**2. Principles of myocardial deformation**

During contraction of the heart, deformation of the whole muscle occurs in four quantifiable dimensions. In general, these have been identified as: longitudinal shortening (=longitudinal strain, %), circumferential shortening (circumferential strain, %), radial lengthening (=radial strain, %) and rotation (apical − basal rotation = net twist angle, degrees), as well as the diastolic reversal of all of these indices. In addition, the rate of systolic shortening and diastolic lengthening can be measured, which is referred to as strain rate, twisting rate, and untwisting rate. An important distinction must be made between myocardial deformation and pure "velocities", which do not consider the relative shortening (contraction) or lengthening (relaxation) of heart muscle itself but only consider the linear displacement of single myocardial points. Although myocardial velocities can also be measured, they are not representative of the contraction and relaxation of heart muscle. For these reasons, parameters such as E' ("E prime"), which typically represent myocardial velocities in a single location on the mitral annulus, are not discussed in this chapter.

The conventional categorizations of deformation into strain and twist are logical from a biophysics and bioengineering perspective, since deformation of the heart can indeed be detected in these distinct 2-dimensional echocardiographic imaging planes. However, as will be reviewed in the following section on the anatomy and electrical conductance, the structure of the heart is far from symmetrical and—to achieve the final coordination of all components with each heartbeat—important functional differences in the various regions within the heart are present. These intricate deformational patterns can be conceptually simplified by considering the region-specific deformation in a 2-dimensional plane, allowing for easier evaluation of cardiac mechanics in both the laboratory and the clinic. However, one must consider the 3D deformation of the heart muscle, where the deformation of the four imaging planes occur simultaneously and with many of these aspects anatomically and functionally interwoven. This anatomical complexity is the focus of the next section.

#### **2.1 Anatomy**

Historical reviews have often credited Leonardo da Vinci's observations in the 15th century as some of the first to describe the gross anatomy of the heart and his speculations about the resulting function. In his drawings1 , da Vinci refers to the importance of vortices, which necessitate the presence of helical structures and/or motions that were apparent as "clockwise and counterclockwise spirals within the aorta as the outlet of the left ventricle" [1]. More than a century after da Vinci's death, William Harvey published his seminal book *Exercitatio Anatomica De Motu Cordis Et Sanguinis In Animalibus* (An Anatomical Study on the Motion of the Heart and Blood in Living Beings, 1628 [2]), in which he established the circulation—including the anatomy

**11**

largely focused on longitudinal strain.

**2.2 Definitions and selection of myocardial deformation parameters**

Because of the increasing number of studies focused on myocardial deformation mentioned in the introduction to this chapter, it has been inevitable that some inconsistencies exist regarding the nomenclature in the literature (**Table 1**). Here, a

*Echocardiographic Assessment of Myocardial Deformation during Exercise*

Greenbaum et al. confirmed the observations in human cadavers [8, 9].

and motion of the heart—as we mostly know it today, thereby also popularizing the previous work by Ibn al-Nafis [3]. In 1669, Richard Lower provided remarkable detail on the anatomy of the heart in his publication of *Tractatus de Corde…* (Treatise on the Heart. … [4]). Despite these early discoveries, it wasn't until the contributions by McCallum and then Mall in the early twentieth century that there were new advancements in this field [5, 6]. During the second World War, Robb & Robb provided an exceptionally detailed overview of the accumulated knowledge that covered five centuries of discoveries [7]. Then, 27 years later, in 1969, Streeter et al. published the much-cited myocardial fiber distribution of the left ventricle (LV) in dogs, and

