformation among
various types of LV adaptive response in hypertension
have also been demonstrated.122 In obese children aged
13.3 ± 2.7 years, 3D speckle tracking-­derived LV longitu­
dinal and circumferential strain, as well as twist and
torsion were found to be reduced.123
With the additional information provided by the third
dimension, 3D wall motion tracking could improve
detection of subclinical cardiac dysfunction in condi-
tions such as chemotherapy-induced cardio­toxicity,124,125
diabetes mellitus,126 and renal insufficiency.127 Superiority
of 3D over 2D speckle tracking in this regard, however,
has not yet been demonstrated. The results of several
studies suggest associations between 2D speckle track-
ing strain parameters and clinical outcomes in patients
with acute128,129 or chronic130 heart failure. Further studies
to define the role of 3D speckle tracking para­meters
in predicting outcome of patients with heart failure
are warranted.
Adoption of myocardial deformation parameters as
end points in clinical trials of patients with heart failure
could be advantageous given the semiautomatic quantifi­
cation, multidimensional assessment of myocardial
mechanics, and comprehensive evaluation of global and
regional deformation.131 For 3D speckle tracking echo­
cardiography, however, the lack of standardization of raw
data format and tracking algorithms among manufac­
turers currently constitutes a formidable obstacle to its
use in clinical trials.
Current limitations
The accuracy of 3D wall motion tracking largely depends
on image quality. Feasibility of 3D speckle tracking echo-
cardiography has been reported to vary from 75% to 100%,
with failures attributed to either suboptimal image quality or
limited acoustic window.60,61,73,75,78,79,83,84,87,91,92,97,98,103–105,108,117
The relatively low spatial resolution of 3D wall motion
tracking can affect the delineation of endocardial and
epicardial surfaces and, in turn, the accuracy of track-
ing. Nonetheless, with the rapid evolution of ultrasound
technolog­y, improvement in spatial resolution is to
be expected.
The temporal resolution of 20–30 volumes per second is
another limitation of current 3D technology. At its present
level, the temporal resolution of the 3D technique renders
analysis of rapid cardiac events during the isovolumic
contraction and relaxation phases difficult. In addition,
3D speckle tracking-derived rates of systolic and dia-
stolic deformation and velocities of twisting and untwist-
ing are yet to be included in the analysis software and
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© 2012 Macmillan Publishers Limited. All rights reserved
validated. Although capturing of four subvolumes over
four consecu­tive cardiac cycles is preferable to a single-
cycle acquisition to improve resolution, stitch artifacts
become inevitable in uncooperative patients and in those
with cardiac arrhythmias.
Manufacturer-dependent proprietary algorithms are
currently used for analysis of 3D speckle tracking para­
meters. Intertechnique agreement has been shown to
be suboptimal, both for images acquired from different
machines and images acquired from the same machine
using different software.132 When appraising the literature
on 3D speckle tracking, discordance in measurements
between manufacturers should be taken into account.
3D wall motion tracking is in its infancy. However,
the results of validation, feasibility, and clinical studies
published to date suggest a role for this new, noninva-
sive technology in the assessment and manage­ment
of patients with heart failure. The European Association of
Echocardiography/American Society of Echocardiography
document on 3D echo­c ardiography, published in
January 2012, acknowledges the great potential for
future clinical application of 3D strain measurements.133
Additional studies are undoubtedly required to assess
whether 3D speckle tracking is superior to the 2D method,
and to define the value of 3D speckle tracking in a wide
variety of clinical scenarios.15
Future developments
Assessment of right ventricular function is important
in patients with pulmonary hypertension,134 after repair
of tetralogy of Fallot in both children and adults,135,136
and in patients with a systemic right ventricle. 136 The
complex geometry of the right ventricle, however, renders
assessment by 2D echocardiographic imaging difficult.
Although not designed for right ventricular deformation
analysis, the 3D wall motion tracking algorithm has been
applied in vitro to 3D volume datasets acquired from pig
hearts with incorporation of the entire right ventricle.137
Further research in this area is warranted.
Layer-specific myocardial deformation analysis
for assessing lack of transmural homogeneity by 2D
speckle tracking echocardiography was introduced in
2010.138 Significant reductions in transmural gradients
of LV circum­ferential strain and twist have been found
in patients with heart failure.139 Assessment of 3D sub­
endocardial deformation and transmural gradients
of myocardial deformation and twist could provide
additional insights into LV mechanics in ischemic and
nonischemi­c heart diseases.
Conclusions
Comprehensive assessment of cardiac function is inte-
gral to the management of patients with heart failure.
