Four-Dimensional XStrain Echocardiographic Assessment of Left Ventricular Strain and Rotational Mechanics: Technology, Clinical Applications, Advantages and Limitations

Abstract

Because of its excellent ability to non-invasively assess left ventricular (LV) systolic function, two-dimensional speckle tracking echocardiography (STE) is increasingly being used in echocardiographic laboratories worldwide. Two-dimensional STE is the most sought-after method to evaluate LV strain, rotation, twist and torsion. Two dimensional, three-dimensional and four-dimensional (4D) deformation estimation by STE has several intrinsic limitations. For better appraisal of LV contractile properties, a recently introduced updated version of 4D XStrain STE has been used to analyse the various complex multidimensional LV mechanics. This novel technology is a reliable, economical and simple tool for estimating regional and global myocardial function. Furthermore, 4D XStrain STE can accurately quantify the 4D LV ejection-fraction, LV volume and sphericity index. However, this technology has not been extensively implemented, and its assessment remains limited primarily to research applications. Hence, we aim to promote this innovative technology by comprehensively addressing its technique, advantages and limitations, so that it can be better applied in cardiovascular disease.

Main article text

Introduction

Global longitudinal strain (GLS) automatically derived by speckle tracking echocardiography (STE) has been extensively researched worldwide [1]. After a critical evaluation of the extensive data on GLS, the American Society of Echocardiography recommended a normal GLS value of ≥ 20 + 2% [2]. Three-dimensional (3D) STE requires a single apical acquisition, thus decreasing acquisition duration and enabling estimation of all strain components from a solitary cardiac cycle [3]. In contrast, the inferior temporal and spatial resolution of 3D STE adversely affects its tracking quality. Intermittently, multi-beat acquisition may produce a stitching artifact between sub-volumes, which may result in imprecise speckle tracking analysis [4, 5]. XStrain 4D is a pioneering technology combining Tomtec GMBH’s 3D/four-dimensional (4D) rendition and Beutel™ computing [6]. This unique tool combines the speckle tracking data obtained from apical 3CH, 4CH and 2CH views, and provides a detailed picture of cardiac function (Figure 1). This tool, because of its superior two-dimensional (2D) spatial and temporal resolution, addresses the various constraints of full volume 3D STE [7–11].

Figure 1

4D XStrain Speckle Tracking Echocardiography.

A) 3D remodelling after sequential structural arrangement. B) Epicardial bull’s eye deformation values. C) Endocardial Bull’s eye in a 17 segment model. D) Graphs of trends in longitudinal deformation values over time.

Considerable differences were observed in strain measurements between 2D and 3D speckle tracking echocardiography (Table 1). The JASE consensus declaration [12] has recognized that the limitation of analysis of rapid events of isovolumic contraction and relaxation is a consequence of the slower frame rates of 3D STE than 2D STE.

Table 1

Comparative Features of 2D and 3D Deformation of LV (Modification of Table 1, Muraru et al.) [6].

Features	3D deformation	2D deformation
Acquisition	Solitary apical view	Numerous apical and parasternal views
Heart rhythm requisite	Regular	Regular
Feasibility	Acceptable	Superior
Dependence on excellent image resolution	Yes (++)	Yes (+)
Temporal resolution	34–50 volumes/sec	40–75 frames/sec
Parameters	All deformation parameters (longitudinal, radial, circumferential)	All deformation parameters (longitudinal, radial, circumferential)
Area deformation parameter	Evaluated	Cannot be evaluated
Mapping of bull’s eye	Dynamic	Fixed
Global strain calculation	Concomitant	Non-concomitant
Radial strain calculation	Estimated from area strain	Calculated directly
Speckle motion	Any direction	Out-of-plane
Positive peak principle	Absent	Present
Demarcation of end-systole	Minimal volume of LV	Closure of aortic valve

Single plane 3D echocardiography imaging is achieved through fragmentation of the 3D STE by tracking 3D successive volumes within the region of interest with a 3D template matching algorithm. Nevertheless, the resultant 3D resolution is of ordinary quality with respect to 2D imaging [6]. Image quality is a critical factor in temporal and spatial resolution; consequently, 3D STE is adversely affected in defining the endocardial and epicardial boundaries. In contrast, XStrain™ 4D, which does not have these limitations, is an excellent, reliable and operator friendly tool for estimation of global and regional myocardial deformation.