Today, after centuries of observations, there is still debate on the exact origins and arrangements of the heart [10]. However, general consensus exists that the mammalian LV consists of oblique fibers in the endocardium that gradually change into circumferential fibers in the midwall and continue to oblique fibers in the subepicardium, orientated in the opposite direction to those in the endocardium, thus creating what is often referred to as a helical arrangement [11–14]. Noteworthy insight has also been provided by the description of sheets and laminae, which may not only impact the effect of individual myofibres but also the electrical propagation across the myocardium [15, 16]. With regard to the latter, the coordinated sequence of electrical propagation and activation of the LV occurs in a specific apex-to-base and endocardialto-epicardial order during systole [17]. Due to these different electrical activation times, each part of the heart muscle is activated for different durations, therefore shortening and lengthening velocities (or systolic and diastolic "strain rates") vary significantly in the different regions of the LV and are not associated with the overall heart rate [18]. A significant addition to the longstanding knowledge on oblique and circumferential fibers was provided by Lunkenheimer et al., who provided evidence for the existence of transmural myofibres that may be of fundamental relevance to the regulation of forces associated with normal myocardial contraction and relaxation [19]. Finally, there is important structural diversity on the myocyte level that contributes to the overall elasticity of the cardiomyocyte, as revealed by different isoforms of the giant protein titin, which may influence myocardial deformation in systole and diastole, not least during exercise [20, 21]. Collectively, the current knowledge indicates a non-uniform, complex mesh of diverse cardiac myofibre arrangements which may be grouped in sheets and laminae, influencing the electrical activation sequence of the heterogeneously distributed autonomic nerves in the heart (**Figure 1**, [22]). In comparison to the LV, the macro-structure of the right ventricle (RV) is not cone-shaped but resembles that of a crescent, almost wrapping around the LV. Yet, the underlying micro-structure is similar to the LV, albeit with some key differences. Like the LV, the epicardial and endocardial fibers are arranged helically, but with a smaller range of oblique angles [23]. The main difference to the LV seems to be in the myofiber arrangement of the midwall. Here, "the circumferentially arranged middle fibres are confined to the LV and septum" [8] and "without such beneficial architectural remodeling […] seem unsuited structurally to sustain a permanent increase in afterload" [23]. It is probably because of the overall crescent shape (that makes echocardiographic image acquisition in any plane other than the longitudinal challenging), and the lack of an obvious torsional motion, that the assessment of right ventricular deformation has

*DOI: http://dx.doi.org/10.5772/intechopen.93002*

<sup>1</sup> In 2019, an exhibition across the UK celebrated the drawings by Leonardo da Vinci, including some of his anatomical sketches (https://www.rct.uk/collection/themes/exhibitions/ leonardo-da-vinci-a-life-in-drawing/the-queens-gallery-palace-of).

#### *Echocardiographic Assessment of Myocardial Deformation during Exercise DOI: http://dx.doi.org/10.5772/intechopen.93002*

*Advanced Concepts in Endocarditis - 2021*

health and disease will be reviewed.

**2. Principles of myocardial deformation**

that highlights important general principles of cardiac physiology, including the responses to exercise. To achieve this aim, first a brief overview of the principles and mechanisms governing myocardial deformation will be provided summarised and the key terminology will be defined. Then, the general role of exercise stress testing will be discussed, before the benefits of obtaining myocardial deformation during exercise in

During contraction of the heart, deformation of the whole muscle occurs in four quantifiable dimensions. In general, these have been identified as: longitudinal shortening (=longitudinal strain, %), circumferential shortening (circumferential strain, %), radial lengthening (=radial strain, %) and rotation (apical − basal rotation = net twist angle, degrees), as well as the diastolic reversal of all of these indices. In addition, the rate of systolic shortening and diastolic lengthening can be measured, which is referred to as strain rate, twisting rate, and untwisting rate. An important distinction must be made between myocardial deformation and pure "velocities", which do not consider the relative shortening (contraction) or lengthening (relaxation) of heart muscle itself but only consider the linear displacement of single myocardial points. Although myocardial velocities can also be measured, they are not representative of the contraction and relaxation of heart muscle. For these reasons, parameters such as E' ("E prime"), which typically represent myocardial velocities in a single location on the mitral annulus, are not discussed in this chapter. The conventional categorizations of deformation into strain and twist are logical from a biophysics and bioengineering perspective, since deformation of the heart can indeed be detected in these distinct 2-dimensional echocardiographic imaging planes. However, as will be reviewed in the following section on the anatomy and electrical conductance, the structure of the heart is far from symmetrical and—to achieve the final coordination of all components with each heartbeat—important functional differences in the various regions within the heart are present. These intricate deformational patterns can be conceptually simplified by considering the region-specific deformation in a 2-dimensional plane, allowing for easier evaluation of cardiac mechanics in both the laboratory and the clinic. However, one must consider the 3D deformation of the heart muscle, where the deformation of the four imaging planes occur simultaneously and with many of these aspects anatomically and functionally