Recognition of the need to evaluate myocardial perfor-
mance beyond the 2D approach and measurement of LV
ejection fraction has led to the development of 3D wall
motion tracking. This new technology capitalizes on the
vast amount of information contained within the 3D full
volume dataset and the angle-independence of speckle
tracking technology. Assessments of 3D volumes, regional
 REVIEWS

myocardial and endocardial surface defor­mation, and Review criteria

twist mechanics by this technique have been validated and
shown to be reproducible. Novel 3D deformation para­
meters have provided new insights into the LV mechanics
of patients with ischemic and nonischemic heart diseases.
Although the technology is in its infancy, it has begun to
have a role in the clinical assessment of global and regional
myocardial function in heart failure and its manage-
ment, in particular by CRT. Improvements in the spatial
and temporal resolution of 3D wall motion tracking are
expected with the rapid advance in 3D echocardiographic
technology. Future developments in the 3D assessment of
right ventricular and myocardial layer-specific mechanics
are awaited.
References cited in this article were selected by
searching the PubMed database for publications in
English with no date limits. The search terms included
“heart failure”, “cardiac function”, “cardiac dysfunction”,
“cardiac mechanics” “ventricular function”, “three-
dimensional wall motional tracking”, “three-dimensional
speckle tracking”, “deformation imaging”, and “strain
imaging”. The reference lists of key papers were
also searched for additional publications. Meeting
abstracts reporting on the latest developments and
clinical applications of the technology most relevant
to this Review and published since April 2011 were
also considered.

1. [No authors listed] Editorial. On the horizon in
heart failure. Lancet 378, 637 (2011).
2. Roger, V. L. et al. Heart disease and stroke
statistics—2012 update: a report from the
American Heart Association. Circulation 125,
e2–e220 (2012).
3. Cowie, M. R. et al. The epidemiology of heart
failure. Eur. Heart J. 18, 208–225 (1997).
4. Davies, M. et al. Prevalence of left-ventricular
systolic dysfunction and heart failure in the
Echocardiographic Heart of England Screening
study: a population based study. Lancet 358,
439–444 (2001).
5. Huffman, M. D. & Prabhakaran, D. Heart failure:
epidemiology and prevention in India. Natl Med.
J. India 23, 283–288 (2010).
6. Jiang, H. & Ge, J. Epidemiology and clinical
management of cardiomyopathies and heart
failure in China. Heart 95, 1727–1731
(2009).
7. Celermajer, D. S., Chow, C. K., Marijon, E.,
Anstey, N. M. & Woo, K. S. Cardiovascular
disease in the developing world: prevalences,
patterns, and the potential of early disease
detection. J. Am. Coll. Cardiol. http://
dx.doi.org/10.1016/j.jacc.2012.03.074.
8. Moons, P., Bovijn, L., Budts, W., Belmans, A.
& Gewillig, M. Temporal trends in survival to
adulthood among patients born with congenital
heart disease from 1970 to 1992 in Belgium.
Circulation 122, 2264–2272 (2010).
9. Bolger, A. P., Coats, A. J. & Gatzoulis, M. A.
Congenital heart disease: the original heart
failure syndrome. Eur. Heart J. 24, 970–976
(2003).
10. Hunt, S. A. ACC/AHA 2005 guideline update for
the diagnosis and management of chronic heart
failure in the adult: a report of the American
College of Cardiology/American Heart
Association Task Force on Practice Guidelines
(Writing Committee to Update the 2001
Guidelines for the Evaluation and Management
of Heart Failure). J. Am. Coll. Cardiol. 46, e1–e82
(2005).
11. Gottdiener, J. S. et al. American Society of
Echocardiography recommendations for use of
echocardiography in clinical trials. J. Am.
Soc. Echocardiogr. 17, 1086–1119 (2004).
12. Lang, R. M. et al. Recommendations for chamber
quantification: a report from the American
Society of Echocardiography’s Guidelines and
Standards Committee and the Chamber
Quantification Writing Group, developed in
conjunction with the European Association of
Echocardiography, a branch of the European
Society of Cardiology. J. Am. Soc. Echocardiogr.
18, 1440–1463 (2005).
13. Shah, A. M. & Solomon, S. D. Myocardial
deformation imaging: current status and future
directions. Circulation 125, e244–e248 (2012).
14. Gorcsan, J. 3rd & Tanaka, H. Echocardiographic
assessment of myocardial strain. J. Am.
Coll. Cardiol. 58, 1401–1413 (2011).
15. Mor-Avi, V. et al. Current and evolving
echocardiographic techniques for the
quantitative evaluation of cardiac mechanics:
ASE/EAE consensus statement on methodology
and indications endorsed by the Japanese
Society of Echocardiography. Eur. J. Echocardiogr.
12, 167–205 (2011).
