View of The clinical usefulness of novel myocardial deformation imaging in daily echocardiographic examinations

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Department of Cardiology, Division of Internal Medicine, University Medical Centre Ljubljana, Ljubljana, Slovenia Correspondence/

Korespondenca:

Marta Cvijič, e: marta.

cvijic@gmail.com Key words:

echocardiography; strain;

GLS; speckle tracking imaging

Ključne besede:

ehokardiografija;

deformacija; GLS; metoda sledenja ultrazvočnega vzorca

Received: 8. 9. 2018 Accepted: 6. 1. 2019

en article-lang

10.6016/ZdravVestn.2867 doi

8.9.2018 date-received

6.1.2019 date-accepted

Cardiovascular system Srce in ožilje discipline

Professional article Strokovni članek article-type

The clinical usefulness of novel myocardial deformation imaging in daily echocardiographic examinations

Uporabnost novejših metod za oceno deformacije miokarda pri vsakdanji ultrazvočni preiskavi srca

article-title

The clinical usefulness of novel myocardial deformation imaging in daily echocardiographic examinations

Uporabnost novejših metod za oceno deformacije miokarda pri vsakdanji ultrazvočni preiskavi srca

alt-title

echocardiography, strain, GLS, speckle track-

ing imaging ehokardiografija, deformacija, GLS, metoda

sledenja ultrazvočnega vzorca

kwd-group The authors declare that there are no conflicts

of interest present. Avtorji so izjavili, da ne obstajajo nobeni

konkurenčni interesi. conflict

year volume first month last month first page last page

2019 88 1 2 77 92

name surname aff email

Marta Cvijič 1 marta.cvijic@gmail.com

name surname aff

Jana Ambrozic 1

Andreja Čerček Černe 1

Mojca Bervar 1

Janez Toplišek 1

eng slo aff-id

Department of Cardiology, Division of Internal Medicine, University Medical Centre Ljubljana, Ljubljana, Slovenia

Klinični oddelek za kardiologijo, Interna klinika, Univerzitetni klinični center Ljubljana, Ljubljana, Slovenija

1

The clinical usefulness of novel

myocardial deformation imaging in daily echocardiographic examinations

Uporabnost novejših metod za oceno deformacije miokarda pri vsakdanji ultrazvočni preiskavi srca

Marta Cvijič, Jana Ambrozic, Andreja Čerček Černe, Mojca Bervar, Janez Toplišek

Abstract

Investigation of myocardial deformation by speckle tracking imaging (STI) is a novel method in echocardiography, which provides an insight into cardiac mechanics and is becoming more widely used in daily clinical practice. This method has introduced a new global parameter of left ventricular longitudinal deformation (global longitudinal strain, GLS), which has turned out to be more sensitive for early detection of myocardial impairment compared to conventional echocardiographic systolic function parameters. It has been proved that myocardial deformation parameters have diagnostic as well as prognostic value in several cardiac diseases. Typical findings that can be demonstrated by STI in ischemic heart disease are lower values of systolic deformation, early systolic lengthening and post-systolic shortening in ischemic myocardium. STI can be helpful in early detection of systolic dysfunction in patients with left ventricular hypertrophy and in the differentiation of the causes of left ventricular hypertrophy. By using STI we can detect an early subclinical myocardial impairment after chemotherapy, and therefore European recommendations have given priority to STI over classical echocardiographic parameters in further decision-making. In asymptomatic patients with moderate to severe valvular heart disease lower GLS values suggest subtle myocardial damage and predict higher risk of postoperative compli- cations. In patients with myocarditis STI can identify lower values of segmental myocardial deformation, reflecting focal damage of the left ventricular. Additionally, myocardial deformation can also successfully predict response in patients treated by cardiac resynchronization therapy.

The present paper provides a detailed step-by-step description of the GLS analysis, which can be used regardless of the type of ultrasound machine and software package. The use of STI is presented for particular cardiac diseases where clinical usefulness of STI has been confirmed.

