**3. Echocardiographic assessment of myocardial deformation during exercise**

#### **3.1 Why exercise?**

Even if all humans were elite athletes, we would spend most of the time in a day in a biological state of rest—or certainly in a state of low physical activity that only constitutes a fraction of the total capacity of our cardiovascular system. Accordingly, the routine clinical practice of examining cardiac function at rest is a good representation of the condition we find ourselves in most of the time. However, when a person requires an echocardiographic examination, it is typically for clinical reasons initiated by the presence of negative symptoms, often presenting as "exertional dyspnea" or angina. If an echocardiographic examination then detects structural and functional abnormalities of the heart that are congruent with the individual's symptoms, the diagnosis of heart disease is likely. However, resting assessment of cardiac function often fails to recapitulate conditions of exertional dyspnea, and thus can sometimes lead to misdiagnosis. Equally, waiting until the emergence of symptoms postpones clinical treatment. For this reason, "stress testing" has been suggested to offer the opportunity of a "window into the future". By taking the person out of their typical state of rest or low physical activity and stressing the full range of their cardiovascular system until maximum effort, underlying abnormalities may be detected that remain otherwise unknown. Examples for the benefit of exercise testing have been presented in relation to "unmasking masked hypertension" [32, 33]. Similarly, in pregnancy it has been proposed that the cardiovascular responses to exercise tests prior to conception may be indicators of the presence or absence of complications during future pregnancies [34–37]. Furthermore, the complex etiology of heart failure has justified detailed exercise testing to identify the most important contributors out of the numerous cardiac or peripheral factors that may be involved in the development and/or the state of heart failure [38–40].

It is now recognized among clinical practitioners that the investigation of myocardial deformation during exercise can provide additive value, since previous research studies have revealed new (and sometimes surprising) insight into the behavior of the heart during exercise. As will be discussed in detail in Section 3.3, these findings have informed our basic understanding of cardiac function and sometimes guided future clinical investigation. Since myocardial function, including parameters of myocardial deformation, are influenced by the general loading state of the heart, any exercise responses must be seen in the context of general cardiovascular responses, as discussed in the next section.

**15**

*Echocardiographic Assessment of Myocardial Deformation during Exercise*

In the context of myocardial deformation, the most relevant cardiovascular and cardiopulmonary responses to a standardized exercise test pertain to stroke volume, cardiac output, end-diastolic volume, blood pressure, arterial resistance, lactate, and maximal oxygen consumption (VO2max). In healthy individuals, a clear change in these parameters can be expected at the onset of low intensity dynamic exercise that should continue to change linearly up to moderate intensities. Importantly, dynamic exercise tests cause a disproportionate peripheral vasodilation in relation to the increase in cardiac output, and hence total peripheral resistance drops sharply at the onset of exercise and then remains constant across moderate and high exercise intensities [41]. From a diastolic perspective, end-diastolic volume has been shown to increase in some studies while others have not observed any change with exercise. This is not trivial since an acute increase in end-diastolic volume has been associated with an increased stroke volume, an effect also known as the Frank-Starling mechanism [42]. However, the overall contribution of end-diastolic volume to stroke volume is still relatively low because most of the increase in stroke volume has been attributed to the enhanced contractility that reduces the end-systolic volume.

At workloads above moderate intensity, several important physiological changes occur in healthy individuals. Blood lactate concentrations increase exponentially and CO2 production rises above O2 consumption, both reflecting the greater contribution of anaerobic metabolic pathways to overall energy utilization and causing a strong stimulus for vasodilation not least in the cerebral circulation. During the highest effort, stroke volume and VO2 have been reported to plateau and even decrease, but the exact pattern and the underlying mechanisms to this response remain a matter of debate [43]. Fortunately, this does not seem to impact the interpretation of cardiovascular responses to exercise in patients, since the sub-maximal data are currently thought to be of sufficient clinical value to determine whether exercise performance is

One important distinction between the LV and RV responses to exercise is the potential for a "disproportionate load" on the RV [45], which is perhaps explained by both a greater relative rise in pulmonary blood pressure compared with that in the aorta, and differences in RV intrinsic factors such as force development. The differences between the LV and RV responses to exercise highlight the specific impact exercise has on the cardiovascular system. Consequently, determining the true origin of exercise limitations is challenging because many components of the cardiovascular system may be affected. For example, studies have shown that an exaggerated rise in blood pressure during exercise may be associated with negative outcomes, but whether this is caused by the heart or the periphery may be more difficult to determine [46–48]. Even in heart failure, the reduced exercise tolerance has been suggested to be a result of both central and non-cardiac limitations [38–40, 49]. Consequently, assessing myocardial deformation *in relation* to conventional exercise responses is essential for the quantification of the contributions of the heart muscle itself.