interwoven. This anatomical complexity is the focus of the next section.

tions about the resulting function. In his drawings1

leonardo-da-vinci-a-life-in-drawing/the-queens-gallery-palace-of).

Historical reviews have often credited Leonardo da Vinci's observations in the 15th century as some of the first to describe the gross anatomy of the heart and his specula-

of vortices, which necessitate the presence of helical structures and/or motions that were apparent as "clockwise and counterclockwise spirals within the aorta as the outlet of the left ventricle" [1]. More than a century after da Vinci's death, William Harvey published his seminal book *Exercitatio Anatomica De Motu Cordis Et Sanguinis In Animalibus* (An Anatomical Study on the Motion of the Heart and Blood in Living Beings, 1628 [2]), in which he established the circulation—including the anatomy

1 In 2019, an exhibition across the UK celebrated the drawings by Leonardo da Vinci, including some of his anatomical sketches (https://www.rct.uk/collection/themes/exhibitions/

, da Vinci refers to the importance

**10**

**2.1 Anatomy**

and motion of the heart—as we mostly know it today, thereby also popularizing the previous work by Ibn al-Nafis [3]. In 1669, Richard Lower provided remarkable detail on the anatomy of the heart in his publication of *Tractatus de Corde…* (Treatise on the Heart. … [4]). Despite these early discoveries, it wasn't until the contributions by McCallum and then Mall in the early twentieth century that there were new advancements in this field [5, 6]. During the second World War, Robb & Robb provided an exceptionally detailed overview of the accumulated knowledge that covered five centuries of discoveries [7]. Then, 27 years later, in 1969, Streeter et al. published the much-cited myocardial fiber distribution of the left ventricle (LV) in dogs, and Greenbaum et al. confirmed the observations in human cadavers [8, 9].

Today, after centuries of observations, there is still debate on the exact origins and arrangements of the heart [10]. However, general consensus exists that the mammalian LV consists of oblique fibers in the endocardium that gradually change into circumferential fibers in the midwall and continue to oblique fibers in the subepicardium, orientated in the opposite direction to those in the endocardium, thus creating what is often referred to as a helical arrangement [11–14]. Noteworthy insight has also been provided by the description of sheets and laminae, which may not only impact the effect of individual myofibres but also the electrical propagation across the myocardium [15, 16]. With regard to the latter, the coordinated sequence of electrical propagation and activation of the LV occurs in a specific apex-to-base and endocardialto-epicardial order during systole [17]. Due to these different electrical activation times, each part of the heart muscle is activated for different durations, therefore shortening and lengthening velocities (or systolic and diastolic "strain rates") vary significantly in the different regions of the LV and are not associated with the overall heart rate [18]. A significant addition to the longstanding knowledge on oblique and circumferential fibers was provided by Lunkenheimer et al., who provided evidence for the existence of transmural myofibres that may be of fundamental relevance to the regulation of forces associated with normal myocardial contraction and relaxation [19]. Finally, there is important structural diversity on the myocyte level that contributes to the overall elasticity of the cardiomyocyte, as revealed by different isoforms of the giant protein titin, which may influence myocardial deformation in systole and diastole, not least during exercise [20, 21]. Collectively, the current knowledge indicates a non-uniform, complex mesh of diverse cardiac myofibre arrangements which may be grouped in sheets and laminae, influencing the electrical activation sequence of the heterogeneously distributed autonomic nerves in the heart (**Figure 1**, [22]). In comparison to the LV, the macro-structure of the right ventricle (RV) is not cone-shaped but resembles that of a crescent, almost wrapping around the LV. Yet, the underlying micro-structure is similar to the LV, albeit with some key differences. Like the LV, the epicardial and endocardial fibers are arranged helically, but with a smaller range of oblique angles [23]. The main difference to the LV seems to be in the myofiber arrangement of the midwall. Here, "the circumferentially arranged middle fibres are confined to the LV and septum" [8] and "without such beneficial architectural remodeling […] seem unsuited structurally to sustain a permanent increase in afterload" [23]. It is probably because of the overall crescent shape (that makes echocardiographic image acquisition in any plane other than the longitudinal challenging), and the lack of an obvious torsional motion, that the assessment of right ventricular deformation has largely focused on longitudinal strain.

