Heart Fail Rev (2016) 21:77–94

DOI 10.1007/s10741-015-9521-8

Echocardiographic assessment of left ventricular systolic function:

from ejection fraction to torsion
Matteo Cameli1 • Sergio Mondillo1 • Marco Solari1 • Francesca Maria Righini1 •
Valentina Andrei1 • Carla Contaldi2 • Eugenia De Marco3 • Michele Di Mauro4 •
Roberta Esposito5 • Sabina Gallina5 • Roberta Montisci6 • Andrea Rossi7 •
Maurizio Galderisi5 • Stefano Nistri8 • Eustachio Agricola9 • Donato Mele10

Published online: 28 December 2015

Ó Springer Science+Business Media New York 2015

Abstract Assessment of left ventricular (LV) systolic angle independent, not affected by translation cardiac
function is the cornerstone of the echocardiographic movements, and can assess simultaneously the entire
examination. There are many echocardiographic parame- myocardium along all the three-dimensional geometrical
ters that can be used for clinical and research purposes, (longitudinal, circumferential, and radial) axes. Speckle
each one with its pros and cons. The LV ejection fraction is tracking echocardiography also allows the analysis of LV
the most used one due to its feasibility and predictability, torsion. The aim of this paper was to review the main
but it also has many limits, related to both the imaging echocardiographic parameters of LV systolic function and
technique used for calculation and to the definition itself. to describe its pros and cons.
LV longitudinal function is expression of subendocardial
fibers contraction. Because the subendocardium is often Keywords Stroke volume  Ejection fraction  Speckle
involved early in many pathological processes, its analysis tracking  Strain  Torsion
has been a fertile field for the development of sensitive
parameters. Longitudinal function can be evaluated in
many ways, such as M-mode echocardiography, tissue Introduction
Doppler imaging, and speckle tracking echocardiography.
This latter is a relatively new tool to assess LV function The human heart has a complex structure of muscular
through measurement of myocardial strain, with a high fibers, organized in layers. Left ventricular (LV) sub-en-
temporal and spatial resolution and a better inter- and intra- docardial and sub-epicardial fibers have a longitudinal
observer reproducibility compared to Doppler strain. It is disposition, from the apex to the base, drawing a spiral
around the ventricle (sub-epicardial are clockwise oriented,
sub-endocardial are counter clockwise, seen from apex to
On behalf of Gruppo di Studio Ecocardiografia of the Società Italiana
di Cardiologia. the base), while the mid-wall fibers are circumferential [1].

& Matteo Cameli 5

Dipartimento di Scienze Biomediche Avanzate, Federico II
[email protected] University, Naples, Italy
6
1 Department of Cardiovascular and Neurological Science,
Cardiology Department of Cardiovascular Diseases,
University of Cagliari, Cagliari, Italy
University of Siena, Policlinico Le Scotte, Viale Bracci No 1,
7
53100 Siena, Italy Section of Cardiology, Department of Medicine, University
2 of Verona, Verona, Italy
Department of Clinical Medicine, Cardiovascular &
8
Immunological Sciences, Federico II University School of Cardiology Service, CMSR-Veneto Medica,
Medicine, Naples, Italy Altavilla Vicentina, VI, Italy
3 9
Cardiology Department, Catholic University of Sacred Heart, Division of NonInvasive Cardiology, San Raffaele Hospital,
Rome, Italy Milan, Italy
4 10
Department of Cardiology, University of L’Aquila, L’Aquila, Cardiology Unit, University of Ferrara, Ferrara, Italy
Italy

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78 Heart Fail Rev (2016) 21:77–94

Contraction and release of all these fibers generates a advantages of 3D echocardiographic volume measurements
complex deformation and movement of the LV walls both is that they do not rely on geometric assumptions. In
in systole and diastole. The final global result is systolic patients with good image quality, 3D echocardiographic
blood ejection into the aorta and diastolic ventricular measurements are accurate and reproducible and are rec-
filling. ommended when available and feasible [13].
In the last decades, many noninvasive imaging tech- The LVEF is defined as the ratio of the difference
niques have demonstrated to be feasible and reproducible between the end-systolic and the end-diastolic volumes
for assessment of both systolic and diastolic function in the (i.e., the global stroke volume, SV) and the end-diastolic
human heart; among these, echocardiography has gained a volume (EDV) itself (Fig. 1); it is a dimensionless
predominant role in clinical practice [2]. Over the years, parameter, and it is expressed as a percentage (%).
many echocardiographic parameters have been proposed to According to the European and American Society of
assess LV systolic function: Each one has its pros and cons, Echocardiography, its normal value is above 55 %, while a
but none of those applicable in practice can express the value ranging from 45 to 54 %, 30 to 44 %, and \30 %
global LV systolic contraction in its overall complexity: represents a mild, moderate, and severe systolic dysfunc-
Cardiologists, therefore, should rely on more than a single tion, respectively [2].
parameter for a comprehensive evaluation of LV systolic The LVEF provides a ratio of SV to EDV and allows
function. comparison of pump function across a spectrum of differ-
The aim of this review was to describe the main ent patients; this made it, in physician’s imagination, as a
echocardiographic techniques currently available to assess sort of a ‘‘magic number’’ that sum up the global systolic
the LV systolic function, from traditional to innovative function of the heart. However, the LVEF is well away
parameters, with their advantages and their limits from this, since it has many limitations [14], and some of
(Tables 1, 2) and with particular reference to speckle these are related to the imaging techniques and others
tracking echocardiography, which has recently entered into related to the definition itself.
clinical practice.
Limitations of ejection fraction measurement