Whatever myocardial parameter one chooses to examine during exercise, the interpretation of the responses can be tricky. For example, an increase in myocardial deformation with sub-maximal cycle exercise along with a typical drop in arterial resistance and concomitant reductions in end-systolic volume, in the presence of no adverse structural remodeling would be reflective of a "healthy" response. Equally, it is theoretically possible that the absence of a clear increase in myocardial deformation—which could be interpreted to represent myocardial

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

normal or impaired [44].

**3.3 Myocardial deformation during exercise**

**3.2 General cardiovascular responses to exercise**

## **3.2 General cardiovascular responses to exercise**

*Advanced Concepts in Endocarditis - 2021*

**during exercise**

of heart failure [38–40].

**3.1 Why exercise?**

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**.

**3. Echocardiographic assessment of myocardial deformation** 

Even if all humans were elite athletes, we would spend most of the time in a day in a biological state of rest—or certainly in a state of low physical activity that only constitutes a fraction of the total capacity of our cardiovascular system. Accordingly, the routine clinical practice of examining cardiac function at rest is a good representation of the condition we find ourselves in most of the time. However, when a person requires an echocardiographic examination, it is typically for clinical reasons initiated by the presence of negative symptoms, often presenting as "exertional dyspnea" or angina. If an echocardiographic examination then detects structural and functional abnormalities of the heart that are congruent with the individual's symptoms, the diagnosis of heart disease is likely. However, resting assessment of cardiac function often fails to recapitulate conditions of exertional dyspnea, and thus can sometimes lead to misdiagnosis. Equally, waiting until the emergence of symptoms postpones clinical treatment. For this reason, "stress testing" has been suggested to offer the opportunity of a "window into the future". By taking the person out of their typical state of rest or low physical activity and stressing the full range of their cardiovascular system until maximum effort, underlying abnormalities may be detected that remain otherwise unknown. Examples for the benefit of exercise testing have been presented in relation to "unmasking masked hypertension" [32, 33]. Similarly, in pregnancy it has been proposed that the cardiovascular responses to exercise tests prior to conception may be indicators of the presence or absence of complications during future pregnancies [34–37]. Furthermore, the complex etiology of heart failure has justified detailed exercise testing to identify the most important contributors out of the numerous cardiac or peripheral factors that may be involved in the development and/or the state

It is now recognized among clinical practitioners that the investigation of myocardial deformation during exercise can provide additive value, since previous research studies have revealed new (and sometimes surprising) insight into the behavior of the heart during exercise. As will be discussed in detail in Section 3.3, these findings have informed our basic understanding of cardiac function and sometimes guided future clinical investigation. Since myocardial function, including parameters of myocardial deformation, are influenced by the general loading state of the heart, any exercise responses must be seen in the context of general

cardiovascular responses, as discussed in the next section.

**14**

In the context of myocardial deformation, the most relevant cardiovascular and cardiopulmonary responses to a standardized exercise test pertain to stroke volume, cardiac output, end-diastolic volume, blood pressure, arterial resistance, lactate, and maximal oxygen consumption (VO2max). In healthy individuals, a clear change in these parameters can be expected at the onset of low intensity dynamic exercise that should continue to change linearly up to moderate intensities. Importantly, dynamic exercise tests cause a disproportionate peripheral vasodilation in relation to the increase in cardiac output, and hence total peripheral resistance drops sharply at the onset of exercise and then remains constant across moderate and high exercise intensities [41]. From a diastolic perspective, end-diastolic volume has been shown to increase in some studies while others have not observed any change with exercise. This is not trivial since an acute increase in end-diastolic volume has been associated with an increased stroke volume, an effect also known as the Frank-Starling mechanism [42]. However, the overall contribution of end-diastolic volume to stroke volume is still relatively low because most of the increase in stroke volume has been attributed to the enhanced contractility that reduces the end-systolic volume.