#### **2.2 Definitions and selection of myocardial deformation parameters**

Because of the increasing number of studies focused on myocardial deformation mentioned in the introduction to this chapter, it has been inevitable that some inconsistencies exist regarding the nomenclature in the literature (**Table 1**). Here, a

#### **Figure 1.**

*LV anatomy, strain and twist. (A) Although the detailed anatomy of the heart is still a matter of debate, the most comprehensive, evidence-based model includes a mesh of oblique, circumferential and transmural fibers (1–5). (B) LV strain is typically assessed in three planes, the longitudinal plane (from the apex to the base, L), the circumferential plane, C, and the radial plane (from the endocardium to epicardium, R). Owing to the specific anatomy, contraction of the LV results in a twisting motion around the long-axis, with an opposing rotational movement at the base compared with the apex that is rapidly released in diastole. Resultant twist and twist velocity curves produce a clear signal for peak LV twist and early diastolic untwisting rate (red arrows). Please see further details and the original figures in Refs. [14, 24].*

summary of the most common definitions is provided and the reader is also referred to previous review articles for further details on the terminology [24–26].

With regard to the LV, three strain components have been established: longitudinal, circumferential and radial strain [25]. Systolic strain rate was once thought to reflect contractility; however, these hopes have not been sustained. Furthermore, the anatomy of the heart does not support the measurement of radial strain since there are no radial

**13**

**Figure 2.**

*Echocardiographic Assessment of Myocardial Deformation during Exercise*

fibers in the LV or RV. Although the transmural fibers may somewhat relate to this type of strain, they maximally constitute ~20% to overall deformation and do not seem to run strictly in the radial direction. Second, the classification of twist or torsion as a "shear strain" or fourth dimension of deformation does not fit the underlying anatomy of the heart either. There is currently no empirical evidence for the existence of a

Percentage shortening of the circumference

plane (for example a 4-chamber view)

circumferential shear strain"

tissue Doppler strain

Untwisting rate (°/s) The maximal early diastolic rate of reversal of twist

speckle tracking echocardiography Strain rate (/s) The rate of shortening (strain) or lengthening (strain) of each strain

Shear strain The strain resulting from two different normal strains, for example "longitudinal-

Strain (rate) imaging Generic term that can refer to strain data obtained with either tissue Doppler or

dependent than speckle tracking echocardiography

Twist (degrees) Also called the net twist angle, obtained from the net difference in rotation

Typically, the average strain of multiple walls obtained from different echocardiographic windows (4-chamber, 2-chamber, 3-chamber)

Shortening along the long-axis of the ventricles in a single 2-dimensional imaging

Strain obtained with tissue Doppler echocardiography, which is more angle-

Echocardiographic imaging based upon Doppler modality, often synonymous with

between the left ventricular base and apex. Not to be confused with torsion or rotation, the latter referring to the local angular deformation at the base and apex