Left ventricular ejection fraction The principal technical limitations are the difficulty to
obtain true two- and four-chamber apical views in some
The LV ejection fraction (EF) has important implications patients and the not-infrequent finding of sub-optimal
in diagnosis, management, and prognosis of many patho- images. In the latter case, when endocardial border cannot
logical conditions, especially in heart failure, ischemic, and be evaluated sufficiently, contrast should be used to
valvular diseases [3–7]. It is well known not only to car- enhance it. In experienced hands, a standard error of 6.3 %,
diologists but also to all physicians and is one of the most a upper limit of confidence of 11.4 %, and an inter-ob-
used parameters to evaluate the LV systolic function both server variability of 8.2 % have been reported for two-
in clinical practice and research settings. LVEF could be dimensional LVEF measurement [15], which can be
easily calculated through endocardial border delineation improved by three-dimensional echocardiography [16].
[8], or alternatively, it can be ‘‘eyeball’’ estimated, Three-dimensional echocardiography is a highly repro-
although the latter method could suffer from the intrinsic ducible method that allows improvements in accuracy and
limitations of subjective evaluation [9]; there are many feasibility [17–19] of LV volumes and EF estimations by
methods to calculate EF, but they suffer of low accuracy in eliminating the need for geometric modelling, which is
patients with marked regional difference in function (e.g., inaccurate in case of ventricular aneurysms, asymmetrical
clinically relevant myocardial infarction) [10]. The previ- ventricles, wall motion abnormalities, and the error caused
ously used Teichholz or Quinones methods of calculating by foreshortened views, also in symmetrical ventricles [20,
LV ejection fraction from LV linear dimensions may result 21]; however, this approach requires expertise [21, 22] and
in inaccuracies due to the geometric assumptions required could be time consuming.
to convert a linear measurement to a 3D volume [11, 12]. As mentioned above, the LVEF formula has two vari-
Accordingly, the use of linear measurements to calculate ables: the SV and the EDV. Consequently, the LVEF
LV EF is not recommended for clinical practice [2]. depends, first of all, on all the factors affecting the SV, i.e.,
The most commonly used and recommended echocar- myocardial contractility, heart rate, loading conditions, and
diographic 2-D measurement for volume measurements is dyssynchrony of contraction. The LVEF, also, is not
the modified Simpson’s rule with biplane planimetry [2], weighed to the body surface area (BSA) and this could be a
although a three-dimensional evaluation is today possible problem especially in people with lower BSA [23].
using new-generation echo scanners [13]. One of the Moreover, depending also on EDV, interpretation of the

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Table 1 Pros and cons of each echocardiographic technique for left ventricular systolic function assessment
Technique Advantages Disadvantages

Ejection fraction (EF) Well known Dependence on loading conditions, heart rate, and
Easily understandable dyssynchrony
Simply calculated or eyeball estimated Dependence on stroke volume and end-diastolic volume
Useful for clinical decisions Overestimating values in case of mitral regurgitation or
interventricular shunt
Prognostic value
Nonspecific for clinical findings of heart failure
Low sensitivity in detecting subtle LV systolic
impairment
Doppler dP/dt Good correlation with the invasive-derived dP/dt Require a well-delineated velocity spectral envelope
Beat-by-beat repeatable measure from mitral regurgitation
Highly feasible in heart failure patients Angle-dependant measure
Poorly influenced by changes in afterload Not feasible in eccentric mitral regurgitation
Mildly influenced by changes in preload
Not affected by wall motion abnormalities
Myocardial performance Combine diastolic and systolic evaluation Affected by valvular heart diseases
index (Tei Index) Feasible in the most of cases Significantly changes after valve surgery
Good correlation and prognostic value in many clinic cases Not feasible in patients with variable cardiac cycle
duration
Not method of choice in PM recipient and with
intraventricular dyssynchrony
M-mode annular plane Simple method Angle dependent
analysis (MAPSE) Highly reproducible Limited to the mitral annulus
Quickly performed Suffers of translation movements in case of regional wall
Sensitive parameter of LV systolic dysfunction motion impairment
Prognostic value in many pathological conditions Dependent on atrial contraction
Tissue Doppler imaging Simple method Angle dependent
(TDI) Highly reproducible Suffers of translation movements in case of regional wall
Feasible also in suboptimal images motion impairment
Sensitive parameter of LV systolic dysfunction
High temporal resolution
Speckle tracking Highly reproducible Off-line method in most cases
echocardiography (STE) Accurate method Significant time required for post-processing for some
High temporal resolution softwares
Not affected by translation movements Strict dependence on frame rate (60–110 fps)
Angle independent Dependency on 2D image quality
Assessment of entire myocardial wall Heterogeneity in LV myocardial thickness and geometry
High sensitive parameters in many cardiac condition Variations in lateral wall resolution
Suboptimal test–retest reproducibility
Lack of established validated normal reference
Possible vendor differences
Twist Feasible in most patients, both at rest and during stress test Dependence on preload, afterload, contractility, heart
Elevated values can express a subendocardial impairment, rate and sympathetic activation
typical of many cardiac pathologies Off-line method in most cases
Significant time required for post-processing for some
softwares
Strict dependence on frame rate (60–110 fps)
Dependency on 2D image quality
Heterogeneity in LV myocardial thickness and geometry
Suboptimal test–retest reproducibility
Lack of established validated normal reference