At workloads above moderate intensity, several important physiological changes occur in healthy individuals. Blood lactate concentrations increase exponentially and CO2 production rises above O2 consumption, both reflecting the greater contribution of anaerobic metabolic pathways to overall energy utilization and causing a strong stimulus for vasodilation not least in the cerebral circulation. During the highest effort, stroke volume and VO2 have been reported to plateau and even decrease, but the exact pattern and the underlying mechanisms to this response remain a matter of debate [43]. Fortunately, this does not seem to impact the interpretation of cardiovascular responses to exercise in patients, since the sub-maximal data are currently thought to be of sufficient clinical value to determine whether exercise performance is normal or impaired [44].

One important distinction between the LV and RV responses to exercise is the potential for a "disproportionate load" on the RV [45], which is perhaps explained by both a greater relative rise in pulmonary blood pressure compared with that in the aorta, and differences in RV intrinsic factors such as force development. The differences between the LV and RV responses to exercise highlight the specific impact exercise has on the cardiovascular system. Consequently, determining the true origin of exercise limitations is challenging because many components of the cardiovascular system may be affected. For example, studies have shown that an exaggerated rise in blood pressure during exercise may be associated with negative outcomes, but whether this is caused by the heart or the periphery may be more difficult to determine [46–48]. Even in heart failure, the reduced exercise tolerance has been suggested to be a result of both central and non-cardiac limitations [38–40, 49]. Consequently, assessing myocardial deformation *in relation* to conventional exercise responses is essential for the quantification of the contributions of the heart muscle itself.

#### **3.3 Myocardial deformation during exercise**

Whatever myocardial parameter one chooses to examine during exercise, the interpretation of the responses can be tricky. For example, an increase in myocardial deformation with sub-maximal cycle exercise along with a typical drop in arterial resistance and concomitant reductions in end-systolic volume, in the presence of no adverse structural remodeling would be reflective of a "healthy" response. Equally, it is theoretically possible that the absence of a clear increase in myocardial deformation—which could be interpreted to represent myocardial dysfunction—may be a normal response if the increase in blood pressure and peripheral resistance were excessively high (or the exercise test did in fact create a condition of increased afterload). In this case, it is conceivable that the origin of the exercise limitation may not be cardiac despite the attenuated deformation, but perhaps peripheral in nature causing an exercise failure before the cardiac reserve is fully used [39]. Therefore, this section provides an overview of the general trend of myocardial deformation during exercise, but the reader is alerted that a qualitative interpretation must be performed after consideration of the wider physiology. Articles in this section were included if the studies had obtained data with echocardiography during exercise (tissue Doppler and tissue velocity imaging data were mostly excluded because both techniques are angle-dependent and typically represent only data from a single segment within the mitral annulus). Although a promising and exciting alternative to echocardiography, myocardial deformation during exercise obtained using MRI is not the focus of this chapter [50, 51]. Studies were also excluded if they obtained data immediately following exercise effort, as discussed in more detail in the section on methodological considerations. Finally, the avid reader is referred to some excellent review articles that cover more of the literature than this book chapter can accommodate [52–55].

#### *3.3.1 Physiological insight from healthy individuals*

The physiology of myocardial deformation during exercise in healthy people is the fundamental basis upon which to interpret the responses in patient populations. Although many clinical research studies also include a healthy control group, sometimes these are matched to the patient groups in their demographics and, therefore, may not represent truly "healthy" individuals. Wherever possible, the data presented here will be from populations purposefully recruited as young healthy reference groups. To date, studies have revealed a variety of new perspectives that may be of great importance for the interpretation of clinical populations.