16. Heimdal, A., Stoylen, A., Torp, H. & Skjaerpe, T.
Real-time strain rate imaging of the left ventricle
by ultrasound. J. Am. Soc. Echocardiogr. 11,
1013–1019 (1998).
17. Urheim, S., Edvardsen, T., Torp, H., Angelsen, B.
& Smiseth, O. A. Myocardial strain by Doppler
echocardiography. Validation of a new method to
quantify regional myocardial function. Circulation
102, 1158–1164 (2000).
18. Leitman, M. et al. Two-dimensional strain—a
novel software for real-time quantitative
echocardiographic assessment of myocardial
function. J. Am. Soc. Echocardiogr. 17,
1021–1029 (2004).
19. Reisner, S. A. et al. Global longitudinal strain: a
novel index of left ventricular systolic function.
J. Am. Soc. Echocardiogr. 17, 630–633 (2004).
20. Amundsen, B. H. et al. Noninvasive myocardial
strain measurement by speckle tracking
echocardiography: validation against
sonomicrometry and tagged magnetic resonance
imaging. J. Am. Coll. Cardiol. 47, 789–793 (2006).
21. Crosby, J. et al. 3‑D speckle tracking for
assessment of regional left ventricular function.
Ultrasound Med. Biol. 35, 458–471 (2009).
22. Takeguchi, T., Nishiura, M., Abe, Y., Ohuchi, H.
& Kawagishi, T. Practical considerations for a
method of rapid cardiac function analysis based
on three-dimensional speckle tracking in a three-
dimensional diagnostic ultrasound system.
J. Med. Ultrasonics 37, 41–49 (2010).
23. Jessup, M. & Brozena, S. Heart failure. N. Engl.
J. Med. 348, 2007–2018 (2003).
24. Shah, A. M. & Mann, D. L. In search of new
therapeutic targets and strategies for heart
failure: recent advances in basic science. Lancet
378, 704–712 (2011).
25. Mudd, J. O. & Kass, D. A. Tackling heart failure in
the twenty-first century. Nature 451, 919–928
(2008).
26. Diwan, A. & Dorn, G. W. 2nd. Decompensation of
cardiac hypertrophy: cellular mechanisms and
novel therapeutic targets. Physiology (Bethesda)
22, 56–64 (2007).
27. van Heerebeek, L. et al. Myocardial structure and
function differ in systolic and diastolic heart
failure. Circulation 113, 1966–1973 (2006).
28. Zile, M. R. et al. Prevalence and significance of
alterations in cardiac structure and function in
patients with heart failure and a preserved
ejection fraction. Circulation 124, 2491–2501
(2011).
29. Foo, R. S., Mani, K. & Kitsis, R. N. Death begets
failure in the heart. J. Clin. Invest. 115, 565–571
(2005).
30. Olivetti, G. et al. Apoptosis in the failing human
heart. N. Engl. J. Med. 336, 1131–1141 (1997).
31. Wencker, D. et al. A mechanistic role for cardiac
myocyte apoptosis in heart failure. J. Clin. Invest.
111, 1497–1504 (2003).
32. Nakayama, H. et al. Ca2+-and mitochondrial-
dependent cardiomyocyte necrosis as a primary
mediator of heart failure. J. Clin. Invest. 117,
2431–2444 (2007).
33. Matsui, T. et al. Phenotypic spectrum caused by
transgenic overexpression of activated Akt in the
heart. J. Biol. Chem. 277, 22896–22901 (2002).
34. Kung, G., Konstantinidis, K. & Kitsis, R. N.
Programmed necrosis, not apoptosis, in the
heart. Circ. Res. 108, 1017–1036 (2011).
35. Nishida, K., Kyoi, S., Yamaguchi, O.,
Sadoshima, J. & Otsu, K. The role of autophagy
in the heart. Cell Death Differ. 16, 31–38 (2009).
36. Zhu, H. et al. Cardiac autophagy is a maladaptive
response to hemodynamic stress. J. Clin. Invest.
117, 1782–1793 (2007).
37. Weber, K. T. et al. Fibrillar collagen and
remodeling of dilated canine left ventricle.
Circulation 82, 1387–1401 (1990).
38. Volders, P. G. et al. Interstitial collagen is
increased in the non-infarcted human
myocardium after myocardial infarction. J. Mol.
Cell. Cardiol. 25, 1317–1323 (1993).
39. Spinale, F. G. et al. Matrix metalloproteinase
inhibition during the development of congestive
heart failure: effects on left ventricular
dimensions and function. Circ. Res. 85,
364–376 (1999).
40. Thomas, C. V. et al. Increased matrix
metalloproteinase activity and selective
upregulation in LV myocardium from patients
with end-stage dilated cardiomyopathy.
Circulation 97, 1708–1715 (1998).