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Table 2 Normal reference

Variable Normal values References
values for the
echocardiographic parameters Ejection Fraction 60 ± 5 % [2, 5–7]
of left ventricular systolic
function Noninvasive dP/dt [1200 mmHg/sec (\27 ms) [27]
TEI index 0.39 ± 0.05 [28]
MAPSE [15 mm [41–43]
Lateral S’ 9.9 ± 2.4 cm/sec [43]
Septal S’ 8.3 ± 1.7 cm/sec [43]
Global longitudinal strain -19.7 ± 0.8 % [103]
LV twisting 9.3 ± 1.8 [6, 11]

Fig. 1 Measurement of LV
ejection fraction and stroke
volume

LVEF values can be misleading when the EDV is too big Conventional Doppler indices of global left
or too small: in fact, patients with the same EF may have ventricular function
different SVs and, vice versa, patients with identical SV
may have different EFs. Therefore, EF and SV should not The Doppler dP/dt
be evaluated alone but integrated each other and together
with other parameters in a more complex assessment of LV The invasive LV dP/dtmax, that is, the change in maximum
systolic function. rate of systolic pressure rise, is a sensitive parameter of
myocardial performance that closely approximates changes
Cardiac index measurement of contractility; however, its utility has been limited
because it needs an intra-ventricular catheter for its
The effective (forward) aortic stroke volume and cardiac assessment.
index can be calculated using an integrated echo-Doppler Doppler echocardiography can estimate the rate of
method (Fig. 1). Cardiac index provides temporal assess- pressure gradient changes by using the continuous wave
ment of cardiac function via consideration of heart rate, a Doppler signal of mitral regurgitation [24]; this method has
parameter devoid from SV or EF assessment alone. In fact, a good correlation with the corresponding invasive-derived
since EF is a difference of volumes, it expresses global, not parameter [25–27]. This beat-by-beat and repeatable esti-
effective (forward) aortic stroke volume. This becomes mation should be very useful in patients with heart failure
important in particular conditions, such as mitral regurgi- and mitral regurgitation [26, 27]; in this settings this
tation or interventricular septum defect, when LV antero- parameter is highly feasible because a mitral regurgitation
grade ejection is overestimated by LVEF; this is even more is a common finding in patients with congestive heart
evident when mitral regurgitation or interventricular sep- failure [27].
tum defect occur acutely (e.g., because of ischemic papil- The Doppler LV dP/dt is calculated as the difference in
lary muscle dysfunction or interventricular septum pressures (which can be derived utilizing mitral regurgi-
rupture). tation velocities via the modified Bernoulli equation)

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decades, the Tei index has proved to be a reliable method