A decade ago, two studies revealed the strain and twist responses during incremental exercise. First, Doucende et al. showed that left ventricular twist and circumferential strain increased linearly up to moderate exercise intensities, while longitudinal strain increased initially but then plateaued at low exercise efforts [56]. This study also highlighted the interdependence of systolic and diastolic deformation, the role of untwisting rate in LV filling during exercise and the contribution of the LV apex to the overall myocardial response. Second, it was shown that LV twist and untwisting rate increased linearly up to near-maximal efforts, correlating with stroke volume and, thus, perhaps contributing to maximal exercise capacity in humans [57]. The importance of regional LV deformation, at the LV apex, was again highlighted. Several other studies have revealed similar patterns of LV twist during exercise in pre- and postmenopausal women, in athletes and of humans ascending to high altitude [58–62]. Consequently, it is now generally accepted that an increase in LV twist with exercise up to moderate intensities can be expected as a normal response (**Figure 3**). Surprisingly few studies dedicated to healthy individuals have measured LV strain during exercise, but they agree in general that longitudinal strain also increases with exercise [56, 61–64]. Because of the risk of potential confounders, it is not possible to directly compare the response in LV twist and strain obtained in different studies. But in general, it is of great importance to note that the patters of the responses to exercise are not always the same for the two parameters, reminding us that they do not represent the same myocardial deformation. In agreement with the general physiological response to incremental exercise, LV twist increases linearly while longitudinal strain seems to plateau at low exercise efforts. This was more recently confirmed by Williams et al., who reported the same

**17**

**Figure 3.**

strongly suggests that the mechanical2

*Echocardiographic Assessment of Myocardial Deformation during Exercise*

disparity between parameters in young healthy men [62]. Interestingly, in the same study, women seemed to have more of a linear response in longitudinal strain akin to LV twist. The disparity between LV twist and longitudinal strain has also been noted in studies on aging where LV twist consistently increases, but longitudinal strain does not change or decreases. Considering the well-established progression of aortic stiffness with aging [65], longitudinal strain appears to be at odds again with general physiology. Future studies should not only examine the parameters in relation to their sensitivity as a clinical marker but also consider the fit with general physiology. Studying the acute effects of exercise on myocardial deformation may be influenced by the chronic remodeling that humans have experienced. In this regard, Burns et al. showed that aging seems to be associated with a reduced LV twist reserve during exercise in a population of 60-year old individuals [66]. Similarly, "female aging", as represented by the menopause, seems to impact the myocardial response to exercise, which may be further altered by exercise training [58]. One of the more surprising observations has been that of Cooke et al. who proposed that endurance trained athletes with enlarged "athlete's heart" and a greater stroke volume had a similar systolic LV function, including LV twist, during submaximal exercise compared to untrained humans with smaller stroke volume [67]. Similar to the results presented by Doucende and Williams discussed above [56, 62], this particular exercise response

*apical and basal data. Please see further details and the original figure in Ref. [57].*

*Myocardial deformation to incremental exercise. LV twist curves during incremental exercise, revealing a linear increase up to 70–80% of maximal individual exercise effort for both peak systolic LV twist (highest value in black lines top row) and peak diastolic untwisting rate (lowest value within black lines bottom row). Red lines represent myocardial deformation at the LV apex, blue lines at the LV base. Black lines are the composite of* 

strictly associated with its output (stroke volume). Some mathematical calculations support the potentially poor linear association between systolic LV mechanical function and ejection fraction while others suggest a strong relationship [68]. In any case, the previous findings suggest that future investigations into the interaction between systolic deformation and ejection, and diastolic deformation and filling are needed to clarify the current uncertainty. One reason for the existing disagreement between

<sup>2</sup> The term mechanical is most commonly used in the literature on myocardial deformation. However,

from a biophysical perspective, it may be more appropriate to refer to "kinematics".

systolic function of the heart may not be

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

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

#### **Figure 3.**

*Advanced Concepts in Endocarditis - 2021*

dysfunction—may be a normal response if the increase in blood pressure and peripheral resistance were excessively high (or the exercise test did in fact create a condition of increased afterload). In this case, it is conceivable that the origin of the exercise limitation may not be cardiac despite the attenuated deformation, but perhaps peripheral in nature causing an exercise failure before the cardiac reserve is fully used [39]. Therefore, this section provides an overview of the general trend of myocardial deformation during exercise, but the reader is alerted that a qualitative interpretation must be performed after consideration of the wider physiology. Articles in this section were included if the studies had obtained data with echocardiography during exercise (tissue Doppler and tissue velocity imaging data were mostly excluded because both techniques are angle-dependent and typically represent only data from a single segment within the mitral annulus). Although a promising and exciting alternative to echocardiography, myocardial deformation during exercise obtained using MRI is not the focus of this chapter [50, 51]. Studies were also excluded if they obtained data immediately following exercise effort, as discussed in more detail in the section on methodological considerations. Finally, the avid reader is referred to some excellent review articles that cover more of the

literature than this book chapter can accommodate [52–55].