This article comprehensively describes the systematic approach to technique, the clinical applications, and the advantages and limitations of this outstanding procedure.

4D Xstrain Speckle Tracking Echocardiography

Technique

Echocardiographic evaluation is performed by a qualified and skilled operator. The procedure necessitates acquisition of images by using a harmonic variable frequency (1–5 Mhz) electronic single crystal array transducer, with the patient lying in the left lateral decubitus position [6, 13]. The technique requires a systematized approach for obtaining high quality information regarding a variety of variables in LV deformation, rotation, EF, etc.

ECG Gating

Because ECG gating is a salient feature of STE, pristine ECG signal quality is required. Efforts should be made to acquire all images at similar heart rates.

Image Acquisition

The 2D digital cine loops are acquired with a frame rate of 40–75 frames/sec along with simultaneous ECG gating from apical 3CH, 4CH and 2CH views. A minimum of three cine loops are acquired.

An endocardial frame with a clearly outlined endocardial and epicardial border is selected. The border is demarcated by 13 equidistant tracking points (Figure 2), which automatically align over tracking points, under the supervision of a border segmentation tool called Aided Heart Segmentation.

Figure 2

Endocardial border mapping by 4D Xstrain STE.

A) Illustration of 4D XStrain STE border mapping by insertion of 13 equidistant points on the endocardium of the LV cavity. B) Similar procedure being followed in one of our study participant.

The LV wall of each apical view is automatically divided into six segments and tracked throughout the cardiac cycle. The tracking quality is optically assessed and is considered appropriate if the movements of tracking points are tagged along the endocardial border throughout the entire cardiac cycle. When required, manual adjustment of tracking points is performed. The cardiac cycles with decent tracking quality and absence of arrhythmia are selected for off-line analysis.

Offline Analysis

The 2D STE analysis is implemented off-line by the same operator using the XStrain-4D™ (Esaote, Italy) software package, a dedicated border tracking application [13]. The principal purpose of XStrain-4D™ is to amalgamate and systematically refine the information gathered from three 2D apical views. After 3D reformation, XStrain-4D software provides values of multitudinal segmental, regional and global deformation, and rotational parameters [13]. Moreover, the “Beutel model” method (Tomtech, Germany) of X4D-EF [14–16] quantifies the 4D LV volumes, EF, CO and sphericity index in diastole and systole. Finally, an LV bull’s eye plot is portrayed in a 17-segment model [13]. Graphics and curves of the estimated parameters are displayed, and numerous strain, strain rate, displacement and velocity indices are elucidated from the endocardial regions of the myocardium (Figures 3–5). LV global and regional mean values of endocardial deformation of variables are described as displacement (mm), velocity (mm/sec), strain (%) and strain rate (1/sec).

Figure 3

Regional and Global GLS Analysis and Bull’s Eye Graph and Plot.

A) Apical 3CH GLS analysis. B) Apical 4CH GLS analysis. C) Apical 2CH GLS analysis. D) GLS bull’s eye graph and plot. E) GLS bull’s eye plot. F) Longitudinal time to peak strain plot.

Figure 4

Graphic Representation of GLS, GLSR, GCS, GCSR, GRS, GRSR.

A) LV GLS. B) GLSR. C) LV GCS. D) LV GCSR. E) LV GRS. F) LV GRSR. GRSR, global longitudinal strain; GLSR, global longitudinal strain rate; GCS, global circumferential strain; GCSR, global circumferential strain rate; GRS, global radial strain; GRSR, global radial strain rate.

Figure 5

Determination of 4D XStrain Strain and Volumetric Data.

A) 3D reconstruction of the three 2D apical views by 4D XStrain software. B) Determination of 4D volumes, EF%, cardiac output and sphericity index in diastole and systole.

Special Precautions for High Quality 4D XStrain Speckle Tracking Echocardiography [17]

Obtaining high quality 4D XStrain STE images is critical, and certain instructions must be followed during image acquisition.

• Special attention must be paid to obtaining the highest quality ECG tracing. The position of electrodes on the chest should be adjusted, and the lead (from the PHYSIO menu of the echocardardiography system) that displays the smoothest trace should be chosen, with well-defined R/Q waves with minimal noise. Traces with prominent P or T waves, which interfere with gating during 4D XStrain STE data acquisition, should be avoided.