for the evaluation of LV myocardial performance, with
clear advantages over older established indices and prog-
nostic value in many kinds of heart disease [29].
Initially, using the pulsed wave Doppler technique in the
apical four-chamber view, with the sample volume placed
at the tips of the mitral leaflets, the time between the end of
the A wave and the beginning of the subsequent E wave of
mitral inflow is measured (Fig. 3); this time interval
(a) includes the isovolumic contraction time (IVCT), the
ejection time (ET) and the isovolumic relaxation time
(IVRT) (Fig. 3). Then, placing the sample volume below
Fig. 2 dP/dt measurement the aortic valve, in the apical five-chamber view, the LV
ejection time (b) can be measured (Fig. 3). Like the LVEF,
the Tei index is a dimensionless number, as it is a ratio of
divided by the difference in time of these measurements two time intervals.
[27] (Fig. 2). This parameter is less influenced by change A study of children from 30 to 18 years with no car-
in afterload and mildly influenced by changes in preload; diovascular disease determined the range of normal values
notably, it is not affected by wall motion abnormalities. for the Tei index and the effect of age [28, 30]. In patients
For this estimate, a well-delineated velocity spectral with dilated cardiomyopathy and myocardial infarction the
envelope from mitral regurgitation is mandatory for accu- Tei Index showed significative correlation with invasive
rate measure of pressure gradients. Therefore, careful hemodynamic parameters, such as the systolic dP/dtmax,
scanning is necessary to align the cursor parallel to the the maximum rate of pressure decrease (diastolic -dP/
mitral regurgitant flow to obtain the optimal velocity dtmax), and the time constant of pressure reduction during
spectrum and prevent underestimation of dP/dt. Sometimes isovolumic relaxation (tau) [31].
mitral regurgitant jet velocities can be difficult to record in The Tei Index was assessed in dilated cardiomyopathy
case of eccentric regurgitant jets. [32] and heart failure [33, 34] and showed a good corre-
lation with the LVEF and NYHA class as well a prognostic
The myocardial performance index value for short- and long-term outcome. Patients with acute
myocardial infarction had Tei Index values higher than
As mentioned before, there are many limitations to the use healthy controls, and higher values have been observed in
of classical echocardiographic indices for the estimation of patients with more severe coronary disease and with more
systolic LV function. The LVEF and volumes by the complicated course [35].
Simpson’s method, for example, are subject to significant Unfortunately, the Tei index has important limitations.
errors when the ellipsoid shape of the heart becomes For example, it is affected by valvular heart diseases and
spherical. Tei et al. [28] devised and published an index of significantly changes after valve surgery, especially in
myocardial performance (the Tei index) that combines the patients with aortic stenosis [36]. Moreover, in healthy
evaluation of the LV systolic and diastolic function. In last controls the Tei index increases significantly during the
Valsalva maneuver (mainly as a result of a reduction in
ET), after passive leg raising (primarily as a consequence
of an increase in IVCT) and after nitroglycerine adminis-
tration (as a result of a reduction in ET and a prolongation
of IVCT), while no significative changes in patients with
previous myocardial infarction were demonstrated [37].
Considering that beat-to-beat variability can significantly
influence measurements, the Tei Index is not feasible in
patients with variable cardiac cycle duration, as it occurs in
atrial fibrillation and other atrial tachycardias, frequent
supraventricular and ventricular extrasystoles, and atri-
oventricular conduction abnormalities. In addition, it does
not represent the method of choice in patients with ven-
Fig. 3 Tei index method measurement tricular pacing and intraventricular dyssynchrony [38].

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Left ventricular longitudinal function moreover an independent predictor of adverse outcome in

many pathological conditions, as chronic HF [48],
The LV longitudinal function entails the movement of the stable CAD [49], and chronic AF [50].
mitral annulus toward the cardiac apex. It depends on the
shortening of the LV longitudinal myocardial fibers, Limitations of M-mode echocardiography
mainly those present in the subendocardial layer [1]. It has
been demonstrated that, in healthy subjects and in patients The AVPD has many limitations. First of all, the AVPD is
with advanced dilated cardiomyopathy, longitudinal func- an angle-dependent measure, so it could be erroneous if the
tion accounts for up to the 60 % of the SV [39]. Also, ultrasound beam is not properly aligned to the mitral
because the subendocardium is the first layer to be involved annulus. Also, because the AVPD is limited to the mitral
in many cardiac diseases (such as the ischemic, hyperten- annulus, it can be reduced in case of regional motion
sive, diabetic and valvular heart diseases), longitudinal impairment even with no significant reduction of global LV
function is expected to be impaired early. The LV longi- function. Notably, left atrial contraction has been proposed
tudinal function can be assessed in different ways. to affect AVPD via the Frank–Starling mechanism [51], a
finding that may explain the presence of reduced AVPD in
M-mode echocardiography patients with atrial fibrillation (AF) as compared to age-
matched controls in sinus rhythm [52]. Despite the fact that
This technique allows measuring the atrioventricular plane AVPD has been shown to be feasible in many patients,
displacement (AVPD), also known as mitral annular plane there are several cases where it is difficult to measure:
systolic excursion (MAPSE). The measurement is per- mitral annulus calcification, mitral and aortic valve pros-
formed at the septal and/or lateral annulus level in the theses, mitral valve surgery, prominent hypertrophic
apical four-chamber view, as the distance between the interventricular basal septum, and septal papillary muscle
nadir of the M-mode annular motion profile—correspond- (which may obstacle appropriate ultrasound beam orien-
ing to the maximal backward displacement from LV apex tation and AVPD visualization especially on the septal side
after the electrocardiographic P wave—and the peak of the mitral annulus). Furthermore, it should be considered
shortening, i.e., the point of maximum upward excursion that the AVPD is by definition taken at the maximum
toward the LV apex (Fig. 4). This method is simple, upward excursion toward the LV apex, which may not
quickly performed, and feasible [40]. According to the coincide with the end of systole but rather be post-systolic.
modern literature [41–43] values C15 mm are supposed to Finally, timing of peak upward excursion may vary at the
be normal. septal and lateral side of the mitral annulus if the LV
A depression of MAPSE can evidence subtle systolic contraction is dyssynchronous (such as in presence of left
impairment in nearly one quarter of patients with HF and bundle branch block): In this case the average of the septal
preserved EF [44] and in other conditions often charac- and lateral AVPD measures can be questionable.
terized by normal EF, such as arterial hypertension [45]
and aortic stenosis [46]. In the clinical history of hyper- Tissue Doppler Imaging
tensive cardiomyopathy, a reduction in MAPSE precedes
that in circumferential systolic function even when the By eliminating the wall filter and using low-gain amplifi-
latter is evaluated at the mid-wall level [47]. AVPD is cation, myocardial tissue velocities can be displayed by