Izvleček

Slikovna preiskava deformacije miokarda s sledenjem ultrazvočnega vzorca (angl. speckle tracking imaging, STI) je novejša metoda v ehokardiografiji, ki omogoča vpogled v mehaniko delovan- ja srčne mišice in se vse pogosteje uporablja pri vsakdanjem kliničnem delu. S to metodo se je uveljavil tudi nov globalni kazalec deformacije levega prekata v longitudinalni smeri (angl. global longitudinal strain, GLS), ki se je izkazal kot bolj občutljiv kazalec za odkrivanje zgodnje okvare miokarda kot klasični ehokardiografski kazalci sistolične funkcije. Kazalci deformacije imajo tako diagnostično kot prognostično vrednost pri številnih bolezenskih stanjih. Značilne spremembe, ki jih lahko zaznamo s STI pri ishemični bolezni srca, so znižanje deformacije v sistoli, raztezanje miokarda v zgodnji sistoli in skrajšanje miokarda po koncu sistole. Metoda STI nam je v pomoč pri odkrivanju zgodnje okvare sistolične funkcije pri bolnikih s hipertrofijo miokarda in pri raz- likovanju vzrokov hipertrofij. S STI lahko prepoznamo subklinično okvaro miokarda po kemoter-

Slovenian Medical

Journal

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1 Introduction

For decades, the echocardiographic assessment of global and regional myocardial function was based on the calculation of ejection fraction and visual assessment of segmental wall motion abnormalities.

Recent advances in echocardiographic technology and the development of new methods for myocardial deformation assessment give us a completely new under- standing of cardiac mechanics. At first, modern methods of myocardial deformation were only used for research pur- poses. Whit increasing number of studies showing the advantages of myocardial deformation parameters over conventional echocardiographic parameters, novel methods were gradually introduced into clinical practice. Nowaday, myocardial deformation is additional echocardiographic method in daily clinical practice (1). This paper presents the basics of myocardial deformation, and describe their role in clinical practice.

apiji, zato ji dajejo evropska priporočila prednost pred klasičnimi ehokardiografskimi kazalci pri nadaljnjem kliničnem odločanju. Pri bolnikih brez simptomov z zmerno do hudo boleznijo srčnih zaklopk znižane vrednosti GLS kažejo na prikrito okvaro miokarda in napovedujejo večje tveganje za zaplete po operaciji. Pri bolnikih z miokarditisom s STI zaznamo znižane vrednosti segmentne deformacije in zrcalijo žariščno prizadetost levega prekata. Prav tako pa kazalniki deformacije miokarda tudi dobro napovedujejo uspešnost zdravljenja pri bolnikih z resinhroni- zacijskim spodbujevalnikom.

V prispevku želimo predstaviti osnove analizo GLS, po posameznih korakih, ki veljajo ne glede na vrsto ultrazvočnega aparata ali programske opreme, ter predstaviti primere uporabe STI pri posameznih bolezenskih stanjih, za katere obstaja največ dokazov klinične uporabnosti.

Cite as/Citirajte kot: Cvijič M, Ambrozic J, Čerček Černe A, Bervar M, Toplišek J. The clinical usefulness of novel myocardial deformation imaging in daily echocardiographic examinations. Zdrav Vestn. 2019;88(1–

2):77–92.

DOI: https://doi.org/10.6016/ZdravVestn.2867

2 What is myocardial deformation?

Myocardial deformation is a complex process in which muscle fibres shorten longitudinally and circumferentially, and thicken radially during the systole, accompanied by rotation along the longitudinal axis (Figure 1). The muscle fibres subsequently stretch and become thinner during the diastole. Myocardial deformation imaging allows us to directly estimate the shortening and stretching of myocardium and their velocity throughout the cardiac cycle for separate myocardial segments or the entire heart. Strain describes the change in the length of a myocardial segment from its baseline length, and is expressed as a percentage (Lagrangian strain). Strain rate is defined as a change of strain per a time unit (2). Lengthening or thickening has positive strain values, while shortening or thinning is expressed as negative strain values. The baseline i.e.

the baseline length of myocardium is de-

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termined at the beginning of the cardiac cycle. From the physiological aspect, this is end-diastole or mitral valve closure, however most ultrasound machines ap- proximate this point by detecting the QRS complex in the ECG (3).

Myocardial deformation can be measured using tissue Doppler imaging (TDI), or speckle tracking imaging (STI) (2). TDI is the older of two techniques. This method first defined deformation parameters (strain rate and strain), which are calculated based on the data of myocardial velocity. TDI was never widely used for analysing the deformation in clinical practice, primarily due to two major limitations:

results strongly depend on the angle, and the whole analysis of deformation of LV is time-consuming process. STI overcame these limitations. The method is based on tracking the motion of hyperechoic speckle patterns within the myocardium Figure 1: Left ventricular strain, and orientation of muscle fibres.