• The operator must ascertain whether the patient can cooperate in breath holding manoeuvres. To avoid translation motion and breathing artifacts, breath holding must be ensured during data acquisition.

• LV should occupy most of the image sector; avoiding foreshortening is imperative.

• While performing endocardial tracking, care should be taken to avoid the papillary muscle bulges in the LV cavity.

• For evaluation of LV circumferential and radial strain, rotation and twist, excellent quality images in short axis views at the mitral valve level, papillary muscle level and apical level are necessary.

• The software automatically calculates the rotation parameters. Conventionally, a positive value is used to designate anticlockwise rotation, and a negative value is used to designate clockwise rotation; thus, the apical rotation is positive, and the basal rotation is negative.

• Calculation of LV twist is achieved by subtracting the basal from the apical rotation and torsion by dividing the twist value by the length of LV (Figure 6).

Figure 6

Calculation of LV Twist and Torsion.

Parameters Derived from 4D XStrain STE

Myriad parameters can be derived from the updated version of 4D XStrain STE.

Deformation Parameters

The deformation parameters are GLS, global longitudinal strain rate (GLSR), global circumferential strain (GCS), global circumferential strain rate (GCSR), global radial strain (GRS), global radial strain rate (GRSR), transverse strain, transverse strain rate, transverse velocity, longitudinal velocity, radial velocity, rotational velocity, shear and shear rate. Negative values are assigned to GLS and GCS. In contrast, GRS is designated with positive values. Likewise, the values of %, 1/sec, and cm/sec are assigned to strain, strain rate and velocity, respectively.

Rotational Parameters

The derived rotational parameters are peak apical rotation, time to peak apical rotation, peak twist, time to peak twist, twist rate, time to peak twist rate, untwist rate and time to peak untwist rate (Figure 7). The values of rotation, twist, untwist rate and time to untwist rate are demarcated in 0, ms and 0/s, where appropriate.

Figure 7

LV Twist Mechanism and Generation of LV Rotational and Twist Parameters.

A) LV twist mechanism. The basal segment revolves in a counterclockwise course, and the apex resolves in a clockwise route. L, distance between the base and apex. B), C) and D) Graphs of LV rotational twist parameters generated by XStrain4D™ software.

Volumetric Parameters

LV end-diastolic volume (EDV) and end-systolic volume (ESV), cardiac output (CO) 4D-EF% and sphericity index (SI).

Clinical Applications

In diverse clinical settings, STE is an invaluable tool for the detection of subclinical LV systolic dysfunction. The application of this promising technology has markedly increased in the past decade, as evidenced by the abundance of published research and scientific literature on this approach.

In the academic literature, we encountered multiple studies using XStrain 4D STE in multiple clinical disease states, including congenital heart disease, coronary artery disease, hypertrophic cardiomyopathy, dilated cardiomyopathy, amyloidosis, psoriasis, acute myocarditis and progressive systemic sclerosis. Notably, a substantial number of research studies have been published in healthy adult populations [12, 16–22], with the aim of determining the normative value ranges of several strain, rotation and twist parameters.

Current clinical applications of XStrain 4D STE are summarized below.

• Coronary Artery Disease

  GLS is significantly impaired in the region of myocardial infarction [23–25]. Additionally, a parallel decrease in strain values within the infarcted myocardium has been observed. In patients with recent non-ST elevation myocardial infarction undergoing percutaneous coronary intervention (PCI), D’Andrea et al. [23] have outlined the effectiveness of global and regional longitudinal strain, as assessed with XStrain 4D STE. In that study, strain values were achievable in 95% of LV segments; akinetic segments showed more myocardial deformation, which did not recover after PCI; peak troponin I values after PCI correlated with GLS; and deterioration of baseline GLS and its insufficient improvement after PCI were found to be robust indicators of negative LV remodelling at 6 months. The authors have concluded that the utility and outcomes of PCI in the setting of recent non-ST elevation myocardial infarction are influenced not only by PCI but also by the magnitude of the scarred LV myocardium.