41. Shiojima, I. et al. Disruption of coordinated
cardiac hypertrophy and angiogenesis
contributes to the transition to heart failure.
J. Clin. Invest. 115, 2108–2118 (2005).
42. Lehnart, S. E., Maier, L. S. & Hasenfuss, G.
Abnormalities of calcium metabolism and
myocardial contractility depression in the failing
heart. Heart Fail. Rev. 14, 213–224 (2009).

NATURE REVIEWS | CARDIOLOGY VOLUME 9  |  NOVEMBER 2012  |  655

© 2012 Macmillan Publishers Limited. All rights reserved
REVIEWS
43. Ingwall, J. S. Energy metabolism in heart failure
and remodelling. Cardiovasc. Res. 81, 412–419
(2009).
44. McCulloch, A. D. in The Biomedical Engineering
Handbook 2nd edn (ed. Bronzino, J. D.) 1–27
(CRC Press LLC, Boca Raton, 2000).
45. Geyer, H. et al. Assessment of myocardial
mechanics using speckle tracking
echocardiography: fundamentals and clinical
applications. J. Am. Soc. Echocardiogr. 23,
351–369 (2010).
46. Sengupta, P. P. et al. Left ventricular structure
and function: basic science for cardiac imaging.
J. Am. Coll. Cardiol. 48, 1988–2001 (2006).
47. Buckberg, G., Hoffman, J. I., Mahajan, A.,
Saleh, S. & Coghlan, C. Cardiac mechanics
revisited: the relationship of cardiac architecture
to ventricular function. Circulation 118,
2571–2587 (2008).
48. D’Hooge, J. et al. Regional strain and strain rate
measurements by cardiac ultrasound: principles,
implementation and limitations. Eur. J.
Echocardiogr. 1, 154–170 (2000).
49. Dandel, M. & Hetzer, R. Echocardiographic strain
and strain rate imaging—clinical applications.
Int. J. Cardiol. 132, 11–24 (2009).
50. Vendelin, M., Bovendeerd, P. H., Engelbrecht, J.
& Arts, T. Optimizing ventricular fibers: uniform
strain or stress, but not ATP consumption, leads
to high efficiency. Am. J. Physiol. Heart
Circ. Physiol. 283, H1072–H1081 (2002).
51. Geerts, L., Bovendeerd, P., Nicolay, K. & Arts, T.
Characterization of the normal cardiac myofiber
field in goat measured with MR‑diffusion tensor
imaging. Am. J. Physiol. Heart Circ. Physiol. 283,
H139–H145 (2002).
52. Lorenz, C. H., Pastorek, J. S. & Bundy, J. M.
Delineation of normal human left ventricular
twist throughout systole by tagged cine magnetic
resonance imaging. J. Cardiovasc. Magn. Reson.
2, 97–108 (2000).
53. Notomi, Y. et al. Ventricular untwisting: a
temporal link between left ventricular relaxation
and suction. Am. J. Physiol. Heart Circ. Physiol.
294, H505–H513 (2008).
54. Notomi, Y. et al. Enhanced ventricular untwisting
during exercise: a mechanistic manifestation of
elastic recoil described by Doppler tissue
imaging. Circulation 113, 2524–2533 (2006).
55. Burns, A. T., La Gerche, A., Prior, D. L. &
Macisaac, A. I. Left ventricular untwisting is an
important determinant of early diastolic function.
JACC Cardiovasc. Imaging 2, 709–716 (2009).
56. Notomi, Y. et al. Assessment of left ventricular
torsional deformation by Doppler tissue imaging:
validation study with tagged magnetic resonance
imaging. Circulation 111, 1141–1147 (2005).
57. Notomi, Y. et al. Measurement of ventricular
torsion by two-dimensional ultrasound speckle
tracking imaging. J. Am. Coll. Cardiol. 45,
2034–2041 (2005).
58. Blessberger, H. & Binder, T. Two dimensional
speckle tracking echocardiography: basic
principles. Heart 96, 716–722 (2010).
59. Henson, R. E., Song, S. K., Pastorek, J. S.,
Ackerman, J. J. & Lorenz, C. H. Left ventricular
torsion is equal in mice and humans. Am. J.
Physiol. Heart Circ. Physiol. 278, H1117–H1123
(2000).
60. Maffessanti, F. et al. Quantitative evaluation of
regional left ventricular function using three-
dimensional speckle tracking echocardiography
in patients with and without heart disease.
Am. J. Cardiol. 104, 1755–1762 (2009).
61. Nesser, H. J. et al. Quantification of left
ventricular volumes using three-dimensional
echocardiographic speckle tracking: comparison
with MRI. Eur. Heart J. 30, 1565–1573 (2009).