Longitudinal strain is measured from apical views (A), while radial and circumferential strain are measured in parasternal short-axis view (B). (C) Strain is the ratio between the change in length and the baseline length expressed in percent. (D) Fibres in the subendocardial layer are organized in a left-handed helix, in mid-myocardium they are mainly oriented circumferentially, and in the subepicardial layer they are organized in a right-handed helix.

throughout the cardiac cycle. Tracking of the speckles within a particular myocardial segment over time allows specific quantification of deformation, during systole and diastole. Primarily, the method was developed for quantitative assessment of segmental cardiac function. However, with the use of STI, a new global strain parameter that assesses the left ventricular (LV) global function was established. De- formation analysis of all three apical views allows us to assess global LV longitudinal strain (GLS).

LV mechanics are primarily determined by the orientation of muscle fibres, which form a clockwise and counterclock- wise helix (Figure 1) (4). Therfore, subendocardial muscular fibres are primarily responsible for longitudinal shortening, while the mid-myocardium and subepi- cardium for the radial, circumferential and rotational deformation (5,6). Reduc- tion in longitudinal shortening (less negative value) is often found as early sign of myocardial disease as subendocardial fibers are frequently the first to be affected (5,6). In the early stage of the disease, reduction of the longitudinal strain (LS) can be compensated to keep ejection fraction unaltered by change in radial and circumferential strains and LV geometry (7). As the myocardial disease progressed, both radial and circumferential strain are also affected. LS is significantly more repro- ducible than the radial and circumferential strain (8). Therefor, it is not surprising that GLS is the most useful and most frequently used myocardial deformation parameter in clinical practice (9). Addi- tionally, GLS is more sensitive and robust parameter for detecting subclinical myocardial dysfunction than the conventional echocardiographic parameters (10).

3 Steps for strain measurments and practical guidance

A number of echocardiographic sys- tems are now available for assessment of myocardial deformation. The instructions

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for the GLS analysis are presented here, however the basic steps for analysing other myocardial deformation parameters are similar.

The following seven practical recommendations are necessary for accurate and correct GLS analysis (8,11):

1. Image acquisition. 2D images of the LV from a four-chamber view, two-chamber view, and apical long-axis view should be acquired at the same imaging depth and width. It is essential to avoid apical foreshortening. It is recommended to save at least 3 cardiac cycles for each view, with the gray-scale fame rate of 40–80 frames per second (fps). Good ECG signal is necessary for proper gating of the images. Effort must be made to obtain all the images at stable heart rates. All the images should be acquired in breath-hold to avoid any breathing artifacts. Acquisi-

tion of all apical views is a part of ev- ery echocardiographic examination, so this step will not further prolong the examination (12).

2. Defining end-diastole and end-systole.

Most STI analysis softwares determine end-diastole and end-systole automatically based on the QRS complex in ECG. This method is a reliable approx- imation, if the patient does not have intraventricular conduction delay (3).

The end of diastole is defined as the point when the curves of motion and deformation are zero. The end of systole is defined as aortic valve closure (AVC)(13). A variety of methods are used to determine end-systole: detection of the end of T-wave in the ECG, direct observation of aortic valve closure, automatic selection of end-systole based on the analysis of deformation curves and blood-Doppler data from

8. Repeat steps 5–7 until the tracking qual- ity is adequate. At this point, we can manually further adjust ROI, if tracking is insufficient. Segments where speckle tracking is not possible (poor image quality) or is not acceptable (speckle motion does not follow the myocardial motion) are excluded from further analysis. The software then dis- plays the results as a strain curve for each segment. These curves give the information on segmental strain (Figure 2). Different strain parameters can be determined form strain curves: peak systolic strain, end systolic strain and postsystolic strain (PSS). After analysing images from all three apical views, the results are presented in a 16- or 18-segment polar map with segmental systolic strain values displayed in the bull’s eye, and with the GLS value (Fig- ure 2). GLS value is defined as the average peak longitudinal strain of the LV. If the quality of speckle tracking is suboptimal and more than two segments in a single view or more than 1 segment from each view are excluded, the calculation of GLS is unreliable (14,15). STE analysis on the echocardiography machine itself is relatively cumbersome. Therfore offline analysis of stored images is more convenient. To speed up the analysis and facilitate the clinical use, a sim- plified and modified automated method for calculating GLS was developed. Au- tomated functional imaging (AFI or Au- toSTRAIN), can be performed quickly directly on the ultrasound machine. The average time of analysis using automated GLS calculation method is 2–3 minutes, while the average duration of a standard analysis is at least twice as long (16).

The GLS calculation method varies between different vendors, meaning that the measurements obtained on one ech- cardiographic machine or postprocessing software are not identical to the measurements obtained on another system (15,17). Therfore, the equipment used for the anal- Figure 2: Segmental strain curves in a healthy individual, and example of results presented in a

bull’s eye.