The physiology of myocardial deformation during exercise in healthy people is the fundamental basis upon which to interpret the responses in patient populations. Although many clinical research studies also include a healthy control group, sometimes these are matched to the patient groups in their demographics and, therefore, may not represent truly "healthy" individuals. Wherever possible, the data presented here will be from populations purposefully recruited as young healthy reference groups. To date, studies have revealed a variety of new perspectives that

may be of great importance for the interpretation of clinical populations. A decade ago, two studies revealed the strain and twist responses during incremental exercise. First, Doucende et al. showed that left ventricular twist and circumferential strain increased linearly up to moderate exercise intensities, while longitudinal strain increased initially but then plateaued at low exercise efforts [56]. This study also highlighted the interdependence of systolic and diastolic deformation, the role of untwisting rate in LV filling during exercise and the contribution of the LV apex to the overall myocardial response. Second, it was shown that LV twist and untwisting rate increased linearly up to near-maximal efforts, correlating with stroke volume and, thus, perhaps contributing to maximal exercise capacity in humans [57]. The importance of regional LV deformation, at the LV apex, was again highlighted. Several other studies have revealed similar patterns of LV twist during exercise in pre- and postmenopausal women, in athletes and of humans ascending to high altitude [58–62]. Consequently, it is now generally accepted that an increase in LV twist with exercise up to moderate intensities can be expected as a normal response (**Figure 3**). Surprisingly few studies dedicated to healthy individuals have measured LV strain during exercise, but they agree in general that longitudinal strain also increases with exercise [56, 61–64]. Because of the risk of potential confounders, it is not possible to directly compare the response in LV twist and strain obtained in different studies. But in general, it is of great importance to note that the patters of the responses to exercise are not always the same for the two parameters, reminding us that they do not represent the same myocardial deformation. In agreement with the general physiological response to incremental exercise, LV twist increases linearly while longitudinal strain seems to plateau at low exercise efforts. This was more recently confirmed by Williams et al., who reported the same

*3.3.1 Physiological insight from healthy individuals*

**16**

*Myocardial deformation to incremental exercise. LV twist curves during incremental exercise, revealing a linear increase up to 70–80% of maximal individual exercise effort for both peak systolic LV twist (highest value in black lines top row) and peak diastolic untwisting rate (lowest value within black lines bottom row). Red lines represent myocardial deformation at the LV apex, blue lines at the LV base. Black lines are the composite of apical and basal data. Please see further details and the original figure in Ref. [57].*

disparity between parameters in young healthy men [62]. Interestingly, in the same study, women seemed to have more of a linear response in longitudinal strain akin to LV twist. The disparity between LV twist and longitudinal strain has also been noted in studies on aging where LV twist consistently increases, but longitudinal strain does not change or decreases. Considering the well-established progression of aortic stiffness with aging [65], longitudinal strain appears to be at odds again with general physiology. Future studies should not only examine the parameters in relation to their sensitivity as a clinical marker but also consider the fit with general physiology.

Studying the acute effects of exercise on myocardial deformation may be influenced by the chronic remodeling that humans have experienced. In this regard, Burns et al. showed that aging seems to be associated with a reduced LV twist reserve during exercise in a population of 60-year old individuals [66]. Similarly, "female aging", as represented by the menopause, seems to impact the myocardial response to exercise, which may be further altered by exercise training [58]. One of the more surprising observations has been that of Cooke et al. who proposed that endurance trained athletes with enlarged "athlete's heart" and a greater stroke volume had a similar systolic LV function, including LV twist, during submaximal exercise compared to untrained humans with smaller stroke volume [67]. Similar to the results presented by Doucende and Williams discussed above [56, 62], this particular exercise response strongly suggests that the mechanical2 systolic function of the heart may not be strictly associated with its output (stroke volume). Some mathematical calculations support the potentially poor linear association between systolic LV mechanical function and ejection fraction while others suggest a strong relationship [68]. In any case, the previous findings suggest that future investigations into the interaction between systolic deformation and ejection, and diastolic deformation and filling are needed to clarify the current uncertainty. One reason for the existing disagreement between

<sup>2</sup> The term mechanical is most commonly used in the literature on myocardial deformation. However, from a biophysical perspective, it may be more appropriate to refer to "kinematics".

mechanical function and associated hemodynamics may be the technical limitations causing restricted views from a 2D echocardiographic window. In the case of exercise responses, this may be particularly evident at the LV apex, since the apex has been proposed as an important contributor to exercise responses (in particular in diastolic function) [56, 57, 69]. However, in the echocardiographic images relevant for the measurement of global longitudinal strain, the representation of the apical segments is proportionately small and their contribution to longitudinal strain and strain rate may be underestimated compared with short-axis views [18]. Thus, some of the insight provided by myocardial deformation during exercise in healthy people relates to our more general understanding of cardiac function.