656  |  NOVEMBER 2012  |  VOLUME 9  www.nature.com/nrcardio
62. Meunier, J. Tissue motion assessment from 3D
echographic speckle tracking. Phys. Med. Biol.
43, 1241–1254 (1998).
63. Yu, W., Yan, P., Sinusas, A. J., Thiele, K. &
Duncan, J. S. Towards pointwise motion tracking
in echocardiographic image sequences—
comparing the reliability of different features for
speckle tracking. Med. Image Anal. 10, 495–508
(2006).
64. Jia, C. et al. 4D elasticity imaging of PVA LV
phantom integrated with pulsatile circulation
system using 2D phased array. 2007 IEEE
Ultrasonics Symposium Proceedings, 876–879
(2007).
65. Chen, X. et al. 3‑D correlation-based speckle
tracking. Ultrason. Imaging 27, 21–36 (2005).
66. Brekke, S., Rabben, S. T., Haugen, A.,
Haugen, G. U., Steen, E. N. & Torp, H. G.
Real-time volume stitching in 4D
echocardiography. 2005 IEEE Ultrasonics
Symposium Proceedings 2, 1228–1231 (2005).
67. von Ramm, O. T., Smith, S. W. & Pavy, H. R.
High-speed ultrasound volumetric imaging
system. II. Parallel processing and image
display. IEEE Trans. Ultrason. Ferroelectr.
Freq. Control 38, 109–115 (1991).
68. Ogawa, K. et al. Usefulness of automated
quantitation of regional left ventricular wall
motion by a novel method of two-dimensional
echocardiographic tracking. Am. J. Cardiol. 98,
1531–1537 (2006).
69. Seo, Y. et al. Validation of 3‑dimensional speckle
tracking imaging to quantify regional myocardial
deformation. Circ. Cardiovasc. Imaging 2,
451–459 (2009).
70. Schiller, N. B. et al. Recommendations for
quantitation of the left ventricle by two-
dimensional echocardiography. American Society
of Echocardiography Committee on Standards,
Subcommittee on Quantitation of Two-
Dimensional Echocardiograms. J. Am.
Soc. Echocardiogr. 2, 358–367 (1989).
71. Cerqueira, M. D. et al. Standardized myocardial
segmentation and nomenclature for tomographic
imaging of the heart: a statement for healthcare
professionals from the Cardiac Imaging
Committee of the Council on Clinical Cardiology
of the American Heart Association. Circulation
105, 539–542 (2002).
72. Gérard, O. et al. Efficient model-based
quantification of left ventricular function in 3‑D
echocardiography. IEEE Trans. Med. Imaging 21,
1059–1068 (2002).
73. Kleijn, S. A., Aly, M. F., Terwee, C. B.,
van Rossum, A. C. & Kamp, O. Reliability of left
ventricular volumes and function measurements
using three-dimensional speckle tracking
echocardiography. Eur. Heart J.
Cardiovasc. Imaging 13, 159–168 (2012).
74. Kleijn, S. A. et al. Comparison between three-
dimensional speckle-tracking echocardiography
and cardiac magnetic resonance imaging for
quantification of left ventricular volumes and
function. Eur. Heart J. Cardiovasc. Imaging
http://dx.doi.org/10.1093/ehjci/jes030.
75. Kleijn, S. A., Aly, M. F., Terwee, C. B.,
van Rossum, A. C. & Kamp, O. Comparison
between direct volumetric and speckle tracking
methodologies for left ventricular and left atrial
chamber quantification by three-dimensional
echocardiography. Am. J. Cardiol. 108,
1038–1044 (2011).
76. Abhayaratna, W. P. et al. Left atrial size: physiologic
determinants and clinical applications. J. Am.
Coll. Cardiol. 47, 2357–2363 (2006).
77. Rossi, A. et al. Independent relationship of left
atrial size and mortality in patients with heart
failure: an individual patient meta-analysis of
© 2012 Macmillan Publishers Limited. All rights reserved
longitudinal data (MeRGE Heart Failure). Eur. J.
Heart Fail. 11, 929–936 (2009).
78. Pérez de Isla, L. et al. Three‑dimensional‑wall
motion tracking: a new and faster tool for
myocardial strain assessment: comparison with
two‑dimensional‑wall motion tracking. J. Am.
Soc. Echocardiogr. 22, 325–330 (2009).
79. Saito, K. et al. Comprehensive evaluation of left
ventricular strain using speckle tracking
echocardiography in normal adults: comparison
of three-dimensional and two-dimensional
approaches. J. Am. Soc. Echocardiogr. 22,
1025–1030 (2009).