Each curve represents one segment of the left venricle. A. 4-chamber view. B. 2-chamber view.

C. 3-chamber view. D. 18-segment model. The numbers in segments in bull’s eye are the peak longitudinal strain values in systole. The calculated value of global longitudinal strain (GLS) is marked with an arrow (→). AVC – aortic valve closure.

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the aortic valve (14). The last method is currently the most reliable and is the recommended method for determin- ing end-systole (3).

3. Selecting images for STI. From the saved images, the cycle with the most clearly visible LV myocardium( without artifacts and shadows), and with minimal cardiac motion due to external causes (breathing) should be selected. We always try to select an image where the endocardial border is clearly visible during the entire cardiac cycle.

4. Defining the base and apex. We usu- ally start the analysis with the apical long-axis view, and then repeat steps 4–8 for other apical views. It is essential to correctly define the LV base and apex. When defining the LV base, we should be careful to place a point on the insertion of the mitral valve leaf- lets, while in the anteroseptum, the base should be defined in basal septal segment and not into LV outflow tract.

5. Tracing the endocardial border. In the final systolic image, we manually trace the endocardium from one side of the mitral annulus to the apex, finishing on the opposite side of the mitral annulus.

The papillary muscle and trabeculae are considered as part of the LV cavity and should not be included in the region of interest.

6. Adjusting the region of interest (ROI).

After endocardial border is traced, the software will automatically trace the epicardium and set the width of the region of interest. ROI should be manually adjusted to avoid including bright, echogenic pericardium. If the pericardium is included in ROI, the LS value can be underestimated (11).

7. Assessing the tracking quality. After manually adjusting the width and shape of ROI, the software will automatically divide the LV into 6 segments. Manual corrections are frequently needed and should be done if tracking markers do not follow the underlying tissue motion.

8. Repeat steps 5–7 until the tracking qual- ity is adequate. At this point, we can manually further adjust ROI, if tracking is insufficient. Segments where speckle tracking is not possible (poor image quality) or is not acceptable (speckle motion does not follow the myocardial motion) are excluded from further analysis. The software then dis- plays the results as a strain curve for each segment. These curves give the information on segmental strain (Figure 2). Different strain parameters can be determined form strain curves: peak systolic strain, end systolic strain and postsystolic strain (PSS). After analysing images from all three apical views, the results are presented in a 16- or 18-segment polar map with segmental systolic strain values displayed in the bull’s eye, and with the GLS value (Fig- ure 2). GLS value is defined as the average peak longitudinal strain of the LV.

If the quality of speckle tracking is suboptimal and more than two segments in a single view or more than 1 segment from each view are excluded, the calculation of GLS is unreliable (14,15).

STE analysis on the echocardiography machine itself is relatively cumbersome.

Therfore offline analysis of stored images is more convenient. To speed up the analysis and facilitate the clinical use, a sim- plified and modified automated method for calculating GLS was developed. Au- tomated functional imaging (AFI or Au- toSTRAIN), can be performed quickly directly on the ultrasound machine. The average time of analysis using automated GLS calculation method is 2–3 minutes, while the average duration of a standard analysis is at least twice as long (16).

The GLS calculation method varies between different vendors, meaning that the measurements obtained on one ech- cardiographic machine or postprocessing software are not identical to the measurements obtained on another system (15,17).

Therfore, the equipment used for the anal- Figure 2: Segmental strain curves in a healthy individual, and example of results presented in a

bull’s eye.

Each curve represents one segment of the left venricle. A. 4-chamber view. B. 2-chamber view.

C. 3-chamber view. D. 18-segment model. The numbers in segments in bull’s eye are the peak longitudinal strain values in systole. The calculated value of global longitudinal strain (GLS) is marked with an arrow (→). AVC – aortic valve closure.

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ysis must be mentioned in the echocardiographic report. In order to compare deformation parameters for the same patient, over the course of follow-up, the same software version should be used. Normal GLS values for different vendors and softwares are listed in Table 1. In the latest recommendations, GLS value for healthy individuals is - 20 ± 2% (15), while others report normal values between - 18% and - 25% (18,19). Women have higher absolute GLS values than men, and the values decrease with age (10).

The reproducibility of GLS measurements is very good (with relative mean error for GLS of 5.4–8.6% (intraobserv- er) and 4.9–7.3% (interobserver)), and is comparable to conventional echocardiographic parameters (ejection fraction, LV end-diastolic diameter) (17,20). However, the reproducibility of segmetnal strains is low. Therfore, using absolute segmental values is not recommended in clinical practice (15,21). When assessing segmental strain, the shape of the curve for individual segments and regional differences visible on the polar map are more relevant than absolute numerical values (22).