Fig. 4 Measurement of mitral

annular plane systolic excursion
(MAPSE)

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Fig. 5 Tissue Doppler imaging of the mitral annulus systolic velocity

tissue Doppler imaging (TDI) using the pulsed wave completion of systole (mainly during the isovolumetric
Doppler technique, the two-dimensional color Doppler relaxation time) and that does not contribute to the ejection
map, and the color M-mode image [53, 54]. of the blood [70]. During the last decade, many studies
Taking advantage of the differences in velocity of the have demonstrated the utility of this parameter for detect-
LV wall segments (higher at the base, lower at the apex), ing acute ischemia [71], adding improved accuracy com-
the pulsed wave TDI sample volume can be placed at the pared to conventional visual wall motion reading [72].
LV base allowing a real-time recording of instantaneous However, Claus et al. [73] demonstrated that PSS is made
maximal velocities with high temporal resolution [14]. The by heterogeneity of contraction among myocardial regions
normal myocardial velocity curve during systole includes and can be observed in other condition such as hypertrofic
an initial positive or biphasic deflection corresponding to and dilated cardiomyopathy, hypertensive heart disease,
the LV isovolumic contraction (S1), and a second larger pulmonary hypertension, left bundle branch block, and
positive wave (S2), usually referred to as S’, corresponding even up to one-third of myocardial segments in healthy
to the LV ejection phase (Fig. 5). This measure is generally subjects [74] (physiologic PSS). This lack of specificity of
taken in the apical four-chamber view: The annular this parameter hampered a widespread use in the clinical
velocity can be evaluated at the septal [55] and the lateral setting. Recently, it has been reported that PSS could rec-
annulus [56], and the values can be averaged [57]. The ognize past myocardial ischemic insults (i.e., ischemic
average value should be preferred because of velocity memory), and this could give interest for the use of this
inhomogeneity along the annular circumference. parameter [75].
TDI is used in clinical practice because of measurement There are, however, many limitations of TDI. The most
simplicity, good reproducibility, and feasibility in almost important one is related to its angle dependence, as any
all patients regardless of echocardiographic image quality. other Doppler method. A second limitation is that mitral
Its role as a sensitive parameter of LV systolic function has annulus TDI velocities are affected by translational
been established in many pathological conditions such as motions of the whole heart and by tethering effects, that is,
arterial hypertension [58], hypertrophic cardiomyopathy passive motion of LV hypokinetic/akinetic myocardial
[59], chronic aortic regurgitation [60], cardiac amyloidosis segments due to adjacent segments with preserved systolic
[61], heart transplantation [62], and obesity [63]. It also has contraction. Third, TDI does not track mitral annulus
been shown to discriminate between hypertrophic car- motion; therefore, during both systole and diastole, the left
diomyopathy and ‘‘physiologic’’ hypertrophy [64]. Finally, atrial wall may cross the pulsed wave TDI cursor.
its high temporal resolution allows detection of post-sys-
tolic shortening and evaluation of LV dyssynchrony for Speckle tracking echocardiography
cardiac resynchronization therapy [65, 66]. Its high tem-
poral resolution could, moreover, help us to identify the Speckle tracking echocardiography (STE) is a novel
presence of post-systolic shortening (PSS) [67–69], echocardiographic tool to assess myocardial function [76].
myocardial contraction that continues to occur following The echocardiographic speckle pattern obtained using