80. Seo, Y., Ishizu, T., Enomoto, Y., Sugimori, H. &
Aonuma, K. Endocardial surface area tracking
for assessment of regional LV wall deformation
with 3D speckle tracking imaging.
JACC Cardiovasc. Imaging 4, 358–365 (2011).
81. Li, S. N., Wong, S. J. & Cheung, Y. F. Novel area
strain based on three-dimensional wall motion
analysis for assessment of global left ventricular
performance after repair of tetralogy of Fallot.
J. Am. Soc. Echocardiogr. 24, 819–825 (2011).
82. Jantunen, E. & Collan, Y. Transmural differences
in ischaemic heart disease: a quantitative
histologic study. Appl. Pathol. 7, 179–187 (1989).
83. Kleijn, S. A., Aly, M. F., Terwee, C. B.,
van Rossum, A. C. & Kamp, O. Three-
dimensional speckle tracking echocardiography
for automatic assessment of global and regional
left ventricular function based on area strain.
J. Am. Soc. Echocardiogr. 24, 314–321 (2011).
84. Thebault, C. et al. Real-time three-dimensional
speckle tracking echocardiography: a novel
technique to quantify global left ventricular
mechanical dyssynchrony. Eur. J. Echocardiogr.
12, 26–32 (2011).
85. Zhou, Z. et al. Three-dimensional speckle-
tracking imaging for left ventricular rotation
measurement: an in vitro validation study.
J. Ultrasound Med. 29, 903–909 (2010).
86. Ashraf, M., Zhou, Z., Nguyen, T., Ashraf, S. &
Sahn, D. J. Apex to base left ventricular twist
mechanics computed from high frame rate
two-dimensional and three-dimensional
echocardiography: a comparison study. J. Am.
Soc. Echocardiogr. 25, 121–128 (2012).
87. Andrade, J. et al. Left ventricular twist: comparison
between two- and three-dimensional speckle-
tracking echocardiography in healthy volunteers.
Eur. J. Echocardiogr. 12, 76–79 (2011).
88. Gorcsan, J. 3rd & Suffoletto, M. S. The role of
tissue Doppler and strain imaging in predicting
response to CRT. Europace 10 (Suppl. 3),
iii80–iii87 (2008).
89. Nesser, H. J. & Winter, S. Speckle tracking in the
evaluation of left ventricular dyssynchrony.
Echocardiography 26, 324–336 (2009).
90. Kapetanakis, S. et al. Real-time three-dimensional
echocardiography: a novel technique to quantify
global left ventricular mechanical dyssynchrony.
Circulation 112, 992–1000 (2005).
91. Tanaka, H., Hara, H., Saba, S. & Gorcsan, J. 3rd.
Usefulness of three-dimensional speckle
tracking strain to quantify dyssynchrony and the
site of latest mechanical activation. Am. J.
Cardiol. 105, 235–242 (2010).
92. Tanaka, H. et al. Comparative mechanical
activation mapping of RV pacing to LBBB by 2D
and 3D speckle tracking and association with
response to resynchronization therapy.
JACC Cardiovasc. Imaging 3, 461–471 (2010).
93. Tanaka, H. et al. Multidirectional left ventricular
performance detected with three-dimensional
speckle-tracking strain in patients with chronic
right ventricular pacing and preserved ejection
fraction. Eur. Heart J. Cardiovasc. Imaging
http://dx.doi.org/10.1093/ehjci/jes056.

94. Li, C. H. et al. Mechanical left ventricular
dyssynchrony detection by endocardium
displacement analysis with 3D speckle tracking
technology. Int. J. Cardiovasc. Imaging 26,
867–870 (2010).
95. Tatsumi, K. et al. Mechanical left ventricular
dyssynchrony in heart failure patients with
narrow QRS duration as assessed by three-
dimensional speckle area tracking strain. Am. J.
Cardiol. 108, 867–872 (2011).
96. Tatsumi, K. et al. Strain dyssynchrony index
determined by three-dimensional speckle area
tracking can predict response to cardiac
resynchronization therapy.
Cardiovasc. Ultrasound 9, 11 (2011).
97. Tatsumi, K. et al. Relation between strain
dyssynchrony index determined by
comprehensive assessment using speckle-
tracking imaging and long-term outcome after
cardiac resynchronization therapy for patients
with heart failure. Am. J. Cardiol. 109,
1187–1193 (2012).
98. Matsumoto, K. et al. Left ventricular dyssynchrony
using three-dimensional speckle-tracking imaging
as a determinant of torsional mechanics in
patients with idiopathic dilated cardiomyopathy.
Am. J. Cardiol. 109, 1197–1205 (2012).
99. Zhang, X. et al. Noninvasive three-dimensional
electrocardiographic imaging of ventricular
activation sequence. Am. J. Physiol. Heart
Circ. Physiol. 289, H2724–H2732 (2005).