STI can also be used for analyzing myocardial deformation of other cardiac chambers. Recently, the European Associ- ation of Cardiovascular Imaging and the Industry Task Force standardized definitions and techniques for using 2D STI for left atrial, right ventricular, and right atrial (23). STI of right ventricular is already

Table 1: Normal left ventricle global longitudinal strain (GLS) values for specific vendors’

equipment based on data from research and literature (modified from Lang R, et al.) (15).

Manufacturer Software Average standard

deviation of GLS (%) Lower limit of normal (%)

GE EchoPAC BT12 -21.5 ± 2.0 -18

Philips QLAB 7.1 -18.9 ± 2.5 -14

Toshiba Ultra Extend -19.9 ± 2.4 -15

Siemens VVI -19.8 ± 4.6 -11

Esaote Mylab 50 -19.5 ± 3.1 -13

recommended as an additional methods in routine clinical practice for some right heart diseases (24). However, analysing atrial deformation by STI is now limited to research purpose only.

3.1 Limitations and weaknesses of STI

The main limitation of STI is the need for high-quality apical images. Subopti- mal endocardial border or temporal in- stability of the speckles result in insufficient tracking, and subsequently incorrect strain calculation. According to published results, GLS analysis could be performed in about 90% of patients selected in the studies (17,20,25). It should be noted that the rate of successfully perforemed analyses would probably be lower in unselected population, since certain physical conditions (obesity) or diseases (emphysema, post-mastectomy patients) notably affect the image quality. As deformation analysis requires a stable heart rate, the presence of atrial fibrillation significantly reduces its feasibility (GLS analysis is only feasible in 69% of patients with atrail fibrillation) (25). This limitation can be overcame by using echocardiographic machine which supports triplane acquisition.

Intervendor differences in LV GLS measurements limit broad clinical appli- cations (15,17); therefore direct comparison of absulute strain values between different vendors are not recommended.

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4 When and where can we use STI?

STI gives us a completely new insight into cardiac mechanics in normal physiological conditions as well as diseases. Data obtained by STI is beyond the conventional echocardiographic analysis, therfore it is not surprising that multiple studies have shown the usefulness of STI in various cardiac disease. Reduced LS absolute value (less negative value) has prognostic value, in acute and chronic cardiac conditions (19,22), and it is also linked with worse prognosis and increased risk of cardiovascular events (26). The following section presents data for cardiac diseases where clinical usefulness of STI has been confirmed.

4.1 Ischemic heart disease

Myocardial ischemia first affects the subendocardium. Since longitudinal fibres are located predominantly in the subendocardium, longitudinal strain is the first affected component of myocardial deformation. In addition to lower peak systolic strain values, systolic lengthening and post-systolic shortening (PSS) are also specific markers of ischemia (Figure 3) (27,28). While PSS is a very sensitive sign of myocardial ischemia, it is not completely specific for ischemia at rest. Therfore, the strain curves should always be considered together with other echocardiographic findings and clinical presentation (29). Suboptimal image quality and noise artefacts can complicate data interpreta- tion. The finding of characteristic strain features of ischaemia in more than one myocardial segment favours ischaema rather than noise artefacts. Figure 4 shows typical strain curves of ischemia in a patient with acute occlusion of left coronary artery.

Additionally, STI is very useful in stress echocardiography (30,31). The longitudinal strain analysis during stress testing improves the accuracy of detecting myocardial ischemia and viability assessment.

The occurrence of PSS during stress is clear evidence of inducible ischemia (31).

The extent of PSS during stress is usually greater than the extent of wall motion ab- normalites.

In patients with ischemic heart disease, the GLS value correlates with myocardial infarct mass (32). Patients with myocardial infarction, ejection fraction (EF) >

40% and GLS < - 14% have higher risk for cardiovascualar events (death, heart failure hospitalization) than those with GLS

> - 14% (33). In this study, besides GLS, also the ratio between transmitral (E) and myocardial peak early velocity obtained Figure 3: Comparison of strain curves in a segment with ischemia (red

curve) and segment without ischemia (yellow curve).

The red curve shows all changes, characteristic for ischemia: 1. early lengthening, 2. lower strain curve values during systole, and 3. postsystolic shortening (PSS). ED – end-diastole, AVC – aortic valve closure, ECG – electrocardiogram.

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by Doppler methods (E/e’) has independent prognostic value. In ischemic heart disease GLS has been proven to have higher prognostic value than EF (26,33,34).