Compared with LV strain, RV longitudinal strain seems to be ~10 percentage points higher in healthy young humans at rest, likely reflecting the different anatomy combined with a lower pulmonary resistance compared with the aorta. Most studies reporting RV strain in healthy individuals during exercise have done so by including healthy controls as comparators to cardiac patients. From those studies, some patterns have emerged that suggest a consistently increased RV longitudinal strain during submaximal exercise in healthy individuals [28, 31, 70]. The mechanisms for this are probably similar to those of the LV, where an increased sympathetic state increases contractility while peripheral (pulmonary) vasodilation decreases downstream resistance [71]. However, during intense exercise, it seems that right ventricular myocardial deformation increases perhaps less than the LV, and it has even been shown to *decrease*. Given that both ventricles should produce approximately the same stroke volume under stable conditions, the lower RV strain during exercise is another indicator that the interaction between the mechanical function of the ventricles and the circulation may depend as much on the local arterial resistance as it may depend on the muscular performance (and therefore health) of the ventricles, and thus fitting the long-standing concept of a greater afterload-sensitivity of the RV. Recent studies in advanced heart failure patients who were surgically implanted with left ventricular assist devices (LVAD) may support this, since the mechanical pumps "unload" the LV and shift blood volume to the rest of the circulation, maybe creating "A Different Kind of Stress Test for the RV" [72, 73]. The accurate measurement of pulmonary and aortic resistance beyond the measurement or estimation of blood pressure is certainly going to elucidate the differential exposure and performance of the two ventricles [74]. At present, it seems that exercise does indeed cause a greater afterload challenge for the RV compared with the LV. In fact, it is worth noting that the exercise modalities used in the studies presented so far in this section have mostly employed "dynamic" exercise (see Section 3.4). In this context, it is essential to point out that this type of exercise increases sympathetic activation of the myocardium and reduces arterial resistance compared with the resting state, therefore creating an environment for the LV (and at low intensities for the RV) that is characterized by reduced afterload. During higher exercise intensities, pulmonary resistance can increase during dynamic exercise and create an augmented afterload challenge [45]. Strength exercise, also called resistance exercise, and isometric handgrip exercise are two other modalities that can provide an afterload challenge for the LV [75]. Interestingly, studies employing these exercise modalities in a number of different populations have consistently shown that the reduced systolic deformation is in part compensated for by an increase in heart rate, but can also be uncoupled from diastolic function [76–79]. Given that resistance exercise produces a very different challenge to dynamic exercise, and that strength training is an important addition to rehabilitation, future research should consider incorporating responses during high resistive efforts [80, 81].

**19**

sion of cardiac disease [93].

RV myocardial response to exercise.