100. Han, C., Pogwizd, S. M., Killingsworth, C. R. &
He, B. Noninvasive imaging of three-dimensional
cardiac activation sequence during pacing and
ventricular tachycardia. Heart Rhythm 8,
1266–1272 (2011).
101. Eyster, J. A. The relation between electrical and
mechanical events in the dog’s heart. Am. J.
Physiol. 131, 760–767 (1940).
102. Onishi, T. et al. Activation imaging: a novel
approach to three-dimensional mechanical
mapping using speckle tracking strain
[abstract 907–7]. J. Am. Coll. Cardiol. 59, E1365
(2012).
103. Wen, H., Liang, Z., Zhao, Y. & Yang, K. Feasibility
of detecting early left ventricular systolic
dysfunction using global area strain: a novel
index derived from three-dimensional speckle-
tracking echocardiography. Eur. J. Echocardiogr.
12, 910–916 (2011).
104. Reant, P. et al. Evaluation of global left
ventricular systolic function using three-
dimensional echocardiography speckle-tracking
strain parameters. J. Am. Soc. Echocardiogr. 25,
68–79 (2012).
105. Pérez de Isla, L. et al. 3D-wall motion tracking: a
new tool for myocardial contractility analysis.
J. Cardiovasc. Med. (Hagerstown) http://
dx.doi.org/10.2459/JCM.0b013e3283405b9b.
106. Burns, A. T., La Gerche, A., D’hooge, J.,
MacIsaac, A. I. & Prior, D. L. Left ventricular
strain and strain rate: characterization of the
effect of load in human subjects. Eur. J.
Echocardiogr. 11, 283–289 (2010).
107. Park, S. J., Nishimura, R. A., Borlaug, B. A.,
Sorajja, P. & Oh, J. K. The effect of loading
alterations on left ventricular torsion: a
simultaneous catheterization and two-
dimensional speckle tracking echocardiographic
study. Eur. J. Echocardiogr. 11, 770–777 (2010).
108. Hayat, D. et al. Comparison of real-time three-
dimensional speckle tracking to magnetic
resonance imaging in patients with coronary
NATURE REVIEWS | CARDIOLOGY VOLUME 9  |  NOVEMBER 2012  |  657
heart disease. Am. J. Cardiol. 109, 180–186
(2012).
109. Cazeau, S. et al. Effects of multisite biventricular
pacing in patients with heart failure and
intraventricular conduction delay. N. Engl. J. Med.
344, 873–880 (2001).
110. Abraham, W. T. et al. Cardiac resynchronization in
chronic heart failure. N. Engl. J. Med. 346,
1845–1853 (2002).
111. Cleland, J. G. et al. The effect of cardiac
resynchronization on morbidity and mortality in
heart failure. N. Engl. J. Med. 352, 1539–1549
(2005).
112. Chung, E. S. et al. Results of the Predictors of
Response to CRT (PROSPECT) trial. Circulation
117, 2608–2616 (2008).
113. Kleijn, S. A. et al. A meta-analysis of left
ventricular dyssynchrony assessment and
prediction of response to cardiac
resynchronization therapy by three-dimensional
echocardiography. Eur. Heart J.
Cardiovasc. Imaging 13, 763–775 (2012).
114. Tanaka, H. et al. Dyssynchrony by speckle-
tracking echocardiography and response to
cardiac resynchronization therapy: results of the
Speckle Tracking and Resynchronization (STAR)
study. Eur. Heart J. 31, 1690–1700 (2010).
115. Meluzin, J. et al. Left ventricular mechanics in
idiopathic dilated cardiomyopathy: systolic-
diastolic coupling and torsion. J. Am.
Soc. Echocardiogr. 22, 486–493 (2009).
116. Duan, F. et al. Preliminary clinical study of left
ventricular myocardial strain in patients with
non-ischemic dilated cardiomyopathy by three-
dimensional speckle tracking imaging.
Cardiovasc. Ultrasound 10, 8 (2012).
117. Urbano Moral, J. A. et al. Left ventricular twist
mechanics in hypertrophic cardiomyopathy
assessed by three-dimensional speckle tracking
echocardiography. Am. J. Cardiol. 108,
1788–1795 (2011).
118. Baccouche, H. et al. Differentiating cardiac
amyloidosis and hypertrophic cardiomyopathy by
use of three-dimensional speckle tracking
echocardiography. Echocardiography 29,
668–677 (2012).
119. Baccouche, H., Maunz, M., Beck, T., Fogarassy, P.
& Beyer, M. Echocardiographic assessment and
monitoring of the clinical course in a patient with
Tako-Tsubo cardiomyopathy by a novel
3D‑speckle‑tracking-strain analysis. Eur. J.