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grayscale B-mode echocardiography represents the result and this allowed the American FDA to approve longitu-
of random interferences between tissue scatterers. As a dinal speckle tracking analysis directly on newer echo-
consequence, each myocardial region is characterized by a scanners, while other STE analyses can be performed off-
definite, relatively stable, unique speckle pattern that can line.
be used to differentiate it from other regions throughout the In general, the maximal extent of longitudinal systolic
cardiac cycle. Consequently, after defining a region in one myocardial deformation (peak systolic strain) and its peak
frame, this can be identified in the next frame as the region rate (peak systolic strain rate) have been used, both
with equal size and shape with the most similar speckle regionally and globally, in the literature. Particularly, a
pattern, allowing tracking of a given region from frame to parameter called systolic ‘‘global longitudinal strain’’
frame. In this view, echocardiographic speckles substan- (GLS) has gained increasing interest: It is generally cal-
tially behave as magnetic resonance tags, as they allow culated from the mean of the 17 cardiac segments obtained
direct tracking of myocardial motion. Notably, due to the from the three standard apical four-chamber, two-chamber
rotational/translational motion of the heart and small and long-axis views. A key difference between systolic
changes in the reflector interference pattern, the speckle GLS and other measures of LV longitudinal systolic
pattern does not remain perfectly unchanged during cardiac function, such as AVPD and peak TDI mitral annulus
cycle. Nonetheless, the statistical approach of searching the systolic velocities, is timing of measurement: In fact, the
best matching area (i.e., that with the least difference in GLS is calculated at end-systole, that is, at the time of the
mean pixel signal intensity) provides an accurate tracking aortic valve closure, while AVPD may be affected by post-
of myocardial tissue when compared against ultrasonomi- systolic myocardial contractions, and peak TDI mitral
crometry and tagged cardiac magnetic resonance [77]. annulus systolic velocities occur earlier during systolic
The STE technique assesses myocardial strain (e) ejection. In addition, timing of maximal AVPD and peak
according to the Lagrangian formula: TDI systolic velocities at the septal and lateral side of the
L  L0 mitral annulus may not coincide even in normal subjects:
e¼ In this regard the GLS appears as a more reliable and
L0
pathophysiologically sound parameter since it is calculated
where L0 is the initial myocardial length (by definition the by definition at end-systole for each one of the LV
end-diastolic length of myocardial wall) and L is the myocardial segments.
myocardial length after the deformation [78]. Strain is a GLS has proven to be useful both as a prognostic and a
dimensionless parameter expressed as the percentage (%) diagnostic indicator in addition or as an alternative to the
of myocardial deformation; negative values indicate LVEF. As a prognostic indicator, GLS showed to be
shortening or compression, while positive ones lengthening superior to LVEF and other longitudinal markers in iden-
or stretching. Strain rate (SR) is the first derivative of strain tifying heart failure patients with poor outcome [82–84].
and can be calculated as As a diagnostic indicator, GLS has been successfully
applied to predict cardio-toxicity due to oncologic treat-
De
; ments, allowing earlier recognition of cardiac impairment
DT
compared to conventional evaluation of LV systolic func-
i.e., the strain that occurs per time unit and is expressed as tion [85]. In the field of cardio-toxicity, GLS has the
s- [1]. Peak systolic strain and peak systolic SR are indices potential to become a new standard for recognition of LV
of regional systolic function, but all segmental values may systolic dysfunction.
be averaged to provide parameters of global LV systolic Strain and strain rate measurements by STE are diag-
function. nostic of myocardial infarction with high sensitivity and
The two-dimensional STE technique has a high tem- specificity [86–91] and can potentially distinguish between
poral and spatial resolution and, being a semiautomatic fibrous and viable tissue by assessing movement from
software, has a good inter- and intra-observer repro- scarred tissue tethered to the non-scarred segments [92].
ducibility [79]. Compared to Doppler strain, this technique The STE technique has been also extensively applied in the
had the advantage to be angle independent [80], not field of cardiac resynchronization therapy to quantify LV
affected by translational motions of the heart and can dyssynchrony [93]. Although some studies suggest
assess simultaneously the entire LV myocardium [81]. promising findings, current data are insufficient to advocate
Therefore, STE can allow a reliable assessment of for routine use of STE for patient selection for resyn-
myocardial deformation along the tridimensional geomet- chronization therapy [94].
rical axes (longitudinal, circumferential, and radial strain; Other current clinical applications of strain imaging are
Figs. 6, 7, 8) throughout the cardiac cycle. Longitudinal diagnosis of cardiac amyloidosis [95], myocarditis with
strain, in particular, has a high sensitivity and reliability, normal LVEF [96], and evaluation of cardiomyopathies,

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Fig. 6 Londitudinal strain

measured in 4-, 2- and
3-chamber views

like hypertrophic and dilated cardiomyopathies [97, 98]. has a relatively short duration and a lower frame rate than
Furthermore, its high temporal resolution makes possible TDI, indispensable for the analysis, may reduce the accu-
the quantification of myocardial PSS [75]. However, PSS racy of this parameter [99]. Moreover, there are debates

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Fig. 7 Measurement of basal

circumferential strain

Fig. 8 Measurement of basal

radial strain

about which direction of STE strain should be analyzed: (\40 fps) will result in excessive changes in the speckle
Longitudinal apical strain in apical views could suffer of pattern from frame to frame, thus yielding poor quality of
difficult analysis and vendor differences [100]. tracking. Conversely, elevated high frame rate ([100 fps)
The major limitation of STE is the dependence on two- will result in high levels of noise. A low frame rate, that is,
dimensional frame rate to allow the appropriate tracking of a low temporal resolution, may also preclude adequate
the speckles in all the directions [101]. A low frame rate strain rate analysis, since the strain rate curve is