*Echocardiographic Assessment of Myocardial Deformation during Exercise*

In a seminal study, Notomi et al. provided mechanistic insight into the complex interdependence between systolic and diastolic function in hypertrophic cardiomyopathy [20]. Although the study used Tissue Doppler Imaging, it is a landmark study that has provided new insight and has popularized the use of exercise testing for both basic science and new insight into cardiac performance in patients. The study revealed that LV twist during exercise was significantly reduced in patients with hypertrophic cardiomyopathy. Similarly, two other studies concluded that systolic deformation reserve is reduced in patients with hypertrophic cardiomyopathy [82, 83]. However, one challenge in patient populations is that the change in heart rate is often different compared with control groups, and therefore it is possible that the groups experienced different physiological stimuli. This is a recurring problem in exercise studies that currently reduces the confidence in some conclusions. Equally, sometimes the matching of the change in heart rate between groups may lead to unequal workloads or changes in blood pressure, highlighting again the need to interpret myocardial deformation during exercise in the context of general physiological responses. Notwithstanding, the overall trend is that LV myocardial deformation in patients is reduced in response to an acute exercise challenge, including in cardiac amyloidosis, hypertension, cancer, coronary artery disease, as well as in patients with valve disease before and after surgical correction [84–89]. Some subtle observations, however, are worthy of discussion. For example, in patients with microvascular angina, only the subendocardial strain was reduced, and diastolic function during exercise was more severely affected than systolic reserve [90]. Similarly, myocardial regions can respond differently during exercise in coronary artery disease patients, as shown by differential basal vs. apical rotational mechanics [89]. In an elegant study in patients with hypertrophic cardiomyopathy, Soullier et al. showed that there was significant heterogeneity in the response of the different deformation parameters to exercise, and that resting twist was even increased in patients while diastolic untwisting rate was less affected [83]. In patients with a prior heart transplant, the age of the recipients and donors seem to influence the longitudinal and circumferential strain response to exercise [91, 92]. All these observations highlight the very subtle changes that can occur between parameters, and between systolic and diastolic function. To determine the full significance of such differences should be the focus of future investigations. Furthermore, it will be essential to relate myocardial deformation more often to parameters like cardiac output, to enable the meaningful interpretation of deformation indices and their contribution to the overall capacity of the heart. When this was done in previous studies, the myocardial deformation during exercise provided a clear advancement of our general understanding of the etiology and/or progres-

Because of the prevalence and importance of pulmonary hypertension, and the exercise limitations of heart failure patients, myocardial deformation of the RV during exercise has received heightened attention [94]. Similar to the LV response, the expected increase in RV myocardial deformation during exercise is generally blunted, not just in pulmonary hypertension but also in tetralogy of Fallot, systemic sclerosis, and hypertrophic cardiomyopathy [31, 95–97]. Most often, there is clear evidence that pulmonary artery pressures increased disproportionately in the groups that had a blunted increase in RV longitudinal strain during exercise. Importantly, these patients often have normal pulmonary artery pressures at rest, which not only emphasizes the diagnostic value of exercise testing, it also highlights the possibility that patients with suspected LV pathology should be tested for the

*3.3.2 Exercise responses in patients with cardiovascular disease*

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

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

#### *3.3.2 Exercise responses in patients with cardiovascular disease*

*Advanced Concepts in Endocarditis - 2021*

more general understanding of cardiac function.

mechanical function and associated hemodynamics may be the technical limitations causing restricted views from a 2D echocardiographic window. In the case of exercise responses, this may be particularly evident at the LV apex, since the apex has been proposed as an important contributor to exercise responses (in particular in diastolic function) [56, 57, 69]. However, in the echocardiographic images relevant for the measurement of global longitudinal strain, the representation of the apical segments is proportionately small and their contribution to longitudinal strain and strain rate may be underestimated compared with short-axis views [18]. Thus, some of the insight provided by myocardial deformation during exercise in healthy people relates to our

Compared with LV strain, RV longitudinal strain seems to be ~10 percentage points higher in healthy young humans at rest, likely reflecting the different anatomy combined with a lower pulmonary resistance compared with the aorta. Most studies reporting RV strain in healthy individuals during exercise have done so by including healthy controls as comparators to cardiac patients. From those studies, some patterns have emerged that suggest a consistently increased RV longitudinal strain during submaximal exercise in healthy individuals [28, 31, 70]. The mechanisms for this are probably similar to those of the LV, where an increased sympathetic state increases contractility while peripheral (pulmonary) vasodilation decreases downstream resistance [71]. However, during intense exercise, it seems that right ventricular myocardial deformation increases perhaps less than the LV, and it has even been shown to *decrease*. Given that both ventricles should produce approximately the same stroke volume under stable conditions, the lower RV strain during exercise is another indicator that the interaction between the mechanical function of the ventricles and the circulation may depend as much on the local arterial resistance as it may depend on the muscular performance (and therefore health) of the ventricles, and thus fitting the long-standing concept of a greater afterload-sensitivity of the RV. Recent studies in advanced heart failure patients who were surgically implanted with left ventricular assist devices (LVAD) may support this, since the mechanical pumps "unload" the LV and shift blood volume to the rest of the circulation, maybe creating "A Different Kind of Stress Test for the RV" [72, 73]. The accurate measurement of pulmonary and aortic resistance beyond the measurement or estimation of blood pressure is certainly going to elucidate the differential exposure and performance of the two ventricles [74]. At present, it seems that exercise does indeed cause a greater afterload challenge for the RV compared with the LV. In fact, it is worth noting that the exercise modalities used in the studies presented so far in this section have mostly employed "dynamic" exercise (see Section 3.4). In this context, it is essential to point out that this type of exercise increases sympathetic activation of the myocardium and reduces arterial resistance compared with the resting state, therefore creating an environment for the LV (and at low intensities for the RV) that is characterized by reduced afterload. During higher exercise intensities, pulmonary resistance can increase during dynamic exercise and create an augmented afterload challenge [45]. Strength exercise, also called resistance exercise, and isometric handgrip exercise are two other modalities that can provide an afterload challenge for the LV [75]. Interestingly, studies employing these exercise modalities in a number of different populations have consistently shown that the reduced systolic deformation is in part compensated for by an increase in heart rate, but can also be uncoupled from diastolic function [76–79]. Given that resistance exercise produces a very different challenge to dynamic exercise, and that strength training is an important addition to rehabilitation, future research should consider incorporating responses during high resistive efforts [80, 81].