*RV strain. The measurement of RV strain at rest (left) and during exercise (right) in a patient with* 

*further details and the original figure in: Wu et al. [31].*

*hypertrophic cardiomyopathy. Because of the anatomical arrangement of the RV, longitudinal strain is the most commonly investigated parameter, although further clarity is required whether to always include or exclude the septum [28]. From a functional perspective, there is strong evidence that the septal deformation is more similar to that of the LV than the RV free wall, as supported by evidence of a shared morphology [29, 30]. Please see* 

*DOI: http://dx.doi.org/10.5772/intechopen.93002*

**Parameter (unit) Description**

Circumferential strain (%)

Longitudinal strain (%)

Tissue Doppler strain (%)

Tissue velocity imaging (%)

*Deformation parameters.*

**Table 1.**

Global longitudinal strain (%)

### *Echocardiographic Assessment of Myocardial Deformation during Exercise DOI: http://dx.doi.org/10.5772/intechopen.93002*

fibers in the LV or RV. Although the transmural fibers may somewhat relate to this type of strain, they maximally constitute ~20% to overall deformation and do not seem to run strictly in the radial direction. Second, the classification of twist or torsion as a "shear strain" or fourth dimension of deformation does not fit the underlying anatomy of the heart either. There is currently no empirical evidence for the existence of a


#### **Table 1.**

*Advanced Concepts in Endocarditis - 2021*

**12**

**Figure 1.**

summary of the most common definitions is provided and the reader is also referred

*LV anatomy, strain and twist. (A) Although the detailed anatomy of the heart is still a matter of debate, the most comprehensive, evidence-based model includes a mesh of oblique, circumferential and transmural fibers (1–5). (B) LV strain is typically assessed in three planes, the longitudinal plane (from the apex to the base, L), the circumferential plane, C, and the radial plane (from the endocardium to epicardium, R). Owing to the specific anatomy, contraction of the LV results in a twisting motion around the long-axis, with an opposing rotational movement at the base compared with the apex that is rapidly released in diastole. Resultant twist and twist velocity curves produce a clear signal for peak LV twist and early diastolic untwisting rate (red* 

With regard to the LV, three strain components have been established: longitudinal, circumferential and radial strain [25]. Systolic strain rate was once thought to reflect contractility; however, these hopes have not been sustained. Furthermore, the anatomy of the heart does not support the measurement of radial strain since there are no radial

to previous review articles for further details on the terminology [24–26].

*arrows). Please see further details and the original figures in Refs. [14, 24].*

*Deformation parameters.*

#### **Figure 2.**

*RV strain. The measurement of RV strain at rest (left) and during exercise (right) in a patient with hypertrophic cardiomyopathy. Because of the anatomical arrangement of the RV, longitudinal strain is the most commonly investigated parameter, although further clarity is required whether to always include or exclude the septum [28]. From a functional perspective, there is strong evidence that the septal deformation is more similar to that of the LV than the RV free wall, as supported by evidence of a shared morphology [29, 30]. Please see further details and the original figure in: Wu et al. [31].*

meaningful number of longitudinal fibers that could determine longitudinal deformation of the ventricles. Instead, the oblique fibers that make up most of the fibers within the left ventricular walls are likely responsible for deformation in the longitudinal direction. Consequently, it does not seem appropriate to calculate twist or torsion from the longitudinal and circumferential shear angle, also because this approach does not capture the potential regional differences that exist between the base and apex in both the LV and RV. Despite these drawbacks to the radial and longitudinal parameters, it must be acknowledged that longitudinal strain has become the most established measure as a clinical marker with diagnostic potential [27]. For these reasons, in the context of this chapter, it seems appropriate to ignore LV radial strain but include LV longitudinal and circumferential strain as well as twist and untwisting rate. Since no clear circumferential fibers or twisting motion have been detected in the RV, the focus for that chamber will be exclusively on longitudinal strain **Figure 2**.