Echocardiogr. 10, 729–731 (2009).
120. Blessberger, H. & Binder, T. Two dimensional
speckle tracking echocardiography: clinical
applications. Heart 96, 2032–2040 (2010).
121. Galderisi, M. et al. Correlates of global area
strain in native hypertensive patients: a three-
dimensional speckle-tracking echocardiography
study. Eur. Heart J. Cardiovasc. Imaging 13,
730–738 (2012).
122. Saltijeral, A. et al. Myocardial strain
characterization in different left ventricular
adaptative responses to high blood pressure: a
study based on 3D-wall motion tracking analysis.
Echocardiography 27, 1238–1246 (2010).
123. Saltijeral, A. et al. Early myocardial deformation
changes associated to isolated obesity: a study
based on 3D-wall motion tracking analysis.
Obesity (Silver Spring) 19, 2268–2273 (2011).
124. Hare, J. L. et al. Use of myocardial deformation
imaging to detect preclinical myocardial
dysfunction before conventional measures in
patients undergoing breast cancer treatment
© 2012 Macmillan Publishers Limited. All rights reserved
REVIEWS
with trastuzumab. Am. Heart J. 158, 294–301
(2009).
125. Cheung, Y. F., Hong, W. J., Chan, G. C.,
Wong, S. J. & Ha, S. Y. Left ventricular
myocardial deformation and mechanical
dyssynchrony in children with normal ventricular
shortening fraction after anthracycline therapy.
Heart 96, 1137–1141 (2010).
126. Fonseca, C. G. et al. Three-dimensional
assessment of left ventricular systolic strain in
patients with type 2 diabetes mellitus, diastolic
dysfunction, and normal ejection fraction. Am. J.
Cardiol. 94, 1391–1395 (2004).
127. Nasir, K. et al. Regional left ventricular function
in individuals with mild to moderate renal
insufficiency: the Multi-Ethnic Study of
Atherosclerosis. Am. Heart J. 153, 545–551
(2007).
128. Cho, G. Y. et al. Global 2‑dimensional strain as a
new prognosticator in patients with heart failure.
J. Am. Coll. Cardiol. 54, 618–624 (2009).
129. Hung, C. L. et al. Longitudinal and circumferential
strain rate, left ventricular remodeling, and
prognosis after myocardial infarction. J. Am.
Coll. Cardiol. 56, 1812–1822 (2010).
130. Nahum, J. et al. Impact of longitudinal myocardial
deformation on the prognosis of chronic heart
failure patients. Circ. Cardiovasc. Imaging 3,
249–256 (2010).
131. Kalogeropoulos, A. P., Georgiopoulou, V. V.,
Gheorghiade, M. & Butler, J. Echocardiographic
evaluation of left ventricular structure and
function: new modalities and potential
applications in clinical trials. J. Card. Fail. 18,
159–172 (2012).
132. Gayat, E., Ahmad, H., Weinert, L., Lang, R. M.
& Mor-Avi, V. Reproducibility and inter-vendor
variability of left ventricular deformation
measurements by three-dimensional
speckle-tracking echocardiography. J. Am.
Soc. Echocardiogr. 24, 878–885 (2011).
133. Lang, R. M. et al. EAE/ASE recommendations
for image acquisition and display using
three-dimensional echocardiography. J. Am.
Soc. Echocardiogr. 25, 3–46 (2012).
134. Champion, H. C., Michelakis, E. D. &
Hassoun, P. M. Comprehensive invasive and
noninvasive approach to the right ventricle-
pulmonary circulation unit: state of the art and
clinical and research implications. Circulation
120, 992–1007 (2009).
135. Apitz, C., Webb, G. D. & Redington, A. N.
Tetralogy of Fallot. Lancet 374, 1462–1471
(2009).
136. Warnes, C. A. Adult congenital heart disease
importance of the right ventricle. J. Am.
Coll. Cardiol. 54, 1903–1910 (2009).
137. Sahn, D. J. et al. Simultaneously derived
circumferential and longitudinal right ventricular
strains from 4D ultrasound using a new method
for 4D cardiac mechanics: validation by
sonomicrometry [poster 1165–219]. J. Am.
Coll. Cardiol. 57, E856 (2011).
138. Ishizu, T. et al. Experimental validation of left
ventricular transmural strain gradient with
echocardiographic two-dimensional speckle
tracking imaging. Eur. J. Echocardiogr. 11,
377–385 (2010).
139. Zhang, Q. et al. A novel multi-layer approach of
measuring myocardial strain and torsion by 2D
speckle tracking imaging in normal subjects and
patients with heart diseases. Int. J. Cardiol. 147,
32–37 (2011).