**18**

In a seminal study, Notomi et al. provided mechanistic insight into the complex interdependence between systolic and diastolic function in hypertrophic cardiomyopathy [20]. Although the study used Tissue Doppler Imaging, it is a landmark study that has provided new insight and has popularized the use of exercise testing for both basic science and new insight into cardiac performance in patients. The study revealed that LV twist during exercise was significantly reduced in patients with hypertrophic cardiomyopathy. Similarly, two other studies concluded that systolic deformation reserve is reduced in patients with hypertrophic cardiomyopathy [82, 83]. However, one challenge in patient populations is that the change in heart rate is often different compared with control groups, and therefore it is possible that the groups experienced different physiological stimuli. This is a recurring problem in exercise studies that currently reduces the confidence in some conclusions. Equally, sometimes the matching of the change in heart rate between groups may lead to unequal workloads or changes in blood pressure, highlighting again the need to interpret myocardial deformation during exercise in the context of general physiological responses. Notwithstanding, the overall trend is that LV myocardial deformation in patients is reduced in response to an acute exercise challenge, including in cardiac amyloidosis, hypertension, cancer, coronary artery disease, as well as in patients with valve disease before and after surgical correction [84–89]. Some subtle observations, however, are worthy of discussion. For example, in patients with microvascular angina, only the subendocardial strain was reduced, and diastolic function during exercise was more severely affected than systolic reserve [90]. Similarly, myocardial regions can respond differently during exercise in coronary artery disease patients, as shown by differential basal vs. apical rotational mechanics [89]. In an elegant study in patients with hypertrophic cardiomyopathy, Soullier et al. showed that there was significant heterogeneity in the response of the different deformation parameters to exercise, and that resting twist was even increased in patients while diastolic untwisting rate was less affected [83]. In patients with a prior heart transplant, the age of the recipients and donors seem to influence the longitudinal and circumferential strain response to exercise [91, 92]. All these observations highlight the very subtle changes that can occur between parameters, and between systolic and diastolic function. To determine the full significance of such differences should be the focus of future investigations. Furthermore, it will be essential to relate myocardial deformation more often to parameters like cardiac output, to enable the meaningful interpretation of deformation indices and their contribution to the overall capacity of the heart. When this was done in previous studies, the myocardial deformation during exercise provided a clear advancement of our general understanding of the etiology and/or progression of cardiac disease [93].

Because of the prevalence and importance of pulmonary hypertension, and the exercise limitations of heart failure patients, myocardial deformation of the RV during exercise has received heightened attention [94]. Similar to the LV response, the expected increase in RV myocardial deformation during exercise is generally blunted, not just in pulmonary hypertension but also in tetralogy of Fallot, systemic sclerosis, and hypertrophic cardiomyopathy [31, 95–97]. Most often, there is clear evidence that pulmonary artery pressures increased disproportionately in the groups that had a blunted increase in RV longitudinal strain during exercise. Importantly, these patients often have normal pulmonary artery pressures at rest, which not only emphasizes the diagnostic value of exercise testing, it also highlights the possibility that patients with suspected LV pathology should be tested for the RV myocardial response to exercise.