4.2 Cardiomyopathy

STI has proven to be useful diagnostic tool for cardiomyopathies in the early stage of the disease. When there is an overt cardiomyopathy with typical clinical findings, the added diagnostic value of STI is small. In patients with LV hypertrophy, re- Figure 4: Segmental strain curves of a patient with acute left coronary artery (LAD) occlusion.

A. Coronary angiogram (CRA 30 ° projection) shows a LAD occlusion in the first section (marked with an arrow). B. Representative region of interest for speckle tracking in a two-chamber view, with marked left ventricle segments. C. Segmental strain curves in a two-chamber view. Curve colours match segment colours in figure B. Segments representing LAD bed (left ventricle anterior wall and apex) have changed strain curves, with changes characteristic of ischemia. ANT – anterior wall, INF – inferior wall, AVC – aortic valve closure, ECG – electrocardiogram.

gardless of the cause, LV EF is preserved or even “supernormal”, while GLS is already impaired. Therfore, GLS is more sensitive than LVEF for detecting myocardial dysfunction in patients with hypertrophy, since reduction of GLS could be compensated by a small increase of circumferent strain or wall thickness (7).

Patients with cardiac amyloidosis have reduced GLS and typical regional strain pattern (35). This pattern is characterised by reduced longitudinal strain in basal segments and apical sparing of longitudinal strain (Figure 5A). This is a very sensitive and specific sign of cardiac amyloidosis (35). In patients with early stage of cardiac amyloidosis the absolute basal-to-apical gradient of longitudinal strain is above 8%, and reflects differences in the distri- bution of the amyloid deposits in the heart (37). With the progression of disease, the segmental longitudinal strain further im- pairs and also base-to-apical gradient decreases. In healthy individuals, the normal absolute apical-basal strain differences are of approximately 2-4% (38).

In patients with hypertrophic cardiomyopathy (HCM) and preserved EF, early myocardial dysfunction can be proven with reduced GLS values (39), as well as with reduced systolic longitudinal strain in hypertrophic segments (Figure 5B) (40). Reduced longitudinal strain can be abnormal before the development of increased wall thickness in genetically affected relatives (41). The latest European guidelines on diagnosis and management of HCM (42) recommends using STI for detection subclinical systolic dysfunction in this group of patients. GLS has also prognostic value in HCM, and lower GLS is associated with worse clinical outcomes and higher occurence of arrhythmias (43).

Previous studies also showed that STI is clinically useful in distinguish different causes of LV hypertrophy (35). Global longitudinal strain values and segmental longitudinal strain values can help us differentiate hypertensive heart disease, cardiac amyloidosis, HCM and physiolog-

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ical hypertrophy or athlete’s heart (44,45).

Patients with pathologic hypertrophy and normal ejection fraction had absolutely lower longitudinal strain values than ath- letes (46). Figure 5 shows polar maps of patients with different causes of LV hypertrophy.

STI should not be used as a only diagnostic method for differentiate etiology of thick heart However, it can be helpful for planning further diagnstic tests. Additon- all, in patients with thick hearts, GLS has better prognostic value than EF (26,47).

4.3 Patients after chemotherapy Cardiotoxicity is a important side effect of chemotherapy. Importantly, detection of subclinical cardiotoxicity is essential for timely action and treatment (48-50). STI can detect subtle and subclinical cardiotoxicity, which cannot be detected with conventional echocardiography (51,52).

GLS value accurately predicts further reduction of LV EF in this group of patients (53). A relative reduction of GLS of >15%

from baseline is considered abnormal and is a marker of LV subclinical dysfunction.

The European Society of Cardiology recommends using STI, when available, for

Figure 5: Polar maps of patients with left ventricular hypertrophy caused by different factors.

A. A patient with cardiac amyloidosis. Systolic values of the longitudinal strain are reduced in basal and mid-cavity segments. B. Patient with hypertrophic cardiomyopathy (asymmetric hypertrophy of interventricular septum). Lower longitudinal strain values occur in basal and mid segments of the interventricular septum, where hypertrophy is present. C. Patient with hypertensive heart disease (moderate concentric LV hypertrophy). This group of patients does not have a specific segmental LS pattern.

the detection of myocardial dysfunction before, during and after cancer therapy (49,50,54). It should be noted that the recommendations clearly state that the decision on changing the dosage or discontin- uing chemotherapy should not be based on GLS measurements alone. It is recommended that STI is part of the echocardi- graphic measurments in all patients treated with cardiotoxic drugs. Figure 6 shows the algorithm for using GLS to identify patients suffering from cardiotoxicity. Lat- est research shows that monitoring these patients using STI improves the quality of treatment, and reduces the cost (55).