  Attenuation of GLS at rest in patients with ischemic heart disease is associated with the hypoperfusion and decrease in blood supply to the subendocardial region of LV, an area highly susceptible to the effects of ischemia [26, 27]. Rostamzadeh et al. [26] observed impaired LV GLS, GLSR and based median radial strain rate in a patient suspected to be having coronary artery disease (CAD), without regional wall motion abnormalities at rest. These features can be effectively used to identify patients with high risk of CAD. The authors have suggested that GLS, GLSR and median radial strain rate can be used in routine examinations for CAD diagnosis and risk stratification.

  To facilitate superior correlation of optical assessment of regional wall motion kinesis and the magnitude of regional deformation, D’Andrea and colleagues [27] have suggested that XStrain 4D STE is useful for intensified focus on deformation analysis in a single artery supply territory (Figure 8).

• Valvular Heart Disease

  XStrain STE can indicate the existence of LV subclinical myocardial dysfunction (Figure 9). Because of adaptive remodelling of LV, these patients may be asymptomatic for long durations despite the presence of severe valvular disease [28].

  In a study of athletes with a bicuspid aortic valve and normal LVEF, Stefani et al. [29] have observed a lower peak longitudinal systolic strain than in the control group. Therefore, the authors have recommended yearly follow up for comparison of the behaviour of LV deformation in these patients.

• Hypertrophic Cardiomyopathy

  XStrain STE has been used to evaluate subclinical myocardial damage (Figure 10) in patients with left ventricular hypertrophy and to characterize its various causes [30–33]. Badran et al. [33] have shown that right atrial (RA) mechanics entirely follows right ventricular (RV) and LV function, as well as disease severity. A marked deterioration was observed in all components of RA functions; reservoir function, conduit function, and booster pump function, and a predominant decline in RA reservoir and conduit function was observed in patients with hypertrophic cardiomyopathy with preserved LV ejection fraction. In contrast, contractile function remained unaltered in the control group.

  Furthermore, the attenuation of RA conduit function was strongly associated with the severity of LV cardiomyopathy and LV deformation.

• Dilated Cardiomyopathy

  Several studies using XStrain STE in patients with dilated cardiomyopathy (DCM) have indicated a deterioration in LV myocardial strain in all three directions (Figure 11).

  STE has been suggested to be applicable in DCM detection [34, 35]. Badran et al. [35] have investigated the role of XStrain STE in assessing RV mechanics in patients with DCM and have suggested that the pathologic mechanism affecting the RV also causes LV involvement, with a noteworthy decrease in RV systolic and diastolic function, as well as global and right ventricular free wall function.

• Subclinical Myocardial Deformation in Systemic Diseases

  The unique Xstrain STE technology has shown utility in the detection of preclinical states of systemic diseases, such as Kawasaki disease, rheumatoid arthritis, lupus nephritis, psoriasis, systemic sclerosis, thalassemia major and cardiac amyloidosis (Figures 12–15) [36–42].

• Miscellaneous Conditions

  1. Acute Myocarditis

     In a small study in 13 patients [43] with acute myocarditis, with absence of regional wall motion abnormalities and with preserved LV ejection fraction, diffuse impairment of GLS has been demonstrated (Figure 16), although the circumferential strain was regionally attenuated. The authors have suggested that these results might have been due to subepicardial damage. Deterioration in GLS and regional circumferential strain, along with non-visualization of regional wall motion abnormalities, are additional findings supporting focal myocarditis.

  2. Cardiotoxicity in Oncology

     Before cancer chemotherapy/radiotherapy is administered, knowledge of LV contractility in the potential recipient is essential, because such therapies may cause subclinical myocardial damage. Stefani et al. [44] have indicated that GLS is a valuable parameter to authenticate or exclude the existence of preclinical myocardial dysfunction.

     The presence or absence of early LV dysfunction may have far reaching consequences, by permitting or contraindicating rigorous physical activity or sports. This aspect is important in patients who are fully asymptomatic or have a history of transitory heart failure, in whom regular and long-term follow up is essential.

  3. Cyanotic Congenital Heart Disease

     The assessment of LV deformation is crucial in patients with transposition of great arteries after arterial switch surgery. In this surgery, the coronary arteries may be at risk of injury. Rad et al. [45] have reported normal GLS, GLSR and global time to peak strain in 20 postoperative children 15 ± 5 months of age, after a successful arterial switch surgery. Nonetheless, the time to peak systolic strain did not normalize in this time period. The authors have concluded that some segments of LV myocardium may fully recover, whereas others may not.