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multiphasic throughout the cardiac cycle, while the strain found excellent correlation between visual assessment of
curve generally reaches a single peak (positive or negative the MRI images and the values obtained for peak radial and
depending on the type of strain). Other limitations include circumferential strains. Furthermore, they showed that this
the dependency on two-dimensional image quality, technique had good inter- and intra-observer variabilities
heterogeneity in LV myocardial thickness, and geometry, when the same cardiac cycle was used in both measure-
variations in lateral wall resolution, and suboptimal test– ments. They showed that the measurements were repro-
retest reproducibility [102]. The time required for post- ducible by conducting the same examination 2 days apart
processing is generally not significant when longitudinal and showed a range of relative variability from. Both the
strain is evaluated, but it may become much longer with the sensitivity and specificity of this technique in the detection
other types of strain analysis (radial and circumferential). of dyssynergy were 83.5 %.
Inter-vendor differences have been highlighted by several Radial strain was used also for the detection of
investigators, as a source of variation of strain results. myocardial dyssynchrony. Suffoletto et al. [101] found that
However, a recent metanalysis [103] showed that the radial dyssynchrony by 2D strain was higher in the patients
effects of age, gender, body mass index, frame rate, and who showed an acute response to cardiac resynchronization
vendor were not significant determinants of variations and a pre-determined dyssynchrony value of [130 ms
among normal ranges of GLS. This should not be mis- predicted an immediate increase in SV in the day after
construed to mean that these features do not influence CRT with good accuracy and EF after a 6-month long-term
strain; previous work has shown age [104] and female follow-up. Interestingly, they did find a proportion of
gender [105] to be associated with lower GLS. However, it patients with no evidence of longitudinal dyssynchrony but
does enable us to put the impact of vendor in the context of clear evidence of radial dyssynchrony suggesting that
other common influences. while the two often coexist, this may not always be the
In the last years, three-dimensional STE has also been case.
evaluated for assessment of LV systolic function and The limitations of radial and circumferential strain are
dyssynchrony [106, 107]. Although this technique may many. Measurements in the radial plane were shown to
overcome some limitations on the two-dimensional STE, correlate less well with the reference tool of ultrasonomi-
such as the out-of-plane motion of the LV, it is still at its crometry with respect to longitudinal strain. This is due to
infancy and more technical and investigational work is the relatively limited thickness of the LV wall (about 1 cm)
needed before it can be suggested for clinical practice. hence the inability to perform spatial filtering, along with a
greater proportion of movement being perpendicular to the
ultrasound beam which is associated with greater variance
Radial and circumferential strain [108]. An important limitation that should not be ignored is
the plane motion. During systole, the base of the ventricle
Since the speckles can be tracked in any direction, then it is moves toward the apex. This will mean that the speckle
possible to measure its movement in both the axial and pattern present in one frame might be different from that in
azimuth planes. STE allows the assessment of the per- the next frame. While these changes are small, they may
centage of radial thickening (Fig. 8) and of circumferential have an important effect on the data derived [110].
shortening (Fig. 7) of the myocardial wall, using the ima-
ges in the parasternal short axis view and at different
levels: ventricular base, mid-wall (where the papillary
muscles are visible) and apex. Radial strain draws positive Left ventricular twisting
curves, while circumferential strain negative ones. Exper-
imental studies with animal models found a very good LV twisting was first described by Harvey in 1628. LV
correlation between the values obtained from sonomi- twisting and recoil (untwisting) are a result of the dynamic
crometry and 2D strain in both the radial and circumfer- interaction between obliquely oriented epicardial and
ential planes [108]. As assessed above, these methods are endocardial fibers wound oppositely [111]. Twisting of the
not well studied are still reserved for research purposes and LV is the wringing motion of the ventricle around its long
fewer clinical trial applied these to evaluate the systolic axis induced by contracting myofibers in the LV wall
function. Becker et al. [109] compared both radial and [111]. In particular, twisting is generated by the opposite
circumferential strains in both healthy volunteers and those rotation of the LV base and the apex. Basal and apical LV
with previous infarction. Subjects underwent cardiac rotations are expressed in degrees as well as twisting,
magnetic resonance imaging (CMR) to distinguish between which is the result of the algebraic difference between
normokinesis, hypokinesis, and akinesis based on the apical and basal rotation; torsion is obtained dividing
16-segment American Heart Association model. They twisting by the length of the LV cavity, in degrees/cm.

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88 Heart Fail Rev (2016) 21:77–94