4.4 Valvular heart disease

STI can provide additional information especially in asymptomatic moderate-to-severe valvular heart diseases. De- fining the timing of surgery is now usually made based on the LV dimension and EF (56). However, ejection fraction decreases in the advanced stages of the disease, when irreversible myocardial dysfunction is already present. The latest researches in- dicate that interventions earlier in the disease, before EF decreases, result in better clinical outcome. Assessing of myocardial

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function by STI provides added clinical value in asymptomatic moderate-to-severe aortic regurgitation (57-59), aortic stenosis (60) and mitral regurgitation (61,62).

In candidates for mitral valve repair, the absolute GLS value of < –19.9% before the surgery is associated with irreversible myocardial dysfunction in the long-term after the surgery (61). Additionally, GLS value before the surgery is an independent predictor for cardiovascular events and mortality in this group of patients (63).

Current guidelines for the management of valvular heart disease do not yet recommend using STI routinely for detecting subclinical LV dysfunction and making decisions on further treatment (64). However, institutions with expe- rience in STI have already used GLS of

< -16% as the cut-off value for subclinical myocardial dysfunction in this group of patients (19). Recent viewpoint of the Heart Valve Clinic International Database Group provides specific recommendations for utilization of multimodality imaging to optimize risk stratification and therapeutic decision-making processes in asymptomatic severe aortic stenosis (65).

Surgical aortic valve replacement or tran- scatheter aortic valve implantation might

be considered in these patients if GLS is ≤ -15.9%, and accompanied by other factors defining high-risk patients – high calcium score and extensive myocardial fibrosis on cardiac magnetic resonance.

4.5 Myocarditis

Myocarditis, unlike ischemic disease, usually affects subepicardial and more rarely mid-myocardial layers of left ventricular. Inflammation may be diffuse or focal, typicaly not related to the territory of a coronary arteries. Since the inflammation is mostly limited to the subepicardi- um, where supepicardial fibers are oriented relatively parallel to the long-axis of the LV, longitudinal strain is the earliest to get compromised while LV ejection fraction is often preserved (66). Moreover, reduced segmental LS reflects the focal impairment of LV (Figure 7).

A number of studies have confirmed the usefulness of STI in patients with myocarditis. In the acute phase reduced GLS reflects the extent of myocardial edema on a cardiac magnetic resonance (67,68). GLS also correlated with the degree of lympho- cyte infiltration in the myocardium biopsy samples (69). In patients with acute myocarditis, reduced GLS is an independent predictor of poor clinical outcome (70).

In patients with chronic myocarditis and preserved LV ejection fraction, GLS im- proved significantly the diagnostic performance of cardic magnetic resonance (71).

4.6 Cardiac resynchronization therapy

Conventional parameters for assessing dyssynchrony using indices for timing of peak strain or peak velocity are rather complex techniques, and additionally none of these approaches are proven to improve responder rate in patietns with cardiac resynchronization therapy (CRT) (72). It is much easier and simpler to identify specific patterns of mechanical dyssynchrony using STI in CRT candidates.

Figure 6: Algorithm for identification of early myocardial impairment after chemotherapy (modified from Plana J, et al. (50) and Zamorano JL, et al. (49)). EF – ejection fraction. GLS – global longitudinal strain.

LV – left ventricular.

Figure 7: Changes in longitudinal strain and changes present in a myocarditis patient, detected with magnetic resonance imaging.

Polar map with longitudinal strain values and GLS value (marked with the arrow) (A) and a T1 IR (inversion recovery) MRI image with late gadolinium enhancement in a short-axis view (B) four- chamber view (C) in the acute phase of the disease (top) and 6 months later (bottom).

Top: Significantly reduced GLS (–15%) despite preserved ejection fraction (EF 55%) in the acute phase of the disease (1A). Segments with most pathological longitudinal strain values are coloured blue, which reflects the focal impairment of LV, confirmed with a cardiac MRI. Hyperintense signal (yellow arrows) represents subepicardial accumulation of the gadolinium contrast media due to an edema in LV inferior, inferolateral and anterolateral wall, and in mid apical septum (1B, 1C).

Bottom: Relevant improvement of GLS (–21%) with only moderate increase in ejection fraction (58%) after 6 months (2A). A good match between segmental longitudinal strain improvement and reduced signal representing pathological gadolinium accumulation, which represented final fibrotic changes after myocarditis (2B, 2C).