  4. Wrapping of the Left Anterior Descending Artery Around the Left Ventricular Apex

     An Egyptian study [46] in 71 patients with the left anterior descending artery enveloping the LV apex with normal coronary angiogram findings has investigated the LV deformation parameters with XStrain STE. The researchers have concluded that the notable anatomic feature of LV encasing of the left anterior descending artery provides superior myocardial relaxation with escalated rotational and circumferential mechanics when compared to control participants (Figure 17).

  5. Newer Applications: Vortex Analysis in Heart Failure

     The LV vortex is a flow structure with a circular or swirling motion that preserves the momentum of late transmitral flow into the LV outflow tract during the transition from diastole to systole. A pathophysiological link between diastolic filling and systolic ejection can be identified with LV vortex flow [47].

     LV vortex is an important predictor of adverse outcomes in patients with heart failure [47]. The HyperDoppler technique is a newer method for analysis of LV vortex formation (Figures 18 and 19), in which LV contractile function is investigated in a different manner [47]. During the Isovolumic contraction phase of the cardiac cycle, the LV vortex flow is modified, and the blood flow is diverted to the LV outflow tract; an anterior vortex of considerable magnitude forms across the LV inflow-outflow region. Later, blood is ejected after the opening of the aortic valve.

Figure 8

XStrain 4D Regional Deformation Analysis in Various Coronary Artery Territories.

(A) GLS values in the LCX artery perfusion region, (B) left anterior descending artery perfusion region and (C) RCA perfusion region.

Figure 9

XStrain STE of LV in a Patient with a Tricuspid Aortic Valve, Showing GLS Impairment.

Figure 10

GLS Contour in Hypertrophic Cardiomyopathy.

(A) Patients with no obstruction have decreased strain values and increased electromechanical delay. (B) Patients without obstruction have higher strain values and lower electromechanical delay.

Figure 11

XStrain 4D Curves of Strain and Strain Rate in Patients of Dilated Cardiomyopathy with LBBB.

(A) LV tracking in apical 4ch view, (B) curved M-mode of septal and lateral wall segments, (C) strain curves of 6 patterns derived from septal and lateral wall segments and (D) strain rate activity curve of same segments.

Figure 12

XStrain STE in Renal Transplant Recipients, Showing Significantly Impaired GLS with Respect to that in Controls (P < 0.001).

Figure 13

Significantly Lower GLS and GCS Deformation Values in Patients with Systemic Sclerosis than Healthy Participants (P < 0.001).

Figure 14

4D XStrain STE in Patients with Psoriasis.

(A) GLS curve in healthy controls and (B) in patients with psoriasis. GLS is significantly lower in the group with psoriasis than the controls.

Figure 15

4D XStrain STE of Right Ventricular (RV) Mechanics in Participants without Cardiac Amyloidosis (CA) and Patients with Early Stage CA. RV GLS is Impaired in Mid and Basal RV Regions in Early CA. Normal Strain is Depicted in Green, and Mild-Moderate Dysfunction is Depicted in Yellow.

Figure 16

GLS Curve in Acute Myocarditis.

(A) Normal participant: GLS contour of LV. (B) GLS curve in acute myocarditis.

Figure 17

4D Xstrain STE.

GLS curves derived from LV segments in apical 4CH view in a patient of left anterior descending (LAD) artery enveloping the LV apex with normal coronary angiography. (A) GLS in wrapping patient 21% (B) GLS in non-wrapping patient 17%.

Figure 18

HyperDoppler Software Estimation of Intracardiac Flow Dynamics in a Patient with Dilated Cardiomyopathy.

(A) Analysis of the vector flow map, demonstrating circulation along the posterior lateral wall towards the LV apex. (B) Visualization of a rotating vortex of considerable size (blue). (C) Colour map of a smoothly running flow vortex.

Figure 19

HyperDoppler software analysis of intracardiac flow in a healthy participant (A) and (B), and a patient with dilated cardiomyopathy (C) and (D). A scattered distribution of LV haemodynamic forces is seen in a patient with cardiomyopathy.