Fig. 9 Measurement of LV
twisting

During initial isovolumic contraction, the apex and the and the general accessibility to echocardiography (Fig. 9).
base both rotate in a counterclockwise direction [112] With respect to temporal resolution, the frame rates chosen
when viewed from apex to base. Subsequently, during are important, with a range of 60–110 fps generally sug-
systole the base changes direction and starts to rotate in a gested for resting humans [118]. The widespread avail-
clockwise direction, while the apex continues to rotate in ability of this tool may favor the introduction of LV
counterclockwise direction. LV twisting is followed by twisting as a clinical measure for detection of myocardial
rapid isovolumic untwisting of the ventricle. dysfunction.
Sub-endocardial fibers are right-hand-oriented; sub-epi- The disadvantages of STE-derived LV rotation include
cardial fibers are left-handed. The left-handed helix of the the reliance on adequate image quality and the attempt to
epicardium dominates rotational motion due to its longer track a three-dimensional motion with a two-dimensional
lever arm from the center of the LV. The endocardial layer, image. Compared to cardiac magnetic resonance, where the
with a right-handed helix, moves together with the epi- LV slices can be precisely chosen, a limitation exists with
cardium, although providing some opposition to epicardial STE-derived twisting, particularly when measuring the
motion [113]. As a result of twisting, epicardial and apex. Data acquisition at the apex is generally guided by
endocardial sarcomere shortening in all directions tends to acquiring a sample ‘‘below the papillary muscles,’’ which
be equilibrated during ejection, resulting in reduced stress can cause measurements to be taken at varying proximities
between myocardial fibers [114]. to the true apex [119].
The importance of quantifying LV rotation lies in its
LV twisting by speckle tracking echocardiography potential for guiding clinical treatments. Measurements of
peak twisting, time to peak twisting, and rate and time of
The recent introduction of STE drew new attention to LV peak untwisting may provide further insights into pathol-
twisting [115, 116]. The STE technique has been shown to ogy beyond traditional clinical measures such as LVEF and
correlate very well with cardiac magnetic resonance in Doppler indices of diastolic function. Twisting can be
humans (r = 0.93) [116]. Recently, Hui et al. [117] have impaired by cardiac remodelling causing rearrangement of
shown the ability of two-dimensional STE to quantify muscular fibers orientation and synthesis of extracellular
transmural (endocardium and epicardium) twisting. matrix that can alters the capacity of storing potential
The advantages of STE for assessment of LV rotation energy during systole. Moreover, impairment of regional
and twisting include the relatively high temporal resolu- coronary perfusion or arrhythmias can have detrimental
tion, the possibility of acquiring images during exercise, effects on LV torsional movements.

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Heart Fail Rev (2016) 21:77–94 89

The effect of age on LV twisting deserves specific Conclusions

attention. Burns et al. [120] found LV twisting to be
elevated in older males at rest. Also, the augmentation (or For clinical and research purposes, many echocardio-
reserve) of twisting during exercise was shown to be graphic and Doppler indices are available to evaluate the
significantly less in the older cohort. Lumens et al. [121] LV systolic function. This paper has reviewed most of
found reduced endocardial circumferential shortening in them focusing the pro and the cons of each one. First of all,
elderly individuals. They suggested that such a reduced while the traditional parameters, such as the LVEF and SV,
endocardial function would result in less opposition to the evaluate the global pump function of the heart, more recent
dominant epicardium, ultimately causing an increased indices derived by the STE technique specifically focus on
rotation and twisting. It has been proposed that endocar- LV myocardial function, with the possibility to describe the
dial function is more likely to reduce with age due to the mechanism of contraction and its components, such as
sub-endocardium’s greater susceptibility to fibrosis and/or longitudinal and circumferential shortening, radial thick-
subclinical reductions in perfusion. This is in agreement ening, rotation and twisting. Pump and myocardial function
with the observation that, during the first seconds of parameters have a different sensitivity for recognition of
ischemia, apical rotation has been found to increase due subtle or early cardiac impairment in many heart diseases
to dysfunction of only the sub-endocardial fiber layer and should be considered as complementary. However,
[122]. none of these traditional and new parameters per se is truly
The mechanism described above could be considered as representative of contractility and anyone is also dependent
a mechanical reserve to maintain the LVEF when the on load. Thus far, no echocardiographic technique yields a
endocardium is impaired; later, when all myocardium is true measure of contractility. This may relate to the fact
impaired, the twisting inevitably decrease. Clinical support that contractility itself is independent of loading condi-
to this theory is given by studies on hypertensive [123] and tions. There continues to be a need for novel LV parame-
diabetic patients (both type 1 and 2) with preserved LVEF ters that are completely load-independent.
[124] in whom increased values of LV twisting is sug- Also, most of them evaluate the contraction phase of LV
gested to be a precursor to the myocardial alterations found systole and do not consider, with the exception of the Tei
in diabetic cardiomyopathy [125]. Wang et al. [126] index, the isovolumetric contraction and relaxation phases,
showed normal LV twisting in heart failure with preserved both accounting in myocardial oxygen demand. In con-
LVEF, while Fuchs et al. demonstrated a reduction in peak clusion, at present the role of the clinician remains fun-
and peak rates of twisting and untwisting in heart failure damental for selection of the appropriate parameters of LV
with reduced LVEF [127]. systolic function for the single-patient case. In general,
The finding of reduced sub-endocardial function and however, the integration of pump and systolic myocardial
increased twisting in older individuals occurred despite no function indices should result in a deeper and more sensi-
abnormalities in LVEF or mass, indicating that measure- tive evaluation of LV systolic function and should be
ments of twisting may be important for the early detection suggested, especially when the evaluation of LV systolic
of cardiovascular dysfunction [121]. function is needed for crucial clinical decisions.
As the other echocardiographic parameters discussed
above, also torsion is dependent on preload, afterload, Compliance with ethical standards
contractility, heart rate, and sympathetic activation [126, Conflict of interest None.
128, 129]. This is an important issue also because torsion
derives from the analysis of two non-simultaneous heart
beat and this could create variability in the measurement. References
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