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be considered in these patients if GLS is ≤ -15.9%, and accompanied by other factors defining high-risk patients – high calcium score and extensive myocardial fibrosis on cardiac magnetic resonance.

4.5 Myocarditis

Myocarditis, unlike ischemic disease, usually affects subepicardial and more rarely mid-myocardial layers of left ventricular. Inflammation may be diffuse or focal, typicaly not related to the territory of a coronary arteries. Since the inflammation is mostly limited to the subepicardi- um, where supepicardial fibers are oriented relatively parallel to the long-axis of the LV, longitudinal strain is the earliest to get compromised while LV ejection fraction is often preserved (66). Moreover, reduced segmental LS reflects the focal impairment of LV (Figure 7).

A number of studies have confirmed the usefulness of STI in patients with myocarditis. In the acute phase reduced GLS reflects the extent of myocardial edema on a cardiac magnetic resonance (67,68). GLS also correlated with the degree of lympho- cyte infiltration in the myocardium biopsy samples (69). In patients with acute myocarditis, reduced GLS is an independent predictor of poor clinical outcome (70).

In patients with chronic myocarditis and preserved LV ejection fraction, GLS im- proved significantly the diagnostic performance of cardic magnetic resonance (71).

4.6 Cardiac resynchronization therapy

Conventional parameters for assessing dyssynchrony using indices for timing of peak strain or peak velocity are rather complex techniques, and additionally none of these approaches are proven to improve responder rate in patietns with cardiac resynchronization therapy (CRT) (72). It is much easier and simpler to identify specific patterns of mechanical dyssynchrony using STI in CRT candidates.

Figure 6: Algorithm for identification of early myocardial impairment after chemotherapy (modified from Plana J, et al. (50) and Zamorano JL, et al. (49)). EF – ejection fraction. GLS – global longitudinal strain.

LV – left ventricular.

Figure 7: Changes in longitudinal strain and changes present in a myocarditis patient, detected with magnetic resonance imaging.

Polar map with longitudinal strain values and GLS value (marked with the arrow) (A) and a T1 IR (inversion recovery) MRI image with late gadolinium enhancement in a short-axis view (B) four- chamber view (C) in the acute phase of the disease (top) and 6 months later (bottom).

Top: Significantly reduced GLS (–15%) despite preserved ejection fraction (EF 55%) in the acute phase of the disease (1A). Segments with most pathological longitudinal strain values are coloured blue, which reflects the focal impairment of LV, confirmed with a cardiac MRI. Hyperintense signal (yellow arrows) represents subepicardial accumulation of the gadolinium contrast media due to an edema in LV inferior, inferolateral and anterolateral wall, and in mid apical septum (1B, 1C).

Bottom: Relevant improvement of GLS (–21%) with only moderate increase in ejection fraction (58%) after 6 months (2A). A good match between segmental longitudinal strain improvement and reduced signal representing pathological gadolinium accumulation, which represented final fibrotic changes after myocarditis (2B, 2C).

The typical deformation pattern associated with the response to CRT consists of early-systolic shortening in the septum, and early-systolic lengthening combined with peak shortening after after aortic valve closure in the LV lateral wall (Fig- ure 8) (73-75). Additionally, a specific LV mechanical dyssynchrony pattern, charac- terized by apical rocking and septal flash, is also associated with a more favourable outcome after CRT. Apical rocking and septal flash, which can be detected visually, are good predictors of response to CRT (75,76). Althought these echocardio-

graphic parametes have not been included in the currently applicable guidelines for patient selection for CRT (77), they can however still be used as predictors for clinical outcome.

5 Conclusion

Novel deformation imaging methods have been developed to the point where they have become important complemena- try echocardiographic methods in various cardiac diseases. STI provides additional information on left ventricular mechanics,

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and allows to detect subclinical myocardial dysfunction earlier than conventional echocardiographic parameters. STI is also a prognostic marker in patients with different types of cardiomyopathy, and GLS has even higher predicitve value for clinical outcome than EF. Based on the data from literature, novel myocardial deformation imaging is useful additional echocardiographic method, and we encourage all echocardiographist to use it more frequently in routine clinical practice.

Figure 8: Myocardial longitudinal strain curves in a 4-chamber view in a patient with heart failure and left bundle branch block.

It shows a specific pattern: 1. septal shortening in early systole, 2 lateral wall segmental stretch in early systole, and 3. post-systolic peak lateral wall contraction. Ac – aortic valve closure; Ao – aortic valve closure opening; Mc – mitral valve closure; Mo – mitral valve opening.

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