Advantages

The pioneering technology of 4D Xstrain STE has multiple advantages over the freely available 2D STE and represents a step forward in delineating LV deformation mechanics. Various favourable features include the following: a) This remarkable tool has superior spatial and temporal resolution [6], which address the critical disadvantages of full-volume 3D STE of random noise in the image quality; decreased volume rate and a corresponding decrease in temporal resolution; decreased voxel size leading to depression of spatial resolution; and suboptimal myocardial tracking [6]. b) XStrain 4D software is superior because of its simultaneous off-line derivation and estimation of the numerous strain components, volumetric indices, cardiac output, EF% and sphericity index [6, 16]. c) This intuitive software provides an augmented and novel solution to calculate and collate the various constituents of cardiac function in the 3D domain [16, 17]. d) This software is relatively inexpensive in comparison to 3D/4D STE software [16, 17]. e) The interobserver and intraobserver variability are extremely low [6, 16, 17]. f) Acquisition is smooth and relatively rapid, and off-line analysis can be performed quickly [16, 17].

Limitations

Despite being more than a decade old, 4D XStrain STE continues to be a valuable research tool. However, because of certain limitations, its widespread clinical use has been restricted. The limitations are as follows:

1. Lack of multicentre randomized controlled trials in normal healthy children, adolescents and adults, for obtaining normal reference range values of different parameters of strain and rotation.

2. Dependency on an acoustically favourable window for achieving excellent resolution of cardiac anatomy.

3. Exclusion of patients with irregular rhythms from study, because the 4D XStrain STE necessitates acquisition of multiple beats in normal sinus rhythm.

4. Influence of operator experience and training on the accuracy of measurements: because this technology is relatively new, few qualified and trained operators are currently available to conduct studies in a proficient manner.

5. Lack of validation of this method against cardiac MRI, the gold standard of speckle tracking echocardiography.

Future Research Directions

With newer “e Doppler” techniques (for automatic correction of Doppler angle, box position, and sample volume position and steering, for fast and optimized calculation) and “Elaxto” (an echocardiographic revolution for determination of tissue elasticity) on the horizon, accurate interpretation of 4D XStrain STE requires extensive medical education and training, for both scientific research and clinical applications. The dedicated XStrain™ software requires adequate qualifications and operator expertise to obtain high quality images and accurately estimate the projected values of myocardial strain and rotation parameters. We suggest the following future directions:

1. Large scale randomized controlled trials should be conducted to define the cut-off normal value ranges of various strain parameters in a healthy population, and enable the diseased and normal healthy populations to be distinguished.

2. Correlations among strain parameters, and between strain parameters and LV hemodynamic variables as well as demographic characteristics in healthy populations, should be planned and determined in research trials.

3. Clinical trials to study the incremental prognostic value of 4D XStrain STE for forecasting morbidity, mortality and arrhythmic events in comparison with LV ejection fraction and GLS are warranted.

4. Widespread educational initiatives are recommended to increase awareness of 4D Xstrain STE and achieve consistent application of the technology in a variety of clinical settings.

5. Intensified efforts should be made to forge inter-vendor relationships for sharing proprietary software, thus to decrease inter-vendor variability and differences.

6. Clinical studies should be undertaken to validate the technique against cardiac MRI, the current gold standard for deformation analysis.

7. Further clinical studies are warranted to assess the reversibility of myocardial ischemia and corresponding decreases in myocardial deformation impairment. These efforts would increase understanding of the magnitude of strain reversibility with medical therapy/coronary angioplasty.

Conclusion

XStrain 4D is a superior non-invasive advanced echocardiographic tool to investigate myocardial deformation and rotational mechanics. In contrast, no current commercially available 2D STE/3D STE systems enable estimation of multiple parameters. XStrain 4D is relatively inexpensive, as compared with highly priced 3D STE systems. Nonetheless, further clinical research studies are necessary to maximize the clinical use of this method and clearly demarcate its advantages over well-established methods.

Acknowledgements

We humbly acknowledge the incredible efforts of Faiz Illahi Siddiqui, for his immense sincerity in typing the manuscript repeatedly due to multiple revisions suggested by the respected reviewers. His instinctive and intuitive aptitude is exemplified in the creation of the diagrammatic illustration of LV border mapping (Figure 2A).

Conflict of Interest

The authors declare no conflicts of interest.

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